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-[{"text": "JournalofPlastic,Reconstructive&AestheticSurgery(2010)63,1401e1419 Revised UK guidelines for the management *,** of cutaneous melanoma 2010 J.R. Marsdena,*, J.A. Newton-Bishop b, L. Burrows c, M. Cook d, P.G. Corrie e, N.H. Cox a, M.E. Gore f, P. Lorigang, R. MacKieh, P. Nathan i, H. Peachj, B. Powell k, C. Walkera aUniversity HospitalBirmingham, Birmingham B29 6JD,United Kingdom bUniversity of Leeds,Leeds LS9 7TF,United Kingdom cSalisbury District Hospital, Salisbury SP2 8BJ, United Kingdom dRoyal Surrey CountyHospital NHSTrust,Guildford GU27XX, United Kingdom eCambridge University Hospitals NHS FoundationTrust,Cambridge CB2 2QQ,United Kingdom fRoyal Marsden Hospital, LondonSW3 6JJ,United Kingdom gTheChristie NHS Foundation Trust, ManchesterM20 4BX,United Kingdom hUniversity of Glasgow,Glasgow G128QQ, United Kingdom iMount Vernon Hospital, London HA62RN,United Kingdom jStJames\u2019sUniversity Hospital, LeedsLS9 7TF,United Kingdom kStGeorge\u2019sHospital, London SW170QT,United Kingdom KEYWORDS Summary These guidelines for the management of cutaneous melanoma present an Evidence; evidence-basedguidancefortreatment,withidentificationofthestrengthofevidenceavailGuideline; ableatthetimeofpreparationoftheguidelines,andabriefoverviewofepidemiology,diagInvestigation; nosis,investigation,andfollow-up. Melanoma; \u00aa2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons and British Treatment AssociationofDermatologists.Allrightsreserved. *ThisisanupdatedguidelinepreparedfortheBritishAssociationofDermatologists(BAD)ClinicalStandardsUnit,madeupoftheTherapy& GuidelinesSubcommittee(T&G)andtheAudit&ClinicalStandardsSubcommittee(A&CS).MembersoftheClinicalStandardsUnitare:HKBell [ChairmanT&G],LCFuller[ChairmanA&CS],NJLevell,MJTidman,PDYesudian,JLear,JHughes,AJMcDonagh,SPunjabi,NMorar,SWagle [BritishNationalFormulary],SEHulley[BritishDermatologicalNursingGroup],KJLyons[BADScientificAdministrator],andMFMohdMustapa [BADClinicalStandardsManager]. TheseguidelinesarepublishedsimultaneouslyintheBritishJournalofDermatology(doi:10.1111/j.1365-2133.2010.09883.x)andtheJournal ofPlastic,Reconstructive&AestheticSurgery(doi:10.1016/j.bjps.2010.07.006). **Guidelinesproducedin2002bytheBritishAssociationofDermatologists;reviewedandupdated,2009. * Correspondingauthor. E-mailaddress:jerry.marsden@uhb.nhs.uk(J.R.Marsden). 1748-6815/$-seefrontmatter\u00aa2010BritishAssociationofPlastic,ReconstructiveandAestheticSurgeonsandBritishAssociationofDermatologists.Allrightsreserved. doi:10.1016/j.bjps.2010.07.006", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 1}, {"text": "1402 J.R.Marsden etal. Guidelines review process and other publications were identified from the PubMed searches,independentsearchescarriedoutbytheauthors, These guidelines were initially reviewed at a multidisciaswellasmaterialscollectedbytheauthorsaspartoftheir plinarymeetingon8November2007.Thoseattendingwere ongoingprofessionalinterestinthelatestdevelopmentsin theauthors plus: this clinical area. Levels of evidence to support the guideDermatology: V Doherty, D Roberts, F Wojnarowska, lines are quoted according to the criteria stated in HBell,DdeBerker,CHarwood,SBailey,RBarlow,VBataille, Appendix1.TheconsultationprocessforBritishAssociation L Rhodes of Dermatologists guidelines and their compliance with Surgery:A Hayes,J Kenealy,G Perks, M Timmins guideline recommendations have been published elseSpecialist Nursing: H Williams, C McGarr, M Sherman, where.1,2Thereareargumentsinfavourofnewerguideline JDavenport, CWheelhouse gradingmethods,suchasthoseofGRADE,3buttheauthors Histopathology:NKirkham,HRigby,J Theaker believethatthesystemusedhereallowsgreaterpotential Imaging:JSmith, PGuest, A Dancey for consensus in areas of conflicting evidence or where Oncology: N Steven, P Corrie, P Patel, A Goodman, evidence sources are not directly comparable. In some CKelly, PLawton,A Dalgleish instances, this is not due to an absence of high quality Lay representative: TFay (Level Ib) trials but because different entry criteria or Palliative Care:J Speakman,F Calman endpoints preclude direct comparison of results; in other National Institute for Health and Clinical Excellence: cases interpretation of the clinical significance of results NSummerton has been challenged. To assist production of unified Scottish Intercollegiate Guidelines Network:SQureshi guidelines taking account of these issues, the \u2018quality of Primary Care:P Murchie evidence\u2019 grading used in these guidelines differs slightly from that used in other British Association of Dermatologists current guidelines; the strength of Disclaimer recommendationsgradingisthesameasusedinmanyother publications.Wherenolevelisquotedtheevidenceistobe These guidelines reflect the best published data available regarded as representing Level IV (i.e. a consensus at the time the report was prepared. Caution should be statement). exercised in interpreting the data; the results of future The intention of the working party was to agree best studiesmayrequirealterationoftheconclusionsorrecompracticeforthemanagementofmelanomainthebeliefthat mendations in this report. It may be necessary or even this will promote good standards of care across the whole desirable to depart from the guidelines in the interests of country.However,theyareguidelinesonly.Careshouldbe specificpatients andspecial circumstances. Just as adherindividualised wherever appropriate. These guidelines will ence to the guidelines may not constitute defence against berevisedasnecessarytoreflectchangesinpracticeinlight aclaimofnegligence,sodeviationfromthemshouldnotbe ofnewevidence. necessarilydeemednegligent. Integration with national cancer guidance Contributiontotheseguidelineshasbeenmadebyalarge number of clinicians. They have also been endorsed by, or Multidisciplinary care of the patient is held to be the most havehadinputfrom,representativesofthefollowinggroups desirable model as recommended in the Calman/Hine ororganisations:theUKMelanomaStudyGroup,theBritish report.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 2}, {"text": "by, or Multidisciplinary care of the patient is held to be the most havehadinputfrom,representativesofthefollowinggroups desirable model as recommended in the Calman/Hine ororganisations:theUKMelanomaStudyGroup,theBritish report.4 This has been defined by the National Institute for Association of Dermatologists, the British Association of HealthandClinicalExcellenceImprovingOutcomesGuidance Plastic, Reconstructive and Aesthetic Surgeons, the Royal for People with Skin Tumours Including Melanoma (NICE College of Physicians, London, the Association of Cancer IOG).5 Core services will be provided within each Cancer Physicians, the Royal College of Radiologists, London, the Network by Local Skin Cancer Multidisciplinary Teams Royal College of Surgeons, England, the Royal College (LSMDTs). Specialist services will be provided by Specialist ofPathologists(pathologysectiononly),theRoyalCollegeof SkinCancerMultidisciplinaryTeams(SSMDTs).Formelanoma General Practitioners, London, and the Department of thereisacleardemarcationofcaresuchthatmoreadvanced Health. primarymelanoma,raresubtypesofmelanoma,melanomain These consensus guidelines have been drawn up by children,andpatientseligiblefortrialentryorsentinellymph a multidisciplinary working party with membership drawn nodebiopsyshouldbepromptlyreferredforinvestigationand from a variety of groups and coordinated by the United treatmentfromanLSMDTtoanSSMDT(Table1). Kingdom Melanoma Study Group (UKMSG), and the British Association of Dermatologists. The guidelines deal with aspects of the management of melanoma from its prevenPrevention of melanoma tion, through the stages of diagnosis and initial treatment to palliationof advanceddisease. PubMed literature searches for this guidelines revision Individuals,andparticularlychildren,shouldnotgetsunburnt werecarriedouttoidentifypublicationsfrom2000toApril (Level I).6e9 Meta-analysis of case-control studies provides 2010, with search terms including: melanoma genetics, good evidence that melanoma is predominantly caused by epidemiology, early diagnosis, risk factors, clinical intermittent intense sun exposure; fair-skinned individuals features, pathology, surgery, chemotherapy and clinical should therefore limit their recreational exposure through trials. Relevant materials were also isolated from reviews life(LevelI).10Peoplewithfreckles,redorblondhair,skin", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 2}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1403 Table1 MelanomapatientswhomustbereferredfromaLocalSkinCancerMultidisciplinaryTeamtoaSpecialistSkinCancer MultidisciplinaryTeam(SSMDT)(NICEIOG2006).5 (cid:1) Patients with melanoma managed by other site specialist teams (e.g. gynaecological, mucosal and head and neck (excludingocular)) (cid:1) Patients with stage IB or higher primary melanoma when sentinel lymph node biopsy (SLNB) is available within their Network.IntheabsenceofSLNBthenpatientswithstageIIBorhighershouldbereferredtotheSSMDT(AmericanJoint CommitteeonCancer(AJCC)stagingsystem) (cid:1) Patientswithmelanomaatanystagewhoareeligibleforclinicaltrialsthathavebeenapprovedatcancernetworklevel (cid:1) Patientswithmultipleprimarymelanomas (cid:1) Childrenandyoungadultsunder19yearswithmelanoma (cid:1) Anypatientwithmetastaticmelanomadiagnosedatpresentationoronfollow-up (cid:1) Patientswithgiantcongenitalnaeviwherethereissuspicionofmalignanttransformation (cid:1) Patientswithskinlesionsofuncertainmalignantpotential whichburnsinthesun,increasednumbersofnaevi,andthose Lesionswhicharesuspiciousformelanomashouldnotbe withafamilyhistoryofmelanomaareatincreasedriskand removedinprimarycare.Thisisbecauseclinico-pathological shouldheedthisadvice. correlation is vital for diagnostic accuracy, which in turn Adequate sun exposure to allow vitamin D synthesis, or determines prognosis and defines adjuvant treatment sufficientdietaryintakeofvitaminD isessentialtohuman options, andbecause diagnostic surgery requiresspecialist 3, health; insufficiency of vitamin D is now recognised to be training. Early recognition of melanoma presents the best common.11 It would therefore be inappropriate to greatly opportunityforcure15,19e22(LevelIII,GradeA). limitsunexposureinpeoplewithouttheriskfactorslisted All patients presenting with an atypical melanocytic above.RecentstudieshaveshownthatinUKvitaminDlevels lesion or a large number of moles should have a complete areoftensuboptimalinmelanomapatients,andarelowerin skin examination and assessment of risk factors. The derfair-skinnedpeople.12,13Fair-skinnedpeoplewhoavoidthe moscopeisausefultoolforthetrainedclinicianscreening sunrigorouslytoreducetheriskofmelanomashouldconsider pigmentedlesions,asitcanincreasediagnosticaccuracy.23 supplementingtheirintakeofvitaminD intheabsenceof It is also useful for monitoring multiple pigmented lesions 3 medicalcontraindications. wherephotographyofdermoscopicimagesprovidesarecord Thereisevidencefromarecentmeta-analysisthatsunofchange(LevelIa,GradeA).RecommendationsforLSMDT bedusagedoesincreasetheriskofmelanoma,particularly record-keepingofclinicalfeaturesareproposedinTable2. undertheageof35years,andthereforeitisrecommended thatthis shouldbeavoided(LevelIa).14 Screening and surveillance of high-risk individuals Referral and clinical diagnosis Therearesomeindividualsathigherriskofmelanomawho shouldbeconsideredforreferraltospecialistclinics.These Melanomaremainsrelatively uncommonandthereforethe individuals can be divided broadly into two groups based opportunitytodevelopdiagnosticskillsislimitedinprimary upon the degreeof risk: care.Alllesionssuspiciousofmelanomashouldbereferred urgently under the 2-week rule to local screening services usually run by dermatologists. In England and Wales, this wouldbetoanLSMDT.InScotland,referralshouldbemadeto a local Rapid Access Cancer Clinic according to Scottish CancerReferralGuidelines.Theseven-pointchecklistorthe Table 2 Recommendations for Local Skin Cancer MultiABCDrulemaybehelpfulintheidentificationofmelanomas disciplinaryTeamrecord-keepingofclinicalfeatures. althoughtheyaremoresensitivethanspecific.15e18Urgent Asaminimumthefollowingshouldbeincluded: referraltotheLSMDTisindicatedwherethereis: History(thepresenceorabsenceofthesechanges shouldberecorded) (cid:1) Anewmoleappearingaftertheonsetofpubertywhich (cid:1) Durationofthelesion ischanging inshape,colour orsize (cid:1) Changeinsize (cid:1) Along-standingmolewhichischanginginshape,colour (cid:1) Changeincolour orsize (cid:1) Changeinshape (cid:1) Anymolewhichhasthreeormorecoloursorhaslostits (cid:1) Symptoms(itching,bleeding,etc.) symmetry Examination (cid:1) A molewhich isitchingorbleeding (cid:1) Site (cid:1) Any new persistent skin lesion especially if growing, if (cid:1) Size(maximumdiameter) pigmented or vascular in appearance, and if the diag- (cid:1) Elevation(flat,palpable,nodular) nosis isnotclear (cid:1) Description(irregularmargins,irregularpigmentation (cid:1) Anewpigmentedlineinanailespeciallywherethereis andifulcerationispresent) associateddamage to the nail (LevelIII,GradeB) (cid:1) A lesiongrowing under anail.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 3}, {"text": "1404 J.R.Marsden etal. 1. Individuals at moderate increased risk (approximately 8498-cc94b378312a.pdf.Recommendationsforscreeningand 8e10 times that of the general population) should be surveillanceofhigh-riskindividualsaresummarisedinTable3. counselled about this risk and taught how to selfexamine for changing naevi, but long-term follow-up is Biopsy of suspected melanoma notusual.Suchpatientsarethosewitheitheraprevious primary melanoma, or large numbers of moles some of whichmaybeclinicallyatypical(LevelIa,GradeB).24e28 A lesion suspected to be melanoma, or where melanoma Organ transplant recipients are also at this level of needstobeexcluded,shouldbephotographed,andthen increasedrisk(LevelIII,GradeB).29,30 excised completely. The axis of excision should be 2. Those at greatly increased risk of melanoma (more orientated to facilitate possible subsequent wide local than10timesthatofthegeneralpopulation).Patients excision;generallyonthelimbthiswillbealongthelong withagiantcongenitalpigmentedhairynaevus(definiaxis. If uncertain, direct referral to the multidisciplinary tions include \u201820cm or more in diameter\u2019 and \u20185% of team (MDT) will allow appropriate planning for future bodysurfacearea\u2019)shouldbemonitoredbyanexpertfor surgery. The excision biopsy should include the whole theirlifetimebecauseoftheriskofmalignantchange, tumourwithaclinicalmarginof2mmofnormalskin,and whichissignificantbutpoorlyquantified(LevelIII,Grade acuffoffat.Thisallowsconfirmationofthediagnosisby B).31,32 Excision biopsy of suspicious areas in large examination of the entire lesion, such that subsequent congenitalnaevimaybenecessarybutrequiresexpert definitive treatment can be based on Breslow histopathological review. Patients with a strong family thickness.35e37 historyofmelanomaarealsoatgreatlyincreasedrisk.In Diagnosticshavebiopsiesshouldnotbeperformedsince some families, most clearly in mainland Europe and theymayleadtoincorrectdiagnosisduetosamplingerror, NorthAmerica,familiesatriskofmelanomaarealsoat and make accurate pathological staging of the lesion increasedriskofpancreaticcancer.33Thosewiththree impossible(LevelIII).Forthesamereasonspartialremoval ormorecasesofmelanomaorpancreaticcancerinthe ofnaevifordiagnosismustbeavoidedandpartialremoval family should be referred to appropriate clinics of a melanocytic naevus may result in a clinical and managing inherited predisposition to cancer (involving pathological picture very like melanoma (pseudomeladermatologists and/or clinical geneticists) for counselnoma).Thisgivesrisetoneedlessanxietyandisavoidable. ling. It is the consensus of the Melanoma Genetics Incisional or punch biopsy is occasionally acceptable, for Consortium(www.genomel.org)thatitisprematureto example in the differential diagnosis of lentigo maligna suggest gene testing routinely but this may change as (LM) on the face or of acral melanoma, but there is no moreisknownofthegenespredisposingtomelanoma.34 placeforeitherincisionalorpunchbiopsyoutsidetheskin Therisktofamiliesassociatedwiththepresenceoftwo cancer MDT (Level III). It is acceptable in certain circumfamily members affected with melanoma is lower. In stances to excise the lesion entirely but without repair, these families, if affected individuals also have the and to dress the wound while awaiting definitive atypical mole syndrome, or if there is a history of pathology. multipleprimarymelanomasinanindividualorpancreBiopsies of possible subungual melanomas should be atic cancer, then referral should also be made for carried out by surgeons regularly doing so. The nail should counselling;otherwisefamilymembersshouldprobably beremovedsufficientlyforthenailmatrixtobeadequately beconsideredatmoderatelyincreasedrisk. sampled: clinically obvious tumour should be biopsied if present.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 4}, {"text": "cancer, then referral should also be made for carried out by surgeons regularly doing so. The nail should counselling;otherwisefamilymembersshouldprobably beremovedsufficientlyforthenailmatrixtobeadequately beconsideredatmoderatelyincreasedrisk. sampled: clinically obvious tumour should be biopsied if present. Alloftheaboveindividualsatincreasedriskofmelanoma Prophylactic excision of naevi, or of small (<5cm shouldbeadvisedonthespecificchangesthatsuggestmeladiameter) congenital naevi in the absence of suspicious nomaandencouragedtoundertakemonthlyskinself-examifeatures is notrecommended (LevelIII, GradeD). nation(LevelIII,GradeB).Close-upanddistantphotography Full clinical details should be supplied on the histopamaybeausefuladjuncttodetectingearlymelanomaineither thology form, including history of the lesion, relevant of these high-risk groups (Level III). They should be given previous history, site and differential diagnosis. All melawritteninformationandaccesstoimagesofmolesandmelanocytic lesions excised for whatever reason must be sent nomas. Such images are available at: www.genomel.org or for histopathological review to the pathologist associated www.rcplondon.ac.uk/pubs/contents/f36b1656-cc74-4867with the LSMDTor SSMDT. Table3 Recommendationsforscreeningandsurveillanceofhigh-riskindividuals. (cid:1) Patientswhoareatmoderatelyincreasedriskofmelanomashouldbeadvisedofthisandtaughthowtoself-examine.This includespatientswithatypicalmolephenotype,thosewithapreviousmelanoma,andorgantransplantrecipients(LevelIa, GradeB). (cid:1) Patientswithgiantcongenitalpigmentednaeviareatincreasedriskofmelanomaandrequirelong-termfollow-up(Level IIIa,GradeB). (cid:1) Individuals with a family history of three or more cases of melanoma, or of pancreatic cancer, should be referred to aclinicalgeneticistorspecialiseddermatologyservicesforcounselling.Thosewithtwocasesinthefamilymayalsobenefit, especiallyifoneofthecaseshadmultipleprimarymelanomasortheatypicalmolephenotype(LevelIIa,GradeB).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 4}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1405 The diagnosis of melanoma, both in situ and invasive, melanomas (cid:3)1.0mm.40,41 It should be recorded as should be given or supervised by doctors who have number of mitoses per mm(cid:4)2 in the area of greatest received advanced communication skills training, number of mitoses in the vertical growth phase (VGP). following local policies for breaking bad news. A skin It has prognostic value at all thicknesses. cancer trained nurse should be present to provide continuing support. Histologic subtypes. Desmoplastic melanoma with or without neurotropism should be recorded because of its Histopathology different biological behaviour and clinical outcome.42 The subtypes superficial spreading, nodular, lentigo General comments maligna and acral lentiginous melanomas have good clinico-pathological correlation, but their prognostic value has not been established. TheRoyalCollegeofPathologistshasproducedaminimum dataset which should be included in the histopathology report.38 Double reporting is recommended for all melaMargins of excision. This indicates whether excision is completeandtheminimummarginofexcisiontoperipheral nomas and all naevi showing severe dysplasia if resources allowthis tobeachieved within14 days.5 and deep aspects measured in millimetres. If the excision or re-excision is not complete, whether the tumour is in situorinvasiveattheresectionmarginshouldbeindicated. The histopathology report Whenpossibleastatementshouldbemadeofwhetherthe lesion isprimary orsecondarymelanoma. The report shouldincludethe following: Pathologicalstaging.StagingusingTNMandAJCC(Table4), Clinical information andcoding, e.g.SNOMED, shouldbegiven.41 (cid:1) Site of thetumour Growth phase. Invasive melanoma without a vertical (cid:1) Type of surgical procedure: excision or re-excision, growth phase (VGP) is termed microinvasion.43 The incision biopsy,punch biopsy assessment of microstaging criteria should be applied to (cid:1) Anyotherrelevant clinicalinformation the VGPonly. Regression. The presence or absence of tumour regression Macroscopic description has not been shown consistently to affect long-term outcome. Until its relevance is clear it should be reported Contour,colourandsizeofthetumourandtheexcisedskin as segmental replacement of melanoma by fibrosis, since specimenin millimetres. thisis subjectto less observervariation.44 Microscopy Tumour infiltrating lymphocytes (TILs). It remains unclear whether TILs have prognostic value.40 The categories absent, non-brisk and brisk are subject to wide observer Presence or absence of ulceration. Ulceration has progvariation. \u2018Absent\u2019 indicates no lymphocytes infiltrating nostic value, and its presence should be confirmed microamong the tumour cells, but does not exclude scopically as full-thickness loss of epidermis with reactive lymphocytes in the surrounding dermis. \u2018Non-brisk\u2019 is changeswhichincludeafibrinousexudateandattenuation a patchy or discontinuous infiltrate either among the or acanthosis of the adjacent epidermis.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 5}, {"text": "does not exclude scopically as full-thickness loss of epidermis with reactive lymphocytes in the surrounding dermis. \u2018Non-brisk\u2019 is changeswhichincludeafibrinousexudateandattenuation a patchy or discontinuous infiltrate either among the or acanthosis of the adjacent epidermis. These distinguish peripheral cells or in the centre of the tumour, whereas true ulcerationfrom artefact.39 \u2018brisk\u2019 is a continuous infiltrate but may be confined to peripheral cells. These are qualified as mild, moderate or severein intensity. Thickness. The tumour should be measured from the granular layer of the overlying epidermis to the deepest cells in the dermis judged to be malignant, to the nearest Lymphatic or vascular invasion. Vascular or lymphatic 0.1mm. Ulcerated tumours should be measured from the infiltrationhasprognosticvalue,anditspresenceshouldbe base of the ulcer. Tumour forming a sheath around recorded eventhough itis infrequentlyobserved.45 appendages should be excluded when measuring thickness Perineural infiltration. Perineural infiltration occurring except when the melanoma extends out into the adjacent beyond the main bulk of the tumour correlates with reticular dermis when it should be measured in the increasedlocalrecurrence.Itismostcommonlyassociated conventional manner. In the presence of histological with desmoplastic melanoma.46 regression thickness measurements should be of the residual melanoma. Microsatellites should not be included Microsatellites. These are defined as islands of tumour inthickness measurements (LevelIII, GradeB). >0.05mm in the tissue beneath the main invasive mass of melanoma, but separated from it by 0.3mm of normal Mitotic count. The number of mitoses has prognostic collagen (i.e. not tumour stroma or sclerosis of regresvalue and is now included in the American Joint sion).47 Current AJCC staging also requires that satellites Committee on Cancer (AJCC) staging system for must be intralymphatic, which has not previously been", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 5}, {"text": "1406 J.R.Marsden etal. Table4 The2009AmericanJointCommitteeonCancer(AJCC)stagingsystem. Stage Primarytumour(pT) Lymphnodes(LN) Metastases(M) IA <1mm,noulceration,mitosis <1/mm(cid:4)2 IB <1mm,withulcerationor mitoses(cid:5)1/mm(cid:4)2* 1.01e2mm,noulceration IIA 1.01e2mmwithulceration 2.01e4mm,noulceration IIB 2.01e4mm,withulceration >4mm,noulceration IIC >4mm,withulceration IIIA AnyBreslow\u2019sthickness,no Micro-metastases1e3nodes ulceration IIIB AnyBreslow\u2019sthickness,with Micro-metastases1e3nodes ulceration AnyBreslow\u2019sthickness,no 1e3palpablemetastaticnodes ulceration AnyBreslow\u2019sthickness,no Nonodes,butin-transitor ulceration satellitemetastasis/es IIIC AnyBreslow\u2019sthickness,with Upto3palpablelymphnodes ulceration AnyBreslow\u2019sthickness,with 4ormorenodesormatted orwithoutulceration nodesorin-transitdisease \u00felymphnodes AnyBreslow\u2019sthickness,with Nonodes,butin-transitor ulceration satellitemetastasis/es IV,M1a Skin,subcutaneousordistal nodaldisease IV,M1b Lungmetastases IV,M1c Allothersitesoranyothersites ofmetastases withraisedlactate dehydrogenase *Intherarecircumstanceswheremitoticcountcannotbeaccuratelydetermined,aClarklevelofinvasionofeitherIVorVcanbeused todefineT1bmelanoma.EverypatientwithmelanomashouldbeaccuratelystagedusingtheAJCCsystem;thismayincludeperforming asentinellymphnodebiopsywhenthisisrecommendedbytheSpecialistSkinCancerMultidisciplinaryTeam.Stagingshouldbeupdated followingrelapse. required; this may be subject to revision. Microsatellites Equivocal lesions are predictive of regional lymph node metastases; this is reflectedby stage N2c. Itmaynotbepossibletodistinguishpathologicallybetween amelanomaandabenignmelanocyticlesion.Suchpatients Precursornaevus.Thepresenceofcontiguousmelanocytic mustbereferredtotheSSMDTforclinicalandpathological naevusshouldberecorded. review.Adecisiontotreatasamelanomashouldbemade by the SSMDT in discussion with the patient. Thickness Clark level of dermal invasion. This is a less reliable indishould bemeasuredasfor melanoma. cator of prognosis than thickness and is subject to poor observeragreement.ItisnotusedtodefineT1melanomas Sentinel lymph node pathology inthe2009AJCCstagingsystem,exceptthatClarklevelsIV or V may be used for defining T1b melanoma in rare Pathological assessment instances when mitotic count cannot be determined in Thisneedstobedoneinastandardisedwaysothatfindings anon-ulcerated T1 melanoma. betweencentresarecomparable(LevelIII,GradeB). Requirements for microscopy of melanoma Dissection The dissection should be either by bivalving or multiple ThesearegiveninTable5. slicing, although the former is recommended.48e50", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 6}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1407 sentinellymphnodesand/ordistantmetastasesinpatients Table5 Requirementsformicroscopyofmelanoma. with primarymelanoma 53e58(Level IIa,GradeE). (cid:1) Ulceration (cid:1) Growthphase (cid:1) Thickness (cid:1) Regression Sentinel lymph node biopsy and ultrasound/fine (cid:1) Mitoticcounta (cid:1) Tumour-infiltrating (cid:1) Histologicsubtype lymphocytes needle aspiration cytology (cid:1) Marginsofexcision (cid:1) Lymphaticor (cid:1) Pathologicalstaging vascularinvasion Sentinel lymph node biopsy (SLNB), as discussed later, has (cid:1) Perineuralinvasion high sensitivity and specificity for diagnosing subclinical (cid:1) Microsatellitesb regionallymph node involvement. Ultrasoundandfineneedleaspirationcytology(FNAC)is a Mitoticcountisincludedinthe2009AJCCstagingsystem. the next best method but quoted sensitivities range from b Microsatellitesarenotincludedinthicknessmeasurement. 4.7% to 80%, with the higher sensitivities being achieved only by sentinel node mapping and FNAC of the sentinel node in all cases regardless of morphological appearA minimum of six serial sections should be taken, but ance.59e62 Further staging by CT imaging following a posia higher incidence of metastases is detected by extended tive sentinel lymph node, and prior to completion step sectioning with immunohistochemistry at each level. lymphadenectomy,hasaverylowyield.63e65Consequently The clinical relevance of the smaller metastases detected this should be done only after discussion with an informed by theseextended proceduresisstill unclear. patient andthe SSMDT(LevelIIa, GradeD). Staining Stage III and IV melanoma Use of haematoxylin and eosin and immunohistochemistry is essential. S100 and Melan A are most favoured immunoIn stage III and IV melanoma, imaging strategies will be histochemical stains but a composite method such as Panplannedby the SSMDT. Melis alsoappropriate. CTscanningofthehead,chest,abdomenandpelviswill normally adequately exclude metastases, and is most Assessment oftumour burden relevant in stage III melanoma before planning regional Thisgivesadditionalprognosticinformation.Thefollowing lymph node dissection and regional chemotherapy. If arerecommended: patients are considering entry to an adjuvant study Assessing the depth of the metastasis from the inner followinglymphadenectomy,the timingofscansshouldbe aspectofthesentinellymphnodecapsule;categorisingthe determinedby the SSMDT to avoidduplication. metastasis according to its site, either subcapsular or When stage IV disease is suspected clinically, CT scanparenchymal; measuring the maximum dimension of the ning of the head and whole body should be considered. largest confluent groupof melanoma cells.50e52 Further imaging will be determined by symptoms, clinical trial protocols, and for clarification or reassessment of Completion lymphadenectomy specimens previous imaging findings. Generally, the added yield of The pathological examination of regional nodes dissected PET/CT is unlikely to be clinically relevant in established following positive sentinel lymph node biopsy should stage IV melanoma (Level III, Grade D).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 7}, {"text": "yield of The pathological examination of regional nodes dissected PET/CT is unlikely to be clinically relevant in established following positive sentinel lymph node biopsy should stage IV melanoma (Level III, Grade D). Where metainclude an attempt to examine all lymph nodes at least at stasectomy is planned, PET/CT may be useful in excluding onelevel,andcountthenumberinvolved.Thepresenceof disease that might make surgery inappropriate. Serum extracapsular spread and involvement of perinodal fat lactatedehydrogenase(LDH)shouldbedoneinallpatients should be recorded, together with the size of the tumourwith suspectedstage IVmelanoma. freemargin.TheuseofimmunohistochemistrysuchasS100 There is no indication for a bone scanin staging except orMelan Afacilitates this. where symptoms point to possible bone disease. Staging investigations aresummarisedin Table6. Investigations and imaging Treatment of the primary lesion Stage I and II melanoma Surgery is the only curative treatment for melanoma. Routine investigations are not required for asymptomatic Following excision for diagnosis and for measurement of patientswithprimarymelanoma.Bloodtestsareunhelpful. microscopic Breslow thickness, a widerand deeper margin Routinecomputedtomography(CT)isnotrecommended istakentoensurecompleteremovaloftheprimarylesion, forpatientswithstageIandIImelanomaasthishasavery and to remove any micro metastases. The depth of the low incidence of true-positive and high incidence of falsetherapeuticexcisionhasconventionallybeentothemuscle positive findings. Patients with particularly high-risk fascia or deeper, and there is no evidence to support primary melanoma may undergo staging investigations if alteringthis approach. deemedappropriatebytheSSMDTand/orasapre-requisite Lateral surgical excision margins for invasive melanoma to trial entry. There is no indication for routine imaging depend on Breslow thickness and are based on five randowith any other modality including plain X-ray, position mised controlled trials (RCTs) including about 3300 emission tomography (PET)/CT and magnetic resonance patients, and a National Institutes of Health Consensus imaging(MRI).PET/CTisnoteffectiveindetectingpositive Panel.66e73 However, only one of these studies is", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 7}, {"text": "1408 J.R.Marsden etal. difficult to detect. Topical treatment with imiquimod is Table6 Staginginvestigationsformelanoma. as yet of unproven value so should only be used in the (cid:1) Patients with stage I, II,and IIIA melanoma should not context of a clinical trial.82 If the patient with LM is routinelybestagedbyimagingorothermethodsasthe treated by non-surgical means then the reason for this truepositivepick-uprateislowandthefalse-positive choice should be discussed and clearly documented by rateishigh(LevelIIa,GradeE). the MDT. (cid:1) PatientswithstageIIIBorCshouldbeimagedbyCTof LocalrecurrenceofLMoccursinabout5%ofpatientsby head,chest,abdomenandpelvispriortosurgeryafter 2 years.77 Excision with micrographic control of surgical SSMDTreview(LevelIIa,GradeA). margins should be considered, although histological clear- (cid:1) Patients with stage IV melanoma should be imaged anceisoftendifficulttodefine.83Insitumelanomaonacral accordingtoclinicalneedandSSMDTreview.Lactate andgenitalskinisalsoassociatedwithahigherriskoflocal dehydrogenaseshouldalsobemeasured(LevelIII, recurrence,butthisislesscommoninothertypesofinsitu GradeA). melanoma. In theory, in situ melanoma should not metaSSMDT,SpecialistSkinCancerMultidisciplinaryTeam. stasise, but occasional cases do recur. This may be due to histological regressionobscuring a more advanced tumour, missed microinvasion, or progression after incomplete removal of insitu disease. adequately powered, and two provide little scope for detecting reduced disease-free or overall survival due to narrowmargins.68,69,71Mostexcludemelanomaonthehead Melanoma up to 1.0mm Breslow thickness andneckand/orextremities.74Arecentsystematicreview estimated overall survival in favour of wide excision There have been three RCTs of patients with melanomas (hazard ratio 1.04; 95% confidence interval 0.95e1.15; inthisthicknessband.66,68,69,73 Therecommendedsurgical PZ0.40), although the difference was not significant. margins are based on the World Health Organisation Thereforeasmall,butpotentiallyimportant,differencein (WHO) Melanoma Co-operative Group Trial 10.66,73 This overallsurvivalbetweenwideandnarrowexcisionmargins randomised trial compared 1cm and 3cm margins for cannot be confidently ruled out. Current randomised trial melanomas up to 2mm thick. No local metastases, and evidenceisinsufficienttoaddressoptimalexcisionmargins similar overall survival, were seen in patients with melaforprimary cutaneous melanoma.75 nomas < 1mm in depth with either excision margin. The recommended surgicalmargins arethosemeasured However, this was based on analysis of data from only 359 clinically at the time of surgery, but adequacy of excision patients. The French and Swedish studies compared 2cm shouldbe subsequentlyconfirmed by review of re-excision with 5cm margins, and the latter only included patients histology, making an adjustment for average shrinkage of with melanomas 0.8mm or more in thickness in this 20%.76Thefinaldecisionaboutthesizeofthemarginshould group.68,69 A 1cm margin is deemed safe for this group bemadebytheMDT,afterdiscussionwiththepatient.The (Level Ib, Grade A). recommendation should be made with consideration of functionalandcosmeticimplicationsofthemarginchosen. Melanoma 1.01e2.0mm Breslow thickness All patients with primary melanoma stage IB and higher shouldbereferredbeforetreatmenttoanSSMDTwhenthis There have been four randomised studies that have providesaSLNBservice.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 8}, {"text": "Grade A). recommendation should be made with consideration of functionalandcosmeticimplicationsofthemarginchosen. Melanoma 1.01e2.0mm Breslow thickness All patients with primary melanoma stage IB and higher shouldbereferredbeforetreatmenttoanSSMDTwhenthis There have been four randomised studies that have providesaSLNBservice.WhentheSSMDTdoesnotprovide included patients in this category. The WHO study showed this, all primary melanomas stage IIB or IIC should be a small excessof localmetastasis asfirst siteof relapse in referred. There are no RCT data for margin size for LM or the 1cm margins group.66,73 There was no difference in otherin situmelanoma. overall survival between 1 and 3cm margins but the study was inadequately powered to detect this. The Intergroup Lentigo maligna and in situ superficial MelanomaTrialcompared2vs.4cmmarginsofexcisionfor spreading melanoma lesionsof1e4mminthickness.67,70Nodifferencewasseen between the two groups in either local recurrence or LM and other in situ melanomas have no potential for survival. Two other studies have included patients with metastatic spread and the aim should be to excise the melanomas up to 2mm, also treated with either 2or 5cm lesioncompletelywithaclearhistologicalmargin,although margins.68,69Therewasnodifferenceinoutcomebetween margin size remains undefined. No further treatment is the groups. The 1 vs. 3cm, 2 vs. 4cm, and 2 vs. 5cm thenrequired. studies cannot be directly compared, but no study using LM is best treated by complete excision because of 2cm margins as one comparator has shown any advantage the risk of subclinical microinvasion. This may be missed of wider margins than this. However, narrower margins on incisional biopsy due to sampling error.73 The risk of trials have either not been performed (e.g. 1vs. 2cm progression to invasive melanoma is poorly quantified, margins) or have been underpowered, and do not permit and in the very elderly may be unlikely within their a definite conclusion that a 1cm margin is adequate. lifespan. Therefore, for some particular clinical situaEvidence to date shows that a minimum margin of 1cm is tions, treatment by other methods such as radiotherapy, required, although 2cm margins are equally appropriate. or observation only, may be appropriate.77e81 There is The final decision will be determined by anatomical site, little evidence to support the use of cryotherapy, and MDTreview, and after discussion with an informed patient this treatment may make subsequent progression (Level Ib,GradeA).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 8}, {"text": "MDTreview, and after discussion with an informed patient this treatment may make subsequent progression (Level Ib,GradeA).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 2, "page": 8}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1409 Melanoma 2.01e4.0mm Breslow thickness surgical treatment planning and investigations can run in parallel. There is no place for elective lymph node dissecThe Intergroup Melanoma Trial showed no difference in tioninthemanagementofprimarymelanomaunlessthisis rates of local metastasis between patients treated with unavoidable because the primary melanoma lies over the 2cm and those treated with 4cm margins.67 However, lymphnodebasin(LevelIb,GradeA).Patientsshouldhave longer follow-up showed reduced overall survival in the access to a skin cancer specialist nurse when relapse is 2cmmarginsgroup,althoughthisfelljustshortofreaching suspected. statistical significance.70 The results of a randomised trial with 3cm margins showed significantly increased rates of Clinically node-negative patients locoregional recurrence in patients treated with 1cm margins, and a reduction in melanoma-specific survival, SLNB was developed as a means of identifying the first again just short of significance, although no difference in lymph node draining the skin in which the melanoma arioverall survival.71 The significance of this is unclear, and ses.84 The procedure is carried out at the same time as the 2 vs. 4cm and 1 vs. 3cm trials cannot be directly definitive wider excision of the primary melanoma.85 SLNB compared. Until the resulting uncertainty is resolved, givesinformation aboutprognosis,andisincreasinglyused which may not happen as the number of patients required in conjunction with adjuvant therapy clinical trials. to detect a difference between 2 and 3cm margins is Patients with melanoma of Breslow thickness 1.2e3.5mm considerable, the default position should be to minimise and a positive SLNB have a 75% 5-year survival compared locoregional and distant metastatic risk. Therefore with 90% if the SLNB is negative.86 SLNB is normally aminimum2cmmarginisrequired inthisgroup,although considered for patients with melanoma (cid:5)1mm, when 3cm margins are equally appropriate. The final decision about20%arepositive;howevertheriskofapositiveSLNB will be determined by anatomical site, need for skin in a melanoma <1.0mm is still 5%.86,87 The procedure is grafting,MDTreview,andafterdiscussionwithaninformed associatedwitha5%morbidity,whichislessthanthatseen patient (LevelIb, GradeA). withcompletenodaldissection.Inpatientswithapositive SLNB, 20% have pathological evidence of metastases in Melanoma greater than 4mm in thickness additional regional nodes.84 Patients with a positive SLNB usually choose to proceed to completion lymphadenecTheriskoflocoregionalanddistantmetastasisis50%ormore tomy.Inabout5%itisnotpossibletoidentifythesentinel inthisgroup.Nonetheless,thesamesurgicalobjectivesapply node either on lymphoscintigraphy, at surgery, or both. tominimiselocoregionalanddistantmetastaticrisk.Thereis Patients should be aware of this limitation. The relevance onlyonerandomisedstudywhichincludesmelanomasthicker ofincreasinglydetailedevaluationofthesentinelnodeand than4mm.71Thistrialcompared1cmwith3cmmargins.The its correlation with prognosis remains to be defined.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 9}, {"text": "at surgery, or both. tominimiselocoregionalanddistantmetastaticrisk.Thereis Patients should be aware of this limitation. The relevance onlyonerandomisedstudywhichincludesmelanomasthicker ofincreasinglydetailedevaluationofthesentinelnodeand than4mm.71Thistrialcompared1cmwith3cmmargins.The its correlation with prognosis remains to be defined.88 resultsshowasignificantincreaseinlocoregionalrecurrence MSLT-1 showed no overall 5-year survival benefit following when1cmmarginsareused,andareductioninmelanomaSLNB and completion lymphadenectomy, and it is unclear specific survival just short of significance, although no whether SLNB improves local control of lymph node difference in overall survival. As there are no data that basins.85,86Afinalreportwithlongerfollow-upisawaited. margins smaller than 3cm are as effective, the evidence Recommendations for the management of clinically suggests3cmmarginsforthisgroup.Thereisnoevidencethat node-negative patients aresummarised inTable8. marginsgreaterthan3cmarerequired.Thefinaldecisionwill bedeterminedbyanatomicalsite,needforskingrafting,MDT Management of patients with clinically or review,andafterdiscussionwithaninformedpatient(Level radiologically suspicious lymph nodes Ib,GradeB). Recommendedsurgicalexcisionmarginsaresummarised FNACofnodesisrecommendedwhenthereisclinicaldoubt inTable 7. about the significance of the nodes. If there is a negative FNACresultbutongoingsuspicion,thentheFNAshouldbe Management of lymph node basins repeated oranimage-guided core biopsy arranged. Open biopsy is recommended when there is clinical Investigation and management of lymph node basins in suspicion even in the presence of negative FNACs in which melanomapatientsshouldbecarriedoutbySSMDTssothat lymphocytes have been successfully aspirated. If open Table7 Recommendedsurgicalexcisionmargins. Breslowthickness Excisionmargins Levelofevidence Gradingofevidence Insitu 5mmmarginstoachieve III B completehistological excision <1mm 1cm Ib A 1.01e2mm 1e2cm Ib A 2.1e4mm 2e3cm Ib A >4mm 3cm Ib B", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 9}, {"text": "1410 J.R.Marsden etal. (cid:1) A single positive superficial inguinal sentinel node Table 8 Recommendations for the management of clini- (Level Ib,GradeA). callynode-negativepatients. (cid:1) There is no role for elective lymph node dissection ApelvicLND shouldbeconsidered inthe presenceof: (LevelI,GradeE) (cid:1) Sentinel node biopsy can be considered in stage IB (cid:1) More than one 1 clinically palpable inguinal and/or melanomaandupwardsinSSMDTs(LevelIa,GradeA) femoral triangle node/s (cid:1) PatientsshouldbeintroducedtotheconceptofSLNBas (cid:1) CT or ultrasound evidence of more than one inguinal astagingprocedurebutshouldalsounderstandthatit and/or femoral triangle node/s, or of pelvic node hasnoproventherapeuticvalue involvement (cid:1) Surgical risks of SLNB, the possibility of failure to find (cid:1) More than onemicroscopicallyinvolved nodeat SLNB aSLN,andofafalse-negativeresult,shouldalsobe (cid:1) A conglomerate of inguinal or femoral triangle lymph explained nodes SNLB,sentinellymphnodebiopsy (cid:1) Microscopic or macroscopic involvement of Cloquet\u2019s node (Level III,GradeB). biopsy is performed, the incision must be such as to allow Cervical nodal recurrence should be treated by either subsequent complete formal block dissection of the surgeons in the SSMDT specialising in head and neck skin regionalnodeswithoutcompromise.Itshouldonlybedone cancerincludingmelanomaorbyaheadandneckMDTwith bySSMDT members.5 aspecialinterestinmelanoma.5Acomprehensive,andnot Exploration or removal of a mass within a nodal basin aselective,neckdissectionshouldbeperformed(LevelIII, which drains a known primary melanoma site, and prior to GradeA). The term\u2018comprehensive\u2019 allows either: definitive surgical treatment, may increase the risk of melanomarecurrenceinthatbasin.89Anymelanomapatient (cid:1) A radicaldissection of levels1e5 who develops a mass in a nodal basin should be referred (cid:1) Modified radical e the above, sparing spinal accessory urgently to the SSMDT, and without prior investigation, for nerve, internal jugular vein and sternocleidomastoid investigationandtreatmentplanning(LevelIII,GradeB). muscle (cid:1) Extendedradicaleradicaldissectionincludingparotid Management of patients with confirmed and/or posterior occipital chain. positive lymph node metastasis The risk of further locoregional recurrence is 16e32% despite comprehensive surgery.101,102 Radical lymph node dissections (LNDs) should only be performedbySSMDTmemberswhodoacombinedminimumof Locoregional recurrent melanoma: skin 15axillaryandgroinblockdissectionsforskincancereach year.5,90 and soft tissues Preoperativestaginginvestigationsshouldbecarriedout asalreadydiscussedforstageIIImelanoma.Ifsuchstaging Surgery is the treatment of choice for single local or is not feasible prior to surgery, and surgery is considered regional metastases. Excision should be clinically and necessary even if distant metastatic disease were to be histologically complete, but a wide margin is not detected,thena chestX-rayandLDH isrecommended. required. Multiple small (<1cm) dermal lesions respond The block dissection specimen should be marked and well to treatment with the CO laser.103 Dermal disease 2 orientated for the pathologist.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 10}, {"text": "dermal lesions respond The block dissection specimen should be marked and well to treatment with the CO laser.103 Dermal disease 2 orientated for the pathologist. Axillary LND for melanoma which is progressing despite surgery or laser, and shouldincludeallnodesinlevelsIeIII,andthismayrequire subcutaneous or deeper limb metastases, should be either resection or division of pectoralis minor. The considered for regional chemotherapy with isolated limb management of inguinal lymph node metastases is controinfusion (ILI) with melphalan and actinomycin D, or with versial. Between 30% and 44% of patients with clinically isolated limb perfusion (ILP) 104,105 (Level IIb, Grade B). involvedsuperficialinguinalnodeswillhaveinvolvedpelvic ILI is less invasive than ILP, and can be more easily nodes, and the risk increases with the number of involved repeated, but may be less effective.105 ILI is suitable for superficialnodes.91e97IfCloquet\u2019snodeispositivetherisk patientswithlowvolume(<5cm)diseaseandthosewith of pelvic node involvement ranges from 44% to 90%.93,96,97 co-morbidities which prevent ILP. Patients with bulky There is no reported increased morbidity associated with disease (>5cm) may be more likely to benefit from ILP combined pelvic and superficial node dissection.94 using melphalan with tumour necrosis factor, but Following ilioinguinal dissection for palpable inguinal arecenttrialcomparingthiscombinationwithmelphalan disease 5-year survival varies with extent of pelvic alone did not confirm additional benefit from adding involvement: 49% with one pelvic node, 28% with two to TNF.106 Radiotherapy may be considered for disease threenodes, and7% with morethan threenodes.97e100 which cannot otherwise be controlled. Selected patients suitable for ILI/ILP should be referred to specialised A superficial inguinal LND should be considered in the centres. The role of electrochemotherapy using intralepresenceof: sional or systemic bleomycin is still being evaluated. (cid:1) A single clinically involved inguinal node or femoral Recommendations for locoregional recurrent melanoma trianglenode are given in Table 9.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 10}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1411 lymphadenectomy.110Eligiblepatientswere(cid:5)1parotid,(cid:5)2 Table 9 Recommendations for locoregional recurrent cervicaloraxillaryor(cid:5)3groinnodes,orextranodalspread melanoma. of tumour, or node diameter (cid:5)3cm in neck or axilla or (cid:1) Nodes clinically suspicious for melanoma should be (cid:5)4cminthegroin.Interimresultsshowa15%improvement sampledusingfineneedleaspirationcytology(FNAC) in local control following radiotherapy, but there was no priortocarryingoutformalblockdissection.IfFNACis effect on overall survival. There are no data yet on negativealthoughlymphocyteswereseen,acoreor morbidity following this treatment, and so at present the openbiopsyshouldbeperformedifsuspicionremains risk:benefit of adjuvant radiotherapy is unclear. If there is (LevelIII,GradeB) clinicalorhistologicaldoubtabouttheadequacyofsurgery (cid:1) Prior to lymph node dissection, performed by an following recurrence, or about the feasibility of salvage expert,5stagingbyCTscanshouldbecarriedoutother surgery, adjuvant radiotherapy may be considered by the thanwherethiswouldmeanunduedelay(LevelIII, SSMDT (LevelIb,GradeB). GradeB) (cid:1) The treatment of locoregional recurrence in a limb is Occult primary melanoma palliative.Surgicalexcision,CO laser,orisolatedlimb 2 infusionorperfusionmaybeconsidered(LevelIIb, GradeB) Patients with occult primary melanoma may present with a solitary metastasis, lymph node disease, or systemic disease. Such patients should be referred promptly to the SSMDT for investigation and treatment planning. All Adjuvant therapy patients should have a thorough examination of the skin. Occultprimaryuvealtractmelanomanearlyalwayscauses There is no evidence of a survival benefit for adjuvant liver metastases before these are apparent at other sites; chemotherapy inpatients with melanoma.107 Thisincludes searchingforauvealtractprimaryinapatientwithoccult adjuvant regional chemotherapy using ILP, and therefore nodal disease is not appropriate. For patients presenting ILI.108 withinguinallymphadenopathy,examinationofthegenital Interferon has been evaluated in low-, intermediateand urinary tracts, and ano rectum is especially relevant. andhigh-riskpatientsusingvariousdosesandschedules.A AllpatientsshouldbestagedwithCTscansofhead,chest, recent individual patient data meta-analysis concluded abdomenandpelvis.Anumberofreportsfrominstitutionthatinterferonwasassociatedwithasignificantimpacton basedseriessuggestthatpatients presentingwithstage III relapse-free survival and a small effect on overall survival disease from an unknown primary have a better prognosis (5-year survival benefit 3%, P<0.05).109 However, the than patients with a similar stage and a known benefit was seen across all interferon regimens, and was primary.111,112 One published series suggested a survival greatestinthosewithulceratedmelanomas.Therewasno advantage in patients with stage IV disease from an clearindicationastooptimumdoseorduration.Theresults unknown primary compared with those with a declared areawaitedoffurtheranalysisincludingmorerecentdata. primary.113 Interferon is not recommended as standard of care for Patients presenting with lymph node disease from an adjuvant therapy of primary or stage III melanoma (Level occult primary involving a single lymph node basin, should Ia, Grade A).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 11}, {"text": "primary involving a single lymph node basin, should Ia, Grade A). This is because its effect on disease-free be presumed to have regional rather than distant metassurvival is of uncertain clinical relevance, and although tasis, and treated as for stage III disease with lymph node overall survival is improved in meta-analysis, the effect is blockdissection. small and associated with significant drug toxicity. Prospective studies are required to establish whether Metastatic disease a subset of patients who derive most benefit can be identified. All patients should have access to a skin cancer clinical Clinical trials of adjuvant melanoma vaccines have not nurse specialist and a palliative care team providing so farbeensuccessful. expertise in symptom control and psychosocial support. Patients should be offered entry into adjuvant clinical Links should be made with community cancer support trials approved by the local Cancer Network. They should networks as soon as possible. All patients with metastatic have access to a melanoma specialist who is conversant disease should have access to an oncologist specialising in with currentmelanoma adjuvant trials, and whois ableto melanomafor managementadvice. ensuretheiraccesstosuchstudies.Detailsmaybefoundon Selected patients who relapse with oligometastatic thewebsitesoftheNationalCancerResearchNetwork,and disease may benefit from metastatectomy. Although this the European Organisation for Research and Treatment of has not been evaluated in a prospective randomised trial, Cancer. mediansurvivalof21monthsforselectedsurgicallytreated patients hasbeen reported114e119 (Level IIb,GradeB). Adjuvant radiotherapy No systemic therapy has been shown to extend survival significantly. Dacarbazine is a standard chemotherapy The Tasmanian Radiation Oncology Group (TROG) has outside a clinical trial, although its benefits are limited, completedarandomisedstudyofadjuvantradiotherapyto anditisineffectiveinbrainmetastases(LevelIIa,GradeC). dissectednodalbasins,48Gyin20fractions,in250patients The oral dacarbazine derivative temozolomide has greater with a high (>25%) risk of local recurrence following central nervous system (CNS) penetration but has not", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 11}, {"text": "1412 J.R.Marsden etal. shown significant clinical advantages over dacarbazine in Thereisnomedicalreasontojustifydelayingconception twomulticentreclinicaltrials.120,121Biochemotherapy(the afteradiagnosisofmelanoma(LevelIIa)butthesocialand addition of biologically active agents such as interferonfamily effects of developing recurrent melanoma during a and interleukin-2 to chemotherapy) increases response pregnancy or after birth are great.127,130 It is proper thereratesandtoxicitybutdoesnotsignificantlyincreaseoverall foretocounselawomaninthereproductiveagerangeabout survival.122 The same is true for combination chemoherriskofrecurrenceovertimesothatsheandherpartner therapy, and so this is not recommended other than in can make their decision about conception with adequate highly selected patients in whom palliation is dependent information. These social or familyconsiderations may also upon maximising response in symptomatic deposits. High berelevanttoamalepatientwhosepartnerispregnantorif doseinterleukin-2hasnotbeenevaluatedinarandomised heandhispartnerareconsideringapregnancy. phase III trial although a small minority of patients may There is no evidence that the use of the oral contraexperiencedurable completeresponses.123 ceptive pill plays any role in the natural history of melaPatientswithelevatedLDHhaveareducedlikelihoodof noma (Level Ia).130e133 Decisions about the use of the benefiting from currently available systemic treatment. contraceptive pill should be made on the basis of health Giventhelimitedbenefitswithstandardsystemictherapy, issues otherthan melanoma. all patients with metastatic melanoma should be considThereisnoevidencethathormonereplacementtherapy eredforentry into clinicaltrials of novel therapies. plays any role in the natural history of melanoma,130,132 Patients with CNS metastases have a poor prognosis. neither does it worsen prognosis in stage I and II melaSurgeryorstereotacticradiotherapyshouldbeconsidered noma (Level IIa).133 Decisions about use of hormone for selected patients with limited disease.114,115,124e126 replacementtherapyshouldbemadeonthebasisofhealth The benefits of treating patients with cerebral metasissues otherthan melanoma. tases with whole brain radiotherapy are limited, but may In pregnancy, staging using X-rays should be avoided sometimes have palliative value. Supportive care is wherepossible,especiallyinthefirsttrimester.MRIshould thereforethemostappropriatestrategyformanypatients beused inpreference to CTscan,wherefeasible. (Level IIb, Grade B). Because chemotherapy does not have a survival benefit Spinal cord compression should be treated surgically if in stage IV disease its use in pregnancy requires careful feasible, but multiple sites of disease, poor prognosis and discussion. Use of chemotherapy agents in the first poor performance status may make this inappropriate. trimestershouldbeavoided.Therearecasereportsofthe Radiotherapy may be useful for palliation of rapidly successful birth of normal babies who were exposed to enlarging or painful metastases involving soft tissues and dacarbazine in utero later in pregnancy, but this does not bones(LevelIIb,GradeB). exclude later toxicity. Melanoma can metastasise to the Recommendations for metastatic disease are shown in placenta and to the fetus more frequently than any other Table10. solidtumour.Thishasapoorprognosisforbothmotherand baby.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 12}, {"text": "later in pregnancy, but this does not bones(LevelIIb,GradeB). exclude later toxicity. Melanoma can metastasise to the Recommendations for metastatic disease are shown in placenta and to the fetus more frequently than any other Table10. solidtumour.Thishasapoorprognosisforbothmotherand baby. At delivery in patients with stage IV melanoma the Melanoma, hormone replacement therapy placenta should beexamined formelanoma. Recommendations regarding pregnancy and hormone and pregnancy replacement therapy aresummarisedin Table11. Thereisnoevidencethatmelanomaatornearthetimeof Use of drugs in melanoma patients pregnancy adversely affects prognosis.127 Breslow thickness, site and presence of ulceration are still the key determinants of outcome, and are not different from There are theoretical reasons to suggest that L-DOPA may have an adverse effect on patients with melanoma. There acontrolpopulation.128,132Theoutcomesofpregnancyfor are no data to support this idea however, and such an bothmotherandbaby arenotworsened(LevelIIa).128,129 association seems unlikely.134 The use of immunosuppresSurgical treatment should be determined in the normal santsaftermelanomaisacauseforconcern.Theresultsof way,buttherisksofexposuretoionisingradiationandblue a recent cohort study of patients with rheumatoid arthritis dye during sentinel node biopsy will need special consideration. Table 11 Recommendations regarding pregnancy and Table10 Recommendationsformetastaticdisease. hormonereplacementtherapy. (cid:1) All patients should be managed by Specialist Skin Pregnancywithprimarymelanoma CancerMultidisciplinaryTeams.5 (cid:1) Noworseningofprognosis (cid:1) Surgery should be considered for oligometastatic (cid:1) No increase in adverse outcomes for mother or baby diseaseatsitessuchastheskin,brainorbowel(Level Pregnancyinadvancedmelanoma IIb,GradeB),ortopreventpainorulceration. (cid:1) Placental and fetal metastases possible in stage IV (cid:1) Radiotherapy may have a palliative role in the treatdisease mentofmetastases(LevelII,GradeB). Oralcontraceptivesandmelanoma (cid:1) Standardchemotherapyisdacarbazinealthoughitsrole (cid:1) Noincreasedriskofmelanoma ispalliative(LevelII,GradeC). Hormonereplacementtherapy (cid:1) Patients withstageIV melanomashould beconsidered (cid:1) Noincreasedriskofmelanoma forentrytoclinicaltrials. (cid:1) Noworseningofprognosis", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 12}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1413 treated with biologic agents showed an increased risk of Care can be shared with primary care, but only if the melanoma (odds ration 2.3, 95% confidence interval secondarycareteamhasdefinedandexplainedtotheprimary 0.9e5.4).135However,thereisusuallylittlethatcanbedone careteamwhatisrequired,andonlyiftheprimarycareteam toavoidthesedrugswithoutanunacceptablelossofquality arepreparedtoacceptresponsibilityforthis.Intheeventof of life. Their use after treatment of primary or secondary suspectedrecurrence,evenafterdischargefromfollow-up,it melanoma should be discussed between the prescribing isrecommendedthatthepatientcontactthesecondarycare doctorsandpatients,andthedecisiontocontinuetheiruse teamdirectlytoavoidpossibledelayindiagnosis. and their dosage should be subject to ongoing review Screening asymptomatic clinically normal patients with followingadiagnosisofmelanoma(LevelIII,GradeC). lymph node ultrasound is sensitive and can detect nodal disease,butthishasnotbeenshowntobeusefulinprimary Organ and blood donation melanoma follow-up.142 The same applies to CT and PET imaging. These investigations should not be used outside Thedecisionaboutwhetherorgansortissuearesuitablefor a clinicaltrial. transplant is made on an individualised basis, taking into account the patient\u2019s medical history.136 A melanoma In situ melanoma patient wouldnotnormally beconsidered asa donor. Patients with a surgically treated single in situ melanoma Follow-up do not require follow-up, as there is no risk of metastasis. They require a return visit after complete excision to Therearethreemainreasonsforfollow-upaftertreatment explain the diagnosis, cheque the whole skin for further of primary cutaneous melanoma. The first is to detect primary melanoma/s, and to teach self-examination for recurrence when further treatment can improve the proga new primary melanoma. Clinical nurse specialist support nosis, the second is to detect further primary melanomas mayberequired despite the absenceof metastaticrisk. and the third is to provide support, information, and education. Theproportionof patientswith melanomawho Stage IA melanoma have impaired health-related quality of life is comparable to other cancers, and their needs for psychosocial support Patients with invasive primary cutaneous melanoma are likely to be similar.137 Provision of this is an important <1.0mmhavea5-yeardisease-freesurvivalofover90%or partofMDTmanagement.138TherearenoRCTswhichhave better. A recent review of 430 patients with melanomas formally evaluated follow-up. Numerous follow-up regi- <0.5mm showed no recurrences at 5e15 years follow-up mens have been reviewed but few are evidencebut 4% of patients developed a second primary melanoma based.139e141 Sixty-two percent of all recurrences were over this period.143 Patients with invasive, non-ulcerated detected by patients themselves in one review, but defiprimarytumours0.5e1.0mmthickhaveonlyslightlyworse nition of patient or doctor detection is unclear and other 5-year disease-free survival, and are in the same stage series emphasise the importance of physician-detected group. Therefore, for stage IA patients a series of two to recurrence.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 13}, {"text": "detection is unclear and other 5-year disease-free survival, and are in the same stage series emphasise the importance of physician-detected group. Therefore, for stage IA patients a series of two to recurrence.134 Patient opinion was equally divided as to fourvisitsoverupto 12monthsissuggested toteachselfwhether follow-up visits were reassuring or provoked examination,andthentheymaybedischargedfromregular further anxiety. There is little evidence of survival advanfollow-up (LevelIII, GradeB). tage following self-detection of metastases.139e141 Most first relapses occur in the 5 years following diagnosis, but Stage IB and IIA melanoma thereisasignificantriskoflaterfirstrelapse;bothpatients andtheirdoctors shouldbeaware of this. This group are at 15e35% risk of recurrence, but most of A primarymelanoma follow-up clinic shouldbeprovided thisriskisinyears2e4.OncetheyhavelearnthowtoselfbyanMDTofdermatologistsandsurgeonswithclinicalnurse examine for locoregional metastasis and new primaries, specialist support, and there should be continuity of care. andunderstandhowtopromptlyaccessthefollow-upteam Patientsshouldbetaughttoself-examinetodetectlocorefor suspected recurrence, they should be seen every 3 gionalrecurrenceandnewprimarymelanoma.Photography months for 3 years, then 6-monthly to 5 years. No routine canbeuseful for follow-upofpatientswho also haveatypinvestigations arerequired(Level III,GradeB). ical moles. Patients should routinely be examined for locoregional and distant metastases, and the whole skin Stage IIB and IIC melanoma should be checked for new primary melanomas. A defined rapid-access pathway must be provided to all patients and GPs for suspected recurrence. Suspected new primary Thisgroupareat40e70%riskofrecurrence.Mostofthisriskis melanomashouldbereferredasnormalthroughthe2-week in years 2e4. They should be taught self-examination and wait system. For Scotland this needs to be compliant with seen 3-monthly for 3 years, and 6-monthly to 5 years. No the62-dayrule.Follow-upofpatientswithAJCCstageIIIand routineinvestigationsarerequired(LevelIII,GradeB). IVdiseaseshouldbeledbymelanomaSSMDTs. Follow-up intervals and duration should be tailored to Sentinel lymph node biopsy thestagegroupoftheprimarymelanomaandthereforeto theriskofrecurrence.Thefollow-upplanshouldbeagreed PatientswhohavehadanegativeSLNBshouldbefollowed betweenthe patient andthe responsible doctors. uponthe basis of Breslow thickness.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 13}, {"text": "1414 J.R.Marsden etal. MostpatientswhohavehadapositiveSLNBwillhavehad Improving Outcomes Guidance for People with Skin a completion lymphadenectomy. As these patients now Tumours including Melanoma; February 2006, available have at least stage IIIA disease, their follow-up should be at: www.nice.org.uk/nicemedia/pdf/CSG_Skin_Manual/ supervised by the SSMDT, and entry into appropriate trials pdf] considered. Risk of recurrence depends on the extent of 2. Comparisonandappropriatenessofstatedclinical,and sentinellymphnodeinvolvement,andmaybelessthanfor measured histological, surgical margins [referenced to some with stage II melanoma. They should be followed up the standards described in theseguidelines] asforstagesIBeIICmelanoma (LevelIII, GradeB). 3. Useofinvestigationsatdiagnosisinprimarymelanoma by stage grouping [referenced to the standards Stage IIIB, IIIC, and resected stage IV melanoma described in theseguidelines] Theriskoffurthermetastasisinthisgroupishigh.Manywill Acknowledgements beeligibleforadjuvanttrials.Thoseoutsidetrialsshouldbe seen 3-monthly for 3 years from the date of staging, 6The authorship team would like to acknowledge the monthlyto5years,thenannuallyto10yearsbyanSSMDT. contribution to these guidelines made by the late Dr Neil Investigationsshouldbecarriedoutonthebasisofclinical Cox. Neil worked tirelessly to improve care for patients, need,andmayincludeCTsurveillanceifconsideredapproand his clear thinking, expert knowledge and generous priate by the SSMDT. This might be used to monitor a site nature wereinvaluable to us. Weshallmiss himgreatly. considered at high risk of relapse. The SSMDTwill need to balance the use of follow-up investigations for this group againsttheneedforearlydetectionoffurtherstagesIIIand Conflicts of interest IVdisease.Earlydetectionfacilitatesbotheffectivetreatmentandtrialentry(LevelIII,GradeB). None declared. Unresectable stage IV melanoma References These patients should be followed up and investigated by theSSMDTaccordingtoclinicalneed.Theymaybeeligible 1. Griffiths CE. The British Association of Dermatologists\u2019 forclinical trials. guidelinesforthemanagementofskindisease.BrJDermatol 1999;141:396e7. 2. Cox NH, Williams HC. The British Association of dermatoloClinical trials gists therapeutic guidelines: can we AGREE? Br J Dermatol 2003;148:621e5. Many patients will be in clinical trials. These will have 3. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging definedfollow-up intervals which shouldbeadhered to. consensus on rating quality of evidence and strength of Follow-up for melanomais detailedin Table12. recommendations.BrMedJ2008;336:924e6. 4. Calman K, Hine D. Report by the Advisory Group on Cancer ServicestotheChiefMedicalOfficersofEnglandandWales. Table12 Follow-upformelanoma. DepartmentofHealth/WelshOffice;1995. (cid:1) Patientswithinsitumelanomasdonotrequirefollow5. National Institute for Health and Clinical Excellence (NICE). up ImprovingOutcomesGuidanceforPeoplewithSkinTumours (cid:1) Patientswithinvasivemelanomashavedifferingriskof including Melanoma, www.nice.org.uk/nicemedia/pdf/CSG_ Skin_Manual/pdf;February2006(lastaccessed25.05.10). relapseaccordingtotheirstagegroup 6. MarksR,WhitemanD.Sunburnandmelanoma:howstrongis (cid:1) PatientswithstageIAmelanomashouldbeseentwoto theevidence?BrMedJ1994;308:75e6. fourtimesoverupto12months,thendischarged 7. WhitemanD,GreenA.Melanomaandsunburn.CancerCauses (cid:1) PatientswithstageIBeIIIAmelanomashouldbeseen3Control1994;5:564e72. monthlyfor3years,then6-monthlyto5years 8. Armstrong BK. Epidemiology of malignant melanoma: inter- (cid:1) Patients with stage IIIB and IIIC and resected stage IV mittentortotalaccumulatedexposuretothesun?JDermatol melanomashouldbeseen3-monthlyfor3years,then6SurgOncol1988;14:835e49. monthlyto5years,thenannuallyto10years 9. Armstrong B, Kricker A. Sun exposure causes both non- (cid:1) PatientswithunresectablestageIVmelanomaareseen melanocytic skin cancer and malignant melanoma. Proc EnvironUVRadiatHealthEffects;1993:106e13.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 14}, {"text": "melanoma: inter- (cid:1) Patients with stage IIIB and IIIC and resected stage IV mittentortotalaccumulatedexposuretothesun?JDermatol melanomashouldbeseen3-monthlyfor3years,then6SurgOncol1988;14:835e49. monthlyto5years,thenannuallyto10years 9. Armstrong B, Kricker A. Sun exposure causes both non- (cid:1) PatientswithunresectablestageIVmelanomaareseen melanocytic skin cancer and malignant melanoma. Proc EnvironUVRadiatHealthEffects;1993:106e13. accordingtoneed 10. GandiniS, Sera F, Cattaruzza MS, et al. Meta-analysis of risk (LevelIII,GradeB) factors for cutaneous melanoma: III. Family history, actinic damageandphenotypicfactors.EurJCancer2005;41:2040e59. 11. Holick MF. High prevalence of vitamin D inadequacy and Audit points implicationsforhealth.MayoClinProc2006;81:353e73. 12. Newton-BishopJ,BeswickS,Randerson-MoorJ,etal.Serum 25-hydroxyvitamin D3 levels are associated with Breslow Thefollowing aresuggested points foraudit: thicknessatpresentation,andsurvivalfrommelanoma.JClin Oncol2009;27:5439e44. 1. TimelinessandappropriatenessofreferralfromLSMDTto 13. Randerson-Moor JA, Taylor JC, Elliott F, et al. Vitamin D SSMDT[referencedtothestandarddescribedinNational receptor gene polymorphisms, serum 25-hydroxyvitamin D Institute for Health and Clinical Excellence (NICE) levels and melanoma: UK case-control comparisons and", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 14}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1415 ameta-analysisofpublishedVDRdata.EurJCancer2009;45: 35. LedermanJS,SoberAJ.Doesbiopsytypeinfluencesurvivalin 3271e81. clinical stage I cutaneous melanoma? J Am Acad Dermatol 14. InternationalAgencyforResearchonCancerWorkingGroupon 1985;13:983e7. ArtificialUltravioletLightandSkinCancer.Theassociationof 36. Lees VC, Briggs JC. Effect of initial biopsy procedure on use of sunbeds with cutaneous melanoma and other skin prognosisinstageIinvasivecutaneousmalignantmelanoma: cancers:asystematicreview.IntJCancer2007;120:1116e22. reviewof1086patients.BrJSurg1991;78:1108e10. 15. McGovern TW, Litaker MS. Clinical predictors of malignant 37. AustinJR,ByersRM,BrownWD,etal.Influenceofbiopsyon pigmentedlesions.AcomparisonoftheGlasgowseven-point theprognosisofcutaneousmelanomaoftheheadandneck. checklist and the American Cancer Society\u2019s ABCDs of pigHeadNeck1996;18:107e17. mentedlesions.JDermatolSurgOncol1992;18:22e6. 38. AssociationofDirectorsofAnatomicandSurgicalPathology. 16. AbbasiNR,ShawHM,RigelDS,etal.EarlydiagnosisofcutaRecommendations for the reporting of tissues removed as neousmelanoma:revisitingtheABCDcriteria.JAmMedAssoc partofthesurgicaltreatmentofcutaneousmelanoma.Pathol 2004;292:2771e6. Int1998;48:168e70. 17. MacKie RM. Clinical Dermatology. 5th ed. Oxford University 39. SpatzA,CookM,ElderD,etal.Interobserverreproducibility Press;2003.p.345e346. of ulceration assessment in primary cutaneous melanomas. 18. DuVivierAWP,WilliamsHC,BrettJV,etal.Howdomalignant EurJCancer2003;39:1861e5. melanomas present and does this correlate with the seven40. GimottyPA,GuerryD,MingME,etal.Thinprimarycutaneous pointcheck-list?ClinExpDermatol1991;16:344e7. malignantmelanoma:aprognostictreefor10-yearmetastasis 19. Cox NH, Madan V, Sanders T, et al. skin cancer \u2018two-week ismoreaccuratethanAmericanJointCommitteeonCancer rule\u2019 proforma: assessment of potential modifications to staging.JClinOncol2004;22:3668e76. improvereferralaccuracy.BrJDermatol2008;158:1293e8. 41. EdgeSE,ByrdDR,ComptonCC,etal.,editors.Melanomaof 20. MeliaJ,CooperEJ,FrostT,etal.Cancerresearchcampaign theskin.AJCCCancerStagingManual.7thed.NewYork,NY: healtheducationprogrammetopromotetheearlydetection Springer;2009. ofcutaneousmalignantmelanoma.I.Work-loadandreferral 42. Hawkins WG, Busam KJ, Ben-Porat L, et al. Desmoplastic patterns.BrJDermatol1995;132:405e13. melanoma: a pathologically and clinically distinct form of 21. MeliaJ.Earlydetectionofcutaneousmalignantmelanomain cutaneousmelanoma.AnnSurgOncol2005;12:207e13. Britain.IntJEpidemiol1995;24:S39e44. 43. Elder DE, Murphy GF. Malignant Tumours (Melanoma and 22. MacKie RM, Hole D, HunterJAA,et al. Cutaneousmalignant RelatedLesions).ArmedForcesInstituteofPathology;1990. melanoma in Scotland: incidence, survival, and mortality, p.103e205. 1979e94.TheScottishMelanomaGroup.BrMedJ1997;315: 44. Kaur C, Thomas RJ, Desai N, et al. The correlation of 1117e21. regression in primary melanoma with sentinel lymph node 23. Braun RP, OlivieroM, KolmI. Dermoscopy: what\u2019s new?Clin status.JClinPathol2008;61:297e300. Dermatol2009;27:26e34. 45. Straume O, Akslan LA. Independent prognostic importance of 24. Melia J. Changing incidence and mortality from cutaneous vascularinvasioninnodularmelanoma.Cancer1996;78:1211e9. malignantmelanoma.BrMedJ1997;315:1106e7. 46. Quinn MJ, Crotty KA, Thomson JP, et al. Desmoplastic and 25. Parkin DM, Muir CS. Cancer incidence in five continents: desmoplastic neurotropic melanoma experience with 280 comparability and quality of data. IARC Sci Publ 1992;120: patients.Cancer1998;83:1128e35. 45e173. 47. HarristTJ,RigelDS,DayJrCL,etal.Microscopicsatellitesare 26. RhodesAR,WeinstockMA,FitzpatrickTB,etal.Riskfactors morehighlyassociatedwithregionallymphnodemetastases for cutaneous melanoma. A practical method of recognizing thanisprimarymelanomathickness.Cancer1984;53:2183e7. pre-disposedindividuals.JAmMedAssoc1987;258:3146e54. 48. CookMG,DiPalmaS.Pathologyofsentinellymphnodesfor 27. NewtonJA,BatailleV,GriffithsK,etal.Howcommonisthe melanoma.JClinPathol2008;61:897e902. atypical mole syndrome phenotype in apparently sporadic 49. CochranAJ.Surgicalpathologyremainspivotalintheevaluation melanoma?JAmAcadDermatol1993;29:989e96. of\u2018sentinel\u2019lymphnodes.AmJSurgPathol1999;23:1169e72. 28. Bataille V, Newton Bishop JA, Sasieni P, et al. Risk of cuta50. Starz H, Balda BR, Kramer KU, et al. A micromorphometryneousmelanomainrelationtothenumbers,typesandsitesof based concept for routine classification of sentinel lymph naevi:acase-controlstudy.BrJCancer1996;73:1605e11. node metastases and its clinical relevance for patients with 29. Le Mire L, Hollowood K, Gray D, et al. Melanomas in renal melanoma.Cancer2001;91:2110e21. transplantrecipients.BrJDermatol2006;154:472e7.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 15}, {"text": "et al. A micromorphometryneousmelanomainrelationtothenumbers,typesandsitesof based concept for routine classification of sentinel lymph naevi:acase-controlstudy.BrJCancer1996;73:1605e11. node metastases and its clinical relevance for patients with 29. Le Mire L, Hollowood K, Gray D, et al. Melanomas in renal melanoma.Cancer2001;91:2110e21. transplantrecipients.BrJDermatol2006;154:472e7. 51. Dewar DJ, Newell B, Green MA, et al. The microanatomic 30. Brown VL, Matin RN, Cerio R, et al. Melanomas in renal location of metastatic melanoma in sentinel lymph nodes transplant recipients: the London experience and invitation predicts nonsentinel lymph node involvement. J Clin Oncol toparticipateinaEuropeanstudy.BrJDermatol2007;156: 2004;22:3345e9. 165e7. 52. vanAkkooiAC,deWiltJH,VerhoefC,etal.TheRotterdam 31. MarghoobAA,SchoenbachSP,KopfAW,etal.Largecongencriteriaforsentinelnodetumorload:thesimplestprognostic ital melanocytic nevi and the risk for the development of factor?JClinOncol2008;26:2011. malignant melanoma. A prospective study. Arch Dermatol 53. BasseresN,GrobJJ,RichardMA,etal.Cost-effectivenessof 1996;132:170e5. surveillance of stage I melanoma. A retrospective appraisal 32. Illig L, Weidner F, Hundeiker M, et al. Congenital nevi less basedona10-yearexperienceinadermatologydepartment thanorequalto10cmasprecursorstomelanoma:52cases, inFrance.Dermatology1995;191:199e203. a review, and a new conception. Arch Dermatol 1985;121: 54. KhansurT,SandersJ,DasSK.Evaluationofstagingworkupin 1274e81. malignantmelanoma.ArchSurg1989;124:847e9. 33. GoldsteinAM,ChanM,HarlandM,etal.High-riskmelanoma 55. YancovitzM,FineltN, WarychaMA,etal.Roleofradiologic susceptibility genes and pancreatic cancer, neural system imaging at the time of initial diagnosis of stage T1b-T3b tumors, and uveal melanoma across GenoMEL. Cancer Res melanoma.Cancer2007;110:1107e14. 2006;66:9818e28. 56. Maubec E, Lumbroso J, Masson F, et al. F-18 fluorodeoxy-D34. LeachmanSA,CarucciJ,KohlmannW,etal.Selectioncriteria glucose positron emission tomography scan in the initial forgeneticassessmentofpatientswithfamilialmelanoma.J evaluationofpatientswithaprimarymelanomathickerthan AmAcadDermatol2009;61:677.e1e677.e14. 4mm.MelanomaRes2007;17:147e54.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 15}, {"text": "1416 J.R.Marsden etal. 57. ClarkPB,SooV,KrassJ,etal.FutilityoffluorodeoxyglucoseF 76. Silverman MK, Golomb FM, Kopf AW, et al. Verification of 18 positron emission tomography in initial evaluation of aformulafordeterminationofpre-excisionsurgicalmargins patientswithT2toT4melanoma.ArchSurg2006;141:284e8. fromfixed-tissuemelanomaspecimens.JAmAcadDermatol 58. Wagner JD, Schauwecker D, Davidson D, et al. Prospective 1992;27:214e9. study of fluorodeoxyglucose positron emission tomography 77. PrestonP,MateyP,MarsdenJR,etal.Surgicaltreatmentof imagingoflymphnodebasinsinmelanomapatientsundergoing lentigo maligna using 2mm excision margins. Br J Dermatol sentinellymphnodebiopsy.JClinOncol1999;17:1508e15. 2003;149:109e10. 59. vanRijkMC,TeertstraHJ,PeterseJL,etal.Ultrasonography 78. Mahendran RM, Newton-Bishop JA. Survey of U.K. current and fine-needle aspiration cytology in the preoperative practicein thetreatmentof lentigomaligna.Br J Dermatol assessment of melanoma patients eligible for sentinel node 2001;144:71e6. biopsy.AnnSurgOncol2006;13:1511e6. 79. Schmid-WendtnerMH,BrunnerB,KonzB,etal.Fractionated 60. SibonC,ChagnonS,Tchake\u00b4rianA,etal.Thecontributionof radiotherapy of lentigo maligna and lentigo maligna melahigh-resolution ultrasonography in preoperatively detecting nomain64patients.JAmAcadDermatol2000;43:477e82. sentinel-node metastases in melanoma patients. Melanoma 80. TsangRW,LiuFF,WellsW,etal.Lentigomalignaofthehead Res2007;17:233e7. and neck. Results of treatment by radiotherapy. Arch Der61. StarrittEC,UrenRF,ScolyerRA,etal.Ultrasoundexamination matol1994;130:1008e12. of sentinel nodes in the initial assessment of patients with 81. Pitman GH, Kopf AW, Bart RS, et al. Treatment of lentigo primarycutaneousmelanoma.AnnSurgOncol2005;12:18e23. maligna and lentigo maligna melanoma. J Dermatol Surg 62. Voit C, Kron M, Scha\u00a8fer G, et al. Ultrasound-guided fine Oncol1979;5:727e37. needle aspiration cytology prior to sentinel node biopsy in 82. RajparS,MarsdenJR.Imiquimodinthetreatmentoflentigo melanomapatients.AnnSurgOncol2006;13:1682e9. maligna.BrJDermatol2006;155:653e6. 63. Aloia TA, Gershenwald JE, Andtbacka RH, et al. Utility of 83. Walling HW, Scupham RK, Bean AK, et al. Staged excision computedtomographyandmagneticresonanceimagingstaging versusMohsmicrographicsurgeryforlentigomalignaandlenbeforecompletionlymphadenectomyinpatientswithsentinel tigomalignamelanoma.JAmAcadDermatol2007;57:659e64. lymphnode-positivemelanoma.JClinOncol2006;24:2858e65. 84. Morton DL, Wen DR, Wong JH, et al. Technical details of 64. Horn J, Lock-Anderson J, Sj\u00f8strand H, et al. Routine use of intraoperativelymphaticmappingforearlystagemelanoma. FDG-PET scans in melanoma patients with positive sentinel ArchSurg1992;127:392e9. nodebiopsy.EurJNuclMolImaging2006;33:887e92. 85. Morton D, Thompson J, Cochrane A, et al. Sentinel-node 65. Constantinidou A, Hofman M, O\u2019Doherty M, et al. Routine biopsyornodalobservationinmelanoma.NEnglJMed2006; positron emission tomography and emission tomography/- 355:1307e17. computed tomography in melanoma staging with positive 86. MortonDL,CochranAJ,ThompsonJF,etal.Sentinelnodebiopsy sentinel node biopsy is of limited benefit. Melanoma Res forearlystagemelanomaeAccuracyandmorbidityinMSLT-1, 2008;18:56e60. aninternationalmulticentretrial.AnnSurg2005;242:302e13. 66. VeronesiU,CascinelliN,AdamusJ,etal.ThinstageIprimary 87. Wright BE, Scheri RP, Ye X, et al. Importance of sentinel cutaneousmalignantmelanoma.Comparisonofexcisionwith lymphnodebiopsyinpatientswiththinmelanoma.ArchSurg marginsof1or3cm.NEnglJMed1988;318:1159e62. 2008;143:892e9. 67. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2 cm 88. LiW,StallA,ShiversSC,etal.Clinicalrelevanceofmolecular surgical margins for intermediate-thickness melanomas staging for melanoma: comparison of RT-PCR and immuno- (1e4mm):resultsofamulti-institutionalrandomizedsurgical histochemistry staining in sentinel lymph nodes of patients trial.AnnSurg1993;218:262e7. withmelanoma.AnnSurg2000;231:795e803. 68. Cohn-CedermarkG,RutqvistLE,AnderssonR,etal.Longterm 89. NathansohnN,SchachterJ,GutmanH.Patternsofrecurrence resultsofarandomizedstudybytheSwedishMelanomaStudy in patients with melanoma after radical lymph node dissecGroupon2cmversus5cmresectionmarginsforpatientswith tion.ArchSurg2005;140:1172e7. cutaneousmelanomawithatumorthicknessof0.8e2.0mm. 90. NationalCancerPeerReviewProgramme.ManualforCancer Cancer2000;89:1495e501. Services 2008: Skin Measures. 08e2J-212.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 16}, {"text": "and immuno- (1e4mm):resultsofamulti-institutionalrandomizedsurgical histochemistry staining in sentinel lymph nodes of patients trial.AnnSurg1993;218:262e7. withmelanoma.AnnSurg2000;231:795e803. 68. Cohn-CedermarkG,RutqvistLE,AnderssonR,etal.Longterm 89. NathansohnN,SchachterJ,GutmanH.Patternsofrecurrence resultsofarandomizedstudybytheSwedishMelanomaStudy in patients with melanoma after radical lymph node dissecGroupon2cmversus5cmresectionmarginsforpatientswith tion.ArchSurg2005;140:1172e7. cutaneousmelanomawithatumorthicknessof0.8e2.0mm. 90. NationalCancerPeerReviewProgramme.ManualforCancer Cancer2000;89:1495e501. Services 2008: Skin Measures. 08e2J-212. Available at: 69. Khayat D, Rixe O, Martin G, et al. Surgical margins in cutahttp://www.library.nhs.uk/integratedSearch/viewResource. neousmelanoma(2cmversus5cmforlesionsmeasuringless aspx?resID=299673(lastaccessed25.05.10) than 2.1-mm thick). Long-term results of a large European 91. Karakousis CP, Emrich LJ, Rao U, et al. Groin dissection in MulticentricPhaseIIIstudy.Cancer2003;97:1941e6. malignantmelanoma.AmJSurg1986;152:491e5. 70. Balch C, Soong SJ, Smith T, et al. Long term results of 92. BadgwellB,XingY,GershenwaldJE,etal.Pelviclymphnode aprospectivesurgicaltrialcomparing2cmvs.4cmexcision dissectionisbeneficialinsubsetsofpatientswithnode-posimarginsfor740patientswith1e4mmmelanomas.AnnSurg tivemelanoma.AnnSurgOncol2007;14:2867e75. Oncol2001;8:101e8. 93. Finck SJ, Giuliano, Mann BD, et al. Result of ilioinguinal 71. ThomasJ,Newton-BishopJ,A\u2019HernR,etal.Excisionmargins dissectionforstageImelanoma.AnnSurg1982;196:180e6. in high-risk malignant melanoma. N Engl J Med 2004;350: 94. Sterne GD, Murray DS, Grimley RP. Ilioinguinal block dissec757e66. tionformalignantmelanoma.BrJSurg1995;82:1057e9. 72. NIHConsensusConference.Diagnosisandtreatmentofearly 95. EssnerR,ScheriR,KavanaghM,etal.Surgicalmanagementof melanoma.JAmMedAssoc1992;268:1314e9. the groin lymph nodes in melanoma in the era of sentinel 73. Veronesi U, Cascinelli N. Narrow excision (1 cm margin) e lymphnodedissection.ArchSurg2006;141:877e82. a safe procedure for thin cutaneous melanoma. Arch Surg 96. ShenP,ConfortiA,EssnerR,etal.Isthenodeofcloquetthe 1991;126:438e41. sentinelnodefortheiliac/obturatornodegroup?TheCancer 74. Lens M, Nathan P, Bataille V. Excision margins for primary J2000;6:93e7. cutaneousmelanoma:updatedpooledanalysisofrandomized 97. HughesTMD,A\u2019HernR,ThomasJ,etal.Prognosisandsurgical controlledtrials.ArchSurg2007;142:885e91. management of patients with palpable inguinal lymph node 75. SladdenMJ,BalchC,BarzilaiDA,etal.Surgicalexcisionmargins metastasesfrommelanoma.BrJSurg2000;87:892e901. forprimarycutaneousmelanoma.CochraneDatabaseSystRev; 98. KarakousisCP,DriscollDL.Positivedeepnodesinthegroinand 2009;.doi:10.1002/14651858.CD004835.pub2.CD004835. survivalinmalignantmelanoma.AmJSurg1996;171:421e2.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 16}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1417 99. Balch CM, Ross MI. Melanoma patients with iliac nodal 120. MiddletonMR,GrobJJ,AaronsonN,etal.Randomizedphase metastasescanbecured.AnnSurgOncol1999;6:230e1. IIIstudyoftemozolomideversusdacarbazineinthetreatment 100. StrobbeLJA,JonkA,etal.Positiveiliacandobturatornodes of patients with advanced metastatic malignant melanoma. inmelanoma:survivalandprognosticfactors.AnnSurgOncol JClinOncol2000;18:158e66. 1999;6:255e62. 121. PatelP,SuciuS,MortierL,etal.Extendedscheduleescalated 101. O\u2019BrienCJ,CoatesAS,Petersen-SchaeferK,etal.Experience dosetemozolomideversusdacarbazineinstageIVmalignant with998cutaneousmelanomaoftheheadandneckover30 melanoma; final results of the randomised phase 3 study years.AmJSurg1991;182:86e91. (EORTC18032).AnnOncol2009;19:viii3. 102. TurkulaLD,WoodsJ.Limitedorselectivenodaldissectionfor 122. IvesNJ,StoweRL,etal.Chemotherapycomparedwithbiomalignantmelanomaoftheheadandneck.AmJSurg1984; chemotherapy for the treatment of metastatic melanoma: 148:446e8. a meta-analysis of 18 trials involving 2,621 patients. J Clin 103. HillS,ThomasJM.Useofthecarbondioxidelasertomanage Oncol2007;25:5426e34. cutaneous metastases from malignant melanoma. Br J Surg 123. Tarhini AA, Kirkwood JM, et al. Durable completeresponses 1996;83:509e12. withhigh-dosebolusinterleukin-2inpatientswithmetastatic 104. ThompsonJF,KamPC.Currentstatusofisolatedlimbinfusion melanoma who have experienced progression after biowith mild hyperthermia for melanoma. Int J Hyperthermia chemotherapy.JClinOncol2007;25:3802e7. 2008;24:219e25. 124. ZacestAC,BesserM,StevensG,etal.Surgicalmanagement 105. BeasleyGM,PetersenRP,YooJ,etal.Isolatedlimbinfusionof of cerebral metastases from melanoma: outcome in 147 in-transit malignant melanoma of the extremity: a wellpatients treated at a single institution over two decades. tolerated butless effective alternativeto hyperthermic isoJNeurosurg2002;96:552e8. latedlimbperfusion.AnnSurgOncol2008;15:2195e205. 125. Mori Y,KondziolkaD, FlickingerJC, etal. Stereotacticradi106. Cornett WR, McCall LM, Petersen RP, et al. Randomized osurgeryforcerebralmetastaticmelanoma:factorsaffecting multicentertrialofhyperthermicisolatedlimbperfusionwith localdiseasecontrolandsurvival.IntJRadiatOncolBiolPhys melphalan alone compared with melphalan plus tumor 1998;42:581e9. necrosisfactor:AmericanCollegeofSurgeonsOncologyGroup 126. SelekU,ChangE,Hassenbusch3rdSJ,etal.StereotacticradiTrialZ0020.JClinOncol2006;24:4196e201. osurgicaltreatmentin103patientsfor153cerebralmelanoma 107. VeronesiU,AdamusJ,AubertC,etal.Arandomisedtrialof metastases.IntJRadiatOncolBiolPhys2004;59:1097e106. adjuvant chemotherapy and immunotherapy in cutaneous 127. LensMB,RosdahlI,AhlbomA,etal.Effectofpregnancyon melanoma.NEnglJMed1982;307:913e6. survival in women with cutaneous malignant melanoma. 108. KoopsHS,VagliniM,SuciuS,etal.Prophylacticisolatedlimb JClinOncol2004;22:4369e75. perfusion for localized, high-risk limb melanoma: results of 128. O\u2019Meara AT, Cress R, Xing G, et al. Malignant melanoma in a multicenter randomized phase III trial. European Organipregnancy.Apopulation-basedevaluation.Cancer2005;103: zation for Research and Treatment of Cancer Malignant 1217e26. Melanoma Cooperative Group Protocol 18832, the World 129. Daryanani D, Plukker JT, De Hullu JA, et al. Pregnancy and Health Organization Melanoma Program Trial 15, and the early-stagemelanoma.Cancer2003;97:2248e53. NorthAmericanPerfusionGroupSouthwestOncologyGroup130. NaldiL,AltieriA,ImbertiGL,etal.Oncologystudygroupofthe 8593.JClinOncol1998;16:2906e12. Italian Group for Epidemiologic Research in Dermatology 109. WheatleyK,IvesN,EggermontA,etal.Adjuvanttherapyfor (GISED).Cutaneousmalignantmelanomainwomen.Phenotypic melanoma:anindividualpatientmeta-analysisofrandomised characteristics, sun exposure, and hormonal factors: a casetrials.JClinOncol2007;25:8526. controlstudyfromItaly.AnnEpidemiol2005;15:545e50. 110. Henderson MA, Burmeister B, Thompson JF, et al. Adjuvant 131. KaragasMR,StukelTA,DykesJ,etal.Apooledanalysisof10 radiotherapyandregionallymphnodefieldcontrolinmelanoma case-controlstudiesofmelanomaandoralcontraceptiveuse. patients after lymphadenectomy: Results of an intergroup BrJCancer2002;86:1085e92. randomizedtrial.JClinOncol2009;27:18[Suppl;abstrLBA9084]. 132. LeaCS,HollyEA,HartgeP,etal.Reproductiveriskfactorsfor 111. Chang P, Knapper WH. Metastatic melanoma of unknown cutaneous melanoma in women: a case-control study. Am J primary.Cancer1982;49:1106e11. Epidemiol2007;165:505e13. 112. LeeCC,FariesMB,WanekLA,etal.Improvedsurvivalafter 133. MacKie RM, Bray CA. Hormone replacement therapy after lymphadenectomy for nodal metastasis from an unknown surgery for stage I or II cutaneous melanoma. Br J Cancer primarymelanoma.JClinOncol2008;26:535e41. 2004;90:770e2. 113. Lee CC, Faries MB, Wanek LA, et al.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 17}, {"text": "CA. Hormone replacement therapy after lymphadenectomy for nodal metastasis from an unknown surgery for stage I or II cutaneous melanoma. Br J Cancer primarymelanoma.JClinOncol2008;26:535e41. 2004;90:770e2. 113. Lee CC, Faries MB, Wanek LA, et al. Improved survival for 134. SipleJ,SchneiderD,WanlassW,etal.Levodopatherapyand stage IV melanoma from an unknown primary site. J Clin riskofmalignantmelanoma.AnnPharm2000;34:382e5. Oncol2009;27:3489e95. 135. Wolfe F, Michaud K. Biologic treatment of rheumatoid 114. PatchellRA,TibbsPA,WalshJW,etal.Arandomisedtrialof arthritisandtheriskofmalignancy:analysesfromalargeUS surgery in the treatment of single metastases of the brain. observationalstudy.ArthritisRheum2007;56:2886e95. NEnglJMed1990;322:494e500. 136. NHS Blood and Transplant. Organ Donation: How to Become 115. Miller JD. Surgical excision for single cerebral metastasis? a Donor. www.organdonation.nhs.uk/ukt/how_to_become_ Lancet1993;341:1566. a_donor/how_to_become_a_donor.jsp (last accessed 116. SondakV,LiuP,WarnekeJ,etal.Surgicalresectionforstage 25.05.10). IV melanoma: a Southwest Oncology Group Trial (S9430). 137. Cornish D, Holterhues C, van der Poll-Franse L, et al. A JClinOncol2006;24(Suppl.):8019(Abstract). systematic review of health-related quality of life in cuta117. Overett TK, Shiu MH. Surgical treatment of distant metaneousmelanoma.AnnOncol2009;20(Suppl6):51e8. static melanoma. Indications and results. Cancer 1985;56: 138. Sollner W, Zschocke I, Augustin M. Melanoma patients: 1222e30. psychosocialstress,copingwithillnessandsocialsupport.A 118. MeyerT,MerkelS,GoehlJ,etal.Surgicaltherapyfordistant systematicreview.PsychotherPsychosomMedPsychol1998; metastases of malignant melanoma. Cancer 2000;89: 48:338e48. 1983e91. 139. FranckenAB,BastiannetE,HoekstraHJ.Followupinpatients 119. EssnerR,LeeGH,etal.Contemporarysurgicaltreatmentof with localized primary melanoma. Lancet Oncol 2005;6: advanced-stagemelanoma.ArchSurg2004;139:961e7. 608e21.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 17}, {"text": "1418 J.R.Marsden etal. 140. Hofmann U, Szedlak M, Ritgen W, et al. Primary staging and (cid:1) Patients with giant congenital pigmented naevi are at follow up in melanoma patients-monocenter evaluation of increasedriskofmelanomaandrequirelong-termfollowmethodscostsandpatientsurvival.BrJCancer2002;87:151e7. up 141. GarbeC,HauschildA,VolkenandtM,etal.Evidenceandinter- (cid:1) The prophylactic excision of small congenital naevi is disciplinaryconsensus-basedGermanguidelines:diagnosisand not recommended surveillanceofmelanoma.MelanomaRes2007;17:393e9. (cid:1) Individualswithafamilyhistoryofthreeormorecases 142. BalfountaML,BeauchetA,ChagnonS,etal.Ultrasonography ofmelanomashouldbereferredtoaClinicalGeneticist or palpation for detection of melanoma nodal invasion: ameta-analysis.LancetOncol2004;5:673e80. or specialised dermatology services for counselling. 143. Einwachter-Thompson J, MacKie RM. An evidence base for Those with two cases in the family may also benefit, reconsidering current follow-up guidelines for patients with especially if one of the cases had multiple primary cutaneousmelanomalessthan0.5mmthickatdiagnosis.BrJ melanomas or theatypical mole syndrome Dermatol2008;159:337e41. Requirements for microscopy of melanoma Summary of 2010 guidelines for management of melanoma Essential Ulceration Thickness Mitoticcount Histological Marginsof Pathological (See full manuscript for details of evidence and recomsubtype excision staging mendation gradings) DesirableLevelofdermal Growthphase Regression Melanoma patients who must be referred from the invasion Local Skin Cancer Multidisciplinary Team to the TumourinfiltratingLymphaticor Specialist Skin Cancer Multidisciplinary Team lymphocytes vascularinvasion Perineural Microsatellites (cid:1) PatientswithstageIBorhigherprimarymelanomawhen invasion sentinel lymph node biopsy (SLNB) is available within theirNetwork.IntheabsenceofSLNBthenpatientswith Surgical wider excision margins for primary stageIIBorhighershouldbereferredtotheSSMDT melanoma (cid:1) Patients with melanoma stage I or above who are eligible for clinical trials that have been approved at CancerNetwork level Breslowthickness Lateralexcisionmargins (cid:1) Patients with melanoma managed by other site tomuscleormusclefascia specialist teams, e.g. gynaecological, mucosal and headandneck(excluding ocular) Insitu 5mmmarginstoachievecomplete (cid:1) Patientswith multipleprimary melanomas histologicalexcision (cid:1) Childrenyounger than19 yearswith melanoma <1mm 1cm (cid:1) Any patient with metastatic melanoma diagnosed at 1.01e2mm 1e2cm presentationoron follow-up 2.1e4mm 2e3cm (cid:1) Patients with giant congenital naevi where there is >4mm 3cm suspicionof malignanttransformation (cid:1) Patients with skin lesions of uncertain malignant Staging investigations for melanoma potential Recommendations for Local Skin Cancer (cid:1) StagesI,II,andIIIAmelanomapatientsshouldnotroutinely Multidisciplinary Team record keeping of clinical bestagedbyimagingorothermethodsasthetrue-positive features pick-uprateislowandthefalse-positiverateishigh (cid:1) StagesIIIBorCpatientsshouldbeimagedbyCTpriorto surgery andwith SSMDTreview See:National Institute for Health and Clinical Excellence (cid:1) Stage IV melanoma patients should be imaged accord- (NICE) Improving Outcomes Guidance for People with ing to clinical need and SSMDT review; lactate dehySkinTumoursincludingMelanoma.February2006.www. drogenase shouldalso bemeasured nice.org.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 18}, {"text": "dehySkinTumoursincludingMelanoma.February2006.www. drogenase shouldalso bemeasured nice.org.uk/nicemedia/pdf/CSG_Skin_Manual/pdf Recommendationsforthemanagementofclinically node-negative patients Recommendationsforscreeningandsurveillanceof high-risk individuals (cid:1) There is no role for elective lymph node dissection (Level I,GradeE) (cid:1) Patients who are at moderately increased risk of (cid:1) Sentinellymphnodebiopsy(SLNB)canbeconsideredin melanomashouldbeadvisedofthisandtaughthowto stage IB melanoma and upwards in SSMDTs (Level IIa, self-examine.Thisincludespatientswithatypicalmole GradeC) phenotype,thosewithapreviousmelanoma,andorgan (cid:1) SLNBisastagingprocedurewithnoproventherapeutic transplantrecipients value", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 18}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1419 (cid:1) Surgical risks of SLNB, and of a false-negative result, Follow-up of melanoma patients shouldalso beexplained (cid:1) Patientswithinsitumelanomasdonotrequirefollow-up Recommendations for locoregional recurrent (cid:1) Patients with stage IA melanomas should be seen melanoma two to four times over up to 12 months then discharged (cid:1) All patients shouldbemanagedby SSMDTs. (cid:1) Patients with stage IBeIIIA melanomas should be (cid:1) Nodes clinically suspicious for melanoma should be seen 3-monthly for 3 years, then 6-monthly to 5 sampled using fine needle aspiration cytology (FNAC) years priortocarryingoutformalblockdissection.IfFNACis (cid:1) Patients with stage IIIB and IIIC and resected stage negative although lymphocytes were seen, a core or IV melanoma should be seen 3-monthly for 3 open biopsy shouldbeperformed ifsuspicion remains years, 6-monthly to 5 years, then annually to 10 (cid:1) Prior to formal dissection, performed by an expert, years staging by CT scan should be carried out other than (cid:1) Patients with unresectable stage IV melanomas are wherethiswouldmeanunduedelay(LevelIII,GradeB) seenaccordingto need (cid:1) The treatment of locoregional limb recurrence is palliative and, depending on extent and response, includes Appendix 1. Definition of the levels of excisionorCO laser,isolatedlimbinfusionorperfusion 2 evidence used in preparation of the guidelines Recommendations for metastatic disease (cid:1) All patients shouldbemanagedby SSMDTs (cid:1) Surgery should be considered for oligometastatic Level Typeofevidence disease at sites such as the skin, brain or gut, or to Ia Evidenceobtainedfrommeta-analysisof prevent painorulceration (cid:1) Radiotherapy may have a palliative role in the treatrandomisedcontrolledtrials,ormeta-analysisof epidemiologicalstudies ment ofmetastases (cid:1) Standardchemotherapyisdacarbazinealthoughitsrole Ib Evidenceobtainedfromatleastonerandomised controlledtrial ispalliative (cid:1) Patients with stage IV melanoma should be considered IIa Evidenceobtainedfromatleastonewell-designed controlledstudywithoutrandomisation for entry toclinical trials IIb Evidenceobtainedfromatleastoneothertypeof well-designedquasi-experimentalstudy III Evidenceobtainedfromwell-designednonPregnancy, oral contraceptives and hormone experimentaldescriptivestudies,suchas replacement therapy comparativestudies,correlationstudiesandcase studies IV Evidenceobtainedfromexpertcommitteereports oropinionsand/orclinicalexperienceof Pregnancyin Oral Hormone respectedauthorities melanoma contraceptives replacement therapy Gradeofrecommendation Noworseningof Noincreased Noincreased A Thereisgoodevidencetosupporttheuseofthe prognosis riskofmelanoma riskofmelanoma procedure Noincreasein Noworseningof B Thereisfairevidencetosupporttheuseofthe adverse prognosis procedure outcomesfor C Thereispoorevidencetosupporttheuseofthe motherorbaby procedure Placental D Thereisfairevidencetosupporttherejectionof metastases theuseoftheprocedure possiblein E Thereisgoodevidencetosupporttherejectionof stageIVdisease theuseoftheprocedure", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 19}, {"text": "BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists\u2019 guidelines for the care of patients with actinic keratosis 2017 D. de Berker,1 J.M. McGregor,2 M.F. Mohd Mustapa,3 L.S. Exton3 and B.R. Hughes4 1Bristol Dermatology Centre, University HospitalsBristol, Bristol BS2 8HW,U.K. 2Departmentof Dermatology, BartsHealth NHS Trust, LondonE11BB, U.K. 3British Associationof Dermatologists, WillanHouse, 4 Fitzroy Square,London W1T 5HQ, U.K. 4PortsmouthDermatology Centre, PortsmouthHospitals NHSTrust, PortsmouthPO3 6AD, U.K. Correspondence DaviddeBerker. 1.0 Purpose and scope E-mail:guidelines@bad.org.uk The overall objective of the guideline is to provide up-to-date, Acceptedfor publication evidence-based recommendations for the management of acti7September2016 nickeratosis (AK). The document aims (i) to offer an appraisal of all relevant Fundingsources literature up to February 2016, focusing on any key developNone. ments; (ii) to address important, practical clinical questions relating to the primary guideline objective, including accurate Conflictsof interest diagnosis and suitable treatment; (iii) to provide guideline Nonedeclared. recommendations and, where appropriate, some health ecoD.deB.,J.M.M.andB.R.H.aremembersoftheGuidelineDevelopmentGroup,with nomicimplications; and(iv)todiscuss potentialdevelopments technicalsupportfromL.S.E.andM.F.M.M. andfuture directions. The guideline is presented as a detailed review with highThisisanupdatedguidelinepreparedfortheBritishAssociationofDermatologists lighted recommendations for practical use in the clinic (see (BAD)ClinicalStandardsUnit,whichincludestheTherapy&Guidelines(T&G)SubSection 13.0), in addition to an updated patient information committee.MembersoftheClinicalStandardsUnitwhohavebeeninvolvedareP.M. leaflet (PIL), available at the British Association of DermatoloMcHenry(ChairmanT&G),K.Gibbon,D.A.Buckley,I.Nasr,C.E.DuarteWilgists (BAD) website (http://www.bad.org.uk/for-the-public/ liamson,V.J.Swale,T.A.Leslie,E.C.Mallon,S.Wakelin,S.Ungureanu,R.Y.P. patient-information-leaflets). Hunasehally,M.Cork,G.A.Johnston,J.Natkunarajah,F.S.Worsnop,N.Chiang,J. Donnelly(BritishNationalFormulary),C.Saunders(BritishDermatologicalNursing Group),A.G.Brian(BADScientificAdministrator),L.S.Exton(BADInformation 1.1 Exclusions Scientist)andM.F.MohdMustapa(BADClinicalStandardsManager). This guideline does not cover bowenoid AK or actinic Guidelinesproducedin2007bytheBritishAssociationofDermatologists;reviewedand cheilitis. updated,2016. 2.0 Stakeholder involvement and peer review DOI10.1111/bjd.15107 NICEhasrenewedaccreditationoftheprocessusedbytheBritishAssociaTheGuidelineDevelopmentGroup(GDG)consistedofconsultionofDermatologiststoproduceclinicalguidelines.Therenewedaccreditationisvaliduntil31May2021andappliestoguidanceproducedusing tant dermatologists. The draft document was circulated to the theprocessesdescribedinUpdatedguidanceforwritingaBritishAssociationofDermatologistsclinicalguideline\u2013theadoptionoftheGRADE BAD membership, the British Dermatological Nursing Group, methodology2016.Theoriginalaccreditationtermbeganon12May 2010.Moreinformationonaccreditationcanbeviewedatwww.nice. the Primary Care Dermatological Society, the British Society org.uk/accreditation. for Skin Care in Immunosuppressed Individuals, and Age U.K. for comments. These comments were actively considered by the GDG, and peer reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy & Guidelines Subcommittee) priortopublication. 3.0 Methodology This set of guidelines has been developed using the BAD recommended methodology,1 with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument 20 BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 1}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 21 (www.agreetrust.org).2 Recommendations were developed for feature of an AK is epithelial dysplasia. This may be restricted implementation in the National Health Service (NHS) using a to the basal layer or may extend to full-thickness atypia, at process of considered judgement based on the evidence. The which point the lesion is known as SCC in situ (Bowen disPubMed, MEDLINE and EMBASE databases were searched for ease). There is disorderly arrangement and maturation of meta-analyses, randomized and nonrandomized controlled epithelial cells. Multiple buds of epithelial cells may occur at clinical trials, case series, case reports and open studies involvthemembranezone, but noinvasion is seen.Histological variing AK published in the English language from January 2004 ants of AK have been described, including hypertrophic, to February 2016; the search terms and strategies are detailed bowenoid, lichenoid, acantholytic andpigmented. in Appendix S1 (see Supporting Information). Additional releActinic keratoses are generally considered to be premaligvant references were also isolated from citations in the nant lesions with low individual potential for invasive maligreviewed literature, as well as specific targeted searches for nancy andpotential for spontaneous regression. AKs present as systemic treatments and AK developing into squamous cell discrete, sometimes confluent, patchesoferythema andscaling carcinoma (SCC) asaresult ofspecific newtreatments. on predominantly sun-exposed skin, usually in middle-aged All identified titles were screened, and those relevant for and elderly individuals. Clinically, they are graded on a threefirst-round inclusion were selected for further scrutiny. The point scale according to magnitude. Field change might abstracts for the shortlisted references were then reviewed by include any or all of these lesions (Table 1).3 At grade 1 the the GDG, with a third round of review and selection for pholesion is just visible and palpable (gritty to feel and difficult to todynamic therapy (PDT) publications given their number and see), grade 2 lesions are usually red and scaly (easily felt and complexity.Disagreementsinthefinalselectionswereresolved seen), and grade 3 corresponds to thicker, hyperkeratotic by discussion with the entire GDG. The full papers of relevant lesions. Grade 3 AKs can be difficult to differentiate from material were obtained. The structure of the 2007 guidelines small, early SCCs, which, if excised, may be reported to have was then discussed and re-evaluated, with headings and subearly or equivocalinvasion.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 2}, {"text": "material were obtained. The structure of the 2007 guidelines small, early SCCs, which, if excised, may be reported to have was then discussed and re-evaluated, with headings and subearly or equivocalinvasion. headings decided; different coauthors were allocated separate They are often asymptomatic but may occasionally be sore subsections. Each coauthor then performed a detailed appraisal or itch; lesions may be single or multiple. When multiple, the of the selected literature with discussions within the GDG to concept of \u2018field change\u2019 is used to describe an area of skin resolve any issues. All subsections were subsequently collated that is involved extensively with actinic damage.4 The epiandedited toproducethefinal guideline. demiology, risk factors, disease associations and demographics of the \u2018at-risk\u2019 population are all pertinent to patient management. They are discussed together with the available treatment 4.0 Limitations of the guideline options. This document has been prepared on behalf of the BAD and is based on the best data available when the document was pre6.1 Aetiology pared. It is recognized that under certain conditions it may be necessary to deviate from the guidelines, and that the results Actinic keratosesaretheresultofchronicexposuretoultravioof future studies may require some of the recommendations let (UV) radiation, predominantly on skin of the head and herein to be changed. Failure to adhere to these guidelines dorsa of the hands, in fair-skinned individuals.5 In addition, should not necessarily be considered negligent, nor should UVB-specific p53 mutations have been demonstrated in AKs, adherence to these recommendations constitute a defence providing molecular evidence in support of a role for sunagainst a claim of negligence. Limiting the review to Englishlight.6 There is a high prevalence of keratinocyte cancer, language references was a pragmatic decision, but the authors including AKs,in thosereceiving chronicimmunosuppression, recognize this may exclude some important information pubparticularly organ transplant recipients,7 but also patients on lished in otherlanguages. long-term treatment for inflammatory bowel and rheumatological disease, although this is not as well documented. Other possible risk factors include exposure to arsenic8,9 and chronic 5.0 Plans for guideline revision sunbed use.10\u201312 The proposed revision of this set of recommendations is scheduled for 2021; where necessary, important interim Table1 Gradesofactinickeratosis(AK)3 changes willbeupdated ontheBAD website. Grade1 Mild;pinkorgreymarkswithslightscaleorgritty 6.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 2}, {"text": "of this set of recommendations is scheduled for 2021; where necessary, important interim Table1 Gradesofactinickeratosis(AK)3 changes willbeupdated ontheBAD website. Grade1 Mild;pinkorgreymarkswithslightscaleorgritty 6.0 Background totouch Grade2 Moderate;thickerhyperkeratosisandeasilydetected Actinic keratoses (synonymous with solar keratoses) are keraGrade3 Severe;hypertrophic,thickkeratin totic lesions occurring on chronically light-exposed adult skin. Fieldchange Confluentareasofseveralcentimetresormorewith They represent focal areas of abnormal keratinocyte proliferaarangeoffeaturesmatchinganyorallofthe gradesofAK tion and differentiation that carry a low risk of progression to invasive SCC. A spectrum of histology is seen, but the cardinal \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 2}, {"text": "22 Guidelinesforactinickeratosis2017, D.deBerkeretal. prospective photographic monitoring study over 5 years, it 6.2 Incidence andprevalence appeared that 65% of SCCs arose at a site of previously docuIt is likely that the incidence of AKs is underestimated. It is mented AK.20 A recent systematic review of 24 eligible studies difficult to measure the burden of AKs reliably in individuals examining the natural history of AKs concluded that there andin populations.13 were no reliable estimates concerning the frequency of AKs In prevalence studies in Galway, South Wales and developing into invasive carcinoma.26 Merseyside, 19\u201324% of individuals aged > 60 had at least one In summary, combined data suggest the possibility of AK.14\u201316 AKs were also present in 3(cid:1)6% of men aged regression and a low risk of malignant progression for any 40\u201349 years.16 A linear increase in prevalence was found with given AK. The presence of AK (particularly in high-risk age (from 60 to 80 years) in men but not in women in patients\u2013seeSection 7.6\u2013withmultipleAKsorfieldchange) another U.K. study, and the rate of new AKs was estimated to predicts an excess risk for subsequently developing an NMSC be 149 per 1000 person-years.15 Over 30% of those attending or melanoma compared withamatchedpopulation. a dermatology clinic (mean age of attendance 61 years) in Austria had AK. By the age of 70 years, > 70% of those 6.4 Investigation anddiagnosis attending had AK, with the majority (70%) on the head and neck.17 A Rotterdam prevalence study of > 2000 Dutch men Diagnosis of AK may be made in primary or secondary care and women, mean age 72 years, found AK in 49% of men and as part of a general skin examination associated with and28%of women.18 assessment of sun damage, focal keratotic lesions or skin cancer. Teledermatology has been cited as an effective means of diagnosis.27 Dermoscopy can be employed with a range of 6.3 Natural history: spontaneousregression and defined dermoscopic features.28 People with chronic fluctuatmalignant transformation ing disease may learn self-diagnosis but are advised to corrobPatientswithAKhaveachronicdisease.Thepresenceofasinorate their assessment with a healthcare professional. Such gle lesion is a marker of excessive sun exposure and is associmodels of patient-led monitoring and action are advocated in ated with the development of further lesions.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 3}, {"text": "lesion is a marker of excessive sun exposure and is associmodels of patient-led monitoring and action are advocated in ated with the development of further lesions. Point-prevalence otherchronicdiseasessuchasdiabetesmellitus,29wheremotistudies demonstrate that lesions regress and relapse over time vated self-management is a significant element in improved (thisisprobablyrelevantinthecaseofgrade1and2lesions). outcome.30 Diagnosis is typically on clinical grounds. UncerFigures range between 25% and 70% for apparent resolution tainty may arise in distinguishing AKs from superficial BCC, of AKs over a period of 1\u20134 years.15,19,20 Prospective evaluaSCC in situ, invasive SCC and even amelanotic melanoma, tion demonstrates a low rate of malignant transformation, where a skin biopsy or excision for histological examination with less than one in 1000 AKs developing into SCC per may be indicated. Where invasive malignancy is in the differannum.21 In a US study, 0(cid:1)6% of patients developed an SCC ential, the patient care should be shared with a member of a in the AK field within the first year \u2013 rising to 2(cid:1)57% at skin cancer multidisciplinary team. At the diagnosis of AK, the 4 years.20 The higher rate of apparent transformation in the location and thickness (e.g. grade 1, 2 or 3)3 should be docuUS study probably reflects the higher risk status of this premented; locationis best recorded on adiagram. dominantly maleveteran population. Nonetheless, there is evidence that AKs are a marker of 6.5 Shouldactinic keratoses be treated? excess risk for nonmelanoma skin cancer (NMSC). Mathematical models derived from the study undertaken by Marks et al. The natural history of individual lesions suggests that treatpredict that for an individual with an average of 7(cid:1)7 AKs, the ment is not universally required on the basis of preventing probability of developing an SCC within a 10-year period is progression into SCC.15 An indirect benefit of treatment is the approximately 10%.22 demonstration of lesions not responding to normal therapy, When 918 adults (mean age 61 years) with AKs but no which may represent a subgroup with higher malignant previous history of skin cancer were followed prospectively potential.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 3}, {"text": "opinion that believes for 5 years, the incidence rates for basal cell carcinoma (BCC) AKs are part of a spectrum that includes SCC in situ, and that and SCC were estimated at 4106 and 3198 per 100 000 perprevention of SCC is therefore the reason for therapy.31 A son-years, respectively, representing an excess risk compared Cochrane review of treatment of AK did not find any evidence with the general population.23 A sixfold excess risk for NMSC that treatment of AK resulted in reduction in presentation of or melanoma was found in a representative sample of the US invasive SCC.32 There is inadequate evidence to justify treatMedicare population with AKs compared with those without ment ofallAKs totry toprevent malignant change. (P < 0(cid:1)001).24 The most appropriate management plan should be deterDespite the proximity of AKs and SCC when they occur on mined by the patient\u2019s preferences and clinical circumstances, chronically sun-damaged skin, and the histological and molecwhich should take into account the extent, duration and presular similarities between them,25 debate continues concerning ence of symptoms, severity of lesions and other associated risk whether they are separate but similar pathologies developing factors for skin cancer, in addition to the patient\u2019s general in tandem or whether one leads directly to the other. In one healthandwell-being.Aquality-of-life questionnaire(AKQoL) BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 3}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 23 has been established and validated.33 In particular, patients 7.1 Notreatment (strength ofrecommendation A, quality express concern with respect to (i) the disease itself, (ii) sideofevidence 2++) effects and difficulties with treatment, (iii) association with the term cancer where AK is a risk factor for SCC, and (iv) Summaries of the levels of evidence and strengths of recomthe need to adjust sunshine behaviour on a background of mendation are given inAppendices 1and2. long-acquired habits andpreferences.34 Any perspective on nontreatment should be based on a whole-patient assessment,risks,comorbidities andpreferences. The fact that many AKs remit does not diminish the counter7.0 Management balancing point that they are associated with UV exposure and Many options are available for the treatment of AKs. The the development of melanoma, SCC and BCC. All patients main patient-centred considerations are the symptoms and need clear information on this risk and their own risk of SCC cosmetic burden of the AK, the efficacy and burden of treatin general so that, irrespective of the diagnosis of AK, they ment, and the threat of evolution of the AK into a more know to present early for assessment if a lesion bleeds, is bulky lesion or invasive SCC. Healthcare professional considpainful, grows significantly or becomes protuberant. All erations overlap with these, but include others such as effipatients should beadvised regarding sunprotection. cacy, a flexible regimen, availability in primary and secondary care and cost. An additional aspect of management 7.2 Primary care is consideration of the patient\u2019s overall risk of skin cancer and the wider skin examination. In the Rotterdam study on Patients with AK will ask their general practitioner (GP) for the prevalence of AK in the general population, participants diagnosis and treatment advice. Most AKs can be diagnosed with \u2265 10 AKs (13(cid:1)6%) had a threefold higher risk for havand treated in primary care.41 In healthcare systems with a ing a history of SCC compared with participants with four to primary-care physician as the first contact, skin monitoring of nine (4(cid:1)0%).18 Full-body skin examination revealed a skin sun-exposed surfaces of the head and neck and dorsa of hands cancer (BCC, SCC or melanoma) in 4%.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 4}, {"text": "sun-exposed surfaces of the head and neck and dorsa of hands cancer (BCC, SCC or melanoma) in 4%. The correlation is possible on an opportunistic basis and can be coupled with between skin cancer and number of AKs led the Dutch relevant prevention and self-care advice.42 Specialist dermatolgroup to advocate shorter follow-up intervals and more ogy nurses can play a similar role and are able to prescribe active treatment in those with \u2265 10 AKs, while not defining treatment in some healthcare systems.43 The Primary Care an interval and acknowledging the resource implications for Dermatology Society has developed guidance on the managethis 5% of the population. ment of AK in primary care in the U.K.44,45 Teledermatology At the outset of management, the location and grade has been used to support the diagnosis and management of (Table 1) of the AKs should be defined to enable monitoring, AK in primary care with specialist guidance.27 AKs are part of response to treatment or evolution. This can be done using the spectrum of actinic damage, which, once present, is mandrawings, body maps and photography, often with lesions aged rather thancured. numbered. Consider referral forspecialist care when: Management can be directed at individual lesions or over a (cid:129) AK failstorespondtostandard treatments; wider area (Fig. 1). This distinction represents lesion vs. field (cid:129) multiple or relapsing AKs represent a management chaltreatment. Field-based treatment can act to manage a range of lenge; actinic changes in a zone such as theforehead, scalp or central (cid:129) AK occurs inthelong-term immunosuppressed; face, and may provide some benefit in reduction of onset of (cid:129) new lesions.35 Topical therapies, skin peels36\u201339 and PDT are lesions are likely to be AK, but there is concern that they might be SCC (use the 2-week-wait route for possuitable. Usually, focal destructive therapies such as curettage sible skin cancer), for example when they are (i) bleedand cautery or cryotherapy are limited to lesion treatment ing, (ii) painful or (iii) thickened with substance when (Table 2). held between fingerandthumb. AEuropeanAK guideline achieved consensus through avoting and weighting method with advice grouped according to the isolated, field-associated or skin-cancer-associated distribu7.3 Secondary care tion of the AKs. There remained a preference for cryosurgery for isolated lesions and curettage for larger ones.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 4}, {"text": "avoting and weighting method with advice grouped according to the isolated, field-associated or skin-cancer-associated distribu7.3 Secondary care tion of the AKs. There remained a preference for cryosurgery for isolated lesions and curettage for larger ones. Otherwise, Secondary-care referral is required for diagnosis and/or manpreferences revolved largely around different strengths of the agement if the lesion might represent an invasive SCC.41 All common main agents, namely 5-fluorouracil (5-FU), imiquiregions of the U.K. have dedicated 2-week-wait or \u2018urgent mod, ingenol mebutate and variants of PDT. Diclofenac in cancer\u2019 pathways. In addition, if treatment in primary care for hyaluronic acid and imiquimod at 2(cid:1)5% were not favoured. In AK is unsuccessful, then referral is warranted for management immunosuppressed patients there was a preference for the alone. This includes patients with extensive disease or who are stronger formulations of all products. Laser was not considimmunosuppressed (see bulletpoints above). ered a good choice for any circumstance other than treatment Following diagnosisinsecondary care,treatmentcanbeiniof fielddisease.40 tiated with a future management plan for continued patient \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 4}, {"text": "24 Guidelinesforactinickeratosis2017, D.deBerkeretal. Fig1. Venndiagramillustratingtheoverlappingnatureoflesion-andfield-basedtreatmentsforactinickeratosis(AK). self-care (see Section 7.4) in collaboration with the GP. Histoof further lesions and relapse. They may also develop related logical diagnosis can be provided through a range of surgical pathology such as solar lentigo, lentigo simplex, SCC in situ procedures (see Sections 8.3 and 8.4) determined by lesion andNMSC. and circumstance. Follow-up in secondary care can be warPatient education is important in enabling self-care, with ranted to assess outcomes of treatment, extensive disease, early self-diagnosis, ongoing intermittent treatment and patients with associated skin cancers, or those with other conawareness of the risk of skin cancer and how to minimize this siderations such as immunosuppression. Nurse clinicians may risk (see the AK PIL available at http://www.bad.org.uk/forcontribute tothecarepathway. the-public/patient-information-leaflets). Most patients with mild AK will be seen in primary care and can manage their disease with topical therapy. Corroboration of diagnosis with 7.4 Self-care the GP is advisable before treatment of new lesions. ShortActinic keratosis is a chronic disease. Once patients have the term therapies (e.g. 4 weeks) may need renewal of prescripdiagnosis of AK, it is usually the start of a continued process tion when expired to ensure maintained efficacy. 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.tnemtaert .noitpircserp .stnemtaert .snoiselrekciht lacidem tub,rebmemer laitnatsbusfo dicacilycilaS -flesrofdooG seriuqeR salacitcarptoN fonoisivorp secuder stceffe-edis ylbaborp eracdetcerid detacided enituor ;tnemtaert roytilibixefl sesaercni dnatnempiuqe ,tnemtaert -flessevomer rofytiliba rofytilibatius erac-yradnoces sracssevael nacdnaerac ottneitap denekciht ninoisivorp seriuqerdna gnirracsesuac yfidom snoisel secnatsnitsom lacol otgnidrocca citehtseana stceffe-edis nidesuylerar(cid:129);secnatsmucricnognidnepeddesuebnac(cid:129)(cid:129);tnemtaertriaf(cid:129)(cid:129)(cid:129);tnemtaertdooG(cid:129)(cid:129)(cid:129)(cid:129).yparehtcimanydotohpetaniluvealonimalyhtem,TDP-LAM;licaruoroufl,UF;sisotarekcinitca,KA .knurtdnasbmilehtno1(cid:3)ggl005dnaecafehtno1(cid:3)ggl051tadesoDa.secnatsmucriceseht 26 Guidelinesforactinickeratosis2017, D.deBerkeretal. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 7}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 27 important part of patient education is awareness of the side8.0 Treatment effects of treatment before they start therapy. Many cause short-term redness, soreness and sometimes crusting or oozTreatment needs to address a wide range of variables including. If this is not anticipated it can cause distress and abaning thenature oftheAK,thebody site, patientpreference, the donment of treatment, where a pause would have been more premorbid state of the patient and previous treatments tried. appropriate. Added to this is the large number of therapeutic agents, their modes of application andtheflexibility with which eachagent can be used. Given this backdrop, it is to be expected that 7.5 Prevention there is variation in clinical practice. Table 2 attempts to bring There have been three randomized controlled trials (RCTs) a broad perspective to the options. In some instances it might (twoin Australia andoneintheU.S.A.)in patients> 50 years be viewed in combination with Table 3, which is an approxiold, many of whom had a history of AKs, to show that sunmationof asimplified cost\u2013benefit analysis. screen, used to prevent unintentional sun exposure, is associated with a small decrease in the incidence of SCCs and AKs (but notBCCs) over ashort follow-up period.46\u201348 8.1 General More active treatment with a 4-week course of 5-FU, 5% Lifestyle, dietary fat,56 workplace and genetics are likely to twice daily to a field of involved skin can reduce the rate of make a difference to the risk of getting AK, mainly relating to onset of new AKs in that area over the subsequent 18 months thelevels of UVradiation exposure. when compared with placebo.35 There are no studies to show that sun avoidance reduces 8.1.1 Emollient (strength ofrecommendation B, levelof the risk of development of AKs and skin cancer in a popuevidence 2+) lation without AKs. Nonetheless, it is reasonable to hope that the effect of public health campaigns over the last few Elderly, sun-damaged skin is often dry, and emollient can be decades will have an impact on this risk. Such practices part of a management regimen. The direct effect of emollient may have a bearing on vitamin D levels, which warrant on AKs is not clear.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 8}, {"text": "effect of emollient may have a bearing on vitamin D levels, which warrant on AKs is not clear. Additives such as urea or salicylic acid review in those patients subject to high levels of sun avoidmay provide benefit. There are no trials dedicated to the study ance or who have other risk factors for diseases related to of palliative therapy of AKs, but emollient or gel vehicle has low vitamin D.49 been employed in the placebo arm of many trials. The vehicle limb of an RCT of diclofenac gel in hyaluronan vehicle described clearance of the target lesion in 44% of patients 7.6 High-risk cases using the vehicle after 60 days.57 Less dramatic results were Are there high-risk groupsandis their managementdifferent? seen with the cream vehicle used in trials of imiquimod Patients with multiple and confluent AKs are likely to be at applied two or three times a week for 4 weeks, reporting higher risk of NMSC than those with single lesions. Patients complete clearance of treated AKs in 0%,58 2(cid:1)4%59 and on chronic immunosuppressive therapy are at increased risk 14(cid:1)1%,60 with the latter treated three times a week for for skin cancer. Organ transplant recipients are reported as 8 weeks. having 50\u2013100 times the skin cancer risk of an ageand sexmatched control population.50,51 It is recommended that 8.1.2 Sunprotection andsunscreen (strength of high-risk patients have closer follow-up52 and more rigorous recommendation A,levelof evidence1++) treatment40 for premalignant lesions, including SCC in situ and AK, together with a lower index of suspicion for skin biopsy There is no specific information or evidence on sun protection to exclude malignancy. Nonetheless, there is no evidence that other than through studies on sunscreen. Sunscreen has a such measures reduce the risk of new skin cancers, although combined emollient andphotoprotective effect.Arandomized, they may reduce morbidity from surgery and minimize the placebo-controlled trial of sunscreen with sun protection facrisk ofrecurrence. tor (SPF) 17 applied twice daily to the face for 7 months Treatment for AKs in transplant patients may be less effecshowed sunscreen to be more effective than emollient in tive than in the general population.53 Outcomes may be conterms of the total number of AKs and new lesions.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 8}, {"text": "be more effective than emollient in tive than in the general population.53 Outcomes may be conterms of the total number of AKs and new lesions.46 A single, founded by the large number of proliferative and daily application of sunscreen with SPF 16 in Queensland, hyperkeratotic lesions in this group. Studies have not found a Australia, also showed it to be more effective than discrereduction in subsequent skin cancers in areas previously treationary use of the same sunscreen over a 2-year period in the ted for AKs with PDT.51 Oral retinoids have been used to reduction of AKs.61 A similar approach in the same setting reduce the risk of SCC in transplant patients at high risk of also reduced the incidence of cutaneous SCC.48 A 24-month getting skincancer,but theeffecton AKsis not reported. study of daily use of sunscreen (SPF > 50, high UVA absorpA single study reported that capecitabine, used in 15 tion) in 120 case-controlled organ transplant recipients patients, reduced the risk of SCC,54 BCC and AKs in organ showedsignificantreductioninAKsandNMSCsarisingduring transplant recipients, buttoxicityis likely tolimititsuse.55 thestudy.49 \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 8}, {"text": "ecnedivefoslevelehT.serusaememoctuodnagnilpmasralimisnodesabsyawlatoneraspuorgtnemtaertneewtebataD.KAnisnoitpotnemtaertniamehtfognittesdnaytilibixefl,ycacfife,tsoC 3elbaT 4ot++1morfegnarelbatsihtotgnitubirtnoc ninoitcudeR nodesabsKA ffatsfotsocno-ddA lanoitavresboa .tnempiuqeroemit rosTCRb,seiduts roeracyramirP sisylana-atemc otelbanemA .]eracyradnoces[ tonodseulav( noitaulavefodoireP elbanemA eracdetcerid-tneitap elbixelF seriuqeryllacipyTd ssecxetcefler nahtregnol( eracyramirpot gnirotinomdna snemiger stisiv2 metidesnepsiD metirepegnartsoC )lortnocrevo )tnemtaertevitca (cid:129)(cid:129)(cid:129) (cid:129) (cid:129) 0 \u2666 51,a%12otpU etinfiedni,cidoireP tnemtaertoN (cid:129)(cid:129)(cid:129) (cid:129) (cid:129) 0 \u2666 06,75,b%44\u20130 etinfiedni,cidoireP elcihevrotneillomE (cid:129)(cid:129)(cid:129) (cid:129) (cid:129) ]\u2666\u2666[\u2666 Lm005 \u2666 74,64,b%63\u201371 etinfiedni,cidoireP /3AVU(neercsnuS )05\u201371FPS (cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 g04 \u2666 66,63,b%87\u201307 shtnom4\u20132 %5licaruoroulF-5 (cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 stehcas42\u201321 \u2666\u2666/\u2666 57,47,b%48otc%05 shtnom4\u20132 %5domiuqimI (cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 stehcas65\u201382 \u2666\u2666\u2666\u2666/\u2666\u2666\u2666 58,b%63\u201343 shtnom4\u20133 %57(cid:1)3domiuqimI (cid:129)(cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 g001\u201305 \u2666\u2666/\u2666 09,75,b%07\u201391 shtnom4\u20132 %3legcanefolciD (cid:129)(cid:129) \u274d (cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 noitacilppa-elgnis3\u20132 \u2666\u2666 39,29,b%24\u201343 shtnom2\u20131 etatubemlonegnI sebutg-74(cid:1)0 ,ecaf1(cid:3)ggl051( sbmil1(cid:3)ggl005 )knurtdna \u274d \u274d (cid:129)(cid:129) 771829\u00a3\u2013724\u00a3 ebuttnemtaertelgniS \u2666\u2666\u2666 671,721,911,701,b%39\u201396 shtnom2\u20131 TDP-LAM (cid:129) \u274d (cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 elbacilppatoN nwonktoN 601,301,a%88\u201393 shtnom2\u20131 yregrusoyrC seiparehtnoitanibmoC (cid:129)(cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129) ]\u2666\u2666[\u2666 Lm52 \u2666 27,17,b%77ota%55 shtnom4\u20132 %5(cid:1)0 licaruoroulF-5 dicacilycilasdna %01 (cid:129) (cid:129) (cid:129)(cid:129) ]\u2666\u2666[\u2666 g001\u201305 \u2666\u2666/\u2666 751,651,a%001\u201364 shtnom4\u20132 dnalegcanefolciD yregrusoyrc (cid:129) (cid:129) (cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 stehcas42\u201321 \u2666\u2666/\u2666 68,a%5(cid:1)95 shtnom4\u20132 dnadomiuqimI yregrusoyrc \u274d (cid:129) (cid:129)(cid:129) sulpd]\u2666\u2666\u2666\u2666[\u2666\u2666 sulpstehcas42\u201321 \u2666\u2666/\u2666 061,a%98 shtnom4\u20132 dnadomiuqimI 829\u00a3\u2013724\u00a3 ebuttnemtaertelgnis TDP-LAM morfnwardstsoC egakcapdradnatS stnemmoC snoitacilbupSHN esruocroezis :tnemtaertfo 66noitide,4102FNB noitcetorpnus,FPS;lairtdellortnocdezimodnar,TCR;yparehtcimanydotohpetaniluvealonimalyhtem,TDP-LAM;ecivreShtlaeHlanoitaN,SHN;yralumroFlanoitaNhsitirB,FNB;sisotarekcinitca,KA ;ytilibanema/ytilibixefletaredom(cid:129)(cid:129);ytilibanema/ytilibixeflemos(cid:129);elbixeflroelbanematon\u274d:yekeraC.002\u2013051\u00a3\u2666\u2666\u2666\u2666;051\u2013101\u00a3\u2666\u2666\u2666;001\u201315\u00a3\u2666\u2666;05\u20130\u00a3\u2666:yektsoC.Ateloivartlu,AVU;rotcaf 971.44\u00a3:tisivPG.86\u00a3:ecnadnettapu-wolloflatipsoH871.401\u00a3:51\u20134102ffiratSHNecnadnettacinilclatipsohtsriF.elbanema/elbixeflyrev(cid:129)(cid:129)(cid:129) 28 Guidelinesforactinickeratosis2017, D.deBerkeretal. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 9}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 29 A Cochrane review with subsequent meta-analysis of complete 8.2 Active treatments clearance results ranked the efficacy of all of the main treatAll topical therapies for AK may result in side-effects of irritaments andput5-FU atthetop.65 tion. Some AKs proceed to ooze, crusting and soreness with Nine of the trials were controlled; a right\u2013left comparison local swelling. Details are cited in this guideline for the indi- (n = 6)wasthemostcommondesign,butonlyfivewereranvidual treatments and are included in the relevant PILs. It is domized. Numbers in the studies were generally small, with a important that the patient understands the extent of the area mean of 26 patients per trial and fewer than 15 patients in to be treated and anticipates the side-effects. The size of area 50% of the trials. The minimum follow-up was \u2265 12 months will depend on a range of factors including the therapy, focal in only two studies. Many open studies appeared to demonor scattered pathology and the conceptual model (fieldor strate the efficacy of 5-FU in a range of potencies and differlesion-basedtreatment).Wheremorbidityisanascendantconent vehicles in the treatment of AKs when used on the face cern, treatment should be initiated over a small area such as twice daily for 3 weeks. Only two trials studied the use of 54\u201310 cm2 with flexible frequency to establish tolerance and FU in the currently available formulation of a 5% cream in a confidence. Some treatments define a ceiling of surface area well-constructed, controlled manner.36,66 Kurwa et al. exambased on the aliquot of prescribed item, for example one tube ined the lesional area of AKs on the back of the hands before of ingenol mebutate is a single dose for 25 cm2. Imiquimod and after treatment with 5-FU 5% cream twice daily for 5% is issued in 250-mg sachets where directions include \u2018one 3 weeks in a randomized right\u2013left comparison with a single sachet only\u2019 and to \u2018cover the area\u2019 typically with a centimetre treatment with PDT.66 Of the 14 patients evaluable at margin around any pathology. Others recommend a maxi6 months, there was a mean reduction in lesional area of 70% mum basedon toxicity, such as500 cm2for 5-FU 5%. (5-FU) and 73% (PDT), with no statistically significant differPatients should be provided with advice on how to manage encebetweenthem.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 10}, {"text": "there was a mean reduction in lesional area of 70% mum basedon toxicity, such as500 cm2for 5-FU 5%. (5-FU) and 73% (PDT), with no statistically significant differPatients should be provided with advice on how to manage encebetweenthem.Openstudieshavesuggestedthatthisregside-effects, with strategies including a break in treatment, imen is not sufficiently long for effective treatment of AKs on altering the frequency of application, use of emollient and in thehands,67but is adequatefor thoseon theface.36 some instances application oftopicalsteroid. Witheiler et al. used 5-FU 5% cream on the face as the control in a right\u2013left comparison with a single application of Jessner\u2019s solution (14% lactic acid, 14% salicylic acid, 14% 8.2.1 5-Fluorouracil (strength ofrecommendation A, level resorcinol in ethanol) followed by a trichloroacetic acid (TCA) of evidence1++) 35% peel.36 There was a mean reduction in AKs on both sides The majority of the data on topical therapies relate to the 5% of the face from 18 to four (78% reduction with 5-FU and concentration of 5-FU cream. 5-FU works by the inhibition of 79% reduction with TCA). This benefit was sustained for thymidylate synthetase, which is needed for DNA synthesis. It 12 months. The third follow-up at 32 months demonstrated may also interfere with the formation and function of RNA.62 that the number of AKs had risen again to 10 (5-FU) and 15 It is a widely used, flexible and low-cost treatment.63 It can (TCA) in the eight evaluable patients; these differences were be used either as lesional treatment or as part of field treatnot statistically significant. ment. The side-effects with the latter can be substantial, and it The results of using the same formulation of 5-FU less freis important that the patient is counselled about them, includquently, but for prolonged periods, are conflicting. An open ing soreness, redness and possible crusting. All of these can be trial of 10 patients reported clearance of 96% of AKs after a minimized through reduction in the frequency of application mean of 6(cid:1)7 weeks applying treatment twice daily, once or or short breaks in a course of therapy. It is permitted to wash twice per week.68 Six patients were followed for 9 months the area and apply thin emollient. If the reaction is excessive, and showed an 86% clearance rate that was maintained.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 10}, {"text": "of therapy. It is permitted to wash twice per week.68 Six patients were followed for 9 months the area and apply thin emollient. If the reaction is excessive, and showed an 86% clearance rate that was maintained. weak steroid can be applied. It is important that the patient is Epstein followed this study with a similar protocol and sample enabled to learn how to use the treatment, as it is one they size, except that evaluation was done by dermatologists given mayrequireintermittentlyinthefutureandabadinitialexpea series of photographs and blinded to the sequence.69 Eight rience canlimit further use. of 13 patients failed to show any improvement, with the conMany regimens cite twice-daily application over 4 weeks, clusion that pulsing 5-FU over a period < 10 weeks is not but less frequent initial use may enable titration of the freeffective. A comparison of use twice daily for 3 weeks against quency of application against reaction, tolerance and efficacy. twice daily for 1 day a week for 12 weeks showed the infreUse at poor healing sites such as the lower leg should always quent regimen to be 80% as effective when evaluated at the be undertaken with caution and may need supervision. More final assessment at 52 weeks.70 recently, 5-FU 0(cid:1)5% in 10% salicylic acid has been evaluated The mixed quality and size of these studies mean it is diffiand can be prescribed.64 A wide range of open trials, dosecult to provide a firm interpretation, but the indication is that ranging studies and manipulations of the vehicle have been pulsed therapy may work for some patients and enable more reported over the last 45 years, as well as two RCTs, confirmprotracted therapy with reduced morbidity. Such an approach ing efficacy. A large,placebo-controlled RCT showed 5-FU 5% can be useful for sensitive areas or people reluctant to use to be more effective than placebo in AK clearance and the treatments that provoke redness and crusting. However, for reduction of follow-up cryosurgery treatments at 6 months.35 some people it may fail to show benefit, and increased \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 10}, {"text": "increased \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 3, "page": 10}, {"text": "30 Guidelinesforactinickeratosis2017, D.deBerkeretal. frequency of use or an alternative treatment may need to be periods. After a further 24 weeks, these figures changed to employed. 45%, 0% and 14(cid:1)3%, respectively, illustrating that improve5-FU 0(cid:1)5% in 10% salicylic acid has been assessed, where mentcontinuestoprogressaftertheconclusionofimiquimod, salicylic acid may be acting as a keratolytic to enhance the in contrast to other treatments.58 Similar results were reported efficacy of5-FU. Intheinitial opentrial, statistics wereunderfor imiquimod 5% used three times a week for 4 weeks in taken per AK rather than per patient.71 In this framework, itis 126 patients, andrepeated for afurther 4 weeksa monthlater not possible to report the complete cure of any single patient. in 79 of them and compared with cream vehicle. The global However, the clinical clearance rate for individual AKs was complete response in the combined groups was 55%, com77%, with no control or blinding. Subsequent evaluation paredwith2(cid:1)3%forvehicle,illustratingthatpersonalvariation against salicylic acid vehicle and diclofenac 3% in hyaluronic makes it possible to tailor the duration of the regimen to the gel has been undertaken.64 Daily application with a brush for individual.77 An RCT comparing imiquimod 5% cream on the 6\u201312 weeks or the point of clearance was compared with face [three times a week for 4 (40%) or 8 (60%) weeks twice-daily diclofenac gel over the same period. Eight weeks depending on response] with liquid nitrogen spray (10-s post-treatment, complete clearance was determined to be freeze to commencement of thawing) favoured liquid nitroachieved in 55(cid:1)4%, 32% and 15(cid:1)1% of the patients using the gen, with complete clearance in 88% vs. 66(cid:1)9%. However, the study product, diclofenac and vehicle, respectively; the AKs cryosurgery resulted in a higher number of pigmentary were grades 1 and 2. A follow-up phase of the same study changes.78 measured the rate of relapse of individual lesions rather than The side-effects of imiquimod are similar to those of 5-FU, relapse from complete clearance.72 With this measure, the rate with severe erythema (30(cid:1)6%), scabbing andcrusting (29(cid:1)9%) of relapse measured per lesion was less at 12 months with 5and erosions or ulceration (10(cid:1)2%). Flu-like symptoms can FU 0(cid:1)5% in 10% salicylic acid (14(cid:1)2%) thandiclofenac 3% gel also arise and are more likely if multiple sachets are used at (19%) (P = 0(cid:1)02%).", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 11}, {"text": "erosions or ulceration (10(cid:1)2%). Flu-like symptoms can FU 0(cid:1)5% in 10% salicylic acid (14(cid:1)2%) thandiclofenac 3% gel also arise and are more likely if multiple sachets are used at (19%) (P = 0(cid:1)02%).72 The nature of the application makes it each treatment or if it is being used for superficial BCC with suitable for lesion-directed therapy rather than field therapy. more frequent applications than is typically the case for AK.59 The license highlights the benefit of the salicylic acid vehicle An instance of post-treatment eruptive keratoacanthomas has as a means of addressing more keratotic AKs. About 50% of been reported.79 The extent of side-effects is not wholly prepatients discontinue treatment at 6 weeks due to disappeardictable, with some patients manifesting an extreme reaction anceoftheAK.73 and others very little. The clinical response is largely in proportion to the side-effects, and those terminating treatment early due to extreme soreness may still get a good response. 8.2.2 Imiquimod5% cream(strength of recommendation Side-effects are generally well tolerated, but it is important to A,levelof evidence1++) counsel the patient carefully in order to anticipate those who Imiquimod is a topical immune-response modifier. It is availhave moreextremeclinicalreactions.80 able as a 5% and a 3(cid:1)75% cream. Most of the data on treatThere are limited long-term data on relapse after treatment, ment response pertain to the 5% cream and are considered but in a three-armed RCT between cryosurgery, 5-FU 5% and first.IntheU.K.itislicensedforuseinclinicallytypical,nonimiquimod, the proportions of the intention-to-treat populahyperkeratotic, nonhypertrophic AKs on the face or scalp in tion maintaining clearance at 12 months were 1%, 33% and immunocompetent adults, when the size or number of lesions 76%, respectively.81 The cryosurgery treatments were 20\u201340 s limits the efficacy and/or acceptability of cryotherapy, and in duration, which is a dose at which scarring might be other topical treatment options are contraindicated or less expected. This observation poses questions about this limb of appropriate. It isapplied atnight andwashed offin themornthe study. In an observational, 16-month follow-up study, ing 8 h later. Courses are three times a week for 4 weeks, 75(cid:1)3% of those receiving treatment three times a week over whichcan berepeated forafurther 4 weeksifneeded.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 11}, {"text": "of those receiving treatment three times a week over whichcan berepeated forafurther 4 weeksifneeded. 8 weeks were clear at 16 months, in comparison with 57(cid:1)4% A meta-analysis of the use of imiquimod 5% cream from receiving thesametreatment twice aweek.82 five RCTs using it two or three times a week for 12\u201316 weeks There is a small number of studies on imiquimod 3(cid:1)75% demonstrated a 50% complete clearance rate. This is similar to cream (strength of recommendation B, level of evidence 1+), more brief and flexible regimens as per the license.74 A small which is licensed for treatment of AKs of the head and scalp RCT against vehicle placebo showed clearance rates of 84% with application once daily for two, 2-week periods separated when used up to three times per week for 12 weeks.75 Two by 2 weeks. Early studies had longer courses, applied once RCTs with regimens of three times per week for 16 weeks daily for two periods of 3 weeks separated by 3 weeks, over a and follow-up 8 weeks later gave 47% of subjects with com9-week course. Comparison with placebo vehicle 8 weeks plete clearance (vs. 7(cid:1)2% with placebo)76 and 57(cid:1)1% (vs. after conclusion of treatment showed complete clearance rates 2(cid:1)2%for placebo).59 of 5(cid:1)5% (placebo) and 34%.83 Where AKs responded they A head-to-head open trial between imiquimod 5% (twice recurred in 60% of patients within 14 months.84 Where treatper week for 16 weeks), its cream vehicle and diclofenac 3% ment was given as per the licence at weeks 1 and 2, then 5 gel (twice daily for 90 days) showed complete clearance of and 6, complete clearance was seen in 6(cid:1)3% and 35(cid:1)6% for 19(cid:1)1%, 0% and 20% at the end of the respective treatment emollient and imiquimod, respectively.85 Where the BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 11}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 31 comparator wascryosurgery andemollient vehicle, imiquimod the disruption of mitochondrial membranes resulting in dam3(cid:1)75%following cryosurgery resulted in complete clearance in age anddeath of host cells and promotion ofcell-specific anti59(cid:1)5%ofpatients.86 bodies with consequent antibody-dependent, cell-medicated Imiquimod3(cid:1)75%hasalsobeenusedfollowingcryosurgery cellular cytotoxicity. It is licensed for the treatment of nonkerasasupplementarytreatment,improvingtheresultoftreatment atotic, nonhypertrophic AK in adults (grade 1 and 2). It is ofhypertrophicAKsontheforearmanddorsaofthehandsover sold in two strengths (150 and 500 lg g (cid:3)1), with the weaker cryosurgery alone.87 It is possible that the adverse side-effects one applied 3 days in succession to the chosen area on the associated with imiquimod 5% cream are less with the 3(cid:1)75% face and scalp and the stronger one applied 2 days in succesformulation, and this might enable more field-based treatment sion to other sites. Each application is dispensed as a single overlesiontherapyandimprovepatienttolerance. tube of cream (three tubes for the face and scalp or two tubes for other sites) with scope to cover a field 5 9 5 cm. Use of the 150-lg g (cid:3)1 preparation on the face and scalp over 3 days 8.2.3 Diclofenac gel(strength of recommendation A,level resulted in a complete cure rate of 40% vs. 11(cid:1)7% for vehicle of evidence1+) 60 days after starting the treatment in one RCT,92 and 42(cid:1)2% Diclofenac3%ina2(cid:1)5%hyaluronicgelislicensedforapplicavs. 3(cid:1)7%forvehicle in another ofsimilar size.93 tion twice daily for 60\u201390 days and can be applied as a Pooled data from two trials of this treatment regimen follesionor field-based treatment. Its mechanism of action for lowed successfully treated patients for 12 months. There was AK is not known, but may be related to inhibition of the relapse on the head and neck in just over half of the patients cyclooxygenase pathway leading to reduced prostaglandin E2 in the following year.94 If residual lesions are re-treated at synthesis. Diclofenac gel usually causes less intense local skin 8 weeks, clearance at 12 months increases from 27% to reaction than 5-FU or imiquimod 5% cream.88 The reduction 50%.95 Clearance on other body sites is less, at 34(cid:1)1% vs. ofside-effectsismatchedbyreduced efficacywherediclofenac 4(cid:1)7%for vehicle after application of the500-lg g (cid:3)1 cream on gel and 5-FU 5% are compared, but both achieve high levels two consecutive days, with relapse in just over half of the (73% vs. 77%) ofpatientsatisfaction.89 patients at 12 months.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 12}, {"text": "the500-lg g (cid:3)1 cream on gel and 5-FU 5% are compared, but both achieve high levels two consecutive days, with relapse in just over half of the (73% vs. 77%) ofpatientsatisfaction.89 patients at 12 months. Specific sites such as the back of the There are three vehicle-controlled studies in the treatment hand are less likely to clear completely, with 18(cid:1)5% vs. 0% of mild AKs. In the first, patients were treated for a mean of for placebo.96 60 days, with aclearance of 70%of target lesionsin the treatSide-effects peak at 4 days, which is after completion of the ment group compared with 44% in those using the vehicle.57 application of treatment. Common effects are redness, scabIn the second study, treatment was for 90 days; 50% achieved bing, pain and pustules, with most side-effects settling within complete clearance vs. 20% of those treated with vehicle alone 28 days.93,94 (P < 0(cid:1)001).90 In a three-armed RCT comparing diclofenac A 2015 update from the US Food and Drug Administration 3%, imiquimod 5% cream and base cream, the rates of comhighlights the risks of severe adverse reactions, with local and plete clearance at the end of treatment were 19(cid:1)1%, 20% and systemic allergic features and herpes zoster infection. Within 0%. the update they emphasize the need \u2018to avoid applying the gel In summary, these three different studies with diclofenac in, near, and around the mouth, lips and eye area\u2019.97 Extendgel show 26%, 30% and 19(cid:1)1% benefit over vehicle gel or ing the area of treatment of ingenol mebutate to 100 cm2 base cream, respectively.58 Extending treatment from 90 to resulted in no increase in treatment-related adverse events 180 days gave an additional 5% complete clearance without a compared with 25 cm2.98 Clobetasol propionate, used twice significant change in adverse effects.91 Follow-up assessment daily for 4 days post-treatment, did not alleviate the sympwas limited to 30 days post-treatment in the first two studies. toms or efficacy of ingenol mebutate.99 This may be relevant In the third, clearance dropped to 14(cid:1)3% at 24 weeks\u2019 followtoothertreatments causingsoreness. up. Diclofenac 3% gel used as part of a three-armed study with 5-FU 0(cid:1)5% in 10% salicylic acid and vehicle resulted in a 8.2.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 12}, {"text": "causingsoreness. up. Diclofenac 3% gel used as part of a three-armed study with 5-FU 0(cid:1)5% in 10% salicylic acid and vehicle resulted in a 8.2.5 Topicalretinoids (strength ofrecommendation B, 32% rate (17% over vehicle)64 of complete clearance, and a level ofevidence1+) relapse rate of 19% at 12 months.72 These data indicate moderate efficacy with low morbidity in mild AKs. Treatment was A range of older trials demonstrate a modest benefit with the well tolerated and reported side-effects were mainly pruritus use of topical retinoids in AK.100 They may lend some addi- (41% estimated after 30 days\u2019 treatment) and rash (40% estitional benefit with respect to improvement in lentigines and mated after60 days).57 reduced wrinkles. Their use is usually sustained rather than based on a limited course of treatment. Products include ada8.2.4 Ingenol mebutate cream(150 lgg(cid:3)1faceandscalp, palene 0(cid:1)3%, tretinoin 0(cid:1)1% and 0(cid:1)05% and topical isotreti500 lgg(cid:3)1limbsand trunk)(strength ofrecommendation noin 0(cid:1)1%. Where adapalene 0(cid:1)1% was compared with 0(cid:1)3%, the latter was significantly more efficacious in achieving AK A, levelofevidence 1+) count reduction after 9 months.101 Currently, tretinoin and Ingenol mebutate is a diterpene ester extracted from the plant isotretinoin are prescribable in the U.K. only in 0(cid:1)025% and Euphorbia peplus. At a cellular level it appears to work through 0(cid:1)05% concentrations, respectively, as topical antibiotic \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 12}, {"text": "32 Guidelinesforactinickeratosis2017, D.deBerkeretal. combinations licensed for use in acne. A Veterans Association rate of 88% as judged at 24 weeks.106 In a right\u2013left, splitRCT exploring topical retinoid for chemoprevention of skin face study comparing MAL-PDT with a cryosurgery double cancerwasstoppedearlybecauseofexcessiveall-causemortalfreeze\u2013thaw cycle retreated at 12 weeks as needed, MAL-PDT ityin thetreatment groupat interim analysis.102 showed 89(cid:1)1% cured lesions vs. 86(cid:1)1% for cryosurgery, with Keyrecommendations: topical therapies no significant difference between them. Patient and clinician (cid:129) assessment of cosmetic outcome were in favour of MALEmollient and sunscreen with advice on sun protection PDT.107 might be a satisfactory treatment for people with fluctuExtensive cryosurgery over large areas has been referred to ating grade 1AKs. (cid:129) as cryopeeling, and can be used to treat fields of AKs and Education at the outset of using active topical therapies background damage.108 Cryosurgery has been described in is important to ensure a full understanding of how to combination with topical 5-FU, where the duration of treatapplytreatmentandthenatureoftheside-effects,which ment and consequent side-effects of both modalities could be canbemarked. (cid:129) reduced while maintaining efficacy.109 The pretreatment of AK Active topical therapy is suited to use in primary and with 5-FU 0(cid:1)5%for 1 week, prior totreatment of theremainsecondary care. Where possible, a management plan ing lesions with cryosurgery at the 1-month follow-up, may should be formulated that enables the patient to be decrease the AK count at 6 months when compared with managed in primary care. (cid:129) cryosurgery and vehicle pretreatment (reduced to 33% vs. Topical therapy is suited to use as lesionand field55%, P = 0(cid:1)01).110 basedtreatment.Whereusedforfieldtreatment,thesize Cryosurgery is a flexible therapy that requires skill in of the field needs to be defined with the patient to administration. With larger doses it is likely to result in loss ensure anticipation andtolerance ofside-effects. (cid:129) of pigment and scarring. Patient counselling is important conFailure of an individual lesion to respond to topical cerning the shortand long-term side-effects. In particular, therapyindicates aneedfor furtherevaluation. Thismay patients should be aware of blistering, oedema, crusting and include referral from primary care to secondary care or soreness. Doses appropriate for AK are usually < 10 s, but still surgerytoobtainhistology andextendtreatment. carry some risk of damage to underlying structures such as tendons and nerves if applied on the back of the hands.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 13}, {"text": "or soreness. Doses appropriate for AK are usually < 10 s, but still surgerytoobtainhistology andextendtreatment. carry some risk of damage to underlying structures such as tendons and nerves if applied on the back of the hands. Below the knee, slow healing can be a problem, particularly in the 8.3 Cryosurgery(strength ofrecommendation A,level of older patientgrouppresenting withAK. evidence 1++) Cryosurgery is a long-established treatment for AKs requiring 8.4 Surgery a cryospray (or cotton wool and orange sticks) and a supply of liquid nitrogen. Complete clearance rates vary according to There are no trials of surgery for AKs. The nature of the the duration of freeze and the number of treatments, usually pathology makes it likely that a surgical procedure able to separated by 6\u201312 weeks. The relationship between duration remove an area of diseased skin represents an effective therof freeze and clearance was examined in a three-dose study apy. Histological information can be useful in management of with 12-month follow-up after cryosurgery. A duration < 5 s AK. It is unlikely that this would be a first-line treatment showed 39% cure, 5\u201320 s, 69% cure and > 20 s, 83% cure unless there was diagnostic uncertainty. Surgery addresses a on the scalp and face.103 Many more recent studies are based focal lesion, and where AK presents in a field of actinic damon head-to-head trials with PDT. A randomized study comparage, it does not address this. A curettage specimen may make ing cryosurgery with PDT in 193 patients indicated an overall it difficult to determine whether a lesion has an element of 75% complete response rate for cryosurgery in contrast to dermal invasion. In some instances a deep shave or formal 69% in those treated with PDT at 3 months.104 The differenexcision with histological examination might be preferred. If tial success of the two therapies was more marked for thick curettage is used for a hyperkeratotic AK where SCC is a diflesions, with 69% showing complete response to cryosurgery ferential diagnosis, it may be warranted to employ two or vs. 52% to PDT. A double freeze\u2013thaw cycle was used in this three cycles oftherapy.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 13}, {"text": "52% to PDT. A double freeze\u2013thaw cycle was used in this three cycles oftherapy. This will ensure that if the histology is study in contrast to a single cycle, which, when used in a difthat of invasive SCC, or if it is equivocal, the curettage is still ferent study, yielded a68%response.105 likely to represent adequate treatment. Exceptions would be A more recent head-to-head study with methyl aminolaewhere the size, histological type or location of an SCC would vulinate (MAL)-PDT employed cryosurgery (1 9 10-s freeze) make curettageanunacceptable treatment.111 as needed every 3 months for up to four visits with assessment at 12 months. It reported a complete response rate of 8.5 Systemic therapy (strength ofrecommendation C, 85%, with 77% needing only one treatment. Side-effects of level ofevidence 2+) cryosurgery of soreness, blistering, pigmentary change and scarring contributed to an overall patient preference for Systemic retinoids have been assessed for their potential role PDT.78 Inanother study, adoublefreeze\u2013thaw cycle given just in suppression or treatment of multiple AKs. Early studies once with no defined duration provided a complete clearance employing etretinate showed the efficacy of this drug in BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 13}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 33 double-blind, crossover trials.112 Anecdotal evidence over the photosensitizing cream, then the agent is applied under occlulast 20 years suggests that there can be some considerable sion for 3 h prior to irradiation. Surface fluorescence with a morbidity in employing this treatment. In addition, there may Wood\u2019s lamp can help delineate lesions and identify persistent be a rebound effect once the systemic therapy is stopped. disease. Treatment can be painful but can be managed with However, these effects were not observed at the 4-month folcold-air analgesia or nerve blocks.121,122 Erythema and crustlow-up in theone availablereport on thissubject.113 ing often occur but can be reduced by the use of plaster or Use of systemic retinoids may be justified in very high-risk physical sunscreens.123 patients, such as organ transplant recipients, where there is a Four studies report PDT to be more effective than plapresumed increased risk of progression from AK to SCC.54 cebo.105,107,124,125 Three were randomized and one double Renal transplant patients given oral acitretin 0(cid:1)4 mg kg (cid:3)1 blinded, with 80\u2013211 subjects. Efficacy rates appear better for showed some immunohistochemical normalization of keratin the face and scalp than the forearm and hands,126 but there expression patterns, butaresidue ofhistological dysplasia sugare no studies comparing the two sites. Response rates in the gests potential for relapse when the drug is stopped.114 Lowface and scalp range from 69% to 93%. Follow-up reported dose acitretin is currently given as a treatment option in the up to24%recurrence at12 months in anopen-label study.127 \u2018European best practice guidelines\u2019 for renal transplant patients There may be an increased response of PDT with fractionwith multipledysplastic skin lesions.115 ated light128 and pretreatment with laser.129 Both claimed betAn international survey of 28 dermatologists managing skin ter responses, but patient numbers were small and the sidedisease in organ transplant recipients looked at the use of syseffects greater with laser pretreatment. In a side-to-side comtemic retinoid.116 In the setting of AK alone, only where the parative study of PDT vs. CO laser treatment they were of 2 AK was extensive did the majority (56%) advocate systemic equalefficacy but patientpreferencewas forPDT.130 retinoid. Once patients start getting multiple (more than five) Three open-label RCTs compared MAL-PDT with cryosurSCCs in addition to AK, the rate of prescribing increased to gery.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 14}, {"text": "did the majority (56%) advocate systemic equalefficacy but patientpreferencewas forPDT.130 retinoid. Once patients start getting multiple (more than five) Three open-label RCTs compared MAL-PDT with cryosurSCCs in addition to AK, the rate of prescribing increased to gery. Two freeze\u2013thaw cycles were comparable in one between 74% and 81% depending on whether the SCCs were study104 and inferior in terms of relapse in another.107 A sinhigh risk. Acitretin was the most common drug, at a starting gle cycle was inferior in the third study.105 The efficacy of dose of 10 mg (42%) or 25 mg (58%); 12% of respondents PDT was confirmed in a meta-analysis in 2014.131 PDT has used isotretinoin. also been compared side to side in trials with 5-FU.66 A There is little literature on the use of systemic cytotoxic right\u2013left comparison of AK treatment on the backs of the agents in the immunosuppressed, mainly for the treatment of hands showed a similar response for PDT and 5-FU, clearing SCC but in the setting of extensive AK. Capecitabine given to lesions in 73% and 70% of cases, respectively. Three studies 15 organ transplant recipients with frequent SCC, BCC and AK showed nodifference between PDTandimiquimod.132\u2013134 showed reductions in monthly incidence to 22%, 33% and In a randomized study of 30 patients given up to two treat45% of pretreatment levels, respectively.55 Side-effects resulted ments with ALA-PDT or one to two courses of imiquimod in 33% ofpatients stopping after1 year. (three times a week for 4 weeks), equivalent responses were The cyclooxygenase-2 inhibitor, celecoxib, taken for seen 6 months after completion of treatment (65% vs. 9 months can reduce the number of BCCs and SCCs over an 55%).134 PDTwasmoreeffectivefor grade 2lesions. 11-month period, but does not appear to alter the number of A thin, self-adhesive patch has been developed for selfAKs.117 Overall, it may have a role in high-risk patients with application.135,136 In a multicentre RCT involving 449 multiple NMSCs, but it does not have evidence of a role for patients, efficacy with active treatment was 82% after AK.118 12 weeks compared with 19% for placebo and 77% for cryosurgery. It is advocated as allowing self-application and avoiding theneed forpretreatment curettage. 8.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 14}, {"text": "weeks compared with 19% for placebo and 77% for cryosurgery. It is advocated as allowing self-application and avoiding theneed forpretreatment curettage. 8.6 Photodynamic therapy (strength ofrecommendation Daylight PDT involves the application of MAL to the skin A, level ofevidence 1+) without occlusion and subsequent exposure to ambient dayPhotodynamic therapy combines a dedicated light source of light. A high-SPF sunscreen without mineral filters is applied appropriate wavelengths with the application of a photosensi15 min before the photosensitizing cream. Thirty minutes tizing cream to produce apoptosis and necrosis of the target later thepatient spends2 houtdoors. tissue. Photosensitizing agents include 5-aminolaevulinic acid Five RCTs in Europe and Australia have confirmed the effi- (5-ALA) and the methyl ester of 5-ALA, 5-MAL. BF-200ALA cacy of daylight PDT compared with conventional PDT.137\u2013141 was recently used, showing increased stability and penetraThis was in mild (grade 1) to moderate (grade 2) lesions on tion.119,120 the face and scalp. Clearance rates of 70\u201389% were reported. A range of light sources can be used.121 Red narrow-specIn European studies daylight PDT can be performed in all trum light sources permit shorter illumination times and weather conditions,141 but temperatures > 10 \u00b0C are advised appear to give higher response rates.119,120 Current knowledge for patient comfort. Consensus guidelines have also been proof photosensitizers and light sources are detailed in the 2013 duced.142\u2013144 European Guidelines for PDT.121 In most situations superficial One comparative study was a right\u2013left comparison of PDT crust or keratin is first removed with light curettage and with ingenol mebutate in grade 1 and 2 lesions (27 patients). \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 14}, {"text": "34 Guidelinesforactinickeratosis2017, D.deBerkeretal. In both there was a 40% complete response rate, but PDT was product with two active ingredients where, for instance, salibetter tolerated.145 cylic acid 10% may break down surface keratin and improve penetration and hence the efficacy of 5-FU 0(cid:1)5% (see Section 8.2.1). 8.7 Laser therapy (strength ofrecommendation B, level Salicylic acid ointment is sometimes used as a preliminary ofevidence 1+) to topical 5-FU to remove overlying keratin. Salicylic acid In principal, dermabrasion, chemical peels and laser treatment 50% in croton oil has been described as a treatment for AKs should treat AKs, as skin is destroyed to a controlled depth. when used in combination with TCA 20% and pretreatment The majority of studies treat field change as well as individual with topical tretinoin as a serial regimen for facial peel.39 The lesions. These physical therapies come with significant risk of ointment base may be acting as an emollient, with some level long-term side-effects including hypopigmentation and persisofsuccess for grade 1AK3,57 (seeSection 8.1.1). tent erythema and scarring. The risk of such problems is In a case series, patients were pretreated with diclofenac 3% greater with ablative rather than nonablative laser techniques, gel for 12 weeks followed by cryosurgery for the 29% with whichalso requireanti-infective prophylaxis.146 residual lesions. This demonstrated an overall effective There are no studies comparing laser treatment with no response to this combined management approach, with comtreatment or placebo. plete clearance maintained for6\u201320 months (mean10).156 An A good-quality, prospective, randomized study of 5-FU open-label multicentre trial of cryosurgery (freeze time of 4\u2013 (twice daily for 4 weeks) vs. erbium-doped yttrium alu10 s) followed by diclofenac 3%gel 15 days later for the next minium garnet (Er:YAG) laser in 55 patients demonstrated 3 months vs. cryosurgery alone found that complete clearance significantly fewer recurrences in the laser group at 6 and increased from 21% to 46% with the addition of diclofenac. 12 months, but more erythema and hypopigmentation in the The clearance rates for a target lesion were greater at 32% vs. long term. No data were reported on clearance at completion 64%.157 A small, right\u2013left-hand study with 4 weeks\u2019 pretreatoftreatment.147 ment using diclofenac 3% gel and PDT compared with plaA second prospective randomized trial of CO laser vs.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 15}, {"text": "data were reported on clearance at completion 64%.157 A small, right\u2013left-hand study with 4 weeks\u2019 pretreatoftreatment.147 ment using diclofenac 3% gel and PDT compared with plaA second prospective randomized trial of CO laser vs. TCA cebo gel and PDT demonstrated a greater decrease in the 2 30% vs. 5-FU (twice daily for 3 weeks) with small patient number and thickness of AKs on the side with diclofenac prenumbers showed a significant clearance of lesions with all treatment,at 12 months.158 interventions at 3 months. The authors also claimed a delayed Diclofenac 3% as pretreatment for 5-FU 0(cid:1)5% in 10% salitime to recurrence of NMSC compared with controls, but the cylic acid is also reported as an effective sequential regicontrolswere thedropouts fromthestudy.148 men.156 There are reports of 5\u20137 days of 5-FU 5% Three retrospective case studies of CO with or without Er: pretreatment also being safe and effective in combination with 2 YAG lasers show clearance and reduced AKs at follow-up.149 cryosurgery110 or PDT159 or, alternatively, in combination Two of these studies demonstrate 80% and 87% clearance at with glycolic peels.38 PDT followed by imiquimod twice a 12 months.150,151 A split-face study of ablative, fractionated week for 16 weeks was beneficial over PDT and subsequent (i.e. multiple pinpoint treatments) CO laser treatment vehicle cream alone when undertaken in a split-face study.160 2 demonstrated only a short-term reduction in the number of Thecompleteclearanceratewasnotreported,butthepercentAKs, not sustained over 3 months.152 One pilot study of nonage reduction in count was significant at 89(cid:1)9% in the comablative fractional laser in 10 patients reported 46% clearance bined treatment side vs. 74(cid:1)5% on the side treated with PDT at 6 months and claimed minimal acute and long-term sidealone. With PDT as the variable rather than imiquimod, PDT effects.153 did not appear to improve the efficacy of imiquimod alone, Dermabrasion in open studies clears AKs on the face and although the study was small. Similarly, adding imiquimod scalp. Coleman et al. treated 23 patients, 96% of whom were 5% two times a week for 8 weeks to cryosurgery does not clear at 6 months and 54% at 5 years.154 Winton and Salasche appeartoimprove on cryosurgery alone. treated fivepatients successfully, withcompleteclearance.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 15}, {"text": "does not clear at 6 months and 54% at 5 years.154 Winton and Salasche appeartoimprove on cryosurgery alone. treated fivepatients successfully, withcompleteclearance.155 An alternative regimen has been studied for hypertrophic A simple, prospective case series describing treatment of AKs on the forearms and the dorsa of the hands. Imiquimod individual AKs with phenol 100% applied once a month for 3(cid:1)75% was used following a double, 5-s freeze\u2013thaw cycle, up to a maximum of 8 months in 32 patients reported no randomized to the right or left arm and applied in up to two recurrence at12 months.37 sachets per night for 2 weeks, followed by a 2-week break and a further 2 weeks. The comparison was cryosurgery alone on the other arm. Complete cure was not an end point, but 8.8 Combination treatment there was a greater level of clearance in the combination arm There are many trials of combination therapy in the treatment (76%) than the control arm (38%). This difference did not of AK; they are of two kinds. The first is a serial approach emerge until 10 weeks after cryosurgery (4 weeks after comwhere one treatment is advocated to follow the other dependpletion of imiquimod), and maximized at the end of assessing on outcome, or as a specific regimen of pretreatment with ment at 14 weeks.87 Randomizing to 5-FU 0(cid:1)5%, 1 week the possibility that the effects of one treatment will maximize, after cryosurgery resulted in nonsignificant improvement over or consolidate, the response. The second approach is to use a cryosurgery alone.161 BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 15}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 35 Keyrecommendations: physicalandsystemic therapies Studies undertaken in ophthalmology suggest that treatment (cid:129) is possible with close supervision. Treatment can be combined Education at the outset of using physical therapies is with care of the eye. In a case series of 14 patients treating important to ensure a full understanding of the sideperiocular skin with 5-FU 5% twice daily for 2 weeks, antibieffects, which can be marked and include scarring and otic ointment was coprescribed and used until the area had alteredpigmentation. (cid:129) healed.163 Six of the 14 AKs were on the upper eyelid and Cryosurgery is a flexible and effective form of lesionnine abutted a lid margin. Five patients required a second based physical therapy that removes the patient involvecourse of treatment, but overall clearance was complete in all ment in their own care and requires administration in a cases and remained so for a mean follow-up period of servicewith cryosurgery. (cid:129) 38 months. Two patients had transient inflammatory sideCurettage can be warranted for thicker (grade 3) AKs, effects affecting the eye. The potential precision of application wheretheyareresistanttotopicaltherapyandwherethere of 5-FU 0(cid:1)5% in 10% salicylic acid in a collodion base might is suspicion that they may representearly SCC. Histology make it a useful alternative to cream formulation, but there mustalwaysbeobtained.Diagnosticbiopsymaybewarare no dataon this. rantedonthesamebasis,butissubjecttosamplingerror. (cid:129) A retrospective study of the use of imiquimod 5% cream PDT is an effective treatment for confluent AKs, such as for a range of periocular actinic lesions identified 47 patients on the scalp, which are difficult to manage or resistant mainly with AK, mainly on the lower lid.164 Conjunctivitis totreatment in theabsence ofinvasive disease. (cid:129) occurred in 15 and six had ocular stinging, with conjunctivitis PDT has low scarring potential and less risk of poor in three for over 2 weeks. Antibiotics were needed in three, healing in comparison with other physical therapies at for preseptal cellulitis in two of them. Nine patients discontinvulnerable sitessuch asthelower leg. (cid:129) ued imiquimod due to ocular irritation and conjunctivitis, of Pretreatment with topical therapy can increase the effiwhom four patients recommenced and finished the treatment cacy ofphysical therapies. (cid:129) after a rest period.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 16}, {"text": "increase the effiwhom four patients recommenced and finished the treatment cacy ofphysical therapies. (cid:129) after a rest period. At a mean follow-up of 16 weeks, 34 Failure of an individual lesion to respond to physical (72%) patients had clinical clearance of the periocular lesions therapy indicates a need for further evaluation. This and no patient had any residual ophthalmic side-effects from couldinclude formalexcision. (cid:129) imiquimod. Systemic therapy is usually given in the context of mulThere is no good literature on diclofenac gel or ingenol tiple grade 3 AKs, a history of serial SCCs and immunomebutate, but both the PIL and product licence emphasize the suppression. Therapy might be preventive with a importance of avoidingcontact oftheproductwiththeeyes. retinoid and should be undertaken as part of a multidisciplinarydecision,whichmightincludealternatives such asthereduction ofimmunosuppression. 9.1.2 Ears The ear is a common site for the presentation of AK and SCC. The risk of metastasis is higher when SCC arises on 9.0 Special considerations the ear. This means that the context of treatment is slightly different at this site than at others. The wish to treat AK 9.1 Bodysites (strengthof recommendation C, levelof with a view to avoiding evolution to SCC may be a greater evidence 2+) priority. Histological diagnosis of any thicker AKs to Thedatafromavailabletreatmentsindicatethatsometreatments differentiate them from invasive SCC by shave biopsy or are more adaptable than others and that morbidity varies with excision is recommended. These interventions may represent location. The balance ofissues determined by location,charactreatment of such AKs or a preliminary to treatment of teristicsoftheAKsandnatureofthepatientaresummarizedin SCC. Table 3.Thescoringisbasedontheauthors\u2019evaluationofefficacy,easeofuse,morbidityandcost-benefit. 9.1.3 Forearm andhands Actinickeratosesonthedorsumofthehandareoftenmultiple 9.1.1 Periocular and hyperkeratotic. Early management with topical therapy or The main consideration for treatment of periocular AK is the PDT may reduce the need for surgical interventions later. The risk of adverse events involving the eye. All products licensed skin is more tolerant of the side-effects of inflammatory treatfor treatment of AK have cautions in the PIL and/or summary ments and hence permits prolongation of the course of treatof product characteristics concerning getting treatment in the ment in some instances. This may be required due to the eye.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 16}, {"text": "instances. This may be required due to the eye. Creams used near the eye can smear into it, and inflamthicker skin or hindrance to treatment penetration by keratin mation caused by local destructive or inflammatory treatments in thicker AKs. Combinations of salicylic acid and 5-FU or such as cryosurgery may impinge upon the eye either directly curettage can be useful elements of treatment for the grade 3 or indirectly. Typically, liquid nitrogen is used with a contact AKs found on the forearm and back of hands (see Secprobe, ensuring thatcold vapour doesnotdamage theeye.162 tion 8.8) \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 16}, {"text": "36 Guidelinesforactinickeratosis2017, D.deBerkeretal. Anecdotal and limited trial data suggest that treatments for 9.1.4 Below theknee AKs in transplant patients are less effective than in the general Actinic keratosis below the knee are often mixed with SCC population,53 perhaps because AKs are more proliferative and in situ, a disposition to NMSC, including atypical BCCs and hyperkeratotic in this group or because new lesions appear other actinic changes. They are a feature of elderly sunrapidly in the treated site. One study in transplant recipients exposed legs and often coincide with decreasing ability to failed to demonstrate a reduction in the development of subheal. Treatments need to find the right balance between sequent skin cancers in those areas of skin previously treated managing the disease and causing complications, which for AKs with PDT.51 Where safety studies are undertaken in include nonhealing and soft-tissue infection. Treatment is transplantpatientstheyappeartodemonstratereactionssimilar likely to be intermittent, low intensity and chronic; most tothosein nontransplant patients.167 reports are case series with small numbers. Infrequent or pulsed application of 5-FU has been employed,68 as has more 9.3 Follow-up intensive treatment using 5-FU chemowraps.165 This entails the application of 5-FU 5% once a week under an occlusive There are no data concerning the benefit of follow-up in bandage for 7 days over a period of 4\u20138 weeks. Gaps in treatpatients with AKs. Patients and their carers should be educated ment canbeneeded whereskin breakagedevelops. regarding changes that suggest malignancy. Those at high risk Diclofenac 3% gel might be employed with the expectation of NMSC, such as organ transplant recipients, may warrant of fewer side-effects, but possibly less benefit. PDT is used on follow-up; the presence of at least 10 AKs is an indicator of thelower legs,particularly wherethere may beproblems with this risk.18 healing. Where treatments are likely to require evaluation and Keyrecommendations: special sites (Table 2) adjustment, follow-up in primary, intermediate or secondary (cid:129) care is needed. This could be by any member of the healthPoor healing sites such as below the knee in the elderly careteamwithvalidatedcompetenciesinthesafeandeffective require flexible regimens, heightened supervision and management of AK. Current NHS guidance suggests that consideration ofless destructive treatments such asPDT. (cid:129) patients with AK should be managed in primary care.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 17}, {"text": "supervision and management of AK. Current NHS guidance suggests that consideration ofless destructive treatments such asPDT. (cid:129) patients with AK should be managed in primary care. Where The ears are commonly affected by AK and require this is a sole pathology and not complicated by NMSC or attention early in respect to all modalities of treatment, other factors, the patient should be provided with information including preventive action with a broad-brimmed hat toenableongoing diagnosis and care. andsunscreen. (cid:129) Grade 3 AKs on the ear may warrant curettage early to obtain histology andavoid missedearly SCC. 9.4 Treatment failure (cid:129) The skin of the dorsum of the hands can be more resisAll treatments have some risk of failing to achieve clearance of tant to treatment than the head and neck, and warrants anindividuallesion.Wherethisisthecase,thereasonforfailextendedperiods oftopical therapy. (cid:129) ure needs assessment, where one of the possible explanations All licensed treatments include warnings about use near might be that the diagnosis is incorrect. Lesions within the the eye. Periocular AK needs careful assessment in secdifferential diagnosis of AK include SCC in situ, invasive SCC, ondary care. Topical treatments may be possible, but seborrhoeic keratosis, actinic porokeratosis, viral wart and clearguidance andsupervision areneeded. others. Depending on the outcome of this clinical assessment, treatment might be escalated in intensity, duration or type, or thelesion might bebiopsied or treated surgically. 9.2 Immunosuppressed patients An alternative interpretation of failure is that the patient Data on the epidemiology and natural progression of AK in continues to get new AKs. This is not true failure, but more the immunosuppressed are less detailed than in the normal an illustration of the nature of the disease. Once someone is population. The risk of progression to SCC is likely to be diagnosed with AK, they are likely to need intermittent, lifehigher, and therefore there is a greater need for treatment of long treatment. AK. Wallingford et al. highlighted the need to monitor transplant patients with field-change AK disease.166 Within a large 10.0 Economic considerations cohort of renal transplant patients, nearly one-third were found to have AKs. Of these, half were isolated AKs and half Table 3summarizes thecost-effectiveness of therapy. were AKs within a field of AK and actinic change.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 17}, {"text": "found to have AKs. Of these, half were isolated AKs and half Table 3summarizes thecost-effectiveness of therapy. were AKs within a field of AK and actinic change. In the subIt is likely that the number of treatment episodes for AK sequent year, the rate of development of SCC associated with will increase. Australian Medicare data demonstrate an increase the isolated AK was 7%, in comparison with 21% of those of 160% between 1994 and 2012 in claims for use of cryowith field change, most of which (11 of 15) arose within the surgery to treat 10 or more AKs. Many studies have tried to field. Other differences between the two groups were that the assess the cost-effectiveness of treatment for AK.168\u2013171 Howpatients with isolated AKs tended to be transplanted later in ever, the methods of calculation and the different healthcare lifeandhadashorter duration ofimmunosuppression.166 systems andtheirwaysof fundingprevent comparison. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 17}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 37 Two nonindustry studies have been published from the quantitative assessment. Examples of all this are found in the U.K. Wilsontried tocomparethecostofPDTandimiquimod, studies referencedin this guideline. taking into account quality of life.172 The author comments Areas of uncertainty in thetreatment of AK that requirefurthat a head-to-head study of imiquimod vs. PDT was required ther studies include (i) measurement and relevance of vitamin to enable more accurate calculations. Muston et al. used effiD and (ii) prospective studies looking at the effect of treatcacy data from the literature to assess the cost\u2013benefit ratio ment ofAKs on subsequent SCCreduction. and reported that the costs and effectiveness of PDT compare well withothertreatmentsfor AK.173 12.0 Recommended audit points At a practical local level, prescriptions that enable the patient tore-treat, extend treatment or treat new areas have an Inthelast20consecutive patients withAKis there cleardocuinherent economic value and enable the patient to exercise mentation of: their judgement. Imiquimod and ingenol mebutate are dis- (cid:129) the location of the AKs indicated on a drawing or a pensed in aliquot packages that are single-treatment doses and head andneckor body map; provided in a number to complete a course of treatment. This (cid:129) the grade or bulk of the AKs (e.g. grade 1, 2, 3 or tightly defines the cost per course of treatment and the terridescriptive; seeTable 1); tory that can be treated. By contrast, Gibbs and Davis noted (cid:129) treatment modality anddosage; that patients used only 31% of the content of a tube of 5-FU (cid:129) information (e.g. a PIL or other suitable source of infor5% in a single course of treatment, which enables substantial mation) provided to the patient on side-effects of treatflexibility in thecourseandterritory oftreatment.174,175 ment,where relevant; (cid:129) the patient having received information on the name 11.0 Future directions andnature oftheir diagnosis; (cid:129) information provided for the GP in diagnosis and future Future directions need to address the human element of bearmanagement, in primary carewhere relevant. ing thelong-term diagnosis of AKand thetechnical challenges of treating AK effectively with low morbidity and acceptable The audit recommendation of 20 cases per department is to cost. The clinical challenge comprises an ageing person with reduce variation in the results due to a single patient, and to barely symptomatic dry areas of skin.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 18}, {"text": "audit recommendation of 20 cases per department is to cost. The clinical challenge comprises an ageing person with reduce variation in the results due to a single patient, and to barely symptomatic dry areas of skin. Education, prevention allow benchmarking between different units. However, and empowerment at this stage may help avoid the situation departments unable to achieve this recommendation may in 10\u201320 years where multiple untreated AKs accumulate and choose toauditallcases seenin thepreceding12 months. the patient presents with advanced AKs mingled with possible SCCs. The earliest stage in the prevention strategy shares 13.0 Summary ground with strategies for the avoidance of skin cancer, and equally shares its concerns of compromised vitamin D levels The findings are summarized in Table 2. See the text for and loss of the indirect benefits of UV exposure. Collaborative details ofevidence. work between patient groups and primary and secondary care Actinic keratoses are a multifocal manifestation of sun damshould aim to find a suitable balanced approach to global care age, comprising a spectrum of clinical complaint and patholof patientswith thisdiagnosis. ogy. They are relapsing and remitting and constitute a chronic Technical assessment of the efficacy of treatments should disease. Most patients can be diagnosed and managed in pricontinue, but usingastandardized modelofreporting. Review mary care. In many instances, management may entail little or of data of AK treatment illustrates the variety of end points in no medical treatment other than advice on sun avoidance and studies, which makes comparison between them difficult. self-monitoring. Where there is clinical concern or the patient These include percentage clearance of lesion number within a specifically wants treatment, therapy can be employed taking person, percentage of people within a study having complete into consideration the specifics of the situation. If there is clearance, percentage of target lesions clearing, and mathematdiagnostic concern or failure torespond tofirst-line treatment, ical models with projected AK behaviour based on withina histological specimen, such as obtained at curettage, shave study data. or formal excision, may be diagnostic and curative. Where The time points at which these measures are defined also AKs are multiple or confluent, at sites of poor healing or with vary and have the scope to alter the result greatly. Treatments poorresponsetostandardtherapies, PDTmay behelpful.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 18}, {"text": "which these measures are defined also AKs are multiple or confluent, at sites of poor healing or with vary and have the scope to alter the result greatly. Treatments poorresponsetostandardtherapies, PDTmay behelpful. Such have optimum times when their outcome is at its best, which patients may also warrant long-term follow-up for the assocican be up to 10 weeks after completion of treatment in the ated increased risk ofNMSC. case of imiquimod. Equally, in the setting of a chronic relapsing and remitting disease, 12and 24-month evaluation Acknowledgments points are relevant. As AK is a multifocal manifestation of sun damage, AKs within a zone at 12 months may represent a We are very grateful to everyone who commented on the mix of relapse and new lesions, which can further complicate draft duringtheconsultation period. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 18}, {"text": "38 Guidelinesforactinickeratosis2017, D.deBerkeretal. References 22 Dodson JM, DeSpain J, Hewett JE etal. Malignant potential of actinic keratoses and the controversy over treatment. A patient1 BellHK,OrmerodAD.WritingaBritishAssociationofDermatolorientedperspective.ArchDermatol1991;127:1029\u201331. ogists clinical guideline: an update on the process and guidance 23 Foote JA, Harris RB, Giuliano AR etal. Predictors for cutaneous forauthors.BrJDermatol2009;160:725\u20138. basaland squamous-cell carcinoma among actinically damaged 2 Brouwers MC, Kho ME, Browman GP etal. AGREE II: advancing adults.IntJCancer2001;95:7\u201311. guideline development, reporting and evaluation in health care. 24 Chen GJ, Feldman SR, Williford PM etal. Clinical diagnosis of CMAJ2010;182:E839\u201342. actinic keratosis identifies an elderly population at high risk of 3 Olsen EA, Abernethy ML, Kulp-Shorten C etal. A double-blind, developingskincancer.DermatolSurg2005;31:43\u20137. vehicle-controlled study evaluating masoprocol cream in the 25 LambertSR,MladkovaN,GulatiAetal.Keydifferencesidentified treatment of actinic keratoses on the head and neck. J Am Acad betweenactinickeratosisandcutaneoussquamouscellcarcinoma Dermatol1991;24:738\u201343. bytranscriptomeprofiling.BrJCancer2014;110:520\u20139. 4 Vatve M, Ortonne JP, Birch-Machin MA etal. Management of 26 Werner RN, Sammain A, Erdmann R etal. The natural history of field change in actinic keratosis. Br J Dermatol 2007; 157(Suppl. actinic keratosis: a systematic review. Br J Dermatol 2013; 2):21\u20134. 169:502\u201318. 5 Freeman RG. Carcinogenic effects of solar radiation and preven27 Janda M. Teledermatology: its use in the detection and managetionmeasures.Cancer1968;21:1114\u201320. mentofactinickeratosis.CurrProblDermatol2015;46:101\u20137. 6 Ziegler A, Jonason AS, Leffell DJ etal. Sunburn and p53 in the 28 Huerta-Brogeras M, Olmos O, Borbujo J etal. Validation of deronsetofskincancer.Nature1994;372:773\u20136. moscopyasareal-timenoninvasivediagnosticimagingtechnique 7 BarrBB,BentonEC,McLarenKetal.Papillomavirusinfectionand foractinickeratosis.ArchDermatol2012;148:1159\u201364. skincancerinrenalallograftrecipients.Lancet1989;2:224\u20135. 29 Scottish Intercollegiate Guidelines Network. Management of dia8 Baudouin C, Charveron M, Tarroux R etal. Environmental pollubetes:anationalclinicalguideline.Availableat:www.sign.ac.uk/ tantsandskincancer.CellBiolToxicol2002;18:341\u20138. pdf/sign116.pdf(lastaccessed16September2016). 9 Wong ST, Chan HL, Teo SK. The spectrum of cutaneous and 30 Shigaki C, Kruse RL, Mehr D etal. Motivation and diabetes selfinternal malignancies in chronic arsenic toxicity. Singapore Med J management.ChronicIlln2010;6:202\u201314. 1998;39:171\u20133. 31 Stockfleth E. The paradigm shift in treating actinic keratosis: a 10 Norris JF. Sunscreens, suntans, and skin cancer. Local councils comprehensivestrategy.JDrugsDermatol2012;11:1462\u20137. should remove sunbeds from leisure centres. BMJ 1996; 32 Gupta AK, Paquet M, Villanueva E etal. Interventions for actinic 313:941\u20132. keratoses.CochraneDatabaseSystRev2012;12:CD004415. 11 BajdikCD,GallagherRP,AstrakianakisGetal.Non-solarultravio33 Esmann S, Vinding GR, Christensen KB etal. Assessing the influlet radiationand the risk of basaland squamous cell skincancer. ence of actinic keratosis on patients\u2019 quality of life: the AKQoL BrJCancer1996;73:1612\u20134. questionnaire.BrJDermatol2013;168:277\u201383. 12 RoestMA,KeaneFM,AgnewKetal.Multiplesquamousskincar34 EsmannS.Patients\u2019perspectivesonactinickeratosis.CurrProblDercinomas following excess sunbed use. J R Soc Med 2001; 94:636\u2013 matol2015;46:8\u201313. 7. 35 PomerantzH,HoganD,EilersDetal.Long-termefficacyoftopi13 AtkinsD,BangRH,SternbergMRetal.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 19}, {"text": "skincancer. ence of actinic keratosis on patients\u2019 quality of life: the AKQoL BrJCancer1996;73:1612\u20134. questionnaire.BrJDermatol2013;168:277\u201383. 12 RoestMA,KeaneFM,AgnewKetal.Multiplesquamousskincar34 EsmannS.Patients\u2019perspectivesonactinickeratosis.CurrProblDercinomas following excess sunbed use. J R Soc Med 2001; 94:636\u2013 matol2015;46:8\u201313. 7. 35 PomerantzH,HoganD,EilersDetal.Long-termefficacyoftopi13 AtkinsD,BangRH,SternbergMRetal.Reliablemethodstoevalcal fluorouracil cream, 5%, for treating actinic keratosis: a ranuate the burden of actinic keratoses. J Invest Dermatol 2006; domizedclinicaltrial.JAMADermatol2015;151:952\u201360. 126:591\u20134. 36 Witheiler DD, Lawrence N, Cox SE etal. Long-term efficacy and 14 O\u2019Beirn SFO, Judge P, Maccon CF etal. Skin cancer in County safety of Jessner\u2019s solution and 35% trichloroacetic acid versus Galway, Ireland. In: Proceedings of the Sixth National Cancer Conference, 5% fluorouracilin the treatmentofwidespreadfacial actinickersponsoredbytheAmericanCancerSocietyInc.andtheNationalCancerInstitute, atoses.DermatolSurg1997;23:191\u20136. September1968.Philadelphia:Lippincott,1970;489\u2013500. 37 KaminakaC,YamamotoY,YoneiNetal.Phenolpeelsasanovelther15 Harvey I, Frankel S, Marks R etal. Non-melanoma skin cancer apeuticapproachforactinickeratosisandBowendisease:prospective and solar keratoses. I. Methods and descriptive results of the pilottrialwithassessmentofclinical,histologic,andimmunohistoSouthWalesSkinCancerStudy.BrJCancer1996;74:1302\u20137. chemicalcorrelations.JAmAcadDermatol2009;60:615\u201325. 16 Memon AA, Tomenson JA, Bothwell J etal. Prevalence of solar 38 Ditre CM. Treatment of actinic keratosis and photodamaged skin damageandactinickeratosisinaMerseysidepopulation.BrJDerwith 5-fluorouracil 5% cream and glycolic acid peels. Cosmet Dermatol2000;142:1154\u20139. matol2004;17:25\u20137. 17 Eder J, Prillinger K, Korn A etal. Prevalence of actinic keratosis 39 Swinehart JM. Salicylic acid ointment peeling of the hands and among dermatology outpatients in Austria. Br J Dermatol 2014; forearms.Effectivenonsurgicalremovalofpigmentedlesionsand 171:1415\u201321. actinicdamage.JDermatolSurgOncol1992;18:495\u20138. 18 Flohil SC, van der Leest RJ, Dowlatshahi EA etal. Prevalence of 40 Werner RN, Stockfleth E, Connolly SM etal. Evidenceand conactinickeratosisanditsriskfactorsinthegeneralpopulation:the sensus-based(S3)GuidelinesfortheTreatmentofActinicKeratoRotterdamStudy.JInvestDermatol2013;133:1971\u20138. sis \u2013 International League of Dermatological Societies in 19 Marks R, Foley P, Goodman G etal. Spontaneous remission of cooperation with the European Dermatology Forum \u2013 short versolarkeratoses:thecaseforconservativemanagement.BrJDermasion.JEurAcadDermatolVenereol2015;29:2069\u201379. tol1986;115:649\u201355. 41 National Institute for Health and Care Excellence. Improving 20 Criscione VD, Weinstock MA, Naylor MF etal. Actinic keratoses: outcomes for people with skin tumours including melanoma. naturalhistoryandriskofmalignanttransformationintheVeterAvailable at: https://www.nice.org.uk/guidance/csg8 (last ansAffairsTopicalTretinoinChemopreventionTrial.Cancer2009; accessed16September2016). 115:2523\u201330. 42 Chetty P, Choi F, Mitchell T. Primary care review of actinic ker21 Marks R, Rennie G, Selwood TS. Malignant transformation of atosis and its therapeutic options: a global perspective. Dermatol solarkeratosestosquamouscellcarcinoma.Lancet1988;1:795\u20137. Ther(Heidelb)2015;5:19\u201335. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 19}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 39 43 Englert C, Hughes B. A review of actinic keratosis for the nurse 62 Eaglstein WH, Weinstein GD, Frost P. Fluorouracil: mechanism practitioner: diagnosis, treatment, and clinical pearls. J Am Acad of action in human skin and actinic keratoses. I. Effect on DNA NursePract2012;24:290\u20136. synthesisinvivo.ArchDermatol1970;101:132\u20139. 44 Primary Care Dermatology Society. Actinic (solar) keratosis: pri63 Ingenol mebutate (Picato) for actinic keratosis. Med Lett Drugs Ther mary care treatment pathway. Available at: http://www.pcds.or2012;54:35\u20136. g.uk/ee/images/uploads/general/Actinic_%28Solar%29_Kerato64 StockflethE, KerlH, ZwingersT etal. Low-dose5-fluorouracilin sis_Primary_Care_Treatment_Pathway.pdf (last accessed 16 combination with salicylic acid as a new lesion-directed option September2016). to treat topically actinic keratoses: histological and clinical study 45 Primary Care Dermatology Society. Actinic keratosis (syn. solar results.BrJDermatol2011;165:1101\u20138. keratosis). Available at: http://www.pcds.org.uk/clinical-gui65 GuptaAK,PaquetM.Networkmeta-analysisoftheoutcome\u2018pardance/actinic-keratosis-syn.-solar-keratosis (last accessed 16 ticipant complete clearance\u2019 in non-immunosuppressed particiSeptember2016). pantsofeightinterventionsforactinickeratosis:afollow-upona 46 ThompsonSC,JolleyD,MarksR.Reductionofsolarkeratosesby Cochranereview.BrJDermatol2013;169:250\u20139. regularsunscreenuse.NEnglJMed1993;329:1147\u201351. 66 Kurwa HA, Yong-Gee SA, Seed PT etal. A randomized paired 47 Naylor MF, Boyd A, Smith DW etal. High sun protection factor comparison of photodynamic therapy and topical 5-fluorouracil sunscreens in the suppression of actinic neoplasia. Arch Dermatol in the treatment of actinic keratoses. J Am Acad Dermatol 1999; 1995;131:170\u20135. 41:414\u20138. 48 Green A, Williams G, Neale R etal. Daily sunscreen application 67 Robinson TA, Kligman AM. Treatment of solar keratoses of the and betacarotene supplementation in preventionof basal-celland extremities with retinoic acid and 5-fluorouracil. Br J Dermatol squamous-cell carcinomas of the skin: a randomised controlled 1975;92:703\u20136. trial.Lancet1999;354:723\u20139. 68 Pearlman DL. Weekly pulse dosing: effective and comfortable 49 Ulrich C, Jurgensen JS, Degen A etal. Prevention of non-melatopical 5-fluorouracil treatment of multiple facial actinic kernomaskincancerinorgantransplantpatientsbyregularuseofa atoses.JAmAcadDermatol1991;25:665\u20137. sunscreen:a24months,prospective,case\u2013controlstudy.BrJDer69 Epstein E. Does intermittent \u2018pulse\u2019 topical 5-fluorouracil therapy matol2009;161(Suppl.3):78\u201384. allow destruction of actinic keratoses without significant inflam50 Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transmation?JAmAcadDermatol1998;38:77\u201380. plantation.NEnglJMed2003;348:1681\u201391. 70 Jury CS, Ramraka-Jones VS, Gudi V etal. A randomized trial of 51 deGraafYG,KennedyC,WolterbeekRetal.Photodynamicthertopical5%5-fluorouracil(Efudixcream)inthetreatmentofactiapy does not prevent cutaneous squamous-cell carcinoma in nickeratosescomparingdailywithweeklytreatment.BrJDermatol organ-transplant recipients: results of a randomized-controlled 2005;153:808\u201310. trial.JInvestDermatol2006;126:569\u201374. 71 Schlaak M, Simon JC. Topical treatment of actinic keratoses with 52 HarwoodCA,MesherD,McGregorJMetal.Asurveillancemodel low-dose5-fluorouracilincombinationwithsalicylicacid\u2013pilot forskin cancer in organ transplant recipients: a 22-yearprospecstudy.JDtschDermatolGes2010;8:174\u20138. tive study in an ethnically diverse population. Am J Transplant 72 Stockfleth E, Zwingers T, Willers C. Recurrence rates and patient 2013;13:119\u201329. assessedoutcomesof0.5%5-fluorouracilincombinationwithsali53 Dragieva G, Hafner J, Dummer R etal. Topical photodynamic cylicacidtreatingactinickeratoses.EurJDermatol2012;22:370\u20134.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 20}, {"text": "recipients: a 22-yearprospecstudy.JDtschDermatolGes2010;8:174\u20138. tive study in an ethnically diverse population. Am J Transplant 72 Stockfleth E, Zwingers T, Willers C. Recurrence rates and patient 2013;13:119\u201329. assessedoutcomesof0.5%5-fluorouracilincombinationwithsali53 Dragieva G, Hafner J, Dummer R etal. Topical photodynamic cylicacidtreatingactinickeratoses.EurJDermatol2012;22:370\u20134. therapyin thetreatmentofactinickeratosesand Bowen\u2019sdisease 73 Szeimies RM, Dirschka T, Prechtl A etal. Efficacy of low-dose 5intransplantrecipients.Transplantation2004;77:115\u201321. fluorouracil/salicylic acid in actinic keratoses in relation to treat54 McNamara IR, Muir J, Galbraith AJ. Acitretin for prophylaxis of mentduration.JDtschDermatolGes2015;13:430\u20138. cutaneous malignancies after cardiac transplantation. J Heart Lung 74 Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: Transplant2002;21:1201\u20135. systematic review and meta-analysis. J Invest Dermatol 2006; 55 Jirakulaporn T,EndrizziB, LindgrenBetal. Capecitabineforskin 126:1251\u20135. cancer prevention in solid organ transplant recipients. Clin Trans75 Stockfleth E, Meyer T, Benninghoff B etal. A randomized, douplant2011;25:541\u20138. ble-blind,vehicle-controlledstudytoassess5%imiquimodcream 56 Black HS, Herd JA, Goldberg LH etal. Effect of a low-fat diet on forthetreatmentofmultipleactinickeratoses.ArchDermatol2002; theincidenceofactinickeratosis.NEnglJMed1994;330:1272\u20135. 138:1498\u2013502. 57 RiversJK,ArletteJ,ShearNetal.Topicaltreatmentofactinicker76 Korman N, Moy R, Ling M etal. Dosing with 5% imiquimod atoseswith 3.0%diclofenacin 2.5%hyaluronangel.Br JDermatol cream 3 times per week for the treatment of actinic keratosis: 2002;146:94\u2013100. resultsoftwophase3,randomized,double-blind,parallel-group, 58 Akarsu S, Aktan S, Atahan A etal. Comparison of topical 3% vehicle-controlledtrials.ArchDermatol2005;141:467\u201373. diclofenac sodium gel and 5% imiquimod cream for the treat77 Alomar A, Bichel J, McRae S. Vehicle-controlled, randomized, mentofactinickeratoses.ClinExpDermatol2011;36:479\u201384. double-blindstudytoassesssafetyandefficacyofimiquimod5% 59 Szeimies RM, Gerritsen MJ, Gupta G etal. Imiquimod 5% cream creamappliedoncedaily3daysperweekinoneortwocourses for the treatment of actinic keratosis: results from a phase III, of treatment of actinic keratoses on the head. Br J Dermatol 2007; randomized, double-blind, vehicle-controlled, clinical trial with 157:133\u201341. histology.JAmAcadDermatol2004;51:547\u201355. 78 FoleyP,MerlinK,CummingSetal.Acomparisonofcryotherapy 60 Jorizzo J, Dinehart S, Matheson R etal. Vehicle-controlled, douand imiquimod for treatment of actinic keratoses: lesion clearble-blind, randomized study of imiquimod 5% cream applied ance, safety, and skin quality outcomes. J Drugs Dermatol 2011; 3days per week in one or two courses of treatment for actinic 10:1432\u20138. keratosesonthehead.JAmAcadDermatol2007;57:265\u20138. 79 Pini AM, Koch S, Scharer L etal. Eruptive keratoacanthoma fol61 DarlingtonS,WilliamsG,NealeRetal.Arandomizedcontrolledtrial lowing topical imiquimod for in situ squamous cell carcinoma of toassesssunscreenapplicationandbetacarotenesupplementationin the skin in a renal transplant recipient. J Am Acad Dermatol 2008; thepreventionofsolarkeratoses.ArchDermatol2003;139:451\u20135. 59(5Suppl.):S116\u20137. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 20}, {"text": "Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 20}, {"text": "40 Guidelinesforactinickeratosis2017, D.deBerkeretal. 80 Serra-GuillenC,NagoreE,HuesoLetal.Arandomizedcompara96 Anderson L, Melgaard A, Schmeider G etal. Two-day topical tivestudyoftoleranceandsatisfactioninthetreatmentofactinic treatment with ingenol mebutate gel, 0.05% for actinic keratoses keratosisofthefaceandscalpbetween5%imiquimodcreamand on the trunk and extremities: analysis of data pooled from two photodynamictherapywithmethylaminolaevulinate.BrJDermatol trials.JAmAcadDermatol2012;66:AB159. 2011;164:429\u201333. 97 US Food and Drug Administration. Picato (ingenol mebutate) 81 Krawtchenko N, Roewert-Huber J, Ulrich M etal. A randomised gel: drug safety communication \u2013 FDA warns of severe adverse studyoftopical5%imiquimodvs.topical5-fluorouracilvs.cryoevents,requireslabelchanges.Availableat:http://www.fda.gov/ surgery in immunocompetent patients with actinic keratoses: a Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicomparisonofclinicalandhistologicaloutcomesincluding1-year calProducts/ucm459311.htm(lastaccessed16September2016). follow-up.BrJDermatol2007;157(Suppl.2):34\u201340. 98 KuJ.Clinicalreview.NDA202833.PICATOTM(ingenolmebutate 82 LeePK,HarwellWB,LovenKHetal.Long-termclinicaloutcomes gel, PEP005 gel). Available at: http://www.accessdata.fda.- following treatment of actinic keratosis with imiquimod 5% gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf cream.DermatolSurg2005;31:659\u201364. (lastaccessed16September2016). 83 HankeCW,BeerKR,StockflethEetal.Imiquimod2.5%and3.75% 99 Erlendsson AM, Karmisholt KE, Haak CS etal. Topical corticosforthetreatmentofactinickeratoses:resultsoftwoplacebo-conteroidhasnoinfluenceon inflammation or efficacyafteringenol trolledstudiesofdailyapplicationtothefaceandbaldingscalpfor mebutatetreatmentofgradeItoIIIactinickeratoses(AK):arantwo3-weekcycles.JAmAcadDermatol2010;62:573\u201381. domizedclinicaltrial.JAmAcadDermatol2016;74:709\u201315. 84 Hanke CW, Swanson N, Bruce S etal. Complete clearance is sus100 IanhezM,FleuryLFJr,MiotHAetal.Retinoidsforpreventionand tained for at least 12months after treatment of actinic keratoses treatmentofactinickeratosis.AnBrasDermatol2013;88:585\u201393. of the face or balding scalp via daily dosing with imiquimod 101 KangS, GoldfarbMT,Weiss JS etal.Assessmentofadapalenegel 3.75%or2.5%cream.JDrugsDermatol2011;10:165\u201370. for the treatment of actinic keratoses and lentigines: a random85 SwansonN,AbramovitsW,BermanBetal.Imiquimod2.5%and izedtrial.JAmAcadDermatol2003;49:83\u201390. 3.75% for the treatment of actinic keratoses: results of two pla102 WeinstockMA,BinghamSF,LewRAetal.Topicaltretinointhercebo-controlled studies of daily application to the face and baldapyandall-causemortality.ArchDermatol2009;145:18\u201324. ing scalp for two 2-week cycles. J Am Acad Dermatol 2010; 103 Thai KE, Fergin P, Freeman M etal. A prospective study of the 62:582\u201390. useofcryosurgeryforthetreatmentofactinickeratoses.IntJDer86 Jorizzo JL, Markowitz O, Lebwohl MG etal. A randomized, doumatol2004;43:687\u201392. ble-blinded, placebo-controlled, multicenter, efficacy and safety 104 Szeimies RM, Karrer S, Radakovic-Fijan S etal. Photodynamic study of 3.75% imiquimod cream following cryosurgery for the therapy using topical methyl 5-aminolevulinate compared with treatmentofactinickeratoses.JDrugsDermatol2010;9:1101\u20138. cryotherapy for actinic keratosis: a prospective, randomized 87 Goldenberg G, Linkner RV, Singer G etal. An investigatorstudy.JAmAcadDermatol2002;47:258\u201362. initiated study to assess the safety and efficacy of imiquimod 105 FreemanM,VinciulloC,FrancisDetal.Acomparisonofphotody3.75% cream when used after cryotherapy in the treatment of namictherapyusingtopicalmethylaminolevulinate(Metvix)with hypertrophic actinic keratoses on dorsal hands and forearms. J single cycle cryotherapy in patients with actinic keratosis: a ClinAesthetDermatol2013;6:36\u201343. prospective,randomizedstudy.JDermatologTreat2003;14:99\u2013106. 88 Smith SR, Morhenn VB, Piacquadio DJ. Bilateral comparison of 106 KaufmannR,SpelmanL,WeightmanWetal.Multicentreintrainthe efficacyandtolerabilityof3% diclofenacsodiumgeland 5% dividual randomized trial of topical methyl aminolaevulinate5-fluorouracil cream in the treatment of actinic keratoses of the photodynamic therapy vs. cryotherapy for multiple actinic kerfaceandscalp.JDrugsDermatol2006;5:156\u20139. atosesontheextremities.BrJDermatol2008;158:994\u20139. 89 Segatto MM, Dornelles SI, Silveira VB etal.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 21}, {"text": "of topical methyl aminolaevulinate5-fluorouracil cream in the treatment of actinic keratoses of the photodynamic therapy vs. cryotherapy for multiple actinic kerfaceandscalp.JDrugsDermatol2006;5:156\u20139. atosesontheextremities.BrJDermatol2008;158:994\u20139. 89 Segatto MM, Dornelles SI, Silveira VB etal. Comparative study of 107 Morton C, Campbell S, Gupta G etal. Intraindividual, right\u2013left actinickeratosistreatmentwith3%diclofenacsodiumand5%5comparison of topical methyl aminolaevulinate-photodynamic fluorouracil.AnBrasDermatol2013;88:732\u20138. therapyandcryotherapyinsubjectswithactinickeratoses:amul90 Wolf JE, Taylor JR, Tschen E etal. Topical 3.0% diclofenac in ticentre, randomized controlled study. Br J Dermatol 2006; 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J 155:1029\u201336. Dermatol2001;40:709\u201313. 108 Chiarello SE. Cryopeeling (extensive cryosurgery) for treatment 91 Pflugfelder A, Welter AK, Leiter U etal. Open label randomized of actinic keratoses: an update and comparison. Dermatol Surg studycomparing3monthsvs.6monthstreatmentofactinicker2000;26:728\u201332. atoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of 109 AbadirDM.Combinationoftopical5-fluorouracilwithcryothertheGermanDermatologicCooperativeOncologyGroup.JEurAcad apy for treatment of actinic keratoses. J Dermatol Surg Oncol 1983; DermatolVenereol2012;26:48\u201353. 9:403\u20134. 92 Anderson L, Schmieder GJ, Werschler WP etal. Randomized, 110 JorizzoJ,WeissJ,FurstKetal.Effectofa1-weektreatmentwith double-blind,double-dummy,vehicle-controlledstudyofingenol 0.5% topical fluorouracil on occurrence of actinic keratosis after mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad cryosurgery: a randomized, vehicle-controlled clinical trial. Arch Dermatol2009;60:934\u201343. Dermatol2004;140:813\u20136. 93 Lebwohl M,SwansonN, AndersonLL etal. Ingenol mebutategel 111 MotleyR,KerseyP,LawrenceCetal.Multiprofessionalguidelines foractinickeratosis.NEnglJMed2012;366:1010\u20139. forthemanagementofthepatientwithprimarycutaneoussqua94 Lebwohl M, Shumack S, Stein Gold L etal. Long-term follow-up mouscellcarcinoma.BrJDermatol2002;146:18\u201325. study of ingenol mebutate gel for the treatment of actinic ker112 MoriartyM,DunnJ,DarraghAetal.Etretinateintreatmentofactiatoses.JAMADermatol2013;149:666\u201370. nickeratosis.Adouble-blindcrossoverstudy.Lancet1982;1:364\u20135. 95 Garbe C, Basset-Seguin N, Poulin Y etal. Efficacy and safety of 113 Watson AB. Preventative effect of etretinate therapy on multiple follow-upfieldtreatmentofactinickeratosiswithingenolmebuactinickeratoses.CancerDetectPrev1986;9:161\u20135. tate 0.015% gel: a randomized, controlled 12-month study. Br J 114 Smit JV, de Sevaux RG, Blokx WA etal. Acitretin treatment in Dermatol2016;174:505\u201313. (pre)malignant skin disorders of renal transplant recipients: BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 21}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 41 histologic and immunohistochemical effects. J Am Acad Dermatol 130 Scola N, Terras S, Georgas D etal. A randomized, half-side com2004;50:189\u201396. parativestudyofaminolaevulinatephotodynamictherapyvs.CO 2 115 EBPGExpertGrouponRenalTransplantation.Europeanbestpraclaserablationinimmunocompetentpatientswithmultipleactinic tice guidelines for renal transplantation. Section IV: long-term keratoses.BrJDermatol2012;167:1366\u201373. management of the transplant recipient. IV.6.2. Cancer risk after 131 Patel G, Armstrong AW, Eisen DB. Efficacy of photodynamic renal transplantation. Skin cancers: prevention and treatment. therapy versus other interventions in randomized clinical trials NephrolDialTransplant2002;17:S31\u20136. for the treatment of actinic keratoses: a systematic review and 116 Kovach BT, Murphy G, Otley CC etal. Oral retinoids for chemometa-analysis.JAMADermatol2014;150:1281\u20138. prevention of skin cancers in organ transplant recipients: results 132 Serra-Guillen C, Nagore E, Hueso L etal. A randomized pilot ofasurvey.TransplantProc2006;38:1366\u20138. comparative study of topical methyl aminolevulinate photody117 Elmets CA, Viner JL, Pentland AP etal. Chemoprevention of nonnamic therapy versus imiquimod 5% versus sequential applicamelanomaskincancerwithcelecoxib:arandomized,double-blind, tionofboththerapiesinimmunocompetentpatientswithactinic placebo-controlledtrial.JNatlCancerInst2010;102:1835\u201344. keratosis: clinical and histologic outcomes. J Am Acad Dermatol 118 LiebmanTN,SteinJA,PolskyD.Cyclo-oxygenase-2inhibitorsfor 2012;66:e131\u20137. chemoprevention of nonmelanoma skin cancer: is there a role 133 Hadley J, Tristani-Firouzi P, Hull C etal. Results of an investigafortheseagents?JAmAcadDermatol2013;68:173\u20136. tor-initiated single-blind split-face comparison of photodynamic 119 Dirschka T, Radny P, Dominicus R etal. Photodynamic therapy therapy and 5% imiquimod cream for the treatment of actinic withBF-200ALAforthetreatmentofactinickeratosis:resultsof keratoses.DermatolSurg2012;38:722\u20137. a multicentre, randomized, observer-blind phase III study in 134 Sotiriou E, Apalla Z, Maliamani F etal. Intraindividual, right-left comparison with a registered methyl-5-aminolaevulinate cream comparison of topical 5-aminolevulinic acid photodynamic therandplacebo.BrJDermatol2012;166:137\u201346. apy vs. 5% imiquimod cream for actinic keratoses on the upper 120 Szeimies RM, Radny P, Sebastian M etal. Photodynamic therapy extremities.JEurAcadDermatolVenereol2009;23:1061\u20135. withBF-200ALAforthetreatmentofactinickeratosis:resultsof 135 HauschildA,StockflethE,PoppGetal.Optimizationofphotodya prospective, randomized, double-blind, placebo-controlled namic therapy with a novel self-adhesive 5-aminolaevulinic acid phaseIIIstudy.BrJDermatol2010;163:386\u201394. patch:resultsoftworandomizedcontrolledphaseIIIstudies.BrJ 121 Morton CA, Szeimies RM, Sidoroff A etal. European guidelines Dermatol2009;160:1066\u201374. for topical photodynamic therapy part 1: treatment delivery and 136 Szeimies RM, Stockfleth E, Popp G etal. Long-term follow-up of currentindications\u2013actinickeratoses,Bowen\u2019sdisease,basalcell photodynamic therapy with a self-adhesive 5-aminolaevulinic carcinoma.JEurAcadDermatolVenereol2013;27:536\u201344. acidpatch:12monthsdata.BrJDermatol2010;162:410\u20134. 122 Klein A, Karrer S, Horner C etal. Comparing cold-air analgesia, 137 Wiegell SR, Haedersdal M, Philipsen PA etal. Continuous activasystemically administered analgesia and scalp nerve blocks for tion of PpIX by daylight is as effective as and less painful than pain management during photodynamic therapy for actinic kerconventional photodynamic therapy for actinic keratoses; a ranatosisofthescalppresentingasfieldcancerization:arandomized domized, controlled, single-blinded study.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 22}, {"text": "for tion of PpIX by daylight is as effective as and less painful than pain management during photodynamic therapy for actinic kerconventional photodynamic therapy for actinic keratoses; a ranatosisofthescalppresentingasfieldcancerization:arandomized domized, controlled, single-blinded study. Br J Dermatol 2008; controlledtrial.BrJDermatol2015;173:192\u2013200. 158:740\u20136. 123 Petersen B, Wiegell SR, Wulf HC. Light protection of the skin 138 Wiegell SR, Haedersdal M, Eriksen P etal. Photodynamic therapy after photodynamic therapy reduces inflammation: an unblinded of actinic keratoses with 8% and 16% methyl aminolaevulinate randomizedcontrolledstudy.BrJDermatol2014;171:175\u20138. andhome-baseddaylightexposure:adouble-blindedrandomized 124 Tarstedt M, Rosdahl I, Berne B etal. A randomized multicenter clinicaltrial.BrJDermatol2009;160:1308\u201314. study to compare two treatment regimens of topical methyl 139 Wiegell SR, Fabricius S, Stender IM etal. A randomized, multiaminolevulinate (Metvix(cid:1))-PDT in actinic keratosis of the face centre studyof directeddaylight exposure timesof 1\u00bd vs.2\u00bd h andscalp.ActaDermVenereol2005;85:424\u20138. in daylight-mediated photodynamic therapy with methyl amino125 Piacquadio DJ, Chen DM, Farber HF etal. Photodynamic therapy laevulinate in patients with multiple thin actinic keratoses of the withaminolevulinicacidtopicalsolutionandvisiblebluelightin faceandscalp.BrJDermatol2011;164:1083\u201390. the treatment of multiple actinic keratoses of the face and scalp: 140 Rubel DM, Spelman L, Murrell DF etal. Daylight photodynamic investigator-blinded, phase 3, multicenter trials. Arch Dermatol therapywithmethylaminolevulinatecreamasaconvenient,sim2004;140:41\u20136. ilarly effective, nearly painless alternative to conventional photo126 Taub AF, Garretson CB. A randomized, blinded, bilateral intraindynamic therapy in actinic keratosis treatment: a randomized dividual, vehicle-controlled trial of the use of photodynamic controlledtrial.BrJDermatol2014;171:1164\u201371. therapy with 5-aminolevulinic acid and blue light for the treat141 Lacour JP, Ulrich C, Gilaberte Y etal. Daylight photodynamic mentofactinickeratosesoftheupperextremities.JDrugsDermatol therapy with methyl aminolevulinate cream is effective and 2011;10:1049\u201356. nearly painless in treating actinic keratoses: a randomised, inves127 Tschen EH, Wong DS, Pariser DM etal. Photodynamic therapy tigator-blinded, controlled, phase III study throughout Europe. J using aminolaevulinic acid for patients with nonhyperkeratotic EurAcadDermatolVenereol2015;29:2342\u20138. actinic keratoses of the face and scalp: phase IV multicentre 142 Morton CA, Wulf HC, Szeimies RM etal. Practical approach to clinical trial with 12-month follow up. Br J Dermatol 2006; the use of daylight photodynamic therapy with topical methyl 155:1262\u20139. aminolevulinate for actinic keratosis: a European consensus. J Eur 128 SotiriouE,ApallaZ,ChovardaEetal.Singlevs.fractionatedphoAcadDermatolVenereol2015;29:1718\u201323. todynamictherapyforfaceandscalpactinickeratoses:arandom143 SeeJA,ShumackS,MurrellDFetal.Consensusrecommendations ized,intraindividualcomparisontrialwith12-monthfollow-up.J on the use of daylight photodynamic therapy with methyl EurAcadDermatolVenereol2012;26:36\u201340. aminolevulinatecreamforactinickeratosesin Australia.AustralasJ 129 Togsverd-Bo K, Haak CS, Thaysen-Petersen D etal. Intensified Dermatol2016;57:167\u201374. photodynamic therapy of actinic keratoses with fractional CO 144 Wiegell SR, Wulf HC, Szeimies RM etal.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 22}, {"text": "of daylight photodynamic therapy with methyl EurAcadDermatolVenereol2012;26:36\u201340. aminolevulinatecreamforactinickeratosesin Australia.AustralasJ 129 Togsverd-Bo K, Haak CS, Thaysen-Petersen D etal. Intensified Dermatol2016;57:167\u201374. photodynamic therapy of actinic keratoses with fractional CO 144 Wiegell SR, Wulf HC, Szeimies RM etal. Daylight photodynamic 2 laser:arandomizedclinicaltrial.BrJDermatol2012;166:1262\u20139. therapy for actinic keratosis: an international consensus: \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 22}, {"text": "42 Guidelinesforactinickeratosis2017, D.deBerkeretal. International Society for Photodynamic Therapy in Dermatology. 164 Cannon PS, O\u2019Donnell B, Huilgol SC etal. The ophthalmic sideJEurAcadDermatolVenereol2012;26:673\u20139. effects of imiquimod therapy in the management of periocular 145 Genovese G, Fai D, Fai C etal. Daylight methyl-aminolevulinate skinlesions.BrJOphthalmol2011;95:1682\u20135. photodynamictherapyversusingenolmebutateforthetreatment 165 Tallon B, Turnbull N. 5% Fluorouracil chemowraps in the manof actinic keratoses: an intraindividual comparative analysis. Deragement of widespread lower leg solar keratoses and squamous matolTher2016;29:191\u20136. cellcarcinoma.AustralasJDermatol2013;54:313\u20136. 146 de Vries K, Prens EP. Laser treatment and its implications for 166 Wallingford SC, Russell SA, Vail A etal. Actinic keratoses, actinic photodamagedskinand actinickeratosis.CurrProblDermatol2015; field change and associations with squamous cell carcinoma in 46:129\u201335. renal transplant recipients in Manchester, U.K. Acta Derm Venereol 147 Ostertag JU, Quaedvlieg PJ, van der Geer S etal. A clinical com2015;95:830\u20134. parison and long-term follow-up of topical 5-fluorouracil versus 167 InghamAI,WeightmanW.Theefficacyandsafetyoftopical5% laserresurfacinginthetreatmentofwidespreadactinickeratoses. 5-fluorouracil in renal transplant recipients for the treatment of LasersSurgMed2006;38:731\u20139. actinickeratoses.AustralasJDermatol2014;55:204\u20138. 148 Hantash BM, Stewart DB, Cooper ZA etal. Facial resurfacing for 168 Annemans L, Caekelbergh K, Roelandts R etal. Real-life practice nonmelanoma skin cancer prophylaxis. Arch Dermatol 2006; study of the clinical outcome and cost-effectiveness of photody142:976\u201382. namic therapy using methyl aminolevulinate (MAL-PDT) in the 149 SherrySD,MilesBA,FinnRA.Long-termefficacyofcarbondioxmanagement of actinic keratosis and basal cell carcinoma. Eur J idelaserresurfacingforfacialactinickeratosis.JOralMaxillofacSurg Dermatol2008;18:539\u201346. 2007;65:1135\u20139. 169 CaekelberghK,AnnemansL,LambertJetal.Economicevaluation 150 IyerS,FriedliA,BowesLetal.Fullfacelaserresurfacing:therapy of methyl aminolaevulinate-based photodynamic therapy in the and prophylaxis for actinic keratoses and non-melanoma skin management of actinic keratosis and basal cell carcinoma. Br J cancer.LasersSurgMed2004;34:114\u20139. Dermatol2006;155:784\u201390. 151 Ostertag JU, Quaedvlieg PJF, Neumann MHAM, Krekels GA. 170 Colombo GL, Chimenti S, Di Matteo S etal. Cost-effectiveness Recurrence rates and long-term follow-up after laser resurfacing analysis of topical treatments for actinic keratosis in the perspecasatreatmentforwidespreadactinickeratosesinthefaceandon tive of the Italian health care system. G Ital Dermatol Venereol 2010; thescalp.DermatolSurg2006;32:261\u20137. 145:573\u201381. 152 GanSD,HsuSH,ChuangGetal.Ablativefractionallasertherapy 171 GoldMH. Pharmacoeconomicanalysisofthe treatmentofmultiforthetreatmentofactinickeratosis:asplit-facestudy.JAmAcad pleactinickeratoses.JDrugsDermatol2008;7:23\u20135. Dermatol2016;74:387\u20139. 172 Wilson EC. Cost effectiveness of imiquimod 5% cream compared 153 Prens SP, de Vries K, Neumann HA etal. Non-ablative fractional with methyl aminolevulinate-based photodynamic therapy in the resurfacingincombinationwithtopicaltretinoincreamasafield treatment of non-hyperkeratotic, non-hypertrophic actinic (solar) treatment modality for multiple actinic keratosis: a pilot study keratoses: a decision tree model. Pharmacoeconomics 2010; 28:1055\u2013 and areview of other fieldtreatmentmodalities.J DermatologTreat 64. 2013;24:227\u201331. 173 MustonD,DownsA,RivesV.Aneconomicevaluationoftopical 154 ColemanWP,YarboroughJM,MandySH.Dermabrasionforprotreatments for actinic keratosis.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 23}, {"text": "keratosis: a pilot study keratoses: a decision tree model. Pharmacoeconomics 2010; 28:1055\u2013 and areview of other fieldtreatmentmodalities.J DermatologTreat 64. 2013;24:227\u201331. 173 MustonD,DownsA,RivesV.Aneconomicevaluationoftopical 154 ColemanWP,YarboroughJM,MandySH.Dermabrasionforprotreatments for actinic keratosis. J Dermatolog Treat 2009; 20:266\u2013 phylaxis and treatment of actinic keratoses. Dermatol Surg 1996; 75. 22:17\u201321. 174 GibbsS,DavisT.Usageandpatientexperienceof5%fluorouracil 155 WintonGB,SalascheSJ.Dermabrasionofthescalpasatreatment cream.ClinExpDermatol2015;40:88. foractinicdamage.JAmAcadDermatol1986;14:661\u20138. 175 PereraE,McGuiganS,SinclairR.Costforthetreatmentofactinic 156 MastrolonardoM.Topicaldiclofenac3%gelpluscryotherapyfor keratosisontheriseinAustralia.F1000Res2014;3:184. treatmentofmultipleandrecurrentactinickeratoses.ClinExpDer176 Pariser DM, Lowe NJ, Stewart DM etal. Photodynamic therapy matol2009;34:33\u20135. with topical methyl aminolevulinate for actinic keratosis: results 157 BerlinJM,RigelDS.Diclofenacsodium3%gelinthetreatmentof of a prospective randomized multicenter trial. J Am Acad Dermatol actinickeratosespostcryosurgery.JDrugsDermatol2008;7:669\u201373. 2003;48:227\u201332. 158 VanderGeerS,KrekelsGA.Treatmentofactinickeratosesonthe 177 Colechin E, Sims A, Reay C etal. Ambulight photodynamic therdorsum of the hands: ALA-PDT versus diclofenac 3% gel folapy.Availableat:http://www.nice.org.uk/guidance/mtg6/doculowed by ALA-PDT. A placebo-controlled, double-blind, pilot ments/ambulight-photodynamic-therapy-for-the-treatment-ofstudy.JDermatologTreat2009;20:259\u201365. nonmelanoma-skin-cancer-external-assessment-centre-report2 159 Gilbert DJ. Treatmentof actinic keratoseswith sequential combi- (lastaccessed16September2016). nationof5-fluorouracilandphotodynamictherapy.JDrugsDerma178 Gov.uk. National tariff payment system 2014/15. Available at: tol2005;4:161\u20133. https://www.gov.uk/government/publications/national-tariff-pay160 ShaffelburgM.Treatmentofactinickeratoseswithsequentialuse ment-system-2014-to-2015.(lastaccessed16September2016). ofphotodynamictherapy;and imiquimod5% cream.JDrugs Der179 Personal Social Services Research Unit. Unit costs of health and matol2009;8:35\u20139. social care 2015. Available at: http://www.pssru.ac.uk/project161 HooverWD3rd,JorizzoJL,ClarkARetal.Efficacyofcryosurgery pages/unit-costs/2015(lastaccessed16September2016). and5-fluorouracilcream0.5%combinationtherapyforthetreatmentofactinickeratosis.Cutis2014;94:255\u20139. Supporting information 162 Tuppurainen K. Cryotherapy for eyelid and periocular basal cell carcinomas: outcome in 166 cases over an 8-year period. Graefes AdditionalSupportingInformationmaybefoundintheonline ArchClinExpOphthalmol1995;233:205\u20138. version ofthis articleat thepublisher\u2019s website: 163 Couch SM, Custer PL. Topical 5-fluorouracil for the treatment of periocular actinic keratosis and low-grade squamous malignancy. Appendix S1.Search strategy. OphthalPlastReconstrSurg2012;28:181\u20133. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 23}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 43 Appendix 1 Levelsofevidence Levelofevidence Typeofevidence 1++ High-qualitymeta-analyses,systematicreviewsofRCTs,orRCTswithaverylowriskofbias 1+ Well-conductedmeta-analyses,systematicreviewsofRCTs,orRCTswithalowriskofbias 1(cid:3) Meta-analyses,systematicreviewsofRCTs,orRCTswithahighriskofbiasa 2++ High-qualitysystematicreviewsofcase\u2013controlorcohortstudies.High-qualitycase\u2013controlorcohortstudieswitha verylowriskofconfounding,biasorchanceandahighprobabilitythattherelationshipiscausal 2+ Well-conductedcase\u2013controlorcohortstudieswithalowriskofconfounding,biasorchance,andamoderateprobability thattherelationshipiscausal 2(cid:3) Case\u2013controlorcohortstudieswithahighriskofconfounding,biasorchanceandasignificantriskthattherelationship isnotcausala 3 Nonanalyticalstudies(forexamplecasereports,caseseries) 4 Expertopinion,formalconsensus RCT,randomizedcontrolledtrial.aStudieswithalevelofevidence\u2018(cid:3)\u2019shouldnotbeusedasabasisformakingarecommendation. Appendix 2 Strengthsofrecommendation Class Evidence A Atleastonemeta-analysis,systematicrevieworRCTratedas1++,anddirectlyapplicabletothetargetpopulation,or AsystematicreviewofRCTsorabodyofevidenceconsistingprincipallyofstudiesratedas1+,directlyapplicabletothetarget populationanddemonstratingoverallconsistencyofresults,or EvidencedrawnfromaNICEtechnologyappraisal B Abodyofevidenceincludingstudiesratedas2++,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistency ofresults,or Extrapolatedevidencefromstudiesratedas1++or1+ C Abodyofevidenceincludingstudiesratedas2+,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistency ofresults,or Extrapolatedevidencefromstudiesratedas2++ D Evidencelevel3or4,or Extrapolatedevidencefromstudiesratedas2+,or Formalconsensus D(GPP) Agoodpracticepoint(GPP)isarecommendationforbestpracticebasedontheexperienceoftheGuidelineDevelopmentGroup RCT,randomizedcontrolledtrial;NICE,NationalInstituteforHealthandCareExcellence. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 24}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 25}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 25}]
\ No newline at end of file
+[{"text": "BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists\u2019 guidelines for the management of cutaneous warts 2014 J.C. Sterling,1 S. Gibbs,2 S.S. Haque Hussain,1 M.F. Mohd Mustapa3 and S.E. Handfield-Jones4 1Addenbrooke\u2019s Hospital,Cambridge University HospitalsNHS Foundation Trust,Hills Road, CambridgeCB2 OQQ, U.K. 2Great WesternHospital,Marlborough Road, SwindonSN3 6BB, U.K. 3British Associationof Dermatologists, WillanHouse, 4 Fitzroy Square,London W1T 5HQ, U.K. 4WestSuffolk Hospital,Hardwick Lane,Bury StEdmunds, Suffolk IP33 2QZ,U.K. 1.0 Purpose and scope Correspondence The overall objective of the guideline is to provide up-to-date, JaneSterling. E-mail:jcs12@cam.ac.uk evidence-based recommendations for the management of infectious cutaneous warts caused by papillomavirus infection. Acceptedfor publication The document aims to (i) offer an appraisal of all relevant lit14July2014 erature since January 1999, focusing on any key developments; (ii) address important practical clinical questions Fundingsources relating to the primary guideline objective, i.e. accurate diagNone. nosis and identification of cases and suitable treatment; (iii) provide guideline recommendations, where appropriate with Conflictsof interest some health economic implications; and (iv) discuss potential J.C.S.hasreceivedtravelandaccommodationexpensesfromLEOPharma(nonspedevelopments andfuturedirections. cific)andhasbeenaninvitedspeakerateducationaleventsforHealthcareEducation The guideline is presented as a detailed review with highServices(nonspecific). lighted recommendations for practical use in the clinic, in J.C.S.,S.G.,S.S.H.H.andS.E.H.J.aremembersoftheguidelinedevelopment addition to an updated patient information leaflet [available group,withtechnicalsupportprovidedbyM.F.M.M. on the British Association of Dermatologists\u2019 (BAD) website, www.bad.org.uk]. ThisisanupdatedsetofguidelinespreparedfortheBritishAssociationofDermatologists(BAD)ClinicalStandardsUnit,whichincludestheTherapy&Guidelines (T&G)Subcommittee.MembersoftheClinicalStandardsUnitwhohavebeen 1.1 Exclusions involvedareJ.R.Hughes(ChairmanT&G),M.Griffiths,A.J.McDonagh,S.PunThis guideline does not cover anogenital warts, bowenoid jabi,D.A.Buckley,I.Nasr,V.J.Swale,C.E.DuarteWilliamson,P.M.McHenry, papulosis, focal epithelial hyperplasia or seborrhoeic keratoses N.J.Levell,T.Leslie,E.Mallon,K.Towers(BritishNationalFormulary),R. (sometimes calledseborrhoeic warts). Davis(BritishDermatologicalNursingGroup),C.Saunders(BritishDermatologicalNursingGroup),A.G.Brian(BADScientificAdministrator),L.S.Exton(BAD InformationScientist)andM.F.MohdMustapa(BADClinicalStandardsMan2.0 Stakeholder involvement and peer review ager). The guideline development group consisted of consultant and Producedin2001bytheBritishAssociationofDermatologists;reviewedand specialty trainee dermatologists and an editor of the Cochrane updated2014. Skin Group. The draft document was circulated to the BAD membership, British Dermatological Nursing Group, Primary DOI10.1111/bjd.13310 Care Dermatological Society, British Kidney Patients Association and Royal Pharmaceutical Society for comments, and was peer reviewed by the Clinical Standards Unit of the BAD NICE has accredited the process used by the British Association of (made up of the Therapy & Guidelines subcommittee) prior Dermatologists to produce guidelines. Accreditation is valid for 5 years from May 2010. More information on accreditation, and fulldetails of topublication. our accreditation can be viewed atwww.nice.org.uk/accreditation. 3.0 Methodology Thissetofguidelines has been developedusing theBAD\u2019s recommended methodology,1 with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument (www.agreetrust.org).2 Recommendations were developed for 696 BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 1}, {"text": "atwww.nice.org.uk/accreditation. 3.0 Methodology Thissetofguidelines has been developedusing theBAD\u2019s recommended methodology,1 with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument (www.agreetrust.org).2 Recommendations were developed for 696 BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 1}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 697 implementation in the National Health Service using a process skin, often as subclinical infections, but they can be associated of considered judgement based on the evidence. PubMed and with squamous cell cancer and premalignant dysplasias, espethe Medline and Embase databases were searched for metacially incases ofimmunosuppression. analyses, randomized controlled trials (RCTs) and non-RCTs, case series, case reports and open studies involving warts, 6.1 Terminology published in the English language from January 1999 to March 2014; search terms and strategies are detailed in the The term \u2018warts\u2019 includes all morphological varieties of warts Supporting Information. The Allied and Complementary Mediandmaysometimes beusedtoname wart-likelesions, suchas cineDatabasewasalsosearchedfor\u2018warts\u2019withthesametime seborrhoeic keratoses or seborrhoeic \u2018warts\u2019, which are not restriction. Additional relevant references were also isolated caused by HPV infection. In this guideline the term \u2018warts\u2019 from citations in the reviewed literature. Each author screened deals only with warts due to HPV infection. HPV-associated their set of identified titles, and those relevant for first-round warts are subdivided on anatomical or morphological grounds inclusion were selected for further scrutiny. Working in pairs, into (i) common wart (Verruca vulgaris); (ii) wart on the sole of the authors then reviewed the abstracts for the shortlisted refthe foot, plantar wart (Verruca plantaris); (iii) flat wart or plane erences, and the full papers of relevant material were wart(Verrucaplana)and(iv)genitalwart(Condylomaaccuminatum). obtained; disagreements in the final selections were resolved bydiscussionamongtheentiredevelopmentgroup.Thestruc6.2 Epidemiologyandcourse ofinfection ture of the 2001 guidelines was then discussed and re-evaluated, with headings and subheadings decided; different HPV can spread from one individual to another by direct concoauthors were allocated separate subsections. Each coauthor tact or via the environment. It is not known exactly how long then performed a detailed appraisal of the selected literature, the infectious virus can persist outside the body, but the and all subsections were subsequently collated and edited to related bovine papillomavirus is believed to retain infectivity produce thefinal guideline. for months or possibly years,3 and the same may be true for HPV. Warts are a common skin disease worldwide. Infection is common in childhood, but can occur at any age. Small 4.0 Limitations of the guideline cohort observational studies have suggested that 5\u201330% of This document has been prepared on behalf of the BAD and is children andyoung adultshave warts.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 2}, {"text": "but can occur at any age. Small 4.0 Limitations of the guideline cohort observational studies have suggested that 5\u201330% of This document has been prepared on behalf of the BAD and is children andyoung adultshave warts.4\u20136 based on the best data available when the document was preWarts can persist for years with little or no sign of inflampared. It is recognized that under certain conditions it may be mation. Spontaneous clearance of the infection, firstly with a necessary to deviate from the guidelines and that the results of reduction in size of the wart and then its disappearance, can future studies may require some of the recommendations occur at any time from a few months to years later. Clearance herein to be changed. Failure to adhere to these guidelines in children can occur after only a few months, with half clear should not necessarily be considered negligent, nor should at 1 year andabouttwo-thirds by 2 years.7 However,warts in adherence to these recommendations constitute a defence adults can be much slower to clear, and persistence for against aclaimof negligence. 5\u201310 years is notuncommon. 5.0 Plans for guideline revision 7.0 Diagnosis The proposed revision for this set of recommendations is Diagnosis of common hand and foot warts is usually not diffischeduled for 2019; where necessary, important interim cult. Paring down awart will often result in pinpoint bleeding changes willbeupdated ontheBAD website. as the capillary loops of the elongated dermal papillae are exposed. Warts need to be distinguished either clinically or histologically from other keratotic lesions on the hands or 6.0 Background feet, such as actinic keratoses, knuckle pads or, more rarely, Warts are caused by infection of keratinocytes (the predomisquamous cell carcinoma or focal palmoplantar keratoderma. nant cell type in the epidermis) by human papillomavirus On the feet, corns and calluses or callosities can be confused (HPV). The development of epidermal thickening and hyperkwith warts,butparing andcloseinspection shouldallow them eratinization occurs following infection at the basal layer and to be distinguished. On limbs, other hyperkeratotic lesions clonal proliferation, which eventually results in a visible wart, such as lichen planus or angiokeratoma may cause confusion, weeks or even monthslater.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 2}, {"text": "in a visible wart, such as lichen planus or angiokeratoma may cause confusion, weeks or even monthslater. and plane warts may need to be distinguished from lichen There are over 150 genotypically different types of HPV, planus orthin actinic or seborrhoeic keratoses. with classification based on defined variation ofthe viral DNA. The majority of common warts are caused by HPV types 1, 2, 7.1 Complications 4, 27 or 57, and plane warts by HPV types 3 or 10. The HPV types originally identified in epidermodysplasia verruciformis Impairment of the immune system, especially cell-mediated (EV) and their closely related genotypes are also found on the immunity, usually results in prolonged duration of warts. \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 2}, {"text": "698 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. When immune function is severely impaired, for example after destructive or other inflammatory treatments, but the after organ or bone marrow transplant or due to severe compoor or absent response to treatments in immunosuppressed bined immune deficiency, warts may be large, extensive and patients would suggestthatit isessential. resistant to treatment. Warts may be the presenting feature of Common variations between studies include (i) no distincmilder immunosuppressed states such as lymphoma, idiotion being made between common and plane warts; (ii) the pathic CD4 lymphocytopenia or HIV infection, so unusually participants may include both children and adults; (iii) clearsevere or prolonged warts should prompt consideration of ance may be assessed by either cleared warts or clear patients; underlying immune deficit. (iv) various body sites can be included; and (v) treatment Papillomavirus infection is also associated with premaligcomparisons may be between participants, or right\u2013left or nancy and squamous cell carcinomas of the skin. In EV, a wart\u2013wart comparisons within individuals. As few treatments familialtendencytodevelopscalyandplanewart-likekeratotic currently used for treating warts have been subjected to large, lesions in the teens, which frequently progress to squamous rigorous trials, the available evidence for a large number of cell cancer in early adult life, is attributed to both a mild different therapies is discussed in these guidelines. Many trials immune deficit and increased carriage of certain HPV types. A have used a treatment period of 3\u20134 months with varying similar skin condition is seen in long-term immunosuppressed follow-up times. Under these circumstances, the cure rate for individuals, particularly organ transplant recipients. Individuals placebo-treated warts is oftheorderof20\u201330%. with these conditions harbour HPV types causing plane warts, and also those types in the subgroup of beta-papillomaviruses, 8.2.1 Destructive treatments which have a greater frequency than those found in immunocompetent people. Epidermal damage can be produced by chemical means, such as (a) salicylic acid and others (c\u2013j) below, or by physical means,including (b)cryotherapy andothers (k\u2013n) below. 8.0 Management 8.2.1.a. Salicylic acid (level of evidence 1+; strength of recommendation A) 8.1 No therapy (see Appendices 1 and 2). Salicylic acid (SA) formulations are the Depending on their site and size, warts may be just a minor mostcommonpreparationusedinthetreatmentofviralwarts. nuisance.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 3}, {"text": "2). Salicylic acid (SA) formulations are the Depending on their site and size, warts may be just a minor mostcommonpreparationusedinthetreatmentofviralwarts. nuisance. If the affected individual is immunocompetent, then SA is thought to work by promoting exfoliation of epidermal an expectant approach to management is entirely acceptable. cells; at high concentrations it is an irritant. These effects are Some warts can be uncomfortable or interfere with function, postulated to be able to stimulate host immunity, which may or may be a major cosmetic bother and embarrassment when beanadditionalmechanismofactionagainstwarts. numerous or on sites such as the face. Under these circumThe most commonly used, over-the-counter products are stances, anumber ofdifferent treatmentsmay beconsidered. SA paints. These contain SA at concentrations of between 10% and 26% in either a collodion or a polyacrylic base; they are often mixed with lactic acid. Plasters containing 40% SA and 8.2 Interventional treatment ointments containing 50% SA are also widely available; There are numerous treatments for warts, and whether used weaker, cream preparations can be made. The latter are somesingly or in combination they often have little evidence base times used to treat facial warts, but without trial evidence to fortheiruse. Homeremediesalsoabound andmay have some confirmefficacy. reasonfor potential efficacy.Ideally treatment should notleave The method of application of SA depends on the formulascars, although many patients may prefer a permanent scar to tion. For wart paints it is recommended that lesions are apersistent, unsightly andtroublesomewart. abraded or pared down and/or soaked prior to application. There is no antiviral treatment that is specific for HPV, but Care should be taken when paring to avoid abrading the sursome of the available therapies interfere with the viral life rounding normal skin, as this may spread the disease. A study cycle. The most common approach to treatment is to damage looking at the effect of occlusion found a benefit when using or destroy the infected epithelium. This can also induce cell a 17% SA gel with lactic acid.8 Qualitative research has shown death and antigen exposure and presentation, thereby potenthat expectation of cure from SA paints is low, and patients tially inducing an immune response. By reducing epidermal find thetreatment difficultdue toirritation of thesurrounding proliferation, or more specifically DNA replication, the wart skin.Compliance withtreatments isthought tobepoor.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 3}, {"text": "cure from SA paints is low, and patients tially inducing an immune response. By reducing epidermal find thetreatment difficultdue toirritation of thesurrounding proliferation, or more specifically DNA replication, the wart skin.Compliance withtreatments isthought tobepoor.9 should become less thick and production of new virus inhibIn 2011 a meta-analysis of five studies of 333 patients ited. Destruction of the virus particles, or virucide, at the surshowed SA (all preparations) to be more effective than plaface is effected by a limited number of agents, but such cebo.The analysis suggested thatwarts treated with SAare 1(cid:1)6 treatments may not affect virus-infected cells in lower epidertimes morelikely toclearthan thosetreated withplacebo, and mal layers. Direct stimulation of the immune system in the that 95% of similar trials would yield a treatment benefit of a locality of the wart could maximize the chance of immuno1(cid:1)15\u20132(cid:1)24 times increased chance of clearance [relative risk logical response to the infected keratinocytes. It is not known (RR) 1(cid:1)60, 95% confidence interval (CI) 1(cid:1)15\u20132(cid:1)24]. A how much the immune response contributes to wart clearance pooledanalysisof16studiesofSAwithatotalof813patients BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 3}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 699 showed that 337 were cured; the mean cure rate was 49%, SA has also been compounded with podophyllotoxin and with a range of 0\u201369%. In contrast, placebo hada cure rate of cantharidin, and used on plantar warts, clearing 95(cid:1)8% of 23% (range 5\u201373%).10 patients (138/144), with 86(cid:1)8% (125/144) needing only a Two important trials published within the last few single application. However, application was complex, and years11,12 are included in a recently updated Cochrane blistering andpain could result.21 review.13 Bruggink et al.11 studied 250 patients in primary care who were randomized to one of three treatment regi8.2.1.b. Cryotherapy (level of evidence 1+; strength of recommendation mens: SA 40% ointment, fortnightly cotton-bud cryotherapy, B). A range of devices and techniques are used to induce taror no treatment for 13 weeks. The curerates for all sitescomgeted cold injury to warts. Liquid nitrogen, delivered by cryobined were 15%, 49% and 8%, respectively; subgroup cure spray or cotton bud, is the most commonly used method in rates were: hand warts, 17%, 46% and 7%, respectively, and medical practice. Compressed-gas devices containing propane plantar warts, 33%, 30% and 23%, respectively. Thus, in this and dimethyl ether can be purchased without prescription but trial SA was less effective than cryotherapy for the treatment do not achieve temperatures as low as liquid nitrogen and are of hand warts, but more effective than no treatment at all. therefore likely to be less effective,22,23 although there is one Neither treatment seemed particularly effective for plantar randomized trialsuggesting thattheyare equally effective.24 warts. A lack of effectiveness of both SA and cryotherapy for Techniques differ between practitioners, with variations in treating plantar warts is also corroborated by data from the freeze times, mode of application and intervals between trial of Cockayne et al.12 This involved 240 patients with plantreatments. Paring before cryotherapy can improve results in tar warts treated in U.K. podiatric practices, with either SA plantar warts, but not hand warts.25 It is common practice to 50% for 12 weeks or \u2018gentle\u2019 cryotherapy (up to four treatfreeze until a halo of frozen tissue appears around the wart, ments delivered by spray or probe usually with prior paring and this is maintained for 5\u201330 s depending on the site and of overlying skin).", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 4}, {"text": "four treatfreeze until a halo of frozen tissue appears around the wart, ments delivered by spray or probe usually with prior paring and this is maintained for 5\u201330 s depending on the site and of overlying skin). There wasneither aplacebonor ano-treatsize of the wart. Standard practice is to repeat the treatment ment group, and both treatments achieved a modest cure rate every 2\u20133 weeks until the warts have cleared, up to a maxiof only 14%. While these recent studies help confirm the effimum of approximately six treatments. The available evidence cacy of SA, there is still a paucity of data on the commonly from randomized trials broadly supports this, except in the used formulations ofSA paint. case of plantar warts where no treatments, including cryother1 Adverse effects. All but very low-strength SA can cause chemapy, have been convincingly demonstrated to be consistently ical burns and should not be used in areas of poor healandsignificantly effective. ing such as neuropathic feet.14 On the face, SA paints are Two trials of cryospray vs. cotton-bud cryotherapy (one contraindicated due to risk of irritant burning, and this RCT and one controlled trial) showed the techniques to be of can also occur on other sites.15 In areas of sensitive skin, equivalent effectiveness.26,27 Cotton-bud application is proba2% SA cream has been used but without any evidence bly preferable when treating warts on the face in children; an base.Contact allergytotheexcipients is alsoreported.16 alternative technique is to freeze the tips of a pair of forceps 2 Combination therapies (level of evidence 2(cid:3)). The most comandthen grip thewart.28,29 monly used combination therapy is cryotherapy and SA. The reported cure rate of cryotherapy for warts at all sites In an open study, a clearance rate of 86% (25/29) was from randomized trials is highly variable, ranging from 0% to reported in a retrospective analysis of cases treated with 69% with a mean of 49%.10 Where possible, subgroup both cryotherapy and SA 70%.17 There were uncontrolled analysis of data from these trials suggests that cure rates are variables in this study: the number and frequency of generally better for hand warts than for plantar warts. Two cryotherapy treatments was decided by the practitioner recently published trials11,12 have provided much betterandthefollow-up period wasup to4(cid:1)5 years.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 4}, {"text": "this study: the number and frequency of generally better for hand warts than for plantar warts. Two cryotherapy treatments was decided by the practitioner recently published trials11,12 have provided much betterandthefollow-up period wasup to4(cid:1)5 years. quality data than previously and have compared cryotherapy directly with SA.13 As discussed in the section on SA In a study of 10 patients with 66 warts, the application of (section 8.2.1.a.), cryotherapy gave equivalent or improved SA 30% prior to pulsed-dye laser (PDL) therapy appeared to rates ofcurewhen compared with SA. decrease the number of laser treatments needed, but while the More aggressive cryotherapy with a longer freeze or a study was randomized, it was a single-blinded trial and double freeze\u2013thaw cycle appears to be more effective than involved within-patient comparisons.18 In an open study, gentler freezing, but the evidence is very heterogeneous and diphencyprone (DPC) 0(cid:1)1% was combined with SA 15% ointthe data are not of very high quality.30\u201333 Not surprisingly, ment in a trial of 50 patients with palmoplantar warts and moreintensecryotherapyalsotendstoresultinmorepainand applied for up to 4 months. The combination showed a 92% blistering and with an increased risk of scarring. The study by clearance in those completing the treatment, with 88% clearBerth-Jones et al.32 is often cited, but it had a very high dropancein intention-to-treat cases.19 out rate (31%), making the apparent advantage of the double SA (either 17% or 40%) has also been combined with freeze\u2013thaw cycle for plantar warts (an improved cure rate of 5-fluorouracil (5-FU, either 0(cid:1)5% or 5%) for plantar warts, 65% vs. 41%) rather less convincing. The study by Connolly with 100% resolution; however, the regimens were complex et al.33 (with a 22% dropout rate) showed that a longer freeze andtreatment continued forup to235 daysin onepatient.20 time (10 s sustained vs. a \u2018traditional\u2019 freeze) improved cure \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 4}, {"text": "700 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. rates at all sites (64% vs. 39%), but the number of patients 8.2.1.f. Glycolic acid 5% (level of evidence 3; strength of recommendation withplantarwartswastoosmallforsubgroupanalysis. D). Glycolic acid is an a-hydroxy acid that acts as a peeling In trials comparing the interval between treatments, most, agent. In a case series of 15 children with facial plane warts it but not all, have suggested that freezing every 2\u20133 weeks was well tolerated, cleared all of the cases and did not proproduces a better clearance at 3 months than treatment every duce scarring. However, spontaneous resolution may have 4 weeks.34\u201337 However, the cure rates after 6 months are occurred, especially in one case that did not clear until after often similar, suggesting that clearance may in fact depend on 4 months.42 An open study of SA 2% combined with glycolic the total number of treatments given. Only one randomized acid 15% in 20 patients aged 7\u201316 years with recalcitrant trial has explored the total number of treatments, and even facial flatwarts reported a100% cureratewithin 8 weeks.43 this trial was not ideally designed to answer this question. There was also a high dropout rate (19% in the first part of 8.2.1.g. Pyruvic acid (level of evidence 3; strength of recommendation the trial and 26% in the second), introducing a considerable D). Pyruvic acid is used as a peeling agent. In a case series risk of bias. In a mixed population of 155 patients with perinvestigating the response of common warts to pyruvic acid sistent warts at all sites that had not cleared after 3 months of 70% alone or in combination with 5-FU 0(cid:1)5%, 80% of 3-weekly cryotherapy treatments (about four treatments), patients showed improvement. The addition of 5-FU did not there was no demonstrable benefit shown after a further increase the effect.44 Hypertrophic scarring was reported in a 3 months oftreatment.25 patient using pyruvic acid 98% with 5-FU 2% for warts on Patients should be warned that cryotherapy is painful and thechest andarms.45 blistering may occur. Adverse effects are more frequently reported in shorter-interval treatment regimes. Caution must 8.2.1.h. Citric acid 50% (level of evidence 2(cid:3)).", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 5}, {"text": "are more frequently reported in shorter-interval treatment regimes. Caution must 8.2.1.h. Citric acid 50% (level of evidence 2(cid:3)). Citric acid was combe used when applying cryotherapy near cutaneous nerves, pared with tretinoin in a prospective randomized, doubletendons and the nail apparatus, and also in patients with blinded study of 75 patients with plane warts on the body. impaired arterial or venous circulation. Hypopigmentation or The study design used a side-to-side comparison and the hyperpigmentation may occur, particularly in patients with results were given as number of warts cleared. After 6 weeks darkerskin types. 64% of citric acid-treated lesions were cleared, vs. 54% of the tretinoin-treated lesions.46 8.2.1.c Silver nitrate (level of evidence 2(cid:3)). A silver nitrate 10% solution was investigated in a placebo-controlled, double8.2.1.i. Formic acid (level of evidence 2(cid:3)). Formic acid is another blinded study of hand and foot warts in 60 children and low-cost treatment. As an acid, it is stronger than SA but adults, and showed a clearance rate of 63% of patients after weaker than trichloroacetic acid. A number of studies have 6 weeks.38 However, the data shown relate only to the suggested its efficacy.47\u201349 Side-effects are common, with 12% response to the silver nitrate, with no data given for the plaof participants in one study developing an infection and needcebo, making interpretation impossible. Yazar and Ba(cid:1)saran ingsystemic antibiotics.47 studied the effect of silver nitrate pencils and reported a cure rate of 43% of patients in the treatment group and 11% with 8.2.1.j. Trichloroacetic acid and monochloroacetic acid (level of evidence 3; placebo.39 strength of recommendation D). These caustic agents have been used to treat warts. Trichloroacetic acid is used regularly to treat 8.2.1.d. Phenol (level of evidence 2+; strength of recommendation genital warts,50 and has been used without adequate trial eviD). Phenol is a caustic agent that has been compared with dence to treat common warts.51 Monochloroacetic acid cryotherapy in a single-blinded, randomized study of 60 showed a success rate of 61%, and the addition of formaldepatients with hand warts. Cryotherapy was applied weekly hyde had no effect on the response rate.52 Monochloroacetic with a cotton stick for 10\u201320 s, and 80% phenol was acid is highly toxic andcorrosive.53 applied weekly.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 5}, {"text": "weekly hyde had no effect on the response rate.52 Monochloroacetic with a cotton stick for 10\u201320 s, and 80% phenol was acid is highly toxic andcorrosive.53 applied weekly. The cure rates of patients were 70% with cryotherapy and 83% with phenol, although the dropout 8.2.1.k. Hyperthermia (level of evidence 2+; strength of recommendation rate with phenol was higher.40 D). Two randomized trials have studied theeffects of localized heat on warts.54,55 The more recent trial involved 60 patients 8.2.1.e. Cantharidin (level of evidence 3; strength of recommendation with plantar warts randomized to hyperthermia with red light D). This is a blistering agent that triggers acantholysis. The (up to 44 \u00b0C for 30 min on three consecutive days) or superficial nature of the injury reduces the risk of scarring. It placebo red light alone. Cure of treated lesions occurred in also has the advantage of painless application, with discomfort 54% (15/28) vs. 12% (three of 26) of patients, respectively developing only when blistering occurs in the 24 h following (RR 3(cid:1)37, 95% CI 1(cid:1)05\u201314(cid:1)18).55 The earlier randomized application. A study of 15 patients who were treated with a trial,54 involving 13 patients with hand warts and using warts cantharidin 0(cid:1)7% solution to treat plane facial warts showed as the unit of analysis, and a case series56 are less rigorous clearance of warts in all15 patients within 16 weeks with one studies, but also suggest that localized hyperthermia can be tofour treatments.41Taken systemically itis highly toxic. effectiveandis reasonably safe. BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 5}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 701 8.2.1.l. Surgical interventions (level of evidence 3; strength of recommenda- (SA and lactic acid) between PDT treatments.68 In total, 75% tion D). There are no high-quality studies published on the of plantar warts completely resolved in 67 ALA-PDT-treated effectiveness of surgical treatments such as curettage, cautery patients (50 mW cm (cid:3)2, 50 J cm (cid:3)2 visible light irradiation, and CO laser, although these treatments are certainly widely three treatments maximum) compared with 23% in the 2 used. One case series of 50 patients treated with 2\u20134-MHz placebo group. Both groups received urea 10% and SA 10% electrowave \u2018electrosection\u2019 (an accurately targeted destructive ointment foraweekprior tocommencing treatment.69 treatment using radio waves rather than heat) claimed a 67% Cohort studies have reported clearance rates of warts success rate with solitary plantar warts and commented that between 58% and 95%.70\u201372 PDT can be used in combination relapse was more common in warts that occurred at weightwith laser; in such a study, 12 patients with periungual warts bearingsites.57 treated with CO fractional laser followed by methyl-5-amino2 laevuninic acid (MAL)-PDT (3 h, 50 J cm (cid:3)2, 15 min, fort8.2.1.m. Lasers (level of evidence 2+; strengthof recommendationC). PDL nightly treatments over 6 weeks) resulted in 90% of treated (585 nm) is the laser used most frequently and acts by warts clearing completely with no recurrence in 6 months.73 destroying wart vessel vasculature through haemoglobin\u2019s In another study, 19 patients with hand and foot warts were absorption peak at 585\u2013595 nm. Direct thermal injury to the treated with MAL-PDT plus a PDL light source, which cleared heat-sensitive HPV virus may also play a role. Treatment pro53% oftreated warts; handwarts cleared moreeffectively than tocols (pulse width, fluence, spot size, number of pulses and plantar warts.74 duration of treatment) vary between studies, making efficacy As with laser treatment, it is difficult to compare efficacy difficult to evaluate. One RCT found no significant difference rates in published papers due to variation in PDT regimens, in outcome between groups treated with PDL, cryotherapy or for example the duration of application of topical photosensicantharidin.58 Cohort studies have reported patient clearance tizers, the type of light source used, fluorescence and the rates with PDL of 32\u201375%,59\u201361 and a case series of 142 number of treatments.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 6}, {"text": "the duration of application of topical photosensicantharidin.58 Cohort studies have reported patient clearance tizers, the type of light source used, fluorescence and the rates with PDL of 32\u201375%,59\u201361 and a case series of 142 number of treatments. Many studies prepare warts before patients with over 700 warts reported 93% clearance of treatreatment, with curettage, blunt scraping, scalpel or keratolytic ted warts afteranaverage of2(cid:1)5 treatments.62 cream to enhance penetration. Azone, a topical penetration Most warts are pared down before PDL to facilitate absorpenhancer, has been used before PDT in two studies, with 83% tion of thelaser energy. Pretreatment with SA 30%for 5 days, clearance of plantar wart75 and 94% clearance of V. plana on followedbyPDL,ledtofastercompleteclearance(2(cid:1)2sessions the face.76 For facial plane warts, a reduction in concentration in the SA-PDL group vs. 3(cid:1)1 sessions in the PDL-only group, of ALA from 20% to 10% can maintain efficacy but reduce P < 0(cid:1)05), with similar proportions of patients responding to thechance ofpost-treatment hyperpigmentation.77 treatment overall.18 Two studies using PDL followed directly by intralesional 8.2.2. Virucidalagents bleomycin led to 60\u201389% wart clearance, including 80% clearance in immunosuppressed patients.63,64 Wart location 8.2.2.a. Formaldehyde (level of evidence 3; strength of recommendation and duration may influence the rate of clearance. Palmar and D). Formaldehyde soaks have been used to treat verrucas, and periungual warts are cleared more effectively than plantar they were reported to give a cure rate of 80% in an open warts.60,61,65 study of 646 children.78 This study applied 3% soaks to pared The main side-effects of PDL include local pain (although plantar warts. If the skin hardened, the concentration was generally not severe enough to warrant stopping treatment), increased to a 10% solution. Formaldehyde is also available as haemorrhagic bullae, pigmentary change and scarring. PDL is a 0(cid:1)75% gel. No randomized study has been completed. well tolerated by children, with two large cohort studies Formaldehyde is allergenic. reporting complete response in 48% of treated warts66 and 75% ofchildren withpalmoplantarwarts.61 8.2.2.b. Glutaraldehyde (level of evidence 3; strength of recommendation CO laser, neodymium-doped yttrium aluminium garnet D). A glutaraldehyde 10% paint was reported as being equiva2 (Nd:YAG), Er:YAG, infrared and potassium titanyl phosphate lent toSApaint inplantar warts.35 Aseriesof25patients with laser have also been used in a small number of cohort studies.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 6}, {"text": "garnet D). A glutaraldehyde 10% paint was reported as being equiva2 (Nd:YAG), Er:YAG, infrared and potassium titanyl phosphate lent toSApaint inplantar warts.35 Aseriesof25patients with laser have also been used in a small number of cohort studies. resistant warts showed a cure rate of 72%, and the treatment The largest of these reported a 96% clearance rate of recalciwas well accepted in children.79 Reports of deep necrosis trant common, palmoplantar and periungual warts in 369 demonstrate the risk of repeated application, and glutaraldepatients treated withNd:YAG laser.67 hyde should be used with caution especially in concentrations > 10%.80 8.2.1.n. Photodynamic therapy (level of evidence 2+; strength of recommendation D). There was a significant difference in wart clearance 8.2.3. Antiproliferative agents after 14 weeks in 45 patients with palmar and plantar lesions treated with 20% aminolaevulinic acid photodynamic 8.2.3.a. Vitamin D analogues (level of evidence 3; strength of recommendatherapy (ALA-PDT) (50 mW cm (cid:3)2, 23-min treatment time, tion D). There are three case series81\u201383 and two case 70 J cm (cid:3)2, six treatments maximum) compared with placeboreports84,85 on the use of vitamin D analogues for treatment PDT. However, patients also applied a keratolytic ointment of warts. The largest case series, by Inaba et al.,82 reported \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 6}, {"text": "702 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. complete regression of warts in 59% of patients (13/22; all 5-FUhasbeenusedinaweakpreparation(0(cid:1)5%)incombinaages, all sites) treated with maxacalcitol and occluded with SA tionwithSA(10%).Inameta-analysis,thecombinationappears plastersfor up to45 days. muchmoreeffectivethanSAalone(63(cid:1)4%clearancevs.11%).96 In a double-blinded RCT, 65% of warts in 40 patients 8.2.3.b. Dithranol (level of evidence 2(cid:3)). One small RCT of dithracleared with up to four injections, given weekly, of intrale- (cid:1) nol 2% cream vs. Verucid (11% SA, 4% lactic acid with copsional 5-FU 4% (in combination with lidocaine and adrenaper), showed a higher cure rate for dithranol: 56% (15/27) line) compared with 35% in the placebo group (P < 0(cid:1)05).97 vs. 26% (eight of 31).86 Three case series showed patient cure Is(cid:1)cimen et al.98 reported a 70% complete clearance of warts in rates of 60\u201370%.87\u201389 In the series of Hjorth et al.,87 71% of asimilar single-blinded RCT. patients (17/24) were cleared of mosaic plantar warts within 10 months ofdailytreatment withdithranol 2%. 8.2.3.e. Bleomycin (level of evidence 2+; strength of recommendation C). Bleomycinisacytotoxicagentusedinsystemicchemother8.2.3.c. Podophyllin and podophyllotoxin (level of evidence 3; strength of apy, but it has been recognized and applied as a therapy for recommendation D). Podophyllotoxin can inhibit cell division by warts for 40 years.99 Bleomycin solution can be injected into interfering with the mitotic spindle, and will affect normal wartsusingasmallneedleandsyringe,orappliedtothesurface skin as well as warts. It can have dangerous systemic effects if and\u2018pricked\u2019intothewartwithaneedle.Thestrengthofbleoused in high concentrations or over large areas, and its use is mycin used has usually been 1 U mL (cid:3)1, equivalent to contraindicated in pregnancy. Although podophyllotoxin (and 1 mg mL (cid:3)1, but weaker strengths of 0(cid:1)5 mg mL (cid:3)1 or even previously the cruder podophyllin) is a standard treatment for 0(cid:1)1 mg mL (cid:3)1seemtoproducesimilareffects.100,101Theintroanogenital warts, its evaluation in cutaneous warts has been duction of bleomycin into the skin is painful, and local anaeslimited. The assumption is that penetration of thethick, cornithesia, either before or together with administration of fied layer of cutaneous warts is poor compared with that bleomycin,helpstomaketheproceduremorecomfortable.The achieved at mucosal sites. A very small open study of 40 effectofbleomycinonthewartproducessomepainthatlastsa patients with plantar warts treated with podophyllin 25% in dayortwo,andthennecrosisdevelopswithablackescharthat liquid paraffin under prolonged adhesive plaster occlusion separates after a few days. This obvious response to treatment reported a67%clearance rate ofpatients at3 months.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 7}, {"text": "plantar warts treated with podophyllin 25% in dayortwo,andthennecrosisdevelopswithablackescharthat liquid paraffin under prolonged adhesive plaster occlusion separates after a few days. This obvious response to treatment reported a67%clearance rate ofpatients at3 months.90Howmakes it difficult to conduct double-blinded trials, and many ever, the side-effects of this treatment include an intense studieshavebeenopenstudiesorhaveusedbleomycinincominflammatory reaction with blistering, which can be very parisonwithsalineinjectionorcryotherapy. painful. There are no recent studies using podophyllotoxin for Open studies have suggested clearance rates of approxicutaneous warts, except as a 1% component of a combination mately 20\u201390% of treated warts with one or more treattherapy with cantharidin and SA, so the contribution of podoments,101,102 with most reporting a patient response rate of phyllotoxin aloneis impossible toevaluate.91 approximately 65\u201385%.101,103 Several trialsofintralesional bleomycinhaveusedsalineasa 8.2.3.d. 5-Fluorouracil (level of evidence 2+; strength of recommendation placebo.Inonestudywhere25patientswereallocatedtoeach C). Topical 5-FU has been used with effect to treat both plane treatment, 96% (82/85) of warts treated with bleomycin warts and common warts on the hands and feet. 5-FU blocks cleared,whileonly11%ofwarts(eightof72)treatedwithsalDNA synthesis and damages dividing basal layer cells. When ineshowedclearanceat3 months.104Asmallerstudy,inwhich used topically or intralesionally, it produces inflammation and 24patientswithmultiplewartshadonewarttreatedwithbleooccasionally erosions. Hyperpigmentation, or less frequently mycinandasimilarwartinjectedwithsaline(control),reported hypopigmentation, canoccur ifitis used forlonger periods. a comparable clearance, with 58% of bleomycin-treated warts In one study, 5-FU 5% cream was applied once a day for clearingcomparedwithonly11%ofthecontrolwarts.105 4 weeksunderocclusiontohandorfootwartsononesideofthe Whencompared withcryotherapy, andusing onebodyside body,whileaplacebocreamwassimultaneouslyappliedtowarts for each treatment, bleomycin produced higher clearance rates ontheothersideofthebody.Attheendofthetreatment,60% (92\u201397% of bleomycin-treated warts vs. 76\u201382% of warts of warts were cleared on the side treated with 5-FU compared treated withcryotherapy).106,107 with17%ontheplacebo-treatedside.92Inasimilarlydesigned The major side-effect of bleomycin is pain at the time of study,treatingadultplantarwartsfor12 weeksledtocomplete injection and for up to 48 h afterwards. Flagellate hyperpigclearancein95%ofpatients(19/20),with10%clearanceinthe mentation, which may occur with standard systemic chemoplaceboarm.93Inasmallopenstudy,applicationofthecreamto therapy, has also been reported,108 as has postinflammatory planewartstwiceadayledtosimilarclearancerates.94 pigmentation, whichusually clears aftersomeweeks.109 Topical 5-FU under occlusion was more effective than occlusion alone in an unblinded RCT of 40 patients. In total, 8.2.3.f. Retinoids. 95% of patients using 5-FU under occlusion cleared their warts compared with 10% in the control group.93 There was 1 Topical retinoids (level of evidence 2+; strength of recommendation C). no difference in outcome when 5-FU was used in combinaRetinoids affect epidermal proliferation and differentiation tion withcryotherapy vs. cryotherapy alone.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 7}, {"text": "(level of evidence 2+; strength of recommendation C). no difference in outcome when 5-FU was used in combinaRetinoids affect epidermal proliferation and differentiation tion withcryotherapy vs. cryotherapy alone.95 and so can reduce wart volume and alter stratum corneBritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 7}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 703 um quality and quantity. Their main side-effect, both 2 months,90 but the first trial of its use was not reported until from topical and systemic administration, is skin dryness 2002.125 A single wart in each of 61 children was treated and skin irritation, which could influence inflammatory with either light cryotherapy (10 s of liquid nitrogen every reactions in the skin and contribute to the drug\u2019s immu2\u20133 weeks) or common silver duct tape applied and left in nomodulatory effects. In spite of ease of access and availplace for 1 week for a total of 8 weeks. In total 60% of the ability, there are very few reports of the use of topical cryotherapy-treated warts cleared, compared with 85% of the retinoids in the treatment of warts. Two small studies warts treated with duct tape. Two further trials have used assessing plane warts in children110 and organ transplant transparent duct tape applied to a single wart for up to patients111 have suggested 85% clearance (compared with 8 weeks, but without a statistically increased rate of clearance. 23% untreated) or 29% lesion clearance (compared with In a trial involving 100 children randomly allocated to either 19% placebo treated), respectively, after 6\u201312 weeks of duct tape over the wart or a ring-shaped corn pad around the treatment with tretinoin 0(cid:1)05% cream. Adapalene 0(cid:1)1% wart, 16% of warts cleared in the treatment group compared gel applied under occlusion for 1 week has also been with 6% in the placebo group.126 In a study of 90 adults treaused,but proper evaluation is lacking.112 ted with the same tape, again applied weekly for up to 2 Systemic retinoids (level of evidence 3; strength of recommendation D). 8 weeks, and compared with adhesive-backed moleskin padThere are many anecdotal reports of oral retinoid use in ding, clearance rates were approximately 20% in both severe warts, including in immunosuppressed patients. groups.127 Although these studies have not confirmed a defiThe effect of acitretin 0(cid:1)5\u20131 mg kg (cid:3)1 per day for up to nite effect of occlusion on warts, there is the possibility that 3 months is usually a reduction in the bulk of lesions, an effect may occur in children.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 8}, {"text": "on warts, there is the possibility that 3 months is usually a reduction in the bulk of lesions, an effect may occur in children. Many other topical treatments but with a high risk of recurrence on discontinuation of for warts may include some form of occlusion, and the role therapy.113 In an observational study of children aged of thispart oftreatment is yet tobeclarified. 2(cid:1)5\u201312(cid:1)5 years treated with oral etretinate for 3 months, 80% (16/20) were clear of all warts at 1 year after fol8.2.4. Immunologicaltherapy low-up.114 Anopenstudyofchildandadultpatients with facial plane warts reported 73% clearance after 2 months 8.2.4.a. Imiquimod (level of evidence 3; strength of recommendation of treatment withisotretinoin 0(cid:1)5 mg kg (cid:3)1per day.115 D). Imiquimod is a well-established treatment for genital and perianal warts. It stimulates a proinflammatory response through the induction, synthesis and release of interferon 8.2.3.g. Cidofovir (level of evidence 3; strength of recommendation D). Ci- (IFN)-a, tumour necrosis factor-a and interleukin (IL)-12, as dofovir is a potent nucleoside analogue that competitively well as promoting natural killer (NK) cell activation. There inhibits DNA polymerase and therefore prevents replication of are no RCTs studying the effect of imiquimod on cutaneous cidofovir-incorporated viral cells. warts. However, two open-label studies have shown > 50% Several case reports have supported the use of intravenous clearance of warts, firstly in 76% of patients when imiquicidofovir in immunosuppressed patients,116\u2013120 but it is genmod was applied twice daily for a maximum of erally used topically. Topical cidofovir is reconstituted from 24 weeks,128 and secondly in 56% of 50 patients, of whom the parenteral form, as either a 1% or 3% cream. It is applied 19 were immunosuppressed, after 9(cid:1)5 weeks of treatment.129 under occlusion for 5 days of the week followed by no treatApplication under occlusion does not appear to enhance the ment for aweek;this cycle canthen berepeated. efficacy.130 There are numerous case reports reporting the Cidofovir1%creamwasusedtotreatlong-standingwartsin effectiveness of imiquimod in both immunocompetent and a case series of seven children, with four achieving complete immunocompromised patients.131,132 It has a tolerable sideclearanceafter8 weeksoftreatment,lastinguptoayearin75% effect profile with mild-to-moderate local pain reported most of cases.121 A child with acute lymphocytic leukaemia applied frequently. cidofovir 1%cream toapainfulplantarwartdailyfor6 weeks leading to complete resolution.122 Cidofovir can also be used 8.2.4.b.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 8}, {"text": "effect profile with mild-to-moderate local pain reported most of cases.121 A child with acute lymphocytic leukaemia applied frequently. cidofovir 1%cream toapainfulplantarwartdailyfor6 weeks leading to complete resolution.122 Cidofovir can also be used 8.2.4.b. Contact immunotherapy (level of evidence 2+; strength of recomintralesionally,andwithanaverageof3(cid:1)2injections,clearance mendation C). Contact immunotherapy with diphenylcyclopof98%ofwartshasbeenreportedinanopenstudy.123 ropenone/diphencyprone (DPC) or squaric acid dibutyl ester Side-effects of intravenous cidofovir include nephrotoxicity, (SADBE) induces a local delayed hypersensitivity reaction at neutropenia and metabolic acidosis. Topical cidofovir appears thewart site triggering alocalimmuneresponse. to be well tolerated other than causing local irritation, An 8-year retrospective review of 48 patients with palmoplalthough one patient with a background of chronic renal failantar warts treated with DPC reported 88% complete clearance ure developed acute deterioration in renal function during of all warts. The median treatment time was 5 months, and treatment.123,124 no recurrences were observedin a2-year follow-up period.133 A similar review of treatment over 7 years reported an 87(cid:1)7% 8.2.3.h. Occlusotherapy (level of evidence 2(cid:3)). The use of occlusion complete response rate.134 Although the clearance rate is for treatment of cutaneous warts has been practised for some reduced in immunosuppressed patients, sensitization is possitime, with a suggestion of 47% of patients cleared at ble andthis treatment canbeeffective.135 \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 8}, {"text": "704 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. Of 443 adults and children who completed treatment with 8.2.4.e. Other systemic immunotherapy (level of evidence 3; strength of recSADBEtwiceweeklyforamaximumof10 weeks,86%underommendation D). Single-patient case reports have described good went complete resolution and 13(cid:1)8% showed no response to outcomes with IFN,147 immunoglobulin148 and valaciclovir149 the contact sensitizer. All plantar warts responded, but statistiin immunosuppressed patients withwarts. cal analyses to identify whether the wart site was a significant variable was not undertaken.136 A retrospective review has 8.2.4.f. Zinc oxide and zinc sulfate (level of evidence 1(cid:3)). The mechasuggested that topical trichloroacetic acid 50% in combination nism of action of zinc in the treatment of warts is uncertain. withSADBEimmunotherapycanenhanceclearancerates.137 Zinc is important for immune regulation and mediates the Side-effects of SADBE and DPC include erythema, desquarole of leucocytes and NK cells. Zinc deficiency causes lympmation, oedema, pruritus and mild burning. A small number hopenia, and can manifest as acrodermatitis enteropathica. of patients may develop autoeczematization or widespread Zinc can be used topically or systemically, but there are no urticaria, andtreatment should bestopped in these cases. robust datatosupportits use in thetreatment ofwarts. Other allergens including products used for immunization, A double-blinded RCT showed no difference between oral such as bacille Calmette\u2013Gu(cid:1)erin (topical) or measles vaccine zinc sulfate and placebo.150 A poor-quality single-blinded RCT (intralesional), havebeen proposedas usefultherapies. Topical showed 87% response in the zinc sulfate patient group, comtherapies may have particular use for children and for the pared with no response in the placebo group, but all patients treatment ofplanewarts.138 had a low serum zinc level pretreatment.151 Yaghoobi et al.,152 who have also published results of a pilot study,153 reported a 8.2.4.c. Intralesional immunotherapy (level of evidence 1(cid:3)). Intralesion78%response withsimilar dosesof zinc. al Candida, mumps and tuberculin antigens have been used to Gastrointestinal side-effects including nausea, vomiting and induce wart clearance through antigenic stimulation of the abdominal pain occur frequently, although they do not always host-cell-mediated immune system. There is no robust evinecessitate withdrawal oftreatment in thepublished studies. dence to support the use of this type of intralesional immunoTopical zinc sulfate 10% is more effective than zinc sulfate therapy, but reported clearance rates range from 47% to 87%.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 9}, {"text": "zinc sulfate 10% is more effective than zinc sulfate therapy, but reported clearance rates range from 47% to 87%. 5% or placebo in the treatment of common and plane warts, A single-blinded RCT of intralesional Candida and IFN-a with 86% complete clearance achieved vs. 10% clearance in showed that patients receiving the antigen were more likely to the placebo group.154 In a double-blinded RCT of zinc oxide respond,butthattheadditionofIFNdidnotsignificantlyalter 20% vs. an SA/lactic acid ointment, 50% of patients achieved theresponse rate.139 clearance in the zinc oxide group compared with 42% in the Phillips et al.140 retrospectively reviewed 149 adults and SA/lactic acid group.155 It is a simple and safe treatment but children treated with Candida immunotherapy. Within 8 weeks has notbeen compared withplacebo. of completing treatment, 72% of patients had achieved complete wart clearance. However, a separate review of 277 8.2.5. Complementaryand alternativetreatments patients comparing Candida antigen with \u2018traditional therapy\u2019 (includingcryotherapyandSA)foundnosignificantdifference Most cultures have a history of charms, herbal treatments and in outcomebetween thedifferent groups.141 other remediesfor warts.156,157 Modern complementary therapies are often derived from these treatments. They can be 8.2.4.d. H2 receptor antagonists (level of evidence 1(cid:3)). H2 receptor divided as follows: (i) psychological treatments, e.g. hypnosis; antagonists are widely used in the treatment of gastro- (ii) herbal treatments; (iii) homeopathic treatments; and (iv) oesophageal reflux. They increase IL-2 and IFN-c expression acupuncture. from T lymphocytes, enhancing cell-mediated immune responses. The efficacy of cimetidine has been demonstrated 8.2.5.a. Psychological treatments for warts (level of evidence 2(cid:3)). In in open-label studies: high-dose cimetidine (30\u201340 mg kg (cid:3)1 many people warts resolve spontaneously within 8 months, so per day) was more effective at clearing warts than low-dose it is therefore very difficult to know whether there is an addicimetidine (20\u201330 mg kg (cid:3)1 per day),142 and 87% of tional effectfromsuggestion or not.157 children who received cimetidine for 3 months had comHypnosis is the most studied technique and can be subdiplete resolution of their warts.143 However, these results vided into direct suggestion and visual imagery. A randomized have not been replicated in RCTs, which have found no study comparing hypnosis with SA, control (no treatment) statistically significant difference between cimetidine and and placebo (base carrier from SA) showed a greater effect placebo.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 9}, {"text": "in RCTs, which have found no study comparing hypnosis with SA, control (no treatment) statistically significant difference between cimetidine and and placebo (base carrier from SA) showed a greater effect placebo.144,145 with hypnosis, but the numbers were small with only 10 Ranitidine, which does not have antiandrogenic activity (as patients per group.158 Studies attempting clearance of warts opposed to cimetidine), has been investigated in one openfrom one-half of the body and not the other have shown conlabel study. In total 49% of patients with multiple common or flicting results.159,160 However, this has to be viewed in the planewartscompletely respondedtoa4-monthcourseofranlight of a paper showing that when warts were treated with itidine 300 mg twice daily, with no recurrence in a 6-month CO laser on one side of the body the warts on the other side 2 follow-up period.146 also cleared.161 BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 9}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 705 A study of 97 patients treated with distant healing showed effect against warts in a study of an extract from garlic, but no effect.162 A more elaborate form of suggestion utilized while there was a control group the study does not appear to simulated X-ray therapy; however, while the report suggested have been randomized.165 Pure garlic can cause skin irritation. that the treatment was successful, only 55% of children (five The sap from figs was compared with cryotherapy in a \u2018left\u2013 of nine)showedclearance in 2 months.163 right\u2019 comparison; 44% (11/25) of warts cleared with fig sap vs. 56% (14/25) with cryotherapy. While the study had 8.2.5.b. Herbal treatments (level of evidence 2(cid:3)). The destructive design flaws,figsapwasfree ofside-effectsandisinexpensive effect of caustic sap has been exploited to treat warts, but in some parts of the world.166 A study compared oral treatburns canresult. Plants usedinclude mayapple (Podophyllum peltment with propolis (45 patients) with Echinacea (40 patients) atum) (the source of podophyllin) and greater celandine (Cheand placebo (50 patients). Clearance was seen in 18, six and lidonium majus).164 Garlic (Allium sativum) was shown to have four patients, respectively. The dropout rate was high and Table1 Summaryofrecommendedtreatmentsforhandwarts Strengthof recommendation Treatment Suggestedmethodofuseforhandwarts A Salicylicacid(SA) Topicalpreparationsof15\u201326%SA,applieddailyafterremovingthickkeratinlayer,with occlusionifpossible.Continuefor3\u20134months11,35 B Cryotherapy Keepwartfrozenfor15\u201330s,repeatingevery2\u20134weeksforatleast3monthsorsix treatments11,35 C Bleomycin A0(cid:1)1\u20131UmL(cid:3)1(0(cid:1)1\u20131mgmL(cid:3)1)solutioninjectedorprickedintowartafterlocal anaesthesia\u2013onetothreetreatments.Painfulduringandaftertreatment101,102 Contactimmunotherapy Afterinitialsensitization,DPCorSADBEatstrengthappropriateforpatient,appliedfrom twiceweeklytoevery3weeksfor3\u20136months133,134 5-Fluorouracil A5%creamapplieddaily+occlusionfor4\u201312weeks92,93 Laser Pulsed-dyelaserafterparingand/orSApretreatment.Twotofourtreatmentsat 7\u201310Jcm(cid:3)2areusuallyneeded59\u201361 D Acupuncture Auricularacupunctureweeklyfor10weeks171 Cantharidin A0(cid:1)7%solutionappliedevery3weeksuptofourtimes41 Cidofovir A1%creamdailyfor5dayseachweekunderocclusionfor8weeks121,122 Formaldehyde A3\u20134%solutionasadaily15\u201320-minsoakforplantarwarts,withemollientprotection ofunaffectedskinforupto8weeks78 Glutaraldehyde A10%solutionapplieddailyafterparingorrubbingdownfor3months79 Hyperthermia Heatwart(s)to40\u201344\u00b0Cfor30minonthreetofiveconsecutivedays55,56 Imiquimod A5%creamtwicedailyforupto6months128 Phenol An80%solutionappliedweeklyforupto6weeks40 Photodynamictherapy ALA-PDTafterparingand/orSApretreatment,uptothreetreatments71 Podophyllin Podophyllinbutnotpodophyllotoxintested.Afterparingorrubbingdown.25%in liquidparaffinappliedunderocclusion.11Authorsadviseweakerstrength(10\u201315%)and cautioususe90 Pyruvicacid A70%solutionapplieddailyforupto2months44 Retinoids,systemic Acitretin0(cid:1)5\u20131mgkg(cid:3)1perdayforupto3months113 Surgery Curettage,cautery,orhyfrecationforfiliformwarts Trichloroaceticacid Trichloroaceticacid50\u201380%solutionappliedweeklyforupto8weeks VitaminDanalogues Maxacalcitolthreetimesadayfor2\u20136months,withorwithoutSAplaster82,83 Calcipotrioloncedailyfor2\u20133months84 Insufficient Citricacid Althoughtheymaybeusedinpractice,furtherstudyisneededbeforethesecanbe evidence Dithranol recommended Formicacid H2receptorantagonists Herbaltreatment Homeopathy Hypnotherapy Intralesionalimmunotherapy Occlusotherapy(e.g.ducttape) Retinoids,topical Silvernitrate Zincoxide Zincsulfate DPC,diphencyprone;SADBE,squaricaciddibutylester;ALA-PDT,aminolaevulinicacidphotodynamictherapy. \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 10}, {"text": "706 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. analysis was not done using intention to treat, so the positive apparent effect of acupuncture for common warts, there is a effect may have been overestimated.167 One study used smoke single-blinded randomized study of auricular acupuncture for from burning the leaves of Populus euphratica; in this singleplane warts. The study compared acupuncture with tretinoin blinded study of 60 patients, smoke was directed into a box0(cid:1)1% ointment. In total 53% (16/30) of patients treated with like structure surrounding the limb. The effect was compared acupuncture cleared, compared with 3% (one of 30) in the with cryotherapy. While the smoke showed a positive effect, tretinoin group.171 the method of administration could have had a mild thermal or placeboeffect.168 8.2.6. Othertreatments 8.2.5.c. Homeopathy (level of evidence 1(cid:3)). Homeopathy has many TherearesinglecasereportsofX-raytreatment163andisolated opponents and theuse of extremedilution of a substance that, limb perfusion also being used.172 A double-blinded RCT of undiluted, causes the symptoms that are being treated has no 40 patients using a topical protein\u2013lipid complex for 3 weeks scientific explanation to date. However, it is probably safe (a-lactalbumin\u2013oleic acid) vs. saline placebo reported a 75% unless the remedy is contaminated. A randomized placeboreduction in wart size.173 However, this has not been investicontrolled study of 60 children using individualized remedies gatedfurther. showed no effect in comparison with placebo; however, the methodof useof homeopathywas criticized.169,170 9.0 Future directions 8.2.5.d. Acupuncture (level of evidence 2+; strength of recommendation Warts are one of the most common skin infections and can D). While there are only isolated case reports showing an persist for many years, but the evidence base for treatment is, Table2 Recommendationsinparticularclinicalsituations Plantarwarts Cureratesareloweratthissiteprobablyduetoathickercornifiedlayerandsubsequentpoorerpenetrationof treatmentstothelowerepidermis.Paring,ifusedtoremoveexcessskinfromwartsbeforetreatment,shouldavoid damagingsurroundingskinbecauseoftheriskofspreadinginfection Salicylicacid(15\u201340%)topicalpaintsorointments12 Cryotherapy,fortnightlyfor3\u20134months12,32 Salicylicacidand/orcryotherapyusedwithmoreaggressiveregimensisprobablymoreeffectivethanstandard regimens,butcareisneededwithworseside-effects.Combinationtreatmentscanbeundertaken10,17,20,21 Othertreatments:dithranol,875-FU,93formaldehyde,78glutaraldehyde,35hyperthermia,55laser,58,65PDT,68,73 podophyllotoxin,90topicalimmunotherapy133,136 Planewarts Onthebacksofthehandsorface,planewartsaremainlyacosmeticproblemandspontaneousclearancecanoften beawaited.Destructiveandcausticagentsaremorelikelytoproducescarringatthesesitesandshouldbeused withcare Salicylicacidcream/ointment2\u201310%orcautioususeofsalicylicacidpaint,12\u201317%,usedwithoutocclusion Cryotherapy,milderfreeze Topicalretinoid110,111 Otherstreatments:acupuncture,171cantharidin,415-FUcream,94formaldehydegel,glutaraldehydesolution10%, glycolicacid15%,42,43imiquimod,131,132PDT,76,115topicalimmunotherapy,138zincoxide,155zincsulfate10% solution154 Facialwarts Planewartsasabove Treatmentoffiliformwartsinthebeardareashouldavoiddamagingadjacentskin,which,likeshaving,canspread theinfection Cryotherapy,curettageorhyfrecationcanbeused Othertreatments:glycolicacid15%,42,43imiquimod,131laser,174PDT,175,176topicalimmunotherapy177,178 Wartsinchildren Wartsinchildrenareoftenrelativelyshortlivedandarelikelytoclearwithinayearortwo.Painfultreatmentsare (handandfootwarts) oftennottoleratedandshouldbeavoidedinyoungchildrenifpossible Salicylicacid(15\u201340%)topicalpaintsorointments12 Cryotherapy,gentle,fortnightlyfor3\u20134months12,32 Othertreatments:cidofovir,121formaldehydesolutionorgel,78glutaraldehyde10%solution,79laser,61,66silver nitrate,39systemicretinoids,114topicalimmunotherapy136 Wartsinthe Treatmentmaynotbelikelytoresultincure,butcanhelptoreducebothsizeofwartsandfunctionalandcosmetic immunosuppressed problems Standardtreatmentswithparing,abrasiveagents,salicylicacidanddestructivemethods(butavoidingdamageto surroundingskin)canhelptoreducewartbulk Othertreatments:cidofovirsystemic,116\u2013119cidofovirtopical,122contactimmunotherapy,135imiquimod,129,179laser (pulsed-dyelaser),180laser+intralesionalbleomycin,63surgery,topicalretinoid,111systemicretinoid181 FU,fluorouracil;PDT,photodynamictherapy. BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 11}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 707 for the most part, weak. Evaluating the results of studies of 9.7 Pretreatmentregimens the large number of available treatments for warts has often been hampered by flaws in study design. In the future, the Treatments requiring an effect on the lower epidermis should evidenceformanagementofwartswouldbehelpedbystudies employ a standardized method to remove stratum corneum in which (i) children and adults are separated into distinct before application of the test treatment. A week of daily applitreatment groups; (ii) the duration of warts before the study cationofSA(15\u201317%)under occlusionfollowedbydailyparcommences is recorded; (iii) study groups are of an adequate ing or rubbing down is suggested. This regimen could be size; (iv) treatment runs for up to 6 months; (v) leftvs. used beforePDT, laser,cryotherapy etc. right-side studies are avoided; (vi) treatment success is measured as clearance of all treated warts; and (vii) recurrence at 10.0 Summary 3 and 6 months following completion of treatment is included whenever possible. Section 8 providesdetails oftheevidence forthevarious treatFor relatively easily available, inexpensive and well-tolerated ments. Table 1 provides a summary of recommended treattreatments, anumber ofquestions needresolution. ments for hand warts. All treatments should be used after paring or rubbing down (debridement) of warts wherever possible. The specificity of treatment regimens has rarely been 9.1 Salicylic acid tested. The treatmentsshould beused as advised by themanu1 Does the concentration of SA and the treatment regimen facturers or under direction by appropriate qualified personnel used affect outcome? who are aware of contraindications and side-effects. The sug2 Does combination withocclusion improve response rate? gestions in Table 1 are based on available trial evidence, case 3 For plantar warts, does a slightly stronger preparation series or casereports or theauthors\u2019 experience. (20\u201330% SA) used after adequate paring for up to Table 2 lists recommendations in particular clinical situa6 monthsresult in wartclearance? tions. Many clinical trials do not specifically test treatments for different types of warts or warts in specific clinical situations. 9.2 Caustics The recommendations in Table 2 are based on available trial 1 Does treatment with phenol, silver nitrate, cantharidin or evidence, case series or case reports or the authors\u2019 experitrichloroacetic acid causewarts toclear? ence. 9.3 Cryotherapy 11.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 12}, {"text": "evidence, case series or case reports or the authors\u2019 experitrichloroacetic acid causewarts toclear? ence. 9.3 Cryotherapy 11.0 Recommended audit points 1 Because of the nature of the treatment, it is difficult to use a \u2018matched\u2019 placebo control for cryotherapy, but 1 In the last 20 consecutive patients receiving cryotherapy cryotherapy could be compared directly with another treatment, were the following items recorded: (i) dose, physical treatment (e.g. laser or heat treatment), and also (ii) duration, (iii) number of cycles, (iv) documentation awell-established treatment such asSA. ofverbal consent? 2 Does combination of cryotherapy with a topical agent 2 In the last 20 consecutive patients receiving cryotherapy improve clearance rates? treatment, was a patient information leaflet on cryotherapy provided? 9.4 Virucidals The audit recommendation of 20 cases per department is to 1 Controlled trials of formaldehyde and glutaraldehyde are reduce variation in the results due to a single patient, and to much needed. allow benchmarking between different units. However, departments unable to achieve this recommendation may 9.5 Antiproliferative treatments choose toauditallcases seenin thepreceding12 months. 1 Podophyllotoxin is effective in genital warts and it is less irritatingthanpodophyllin.Whattreatmentregimencould Acknowledgments betoleratedontheskinandwhatistheresponseofwarts? 2 Do calcipotriol or calcitriol ointments induce wart clearWe are very grateful to Miss Sara Haveron (BAD Scientific ance? Administrator) and Miss Lesley Exton (BAD Information Scien3 What regimen or combination of treatment strengths of tist), as well as everyone who commented on the draft during SA with5-FU is mosteffective? theconsultation period. 9.6 Immunotherapy References 1 In a placebo-controlled study, do plane warts clear with imiquimod? 1 BellHK,OrmerodAD.WritingaBritishAssociationofDermatol2 HoweffectiveistopicalimmunotherapywithDPCinwart ogists clinical guideline: an update on the process and guidance treatment? forauthors.BrJDermatol2009;160:725\u20138. \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 12}, {"text": "708 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 2 Brouwers MC, Kho ME, Browman GP etal. AGREE II: advancing 23 Burkhart CG, Pchalek I, Adler M, Burkhart CN. An in vitro study guideline development, reporting and evaluation in health care. comparing temperatures of over-the-counter wart preparations CMAJ2010;182:E839\u201342. withliquidnitrogen.JAmAcadDermatol2007;57:1019\u201320. 3 JarrettW.Thenaturalhistoryofbovinepapillomavirusinfection. 24 CaballeroMart(cid:1)\u0131nezF, PlazaNohalesC,P(cid:1)erezCanalC etal.[CutaAdvViralOncol1986;5:83\u2013102. neous cryosurgery in family medicine: dimethyl ether\u2013propane 4 KyriakisK,PaganaG,MichailidesCetal.Lifetimeprevalenceflucspray versus liquid nitrogen]. Aten Primaria 1996; 18:211\u201316 (in tuationsofcommonandplaneviralwarts.JEurAcadDermatolVeneSpanish). reol2007;21:260\u20132. 25 Berth-Jones J, Hutchinson PE. Modern treatment of warts: cure 5 Kilkenny M, Merlin K, Young R, Marks R. The prevalence of ratesat3and6months.BrJDermatol1992;127:262\u20135. common skin conditions in Australian school students: 1. Com26 Ahmed I, Agarwal S, Ilchyshyn A etal. Liquid nitrogen cryothermon, plane and plantar viralwarts. Br J Dermatol1998; 138:840\u2013 apy of common warts: cryo-spray vs. cotton wool bud. Br J Der5. matol2001;144:1006\u20139. 6 van HaalenFM,BrugginkSC,GusseklooJ etal.Wartsin primary 27 BleikerTO,BourkeJF,LearJetal.Acomparisonofcryogunverschoolchildren: prevalence and relation with environmental facsus cotton buds for the treatment of warts. Br J Dermatol 1997; tors.BrJDermatol2009;161:148\u201352. 137(Suppl.s50):26. 7 Bruggink SC, Eekhof JA, Egberts PF etal. Natural course of cuta28 Kuwahara RT, Craig SR, AmonetteRA. Forceps and cotton applineouswartsamongprimaryschoolchildren: aprospectivecohort cator method of freezing benign lesions. Dermatol Surg 2001; study.AnnFamMed2013;11:437\u201341. 27:183\u20134. 8 Veien NK, Madsen SM, Avrach W etal. The treatment of plantar 29 Goodheart HP. Surgical Pearl: a rapid technique for destroying warts with a keratolytic agent and occlusion. J Dermatolog Treat smallskintagsandfiliformwarts.DermatolOnlineJ2003;9:34. 1991;2:59\u201361. 30 Sonnex TS, Camp RDR. The treatment of recalcitrant viral warts 9 Thomas KS, Keogh-Brown MR, Chalmers JR etal. Effectiveness with high dose cryosurgery under local anaesthesia. Br J Dermatol and cost-effectiveness of salicylic acid and cryotherapy for cuta1988;119(Suppl.s33):38\u20139. neous warts. An economic decision model. Health Technol Assess 31 HansenJG,SchmidtH.[Plantarwarts.Occurrenceandcryosurgi2006;10:iii,ix\u201387. caltreatment].UgeskrLaeger1986;148:173\u20134.(inDanish). 10 Kwok CS, Holland R, Gibbs S. Efficacy of topical treatments for 32 Berth-Jones J, Bourke J, Eglitis H etal. Value of a second freeze\u2013 cutaneous warts: a meta-analysis and pooled analysis of randomthaw cycle in cryotherapy of common warts. Br J Dermatol 1994; izedcontrolledtrials.BrJDermatol2011;165:233\u201346. 131:883\u20136. 11 Bruggink SC, Gussekloo J, Berger MY etal. Cryotherapy with 33 Connolly M, Bazmi K, O\u2019Connell M etal. Cryotherapy of viral liquidnitrogenversustopicalsalicylicacidapplicationforcutanewarts: a sustained 10-s freeze is more effective than the tradious warts in primary care: randomized controlled trial. CMAJ tionalmethod.BrJDermatol2001;145:554\u20137. 2010;182:1624\u201330. 34 BourkeJF,Berth-JonesJ,HutchinsonPE.Cryotherapyofcommon 12 Cockayne S, Hewitt C, Hicks K etal.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 13}, {"text": "etal. Cryotherapy of viral liquidnitrogenversustopicalsalicylicacidapplicationforcutanewarts: a sustained 10-s freeze is more effective than the tradious warts in primary care: randomized controlled trial. CMAJ tionalmethod.BrJDermatol2001;145:554\u20137. 2010;182:1624\u201330. 34 BourkeJF,Berth-JonesJ,HutchinsonPE.Cryotherapyofcommon 12 Cockayne S, Hewitt C, Hicks K etal. Cryotherapy versus salicylic viral warts at intervals of 1, 2 and 3weeks. Br J Dermatol 1995; acid for the treatment of plantar warts (verrucae): a randomised 132:433\u20136. controlledtrial.BMJ2011;342:d3271. 35 Bunney MH, Nolan MW, Williams DA. An assessment of meth13 KwokCS,GibbsS,BennettC etal.Topicaltreatmentsfor cutaneods of treating viral warts by comparative treatment trials based ouswarts.CochraneDatabaseSystRev2012;9:CD001781. onastandarddesign.BrJDermatol1976;94:667\u201379. 14 Tavakkolizadeh A, Povlsen B. A serious complication of topical 36 Larsen P\u00d8, Laurberg G. Cryotherapy of viral warts. J Dermatolog warttreatmentonthehand.JRSocMed2004;97:180. Treat1996;7:29\u201331. 15 Tiong WH, Kelly EJ. Salicylic acid burn induced by wart 37 Youn SH, Kwon IH, Park EJ etal. A two-week interval is better remover:areportoftwocases.Burns2009;35:139\u201340. than a three-week interval for reducing the recurrence rate of 16 Lachapelle JM, Leroy B. Allergic contact dermatitis to colophony hand-foot viral warts after cryotherapy: a tretrospective review included in the formulation of flexible collodion BP, the vehicle of 560 hand-foot viral wart patients. Ann Dermatol 2011; of a salicylic and lactic acid wart paint. Dermatol Clin 1990; 23:53\u201360. 8:143\u20136. 38 Ebrahimi S, Dabiri N, Jamshidnejad E, Sarkari B. Efficacy of 10% 17 van Brederode RL, Engel ED. Combined cryotherapy/70% salisilver nitrate solution in the treatment of common warts: a placylic acid treatment for plantar verrucae. J Foot Ankle Surg 2001; cebo-controlled, randomized, clinical trial. Int J Dermatol 2007; 40:36\u201341. 46:215\u201317. 18 Akarsu S, Ilknur T, Demirta(cid:1)soglu M, Ozkan S. Verruca vulgaris: 39 Yazar S, Ba(cid:1)saran E. Efficacy of silver nitrate pencils in the treatpulsed dye laser therapy compared with salicylic acid + pulsed mentofcommonwarts.JDermatol1994;21:329\u201333. dyelasertherapy.JEurAcadDermatolVenereol2006;20:936\u201340. 40 Banihashemi M, Pezeshkpoor F, Yazdanpanah MJ, Family S. Effi19 Armour K, Orchard D. Treatment of palmoplantar warts with a cacy of 80% phenol solution in comparison with cryotherapy in diphencyprone and salicylic acid ointment. Australas J Dermatol the treatment of common warts of hands. Singapore Med J 2008; 2006;47:182\u20135. 49:1035\u20137. 20 YoungS,CohenGE.Treatmentofverrucaplantariswithacombi41 Kartal Durmazlar SP, Atacan D, Eskioglu F. Cantharidin treatment nation of topical fluorouracil and salicylic acid. J Am Podiatr Med for recalcitrant facial flat warts: a preliminary study. J Dermatolog Assoc2005;95:366\u20139. Treat2009;20:114\u201319.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 13}, {"text": "Atacan D, Eskioglu F. Cantharidin treatment nation of topical fluorouracil and salicylic acid. J Am Podiatr Med for recalcitrant facial flat warts: a preliminary study. J Dermatolog Assoc2005;95:366\u20139. Treat2009;20:114\u201319. 21 Becerro de Bengoa Vallejo R, Iglesias MEL, G(cid:1)omez-Mart(cid:1)\u0131n B etal. 42 Borbujo J, Olmos O, Zamora E etal. Treatmentof verrucae plana Applicationofcantharidinandpodophyllotoxinforthetreatment with15%glycolicacid.IntJDermatol2000;39:236\u20137. ofplantarwarts.JAmPodiatrMedAssoc2008;98:445\u201350. 43 Rodr(cid:1)\u0131guez-Cerdeira C, S(cid:1)anchez-Blanco E. Glycolic acid 15% plus 22 Gaspar ZS, Dawber RP. An organic refrigerant for cryosurgery: salicylic acid 2%: a new therapeutic pearl for facial flat warts. J factorfiction?AustralasJDermatol1997;38:71\u20132. ClinAesthetDermatol2011;4:62\u20134. BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 13}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 709 44 Halasz CL. Treatment of warts with topical pyruvic acid: with 68 Stender IM, Na R, Fogh H etal. Photodynamic therapy with andwithoutadded5-fluorouracil.Cutis1998;62:283\u20135. 5-aminolaevulinic acid or placebo for recalcitrant foot and hand 45 Donaldson MR, Stetson CL. Hypertrophic scarring after treatment warts:randomiseddouble-blindtrial.Lancet2000;355:963\u20136. with fluorouracil, 2%, in pyruvic acid, 98%, for Verruca vulgaris. 69 Fabbrocini G, Di Costanzo MP, Riccardo AM etal. Photodynamic ArchDermatol2010;146:213\u201314. therapy with topical delta-aminolaevulinic acid for the treatment 46 Vali A, Ferdowsi F. Evaluation of the efficacy of 50% citric acid ofplantarwarts.JPhotochemPhotobiol,B2001;61:30\u20134. solutioninplanewarttreatment.IndianJDermatol2007;52:96\u20138. 70 Schroeter CA, Kaas L, Waterval JJ etal. Successful treatment of 47 BhatRM,VidyaK,KamathG.Topicalformicacidpuncturetechperiungualwartsusingphotodynamictherapy:apilotstudy.JEur nique for the treatment of common warts. Int J Dermatol 2001; AcadDermatolVenereol2007;21:1170\u20134. 40:415\u201319. 71 StenderIM,WulfHC.Photodynamictherapyofrecalcitrantwarts 48 Shamsadini S, Baghery MH. Treatment of warts with topical forwith 5-aminolevulinic acid: a retrospective analysis. Acta Derm micacid.IranJMedSci2005;30:199. Venereol1999;79:400\u20131. 49 Faghihi G, Vali A, Radan M etal. A double-blind, randomized 72 WangYS,TayYK,KwokCetal.Photodynamictherapywith20% trial of local formic acid puncture technique in the treatment of aminolevulinicacidforthetreatmentofrecalcitrantviralwartsin commonwarts.Skinmed2010;8:70\u20131. anAsianpopulation.IntJDermatol2007;46:1180\u20134. 50 Godley MJ, Bradbeer CS, Gellan M, Thin RN. Cryotherapy com73 Yoo KH, Kim BJ, Kim MN. Enhanced efficacy of photodynamic pared with trichloroacetic acid in treating genital warts. Genitourin therapywithmethyl5-aminolevulinicacidin recalcitrantperiunMed1987;63:390\u20132. gual warts after ablative carbon dioxide fractional laser: a pilot 51 Pezeshkpoor F, Banihashemi M, Yazdanpanah MJ etal. Comparastudy.DermatolSurg2009;35:1927\u201332. tivestudyoftopical80%trichloroaceticacidwith35%trichloro74 Fernandez-Guarino M, Harto A, Jaen P. Treatment of recalcitrant acetic acid in the treatment of the common wart. J Drugs Dermatol viral warts with pulsed dye laser MAL-PDT. J Dermatolog Treat 2012;11:e66\u20139. 2011;22:226\u20138. 52 JenningsMB,RickettiJ,GuadaraJetal.Treatmentforsimpleplan75 ZiolkowskiP,OsieckaBJ,SiewinskiMetal.Pretreatmentofplantarverrucae:monochloroaceticacidand10%formaldehydeversus tarwartswithazoneenhancestheeffectof5-aminolevulinicacid 10%formaldehydealone.JAmPodiatrMedAssoc2006;96:53\u20138. photodynamic therapy. J Environ Pathol Toxicol Oncol 2006; 53 BaserNT,YalazB, YilmazAC etal.An unusual andseriouscom25:403\u20139. plication of topical wart treatment with monochloroacetic acid. 76 Lu YG, Wu JJ, He Y etal. Efficacy of topical aminolevulinic acid IntJDermatol2008;47:1295\u20137. photodynamic therapy for the treatment of verruca planae. Pho54 SternP, LevineN.Controlled localizedheat therapyin cutaneous tomedLaserSurg2010;28:561\u20133. warts.ArchDermatol1992;128:945\u20138. 77 Li Q, Jiao B, Zhou F etal. Comparative study of photodynamic 55 HuoW,GaoX-H,SunX-Petal.Localhyperthermiaat44\u00b0Cfor therapywith5%,10%and20%aminolevulinicacidinthetreatthe treatment of plantar warts: a randomized, patient-blinded, mentofgeneralizedrecalcitrantfacialverrucaplana:arandomized placebo-controlledtrial.JInfectDis2010;201:1169\u201372. clinical trial. J Eur Acad Dermatol Venereol 2013. doi:10.1111/ 56 GaoXH,GaoD,SunXPetal.Non-ablativecontrolledlocalhyperjdv.12319[Epubaheadofprint]. thermiaforcommonwarts.ChinMedJ2009;122:2061\u20133. 78 Vickers CF. Treatment of plantar warts in children. BMJ 1961; 57 LelliottPE,RobinsonC.Aretrospectivestudytoevaluateverrucae 2:743\u20135. regrowthfollowingelectrosurgery.BrJPod1999;2:84\u20138. 79 HiroseR,HoriM,ShukuwaTetal.Topicaltreatmentofresistant 58 Robson KJ, Cunningham NM, Kruzan KL etal. Pulsed-dye laser wartswithglutaraldehyde.JDermatol1994;21:248\u201353. versusconventionaltherapyinthetreatmentofwarts:aprospec80 FujisawaY,FurutaJ,KawachiY,OtsukaF.Deepplantarisulcerativerandomizedtrial.JAmAcadDermatol2000;43:275\u201380.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 14}, {"text": "doi:10.1111/ 56 GaoXH,GaoD,SunXPetal.Non-ablativecontrolledlocalhyperjdv.12319[Epubaheadofprint]. thermiaforcommonwarts.ChinMedJ2009;122:2061\u20133. 78 Vickers CF. Treatment of plantar warts in children. BMJ 1961; 57 LelliottPE,RobinsonC.Aretrospectivestudytoevaluateverrucae 2:743\u20135. regrowthfollowingelectrosurgery.BrJPod1999;2:84\u20138. 79 HiroseR,HoriM,ShukuwaTetal.Topicaltreatmentofresistant 58 Robson KJ, Cunningham NM, Kruzan KL etal. Pulsed-dye laser wartswithglutaraldehyde.JDermatol1994;21:248\u201353. versusconventionaltherapyinthetreatmentofwarts:aprospec80 FujisawaY,FurutaJ,KawachiY,OtsukaF.Deepplantarisulcerativerandomizedtrial.JAmAcadDermatol2000;43:275\u201380. tion secondary to the topical treatment of wart with glutaralde59 Park HS, Choi WS. Pulsed dye laser treatment for viral warts: a hyde.JDermatol2009;36:618\u201319. studyof120patients.JDermatol2008;35:491\u20138. 81 Egawa K, Ono T. Topical vitamin D3 derivatives for recalcitrant 60 Ross BS, Levine VJ, Nehal K etal. Pulsed dye laser treatment of warts in three immunocompromised patients. Br J Dermatol 2004; warts:anupdate.DermatolSurg1999;25:377\u201380. 150:374\u20136. 61 Sethuraman G, Richards KA, Hiremagalore RN, Wagner A. Effec82 Inaba H, Suzuki T, Adachi A, Tomita Y. Successful treatment of tiveness of pulsed dye laser in the treatment of recalcitrant warts warts with a combination of maxacalcitol ointment and salicylic inchildren.DermatolSurg2010;36:58\u201365. acidstickingplaster.JDermatol2006;33:383\u20135. 62 Kauvar AN, Geronemus RG. Pulsed-dye laser versus conventional 83 Imagawa I, Suzuki H. Successful treatment of refractory warts therapy in the treatment of warts. J Am Acad Dermatol 2001; with topical vitamin D3 derivative (maxacalcitol, 1a,25-dihydr45:151\u20132. oxy-22-oxacalcitriol)in17patients.JDermatol2007;34:264\u20136. 63 Pollock B, Sheehan-Dare R. Pulsed dye laser and intralesional 84 Labandeira J, Vazquez-Blanco M, Paredes C etal. Efficacy of topibleomycin for treatment of resistant viol hand warts. Lasers Surg calcalcipotriolinthetreatmentofagiantviralwart.PediatrDermaMed2002;30:135\u201340. tol2005;22:375\u20136. 64 Dobson JS, Harland CC. Pulsed dye laser and intralesional bleo85 HayashiJ,MatsuiC,MitsuishiTetal.Treatmentoflocalizedepimycinforthetreatmentofrecalcitrantcutaneouswarts.LasersSurg dermodysplasiaverruciformiswithtacalcitolointment.IntJDermaMed2014;46:112\u201316. tol2002;41:817\u201320. 65 Kopera D. Verrucae vulgares: flashlamp-pumped pulsed dye laser 86 Flindt-Hansen H, Tikj\u00f8b G, Brandrup F. Wart treatment with treatmentin134patients.IntJDermatol2003;42:905\u20138. anthralin.ActaDermVenereol1984;64:177\u20139. 66 Park HS, Kim JW, Jang SJ, Choi JC. Pulsed dye laser therapy for 87 HjorthN,MadsenK,NorgaardM.Anthralinstick(Anthraderm)in pediatricwarts.PediatrDermatol2007;24:177\u201381. thetreatmentofmosaicwarts.ActaDermVenereol1986;66:181\u20132. 67 Han TY, Lee JH, Lee CK etal. Long-pulsed Nd:YAG laser treat88 MircevaV,JessbergerB,KonstantinowAetal.Treatmentofcomment of warts: report on a series of 369 cases. J Korean Med Sci mon warts with dithranol salicylic acid-containing ointment \u2013 2009;24:889\u201393. non-interventionaltrial.AktuelleDermatol2008;34:428\u201332. \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 14}, {"text": "710 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 89 MircevaV,JessbergerB,PapadopulosNAetal.Treatmentofcuta109 Yamamoto T. Bleomycin and the skin. Br J Dermatol 2006; neous warts with a wart cream containing anthralin and salicylic 155:869\u201375. acid: an efficacy study on 44 patients. Aktuelle Dermatol 2007; 110 KubeyinjeEP.Evaluationoftheefficacyandsafetyof0.05%treti33:422\u20137. noin cream in the treatment of plane warts in Arab children. J 90 Duthie DA, McCallum DI. Treatment of plantar warts with elaDermatologTreat1996;7:21\u20132. stoplastandpodophyllin.BMJ1951;2:216\u201318. 111 Euvrard S, Verschoore M, Touraine JL etal. Topical retinoids for 91 Ka(cid:1)car N, Ta(cid:1)sl\u0131 L, Korkmaz S etal. Cantharidin-podophylotoxinwartsandkeratosesintransplantrecipients.Lancet1992;340:48\u20139. salicylicacidversuscryotherapyinthetreatmentofplantarwarts: 112 GuptaR.Plantarwartstreatedwithtopicaladapalene.IndianJDera randomized prospective study. J Eur Acad Dermatol Venereol 2012; matol2011;56:513\u201314. 26:889\u201393. 113 Choi YL, Lee KJ, Kim WS etal. Treatment of extensive and 92 HursthouseMW.Acontrolledtrialontheuseoftopical5-fluororecalcitrantviralwartswithacitretin.IntJDermatol2006;45:480\u2013 uracilonviralwarts.BrJDermatol1975;92:93\u20136. 2. 93 Salk RS, Grogan KA, Chang TJ. Topical 5% 5-fluorouracil cream 114 Gelmetti C, Cerri D, Schiuma AA etal. Treatment of extensive inthetreatmentofplantarwarts:aprospective,randomized,and wartswithetretinate:aclinicaltrialin20children.PediatrDermatol controlledclinicalstudy.JDrugsDermatol2006;5:418\u201324. 1987;4:254\u20138. 94 Lee S, Kim JG, Chun SI. Treatment of verruca plana with 5% 115 Al-HamamyHR,SalmanHA,AbdulsattarNA.Treatmentofplane 5-fluorouracilointment.Dermatologica1980;160:383\u20139. warts with a low-dose oral isotretinoin. ISRN Dermatol 2012; 95 Luk NM, Tang WY, Tang NL etal. Topical 5-fluorouracil has no 2012:163929. additional benefit in treating common warts with cryotherapy: a 116 Cusack C, Fitzgerald D, Clayton TM, Irvine AD. Successful treatsingle-centre, double-blind, randomized, placebo-controlled trial. ment of florid cutaneous warts with intravenous cidofovir in an ClinExpDermatol2006;31:394\u20137. 11-year-oldgirl.PediatrDermatol2008;25:387\u20139. 96 Zschocke I, Hartmann A, Schlo\u20acbe A etal. [Efficacy and benefit of 117 Grone D, Treudler R, de Villiers EM etal. Intravenous cidofovir a 5-FU/salicylic acid preparation in the therapy of common and treatment for recalcitrant warts in the setting of a patient with plantar warts \u2013 systematic literature review and meta-analysis]. myelodysplastic syndrome. J Eur Acad Dermatol Venereol 2006; JDtschDermatolGes2004;2:187\u201393(inGerman). 20:202\u20135. 97 Yazdanfar A, Farshchian M, Fereydoonnejad M. Treatment of 118 Hivnor C, Shepard JW, Shapiro MS, Vittorio CC. Intravenous cicommon warts with an intralesional mixture of 5-fluorouracil, dofovir for recalcitrant Verruca vulgaris in the setting of HIV. Arch lidocaine, and epinephrine: a prospective placebo-controlled, Dermatol2004;140:13\u201314. double-blindrandomizedtrial.DermatolSurg2008;34:656\u20139. 119 Kottke MD, Parker SR. Intravenous cidofovir-induced resolution 98 Is(cid:1)cimen A, Aydemir EH, G\u20acoksu\u20acgu\u20acr N, Engin B. Intralesional of disfiguring cutaneous human papillomavirus infection. J Am 5-fluorouracil, lidocaine and epinephrine mixture for the treatAcadDermatol2006;55:533\u20136. ment of verrucae: a prospective placebo-controlled, single-blind 120 Mackintosh L, Parker A, Leman J. Intravenous cidofovir for the randomizedstudy.JEurAcadDermatolVenereol2004;18:455\u20138.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 15}, {"text": "of disfiguring cutaneous human papillomavirus infection. J Am 5-fluorouracil, lidocaine and epinephrine mixture for the treatAcadDermatol2006;55:533\u20136. ment of verrucae: a prospective placebo-controlled, single-blind 120 Mackintosh L, Parker A, Leman J. Intravenous cidofovir for the randomizedstudy.JEurAcadDermatolVenereol2004;18:455\u20138. treatment of florid cutaneous warts in association with chronic 99 Lewis TG, Nydorf ED. Intralesional bleomycin for warts: a graft-versus-hostdisease.BrJDermatol2012;167(Suppl.1):116. review.JDrugsDermatol2006;5:499\u2013504. 121 Field S, Irvine AD, Kirby B. The treatment of viral warts with 100 Hayes ME, O\u2019Keefe EJ. Reduced dose of bleomycin in the treattopicalcidofovir1%: our experience ofsevenpaediatricpatients. mentofrecalcitrantwarts.JAmAcadDermatol1986;15:1002\u20136. BrJDermatol2009;160:223\u20134. 101 AlGhamdiKM,KhurramH.Successfultreatmentofperiungualwarts 122 TobinAM,CotterM,IrvineAD,KirbyB.Successfultreatmentof with diluted bleomycin using translesional multipuncture techa refractory verruca in a child with acute lymphoblastic leukaenique:apilotprospectivestudy.DermatolSurg2011;37:486\u201392. miawithtopicalcidofovir.BrJDermatol2005;152:386\u20138. 102 Munn SE, Higgins E, Marshall M, Clement M. A new method of 123 BroganelliP,ChiarettaA,FragnelliB,BernengoMG.Intralesional intralesional bleomycin therapy in the treatment of recalcitrant cidofovirforthetreatmentofmultipleandrecalcitrantcutaneous warts.BrJDermatol1996;135:969\u201371. viralwarts.DermatolTher2012;25:468\u201371. 103 van der Velden EM, Ijsselmuiden OE, Drost BH, Baruchin AM. 124 BienvenuB,MartinezF,DevergieAetal.Topicaluseofcidofovir Dermatography with bleomycin as a new treatment for Verrucae inducedacuterenalfailure.Transplantation2002;73:661\u20132. vulgaris.IntJDermatol1997;36:145\u201350. 125 FochtDR,SpicerC,FairchokMP.Theefficacyofducttapeversus 104 Soni P, Khandelwal K, AaraN etal. Efficacyofintralesionalbleocryotherapy in the treatment of Verruca vulgaris (the common mycin in palmo-plantar and periungual warts. J Cutan Aesthet Surg wart).ArchPediatrAdolescMed2002;156:971\u20134. 2011;4:188\u201391. 126 de Haen M, Spigt MG, van Uden CJ etal. Efficacy of duct tape 105 BunneyMH,NolanMW,BuxtonPKetal.Thetreatmentofresisversus placebo in the treatment of Verruca vulgaris (warts) in tantwartswithintralesionalbleomycin:acontrolledclinicaltrial. primary school children. Arch Pediatr Adolesc Med 2006; BrJDermatol1984;111:197\u2013207. 160:1121\u20135. 106 Adalatkhah H, Khalilollahi H, Amini N, Sadeghi-Bazargani H. 127 WennerR,AskariSK,ChamPMetal.Ducttapeforthetreatment Compared therapeutic efficacy between intralesional bleomycin of common warts in adults: a double-blind randomized conand cryotherapy for common warts: a randomized clinical trial. trolledtrial.ArchDermatol2007;143:309\u201313. DermatolOnlineJ2007;13:4. 128 Grussendorf-Conen EI, Jacobs S, Ru\u20acbben A, Dethlefsen U. Top107 Dhar SB, Rashid MM, Islam A, Bhuiyan M. Intralesional bleomyical 5% imiquimod long-term treatment of cutaneous warts cin in the treatment of cutaneous warts: a randomized clinical resistant to standard therapy modalities. Dermatology 2002; trial comparing it with cryotherapy. Indian J Dermatol Venereol Leprol 205:139\u201345. 2009;75:262\u20137. 129 Hengge UR, Goos M, Arndt R. Topical treatment of warts and 108 Abess A, Keel DM, Graham BS. Flagellate hyperpigmentation folmolluscawithimiquimod.AnnInternMed2000;132:95. lowing intralesional bleomycin treatment of verruca plantaris. 130 KimSY,JungSK,LeeSGetal.NewalternativecombinationtherArchDermatol2003;139:337\u20139. apy for recalcitrant common warts: the efficacy of imiquimod BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 15}, {"text": "intralesional bleomycin treatment of verruca plantaris. 130 KimSY,JungSK,LeeSGetal.NewalternativecombinationtherArchDermatol2003;139:337\u20139. apy for recalcitrant common warts: the efficacy of imiquimod BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 15}, {"text": "BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 711 5%creamandducttapecombinationtherapy.AnnDermatol2013; placebo-controlled clinical trial. J Am Acad Dermatol 2009; 60: 25:261\u20133. 706\u20138. 131 Kim MB, Ko HC, Jang HS etal. Treatment of flat warts with 5% 153 SadighhaA.Oralzincsulphateinrecalcitrantmultipleviralwarts: imiquimodcream.JEurAcadDermatolVenereol2006;20:1349\u201350. apilotstudy.JEurAcadDermatolVenereol2009;23:715\u201316. 132 Oster-Schmidt C. Imiquimod: a new possibility for treatment154 SharquieKE,KhorsheedAA,Al-NuaimyAA.Topicalzincsulphate resistantverrucaeplanae.ArchDermatol2001;137:666\u20137. solutionfortreatmentofviralwarts.SaudiMedJ2007;28:1418\u201321. 133 Buckley DA, Keane FM, Munn SE etal. Recalcitrant viral warts 155 Khattar JA, Musharrafieh UM, Tamim H, Hamadeh GN. Topical treated by diphencyprone immunotherapy. Br J Dermatol 1999; zinc oxide vs. salicylic acid-lactic acid combination in the treat141:292\u20136. mentofwarts.IntJDermatol2007;46:427\u201330. 134 Upitis JA, Krol A. The use of diphenylcyclopropenone in the 156 Burns DA. \u2018Warts and all\u2019 \u2013 the history and folklore of warts: a treatmentofrecalcitrantwarts.JCutanMedSurg2002;6:214\u201317. review.JRSocMed1992;85:37\u201340. 135 Audrain H, Siddiqui H, Buckley DA. Diphencyprone immuno157 Rankin S, Swinscoe M. Alternative treatments and folk remedies therapyforviralwartsinimmunosuppressedpatients.BrJDermainthetreatmentofwarts.BrJPod2002;5:12\u201314. tol2013;168:1138\u20139. 158 SpanosNP,WilliamsV,GwynnMI.Effectsofhypnotic,placebo, 136 MicaliG,NascaMR,TedeschiAetal.Useofsquaricaciddibutyand salicylic acid treatments on wart regression. Psychosom Med lester (SADBE) for cutaneous warts in children. Pediatr Dermatol 1990;52:109\u201314. 2000;17:315\u201318. 159 Surman OS, Gottlieb SK, Hackett TP, Silverberg EL. Hypnosis in 137 Silverberg JI, Silverberg NB. Adjunctive trichloroacetic acid therthetreatmentofwarts.ArchGenPsychiatry1973;28:439\u201341. apyenhancessquaricacidresponsetoVerrucavulgaris.JDrugsDerma160 Shenefelt PD. Biofeedback, cognitive-behavioral methods, and tol2012;11:1228\u201330. hypnosis in dermatology: is it all in your mind? Dermatol Ther 138 Salem A, Nofal A, Hosny D. Treatment of common and plane 2003;16:114\u201322. warts in children with topical viable Bacillus Calmette\u2013Gu(cid:1)erin. 161 Dave R, Monk B, Mahaffey P. Spontaneous disappearance of PediatrDermatol2013;30:60\u20133. refractory viral warts at distant sites following carbon-dioxide 139 Horn TD, Johnson SM, Helm RM, Roberson PK. Intralesional lasertreatment.BrJPlastSurg2002;55:696\u20138. immunotherapy of warts with mumps, Candida, and Trichophyton 162 Harkness EF, Abbot NC, Ernst E. A randomized trial of distant skin test antigens: a single-blinded, randomized, and controlled healingforskinwarts.AmJMed2000;108:448\u201352. trial.ArchDermatol2005;141:589\u201394. 163 MeinekeV,ReichrathJ,ReinholdU,TilgenW.Verrucaevulgares 140 PhillipsRC,RuhlTS,PfenningerJL,GarberMR.Treatmentofwarts in children: successful simulated X-ray treatment (a suggestionwithCandidaantigeninjection.ArchDermatol2000;136:1274\u20135. basedtherapy).Dermatology2002;204:287\u20139. 141 Signore RJ. Candida albicans intralesional injection immunotherapy 164 Bedi MK, Shenefelt PD. Herbal therapy in dermatology. Arch Derofwarts.Cutis2002;70:185\u201392. matol2002;138:232\u201342. 142 Mitsuishi T, Iida K, Kawana S. Cimetidine treatment for viral 165 Dehghani F, Merat A, Panjehshahin MR, Handjani F. Healing warts enhances IL-2 and IFN-c expression but not IL-18 expreseffect of garlic extract on warts and corns. Int J Dermatol 2005; sioninlesionalskin.EurJDermatol2003;13:445\u20138. 44:612\u201315. 143 GooptuC,JamesMP.Recalcitrantviralwarts:resultsoftreatment 166 Bohlooli S, Mohebipoor A, Mohammadi S etal. Comparative withtheKTPlaser.ClinExpDermatol1999;24:60\u20133. studyoffigtreeefficacyinthetreatmentofcommonwarts(Ver144 Rogers CJ, Gibney MD, Siegfried EC etal.", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 16}, {"text": "expreseffect of garlic extract on warts and corns. Int J Dermatol 2005; sioninlesionalskin.EurJDermatol2003;13:445\u20138. 44:612\u201315. 143 GooptuC,JamesMP.Recalcitrantviralwarts:resultsoftreatment 166 Bohlooli S, Mohebipoor A, Mohammadi S etal. Comparative withtheKTPlaser.ClinExpDermatol1999;24:60\u20133. studyoffigtreeefficacyinthetreatmentofcommonwarts(Ver144 Rogers CJ, Gibney MD, Siegfried EC etal. Cimetidine therapy for rucavulgaris)vs.cryotherapy.IntJDermatol2007;46:524\u20136. recalcitrant warts in adults: is it any better than placebo? J Am 167 Zedan H, Hofny ER, Ismail SA. Propolis as an alternative treatAcadDermatol1999;41:123\u20137. mentforcutaneouswarts.IntJDermatol2009;48:1246\u20139. 145 Lee SH, Rose B, Thompson CH, Cossart Y. Plantar warts of 168 Rahimi AR, Emad M, Rezaian GR. Smoke from leaves of Populus defined aetiology in adults and unresponsiveness to low dose euphraticaOliviervs.conventionalcryotherapyforthetreatmentof cimetidine.AustralasJDermatol2001;42:220\u20131. cutaneous warts: a pilot, randomized, single-blind, prospective 146 Karaman G, Sendur N, Sevk E. Ranitidine therapy for recalcitrant study.IntJDermatol2008;47:393\u20137. warts in adults: a preliminary study. J Eur Acad Dermatol Venereol 169 Kainz JT, Kozel G, Haidvogl M, Smolle J. Homoeopathic versus 2001;15:495\u20136. placebotherapyof children with warts on the hands: a random147 HamblinTJ.Long-lastingresponseoftherapy-resistantviralwarts ized,double-blindclinicaltrial.Dermatology1996;193:318\u201320. to treatment with interleukin-2 in a patient with chronic lym170 GengouxP.Homeopathicversusplacebotherapyofchildrenwith phocytic leukemia (CLL) and profound immunodeficiency. Leuk wartsonthehands.Dermatology1997;195:183. Res2007;31:413\u201314. 171 Ning S, Li F, Qian L etal. The successful treatment of flat warts 148 Lin JH, Wang KY, Kraft S, Roberts RL. Resolution of warts in withauricularacupuncture.IntJDermatol2012;51:211\u201315. association with subcutaneous immunoglobulin in immune defi172 Damian DL, Barnetson RS, Rose BR etal. Treatment of refractory ciency.PediatrDermatol2009;26:155\u20138. handwartsbyisolatedlimbinfusionwithmelphalanandactino149 Tandeter H, Tandeter ER. Treatment of plantar warts with oral mycinD.AustralasJDermatol2001;42:106\u20139. valacyclovir.AmJMed2005;118:689\u201390. 173 GustafssonL,LeijonhufvudI,AronssonAetal.Treatmentofskin 150 Lo(cid:1)pez-Garc(cid:1)\u0131a DR, Go(cid:1)mez-Flores M, Arce-Mendoza AY etal. Oral papillomas with topical a-lactalbumin\u2013oleic acid. N Engl J Med zinc sulfate for unresponsive cutaneous viral warts: too good to 2004;350:2663\u201372. be true? A double-blind, randomized, placebo-controlled trial. 174 Li Y, Yang K. Treatment of recalcitrant-pigmented flat warts ClinExpDermatol2009;34:e984\u20135. usingfrequency-doubledQ-switchedNd-YAGlaser.LasersSurgMed 151 Al-GurairiFT,Al-WaizM,SharquieKE.Oralzincsulphatein the 2001;29:244\u20137. treatment of recalcitrant viral warts: randomized placebo-con175 Caucanas M, Gillard P, Vanhooteghem O. Efficiency of photodytrolledclinicaltrial.BrJDermatol2002;146:423\u201331. namic therapy in the treatment of diffuse facial viral warts in an 152 Yaghoobi R, Sadighha A, Baktash D. Evaluation of oral zinc immunosuppressedpatient:towardsagoldstandard?CaseRepDersulfate effect on recalcitrant multiple viral warts: a randomized matol2010;2:207\u201313. \u00a92014BritishAssociationofDermatologists BritishJournalofDermatology(2014)171,pp696\u2013712 Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 16}, {"text": "by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 2, "page": 16}, {"text": "712 BADguidelinesforcutaneouswarts2014, J.C.Sterlingetal. 176 Durani BK, Jappe U. Successful treatment of facial plane warts Appendix 2 withimiquimod.BrJDermatol2002;147:1018. 177 Aghaei S. Treatmentofdisseminatedfacial warts throughcontact Strength ofrecommendation immunotherapy with diphenylcyclopropenone (DPCP). Dermatol OnlineJ2006;12:10. 178 Hama N, Hatamochi A, Hayashi S etal. Usefulness of topical Class Evidence immunotherapy with squaric acid dibutylester for refractory commonwartsonthefaceandneck.JDermatol2009;36:660\u20132. A Atleastonemeta-analysis,systematicrevieworRCT 179 WeisshaarE,GollnickH.Potentiatingeffectofimiquimodinthe ratedas1++,anddirectlyapplicabletothetarget treatment of verrucae vulgares in immunocompromised patients. population,or ActaDermVenereol2000;80:306\u20137. AsystematicreviewofRCTsorabodyofevidence 180 L\u20acauchli S, Kempf W, Dragieva G etal. CO 2 laser treatment of consistingprincipallyofstudiesratedas1+,directly warts in immunosuppressed patients.Dermatology 2003; 206:148\u2013 applicabletothetargetpopulationanddemonstrating 52. overallconsistencyofresults 181 Monastirli A, Matsouka P, Pasmatzi E etal. Complete remission EvidencedrawnfromaNICEtechnologyappraisal of recalcitrant viral warts under oral isotretinoin in a patient B Abodyofevidenceincludingstudiesratedas2++, with low-grade B-cell lymphoma. Acta Derm Venereol 2005; directlyapplicabletothetargetpopulationand 85:358\u201360. demonstratingoverallconsistencyofresults,or Extrapolatedevidencefromstudiesratedas1++or1+ C Abodyofevidenceincludingstudiesratedas2+, Supporting Information directlyapplicabletothetargetpopulationand demonstratingoverallconsistencyofresults,or AdditionalSupportingInformationmaybefoundintheonline Extrapolatedevidencefromstudiesratedas2++ version ofthis article atthepublisher\u2019s website: D Evidencelevel3or4,or Data S1.Literature search strategies. Extrapolatedevidencefromstudiesratedas2+,or Formalconsensus D(GPP) Agoodpracticepoint(GPP)isarecommendationfor Appendix 1 bestpracticebasedontheexperienceoftheguideline Levels ofevidence developmentgroup RCT,randomizedcontrolledtrial;NICE,NationalInstitutefor HealthandCareExcellence. Levelof evidencea Typeofevidence 1++ High-qualitymeta-analyses,systematicreviewsof RCTs,orRCTswithaverylowriskofbias 1+ Well-conductedmeta-analyses,systematicreviewsof RCTs,orRCTswithalowriskofbias 1(cid:3) Meta-analyses,systematicreviewsofRCTs,orRCTs withahighriskofbias 2++ High-qualitysystematicreviewsofcase\u2013controlor cohortstudies High-qualitycase\u2013controlorcohortstudieswitha verylowriskofconfounding,biasorchanceand ahighprobabilitythattherelationshipiscausal 2+ Well-conductedcase\u2013controlorcohortstudieswith alowriskofconfounding,biasorchanceanda moderateprobabilitythattherelationshipiscausal 2(cid:3) Case\u2013controlorcohortstudieswithahighriskof confounding,biasorchanceandasignificantrisk thattherelationshipisnotcausal 3 Nonanalyticalstudies(forexamplecasereports,case series) 4 Expertopinion,formalconsensus RCT,randomizedcontrolledtrial.aStudieswithalevelofevidence\u2018(cid:3)\u2019shouldnotbeusedasabasisformakingarecommendation. BritishJournalofDermatology(2014)171,pp696\u2013712 \u00a92014BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/171/4/696/6615605 by guest on 23 February 2026", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 17}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "cutaneous warts.pdf", "chunk_id": 0, "page": 18}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "cutaneous warts.pdf", "chunk_id": 1, "page": 18}, {"text": "JournalofPlastic,Reconstructive&AestheticSurgery(2010)63,1401e1419 Revised UK guidelines for the management *,** of cutaneous melanoma 2010 J.R. Marsdena,*, J.A. Newton-Bishop b, L. Burrows c, M. Cook d, P.G. Corrie e, N.H. Cox a, M.E. Gore f, P. Lorigang, R. MacKieh, P. Nathan i, H. Peachj, B. Powell k, C. Walkera aUniversity HospitalBirmingham, Birmingham B29 6JD,United Kingdom bUniversity of Leeds,Leeds LS9 7TF,United Kingdom cSalisbury District Hospital, Salisbury SP2 8BJ, United Kingdom dRoyal Surrey CountyHospital NHSTrust,Guildford GU27XX, United Kingdom eCambridge University Hospitals NHS FoundationTrust,Cambridge CB2 2QQ,United Kingdom fRoyal Marsden Hospital, LondonSW3 6JJ,United Kingdom gTheChristie NHS Foundation Trust, ManchesterM20 4BX,United Kingdom hUniversity of Glasgow,Glasgow G128QQ, United Kingdom iMount Vernon Hospital, London HA62RN,United Kingdom jStJames\u2019sUniversity Hospital, LeedsLS9 7TF,United Kingdom kStGeorge\u2019sHospital, London SW170QT,United Kingdom KEYWORDS Summary These guidelines for the management of cutaneous melanoma present an Evidence; evidence-basedguidancefortreatment,withidentificationofthestrengthofevidenceavailGuideline; ableatthetimeofpreparationoftheguidelines,andabriefoverviewofepidemiology,diagInvestigation; nosis,investigation,andfollow-up. Melanoma; \u00aa2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons and British Treatment AssociationofDermatologists.Allrightsreserved. *ThisisanupdatedguidelinepreparedfortheBritishAssociationofDermatologists(BAD)ClinicalStandardsUnit,madeupoftheTherapy& GuidelinesSubcommittee(T&G)andtheAudit&ClinicalStandardsSubcommittee(A&CS).MembersoftheClinicalStandardsUnitare:HKBell [ChairmanT&G],LCFuller[ChairmanA&CS],NJLevell,MJTidman,PDYesudian,JLear,JHughes,AJMcDonagh,SPunjabi,NMorar,SWagle [BritishNationalFormulary],SEHulley[BritishDermatologicalNursingGroup],KJLyons[BADScientificAdministrator],andMFMohdMustapa [BADClinicalStandardsManager]. TheseguidelinesarepublishedsimultaneouslyintheBritishJournalofDermatology(doi:10.1111/j.1365-2133.2010.09883.x)andtheJournal ofPlastic,Reconstructive&AestheticSurgery(doi:10.1016/j.bjps.2010.07.006). **Guidelinesproducedin2002bytheBritishAssociationofDermatologists;reviewedandupdated,2009. * Correspondingauthor. E-mailaddress:jerry.marsden@uhb.nhs.uk(J.R.Marsden). 1748-6815/$-seefrontmatter\u00aa2010BritishAssociationofPlastic,ReconstructiveandAestheticSurgeonsandBritishAssociationofDermatologists.Allrightsreserved. doi:10.1016/j.bjps.2010.07.006", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 1}, {"text": "1402 J.R.Marsden etal. Guidelines review process and other publications were identified from the PubMed searches,independentsearchescarriedoutbytheauthors, These guidelines were initially reviewed at a multidisciaswellasmaterialscollectedbytheauthorsaspartoftheir plinarymeetingon8November2007.Thoseattendingwere ongoingprofessionalinterestinthelatestdevelopmentsin theauthors plus: this clinical area. Levels of evidence to support the guideDermatology: V Doherty, D Roberts, F Wojnarowska, lines are quoted according to the criteria stated in HBell,DdeBerker,CHarwood,SBailey,RBarlow,VBataille, Appendix1.TheconsultationprocessforBritishAssociation L Rhodes of Dermatologists guidelines and their compliance with Surgery:A Hayes,J Kenealy,G Perks, M Timmins guideline recommendations have been published elseSpecialist Nursing: H Williams, C McGarr, M Sherman, where.1,2Thereareargumentsinfavourofnewerguideline JDavenport, CWheelhouse gradingmethods,suchasthoseofGRADE,3buttheauthors Histopathology:NKirkham,HRigby,J Theaker believethatthesystemusedhereallowsgreaterpotential Imaging:JSmith, PGuest, A Dancey for consensus in areas of conflicting evidence or where Oncology: N Steven, P Corrie, P Patel, A Goodman, evidence sources are not directly comparable. In some CKelly, PLawton,A Dalgleish instances, this is not due to an absence of high quality Lay representative: TFay (Level Ib) trials but because different entry criteria or Palliative Care:J Speakman,F Calman endpoints preclude direct comparison of results; in other National Institute for Health and Clinical Excellence: cases interpretation of the clinical significance of results NSummerton has been challenged. To assist production of unified Scottish Intercollegiate Guidelines Network:SQureshi guidelines taking account of these issues, the \u2018quality of Primary Care:P Murchie evidence\u2019 grading used in these guidelines differs slightly from that used in other British Association of Dermatologists current guidelines; the strength of Disclaimer recommendationsgradingisthesameasusedinmanyother publications.Wherenolevelisquotedtheevidenceistobe These guidelines reflect the best published data available regarded as representing Level IV (i.e. a consensus at the time the report was prepared. Caution should be statement). exercised in interpreting the data; the results of future The intention of the working party was to agree best studiesmayrequirealterationoftheconclusionsorrecompracticeforthemanagementofmelanomainthebeliefthat mendations in this report. It may be necessary or even this will promote good standards of care across the whole desirable to depart from the guidelines in the interests of country.However,theyareguidelinesonly.Careshouldbe specificpatients andspecial circumstances. Just as adherindividualised wherever appropriate. These guidelines will ence to the guidelines may not constitute defence against berevisedasnecessarytoreflectchangesinpracticeinlight aclaimofnegligence,sodeviationfromthemshouldnotbe ofnewevidence. necessarilydeemednegligent. Integration with national cancer guidance Contributiontotheseguidelineshasbeenmadebyalarge number of clinicians. They have also been endorsed by, or Multidisciplinary care of the patient is held to be the most havehadinputfrom,representativesofthefollowinggroups desirable model as recommended in the Calman/Hine ororganisations:theUKMelanomaStudyGroup,theBritish report.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 2}, {"text": "by, or Multidisciplinary care of the patient is held to be the most havehadinputfrom,representativesofthefollowinggroups desirable model as recommended in the Calman/Hine ororganisations:theUKMelanomaStudyGroup,theBritish report.4 This has been defined by the National Institute for Association of Dermatologists, the British Association of HealthandClinicalExcellenceImprovingOutcomesGuidance Plastic, Reconstructive and Aesthetic Surgeons, the Royal for People with Skin Tumours Including Melanoma (NICE College of Physicians, London, the Association of Cancer IOG).5 Core services will be provided within each Cancer Physicians, the Royal College of Radiologists, London, the Network by Local Skin Cancer Multidisciplinary Teams Royal College of Surgeons, England, the Royal College (LSMDTs). Specialist services will be provided by Specialist ofPathologists(pathologysectiononly),theRoyalCollegeof SkinCancerMultidisciplinaryTeams(SSMDTs).Formelanoma General Practitioners, London, and the Department of thereisacleardemarcationofcaresuchthatmoreadvanced Health. primarymelanoma,raresubtypesofmelanoma,melanomain These consensus guidelines have been drawn up by children,andpatientseligiblefortrialentryorsentinellymph a multidisciplinary working party with membership drawn nodebiopsyshouldbepromptlyreferredforinvestigationand from a variety of groups and coordinated by the United treatmentfromanLSMDTtoanSSMDT(Table1). Kingdom Melanoma Study Group (UKMSG), and the British Association of Dermatologists. The guidelines deal with aspects of the management of melanoma from its prevenPrevention of melanoma tion, through the stages of diagnosis and initial treatment to palliationof advanceddisease. PubMed literature searches for this guidelines revision Individuals,andparticularlychildren,shouldnotgetsunburnt werecarriedouttoidentifypublicationsfrom2000toApril (Level I).6e9 Meta-analysis of case-control studies provides 2010, with search terms including: melanoma genetics, good evidence that melanoma is predominantly caused by epidemiology, early diagnosis, risk factors, clinical intermittent intense sun exposure; fair-skinned individuals features, pathology, surgery, chemotherapy and clinical should therefore limit their recreational exposure through trials. Relevant materials were also isolated from reviews life(LevelI).10Peoplewithfreckles,redorblondhair,skin", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 2}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1403 Table1 MelanomapatientswhomustbereferredfromaLocalSkinCancerMultidisciplinaryTeamtoaSpecialistSkinCancer MultidisciplinaryTeam(SSMDT)(NICEIOG2006).5 (cid:1) Patients with melanoma managed by other site specialist teams (e.g. gynaecological, mucosal and head and neck (excludingocular)) (cid:1) Patients with stage IB or higher primary melanoma when sentinel lymph node biopsy (SLNB) is available within their Network.IntheabsenceofSLNBthenpatientswithstageIIBorhighershouldbereferredtotheSSMDT(AmericanJoint CommitteeonCancer(AJCC)stagingsystem) (cid:1) Patientswithmelanomaatanystagewhoareeligibleforclinicaltrialsthathavebeenapprovedatcancernetworklevel (cid:1) Patientswithmultipleprimarymelanomas (cid:1) Childrenandyoungadultsunder19yearswithmelanoma (cid:1) Anypatientwithmetastaticmelanomadiagnosedatpresentationoronfollow-up (cid:1) Patientswithgiantcongenitalnaeviwherethereissuspicionofmalignanttransformation (cid:1) Patientswithskinlesionsofuncertainmalignantpotential whichburnsinthesun,increasednumbersofnaevi,andthose Lesionswhicharesuspiciousformelanomashouldnotbe withafamilyhistoryofmelanomaareatincreasedriskand removedinprimarycare.Thisisbecauseclinico-pathological shouldheedthisadvice. correlation is vital for diagnostic accuracy, which in turn Adequate sun exposure to allow vitamin D synthesis, or determines prognosis and defines adjuvant treatment sufficientdietaryintakeofvitaminD isessentialtohuman options, andbecause diagnostic surgery requiresspecialist 3, health; insufficiency of vitamin D is now recognised to be training. Early recognition of melanoma presents the best common.11 It would therefore be inappropriate to greatly opportunityforcure15,19e22(LevelIII,GradeA). limitsunexposureinpeoplewithouttheriskfactorslisted All patients presenting with an atypical melanocytic above.RecentstudieshaveshownthatinUKvitaminDlevels lesion or a large number of moles should have a complete areoftensuboptimalinmelanomapatients,andarelowerin skin examination and assessment of risk factors. The derfair-skinnedpeople.12,13Fair-skinnedpeoplewhoavoidthe moscopeisausefultoolforthetrainedclinicianscreening sunrigorouslytoreducetheriskofmelanomashouldconsider pigmentedlesions,asitcanincreasediagnosticaccuracy.23 supplementingtheirintakeofvitaminD intheabsenceof It is also useful for monitoring multiple pigmented lesions 3 medicalcontraindications. wherephotographyofdermoscopicimagesprovidesarecord Thereisevidencefromarecentmeta-analysisthatsunofchange(LevelIa,GradeA).RecommendationsforLSMDT bedusagedoesincreasetheriskofmelanoma,particularly record-keepingofclinicalfeaturesareproposedinTable2. undertheageof35years,andthereforeitisrecommended thatthis shouldbeavoided(LevelIa).14 Screening and surveillance of high-risk individuals Referral and clinical diagnosis Therearesomeindividualsathigherriskofmelanomawho shouldbeconsideredforreferraltospecialistclinics.These Melanomaremainsrelatively uncommonandthereforethe individuals can be divided broadly into two groups based opportunitytodevelopdiagnosticskillsislimitedinprimary upon the degreeof risk: care.Alllesionssuspiciousofmelanomashouldbereferred urgently under the 2-week rule to local screening services usually run by dermatologists. In England and Wales, this wouldbetoanLSMDT.InScotland,referralshouldbemadeto a local Rapid Access Cancer Clinic according to Scottish CancerReferralGuidelines.Theseven-pointchecklistorthe Table 2 Recommendations for Local Skin Cancer MultiABCDrulemaybehelpfulintheidentificationofmelanomas disciplinaryTeamrecord-keepingofclinicalfeatures. althoughtheyaremoresensitivethanspecific.15e18Urgent Asaminimumthefollowingshouldbeincluded: referraltotheLSMDTisindicatedwherethereis: History(thepresenceorabsenceofthesechanges shouldberecorded) (cid:1) Anewmoleappearingaftertheonsetofpubertywhich (cid:1) Durationofthelesion ischanging inshape,colour orsize (cid:1) Changeinsize (cid:1) Along-standingmolewhichischanginginshape,colour (cid:1) Changeincolour orsize (cid:1) Changeinshape (cid:1) Anymolewhichhasthreeormorecoloursorhaslostits (cid:1) Symptoms(itching,bleeding,etc.) symmetry Examination (cid:1) A molewhich isitchingorbleeding (cid:1) Site (cid:1) Any new persistent skin lesion especially if growing, if (cid:1) Size(maximumdiameter) pigmented or vascular in appearance, and if the diag- (cid:1) Elevation(flat,palpable,nodular) nosis isnotclear (cid:1) Description(irregularmargins,irregularpigmentation (cid:1) Anewpigmentedlineinanailespeciallywherethereis andifulcerationispresent) associateddamage to the nail (LevelIII,GradeB) (cid:1) A lesiongrowing under anail.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 3}, {"text": "1404 J.R.Marsden etal. 1. Individuals at moderate increased risk (approximately 8498-cc94b378312a.pdf.Recommendationsforscreeningand 8e10 times that of the general population) should be surveillanceofhigh-riskindividualsaresummarisedinTable3. counselled about this risk and taught how to selfexamine for changing naevi, but long-term follow-up is Biopsy of suspected melanoma notusual.Suchpatientsarethosewitheitheraprevious primary melanoma, or large numbers of moles some of whichmaybeclinicallyatypical(LevelIa,GradeB).24e28 A lesion suspected to be melanoma, or where melanoma Organ transplant recipients are also at this level of needstobeexcluded,shouldbephotographed,andthen increasedrisk(LevelIII,GradeB).29,30 excised completely. The axis of excision should be 2. Those at greatly increased risk of melanoma (more orientated to facilitate possible subsequent wide local than10timesthatofthegeneralpopulation).Patients excision;generallyonthelimbthiswillbealongthelong withagiantcongenitalpigmentedhairynaevus(definiaxis. If uncertain, direct referral to the multidisciplinary tions include \u201820cm or more in diameter\u2019 and \u20185% of team (MDT) will allow appropriate planning for future bodysurfacearea\u2019)shouldbemonitoredbyanexpertfor surgery. The excision biopsy should include the whole theirlifetimebecauseoftheriskofmalignantchange, tumourwithaclinicalmarginof2mmofnormalskin,and whichissignificantbutpoorlyquantified(LevelIII,Grade acuffoffat.Thisallowsconfirmationofthediagnosisby B).31,32 Excision biopsy of suspicious areas in large examination of the entire lesion, such that subsequent congenitalnaevimaybenecessarybutrequiresexpert definitive treatment can be based on Breslow histopathological review. Patients with a strong family thickness.35e37 historyofmelanomaarealsoatgreatlyincreasedrisk.In Diagnosticshavebiopsiesshouldnotbeperformedsince some families, most clearly in mainland Europe and theymayleadtoincorrectdiagnosisduetosamplingerror, NorthAmerica,familiesatriskofmelanomaarealsoat and make accurate pathological staging of the lesion increasedriskofpancreaticcancer.33Thosewiththree impossible(LevelIII).Forthesamereasonspartialremoval ormorecasesofmelanomaorpancreaticcancerinthe ofnaevifordiagnosismustbeavoidedandpartialremoval family should be referred to appropriate clinics of a melanocytic naevus may result in a clinical and managing inherited predisposition to cancer (involving pathological picture very like melanoma (pseudomeladermatologists and/or clinical geneticists) for counselnoma).Thisgivesrisetoneedlessanxietyandisavoidable. ling. It is the consensus of the Melanoma Genetics Incisional or punch biopsy is occasionally acceptable, for Consortium(www.genomel.org)thatitisprematureto example in the differential diagnosis of lentigo maligna suggest gene testing routinely but this may change as (LM) on the face or of acral melanoma, but there is no moreisknownofthegenespredisposingtomelanoma.34 placeforeitherincisionalorpunchbiopsyoutsidetheskin Therisktofamiliesassociatedwiththepresenceoftwo cancer MDT (Level III). It is acceptable in certain circumfamily members affected with melanoma is lower. In stances to excise the lesion entirely but without repair, these families, if affected individuals also have the and to dress the wound while awaiting definitive atypical mole syndrome, or if there is a history of pathology. multipleprimarymelanomasinanindividualorpancreBiopsies of possible subungual melanomas should be atic cancer, then referral should also be made for carried out by surgeons regularly doing so. The nail should counselling;otherwisefamilymembersshouldprobably beremovedsufficientlyforthenailmatrixtobeadequately beconsideredatmoderatelyincreasedrisk. sampled: clinically obvious tumour should be biopsied if present.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 4}, {"text": "cancer, then referral should also be made for carried out by surgeons regularly doing so. The nail should counselling;otherwisefamilymembersshouldprobably beremovedsufficientlyforthenailmatrixtobeadequately beconsideredatmoderatelyincreasedrisk. sampled: clinically obvious tumour should be biopsied if present. Alloftheaboveindividualsatincreasedriskofmelanoma Prophylactic excision of naevi, or of small (<5cm shouldbeadvisedonthespecificchangesthatsuggestmeladiameter) congenital naevi in the absence of suspicious nomaandencouragedtoundertakemonthlyskinself-examifeatures is notrecommended (LevelIII, GradeD). nation(LevelIII,GradeB).Close-upanddistantphotography Full clinical details should be supplied on the histopamaybeausefuladjuncttodetectingearlymelanomaineither thology form, including history of the lesion, relevant of these high-risk groups (Level III). They should be given previous history, site and differential diagnosis. All melawritteninformationandaccesstoimagesofmolesandmelanocytic lesions excised for whatever reason must be sent nomas. Such images are available at: www.genomel.org or for histopathological review to the pathologist associated www.rcplondon.ac.uk/pubs/contents/f36b1656-cc74-4867with the LSMDTor SSMDT. Table3 Recommendationsforscreeningandsurveillanceofhigh-riskindividuals. (cid:1) Patientswhoareatmoderatelyincreasedriskofmelanomashouldbeadvisedofthisandtaughthowtoself-examine.This includespatientswithatypicalmolephenotype,thosewithapreviousmelanoma,andorgantransplantrecipients(LevelIa, GradeB). (cid:1) Patientswithgiantcongenitalpigmentednaeviareatincreasedriskofmelanomaandrequirelong-termfollow-up(Level IIIa,GradeB). (cid:1) Individuals with a family history of three or more cases of melanoma, or of pancreatic cancer, should be referred to aclinicalgeneticistorspecialiseddermatologyservicesforcounselling.Thosewithtwocasesinthefamilymayalsobenefit, especiallyifoneofthecaseshadmultipleprimarymelanomasortheatypicalmolephenotype(LevelIIa,GradeB).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 4}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1405 The diagnosis of melanoma, both in situ and invasive, melanomas (cid:3)1.0mm.40,41 It should be recorded as should be given or supervised by doctors who have number of mitoses per mm(cid:4)2 in the area of greatest received advanced communication skills training, number of mitoses in the vertical growth phase (VGP). following local policies for breaking bad news. A skin It has prognostic value at all thicknesses. cancer trained nurse should be present to provide continuing support. Histologic subtypes. Desmoplastic melanoma with or without neurotropism should be recorded because of its Histopathology different biological behaviour and clinical outcome.42 The subtypes superficial spreading, nodular, lentigo General comments maligna and acral lentiginous melanomas have good clinico-pathological correlation, but their prognostic value has not been established. TheRoyalCollegeofPathologistshasproducedaminimum dataset which should be included in the histopathology report.38 Double reporting is recommended for all melaMargins of excision. This indicates whether excision is completeandtheminimummarginofexcisiontoperipheral nomas and all naevi showing severe dysplasia if resources allowthis tobeachieved within14 days.5 and deep aspects measured in millimetres. If the excision or re-excision is not complete, whether the tumour is in situorinvasiveattheresectionmarginshouldbeindicated. The histopathology report Whenpossibleastatementshouldbemadeofwhetherthe lesion isprimary orsecondarymelanoma. The report shouldincludethe following: Pathologicalstaging.StagingusingTNMandAJCC(Table4), Clinical information andcoding, e.g.SNOMED, shouldbegiven.41 (cid:1) Site of thetumour Growth phase. Invasive melanoma without a vertical (cid:1) Type of surgical procedure: excision or re-excision, growth phase (VGP) is termed microinvasion.43 The incision biopsy,punch biopsy assessment of microstaging criteria should be applied to (cid:1) Anyotherrelevant clinicalinformation the VGPonly. Regression. The presence or absence of tumour regression Macroscopic description has not been shown consistently to affect long-term outcome. Until its relevance is clear it should be reported Contour,colourandsizeofthetumourandtheexcisedskin as segmental replacement of melanoma by fibrosis, since specimenin millimetres. thisis subjectto less observervariation.44 Microscopy Tumour infiltrating lymphocytes (TILs). It remains unclear whether TILs have prognostic value.40 The categories absent, non-brisk and brisk are subject to wide observer Presence or absence of ulceration. Ulceration has progvariation. \u2018Absent\u2019 indicates no lymphocytes infiltrating nostic value, and its presence should be confirmed microamong the tumour cells, but does not exclude scopically as full-thickness loss of epidermis with reactive lymphocytes in the surrounding dermis. \u2018Non-brisk\u2019 is changeswhichincludeafibrinousexudateandattenuation a patchy or discontinuous infiltrate either among the or acanthosis of the adjacent epidermis.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 5}, {"text": "does not exclude scopically as full-thickness loss of epidermis with reactive lymphocytes in the surrounding dermis. \u2018Non-brisk\u2019 is changeswhichincludeafibrinousexudateandattenuation a patchy or discontinuous infiltrate either among the or acanthosis of the adjacent epidermis. These distinguish peripheral cells or in the centre of the tumour, whereas true ulcerationfrom artefact.39 \u2018brisk\u2019 is a continuous infiltrate but may be confined to peripheral cells. These are qualified as mild, moderate or severein intensity. Thickness. The tumour should be measured from the granular layer of the overlying epidermis to the deepest cells in the dermis judged to be malignant, to the nearest Lymphatic or vascular invasion. Vascular or lymphatic 0.1mm. Ulcerated tumours should be measured from the infiltrationhasprognosticvalue,anditspresenceshouldbe base of the ulcer. Tumour forming a sheath around recorded eventhough itis infrequentlyobserved.45 appendages should be excluded when measuring thickness Perineural infiltration. Perineural infiltration occurring except when the melanoma extends out into the adjacent beyond the main bulk of the tumour correlates with reticular dermis when it should be measured in the increasedlocalrecurrence.Itismostcommonlyassociated conventional manner. In the presence of histological with desmoplastic melanoma.46 regression thickness measurements should be of the residual melanoma. Microsatellites should not be included Microsatellites. These are defined as islands of tumour inthickness measurements (LevelIII, GradeB). >0.05mm in the tissue beneath the main invasive mass of melanoma, but separated from it by 0.3mm of normal Mitotic count. The number of mitoses has prognostic collagen (i.e. not tumour stroma or sclerosis of regresvalue and is now included in the American Joint sion).47 Current AJCC staging also requires that satellites Committee on Cancer (AJCC) staging system for must be intralymphatic, which has not previously been", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 5}, {"text": "1406 J.R.Marsden etal. Table4 The2009AmericanJointCommitteeonCancer(AJCC)stagingsystem. Stage Primarytumour(pT) Lymphnodes(LN) Metastases(M) IA <1mm,noulceration,mitosis <1/mm(cid:4)2 IB <1mm,withulcerationor mitoses(cid:5)1/mm(cid:4)2* 1.01e2mm,noulceration IIA 1.01e2mmwithulceration 2.01e4mm,noulceration IIB 2.01e4mm,withulceration >4mm,noulceration IIC >4mm,withulceration IIIA AnyBreslow\u2019sthickness,no Micro-metastases1e3nodes ulceration IIIB AnyBreslow\u2019sthickness,with Micro-metastases1e3nodes ulceration AnyBreslow\u2019sthickness,no 1e3palpablemetastaticnodes ulceration AnyBreslow\u2019sthickness,no Nonodes,butin-transitor ulceration satellitemetastasis/es IIIC AnyBreslow\u2019sthickness,with Upto3palpablelymphnodes ulceration AnyBreslow\u2019sthickness,with 4ormorenodesormatted orwithoutulceration nodesorin-transitdisease \u00felymphnodes AnyBreslow\u2019sthickness,with Nonodes,butin-transitor ulceration satellitemetastasis/es IV,M1a Skin,subcutaneousordistal nodaldisease IV,M1b Lungmetastases IV,M1c Allothersitesoranyothersites ofmetastases withraisedlactate dehydrogenase *Intherarecircumstanceswheremitoticcountcannotbeaccuratelydetermined,aClarklevelofinvasionofeitherIVorVcanbeused todefineT1bmelanoma.EverypatientwithmelanomashouldbeaccuratelystagedusingtheAJCCsystem;thismayincludeperforming asentinellymphnodebiopsywhenthisisrecommendedbytheSpecialistSkinCancerMultidisciplinaryTeam.Stagingshouldbeupdated followingrelapse. required; this may be subject to revision. Microsatellites Equivocal lesions are predictive of regional lymph node metastases; this is reflectedby stage N2c. Itmaynotbepossibletodistinguishpathologicallybetween amelanomaandabenignmelanocyticlesion.Suchpatients Precursornaevus.Thepresenceofcontiguousmelanocytic mustbereferredtotheSSMDTforclinicalandpathological naevusshouldberecorded. review.Adecisiontotreatasamelanomashouldbemade by the SSMDT in discussion with the patient. Thickness Clark level of dermal invasion. This is a less reliable indishould bemeasuredasfor melanoma. cator of prognosis than thickness and is subject to poor observeragreement.ItisnotusedtodefineT1melanomas Sentinel lymph node pathology inthe2009AJCCstagingsystem,exceptthatClarklevelsIV or V may be used for defining T1b melanoma in rare Pathological assessment instances when mitotic count cannot be determined in Thisneedstobedoneinastandardisedwaysothatfindings anon-ulcerated T1 melanoma. betweencentresarecomparable(LevelIII,GradeB). Requirements for microscopy of melanoma Dissection The dissection should be either by bivalving or multiple ThesearegiveninTable5. slicing, although the former is recommended.48e50", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 6}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1407 sentinellymphnodesand/ordistantmetastasesinpatients Table5 Requirementsformicroscopyofmelanoma. with primarymelanoma 53e58(Level IIa,GradeE). (cid:1) Ulceration (cid:1) Growthphase (cid:1) Thickness (cid:1) Regression Sentinel lymph node biopsy and ultrasound/fine (cid:1) Mitoticcounta (cid:1) Tumour-infiltrating (cid:1) Histologicsubtype lymphocytes needle aspiration cytology (cid:1) Marginsofexcision (cid:1) Lymphaticor (cid:1) Pathologicalstaging vascularinvasion Sentinel lymph node biopsy (SLNB), as discussed later, has (cid:1) Perineuralinvasion high sensitivity and specificity for diagnosing subclinical (cid:1) Microsatellitesb regionallymph node involvement. Ultrasoundandfineneedleaspirationcytology(FNAC)is a Mitoticcountisincludedinthe2009AJCCstagingsystem. the next best method but quoted sensitivities range from b Microsatellitesarenotincludedinthicknessmeasurement. 4.7% to 80%, with the higher sensitivities being achieved only by sentinel node mapping and FNAC of the sentinel node in all cases regardless of morphological appearA minimum of six serial sections should be taken, but ance.59e62 Further staging by CT imaging following a posia higher incidence of metastases is detected by extended tive sentinel lymph node, and prior to completion step sectioning with immunohistochemistry at each level. lymphadenectomy,hasaverylowyield.63e65Consequently The clinical relevance of the smaller metastases detected this should be done only after discussion with an informed by theseextended proceduresisstill unclear. patient andthe SSMDT(LevelIIa, GradeD). Staining Stage III and IV melanoma Use of haematoxylin and eosin and immunohistochemistry is essential. S100 and Melan A are most favoured immunoIn stage III and IV melanoma, imaging strategies will be histochemical stains but a composite method such as Panplannedby the SSMDT. Melis alsoappropriate. CTscanningofthehead,chest,abdomenandpelviswill normally adequately exclude metastases, and is most Assessment oftumour burden relevant in stage III melanoma before planning regional Thisgivesadditionalprognosticinformation.Thefollowing lymph node dissection and regional chemotherapy. If arerecommended: patients are considering entry to an adjuvant study Assessing the depth of the metastasis from the inner followinglymphadenectomy,the timingofscansshouldbe aspectofthesentinellymphnodecapsule;categorisingthe determinedby the SSMDT to avoidduplication. metastasis according to its site, either subcapsular or When stage IV disease is suspected clinically, CT scanparenchymal; measuring the maximum dimension of the ning of the head and whole body should be considered. largest confluent groupof melanoma cells.50e52 Further imaging will be determined by symptoms, clinical trial protocols, and for clarification or reassessment of Completion lymphadenectomy specimens previous imaging findings. Generally, the added yield of The pathological examination of regional nodes dissected PET/CT is unlikely to be clinically relevant in established following positive sentinel lymph node biopsy should stage IV melanoma (Level III, Grade D).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 7}, {"text": "yield of The pathological examination of regional nodes dissected PET/CT is unlikely to be clinically relevant in established following positive sentinel lymph node biopsy should stage IV melanoma (Level III, Grade D). Where metainclude an attempt to examine all lymph nodes at least at stasectomy is planned, PET/CT may be useful in excluding onelevel,andcountthenumberinvolved.Thepresenceof disease that might make surgery inappropriate. Serum extracapsular spread and involvement of perinodal fat lactatedehydrogenase(LDH)shouldbedoneinallpatients should be recorded, together with the size of the tumourwith suspectedstage IVmelanoma. freemargin.TheuseofimmunohistochemistrysuchasS100 There is no indication for a bone scanin staging except orMelan Afacilitates this. where symptoms point to possible bone disease. Staging investigations aresummarisedin Table6. Investigations and imaging Treatment of the primary lesion Stage I and II melanoma Surgery is the only curative treatment for melanoma. Routine investigations are not required for asymptomatic Following excision for diagnosis and for measurement of patientswithprimarymelanoma.Bloodtestsareunhelpful. microscopic Breslow thickness, a widerand deeper margin Routinecomputedtomography(CT)isnotrecommended istakentoensurecompleteremovaloftheprimarylesion, forpatientswithstageIandIImelanomaasthishasavery and to remove any micro metastases. The depth of the low incidence of true-positive and high incidence of falsetherapeuticexcisionhasconventionallybeentothemuscle positive findings. Patients with particularly high-risk fascia or deeper, and there is no evidence to support primary melanoma may undergo staging investigations if alteringthis approach. deemedappropriatebytheSSMDTand/orasapre-requisite Lateral surgical excision margins for invasive melanoma to trial entry. There is no indication for routine imaging depend on Breslow thickness and are based on five randowith any other modality including plain X-ray, position mised controlled trials (RCTs) including about 3300 emission tomography (PET)/CT and magnetic resonance patients, and a National Institutes of Health Consensus imaging(MRI).PET/CTisnoteffectiveindetectingpositive Panel.66e73 However, only one of these studies is", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 7}, {"text": "1408 J.R.Marsden etal. difficult to detect. Topical treatment with imiquimod is Table6 Staginginvestigationsformelanoma. as yet of unproven value so should only be used in the (cid:1) Patients with stage I, II,and IIIA melanoma should not context of a clinical trial.82 If the patient with LM is routinelybestagedbyimagingorothermethodsasthe treated by non-surgical means then the reason for this truepositivepick-uprateislowandthefalse-positive choice should be discussed and clearly documented by rateishigh(LevelIIa,GradeE). the MDT. (cid:1) PatientswithstageIIIBorCshouldbeimagedbyCTof LocalrecurrenceofLMoccursinabout5%ofpatientsby head,chest,abdomenandpelvispriortosurgeryafter 2 years.77 Excision with micrographic control of surgical SSMDTreview(LevelIIa,GradeA). margins should be considered, although histological clear- (cid:1) Patients with stage IV melanoma should be imaged anceisoftendifficulttodefine.83Insitumelanomaonacral accordingtoclinicalneedandSSMDTreview.Lactate andgenitalskinisalsoassociatedwithahigherriskoflocal dehydrogenaseshouldalsobemeasured(LevelIII, recurrence,butthisislesscommoninothertypesofinsitu GradeA). melanoma. In theory, in situ melanoma should not metaSSMDT,SpecialistSkinCancerMultidisciplinaryTeam. stasise, but occasional cases do recur. This may be due to histological regressionobscuring a more advanced tumour, missed microinvasion, or progression after incomplete removal of insitu disease. adequately powered, and two provide little scope for detecting reduced disease-free or overall survival due to narrowmargins.68,69,71Mostexcludemelanomaonthehead Melanoma up to 1.0mm Breslow thickness andneckand/orextremities.74Arecentsystematicreview estimated overall survival in favour of wide excision There have been three RCTs of patients with melanomas (hazard ratio 1.04; 95% confidence interval 0.95e1.15; inthisthicknessband.66,68,69,73 Therecommendedsurgical PZ0.40), although the difference was not significant. margins are based on the World Health Organisation Thereforeasmall,butpotentiallyimportant,differencein (WHO) Melanoma Co-operative Group Trial 10.66,73 This overallsurvivalbetweenwideandnarrowexcisionmargins randomised trial compared 1cm and 3cm margins for cannot be confidently ruled out. Current randomised trial melanomas up to 2mm thick. No local metastases, and evidenceisinsufficienttoaddressoptimalexcisionmargins similar overall survival, were seen in patients with melaforprimary cutaneous melanoma.75 nomas < 1mm in depth with either excision margin. The recommended surgicalmargins arethosemeasured However, this was based on analysis of data from only 359 clinically at the time of surgery, but adequacy of excision patients. The French and Swedish studies compared 2cm shouldbe subsequentlyconfirmed by review of re-excision with 5cm margins, and the latter only included patients histology, making an adjustment for average shrinkage of with melanomas 0.8mm or more in thickness in this 20%.76Thefinaldecisionaboutthesizeofthemarginshould group.68,69 A 1cm margin is deemed safe for this group bemadebytheMDT,afterdiscussionwiththepatient.The (Level Ib, Grade A). recommendation should be made with consideration of functionalandcosmeticimplicationsofthemarginchosen. Melanoma 1.01e2.0mm Breslow thickness All patients with primary melanoma stage IB and higher shouldbereferredbeforetreatmenttoanSSMDTwhenthis There have been four randomised studies that have providesaSLNBservice.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 8}, {"text": "Grade A). recommendation should be made with consideration of functionalandcosmeticimplicationsofthemarginchosen. Melanoma 1.01e2.0mm Breslow thickness All patients with primary melanoma stage IB and higher shouldbereferredbeforetreatmenttoanSSMDTwhenthis There have been four randomised studies that have providesaSLNBservice.WhentheSSMDTdoesnotprovide included patients in this category. The WHO study showed this, all primary melanomas stage IIB or IIC should be a small excessof localmetastasis asfirst siteof relapse in referred. There are no RCT data for margin size for LM or the 1cm margins group.66,73 There was no difference in otherin situmelanoma. overall survival between 1 and 3cm margins but the study was inadequately powered to detect this. The Intergroup Lentigo maligna and in situ superficial MelanomaTrialcompared2vs.4cmmarginsofexcisionfor spreading melanoma lesionsof1e4mminthickness.67,70Nodifferencewasseen between the two groups in either local recurrence or LM and other in situ melanomas have no potential for survival. Two other studies have included patients with metastatic spread and the aim should be to excise the melanomas up to 2mm, also treated with either 2or 5cm lesioncompletelywithaclearhistologicalmargin,although margins.68,69Therewasnodifferenceinoutcomebetween margin size remains undefined. No further treatment is the groups. The 1 vs. 3cm, 2 vs. 4cm, and 2 vs. 5cm thenrequired. studies cannot be directly compared, but no study using LM is best treated by complete excision because of 2cm margins as one comparator has shown any advantage the risk of subclinical microinvasion. This may be missed of wider margins than this. However, narrower margins on incisional biopsy due to sampling error.73 The risk of trials have either not been performed (e.g. 1vs. 2cm progression to invasive melanoma is poorly quantified, margins) or have been underpowered, and do not permit and in the very elderly may be unlikely within their a definite conclusion that a 1cm margin is adequate. lifespan. Therefore, for some particular clinical situaEvidence to date shows that a minimum margin of 1cm is tions, treatment by other methods such as radiotherapy, required, although 2cm margins are equally appropriate. or observation only, may be appropriate.77e81 There is The final decision will be determined by anatomical site, little evidence to support the use of cryotherapy, and MDTreview, and after discussion with an informed patient this treatment may make subsequent progression (Level Ib,GradeA).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 8}, {"text": "MDTreview, and after discussion with an informed patient this treatment may make subsequent progression (Level Ib,GradeA).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 2, "page": 8}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1409 Melanoma 2.01e4.0mm Breslow thickness surgical treatment planning and investigations can run in parallel. There is no place for elective lymph node dissecThe Intergroup Melanoma Trial showed no difference in tioninthemanagementofprimarymelanomaunlessthisis rates of local metastasis between patients treated with unavoidable because the primary melanoma lies over the 2cm and those treated with 4cm margins.67 However, lymphnodebasin(LevelIb,GradeA).Patientsshouldhave longer follow-up showed reduced overall survival in the access to a skin cancer specialist nurse when relapse is 2cmmarginsgroup,althoughthisfelljustshortofreaching suspected. statistical significance.70 The results of a randomised trial with 3cm margins showed significantly increased rates of Clinically node-negative patients locoregional recurrence in patients treated with 1cm margins, and a reduction in melanoma-specific survival, SLNB was developed as a means of identifying the first again just short of significance, although no difference in lymph node draining the skin in which the melanoma arioverall survival.71 The significance of this is unclear, and ses.84 The procedure is carried out at the same time as the 2 vs. 4cm and 1 vs. 3cm trials cannot be directly definitive wider excision of the primary melanoma.85 SLNB compared. Until the resulting uncertainty is resolved, givesinformation aboutprognosis,andisincreasinglyused which may not happen as the number of patients required in conjunction with adjuvant therapy clinical trials. to detect a difference between 2 and 3cm margins is Patients with melanoma of Breslow thickness 1.2e3.5mm considerable, the default position should be to minimise and a positive SLNB have a 75% 5-year survival compared locoregional and distant metastatic risk. Therefore with 90% if the SLNB is negative.86 SLNB is normally aminimum2cmmarginisrequired inthisgroup,although considered for patients with melanoma (cid:5)1mm, when 3cm margins are equally appropriate. The final decision about20%arepositive;howevertheriskofapositiveSLNB will be determined by anatomical site, need for skin in a melanoma <1.0mm is still 5%.86,87 The procedure is grafting,MDTreview,andafterdiscussionwithaninformed associatedwitha5%morbidity,whichislessthanthatseen patient (LevelIb, GradeA). withcompletenodaldissection.Inpatientswithapositive SLNB, 20% have pathological evidence of metastases in Melanoma greater than 4mm in thickness additional regional nodes.84 Patients with a positive SLNB usually choose to proceed to completion lymphadenecTheriskoflocoregionalanddistantmetastasisis50%ormore tomy.Inabout5%itisnotpossibletoidentifythesentinel inthisgroup.Nonetheless,thesamesurgicalobjectivesapply node either on lymphoscintigraphy, at surgery, or both. tominimiselocoregionalanddistantmetastaticrisk.Thereis Patients should be aware of this limitation. The relevance onlyonerandomisedstudywhichincludesmelanomasthicker ofincreasinglydetailedevaluationofthesentinelnodeand than4mm.71Thistrialcompared1cmwith3cmmargins.The its correlation with prognosis remains to be defined.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 9}, {"text": "at surgery, or both. tominimiselocoregionalanddistantmetastaticrisk.Thereis Patients should be aware of this limitation. The relevance onlyonerandomisedstudywhichincludesmelanomasthicker ofincreasinglydetailedevaluationofthesentinelnodeand than4mm.71Thistrialcompared1cmwith3cmmargins.The its correlation with prognosis remains to be defined.88 resultsshowasignificantincreaseinlocoregionalrecurrence MSLT-1 showed no overall 5-year survival benefit following when1cmmarginsareused,andareductioninmelanomaSLNB and completion lymphadenectomy, and it is unclear specific survival just short of significance, although no whether SLNB improves local control of lymph node difference in overall survival. As there are no data that basins.85,86Afinalreportwithlongerfollow-upisawaited. margins smaller than 3cm are as effective, the evidence Recommendations for the management of clinically suggests3cmmarginsforthisgroup.Thereisnoevidencethat node-negative patients aresummarised inTable8. marginsgreaterthan3cmarerequired.Thefinaldecisionwill bedeterminedbyanatomicalsite,needforskingrafting,MDT Management of patients with clinically or review,andafterdiscussionwithaninformedpatient(Level radiologically suspicious lymph nodes Ib,GradeB). Recommendedsurgicalexcisionmarginsaresummarised FNACofnodesisrecommendedwhenthereisclinicaldoubt inTable 7. about the significance of the nodes. If there is a negative FNACresultbutongoingsuspicion,thentheFNAshouldbe Management of lymph node basins repeated oranimage-guided core biopsy arranged. Open biopsy is recommended when there is clinical Investigation and management of lymph node basins in suspicion even in the presence of negative FNACs in which melanomapatientsshouldbecarriedoutbySSMDTssothat lymphocytes have been successfully aspirated. If open Table7 Recommendedsurgicalexcisionmargins. Breslowthickness Excisionmargins Levelofevidence Gradingofevidence Insitu 5mmmarginstoachieve III B completehistological excision <1mm 1cm Ib A 1.01e2mm 1e2cm Ib A 2.1e4mm 2e3cm Ib A >4mm 3cm Ib B", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 9}, {"text": "1410 J.R.Marsden etal. (cid:1) A single positive superficial inguinal sentinel node Table 8 Recommendations for the management of clini- (Level Ib,GradeA). callynode-negativepatients. (cid:1) There is no role for elective lymph node dissection ApelvicLND shouldbeconsidered inthe presenceof: (LevelI,GradeE) (cid:1) Sentinel node biopsy can be considered in stage IB (cid:1) More than one 1 clinically palpable inguinal and/or melanomaandupwardsinSSMDTs(LevelIa,GradeA) femoral triangle node/s (cid:1) PatientsshouldbeintroducedtotheconceptofSLNBas (cid:1) CT or ultrasound evidence of more than one inguinal astagingprocedurebutshouldalsounderstandthatit and/or femoral triangle node/s, or of pelvic node hasnoproventherapeuticvalue involvement (cid:1) Surgical risks of SLNB, the possibility of failure to find (cid:1) More than onemicroscopicallyinvolved nodeat SLNB aSLN,andofafalse-negativeresult,shouldalsobe (cid:1) A conglomerate of inguinal or femoral triangle lymph explained nodes SNLB,sentinellymphnodebiopsy (cid:1) Microscopic or macroscopic involvement of Cloquet\u2019s node (Level III,GradeB). biopsy is performed, the incision must be such as to allow Cervical nodal recurrence should be treated by either subsequent complete formal block dissection of the surgeons in the SSMDT specialising in head and neck skin regionalnodeswithoutcompromise.Itshouldonlybedone cancerincludingmelanomaorbyaheadandneckMDTwith bySSMDT members.5 aspecialinterestinmelanoma.5Acomprehensive,andnot Exploration or removal of a mass within a nodal basin aselective,neckdissectionshouldbeperformed(LevelIII, which drains a known primary melanoma site, and prior to GradeA). The term\u2018comprehensive\u2019 allows either: definitive surgical treatment, may increase the risk of melanomarecurrenceinthatbasin.89Anymelanomapatient (cid:1) A radicaldissection of levels1e5 who develops a mass in a nodal basin should be referred (cid:1) Modified radical e the above, sparing spinal accessory urgently to the SSMDT, and without prior investigation, for nerve, internal jugular vein and sternocleidomastoid investigationandtreatmentplanning(LevelIII,GradeB). muscle (cid:1) Extendedradicaleradicaldissectionincludingparotid Management of patients with confirmed and/or posterior occipital chain. positive lymph node metastasis The risk of further locoregional recurrence is 16e32% despite comprehensive surgery.101,102 Radical lymph node dissections (LNDs) should only be performedbySSMDTmemberswhodoacombinedminimumof Locoregional recurrent melanoma: skin 15axillaryandgroinblockdissectionsforskincancereach year.5,90 and soft tissues Preoperativestaginginvestigationsshouldbecarriedout asalreadydiscussedforstageIIImelanoma.Ifsuchstaging Surgery is the treatment of choice for single local or is not feasible prior to surgery, and surgery is considered regional metastases. Excision should be clinically and necessary even if distant metastatic disease were to be histologically complete, but a wide margin is not detected,thena chestX-rayandLDH isrecommended. required. Multiple small (<1cm) dermal lesions respond The block dissection specimen should be marked and well to treatment with the CO laser.103 Dermal disease 2 orientated for the pathologist.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 10}, {"text": "dermal lesions respond The block dissection specimen should be marked and well to treatment with the CO laser.103 Dermal disease 2 orientated for the pathologist. Axillary LND for melanoma which is progressing despite surgery or laser, and shouldincludeallnodesinlevelsIeIII,andthismayrequire subcutaneous or deeper limb metastases, should be either resection or division of pectoralis minor. The considered for regional chemotherapy with isolated limb management of inguinal lymph node metastases is controinfusion (ILI) with melphalan and actinomycin D, or with versial. Between 30% and 44% of patients with clinically isolated limb perfusion (ILP) 104,105 (Level IIb, Grade B). involvedsuperficialinguinalnodeswillhaveinvolvedpelvic ILI is less invasive than ILP, and can be more easily nodes, and the risk increases with the number of involved repeated, but may be less effective.105 ILI is suitable for superficialnodes.91e97IfCloquet\u2019snodeispositivetherisk patientswithlowvolume(<5cm)diseaseandthosewith of pelvic node involvement ranges from 44% to 90%.93,96,97 co-morbidities which prevent ILP. Patients with bulky There is no reported increased morbidity associated with disease (>5cm) may be more likely to benefit from ILP combined pelvic and superficial node dissection.94 using melphalan with tumour necrosis factor, but Following ilioinguinal dissection for palpable inguinal arecenttrialcomparingthiscombinationwithmelphalan disease 5-year survival varies with extent of pelvic alone did not confirm additional benefit from adding involvement: 49% with one pelvic node, 28% with two to TNF.106 Radiotherapy may be considered for disease threenodes, and7% with morethan threenodes.97e100 which cannot otherwise be controlled. Selected patients suitable for ILI/ILP should be referred to specialised A superficial inguinal LND should be considered in the centres. The role of electrochemotherapy using intralepresenceof: sional or systemic bleomycin is still being evaluated. (cid:1) A single clinically involved inguinal node or femoral Recommendations for locoregional recurrent melanoma trianglenode are given in Table 9.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 10}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1411 lymphadenectomy.110Eligiblepatientswere(cid:5)1parotid,(cid:5)2 Table 9 Recommendations for locoregional recurrent cervicaloraxillaryor(cid:5)3groinnodes,orextranodalspread melanoma. of tumour, or node diameter (cid:5)3cm in neck or axilla or (cid:1) Nodes clinically suspicious for melanoma should be (cid:5)4cminthegroin.Interimresultsshowa15%improvement sampledusingfineneedleaspirationcytology(FNAC) in local control following radiotherapy, but there was no priortocarryingoutformalblockdissection.IfFNACis effect on overall survival. There are no data yet on negativealthoughlymphocyteswereseen,acoreor morbidity following this treatment, and so at present the openbiopsyshouldbeperformedifsuspicionremains risk:benefit of adjuvant radiotherapy is unclear. If there is (LevelIII,GradeB) clinicalorhistologicaldoubtabouttheadequacyofsurgery (cid:1) Prior to lymph node dissection, performed by an following recurrence, or about the feasibility of salvage expert,5stagingbyCTscanshouldbecarriedoutother surgery, adjuvant radiotherapy may be considered by the thanwherethiswouldmeanunduedelay(LevelIII, SSMDT (LevelIb,GradeB). GradeB) (cid:1) The treatment of locoregional recurrence in a limb is Occult primary melanoma palliative.Surgicalexcision,CO laser,orisolatedlimb 2 infusionorperfusionmaybeconsidered(LevelIIb, GradeB) Patients with occult primary melanoma may present with a solitary metastasis, lymph node disease, or systemic disease. Such patients should be referred promptly to the SSMDT for investigation and treatment planning. All Adjuvant therapy patients should have a thorough examination of the skin. Occultprimaryuvealtractmelanomanearlyalwayscauses There is no evidence of a survival benefit for adjuvant liver metastases before these are apparent at other sites; chemotherapy inpatients with melanoma.107 Thisincludes searchingforauvealtractprimaryinapatientwithoccult adjuvant regional chemotherapy using ILP, and therefore nodal disease is not appropriate. For patients presenting ILI.108 withinguinallymphadenopathy,examinationofthegenital Interferon has been evaluated in low-, intermediateand urinary tracts, and ano rectum is especially relevant. andhigh-riskpatientsusingvariousdosesandschedules.A AllpatientsshouldbestagedwithCTscansofhead,chest, recent individual patient data meta-analysis concluded abdomenandpelvis.Anumberofreportsfrominstitutionthatinterferonwasassociatedwithasignificantimpacton basedseriessuggestthatpatients presentingwithstage III relapse-free survival and a small effect on overall survival disease from an unknown primary have a better prognosis (5-year survival benefit 3%, P<0.05).109 However, the than patients with a similar stage and a known benefit was seen across all interferon regimens, and was primary.111,112 One published series suggested a survival greatestinthosewithulceratedmelanomas.Therewasno advantage in patients with stage IV disease from an clearindicationastooptimumdoseorduration.Theresults unknown primary compared with those with a declared areawaitedoffurtheranalysisincludingmorerecentdata. primary.113 Interferon is not recommended as standard of care for Patients presenting with lymph node disease from an adjuvant therapy of primary or stage III melanoma (Level occult primary involving a single lymph node basin, should Ia, Grade A).", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 11}, {"text": "primary involving a single lymph node basin, should Ia, Grade A). This is because its effect on disease-free be presumed to have regional rather than distant metassurvival is of uncertain clinical relevance, and although tasis, and treated as for stage III disease with lymph node overall survival is improved in meta-analysis, the effect is blockdissection. small and associated with significant drug toxicity. Prospective studies are required to establish whether Metastatic disease a subset of patients who derive most benefit can be identified. All patients should have access to a skin cancer clinical Clinical trials of adjuvant melanoma vaccines have not nurse specialist and a palliative care team providing so farbeensuccessful. expertise in symptom control and psychosocial support. Patients should be offered entry into adjuvant clinical Links should be made with community cancer support trials approved by the local Cancer Network. They should networks as soon as possible. All patients with metastatic have access to a melanoma specialist who is conversant disease should have access to an oncologist specialising in with currentmelanoma adjuvant trials, and whois ableto melanomafor managementadvice. ensuretheiraccesstosuchstudies.Detailsmaybefoundon Selected patients who relapse with oligometastatic thewebsitesoftheNationalCancerResearchNetwork,and disease may benefit from metastatectomy. Although this the European Organisation for Research and Treatment of has not been evaluated in a prospective randomised trial, Cancer. mediansurvivalof21monthsforselectedsurgicallytreated patients hasbeen reported114e119 (Level IIb,GradeB). Adjuvant radiotherapy No systemic therapy has been shown to extend survival significantly. Dacarbazine is a standard chemotherapy The Tasmanian Radiation Oncology Group (TROG) has outside a clinical trial, although its benefits are limited, completedarandomisedstudyofadjuvantradiotherapyto anditisineffectiveinbrainmetastases(LevelIIa,GradeC). dissectednodalbasins,48Gyin20fractions,in250patients The oral dacarbazine derivative temozolomide has greater with a high (>25%) risk of local recurrence following central nervous system (CNS) penetration but has not", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 11}, {"text": "1412 J.R.Marsden etal. shown significant clinical advantages over dacarbazine in Thereisnomedicalreasontojustifydelayingconception twomulticentreclinicaltrials.120,121Biochemotherapy(the afteradiagnosisofmelanoma(LevelIIa)butthesocialand addition of biologically active agents such as interferonfamily effects of developing recurrent melanoma during a and interleukin-2 to chemotherapy) increases response pregnancy or after birth are great.127,130 It is proper thereratesandtoxicitybutdoesnotsignificantlyincreaseoverall foretocounselawomaninthereproductiveagerangeabout survival.122 The same is true for combination chemoherriskofrecurrenceovertimesothatsheandherpartner therapy, and so this is not recommended other than in can make their decision about conception with adequate highly selected patients in whom palliation is dependent information. These social or familyconsiderations may also upon maximising response in symptomatic deposits. High berelevanttoamalepatientwhosepartnerispregnantorif doseinterleukin-2hasnotbeenevaluatedinarandomised heandhispartnerareconsideringapregnancy. phase III trial although a small minority of patients may There is no evidence that the use of the oral contraexperiencedurable completeresponses.123 ceptive pill plays any role in the natural history of melaPatientswithelevatedLDHhaveareducedlikelihoodof noma (Level Ia).130e133 Decisions about the use of the benefiting from currently available systemic treatment. contraceptive pill should be made on the basis of health Giventhelimitedbenefitswithstandardsystemictherapy, issues otherthan melanoma. all patients with metastatic melanoma should be considThereisnoevidencethathormonereplacementtherapy eredforentry into clinicaltrials of novel therapies. plays any role in the natural history of melanoma,130,132 Patients with CNS metastases have a poor prognosis. neither does it worsen prognosis in stage I and II melaSurgeryorstereotacticradiotherapyshouldbeconsidered noma (Level IIa).133 Decisions about use of hormone for selected patients with limited disease.114,115,124e126 replacementtherapyshouldbemadeonthebasisofhealth The benefits of treating patients with cerebral metasissues otherthan melanoma. tases with whole brain radiotherapy are limited, but may In pregnancy, staging using X-rays should be avoided sometimes have palliative value. Supportive care is wherepossible,especiallyinthefirsttrimester.MRIshould thereforethemostappropriatestrategyformanypatients beused inpreference to CTscan,wherefeasible. (Level IIb, Grade B). Because chemotherapy does not have a survival benefit Spinal cord compression should be treated surgically if in stage IV disease its use in pregnancy requires careful feasible, but multiple sites of disease, poor prognosis and discussion. Use of chemotherapy agents in the first poor performance status may make this inappropriate. trimestershouldbeavoided.Therearecasereportsofthe Radiotherapy may be useful for palliation of rapidly successful birth of normal babies who were exposed to enlarging or painful metastases involving soft tissues and dacarbazine in utero later in pregnancy, but this does not bones(LevelIIb,GradeB). exclude later toxicity. Melanoma can metastasise to the Recommendations for metastatic disease are shown in placenta and to the fetus more frequently than any other Table10. solidtumour.Thishasapoorprognosisforbothmotherand baby.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 12}, {"text": "later in pregnancy, but this does not bones(LevelIIb,GradeB). exclude later toxicity. Melanoma can metastasise to the Recommendations for metastatic disease are shown in placenta and to the fetus more frequently than any other Table10. solidtumour.Thishasapoorprognosisforbothmotherand baby. At delivery in patients with stage IV melanoma the Melanoma, hormone replacement therapy placenta should beexamined formelanoma. Recommendations regarding pregnancy and hormone and pregnancy replacement therapy aresummarisedin Table11. Thereisnoevidencethatmelanomaatornearthetimeof Use of drugs in melanoma patients pregnancy adversely affects prognosis.127 Breslow thickness, site and presence of ulceration are still the key determinants of outcome, and are not different from There are theoretical reasons to suggest that L-DOPA may have an adverse effect on patients with melanoma. There acontrolpopulation.128,132Theoutcomesofpregnancyfor are no data to support this idea however, and such an bothmotherandbaby arenotworsened(LevelIIa).128,129 association seems unlikely.134 The use of immunosuppresSurgical treatment should be determined in the normal santsaftermelanomaisacauseforconcern.Theresultsof way,buttherisksofexposuretoionisingradiationandblue a recent cohort study of patients with rheumatoid arthritis dye during sentinel node biopsy will need special consideration. Table 11 Recommendations regarding pregnancy and Table10 Recommendationsformetastaticdisease. hormonereplacementtherapy. (cid:1) All patients should be managed by Specialist Skin Pregnancywithprimarymelanoma CancerMultidisciplinaryTeams.5 (cid:1) Noworseningofprognosis (cid:1) Surgery should be considered for oligometastatic (cid:1) No increase in adverse outcomes for mother or baby diseaseatsitessuchastheskin,brainorbowel(Level Pregnancyinadvancedmelanoma IIb,GradeB),ortopreventpainorulceration. (cid:1) Placental and fetal metastases possible in stage IV (cid:1) Radiotherapy may have a palliative role in the treatdisease mentofmetastases(LevelII,GradeB). Oralcontraceptivesandmelanoma (cid:1) Standardchemotherapyisdacarbazinealthoughitsrole (cid:1) Noincreasedriskofmelanoma ispalliative(LevelII,GradeC). Hormonereplacementtherapy (cid:1) Patients withstageIV melanomashould beconsidered (cid:1) Noincreasedriskofmelanoma forentrytoclinicaltrials. (cid:1) Noworseningofprognosis", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 12}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1413 treated with biologic agents showed an increased risk of Care can be shared with primary care, but only if the melanoma (odds ration 2.3, 95% confidence interval secondarycareteamhasdefinedandexplainedtotheprimary 0.9e5.4).135However,thereisusuallylittlethatcanbedone careteamwhatisrequired,andonlyiftheprimarycareteam toavoidthesedrugswithoutanunacceptablelossofquality arepreparedtoacceptresponsibilityforthis.Intheeventof of life. Their use after treatment of primary or secondary suspectedrecurrence,evenafterdischargefromfollow-up,it melanoma should be discussed between the prescribing isrecommendedthatthepatientcontactthesecondarycare doctorsandpatients,andthedecisiontocontinuetheiruse teamdirectlytoavoidpossibledelayindiagnosis. and their dosage should be subject to ongoing review Screening asymptomatic clinically normal patients with followingadiagnosisofmelanoma(LevelIII,GradeC). lymph node ultrasound is sensitive and can detect nodal disease,butthishasnotbeenshowntobeusefulinprimary Organ and blood donation melanoma follow-up.142 The same applies to CT and PET imaging. These investigations should not be used outside Thedecisionaboutwhetherorgansortissuearesuitablefor a clinicaltrial. transplant is made on an individualised basis, taking into account the patient\u2019s medical history.136 A melanoma In situ melanoma patient wouldnotnormally beconsidered asa donor. Patients with a surgically treated single in situ melanoma Follow-up do not require follow-up, as there is no risk of metastasis. They require a return visit after complete excision to Therearethreemainreasonsforfollow-upaftertreatment explain the diagnosis, cheque the whole skin for further of primary cutaneous melanoma. The first is to detect primary melanoma/s, and to teach self-examination for recurrence when further treatment can improve the proga new primary melanoma. Clinical nurse specialist support nosis, the second is to detect further primary melanomas mayberequired despite the absenceof metastaticrisk. and the third is to provide support, information, and education. Theproportionof patientswith melanomawho Stage IA melanoma have impaired health-related quality of life is comparable to other cancers, and their needs for psychosocial support Patients with invasive primary cutaneous melanoma are likely to be similar.137 Provision of this is an important <1.0mmhavea5-yeardisease-freesurvivalofover90%or partofMDTmanagement.138TherearenoRCTswhichhave better. A recent review of 430 patients with melanomas formally evaluated follow-up. Numerous follow-up regi- <0.5mm showed no recurrences at 5e15 years follow-up mens have been reviewed but few are evidencebut 4% of patients developed a second primary melanoma based.139e141 Sixty-two percent of all recurrences were over this period.143 Patients with invasive, non-ulcerated detected by patients themselves in one review, but defiprimarytumours0.5e1.0mmthickhaveonlyslightlyworse nition of patient or doctor detection is unclear and other 5-year disease-free survival, and are in the same stage series emphasise the importance of physician-detected group. Therefore, for stage IA patients a series of two to recurrence.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 13}, {"text": "detection is unclear and other 5-year disease-free survival, and are in the same stage series emphasise the importance of physician-detected group. Therefore, for stage IA patients a series of two to recurrence.134 Patient opinion was equally divided as to fourvisitsoverupto 12monthsissuggested toteachselfwhether follow-up visits were reassuring or provoked examination,andthentheymaybedischargedfromregular further anxiety. There is little evidence of survival advanfollow-up (LevelIII, GradeB). tage following self-detection of metastases.139e141 Most first relapses occur in the 5 years following diagnosis, but Stage IB and IIA melanoma thereisasignificantriskoflaterfirstrelapse;bothpatients andtheirdoctors shouldbeaware of this. This group are at 15e35% risk of recurrence, but most of A primarymelanoma follow-up clinic shouldbeprovided thisriskisinyears2e4.OncetheyhavelearnthowtoselfbyanMDTofdermatologistsandsurgeonswithclinicalnurse examine for locoregional metastasis and new primaries, specialist support, and there should be continuity of care. andunderstandhowtopromptlyaccessthefollow-upteam Patientsshouldbetaughttoself-examinetodetectlocorefor suspected recurrence, they should be seen every 3 gionalrecurrenceandnewprimarymelanoma.Photography months for 3 years, then 6-monthly to 5 years. No routine canbeuseful for follow-upofpatientswho also haveatypinvestigations arerequired(Level III,GradeB). ical moles. Patients should routinely be examined for locoregional and distant metastases, and the whole skin Stage IIB and IIC melanoma should be checked for new primary melanomas. A defined rapid-access pathway must be provided to all patients and GPs for suspected recurrence. Suspected new primary Thisgroupareat40e70%riskofrecurrence.Mostofthisriskis melanomashouldbereferredasnormalthroughthe2-week in years 2e4. They should be taught self-examination and wait system. For Scotland this needs to be compliant with seen 3-monthly for 3 years, and 6-monthly to 5 years. No the62-dayrule.Follow-upofpatientswithAJCCstageIIIand routineinvestigationsarerequired(LevelIII,GradeB). IVdiseaseshouldbeledbymelanomaSSMDTs. Follow-up intervals and duration should be tailored to Sentinel lymph node biopsy thestagegroupoftheprimarymelanomaandthereforeto theriskofrecurrence.Thefollow-upplanshouldbeagreed PatientswhohavehadanegativeSLNBshouldbefollowed betweenthe patient andthe responsible doctors. uponthe basis of Breslow thickness.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 13}, {"text": "1414 J.R.Marsden etal. MostpatientswhohavehadapositiveSLNBwillhavehad Improving Outcomes Guidance for People with Skin a completion lymphadenectomy. As these patients now Tumours including Melanoma; February 2006, available have at least stage IIIA disease, their follow-up should be at: www.nice.org.uk/nicemedia/pdf/CSG_Skin_Manual/ supervised by the SSMDT, and entry into appropriate trials pdf] considered. Risk of recurrence depends on the extent of 2. Comparisonandappropriatenessofstatedclinical,and sentinellymphnodeinvolvement,andmaybelessthanfor measured histological, surgical margins [referenced to some with stage II melanoma. They should be followed up the standards described in theseguidelines] asforstagesIBeIICmelanoma (LevelIII, GradeB). 3. Useofinvestigationsatdiagnosisinprimarymelanoma by stage grouping [referenced to the standards Stage IIIB, IIIC, and resected stage IV melanoma described in theseguidelines] Theriskoffurthermetastasisinthisgroupishigh.Manywill Acknowledgements beeligibleforadjuvanttrials.Thoseoutsidetrialsshouldbe seen 3-monthly for 3 years from the date of staging, 6The authorship team would like to acknowledge the monthlyto5years,thenannuallyto10yearsbyanSSMDT. contribution to these guidelines made by the late Dr Neil Investigationsshouldbecarriedoutonthebasisofclinical Cox. Neil worked tirelessly to improve care for patients, need,andmayincludeCTsurveillanceifconsideredapproand his clear thinking, expert knowledge and generous priate by the SSMDT. This might be used to monitor a site nature wereinvaluable to us. Weshallmiss himgreatly. considered at high risk of relapse. The SSMDTwill need to balance the use of follow-up investigations for this group againsttheneedforearlydetectionoffurtherstagesIIIand Conflicts of interest IVdisease.Earlydetectionfacilitatesbotheffectivetreatmentandtrialentry(LevelIII,GradeB). None declared. Unresectable stage IV melanoma References These patients should be followed up and investigated by theSSMDTaccordingtoclinicalneed.Theymaybeeligible 1. Griffiths CE. The British Association of Dermatologists\u2019 forclinical trials. guidelinesforthemanagementofskindisease.BrJDermatol 1999;141:396e7. 2. Cox NH, Williams HC. The British Association of dermatoloClinical trials gists therapeutic guidelines: can we AGREE? Br J Dermatol 2003;148:621e5. Many patients will be in clinical trials. These will have 3. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging definedfollow-up intervals which shouldbeadhered to. consensus on rating quality of evidence and strength of Follow-up for melanomais detailedin Table12. recommendations.BrMedJ2008;336:924e6. 4. Calman K, Hine D. Report by the Advisory Group on Cancer ServicestotheChiefMedicalOfficersofEnglandandWales. Table12 Follow-upformelanoma. DepartmentofHealth/WelshOffice;1995. (cid:1) Patientswithinsitumelanomasdonotrequirefollow5. National Institute for Health and Clinical Excellence (NICE). up ImprovingOutcomesGuidanceforPeoplewithSkinTumours (cid:1) Patientswithinvasivemelanomashavedifferingriskof including Melanoma, www.nice.org.uk/nicemedia/pdf/CSG_ Skin_Manual/pdf;February2006(lastaccessed25.05.10). relapseaccordingtotheirstagegroup 6. MarksR,WhitemanD.Sunburnandmelanoma:howstrongis (cid:1) PatientswithstageIAmelanomashouldbeseentwoto theevidence?BrMedJ1994;308:75e6. fourtimesoverupto12months,thendischarged 7. WhitemanD,GreenA.Melanomaandsunburn.CancerCauses (cid:1) PatientswithstageIBeIIIAmelanomashouldbeseen3Control1994;5:564e72. monthlyfor3years,then6-monthlyto5years 8. Armstrong BK. Epidemiology of malignant melanoma: inter- (cid:1) Patients with stage IIIB and IIIC and resected stage IV mittentortotalaccumulatedexposuretothesun?JDermatol melanomashouldbeseen3-monthlyfor3years,then6SurgOncol1988;14:835e49. monthlyto5years,thenannuallyto10years 9. Armstrong B, Kricker A. Sun exposure causes both non- (cid:1) PatientswithunresectablestageIVmelanomaareseen melanocytic skin cancer and malignant melanoma. Proc EnvironUVRadiatHealthEffects;1993:106e13.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 14}, {"text": "melanoma: inter- (cid:1) Patients with stage IIIB and IIIC and resected stage IV mittentortotalaccumulatedexposuretothesun?JDermatol melanomashouldbeseen3-monthlyfor3years,then6SurgOncol1988;14:835e49. monthlyto5years,thenannuallyto10years 9. Armstrong B, Kricker A. Sun exposure causes both non- (cid:1) PatientswithunresectablestageIVmelanomaareseen melanocytic skin cancer and malignant melanoma. Proc EnvironUVRadiatHealthEffects;1993:106e13. accordingtoneed 10. GandiniS, Sera F, Cattaruzza MS, et al. Meta-analysis of risk (LevelIII,GradeB) factors for cutaneous melanoma: III. Family history, actinic damageandphenotypicfactors.EurJCancer2005;41:2040e59. 11. Holick MF. High prevalence of vitamin D inadequacy and Audit points implicationsforhealth.MayoClinProc2006;81:353e73. 12. Newton-BishopJ,BeswickS,Randerson-MoorJ,etal.Serum 25-hydroxyvitamin D3 levels are associated with Breslow Thefollowing aresuggested points foraudit: thicknessatpresentation,andsurvivalfrommelanoma.JClin Oncol2009;27:5439e44. 1. TimelinessandappropriatenessofreferralfromLSMDTto 13. Randerson-Moor JA, Taylor JC, Elliott F, et al. Vitamin D SSMDT[referencedtothestandarddescribedinNational receptor gene polymorphisms, serum 25-hydroxyvitamin D Institute for Health and Clinical Excellence (NICE) levels and melanoma: UK case-control comparisons and", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 14}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1415 ameta-analysisofpublishedVDRdata.EurJCancer2009;45: 35. LedermanJS,SoberAJ.Doesbiopsytypeinfluencesurvivalin 3271e81. clinical stage I cutaneous melanoma? J Am Acad Dermatol 14. InternationalAgencyforResearchonCancerWorkingGroupon 1985;13:983e7. ArtificialUltravioletLightandSkinCancer.Theassociationof 36. Lees VC, Briggs JC. Effect of initial biopsy procedure on use of sunbeds with cutaneous melanoma and other skin prognosisinstageIinvasivecutaneousmalignantmelanoma: cancers:asystematicreview.IntJCancer2007;120:1116e22. reviewof1086patients.BrJSurg1991;78:1108e10. 15. McGovern TW, Litaker MS. Clinical predictors of malignant 37. AustinJR,ByersRM,BrownWD,etal.Influenceofbiopsyon pigmentedlesions.AcomparisonoftheGlasgowseven-point theprognosisofcutaneousmelanomaoftheheadandneck. checklist and the American Cancer Society\u2019s ABCDs of pigHeadNeck1996;18:107e17. mentedlesions.JDermatolSurgOncol1992;18:22e6. 38. AssociationofDirectorsofAnatomicandSurgicalPathology. 16. AbbasiNR,ShawHM,RigelDS,etal.EarlydiagnosisofcutaRecommendations for the reporting of tissues removed as neousmelanoma:revisitingtheABCDcriteria.JAmMedAssoc partofthesurgicaltreatmentofcutaneousmelanoma.Pathol 2004;292:2771e6. Int1998;48:168e70. 17. MacKie RM. Clinical Dermatology. 5th ed. Oxford University 39. SpatzA,CookM,ElderD,etal.Interobserverreproducibility Press;2003.p.345e346. of ulceration assessment in primary cutaneous melanomas. 18. DuVivierAWP,WilliamsHC,BrettJV,etal.Howdomalignant EurJCancer2003;39:1861e5. melanomas present and does this correlate with the seven40. GimottyPA,GuerryD,MingME,etal.Thinprimarycutaneous pointcheck-list?ClinExpDermatol1991;16:344e7. malignantmelanoma:aprognostictreefor10-yearmetastasis 19. Cox NH, Madan V, Sanders T, et al. skin cancer \u2018two-week ismoreaccuratethanAmericanJointCommitteeonCancer rule\u2019 proforma: assessment of potential modifications to staging.JClinOncol2004;22:3668e76. improvereferralaccuracy.BrJDermatol2008;158:1293e8. 41. EdgeSE,ByrdDR,ComptonCC,etal.,editors.Melanomaof 20. MeliaJ,CooperEJ,FrostT,etal.Cancerresearchcampaign theskin.AJCCCancerStagingManual.7thed.NewYork,NY: healtheducationprogrammetopromotetheearlydetection Springer;2009. ofcutaneousmalignantmelanoma.I.Work-loadandreferral 42. Hawkins WG, Busam KJ, Ben-Porat L, et al. Desmoplastic patterns.BrJDermatol1995;132:405e13. melanoma: a pathologically and clinically distinct form of 21. MeliaJ.Earlydetectionofcutaneousmalignantmelanomain cutaneousmelanoma.AnnSurgOncol2005;12:207e13. Britain.IntJEpidemiol1995;24:S39e44. 43. Elder DE, Murphy GF. Malignant Tumours (Melanoma and 22. MacKie RM, Hole D, HunterJAA,et al. Cutaneousmalignant RelatedLesions).ArmedForcesInstituteofPathology;1990. melanoma in Scotland: incidence, survival, and mortality, p.103e205. 1979e94.TheScottishMelanomaGroup.BrMedJ1997;315: 44. Kaur C, Thomas RJ, Desai N, et al. The correlation of 1117e21. regression in primary melanoma with sentinel lymph node 23. Braun RP, OlivieroM, KolmI. Dermoscopy: what\u2019s new?Clin status.JClinPathol2008;61:297e300. Dermatol2009;27:26e34. 45. Straume O, Akslan LA. Independent prognostic importance of 24. Melia J. Changing incidence and mortality from cutaneous vascularinvasioninnodularmelanoma.Cancer1996;78:1211e9. malignantmelanoma.BrMedJ1997;315:1106e7. 46. Quinn MJ, Crotty KA, Thomson JP, et al. Desmoplastic and 25. Parkin DM, Muir CS. Cancer incidence in five continents: desmoplastic neurotropic melanoma experience with 280 comparability and quality of data. IARC Sci Publ 1992;120: patients.Cancer1998;83:1128e35. 45e173. 47. HarristTJ,RigelDS,DayJrCL,etal.Microscopicsatellitesare 26. RhodesAR,WeinstockMA,FitzpatrickTB,etal.Riskfactors morehighlyassociatedwithregionallymphnodemetastases for cutaneous melanoma. A practical method of recognizing thanisprimarymelanomathickness.Cancer1984;53:2183e7. pre-disposedindividuals.JAmMedAssoc1987;258:3146e54. 48. CookMG,DiPalmaS.Pathologyofsentinellymphnodesfor 27. NewtonJA,BatailleV,GriffithsK,etal.Howcommonisthe melanoma.JClinPathol2008;61:897e902. atypical mole syndrome phenotype in apparently sporadic 49. CochranAJ.Surgicalpathologyremainspivotalintheevaluation melanoma?JAmAcadDermatol1993;29:989e96. of\u2018sentinel\u2019lymphnodes.AmJSurgPathol1999;23:1169e72. 28. Bataille V, Newton Bishop JA, Sasieni P, et al. Risk of cuta50. Starz H, Balda BR, Kramer KU, et al. A micromorphometryneousmelanomainrelationtothenumbers,typesandsitesof based concept for routine classification of sentinel lymph naevi:acase-controlstudy.BrJCancer1996;73:1605e11. node metastases and its clinical relevance for patients with 29. Le Mire L, Hollowood K, Gray D, et al. Melanomas in renal melanoma.Cancer2001;91:2110e21. transplantrecipients.BrJDermatol2006;154:472e7.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 15}, {"text": "et al. A micromorphometryneousmelanomainrelationtothenumbers,typesandsitesof based concept for routine classification of sentinel lymph naevi:acase-controlstudy.BrJCancer1996;73:1605e11. node metastases and its clinical relevance for patients with 29. Le Mire L, Hollowood K, Gray D, et al. Melanomas in renal melanoma.Cancer2001;91:2110e21. transplantrecipients.BrJDermatol2006;154:472e7. 51. Dewar DJ, Newell B, Green MA, et al. The microanatomic 30. Brown VL, Matin RN, Cerio R, et al. Melanomas in renal location of metastatic melanoma in sentinel lymph nodes transplant recipients: the London experience and invitation predicts nonsentinel lymph node involvement. J Clin Oncol toparticipateinaEuropeanstudy.BrJDermatol2007;156: 2004;22:3345e9. 165e7. 52. vanAkkooiAC,deWiltJH,VerhoefC,etal.TheRotterdam 31. MarghoobAA,SchoenbachSP,KopfAW,etal.Largecongencriteriaforsentinelnodetumorload:thesimplestprognostic ital melanocytic nevi and the risk for the development of factor?JClinOncol2008;26:2011. malignant melanoma. A prospective study. Arch Dermatol 53. BasseresN,GrobJJ,RichardMA,etal.Cost-effectivenessof 1996;132:170e5. surveillance of stage I melanoma. A retrospective appraisal 32. Illig L, Weidner F, Hundeiker M, et al. Congenital nevi less basedona10-yearexperienceinadermatologydepartment thanorequalto10cmasprecursorstomelanoma:52cases, inFrance.Dermatology1995;191:199e203. a review, and a new conception. Arch Dermatol 1985;121: 54. KhansurT,SandersJ,DasSK.Evaluationofstagingworkupin 1274e81. malignantmelanoma.ArchSurg1989;124:847e9. 33. GoldsteinAM,ChanM,HarlandM,etal.High-riskmelanoma 55. YancovitzM,FineltN, WarychaMA,etal.Roleofradiologic susceptibility genes and pancreatic cancer, neural system imaging at the time of initial diagnosis of stage T1b-T3b tumors, and uveal melanoma across GenoMEL. Cancer Res melanoma.Cancer2007;110:1107e14. 2006;66:9818e28. 56. Maubec E, Lumbroso J, Masson F, et al. F-18 fluorodeoxy-D34. LeachmanSA,CarucciJ,KohlmannW,etal.Selectioncriteria glucose positron emission tomography scan in the initial forgeneticassessmentofpatientswithfamilialmelanoma.J evaluationofpatientswithaprimarymelanomathickerthan AmAcadDermatol2009;61:677.e1e677.e14. 4mm.MelanomaRes2007;17:147e54.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 15}, {"text": "1416 J.R.Marsden etal. 57. ClarkPB,SooV,KrassJ,etal.FutilityoffluorodeoxyglucoseF 76. Silverman MK, Golomb FM, Kopf AW, et al. Verification of 18 positron emission tomography in initial evaluation of aformulafordeterminationofpre-excisionsurgicalmargins patientswithT2toT4melanoma.ArchSurg2006;141:284e8. fromfixed-tissuemelanomaspecimens.JAmAcadDermatol 58. Wagner JD, Schauwecker D, Davidson D, et al. Prospective 1992;27:214e9. study of fluorodeoxyglucose positron emission tomography 77. PrestonP,MateyP,MarsdenJR,etal.Surgicaltreatmentof imagingoflymphnodebasinsinmelanomapatientsundergoing lentigo maligna using 2mm excision margins. Br J Dermatol sentinellymphnodebiopsy.JClinOncol1999;17:1508e15. 2003;149:109e10. 59. vanRijkMC,TeertstraHJ,PeterseJL,etal.Ultrasonography 78. Mahendran RM, Newton-Bishop JA. Survey of U.K. current and fine-needle aspiration cytology in the preoperative practicein thetreatmentof lentigomaligna.Br J Dermatol assessment of melanoma patients eligible for sentinel node 2001;144:71e6. biopsy.AnnSurgOncol2006;13:1511e6. 79. Schmid-WendtnerMH,BrunnerB,KonzB,etal.Fractionated 60. SibonC,ChagnonS,Tchake\u00b4rianA,etal.Thecontributionof radiotherapy of lentigo maligna and lentigo maligna melahigh-resolution ultrasonography in preoperatively detecting nomain64patients.JAmAcadDermatol2000;43:477e82. sentinel-node metastases in melanoma patients. Melanoma 80. TsangRW,LiuFF,WellsW,etal.Lentigomalignaofthehead Res2007;17:233e7. and neck. Results of treatment by radiotherapy. Arch Der61. StarrittEC,UrenRF,ScolyerRA,etal.Ultrasoundexamination matol1994;130:1008e12. of sentinel nodes in the initial assessment of patients with 81. Pitman GH, Kopf AW, Bart RS, et al. Treatment of lentigo primarycutaneousmelanoma.AnnSurgOncol2005;12:18e23. maligna and lentigo maligna melanoma. J Dermatol Surg 62. Voit C, Kron M, Scha\u00a8fer G, et al. Ultrasound-guided fine Oncol1979;5:727e37. needle aspiration cytology prior to sentinel node biopsy in 82. RajparS,MarsdenJR.Imiquimodinthetreatmentoflentigo melanomapatients.AnnSurgOncol2006;13:1682e9. maligna.BrJDermatol2006;155:653e6. 63. Aloia TA, Gershenwald JE, Andtbacka RH, et al. Utility of 83. Walling HW, Scupham RK, Bean AK, et al. Staged excision computedtomographyandmagneticresonanceimagingstaging versusMohsmicrographicsurgeryforlentigomalignaandlenbeforecompletionlymphadenectomyinpatientswithsentinel tigomalignamelanoma.JAmAcadDermatol2007;57:659e64. lymphnode-positivemelanoma.JClinOncol2006;24:2858e65. 84. Morton DL, Wen DR, Wong JH, et al. Technical details of 64. Horn J, Lock-Anderson J, Sj\u00f8strand H, et al. Routine use of intraoperativelymphaticmappingforearlystagemelanoma. FDG-PET scans in melanoma patients with positive sentinel ArchSurg1992;127:392e9. nodebiopsy.EurJNuclMolImaging2006;33:887e92. 85. Morton D, Thompson J, Cochrane A, et al. Sentinel-node 65. Constantinidou A, Hofman M, O\u2019Doherty M, et al. Routine biopsyornodalobservationinmelanoma.NEnglJMed2006; positron emission tomography and emission tomography/- 355:1307e17. computed tomography in melanoma staging with positive 86. MortonDL,CochranAJ,ThompsonJF,etal.Sentinelnodebiopsy sentinel node biopsy is of limited benefit. Melanoma Res forearlystagemelanomaeAccuracyandmorbidityinMSLT-1, 2008;18:56e60. aninternationalmulticentretrial.AnnSurg2005;242:302e13. 66. VeronesiU,CascinelliN,AdamusJ,etal.ThinstageIprimary 87. Wright BE, Scheri RP, Ye X, et al. Importance of sentinel cutaneousmalignantmelanoma.Comparisonofexcisionwith lymphnodebiopsyinpatientswiththinmelanoma.ArchSurg marginsof1or3cm.NEnglJMed1988;318:1159e62. 2008;143:892e9. 67. Balch CM, Urist MM, Karakousis CP, et al. Efficacy of 2 cm 88. LiW,StallA,ShiversSC,etal.Clinicalrelevanceofmolecular surgical margins for intermediate-thickness melanomas staging for melanoma: comparison of RT-PCR and immuno- (1e4mm):resultsofamulti-institutionalrandomizedsurgical histochemistry staining in sentinel lymph nodes of patients trial.AnnSurg1993;218:262e7. withmelanoma.AnnSurg2000;231:795e803. 68. Cohn-CedermarkG,RutqvistLE,AnderssonR,etal.Longterm 89. NathansohnN,SchachterJ,GutmanH.Patternsofrecurrence resultsofarandomizedstudybytheSwedishMelanomaStudy in patients with melanoma after radical lymph node dissecGroupon2cmversus5cmresectionmarginsforpatientswith tion.ArchSurg2005;140:1172e7. cutaneousmelanomawithatumorthicknessof0.8e2.0mm. 90. NationalCancerPeerReviewProgramme.ManualforCancer Cancer2000;89:1495e501. Services 2008: Skin Measures. 08e2J-212.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 16}, {"text": "and immuno- (1e4mm):resultsofamulti-institutionalrandomizedsurgical histochemistry staining in sentinel lymph nodes of patients trial.AnnSurg1993;218:262e7. withmelanoma.AnnSurg2000;231:795e803. 68. Cohn-CedermarkG,RutqvistLE,AnderssonR,etal.Longterm 89. NathansohnN,SchachterJ,GutmanH.Patternsofrecurrence resultsofarandomizedstudybytheSwedishMelanomaStudy in patients with melanoma after radical lymph node dissecGroupon2cmversus5cmresectionmarginsforpatientswith tion.ArchSurg2005;140:1172e7. cutaneousmelanomawithatumorthicknessof0.8e2.0mm. 90. NationalCancerPeerReviewProgramme.ManualforCancer Cancer2000;89:1495e501. Services 2008: Skin Measures. 08e2J-212. Available at: 69. Khayat D, Rixe O, Martin G, et al. Surgical margins in cutahttp://www.library.nhs.uk/integratedSearch/viewResource. neousmelanoma(2cmversus5cmforlesionsmeasuringless aspx?resID=299673(lastaccessed25.05.10) than 2.1-mm thick). Long-term results of a large European 91. Karakousis CP, Emrich LJ, Rao U, et al. Groin dissection in MulticentricPhaseIIIstudy.Cancer2003;97:1941e6. malignantmelanoma.AmJSurg1986;152:491e5. 70. Balch C, Soong SJ, Smith T, et al. Long term results of 92. BadgwellB,XingY,GershenwaldJE,etal.Pelviclymphnode aprospectivesurgicaltrialcomparing2cmvs.4cmexcision dissectionisbeneficialinsubsetsofpatientswithnode-posimarginsfor740patientswith1e4mmmelanomas.AnnSurg tivemelanoma.AnnSurgOncol2007;14:2867e75. Oncol2001;8:101e8. 93. Finck SJ, Giuliano, Mann BD, et al. Result of ilioinguinal 71. ThomasJ,Newton-BishopJ,A\u2019HernR,etal.Excisionmargins dissectionforstageImelanoma.AnnSurg1982;196:180e6. in high-risk malignant melanoma. N Engl J Med 2004;350: 94. Sterne GD, Murray DS, Grimley RP. Ilioinguinal block dissec757e66. tionformalignantmelanoma.BrJSurg1995;82:1057e9. 72. NIHConsensusConference.Diagnosisandtreatmentofearly 95. EssnerR,ScheriR,KavanaghM,etal.Surgicalmanagementof melanoma.JAmMedAssoc1992;268:1314e9. the groin lymph nodes in melanoma in the era of sentinel 73. Veronesi U, Cascinelli N. Narrow excision (1 cm margin) e lymphnodedissection.ArchSurg2006;141:877e82. a safe procedure for thin cutaneous melanoma. Arch Surg 96. ShenP,ConfortiA,EssnerR,etal.Isthenodeofcloquetthe 1991;126:438e41. sentinelnodefortheiliac/obturatornodegroup?TheCancer 74. Lens M, Nathan P, Bataille V. Excision margins for primary J2000;6:93e7. cutaneousmelanoma:updatedpooledanalysisofrandomized 97. HughesTMD,A\u2019HernR,ThomasJ,etal.Prognosisandsurgical controlledtrials.ArchSurg2007;142:885e91. management of patients with palpable inguinal lymph node 75. SladdenMJ,BalchC,BarzilaiDA,etal.Surgicalexcisionmargins metastasesfrommelanoma.BrJSurg2000;87:892e901. forprimarycutaneousmelanoma.CochraneDatabaseSystRev; 98. KarakousisCP,DriscollDL.Positivedeepnodesinthegroinand 2009;.doi:10.1002/14651858.CD004835.pub2.CD004835. survivalinmalignantmelanoma.AmJSurg1996;171:421e2.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 16}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1417 99. Balch CM, Ross MI. Melanoma patients with iliac nodal 120. MiddletonMR,GrobJJ,AaronsonN,etal.Randomizedphase metastasescanbecured.AnnSurgOncol1999;6:230e1. IIIstudyoftemozolomideversusdacarbazineinthetreatment 100. StrobbeLJA,JonkA,etal.Positiveiliacandobturatornodes of patients with advanced metastatic malignant melanoma. inmelanoma:survivalandprognosticfactors.AnnSurgOncol JClinOncol2000;18:158e66. 1999;6:255e62. 121. PatelP,SuciuS,MortierL,etal.Extendedscheduleescalated 101. O\u2019BrienCJ,CoatesAS,Petersen-SchaeferK,etal.Experience dosetemozolomideversusdacarbazineinstageIVmalignant with998cutaneousmelanomaoftheheadandneckover30 melanoma; final results of the randomised phase 3 study years.AmJSurg1991;182:86e91. (EORTC18032).AnnOncol2009;19:viii3. 102. TurkulaLD,WoodsJ.Limitedorselectivenodaldissectionfor 122. IvesNJ,StoweRL,etal.Chemotherapycomparedwithbiomalignantmelanomaoftheheadandneck.AmJSurg1984; chemotherapy for the treatment of metastatic melanoma: 148:446e8. a meta-analysis of 18 trials involving 2,621 patients. J Clin 103. HillS,ThomasJM.Useofthecarbondioxidelasertomanage Oncol2007;25:5426e34. cutaneous metastases from malignant melanoma. Br J Surg 123. Tarhini AA, Kirkwood JM, et al. Durable completeresponses 1996;83:509e12. withhigh-dosebolusinterleukin-2inpatientswithmetastatic 104. ThompsonJF,KamPC.Currentstatusofisolatedlimbinfusion melanoma who have experienced progression after biowith mild hyperthermia for melanoma. Int J Hyperthermia chemotherapy.JClinOncol2007;25:3802e7. 2008;24:219e25. 124. ZacestAC,BesserM,StevensG,etal.Surgicalmanagement 105. BeasleyGM,PetersenRP,YooJ,etal.Isolatedlimbinfusionof of cerebral metastases from melanoma: outcome in 147 in-transit malignant melanoma of the extremity: a wellpatients treated at a single institution over two decades. tolerated butless effective alternativeto hyperthermic isoJNeurosurg2002;96:552e8. latedlimbperfusion.AnnSurgOncol2008;15:2195e205. 125. Mori Y,KondziolkaD, FlickingerJC, etal. Stereotacticradi106. Cornett WR, McCall LM, Petersen RP, et al. Randomized osurgeryforcerebralmetastaticmelanoma:factorsaffecting multicentertrialofhyperthermicisolatedlimbperfusionwith localdiseasecontrolandsurvival.IntJRadiatOncolBiolPhys melphalan alone compared with melphalan plus tumor 1998;42:581e9. necrosisfactor:AmericanCollegeofSurgeonsOncologyGroup 126. SelekU,ChangE,Hassenbusch3rdSJ,etal.StereotacticradiTrialZ0020.JClinOncol2006;24:4196e201. osurgicaltreatmentin103patientsfor153cerebralmelanoma 107. VeronesiU,AdamusJ,AubertC,etal.Arandomisedtrialof metastases.IntJRadiatOncolBiolPhys2004;59:1097e106. adjuvant chemotherapy and immunotherapy in cutaneous 127. LensMB,RosdahlI,AhlbomA,etal.Effectofpregnancyon melanoma.NEnglJMed1982;307:913e6. survival in women with cutaneous malignant melanoma. 108. KoopsHS,VagliniM,SuciuS,etal.Prophylacticisolatedlimb JClinOncol2004;22:4369e75. perfusion for localized, high-risk limb melanoma: results of 128. O\u2019Meara AT, Cress R, Xing G, et al. Malignant melanoma in a multicenter randomized phase III trial. European Organipregnancy.Apopulation-basedevaluation.Cancer2005;103: zation for Research and Treatment of Cancer Malignant 1217e26. Melanoma Cooperative Group Protocol 18832, the World 129. Daryanani D, Plukker JT, De Hullu JA, et al. Pregnancy and Health Organization Melanoma Program Trial 15, and the early-stagemelanoma.Cancer2003;97:2248e53. NorthAmericanPerfusionGroupSouthwestOncologyGroup130. NaldiL,AltieriA,ImbertiGL,etal.Oncologystudygroupofthe 8593.JClinOncol1998;16:2906e12. Italian Group for Epidemiologic Research in Dermatology 109. WheatleyK,IvesN,EggermontA,etal.Adjuvanttherapyfor (GISED).Cutaneousmalignantmelanomainwomen.Phenotypic melanoma:anindividualpatientmeta-analysisofrandomised characteristics, sun exposure, and hormonal factors: a casetrials.JClinOncol2007;25:8526. controlstudyfromItaly.AnnEpidemiol2005;15:545e50. 110. Henderson MA, Burmeister B, Thompson JF, et al. Adjuvant 131. KaragasMR,StukelTA,DykesJ,etal.Apooledanalysisof10 radiotherapyandregionallymphnodefieldcontrolinmelanoma case-controlstudiesofmelanomaandoralcontraceptiveuse. patients after lymphadenectomy: Results of an intergroup BrJCancer2002;86:1085e92. randomizedtrial.JClinOncol2009;27:18[Suppl;abstrLBA9084]. 132. LeaCS,HollyEA,HartgeP,etal.Reproductiveriskfactorsfor 111. Chang P, Knapper WH. Metastatic melanoma of unknown cutaneous melanoma in women: a case-control study. Am J primary.Cancer1982;49:1106e11. Epidemiol2007;165:505e13. 112. LeeCC,FariesMB,WanekLA,etal.Improvedsurvivalafter 133. MacKie RM, Bray CA. Hormone replacement therapy after lymphadenectomy for nodal metastasis from an unknown surgery for stage I or II cutaneous melanoma. Br J Cancer primarymelanoma.JClinOncol2008;26:535e41. 2004;90:770e2. 113. Lee CC, Faries MB, Wanek LA, et al.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 17}, {"text": "CA. Hormone replacement therapy after lymphadenectomy for nodal metastasis from an unknown surgery for stage I or II cutaneous melanoma. Br J Cancer primarymelanoma.JClinOncol2008;26:535e41. 2004;90:770e2. 113. Lee CC, Faries MB, Wanek LA, et al. Improved survival for 134. SipleJ,SchneiderD,WanlassW,etal.Levodopatherapyand stage IV melanoma from an unknown primary site. J Clin riskofmalignantmelanoma.AnnPharm2000;34:382e5. Oncol2009;27:3489e95. 135. Wolfe F, Michaud K. Biologic treatment of rheumatoid 114. PatchellRA,TibbsPA,WalshJW,etal.Arandomisedtrialof arthritisandtheriskofmalignancy:analysesfromalargeUS surgery in the treatment of single metastases of the brain. observationalstudy.ArthritisRheum2007;56:2886e95. NEnglJMed1990;322:494e500. 136. NHS Blood and Transplant. Organ Donation: How to Become 115. Miller JD. Surgical excision for single cerebral metastasis? a Donor. www.organdonation.nhs.uk/ukt/how_to_become_ Lancet1993;341:1566. a_donor/how_to_become_a_donor.jsp (last accessed 116. SondakV,LiuP,WarnekeJ,etal.Surgicalresectionforstage 25.05.10). IV melanoma: a Southwest Oncology Group Trial (S9430). 137. Cornish D, Holterhues C, van der Poll-Franse L, et al. A JClinOncol2006;24(Suppl.):8019(Abstract). systematic review of health-related quality of life in cuta117. Overett TK, Shiu MH. Surgical treatment of distant metaneousmelanoma.AnnOncol2009;20(Suppl6):51e8. static melanoma. Indications and results. Cancer 1985;56: 138. Sollner W, Zschocke I, Augustin M. Melanoma patients: 1222e30. psychosocialstress,copingwithillnessandsocialsupport.A 118. MeyerT,MerkelS,GoehlJ,etal.Surgicaltherapyfordistant systematicreview.PsychotherPsychosomMedPsychol1998; metastases of malignant melanoma. Cancer 2000;89: 48:338e48. 1983e91. 139. FranckenAB,BastiannetE,HoekstraHJ.Followupinpatients 119. EssnerR,LeeGH,etal.Contemporarysurgicaltreatmentof with localized primary melanoma. Lancet Oncol 2005;6: advanced-stagemelanoma.ArchSurg2004;139:961e7. 608e21.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 17}, {"text": "1418 J.R.Marsden etal. 140. Hofmann U, Szedlak M, Ritgen W, et al. Primary staging and (cid:1) Patients with giant congenital pigmented naevi are at follow up in melanoma patients-monocenter evaluation of increasedriskofmelanomaandrequirelong-termfollowmethodscostsandpatientsurvival.BrJCancer2002;87:151e7. up 141. GarbeC,HauschildA,VolkenandtM,etal.Evidenceandinter- (cid:1) The prophylactic excision of small congenital naevi is disciplinaryconsensus-basedGermanguidelines:diagnosisand not recommended surveillanceofmelanoma.MelanomaRes2007;17:393e9. (cid:1) Individualswithafamilyhistoryofthreeormorecases 142. BalfountaML,BeauchetA,ChagnonS,etal.Ultrasonography ofmelanomashouldbereferredtoaClinicalGeneticist or palpation for detection of melanoma nodal invasion: ameta-analysis.LancetOncol2004;5:673e80. or specialised dermatology services for counselling. 143. Einwachter-Thompson J, MacKie RM. An evidence base for Those with two cases in the family may also benefit, reconsidering current follow-up guidelines for patients with especially if one of the cases had multiple primary cutaneousmelanomalessthan0.5mmthickatdiagnosis.BrJ melanomas or theatypical mole syndrome Dermatol2008;159:337e41. Requirements for microscopy of melanoma Summary of 2010 guidelines for management of melanoma Essential Ulceration Thickness Mitoticcount Histological Marginsof Pathological (See full manuscript for details of evidence and recomsubtype excision staging mendation gradings) DesirableLevelofdermal Growthphase Regression Melanoma patients who must be referred from the invasion Local Skin Cancer Multidisciplinary Team to the TumourinfiltratingLymphaticor Specialist Skin Cancer Multidisciplinary Team lymphocytes vascularinvasion Perineural Microsatellites (cid:1) PatientswithstageIBorhigherprimarymelanomawhen invasion sentinel lymph node biopsy (SLNB) is available within theirNetwork.IntheabsenceofSLNBthenpatientswith Surgical wider excision margins for primary stageIIBorhighershouldbereferredtotheSSMDT melanoma (cid:1) Patients with melanoma stage I or above who are eligible for clinical trials that have been approved at CancerNetwork level Breslowthickness Lateralexcisionmargins (cid:1) Patients with melanoma managed by other site tomuscleormusclefascia specialist teams, e.g. gynaecological, mucosal and headandneck(excluding ocular) Insitu 5mmmarginstoachievecomplete (cid:1) Patientswith multipleprimary melanomas histologicalexcision (cid:1) Childrenyounger than19 yearswith melanoma <1mm 1cm (cid:1) Any patient with metastatic melanoma diagnosed at 1.01e2mm 1e2cm presentationoron follow-up 2.1e4mm 2e3cm (cid:1) Patients with giant congenital naevi where there is >4mm 3cm suspicionof malignanttransformation (cid:1) Patients with skin lesions of uncertain malignant Staging investigations for melanoma potential Recommendations for Local Skin Cancer (cid:1) StagesI,II,andIIIAmelanomapatientsshouldnotroutinely Multidisciplinary Team record keeping of clinical bestagedbyimagingorothermethodsasthetrue-positive features pick-uprateislowandthefalse-positiverateishigh (cid:1) StagesIIIBorCpatientsshouldbeimagedbyCTpriorto surgery andwith SSMDTreview See:National Institute for Health and Clinical Excellence (cid:1) Stage IV melanoma patients should be imaged accord- (NICE) Improving Outcomes Guidance for People with ing to clinical need and SSMDT review; lactate dehySkinTumoursincludingMelanoma.February2006.www. drogenase shouldalso bemeasured nice.org.", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 18}, {"text": "dehySkinTumoursincludingMelanoma.February2006.www. drogenase shouldalso bemeasured nice.org.uk/nicemedia/pdf/CSG_Skin_Manual/pdf Recommendationsforthemanagementofclinically node-negative patients Recommendationsforscreeningandsurveillanceof high-risk individuals (cid:1) There is no role for elective lymph node dissection (Level I,GradeE) (cid:1) Patients who are at moderately increased risk of (cid:1) Sentinellymphnodebiopsy(SLNB)canbeconsideredin melanomashouldbeadvisedofthisandtaughthowto stage IB melanoma and upwards in SSMDTs (Level IIa, self-examine.Thisincludespatientswithatypicalmole GradeC) phenotype,thosewithapreviousmelanoma,andorgan (cid:1) SLNBisastagingprocedurewithnoproventherapeutic transplantrecipients value", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 1, "page": 18}, {"text": "Revised UKguidelines forthe managementof cutaneousmelanoma 2010 1419 (cid:1) Surgical risks of SLNB, and of a false-negative result, Follow-up of melanoma patients shouldalso beexplained (cid:1) Patientswithinsitumelanomasdonotrequirefollow-up Recommendations for locoregional recurrent (cid:1) Patients with stage IA melanomas should be seen melanoma two to four times over up to 12 months then discharged (cid:1) All patients shouldbemanagedby SSMDTs. (cid:1) Patients with stage IBeIIIA melanomas should be (cid:1) Nodes clinically suspicious for melanoma should be seen 3-monthly for 3 years, then 6-monthly to 5 sampled using fine needle aspiration cytology (FNAC) years priortocarryingoutformalblockdissection.IfFNACis (cid:1) Patients with stage IIIB and IIIC and resected stage negative although lymphocytes were seen, a core or IV melanoma should be seen 3-monthly for 3 open biopsy shouldbeperformed ifsuspicion remains years, 6-monthly to 5 years, then annually to 10 (cid:1) Prior to formal dissection, performed by an expert, years staging by CT scan should be carried out other than (cid:1) Patients with unresectable stage IV melanomas are wherethiswouldmeanunduedelay(LevelIII,GradeB) seenaccordingto need (cid:1) The treatment of locoregional limb recurrence is palliative and, depending on extent and response, includes Appendix 1. Definition of the levels of excisionorCO laser,isolatedlimbinfusionorperfusion 2 evidence used in preparation of the guidelines Recommendations for metastatic disease (cid:1) All patients shouldbemanagedby SSMDTs (cid:1) Surgery should be considered for oligometastatic Level Typeofevidence disease at sites such as the skin, brain or gut, or to Ia Evidenceobtainedfrommeta-analysisof prevent painorulceration (cid:1) Radiotherapy may have a palliative role in the treatrandomisedcontrolledtrials,ormeta-analysisof epidemiologicalstudies ment ofmetastases (cid:1) Standardchemotherapyisdacarbazinealthoughitsrole Ib Evidenceobtainedfromatleastonerandomised controlledtrial ispalliative (cid:1) Patients with stage IV melanoma should be considered IIa Evidenceobtainedfromatleastonewell-designed controlledstudywithoutrandomisation for entry toclinical trials IIb Evidenceobtainedfromatleastoneothertypeof well-designedquasi-experimentalstudy III Evidenceobtainedfromwell-designednonPregnancy, oral contraceptives and hormone experimentaldescriptivestudies,suchas replacement therapy comparativestudies,correlationstudiesandcase studies IV Evidenceobtainedfromexpertcommitteereports oropinionsand/orclinicalexperienceof Pregnancyin Oral Hormone respectedauthorities melanoma contraceptives replacement therapy Gradeofrecommendation Noworseningof Noincreased Noincreased A Thereisgoodevidencetosupporttheuseofthe prognosis riskofmelanoma riskofmelanoma procedure Noincreasein Noworseningof B Thereisfairevidencetosupporttheuseofthe adverse prognosis procedure outcomesfor C Thereispoorevidencetosupporttheuseofthe motherorbaby procedure Placental D Thereisfairevidencetosupporttherejectionof metastases theuseoftheprocedure possiblein E Thereisgoodevidencetosupporttherejectionof stageIVdisease theuseoftheprocedure", "source": "revised UK guideliens for the management of cutaneous melanoma 2010.pdf", "chunk_id": 0, "page": 19}, {"text": "BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists\u2019 guidelines for the management of contact dermatitis 2017 G.A. Johnston,1 L.S. Exton,2 M.F. Mohd Mustapa,2 J.A. Slack,1 I.H. Coulson,3 J.S.C. English4 and J.F. Bourke5 1Department of Dermatology, University Hospitalsof Leicester NHSTrust, Infirmary Square,Leicester LE15WW,U.K. 2British Association of Dermatologists, WillanHouse, 4 Fitzroy Square, LondonW1T 5HQ, U.K. 3Department of Dermatology, Burnley GeneralHospital, CastertonAvenue, Burnley BB10 2PQ, U.K. 4CircleNottingham, ListerRoad, Nottingham NG72FT, U.K. 5Department of Dermatology, SouthInfirmary VictoriaUniversity Hospital, OldBlackrock Road, CorkCity, Ireland Correspondence GrahamA.Johnston. 1.0 Purpose and scope E-mail:graham.johnston@uhl-tr.nhs.uk The overall objective of the guideline is to provide up-to-date, Accepted forpublication evidence-based recommendations for the management of con19September2016 tact dermatitis. The document aims to (i) offer an appraisal of all relevant literature up to February 2016, focusing on any Funding sources key developments; (ii) address important, practical clinical None. questions relating to the primary guideline objective; and (iii) provide guideline recommendations and if appropriate Conflicts ofinterest research recommendations. G.A.J.hasactedasaninvitedspeakerforCrawfordHealthcareLtd(nonspecific)andas aco-authorofBritishOccupationalHealthResearchFoundationguidelinesonoccupaThe guideline is presented as a detailed review with hightionaldermatitis(specific).I.H.C.hasactedasaninvitedspeakerforStiefel(specific). lighted recommendations for practical use in the clinic, in J.S.C.E.hasactedasaninvitedspeakerforStiefel(specific). addition to an updated patient information leaflet [available on the British Association of Dermatologists\u2019 (BAD) website, ThisisanupdatedguidelinepreparedfortheBritishAssociationofDermatologists http://www.bad.org.uk/for-the-public/patient-information- (BAD)ClinicalStandardsUnit,whichincludestheTherapy&GuidelinesSubcommittee leaflets]. (T&G).MembersoftheClinicalStandardsUnitthathavebeeninvolvedare:P.M. McHenry(ChairmanT&G),K.Gibbon,D.A.Buckley,T.A.Leslie,E.C.Mallon,S. Wakelin,S.Ungureanu,R.Y.P.Hunasehally,M.Cork,G.A.Johnston,J.Natkunara1.1 Exclusions jah,F.S.Worsnop,N.Chiang,J.Donnelly(BritishNationalFormulary),C.Saunders This guideline will not cover contact urticaria, prick testing or (BritishDermatologicalNursingGroup),A.G.Brain(BADScientificAdministrator), LSExton(BADInformationScientist),M.F.MohdMustapa(BADClinicalStandards atopy patch testing. Manager). 2.0 Stakeholder involvement and peer review Producedin2001bytheBritishAssociationofDermatologists;reviewedandupdated, 2009,2016. The guideline development group (GDG) consisted of consulE-mail:guidelines@bad.org.uk tant dermatologists, a nurse specialist and patient representatives. The draft document and supporting information was DOI10.1111/bjd.15239 madeavailabletotheBADmembership,BritishDermatological NICEhasaccreditedtheprocessusedbytheBritishAssociationof Nursing Group, Primary Care Dermatological Society, British Dermatologiststoproduceclinicalguidelines.Therenewedaccreditationisvaliduntil31May2021andappliestoguidanceproSociety for Cutaneous Allergy, British Society for Skin Care in ducedusingtheprocessdescribedinUpdatedguidanceforwritinga BritishAssociationofDermatologistsclinicalguidance\u2013theadopImmunocompromised Individuals, Society for Occupational tionoftheGRADEmethodology2016.Theoriginalaccreditation termbeganon12May2010.Moreinformationonaccreditation Medicine and several authorities in occupational health, which canbeviewedatwww.nice.org.uk/accreditation. were actively considered by the GDG. Following further review, the finalized version was sent for peer review by the Clinical Standards Unit of the BAD, made up of the Therapy & Guidelines Subcommittee, prior tosubmission forpublication. 3.0 Methodology This setofguidelines hasbeen developed using theBAD\u2019srecommended methodology,1 with reference to the Appraisal of \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 317 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 1}, {"text": "BritishJournalofDermatology(2017)176,pp317\u2013329 317 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 1}, {"text": "318 BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. Guidelines Research and Evaluation (AGREE II) instrument Table2 Clinicalquestionsinpatientswithcontactdermatitis (www.agreetrust.org),2 and the Grading of Recommendations pertinenttothescopeoftheguidelines Assessment, Development and Evaluation (GRADE).3 RecomDiagnosis Whichandhowmanyallergensshouldbeused mendations were developed for implementation in the U.K.\u2019s intests? NationalHealth Service. Whenshouldtestsbecarriedout? The GDG established several clinical questions pertinent to Doesincreasingthenumberofallergenstested the scope of the guideline and a set of outcome measures of improvediagnosis? importance to patients, ranked according to the GRADE Prevention Doeseducationimproveorpreventhanddermatitis? methodology (see section 3.1). Dobarriercreamsimprovehanddermatitis? Treatment Doestopicaltreatmentwork? A systematic literature search of the PubMed, MEDLINE, Doessystemictreatmentwork? Embase, Cochrane and LILACS databases was conducted to Dosoapsubstitutesimprovecontactdermatitis? identify key articles for contact dermatitis up to February Doeseducationasatreatmentwork? 2016; search terms and strategies are detailed in the SupportDoesphototherapywork? ing Information. Additional references relevant to the topic were also isolated from citations in reviewed literature. Evidence from included studies was graded according to the work (9); (ii) improvement in quality of life (8); (iii) GRADE system (high, moderate, low or very-low quality). improved or clearance of dermatitis (8); (iv) treatment toleraRecommendations are based on evidence drawn from systembility (5); (v) prevention of dermatitis (5); (vi) side-effects of atic reviews of the literature pertaining to the clinical quesinterventions (4). tions identified; the summary of findings with forest plots, The outcome measure used in the diagnosis section was GRADE evidence profiles indicating the quality of evidence, confirmation ofadiagnosis of contactdermatitis. tables linking the evidence to the recommendations, Preferred Reporting Items for Systematic Reviews and Meta-Analyses 4.0 Summary of recommendations (PRISMA) flow diagram and list of excluded studies are detailed in the Supporting Information. The strength of recThe recommendations and ratings shown in Tables 3\u20135 were ommendation is expressed by the wording and symbols agreed upon unanimously by the core members of the GDG shownin Table 1. and patient representatives. For further information on the wording used for recommendations and strength of recom3.1 Clinicalquestions andoutcomes mendation ratings, seesection 3.0. The GDG established several clinical questions pertinent to the 5.0 Background scopeofthe guidelines,in thecategories shownin Table 2. The GDG also established a set of outcome measures of 5.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 2}, {"text": "of 5.1 Definition importance to patients (prevention and treatment), ranked according to the GRADE methodology,4 data on which are The words \u2018eczema\u2019 and \u2018dermatitis\u2019 are used synonymously extracted from included studies: (i) return to/remain in to describe a polymorphic pattern of cutaneous inflammation Table1 Strengthofrecommendationratings Strength Wording Symbols Definition Strongrecommendationfor \u2018Offer\u2019(orsimilar,e.g.\u2018use\u2019, Benefitsoftheinterventionoutweightherisks;most theuseofanintervention \u2018provide\u2019,\u2018take\u2019, patientswouldchoosetheintervention,whileonlya \u2018investigate\u2019,etc.) smallproportionwouldnot;forclinicians,mostoftheir patientswouldreceivetheintervention;forpolicymakers,itwouldbeausefulperformanceindicator Weakrecommendationfor \u2018Consider\u2019 Risksandbenefitsoftheinterventionarefinelybalanced; theuseofanintervention mostpatientswouldchoosetheintervention,butmany wouldnot;clinicianswouldneedtoconsiderthepros andconsforthepatientinthecontextoftheevidence; forpolicy-makersitwouldbeapoorperformance indicatorwherevariabilityinpracticeisexpected Norecommendation Insufficientevidencetosupportanyrecommendation Strongrecommendation \u2018Donotoffer\u2019 Risksoftheinterventionoutweighthebenefits;most againsttheuseofan patientswouldnotchoosetheintervention,whileonlya intervention smallproportionwould;forclinicians,mostoftheir patientswouldnotreceivetheintervention BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 2}, {"text": "BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 319 Table3 Recommendationsandratingsagreeduponbytheguidelinedevelopmentgroupandpatientrepresentatives Summaryofrecommendations Strength Diagnosis Offerpatientswithsuspectedcontactdermatitisapatchtestwithabaselineseriesofallergens Inidentifyingallergensinpatientswithcontactdermatitis,considertestingforadditionalseriesdependentonallergenexposure Consideradditionalreadingsatday6or7iftheresultsareunexpectedlynegativeatday4 Prevention Considerskincareandskinprotectioncreamsinpreventingoccupationaldermatitis Treatment Offeralitretinointopatientswithseverechronichandeczema121 Considertopicaltacrolimustopatientswithcontactdermatitiswheretopicalsteroidsareunsuitableorineffective ConsiderPUVAtherapyfortreatingpatientswithchronichandeczema Considerpatienteducationinoccupationalcontactdermatitis PUVA,psoralenplusultravioletA. Table4 Summaryofgood-practicerecommendations(informal Table5 Summaryofresearchrecommendations consensus) Themethodologyandreportingofresultsoffuturepatchtest studiesshouldbestandardized Summaryofgood-practicerecommendations(informal High-qualitystudiesareneededtoaddresstheefficacyof consensus) interventionsforcontactdermatitis,including: UseclinicalassessmenttoolssuchastheDermatologyLifeQuality topicaltacrolimusvs.topicalcorticosteroids IndexandtheHandEczemaSeverityIndexforboththeinitial combinationoftacrolimusandtopicalcorticosteroids assessmentandtheresponsetotreatmentofpatientswith alitretinoinvs.PUVAforhanddermatitis contactdermatitis developmentandevaluationofskinbarrierrepairproducts Takeadetailedhistory,includingsymptomsandiftheywere developmentofnewwashproductsthatdonotdamagethe relatedtoapplicationoruseofanyparticularproduct,a skinbarrier specificactivityoroccupation Efficacyofsystemictherapies\u2013ciclosporin,azathioprine, Ifrelatedtotheworkplaceinvestigatetheworkpracticeand methotrexate\u2013needstobedetermined productshandledatwork,supplementedbyexaminationof healthandsafetydatasheets PUVA,psoralenplusultravioletA. Provideapatientinformationleafletonpatchtestingaspartofthe counsellingprocess,whichincludesinformationonpotential side-effects.Informedpatientconsentshouldbeobtained exposure or a few brief exposures to strong irritants or caustic Offerpatchtestingforpatientswithchronicorpersistent dermatitisasclinicalfeaturesaloneareunreliablein agents. (iii) Chronic (cumulative) irritant contact dermatitis: distinguishingallergiccontactfromirritantandendogenous occurs following repetitive exposure to weaker irritants that dermatitis,particularlywithhandandfacialdermatitis may be either \u2018wet\u2019, such as detergents, organic solvents, Considerdeferringpatchtestingfor3monthsafterfinishing soaps, weak acids and alkalis, or \u2018dry\u2019, such as low-humidity systemicagentsand6monthsafterfinishingbiologicalagents, air, heat, powders, paper, cardboard and dusts. (iv) Allergic tominimizethechanceoffalse-negativereactions,ifpossible contact dermatitis: this involves sensitization of the immune system to a specific allergen or allergens with resulting dermatitis or exacerbation of pre-existing dermatitis. (v) Phototoxic, photoallergic and photoaggravated contact dermatitis: that, in the acute phase, is characterized by erythema and some allergens are also photoallergens. (vi) Systemic contact vesiculation and, in the chronic phase, by dryness, lichenificadermatitis (systemic allergic dermatitis): seen after the systion and fissuring. Contact dermatitis describes these patterns temic administration of a chemical, usually a drug, to which of reaction in response to external agents (exogenous); these topical sensitization has occurred previously. (vii) Protein conagents can act either as irritants, where a cell-mediated tact dermatitis: repetitive handling of proteins, usually foods, immune response is not involved, or as allergens, where cellresults initially in immediate urticarial symptoms and signs, mediated immunity is involved. but later progresses to a dermatitic reaction. Prick and radioalContact dermatitis may be classified into the following reaclergosorbent tests to the offending protein allergen are position types. (i) Subjective irritancy: idiosyncratic stinging and tive, but patch tests are negative. The proteins may be smarting reactions occur within minutes of contact, usually on vegetables (potato, garlic), meats, fish (in food handlers), the face, in the absence of visible changes. Cosmetic or sunflour, enzymes (in bakers and pharmaceutical manufacture), screen constituents are commonprecipitants. (ii)Acute irritant and animal dander and fluids (in veterinarians and abattoir contact dermatitis: often the result of a single overwhelming workers).5 \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 3}, {"text": "and abattoir contact dermatitis: often the result of a single overwhelming workers).5 \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 3}, {"text": "320 BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. In clinical practice, it is not uncommon for atopic/endoge5.3 Assessment andinvestigation nous, irritant andallergic aetiologies tocoexist in thedevelopment of certain eczemas, particularly hand and footdermatitis. The pattern and morphology of dermatitis, particularly on the It is important to look for a history of occupational and recrehands and face, is unreliable in predicting a cause and in disational factors in both irritantandallergic contactdermatitis. tinguishing atopic/endogenous dermatitis clearly from dermatitis which is contact irritant or contact allergic in aetiology.20,21 This is also true for children with atopic 5.2 Epidemiology dermatitis.22 The point prevalence of dermatitis in the U.K. is estimated to Therefore, it is essential to consider the following points be about 20%. Atopic/endogenous dermatitis makes up the initially in the history of all patients with dermatitis: (i) Is majority of cases. The point prevalence of hand dermatitis has there a personal history of atopic dermatitis in infancy or been reported to be 2%, with a lifetime risk of developing childhood? Are there other atopic features, such as asthma and hand dermatitis of 20%.6 While irritant contact dermatitis is hay fever? Is there a family history of atopy? (ii) Where did more common than allergic contact dermatitis, allergic contact the initial symptoms begin, and where did they spread to dermatitis carries a worse prognosis unless the allergen is later? (iii) Were symptoms related to the application or use of identified and avoided. Contact dermatitis accounts for 4\u20137% any particular product, especially cosmetics, personal-care ofdermatologicalconsultations.Dermatitiscanpersist,particuproducts, topical medication, clothing, bandages or personal larly in those allergic to chromate, epoxy resin and Compositae protection such as gloves? (iv) A detailed history of all wash afterallergenavoidance. products which come into contact with the skin is important The prevalence of contact allergy to specific allergens in the because the majority contain harsh emulsifiers/surfactants that general population in Europe has been estimated at between can cause significant damage to the skin barrier in predisposed 10% and 27%.7,8 Nickel (14(cid:1)5%), fragrance (3(cid:1)7%), cobalt individuals such as those with atopic/endogenous dermatitis (2(cid:1)2%), hydroxyisohexyl cyclohexene carboxaldehyde (1(cid:1)4%) after a short period of exposure. This should detail every wash and p-phenylenediamine (PPD) (1%) were among the most product, including shampoos. (v) Were symptoms related to commonly identified allergens.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 4}, {"text": "(1(cid:1)4%) after a short period of exposure. This should detail every wash and p-phenylenediamine (PPD) (1%) were among the most product, including shampoos. (v) Were symptoms related to commonly identified allergens. any particular activity, such as hairdressing, holidays, home Chromate allergy is reducing in frequency in the European improvements, painting, decorating, recreation or sport? (vi) UnionsincetheadditionofirontocementwasmadecompulAre symptoms related to work or specific activity within the sory.9\u201311 Legislation to reduce the nickel content permitted in workplace? A detailed history should be taken, including jewelleryhas reducedtheincidence ofnickel sensitization.12,13 investigation of practice and products handled at work, supIn contrast, an increase in the permitted level of methylisothplemented by examination of health and safety data sheets. iazolinone in cosmetics and personal-care products has led to Also, personal protection practice such as the use of gloves or a dramatic and unprecedented increase in sensitization since goggles should be determined. (vii) Do symptoms improve 2010.14 when environment changes, for example at weekends and The ongoing UK EPIDERM surveillance scheme records the duringholidays,andrecuronreturn towork?(viii) Dosympepidemiology of occupational skin disease (OSD).15,16 Skin tomsgetworse aftersunlight exposure? disease ranks second (29%) to musculoskeletal conditions The history should also identify any contact with primary (57%) as a cause of occupational disease; dermatitis makes up skin irritants. This should include both wet agents (including 79% of OSD. Occupational hand dermatitis in healthcare water and the frequency of hand washing) and which prodworkers is declining, owing to workplace interventions. While uctshave been used,aswellas dry,desiccating products. there is an overall decrease in sensitization to rubber acceleraClinical assessment tools should be used for both the initial tors, there is increasing sensitization to carbamates and to assessment andtheresponse totreatment ofpatientswithconrarer rubberallergens.17 tactdermatitis.ConsiderbothgenerictoolssuchastheDermaThe prevalence of contact dermatitis in children is unclear. tology Life Quality Index and more specific, objective scoring Alargereviewreports positivepatch-testreactionratesvarying systems such as the Hand Eczema Severity Index.23,24 Simplifrom 27% to 95% of referred children.18 The most common fied tools that assess only three variables in hand dermatitis, allergens reported in North American children are nickel, neosuch as the Investigators Global Assessment (measuring only mycin, cobalt, fragrance and Myroxylon pereirae; many children induration, scaling and fissuring) have the advantage of being had atopic/endogenous dermatitis.", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 4}, {"text": "only mycin, cobalt, fragrance and Myroxylon pereirae; many children induration, scaling and fissuring) have the advantage of being had atopic/endogenous dermatitis. Recalcitrant disease unrequick to perform, but have the disadvantage of being useful sponsive to standard therapy, or dermatitis in new areas, only for certain types of hand dermatitis (chronic hyperkerashould raise the possibility of a super-added allergic contact totic) butnot others(pompholyx). dermatitis. Adolescents have a prevalence of contact allergy Patch testing is the gold-standard investigation in a patient almost as high as adults. Population-based studies show 17% in whom allergic contact dermatitis is considered. Prospective of girls and 13% of 16-year-olds have at least one positive studies support the value of specialist contact dermatitis clinics allergic reaction on patch testing.19 Nickel, fragrance and withaccesstoextended seriesofallergensfortheinvestigation 4-tert-butylphenol formaldehyde resin are the most common of dermatitis in specific anatomical sites, occupational groups allergens. and chemical exposures. Dermatologists select appropriate BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 4}, {"text": "BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 321 allergens, assess products that patients bring, assess any posiIf a patient applies potent topical steroids to the back up to tive reactions, and determine their relevance to the individual 2 days prior to the test being applied,34\u201336 or is taking oral and their dermatitis. An important aspect of the process is corticosteroids,37 there is a significant risk of false-negative clear communication of relevant information to allow the results anddecreased reactivity. patient to identify, avoid or substitute the allergen(s). FollowThe effect of systemic corticosteroid treatment on weaker up visits reiterate andclarifythis information. reactions has not been assessed, but expert consensus is that if the daily dose is no higher than 10 mg prednisolone, suppression of positive patch tests is unlikely.38 While positive 5.4 Patch-testing rate patch-test reactions can be elicited in patients taking immunoAn approximate suggested annual workload for a contact dersuppressant drugs,39 or who are tanned as a result of sun matitis investigation clinic has been estimated at one person bathing or treatment with ultraviolet (UV) radiation,40 any per 700 of the population served, that is, 100 patch tests per associated tanning may also suppress patch-test reactions. annum for a catchment population of 70 000.25 The more However, the amount required to do so and the relevant frequently patch testing is carried out, the lower the rate of interval between exposure andpatch testing are poorly quantirelevant positive reactions becomes.26 fied. Where immunosuppressive treatment cannot be stopped safely, patch testing can yield positive results which, while possibly suboptimal, may be preferable to not testing at all.41 5.5 Who should beinvestigated? Antihistamines do not need to be avoided unless testing for As clinical features alone are unreliable in distinguishing allerurticaria or contacturticarial reactions. gic contact from irritant and endogenous dermatitis, particuPatch testing should be deferred for 6 weeks after natural larly with hand and facial dermatitis, patch testing should be and artificial UV exposure, 3 months after finishing systemic carriedoutinanypatientwithachronicorpersistentdermatiagents and 6 months after finishing biological agents, to minitis,27 or atopic/endogenous dermatitis that was previously mizethe chanceoffalse-negative reactions. well controlled with topical therapy and then becomes diffiThere is no evidence that patch testing when breastfeeding cult orimpossible tocontrol withthesame topicaltreatments. is harmful.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 5}, {"text": "reactions. well controlled with topical therapy and then becomes diffiThere is no evidence that patch testing when breastfeeding cult orimpossible tocontrol withthesame topicaltreatments. is harmful. While there is no evidence that patch testing in pregnancy is harmful, no safety data are available. Therefore, patch testing should be undertaken only when required and 6.0 Diagnostic tests (diagnosis) afterinformed consent is obtained. 6.1 Preparation ofthepatient 6.2 Patchtesting The patient should be counselled that the skin will be covered during testing and on the need to avoid exercise, to keep the Patch testing involves the reproduction under the patch tests back dry and of possible adverse effects. Informed consent of an allergic contact dermatitis in an individual sensitized to should betaken anddocumented. a particular antigen(s). The standard method involves the Adverse events associated with patch testing are rare. application of antigen to the skin at standardized concentraPatients should be counselled that a positive result will protions in an appropriate vehicle and under occlusion. The back duce skin reddening, itching and occasionally blistering at the is most commonly used, principally for convenience because application site,28 but that this usually disappears after a few of the area available, although the limbs, in particular the days. outerupper arms, are alsoused. Patients should be warned that some positive test reactions, This test has a sensitivity and specificity of between 70% for example to gold, may persist for up to 1 month; that a and80%.41 positive patch test may be accompanied by a flare of existing Various application systems are available, of which the most orprevious eczemaatdistantsites;thatanincreaseordecrease commonly used are Finn chambers. With this system, the in pigment may be seen at the site of patch tests; and of the investigator preloads individual allergens onto test discs, small possibility ofinfection orscarring at thetreatment site. which, in turn, are mounted on adhesive tape. Care needs to Active sensitization is also rare. While it was reported as be taken to load the same amount of allergen onto each disc \u2018possible\u2019 in two of 7163 patients patch tested to parthenoas significant variation has been reported.42,43 Micropipetting lide,29 it was not reported in any of 5371 patients tested to is the optimal technique to minimize this variation.", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 5}, {"text": "parthenoas significant variation has been reported.42,43 Micropipetting lide,29 it was not reported in any of 5371 patients tested to is the optimal technique to minimize this variation. Many formaldehyde or textile dyes,30,31 and there is no significant allergens are volatile or degrade over a short time, particularly increase in PPD-positive patch-test reactions in individuals acrylates and fragrances.44,45 Allergen expiration dates should who undergo repeat patch tests compared with those who be noted and allergens should always be stored as directed only hadsingle patchtests.32 and patch tests should be prepared as close to the time of The skin to be tested should be free from dermatitis, and application of the patch test as practical.46,47 This is essential skin disease elsewhere, as well controlled as possible. This will for acrylate, fragrance, isocyanate and aqueous allergens.46 It help avoid the \u2018angry back syndrome\u2019 with numerous falsemay be occasionally necessary to test certain allergens beyond positive results.33 thelabelledexpiry datewhen thealternative isnot totest. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 5}, {"text": "322 BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. Two preprepared series of patch tests are available \u2013 the test reactions has been shown to improve physicians\u2019 differenTRUE (cid:1) (Pharmacia, Milton Keynes, U.K.) and the Epiquick (cid:1) tiation betweenirritant andallergicpatch-test reactions.63 (Hermal, Reinbek, Germany) tests. Preprepared tests are sigThe positivity ratio of an allergen, defined as the percentage nificantly more reliable than operator-prepared tests,48\u201352 but of + reactions divided by the sum of all positive reactions onlylimited numbers ofallergens are available. (+, ++ and +++) can help assess false-positivity.64 Allergens There is also some evidence that larger chambers may give with a lower number, such as tixocortol pivalate and the more reproducible tests,53,54 but this may only apply to some sesquiterpene lactone mix, are less likely to produce falseallergens,55 and can be used to obtain a more definite positive positive reactions.65 reaction when a smaller chamber has given a doubtful one As indicated above, preprepared patch tests are better stanpreviously. dardized in terms of the amount of allergens applied and The International Contact Dermatitis Research Group has therefore are more reproducible but offer only a limited numlaid down the standardization of gradings, methods and ber of allergens and can be prohibitively expensive for largenomenclature for patch testing.56 scale testing. Anassessmentshouldbemadeoftherelevanceofeachpositive reaction to the patient\u2019s presenting dermatitis. A simple 6.3 Timingof patchtest readings and pragmatic way of classifying clinical relevance of positive The optimum timing of patch test readings is on day 2, folallergic patch-test reactions is: (i) current relevance \u2013 the lowed by day 4.57 Because some allergens often do not yield patient has been exposed to allergen during the current epipositivereactionsuntilafterday4,athirdreadingatday7will sode of dermatitis and improves when the exposure ceases; pick up approximately 10% more positive reactions that were (ii) past relevance \u2013 past episode of dermatitis from exposure negativeondays2and4.58,59Theseincludeallergensonmany to allergen; (iii) relevance not known \u2013 not sure if exposure baselineseriessuchasneomycinandtixocortolpivalate. is current or old; (iv) cross-reaction \u2013 the positive test is due tocross-reaction with anotherallergen. 6.4 Reading andrelevanceof positivereactions 6.5 Patch-test series Patch tests should be read in natural daylight andrated as positive, negative or irritant (see Table 6). Those that are positive The usual approach to patch testing is to have a standardized are graded on a scale of +, ++ or +++.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 6}, {"text": "as positive, negative or irritant (see Table 6). Those that are positive The usual approach to patch testing is to have a standardized are graded on a scale of +, ++ or +++.60 A number of factors baseline screening series, which will pick up approximately may affect this stage. Principal among these are the character80% of allergens.66,67 These series vary from country to counistics of the individual allergens and the method of patch testtry and should be revised on a regular basis. There are two ing. Care should be taken not to confuse the clinical principal baseline series, differing between the U.S.A. andEurappearance of the reaction with interpretation of whether this ope. Experienced dermatologists adapt these series by adding reactionrepresents anirritant orallergic reaction.61 allergens thatmay beofimportance or relevancelocally. Some allergens are more likely to cause irritant reactions The British Society for Cutaneous Allergy (BSCA) revises its than others. These reactions may be difficult to interpret and baseline series regularly, removing allergens such as those that are misclassified easily as positive reactions.62 The metal salts diminish in relevance and adding important emerging allerfor nickel, cobalt and potassium dichromate, fragrances and genssuch as methylisothiazolinone.68 the carba mix often cause irritant reactions and so are the Supplemental series are also recommended; these are most frequently misinterpreted allergens in the baseline series. important where the baseline series fails to pick up less comA face-to-face lecture on assessing the morphology of patchmon allergens such as fragrances or rubber chemicals.69 These series areoutlined in Appendix 1. Table6 ScoringofpatchtestreactionsaccordingtoInternational SupplementalseriesshouldbeusedtocomplementthebaseContactDermatitisResearchGrouprecommendations60 line series for particular body sites or types of agents to which the patient is exposed (Appendices 1 and 2). The patient\u2019s Symbol Morphology Interpretation own cosmetics, toiletries and topical medications should be \u2013 Noreaction Negative tested at nonirritant concentrations. This usually means \u2018as is\u2019 ? Erythemaonly,noinfiltration Doubtfulreaction (undiluted product) for leave-on products but requires dilu- + Erythema,infiltration,possibly Weakpositive tions in water for wash-off products. Strong irritants such as discretepapules reaction powder detergents should not be patch-tested. Also, occupa- ++ Erythema,infiltration,papules, Strongpositive tional products should be tested at nonirritant concentrations. vesicles reaction +++ Erythema,infiltration,confluent Extremepositive The most useful compendium of reported test concentrations vesicles reaction and recommended vehicles for chemicals, groups of chemicals ir Differenttypesofreactions(soap Irritantreaction andproductsisthatproducedbyDeGroot.", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 6}, {"text": "be tested at nonirritant concentrations. vesicles reaction +++ Erythema,infiltration,confluent Extremepositive The most useful compendium of reported test concentrations vesicles reaction and recommended vehicles for chemicals, groups of chemicals ir Differenttypesofreactions(soap Irritantreaction andproductsisthatproducedbyDeGroot.70 effect,vesicles,blister,necrosis) Guidelines for testing materials brought from the workplace nt Nottested can be found in the Handbook of Occupational Dermatology.71 However, false-positive and false-negative results often occur when BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 6}, {"text": "BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 323 patch testing products brought by the patient, and should be of allergen is advised with follow-up to confirm/refute the interpreted withcare. hypothesis; (iii) a definite diagnosis cannot be made \u2013 further patch testing may be required and further information obtained from the patient/workplace, to determine the mate6.6 Photopatch testing rials/series thatneed tobetested. Where photoallergic contact dermatitis is suspected, photopatch testing may be carried out.72 While the exact intervals 7.1 Occupationalcontact dermatitis/workplace visit for irradiation and the dose of UVA given vary from centre to centre, the recommended method of photopatch testing Where occupational exposure as a contributing factor to the involves the application of a photoallergen series,73 and any dermatitisissuspected,aworkplacevisitcan:(i)helpdetermine suspected patient materials, in duplicate, on either side of the which allergens need to be considered; (ii) identify hidden upper back. On removal of allergen patches at 2 days,74 one allergensafteranegativepatchtest;(iii)givecluesastowhya side is irradiated with 5 J cm (cid:3)2 UVA and readings are taken patienthasfailedtorespondtoavoidanceofanallergenorirriin parallel afterafurther 2 days.75 tant; (iv) help assess procedures in the work environment and The incidence of true photoallergy in suspected cases is identify areas of possible accidental exposure/contamination; low, at < 5%, although additional readings after day 4 (v)helppreventfurtherunnecessaryexposuretoirritants. increase thedetectionrate.76 Visits shouldbeorganized inconjunction withon-site nursing/medical/safety personnel as their presence during the visit is often invaluable. Material Safety Data Sheets (MSDS) should 6.7 Openpatchtesting be requested for all materials to which workers are exposed. The open patch test is used commonly in cases where potenHowever, these are only required to list those chemicals that tial irritants or sensitizers are being assessed. It is also useful have been assigned a Hazard Statement in accordance with in the investigation of contact urticaria and protein contact U.K. regulations. As there are hundreds of chemicals that have dermatitis. The open patch test is usually performed by applynever been so assigned but can cause contact dermatitis, the ing the suspected agent \u2018as is\u2019 on the skin of the forearm. The risk assessment should consider the work activity, including application site should be assessed regularly for the first all substances hazardous to health, including those used, pro30\u201360 minandafurtherreadingcarriedoutafter3or4 days. duced andcreatedas wasteor asby-products.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 7}, {"text": "for the first all substances hazardous to health, including those used, pro30\u201360 minandafurtherreadingcarriedoutafter3or4 days. duced andcreatedas wasteor asby-products. A repeated open-application test, applying the suspect agent Therefore, it is important to ensure that the normal workon the volar aspect of the forearm, is also useful in the assessing procedures are active on the day of the visit and that the ment of cosmetics and personal-care products where irritancy particular process in question is being carried out on the day or combination effects may interfere with standard patch testof the visit, in order to determine accurately what workers are ing. Usually, this involves application of the product \u2018as is\u2019 actually doing in practice rather than in theory. It is important twice dailyfor 5\u201310 days, stopping ifareactiondevelops. to record as accurately as possible the details of the visit: personnel present, sections visited, processes observed and sources ofpossible exposuretoirritants andallergens.80 6.8 Postinvestigation counselling Information on the allergen(s), its sources and how to avoid 7.2 Avoidance it should be given, backed up with written or online information appropriate to the patient\u2019s level of understanding. It is Avoidance of allergens and irritants is the cornerstone of the important to highlight different names for the same product management of OSD. Assessment of safety procedures at the to the patient. Even with such provision, only 17% rememworkplace visit is needed to eliminate sources of exposure and bered the name of the allergen after 10 years, according to remove the allergen/irritant if a suitable substitute is available. one study, despite 79% of patients remembering that they Personal protective equipment such as clothing or gloves may have hadapositive patch testresult.77 be an adequate solution, although less likely to be effective with potent sensitizers and airborne allergens/irritants. It may be necessary to move the patient to a different area; changing 7.0 Intervention and treatment (management/ occupation is usually the last resort. However, this may be treatment options) preferable,particularlyifseverecontactdermatitis isdiagnosed The cause of contact dermatitis is frequently multifactorial,78 early in training(e.g. hairdressers). and patients may have irritant and/or atopic/endogenous dermatitis in addition toallergic contact dermatitis, particularly in 7.3 Protection occupations such as hairdressing.", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 7}, {"text": "dermatitis in addition toallergic contact dermatitis, particularly in 7.3 Protection occupations such as hairdressing.79 There are three scenarios when patch testing is completed: Protection of the skin against contact with an allergen most (i)acleardiagnosisismade\u2013includingtheexclusionofallercommonly involves the use of gloves in hand dermatitis. The gic contact dermatitis, and appropriate advice and treatment nature of the allergen or irritants involved will determine given; (ii) a possible diagnosis is made \u2013 a trial of avoidance which type of gloves should be used (Appendix 3), and it is \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 7}, {"text": "324 BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. important to check the MSDS to determine the permeation specifically in the treatment of contact dermatitis (see Suppletime for the glove being used. Latex gloves are penetrated by mentary Information). methyl methacrylate in 1 min. Nitrile (5 min), butyl (15 min) and three-layer PVP gloves (20 min; polyethylene 7.7 Diets outer and inner layer, ethylene vinyl copolymer middle layer) givebetter protection, butnone is completelyimpermeable.81 There are no good-quality studies to support exclusion diets It is also important to protect the hands outside the workin themanagementof contactdermatitis.109,110 ing environment. Rubber or polyvinylchloride gloves with a cotton lining are recommended for general household tasks. 8.0 Prognosis (follow-up) There is some evidence that prolonged glove use impairs stratum corneum barrier function;82 however, the clinical releIn a Swedish study, only 25% of 555 patients diagnosed with vance of this is unclear.83\u201385 Barrier creams have shown occupational contact dermatitis had completely healed over a promise in vitro,86 and in volunteers in the prevention of occu10-year period; 50% still had intermittent symptoms and 25% pational hand dermatitis,87 but their efficacy in the workplace had permanent symptoms. In 40% who changed their occupais less certain. Workers who use barrier creams have better tion, the overall prognosis was not improved.111 In an Ausskin-quality scores and reduced transepidermal water loss than tralian study, 55% of 949 patients still had dermatitis after thosewhodonot,88,89butthismaynottranslateintoasignif2 yearsfromdiagnosis. Theprognosis formildercasesofconicant clinicaldifference.90 tact dermatitis depends upon the ease of avoidance.112 The long-term prognosis for occupational contact dermatitis is often verypoor.113 7.4 Substitution Replacement of soaps and detergents with emollients is useful, 8.1 Why is theprognosissometimes so poor? eveniftheyarenotthecauseofthedermatitis,astheyareirritants which will compound the situation.91,92 It is also often Continuation of the exposure \u2013 knowingly or unknowingly \u2013 possible to substitute different materials both in the workplace can occur. Allergens such as chromium, epoxy resin and and outside so that the implicated allergen or irritant can be Compositae appear to trigger chronic dermatitis, even after avoided. Typical examples include the use of thiuram-free avoidance.114,115 Risk factors for a poor prognosis include the gloves,changing biocidesin industrialcoolant oilsandtheuse severity andextentofdermatitis at presentation.116 of isothiazolinone-free creams/cleansers in those patients in whomcontactallergyhasbeenidentifiedtotheseallergens. 8.2 Doeducational interventions help? Educationalprogrammesmayhelpinsecondarypreventionand 7.5 Education outcomes forchronic occupational contactdermatitis.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 8}, {"text": "gloves,changing biocidesin industrialcoolant oilsandtheuse severity andextentofdermatitis at presentation.116 of isothiazolinone-free creams/cleansers in those patients in whomcontactallergyhasbeenidentifiedtotheseallergens. 8.2 Doeducational interventions help? Educationalprogrammesmayhelpinsecondarypreventionand 7.5 Education outcomes forchronic occupational contactdermatitis.94,96,117 Studies in occupational settings have demonstrated improvements in established hand dermatitis after comprehensive 8.3 Shouldajob change berecommended? intervention education programmes.93\u201396 The prevention of hand dermatitis with similar programmes has also been If a worker can completely change their job, that is, elimireported.93,97 Compliance with skin-protection programmes is nate their exposure if suffering from allergic contact often poor.98 Owing to the very low-quality studies identified dermatitis or exposure reduction in the case of irritant conand marginal benefits observed (see Supplementary Informatact dermatitis, they have a better chance of the dermatitis tion), neither education on an individualized basis nor a forclearing.113,116 mal course could be recommended over the other in preventing handdermatitis. 9.0 Practical and economic considerations The management of contact dermatitis includes diagnosis, 7.6 Treatment of persistentcontact dermatitis treatment and prevention. There are few studies that look at Therapy for contact dermatitis persisting despite allergen/irrieconomic considerations. tant removal and skin protection largely follows the management of atopic/endogenous dermatitis. Studies support the 9.1 What istheeconomic burdenofsuffering from efficacy of topical steroids and topical tacrolimus in the treatcontactdermatitis? ment of contact dermatitis.99\u2013104 Second-line treatment includes phototherapy and systemic immunomodulators such The annual societal cost of patients suffering from occupaas methotrexate and mycophenolate mofetil. Psoralen plus tional contact dermatitis is high and comparable with patients UVA, ciclosporin and alitretinoin have been demonstrated to withsevere atopic/endogenous dermatitis or psoriasis.118 be useful in chronic hand dermatitis,105\u2013107 and azathioprine The costs of suffering from contact dermatitis have been in chronic actinic dermatitis,108 but none has been assessed reported as amounting to approximately \u20ac2300 for BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 8}, {"text": "BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 325 occupational contact dermatitis and \u20ac1000 for nonoccuparecognize this may exclude some important information pubtional contact dermatitis per patient per annum.119 As contact lished in otherlanguages. dermatitis is so common, this represents a substantial economic burden. 12.0 Plans for guideline revision The proposed revision date for this set of recommendations is 9.2 Isitworthwhile managing patients withcontact scheduled for 2022; where necessary, important interim dermatitis inamultidisciplinary clinic? changes willbeupdatedon theBAD website. Integrated care programmes with a multidisciplinary team, including a dermatologist specializing in patch testing, a speAcknowledgments cialized nurse and an occupational physician, have been proposed for patients with moderate-to-severe hand dermatitis We are very grateful to patient representatives Wayne Greenfelttobeworkrelated,andthemajorityofwhom wouldhave halghandFrankZagorski,andtheBritishSocietyforCutaneous at least an element of contact dermatitis. These have been Allergycommitteefortheirinvaluableinput,aswellasallthose found tobeeffectivein improving outcomes intheshort term whocommentedonthedraftduringtheconsultationperiod. compared with standard care (patch testing and management by a dermatologist).120 However, this difference disappears References after 12 months. Integrated careprogrammes costsubstantially more thanstandard care(\u20ac3613 vs.\u20ac1576 per patient). 1 Mohd Mustapa MF, Exton LS, Bell HK etal. Update on writing a BritishAssociationofDermatologistsclinicalguideline:theadoptionoftheGRADEmethodology.BrJDermatol2017;176:44\u201351. 10.0 Recommended audit points 2 Brouwers MC, Kho ME, Browman GP etal. AGREE II: advancing guideline development, reporting and evaluation in health care. In the last 20 consecutive patients diagnosed with contact derCMAJ2010;182:E839\u201342. matitis, is there evidence of: (i) the provision of a patient 3 GRADE. GRADE Working Group. Available at: http:// information leaflet on patch testing, which includes informawww.gradeworkinggroup.org/(lastaccessed16March2016). tion on potential side-effects; (ii) informed consent; (iii) 4 Guyatt GH, Oxman AD, Vist GE etal. GRADE: an emerging conapplication of the appropriate national or international basesensus on rating quality of evidence and strength of recommendations.BMJ2008;336:924\u20136. line series; (iv) application of all allergens at the correct con5 Barbaud A, Poreaux C, Penven E etal. Occupational protein concentration and in the correct vehicle; (v) prescription of tactdermatitis.EurJDermatol2015;25:527\u201334. further allergens during the tests to clarify doubtful reactions, 6 Lindberg M, Edman B, Fischer T etal. Time trends in Swedish ifapplicable;(vi)accurateinterpretation ofthepatch-testreacpatch test data from 1992 to 2000. A multi-centre study based tions as either allergic or irritant, and documentation of releon ageand sex-adjusted results of the Swedish standard series. vance; (vii) recording of any adverse outcomes of patch ContactDermatitis2007;56:205\u201310.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 9}, {"text": "irritant, and documentation of releon ageand sex-adjusted results of the Swedish standard series. vance; (vii) recording of any adverse outcomes of patch ContactDermatitis2007;56:205\u201310. testing and actions taken, if applicable; (viii) a discharge letter 7 Thyssen JP, Linneberg A, Menne T etal. Contact allergy to allergens of the TRUE-test (panels 1 and 2) has decreased modestly with a clinical diagnosis and allergen-specific information, inthegeneralpopulation.BrJDermatol2009;161:1124\u20139. where applicable; (ix) collation of local patch-test results into 8 Diepgen TL, Ofenloch RF, Bruze M etal. Prevalence of contact a database; (x) benchmarking of local patch test results against allergy in the general population in different European regions. national collated figures? BrJDermatol2016;174:319\u201329. The audit recommendation of 20 cases per department is to 9 StocksSJ,McNameeR,TurnerSetal.HasEuropeanUnionlegisreduce variation in the results due to a single patient, and lation to reduce exposure to chromate in cement been effective allow benchmarking between different units. However, in reducingtheincidenceofallergiccontactdermatitisattributed tochromateintheUK?OccupEnvironMed2012;69:150\u20132. departments unable to achieve this recommendation may 10 Johansen J, Menn(cid:1)e T, Christophersen J etal. Changes in the patchoose toauditallcases seenin thepreceding12 months. tern of sensitization to common contact allergens in Denmark between1985\u201386and1997\u201398,withaspecialviewtotheeffect 11.0 Limitations of the guideline ofpreventivestrategies.BrJDermatol2000;142:490\u20135. 11 Roto P, Sainio H, Reunala T etal. Addition of ferrous sulfate to This document has been prepared on behalf of the BAD and is cement and risk of chromium dermatitis among construction based on the best data available when the document was preworkers.ContactDermatitis1996;34:43\u201350. 12 TEG. The European Directive restricting the use of Nickel. Availpared. It is recognized that under certain conditions it may be able at: http://www.teg.co.uk/nickel/94-27-EC.htm (last necessary to deviate from the guidelines and that the results of accessed14April2016). future studies may require some of the recommendations 13 TEG.TheEuropeanDirectiveupdaterestrictingtheuseofNickel. herein to be changed. Failure to adhere to these guidelines Available at: http://www.teg.co.uk/nickel/2004-96-EC.htm (last should not necessarily be considered negligent, nor should accessed14April2016). adherence to these recommendations constitute a defence 14 Johnston GA. The rise in prevalence of contact allergy to against a claim of negligence. Limiting the review to Englishmethylisothiazolinone in the British Isles. Contact Dermatitis 2014; 70:238\u201340. language references was a pragmatic decision, but the authors \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 9}, {"text": "was a pragmatic decision, but the authors \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 9}, {"text": "326 BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 15 Meyer JD, Chen Y, Holt DL etal. Occupational contact dermatitis 38 FowlerJFJr,MaibachHI,ZirwasMetal.Effectsofimmunomodin the UK: a surveillance report from EPIDERM and OPRA. Occup ulatory agents on patch testing: expert opinion 2012. Dermatitis Med(Lond)2000;50:265\u201373. 2012;23:301\u20133. 16 Turner S, McNamee R, Agius R etal. Evaluating interventions 39 Wee JS, White JM, McFadden JP etal. Patch testing in patients aimed at reducing occupational exposure to latex and rubber treated with systemic immunosuppression and cytokine inhibigloveallergens.OccupEnvironMed2012;69:925\u201331. tors.ContactDermatitis2010;62:165\u20139. 17 WarburtonKL,UrwinR,CarderMetal.UKratesofoccupational 40 Sjovall P, Christensen OB. Local and systemic effect of ultraviolet skin disease attributed to rubber accelerators, 1996\u20132012. Contact irradiation(UVBandUVA)onhumanallergiccontactdermatitis. Dermatitis2015;72:305\u201311. ActaDermatovenereol1986;66:290\u20134. 18 Admani S, Jacob SE. Allergic contact dermatitis in children: 41 NethercottJR,HolnessDL. Thepositivepredictivevalueofpatch reviewofthepastdecade.CurrAllergyAsthmaRep2014;14:421. testsintheevaluationofpatientswithsuspectedcontactdermati19 Lagrelius M, Wahlgren CF, Matura M etal. High prevalence of tis.ImmunolAllergyClinNorthAm1989;9:549\u201354. contact allergy in adolescence: results from the population-based 42 Frick-Engfeldt M, Gruvberger B, Isaksson M etal. Comparison of BAMSEbirthcohort.ContactDermatitis2016;74:44\u201351. three different techniques for application of water solutions to 20 Cronin E. Clinical prediction of patch test results. Trans St. Johns FinnChambers(R).ContactDermatitis2010;63:284\u20138. HospDermatolSoc1972;58:153\u201362. 43 Hamann D, Hamann CR, Hamann C. A contemporary fischer21 Podmore P, Burrows D, Bingham EA. Prediction of patch test maibach investigation: variations in patch test delivery systems results.ContactDermatitis1984;11:283\u20134. andimplicationsforstandardization.Dermatitis2013;24:302\u201312. 22 ClaytonTH,WilkinsonSM,RawcliffeCetal.Allergiccontactder44 Mose KF, AndersenKE, Christensen LP. Stabilityof selectedvolamatitis in children: should pattern of dermatitis determine refertile contact allergens in different patch test chambers under difral? A retrospective study of 500 children tested between 1995 ferentstorageconditions.ContactDermatitis2012;66:172\u20139. and2004inoneU.K.centre.BrJDermatol2006;154:114\u201317. 45 SiegelPD,FowlerJF,LawBFetal.Concentrationsandstabilityof 23 Agner T, Jungersted JM, Coenraads PJ etal. Comparison of four methyl methacrylate, glutaraldehyde, formaldehyde and nickel methods for assessment of severity of hand eczema. Contact Dersulfate in commercial patchtest allergenpreparations. ContactDermatitis2013;69:107\u201311. matitis2014;70:309\u201315. 24 van der Valk PG, van Gils RF, Boot CR etal. A simple tool with 46 Joy NM, Rice KR, Atwater AR. Stability of patch test allergens. which to study the course of chronic hand eczema in clinical Dermatitis2013;24:227\u201336. practice:areduced-itemscore.ContactDermatitis2013;69:112\u201317. 47 McDonald BS, Buckley DA. Patch testing practice in the U.K. Br J 25 Bhushan M, Beck MH. An audit to identify the optimum referral Dermatol2013;169:45. rate to a contact dermatitis investigation unit. Br J Dermatol 1999; 48 Lachapelle JM, Bruynzeel DP, Ducombs G etal. European multi141:570\u20132. centerstudyoftheTRUETest.ContactDermatitis1988;19:91\u20137. 26 StathamB,MughalA,BodgerO.Therelationshipbetweenthepro49 Fischer T,MaibachHI. Easierpatchtesting withTRUETest.JAm portionofthepopulationtestedannuallyandtherateofpatients AcadDermatol1989;20:447\u201353. withpositivepatchtestreactions.ContactDermatitis2011;64:54\u20137. 50 TRUE Test Study Group.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 10}, {"text": "a contact dermatitis investigation unit. Br J Dermatol 1999; 48 Lachapelle JM, Bruynzeel DP, Ducombs G etal. European multi141:570\u20132. centerstudyoftheTRUETest.ContactDermatitis1988;19:91\u20137. 26 StathamB,MughalA,BodgerO.Therelationshipbetweenthepro49 Fischer T,MaibachHI. Easierpatchtesting withTRUETest.JAm portionofthepopulationtestedannuallyandtherateofpatients AcadDermatol1989;20:447\u201353. withpositivepatchtestreactions.ContactDermatitis2011;64:54\u20137. 50 TRUE Test Study Group. Comparative multicenter studies with 27 Goulden V, Wilkinson SM. Evaluation of a contact allergy clinic. TRUE Test and Finn Chambers in eight Swedish hospitals. J Am ClinExpDermatol2000;25:67\u201370. AcadDermatol1989;21:846\u20139. 28 Spornraft-RagallerP,SchnuchA,UterW.Extremepatchtestreac51 Wilkinson JD, Bruynzeel DP, Ducombs G etal. European multitivity to p-phenylenediamine but not to other allergens in chilcenter study of TRUE Test, Panel 2. Contact Dermatitis 1990; dren.ContactDermatitis2011;65:220\u20136. 22:218\u201325. 29 PaulsenE,AndersenKE.ScreeningforCompositaesensitizationwith 52 Lachapelle JM, Antoine JL. Problems raised by the simultaneous pure allergens: implications of molecular structure, strength of reproducibility of positive allergic patch test reactions in man. J reaction,andtimeoftesting.ContactDermatitis2011;64:96\u2013103. AmAcadDermatol1989;21:850\u20134. 30 Ponten A, Goossens A, Bruze M. Recommendation to include 53 Brasch J, Szliska C, Grabbe J. More positive patch test reactions formaldehyde2.0%aquain theEuropeanbaselinepatchtest serwithlargertestchambers?ResultsfromastudygroupoftheGeries.ContactDermatitis2013;69:372\u20134. man Contact Dermatitis Research Group (DKG). Contact Dermatitis 31 Ryberg K, Goossens A, Isaksson M etal. Patch testing with a tex1997;37:118\u201320. tile dye mix and its constituents in a baseline series. Dermatitis 54 Doumit J, Pratt M. Comparative study of IQ-ultra and Finn 2010;21:49\u201356. Chambers test methodologies in detecting 10 common standard 32 Dawe SA, White IR, Rycroft RJ etal. Active sensitization to paraallergens that cause allergic contact dermatitis. J Cutan Med Surg phenylenediamineanditsrelevance:a10-yearreview.ContactDer2012;16:18\u201322. matitis2004;51:96\u20137. 55 GefellerO,PfahlbergA,GeierJetal.Theassociationbetweensize 33 Bruynzeel DP, Maibach HI. Excited skin syndrome (angry back). of test chamber and patch test reaction: a statistical reanalysis. ArchDermatol1986;122:323\u20138. ContactDermatitis1999;40:14\u201318. 34 Sukanto H, Nater JP, Bleumink E. Influence of topically applied 56 WilkinsonDS,FregertS,MagnussonBetal.Terminologyofconcorticosteroids on patch test reactions. Contact Dermatitis 1981; tactdermatitis.ActaDermatovenereol1970;50:287\u201392. 7:180\u20135. 57 ShehadeSA,BeckMH,HillierVF.Epidemiologicalsurveyofstan35 Clark RA, Rietschel RL. 0.1% triamcinolone acetonide ointment dardseriespatchtestresultsandobservationsonday2andday4 andpatchtestresponses.ArchDermatol1982;118:163\u20135. readings.ContactDermatitis1991;24:119\u201322. 36 Green C. The effect of topically applied corticosteroid on irritant 58 Torp Madsen J, Andersen KE. Outcome of a second patch test andallergicpatchtestreactions.ContactDermatitis1996;35:331\u20133. reading of TRUE Tests(R) on D6/7. Contact Dermatitis 2013; 37 Anveden I, Lindberg M, Andersen KE etal. Oral prednisone sup68:94\u20137. presses allergic but not irritant patch test reactions in individuals 59 JonkerMJ,BruynzeelDP.Theoutcomeofanadditionalpatch-test hypersensitivetonickel.ContactDermatitis2004;50:298\u2013303. readingondays6or7.ContactDermatitis2000;42:330\u20135. BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 10}, {"text": "59 JonkerMJ,BruynzeelDP.Theoutcomeofanadditionalpatch-test hypersensitivetonickel.ContactDermatitis2004;50:298\u2013303. readingondays6or7.ContactDermatitis2000;42:330\u20135. BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 10}, {"text": "BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 327 60 FregertS.ManualofContactDermatitisonBehalfoftheInternationalContact 81 Darre E, Vedel P, Jensen JS. Skin protection against methylDermatitis Research Group and the North American Contact Dermatitis Group, methacrylate.ActaOrthopScand1987;58:236\u20138. 2ndedn.Copenhagen:MunksgaardPublishers,1981. 82 Ramsing DW, Agner T. Effect of glove occlusion on human skin 61 Johnston GA. Standardization of patch tests and the doctors who (II). Long-term experimental exposure. Contact Dermatitis 1996; readthem.BrJDermatol2009;161:493\u20135. 34:258\u201362. 62 UterW,FroschPJ,BeckerDetal.Arewe biasedwhenreadinga 83 BoyleDK,ForsythA,BaggJetal.Aninvestigationoftheeffectof doubtful patch test reaction to a \u2018clear-cut\u2019 allergen such as the prolonged glove wearing on the hand skin health of dental thiurammix?ContactDermatitis2009;60:234\u20135. healthcareworkers.JDentistry2002;30:233\u201341. 63 Svedman C, Isaksson M, Bjork J etal. \u2018Calibration\u2019 of our patch 84 Wetzky U, Bock M, Wulfhorst B etal. Shortand long-term test reading technique is necessary. Contact Dermatitis 2012; effects of single and repetitive glove occlusion on the epidermal 66:180\u20137. barrier.ArchDermatolRes2009;301:595\u2013602. 64 Geier J, Uter W, Lessmann H etal. The positivity ratio \u2013 another 85 Weistenho\u20acferW,WackerM,BernetFetal.Occlusiveglovesandskin parametertoassessthediagnosticqualityofapatchtestpreparaconditions:isthereaproblem?Resultsofacross-sectionalstudyina tion.ContactDermatitis2003;48:280\u20132. semiconductorcompany.BrJDermatol2015;172:1058\u201365. 65 Warshaw EM, Nelsen DD, Sasseville D etal. Positivity ratio and 86 Schliemann S, Petri M, Elsner P. Preventing irritant contact derreaction index: patch-test quality-control metrics applied to the matitis with protective creams: influence of the application dose. North American Contact Dermatitis group database. Dermatitis ContactDermatitis2014;70:19\u201326. 2010;21:91\u20137. 87 WilliamsC,WilkinsonSM,McShanePetal.Adouble-blind,ran66 SherertzEF,SwartzSM.Isthescreeningpatchtesttraystillworth domizedstudytoassesstheeffectivenessofdifferentmoisturizers using?JAmAcadDermatol1993;29:1057\u20138. in preventing dermatitis induced by hand washing to simulate 67 Menn(cid:1)e T, Dooms-Goossens A, Wahlberg JE etal. How large a healthcareuse.BrJDermatol2010;162:1088\u201392. proportion of contact sensitivities are diagnosed with the Euro88 Ku\u20actting B, Baumeister T, Weistenh\u20acofer W etal. Effectiveness of peanstandardseries?ContactDermatitis1992;26:201\u20132. skin protection measures in prevention of occupational hand 68 Bruze M, Engfeldt M, Goncalo M etal. Recommendation to eczema: results of a prospective randomized controlled trial over includemethylisothiazolinoneintheEuropeanbaselinepatchtest afollow-upperiodof1year.BrJDermtol2010;162:362\u201370. series \u2013 on behalf of the European Society of Contact Dermatitis 89 WinkerR,SalamehB,StolkovichSetal.EffectivenessofskinproandtheEuropeanEnvironmentalandContactDermatitisResearch tection creams in the prevention of occupational dermatitis: Group.ContactDermatitis2013;69:26\u2013370. results of a randomized, controlled trial. Int Arch Occup Environ 69 Mann J, McFadden JP, White JM etal. Baseline series fragrance Health2009;82:653\u201362. markers fail to predict contact allergy. Contact Dermatitis 2014; 90 Bauer A, Schmitt J, Bennett C etal. Interventions for preventing 70:276\u201381. occupational irritant hand dermatitis. Cochrane Database Syst Rev 70 de Groot AC. Patch Testing. Test Concentrations and Vehicles for 3700 2010;(6):CD004414. Chemicals,2ndedn.Amsterdam:Elsevier,1994. 91 Lauharanta J, Ojaj\u20acarvi J, Sarna S etal. Prevention of dryness and 71 Jolanki R, Estlander T, Alanko K etal.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 11}, {"text": "Database Syst Rev 70 de Groot AC. Patch Testing. Test Concentrations and Vehicles for 3700 2010;(6):CD004414. Chemicals,2ndedn.Amsterdam:Elsevier,1994. 91 Lauharanta J, Ojaj\u20acarvi J, Sarna S etal. Prevention of dryness and 71 Jolanki R, Estlander T, Alanko K etal. Patch testing with a eczema of the hands of hospital staff by emulsion cleansing patient\u2019sownmaterialshandledatwork.In:HandbookofOccupational insteadofwashingwithsoap.JHospInfect1991;17:207\u201315. Dermatology (Kanerva L, Elsner P, Maibach MD, Howard I, eds), 92 Halkier-S\u00f8rensen L, Thestrup-Pedersen K. The efficacyof a moisBerlin:Springer-Verlag,2000,375\u201383. turizer (Locobase) among cleaners and kitchen assistants during 72 British Photodermatology Group. Photopatch testing \u2013 methods everydayexposuretowateranddetergents.ContactDermatitis1993; andindications.BrJDermatol1997;136:371\u20136. 29:266\u201371. 73 GoncaloM,FergusonJ,BonevalleAetal.Photopatchtesting:rec93 vanGilsRF,BootCR,vanGilsPFetal.Effectivenessofprevention ommendations for a European photopatch test baseline series. programmesforhanddermatitis:asystematicreviewoftheliterContactDermatitis2013;68:239\u201343. ature.ContactDermatitis2011;64:63\u201372. 74 Batchelor RJ, Wilkinson SM. Photopatch testing \u2013 a retrospective 94 van Gils RF, Boot CR, Knol DL etal. The effectiveness of intereview using the 1day and 2day irradiation protocols. Contact grated care for patients with hand eczema: results of a randomDermatitis2006;54:75\u20138. ized,controlledtrial.ContactDermatitis2012;66:197\u2013204. 75 European Multicentre Photopatch Test Study Taskforce. A Euro95 WilkeA,GedigaG,SchlesingerTetal.Sustainabilityofinterdiscipean multicentre photopatch test study. Br J Dermtol 2012; plinary secondary prevention in patients with occupational hand 166:1002\u20139. eczema: a 5-year follow-up survey. Contact Dermatitis 2012; 76 Bryden AM, Moseley H, Ibbotson SH etal. Photopatch testing of 67:208\u201316. 1155 patients: results of the U.K. multicentre photopatch study 96 Ibler KS, Jemec GB, Diepgen TL etal. Skin care education and group.BrJDermtol2006;155:737\u201347. individual counselling versus treatment as usual in healthcare 77 JamilWN,ErikssohnI,LindbergM.Howwellistheoutcomeof workers with hand eczema: randomised clinical trial. BMJ 2012; patchtestingrememberedbythepatients?A10-yearfollow-upof 345:e7822. testingwiththeSwedishbaselineseriesattheDepartmentofDer97 Bregnhoj A, Menne T, Johansen JD etal. Prevention of hand matologyinOrebro,Sweden.ContactDermatitis2012;66:215\u201320. eczema among Danish hairdressing apprentices: an intervention 78 Agner T, Aalto-Korte K, Andersen KE etal. Classification of hand study.OccupEnvironMed2012;69:310\u201316. eczema.JEurAcadDermatolVenereol2015;29:2417\u201322. 98 Ku\u20actting B, Weistenh\u20acofer W, Baumeister T etal. Current accep79 LyonsG,RobertsH,PalmerAetal. Hairdressers presentingtoan tance and implementation of preventive strategies for occupaoccupational dermatology clinic in Melbourne, Australia. Contact tional hand eczema in 1355 metalworkers in Germany. Br J Dermatitis2013;68:300\u20136. Dermtol2009;161:390\u20136. 80 English JSC. Occupational dermatoses. In: Rook\u2019s Textbook in Derma99 Hachem JP, De Paepe K, Vanp(cid:1)ee E etal. Efficacy of topical cortitology (Burns DA, Breathnach SM, Griffiths C, Cox NH, eds), 7th costeroids in nickel-induced contact allergy. Clin Exp Dermatol edn.Oxford:BlackwellPublishing,2004;21.8\u20139. 2002;27:47\u201350. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 11}, {"text": "eds), 7th costeroids in nickel-induced contact allergy. Clin Exp Dermatol edn.Oxford:BlackwellPublishing,2004;21.8\u20139. 2002;27:47\u201350. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 2, "page": 11}, {"text": "328 BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 100 Hachem JP, De Paepe K, Vanp(cid:1)ee E etal. Combination therapy 119 Saetterstr\u00f8m B, Olsen J, Johansen JD. Cost-of-illness of patients improves the recovery of the skin barrier function: an experiwith contact dermatitis in Denmark. Contact Dermatitis 2014; mental model using a contact allergy patch test combined with 71:154\u201361. TEWLmeasurements.Dermatology2001;202:314\u201319. 120 van Gils RF, Bosmans JE, Boot CR etal. Economic evaluation of 101 Parneix-Spake A, Goustas P, Green R. Eumovate (clobetasone an integrated care programme for patients with hand dermatitis. butyrate) 0.05% cream with its moisturizing emollient base has ContactDermatitis2013;69:144\u201352. better healing properties than hydrocortisone 1% cream: a study 121 National Institutefor Health and CareExcellence.Alitretinoinfor in nickel-induced contact dermatitis. J Dermatol Treat 2001; the treatment of severe chronic hand eczema. Available at: 12:191\u20137. https://www.nice.org.uk/guidance/ta177 (last accessed 27 April 102 Queille-Roussel C, Duteil L, Padilla JM etal. Objectiveassessment 2016). of topical anti-inflammatory drug activity on experimentally induced nickel contact dermatitis: comparison between visual Appendix 1 scoring, colorimetry, laser Doppler velocimetry and transepidermalwaterloss.SkinPharmacol1990;3:248\u201355. 103 Vernon HJ, Olsen EA. A controlled trial of clobetasol propionate BritishSocietyforCutaneousAllergy-recommendedbaselineseries ointment0.05%inthetreatmentofexperimentallyinducedRhus dermatitis.JAmAcadDermatol1990;23:829\u201332. Potassiumdichromate 0(cid:1)50% pet. 104 BelsitoD,WilsonDC,WarshawEetal.Aprospectiverandomized Neomycinsulfate 20(cid:1)00% pet. clinical trial of 0.1% tacrolimus ointment in a model of chronic Thiurammix 1(cid:1)00% pet. allergiccontactdermatitis.JAmAcadDermatol2006;55:40\u20136. p-Phenylenediamine 1(cid:1)00% pet. 105 Ros(cid:1)en K, Mobacken H, Swanbeck G. Chronic eczematous derCobaltchloride 1(cid:1)00% pet. matitis ofthehands:acomparisonofPUVA andUVB treatment. CaineMixIII 10(cid:1)00% pet. ActaDermatovenereol1987;67:48\u201354. Formaldehyde 2(cid:1)00% aq. 106 GranlundH,ErkkoP,ReitamoS.Comparisonoftheinfluenceof Colophony 20(cid:1)00% pet. cyclosporineandtopicalbetamethasone-17,21-dipropionatetreatQuinolinemix 6(cid:1)00% pet mentonqualityoflifeinchronichandeczema.ActaDermatovenereol Myroxylonpereirae(BalsamofPeru) 25(cid:1)00% pet. 1997;77:54\u20138. N-Isopropyl-N-phenyl-4-phenylenediamine 0(cid:1)10% pet. 107 Ruzicka T, Lynde CW, Jemec GB etal. Efficacy and safety of oral Lanolinalcohol 30(cid:1)00% pet. alitretinoin (9-cis retinoic acid) in patients with severe chronic Mercaptomix 2(cid:1)00% pet. handeczemarefractorytotopicalcorticosteroids:resultsofaranEpoxyresin 1(cid:1)00% pet. domized, double-blind, placebo-controlled, multicentre trial. Br J Parabensmix 16(cid:1)00% pet. Dermatol2008;158:808\u201317. 4-tert-Butylphenolformaldehyderesin 1(cid:1)00% pet. 108 MurphyGM,MauricePD,NorrisPGetal.Azathioprinetreatment FragrancemixI 8(cid:1)00% pet. in chronicactinicdermatitis:adouble-blindcontrolled trialwith Quaternium15(Dowicil200) 1(cid:1)00% pet. monitoring of exposure to ultraviolet radiation. Br J Dermatol Nickelsulfate 5(cid:1)00% pet. 1989;121:639\u201346. Cl+Me-isothiazolinone 0(cid:1)02% aq. 109 Veien NK, Hattel T, Laurberg G. Low nickel diet: an open, Mercaptobenzothiazole 2(cid:1)00% pet. prospectivetrial.JAmAcadDermatol1993;29:1002\u20137. AmercholL101 50(cid:1)00% pet. 110 AnticoA,SoanaR.Chronicallergic-likedermatopathiesinnickelSesquiterpenelactonemix 0(cid:1)10% pet. sensitive patients. Results of dietary restrictions and challenge p-Chloro-m-Cresol 1(cid:1)00% pet. withnickelsalts.AllergyAsthmaProc1999;20:235\u201342. 2-Bromo-2-nitropropane-1,3-diol(Bronopol) 0(cid:1)50% pet. 111 Fregert S. Occupational dermatitis in a 10-year material. Contact Cetearylalcohol 20(cid:1)00% pet. Dermatitis1975;1:96\u2013107. Sodiumfusidate 2(cid:1)00% pet. 112 Wall LM, Gebauer KA.", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 12}, {"text": "sensitive patients. Results of dietary restrictions and challenge p-Chloro-m-Cresol 1(cid:1)00% pet. withnickelsalts.AllergyAsthmaProc1999;20:235\u201342. 2-Bromo-2-nitropropane-1,3-diol(Bronopol) 0(cid:1)50% pet. 111 Fregert S. Occupational dermatitis in a 10-year material. Contact Cetearylalcohol 20(cid:1)00% pet. Dermatitis1975;1:96\u2013107. Sodiumfusidate 2(cid:1)00% pet. 112 Wall LM, Gebauer KA. A follow-up study of occupational skin Tixocortol-21-pivalate 1(cid:1)00% pet. diseaseinWesternAustralia.ContactDermatitis1991;24:241\u20133. Budesonide 0(cid:1)10% pet. 113 Malkonen T, Alanko K, Jolanki R etal. Long-term follow-up Imidazolidinylurea(Germal115) 2(cid:1)00% pet. study of occupational hand eczema. Br J Dermatol 2010; Diazolidinylurea(Germal11) 2(cid:1)00% pet. 163:999\u20131006. Methyldibromoglutaronitrile 0(cid:1)30% pet. 114 BauerA,GeierJ,MahlerVetal.[ContactallergiesintheGerman Ethylenediaminedihydrochloride 1(cid:1)00% pet. workforce: data of the IVDK network from 2003\u20132013]. Hautarzt 4-Chloro-3,5-xylenol(PCMX) 0(cid:1)50% pet. 2015;66:652\u201364[inGerman]. Carbamix 3(cid:1)00% pet. 115 CahillJ,KeegelT,DharmageSetal.PrognosisofcontactdermatiDisperseBlueMix106/124 1(cid:1)00% pet. tisinepoxyresinworkers.ContactDermatitis2005;52:147\u201353. FragrancemixII 14(cid:1)00% pet. 116 Petersen AH, Johansen JD, Hald M. Hand eczema-prognosis and Hydroxyisohexylcyclohexene 5(cid:1)00% pet. consequences: a 7-year follow-up study. Br J Dermatol 2014; carboxaldehyde(Lyral) 171:1428\u201333. CompositaeMix(Chemotechnique) 2(cid:1)50% pet. 117 ApfelbacherCJ,SoderS,DiepgenTLetal.Theimpactofmeasures Methylisothiazolinone 0(cid:1)20% aq. for secondaryindividual preventionofwork-relatedskin diseases Sodiummetabisulfite 1(cid:1)00% pet. in health care workers: 1-year follow-up study. Contact Dermatitis 2009;60:144\u20139. 118 Diepgen TL, Scheidt R, Weisshaar E etal. Cost of illness from occupational hand eczema in Germany. Contact Dermatitis 2013; 69:99\u2013106. BritishJournalofDermatology(2017)176,pp317\u2013329 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 12}, {"text": "BADguidelinesforcontactdermatitis2017, G.A.Johnstonetal. 329 Appendix 2 Supporting Information AdditionalSupportingInformationmaybefoundintheonline Commerciallyavailableadditionalpatchtestseries version ofthis article atthepublisher\u2019s website: Trolab(cid:1) ChemotechniqueDiagnostics Study selection Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram, summary Antimicrobial,preservativeand Bakery of findings with forest plots, Grading of Recommendations antioxidant Cosmetics Corticosteroid Assessment, Development and Evaluation (GRADE) evidence Dentalmaterials Cosmetics profiles indicating the quality of evidence, Linking the EviHairdressing Dentalscreening dence to the Recommendations (LETR), list of excluded studMedicament(including Epoxy ies andsearch strategy. corticosteroids,antibiotics,local anaestheticsandophthalmics) Metalcompounds Fragrance Metalworking/technicaloils Hairdressing Perfumeandflavours Isocyanate Photoallergens Legulcer Photographicchemicals Medicament Plant Adhesives,dentalandother (meth)acrylate Plasticsandglues Nails\u2013artificial(meth)acrylate Rubberchemicals Printing(meth)acrylate Sunscreenagents Oilandcoolingfluid Textileandleatherdyes Photographicchemicals Vehiclesandemulsifiers Plant Miscellaneous Plasticsandglues Rubberadditives Scandinavianphotopatchtest Shoe Sunscreen Textilecoloursandfinish Variousallergens Appendix 3 Aguidetowhichgloveswillgivesomedegreeofprotectionfor specifictypesofhazard Hazard Typeofglove Microorganisms NRL,thermoplasticelastomer Disinfectants NRL,PVC,PE,EMA Pharmaceuticals NRL(permeabilitytimeveryshort) Compositematerials Nitrile,4H(cid:1)glove (e.g.acrylates) Solvents PE,PVC,nitrile,NRL,neoprene, butylrubber,Viton(cid:1),4H(cid:1)glove Corrosives NRL,PE,PVC,neoprene,butylrubber, Viton(cid:1),4H(cid:1)glove Detergents NRL,EMA,PE,neoprene,PVC,nitrile (ifadditionoforganicsolvents) Machiningoils NRL,PVC,nitrile,neoprene,4H(cid:1)glove NRL,naturalrubberlatex;PVC,polyvinylchloride;PE,polyethylene;EMA,ethylenemethylmethacrylate. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp317\u2013329 Downloaded from https://academic.oup.com/bjd/article/176/2/317/6601881 by guest on 23 February 2026", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 13}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "contact dermatitis guideline.pdf", "chunk_id": 0, "page": 14}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "contact dermatitis guideline.pdf", "chunk_id": 1, "page": 14}, {"text": "BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists guidelines for the management of people with cutaneous squamous cell carcinoma 2020* S.G. Keohane1,2 J. Botting,3,4 P.G. Budny,5,6 O.M. Dolan iD,7 K. Fife iD,8,9 C.A. Harwood iD,10 R. Mallipeddi,1,11 J.R. Marsden,12 R.J. Motley iD,13 C. Newlands,14,15 C. Proby iD,16 A. Rembielak iD,8,17,18 D.N. Slater iD,19 J.A. Smithson,20,21 P. Buckley,22 P. Fairbrother,23 M. Hashme,24 M.F. Mohd Mustapa iD,24 L.S. Exton iD 24 and the British Association of Dermatologists\u2019 Clinical Standards Unit 1British Societyfor Dermatological Surgery, London,UK 2PortsmouthHospitals University NHS Trust,Portsmouth, PO3 6AD, UK 3Royal Collegeof GeneralPractitioners, London,UK 4Glebe Road Surgery,Barnes, SW13 0DR, UK 5British Association of PlasticReconstructive andAesthetic Surgeons, London,UK 6Buckinghamshire HealthcareNHS Trust, Aylesbury,HP21 8AL,UK 7Royal VictoriaHospital,Belfast Health and SocialCare Trust, Belfast,BT12 6BA,UK 8Royal Collegeof Radiologists, Holborn, London,WC2A 3JW, UK 9CambridgeUniversity Hospitals NHS FoundationTrust, Cambridge, CB2 0QQ,UK 10BartsHealth NHSTrust, Centrefor CellBiology and CutaneousResearch, Blizard Institute, Queen MaryUniversity of London,London, E12AT, UK 11StJohn\u2019s Institute of Dermatology, Guy\u2019sand StThomas\u2019 NHSFoundation Trust, London, SE19RT, UK 12Queen ElizabethHospital, Edgbaston, Birmingham, B15 2TH, UK 13University Hospitalof Wales, Health Park,Cardiff, CF14 4XN,UK 14British Associationof Oral &Maxillofacial Surgeons, London, UK 15RoyalSurrey CountyHospital NHSFoundation Trust, Guildford, GU2 7XX, UK 16University of Dundee,Ninewells Hospital andMedical School,Dundee, DD19SY,UK 17The ChristieNHS FoundationTrust, Manchester, M20 4BX,UK 18The University of Manchester, Manchester, M139PL,UK 19RoyalCollegeof Pathologists, London, E18BB, UK 20British Dermatological Nursing Group, Belfast, UK 21EastSussexHealthcare NHSTrust, Eastbourne, BN21 2UD, UK 22Patientrepresentative 23Independent CancerPatients\u2019 Voice, London,UK 24British Associationof Dermatologists, WillanHouse, 4 Fitzroy Square,London, W1T 5HQ, UK NICEhasrenewedaccreditationoftheprocess Correspondence usedbytheBritishAssociationofDermatologists toproduceclinicalguidelines.TherenewedaccredSteveKeohane. itationisvaliduntil31May2021andapplies Emails:stephen.keohane@porthosp.nhs.uk;guidelines@bad.org.uk toguidanceproducedusingtheprocessesdescribed Accepted forpublication intheupdatedguidanceforwritingaBritish AssociationofDermatologistsclinicalguideline\u2013 17October2020 theadoptionoftheGRADEmethodology2016. ConflictsofintereststatementscanbefoundintheAppendix. Theoriginalaccreditationtermbeganon12May 2010.Moreinformationonaccreditationcanbe ThisisanupdatedguidelinepreparedfortheBritishAssociationofDermatologists(BAD) viewedatwww.nice.org.uk/accreditation. ClinicalStandardsUnit,whichincludestheTherapy&GuidelinesSubcommittee.Members oftheClinicalStandardsUnitwhohavecontributedareN.J.Levell(Chair,Therapy& *Plainlanguagesummaryavailableonline GuidelinesSubcommittee),B.McDonald,A.Salim,S.L.Chua,G.Petrof,A.Bardhan,P. Rakvit,M.Hashme(BADInformationScientist),L.S.Exton(BADGuidelineResearch DOI10.1111/bjd.19621 Fellow)andM.F.MohdMustapa(BADDirectorofClinicalStandards). Producedin2002bytheBritishAssociationofDermatologists(BAD).Reviewedand Linked Comment: Leiter-Sto\u20acppke. BrJDermatol2021; 184: updated2009,2020. 384\u2013385. \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 401 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 1}, {"text": "402 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. Purpose and scope importance to patients, ranked according to the GRADE methodology7 (see section 2.1; and Appendix A; see SupportThe overall objective of the guideline is to provide up-toingInformation). date, evidence-based recommendations for the management of The GDG agreed to adopt the Royal College of Pathologists cutaneous squamous cell carcinoma (cSCC). The document dataset for the histological reporting of cSCC.8 Along with aims to (cid:129) Public Health England, this endorses the Union for Internaoffer an appraisal of allrelevant literature up to 30 January tional Cancer Control 8th edition (UICC8)9 (Tables 1 and 2), 2020,focusing on anykey developments, (cid:129) rather than the American Joint Committee on Cancer 8th ediaddress important, practical clinical questions relating to tion cancer staging manual, which covers only head and neck (cid:129) theprimary guideline objective,and cSCC.10 The GDG agreed that risk is part of a spectrum and provide guideline recommendations and if appropriate not dichotomous, and the evidence from the literature researchrecommendations. searches supported a division based on low-, highand very The guideline is presented as a detailed review with highhigh-risk status. As shown in Figure 1, this division was lighted recommendations for practical use in primary, secachieved by integrating clinical, pathological, tumour\u2013nodes\u2013 ondary and tertiary care, in the clinic and in the appropriate metastasis(TNM) staging andmargin criteria. skin cancer multidisciplinary team (MDT) meetings (see section 3.0). These may be either local skin MDTs (LSMDTs) or specialist skin cancer MDTs (SSMDTs), depending on the cliniTable1 TNM8(tumour\u2013nodes\u2013metastasis)classificationforcutaneous copathological features of the SCC. Clinicians treating people squamouscellcarcinoma(cSCC)9 with cSCC should be core members of the appropriate MDT or sanctioned by the MDT to treat the tumour.1 There is also Tcategories an updated patient information leaflet available on the BAD T1 \u22642cmingreatestdimension website (https://www.skinhealthinfo.org.uk/a-z-conditionsT2 >2to4cmingreatestdimension T3 >4cmingreatestdimensionorminorboneerosion treatments/). orspecifiedperineuralinvasion(\u22650.1mmdiameter and/ordeeperthanthedermisand/oranamed nerve)ordeepinvasion(thickness>6mmand/or Exclusions beyondthesubcutaneousfat) The guidelinedoesnot cover T4a Tumourwithgrosscorticalbone/marrowinvasion (cid:129) noncutaneous primary SCC or SCC in situ (Bowen disease); T4b Tumourwithskullbaseoraxialskeletoninvasion there is aseparate guidelinefor SCC insitu,2 includingforaminalinvolvementand/orvertebral (cid:129) forameninvolvementtotheepiduralspace mucosal SCC; for the lip the remit of this guideline stops Ncategoriesfornon-headandneck atthevermillion border, or N1 Metastasisinasinglenode\u22643cmingreatest (cid:129) secondary prevention.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 2}, {"text": "Metastasisinasinglenode\u22643cmingreatest (cid:129) secondary prevention.3,4 dimension N2 Metastasisinasingleipsilaterallymphnode,>3cm but\u22646cmorinmultipleipsilateralnodeswithnone Methodology >6cmingreatestdimension N3 Metastasisinalymphnode>6cmingreatest This set of guidelines has been developed using the BAD\u2019s dimension recommended methodology;5 further information can be Ncategoriesheadandneckregion N1 Metastasisinasingleipsilaterallymphnode\u22643cmin found in Appendix J (see Supporting Information) with greatestdimensionwithoutENEa reference to the AGREE II instrument (www.agreetrust. N2a Metastasisinasingleipsilaterallymphnode>3cm org)6 and GRADE (https://www.gradeworkinggroup.org). but<6cmingreatestdimensionwithoutENE Recommendations were developed for implementation in N2b Metastasisinmultipleipsilaterallymphnodes,where the UK National Health Service (NHS). noneare>6cmingreatestdimensionwithoutENE The guideline development group (GDG) consisted of N2c Metastasisinbilateralorcontralaterallymphnodes, seven consultant dermatologists (representing England, Northwherenoneare>6cmingreatestdimension withoutENE ern Ireland, Scotland and Wales), two consultant clinical N3a Metastasisinasingleormultiplelymphnodes>6cm oncologists (radiation oncologists), a consultant plastic suringreatestdimensionwithoutENE geon, a consultant maxillofacial surgeon, a dermatopatholoN3b Metastasisinasingleormultiplelymphnodeswith gist, a general practitioner, a Macmillan dermatology clinical ENE nurse specialist, two patient representatives and a technical Mcategories team (consisting of an information scientist, a guideline M0 Nodistantmetastasis research fellow and a project manager providing methodologM1 Distantmetastasis(includingcontralateralnodesin non-headandneckcSCC) ical and technical support). The GDG established several clinical questions pertinent to aExtranodalextension(ENE)canbeclinicalorpathological. the scope of the guideline and a set of outcome measures of BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 2}, {"text": "BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. 403 Table2 TNM8(tumour\u2013nodes\u2013metastasis)stagegroupsforcSCC9 ranked according to the GRADE methodology7 by the patient representatives. This uses a nine-point scale, with Stage T N M outcomes ranked 9 being those the patient representatives I T1 N0 M0 considered most important. Outcomes ranked 9, 8 or 7 are II T2 N0 M0 critical for decision-making; those ranked 6, 5 or 4 are III T3 N0 M0 important but not critical for decision-making; and those T1,T2,T3 N1 M0 ranked 3, 2 or 1 are the least important for decision-makIVA T1,T2,T3 N2,N3 M0 ing. Data on these outcome measures were extracted from T4 AnyN M0 the included studies (Appendixes B, C, E, F and G; see SupIVB AnyT AnyN M1 porting Information). Review question 1:treatment In people with \u2018higher-risk\u2019 primary cSCC, how clinically A systematic literature search of the PubMed, MEDLINE, effective are surgical (standard and Mohs) and nonsurgical Embase and Cochrane databases was conducted by the technitreatments (radiotherapy and electrochemotherapy) compared cal team to identify key articles on cSCC from 1 January 2007 with eachother? to 30 January 2020; the search terms and strategies are (cid:129) Survivorship 9 detailed in Appendix K (see Supporting Information). Addi- (cid:129) Recurrence rate 9 tional references relevant to the topic were also isolated from (cid:129) Cosmetic outcome7 citations in the reviewed literature and the previous versions (cid:129) of the guidelines.11,12 Data extraction, critical appraisal and Convenience oftreatment 7 data synthesis were performed by the technical team, who Review question 2:treatment prepared theevidence summaries, lists of excluded studies and In people with low-risk primary cSCC how clinically effecPRISMA diagram. Evidence from included studies was rated tive are surgical (standard excision, Mohs, curettage and cauaccording to the GRADE system (high, moderate, low or very tery, cryosurgery and carbon dioxide laser) and nonsurgical low quality). treatments (topical therapies, photodynamic therapy or radioRecommendations are based on evidence drawn from therapy) compared with each other or with no treatment (obsystematic reviews of the literature pertaining to the cliniservation)? (Radiotherapy includes brachytherapy where cal questions identified, following discussions with the appropriate.) entire GDG and factoring in all four factors that would (cid:129) Convenience oftreatment 9 affect their strength ratings according to the GRADE (cid:129) Cosmetic outcome7 approach (i.e.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 3}, {"text": "appropriate.) entire GDG and factoring in all four factors that would (cid:129) Convenience oftreatment 9 affect their strength ratings according to the GRADE (cid:129) Cosmetic outcome7 approach (i.e. balance between desirable and undesirable (cid:129) Recurrence rate 7 effects, quality of evidence, patient values and preferences, and resource allocation). All GDG members contributed Review question 3:surgical margin towards drafting and/or reviewing the narratives and In people with cSCC who undergo standard surgical exciinformation in the guideline and supporting information sion, whatsurgical marginandsurgical planeshould beused? (cid:129) documents. When there was insufficient evidence from the Lackofclinical recurrenceafter5 years9 (cid:129) literature, informal consensus was reached based on the Lackofclinical recurrenceafter2 years9 experience of the GDG. Review question 4:involved margins The summary of findings with forest plots (Appendix B), In people with cSCC who undergo excision of the primary clinical evidence summary (Appendix C), tables Linking the tumour and where histological analysis shows either one or Evidence To the Recommendations (LETR) (Appendix D), more involved or clear-but-close margins (< 1 mm), what is GRADE evidence profiles indicating the quality of evidence theappropriate subsequent management? (Appendix E), summary of included studies (Appendix F), (cid:129) Survivorship 9 narrative findings for noncomparative studies (Appendix G), (cid:129) Recurrence 9 PRISMAflow diagram(AppendixH) andlist ofexcludedstudies (Appendix I) are detailed in the Supporting Information. Review question 5:adjuvant radiotherapy The strength of recommendation is expressed by the wording In people with primary cSCC following surgical excision andsymbols shownin Table 3. with clear histological margins, what is the role of adjuvant radiotherapy in reducing the risk of local recurrence? [\u2018Adjuvant\u2019 in the guidelines refers to any treatment (radioClinical questions andoutcomes therapy) after primary treatment (surgery).] (cid:129) The GDG established a number of clinical questions pertiSurvivorship 9 (cid:129) nent to the scope of the guideline (for a full review protoRecurrence rate 9 (cid:129) col see Appendix A in the Supporting Information). The Cosmetic outcome7 (cid:129) GDG also established a set of outcome measures of imporConvenience oftreatment 6 (cid:129) tance to patients for each clinical question, which were Patient-reported outcomes 6 \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 3}, {"text": "from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 2, "page": 3}, {"text": "roopfoksirhtiwdetaicossasrotcaF.tnetnievitaruchtiwyregruslanoisicxeneebsahtnemtaerterehw,CCScyramirpotsetalerecnadiuglarrefersihT.sTDMSSdnasTDMSLotlarreferrofecnadiuG 1erugiF lareneg ,PG ;amonicrac llec suomauqs suoenatuc ,CCSc 81\u201331.sisylana etairavitlum ro etairavinu gnisu seiduts elpitlum ni )htaed cfiiceps-esaesid ,sisatsatem ladon ,ecnerrucer lacol( semoctuo detaler-esaesid .maet yranilpicsiditlum recnac niks tsilaiceps ,TDMSS ;ycneicfiedonummi denibmoc ereves ,DICS ;maet yranilpicsiditlum recnac niks lacol ,TDMSL ;ypareht larivorteritna evitca ylhgih ,TRAAH ;renoititcarp ]moc.yrarbilenilnoyeliwtadeweivebnacerugfiruoloC[.TDMkcendnadaehehtfoairetircehtrepebdluohskcendnadaehehtnisnisabladonfoweiveR* 404 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 4}, {"text": "BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. 405 Table3 Strengthofrecommendationratings Strength Wording Symbol Definition Strongrecommendationfor \u2018Offer\u2019(orsimilar,e.g.\u2018use\u2019, \u2191\u2191 Benefitsoftheinterventionoutweightherisks;mostpatientswould theuseofanintervention \u2018provide\u2019,\u2018take\u2019,\u2018investigate\u2019 choosetheinterventionwhileonlyasmallproportionwouldnot; etc.) forclinicians,mostoftheirpatientswouldreceivethe intervention;forpolicymakers,itwouldbeausefulperformance indicator Weakrecommendationfor \u2018Consider\u2019 \u2191 Risksandbenefitsoftheinterventionarefinelybalanced;most theuseofanintervention patientswouldchoosetheinterventionbutmanywouldnot; clinicianswouldneedtoconsidertheprosandconsforthe patientinthecontextoftheevidence;forpolicymakersitwould beapoorperformanceindicatorwherevariabilityinpracticeis expected Norecommendation \u0398 Insufficientevidencetosupportanyrecommendation Strongrecommendation \u2018Donotoffer\u2019 \u2193\u2193 Risksoftheinterventionoutweighthebenefits;mostpatients againsttheuseofan wouldnotchoosetheinterventionwhileonlyasmallproportion intervention would;forclinicians,mostoftheirpatientswouldnotreceivethe intervention Review question 6:metastatic squamous cellcarcinoma diagnosed cSCC. All recommendations would also generally In people with any metastasis from cSCC how clinically relate to children, young people and adults, unless specified effective are standard surgical and nonsurgical treatments otherwise. Those under 24 years of age with cSCC should be (chemotherapeutic therapy, radiotherapy, immunotherapy) managed by the SSMDT but must additionally be referred to comparedwitheachotherorwithnotreatment(observation)? the appropriate children\u2019s, teenagers\u2019 or young adults\u2019 service (Radiotherapyincludesbrachytherapywhereappropriate.) for their specific expertise. These guidelines do not include specific recommendations for subungual or periungual SCCs. (cid:129) Survivorship 9 For further information on the wording used for recom- (cid:129) Recurrence rate 9 mendations and strength of recommendation ratings see (cid:129) Cosmetic outcome7 Table 3. The evidence for recommendations is based on the (cid:129) Convenience oftreatment 7 studies as listed (for details and discussion of the evidence see (cid:129) Patient-reported outcomes 6 AppendixesB\u2013FintheSupportingInformation).TheGDGrecReview question 7:follow-up ommendations relating to referral pathways are based on disIn people with a diagnosed higher-risk cSCC what is the cussion and clinical experience, as evidence-based details are appropriate follow-up periodfollowing treatment? not available at the time of writing. The GDG is aware of the (cid:129) Survivorship 9 lack of high-quality evidence for some of these recommenda- (cid:129) Recurrence 9 tions, and therefore strong recommendations with an asterisk (cid:129) Metastases 9 (*) are based on available evidence, as well as consensus and (cid:129) Patient-reported outcomes 6 specialist experience. Good practice point (GPP) recommendations are derived frominformal consensus. Note: in Mohs surgery the tumour is curetted or surgically debulked, and the defect usually excised with a small (1\u20132 Pretreatment mm) margin of surrounding skin. The patient waits with a dressed wound pending histological confirmation by the Mohs R1 (\u2191\u2191) ObtainhistologicalconfirmationofcSCClesionsinthe surgeon that the tumour has been completely removed. If eventofdiagnosticuncertainty,beforeplanningdefinitivetreatresidual tumour is identified, a further layer of tissue is ment.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 5}, {"text": "a further layer of tissue is ment. This must be a representative sample of the tumour; in removed, and the process repeated until the surgical wound is most instances, this will be a full-thickness incisional biopsy confirmed to be tumour free. The wound is then repaired by ideallyincorporatingboththeperipheralandthedeepmargins. conventional surgical techniques. R2 (GPP) Offer discussion on the risks and benefits of all treatment options (outcomes, function, cosmesis) to people Summary of recommendations with cSCC and their families or carers and make the treatment decision together. There are few randomized controlled trials (RCTs) to support the following guidelines for the management of cSCC. The R3 (\u2191\u2191) Record the maximum clinical cSCC lesion dimension following recommendations and ratings were agreed upon priortoanydiagnosticortreatmentprocedure(usuallydiameunanimously by the core members of the GDG and patient ter, in millimetres), the plane of the deep-excision margin, representatives. The recommendations cover suspected and whether it is a recurrent tumour or in field of previous \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 5}, {"text": "406 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. radiotherapy, and the immune status of the patient, on the Multidisciplinary team discussion specimen request form forthepathologist. R9 (GPP) Document the risk status of cSCC tumour as low R4(GPP)Takeagood-qualityclinicalphotograph ofthecSCC risk,highriskorveryhighriskinthepatientnotes(Figure1). lesion for the patient record to aid future management and assessment of the area after healing. In multisite disease the R10 (\u2193\u2193) T1 cSCC tumours excised with histologically clear lesions to be treated should ideally be marked on the phomargins of at least 1 mm, in the absence of other high-risk tograph tolimittherisk ofwrong-site procedures. factors,donot need routine discussion atanMDT(Figure 1). R11 (\u2191\u2191) Review the histology of people with cSCC with one or more involved or clear-but-close margins (< 1 mm) at an Treatment options forprimary cutaneoussquamous cell appropriate skinMDT(Figure 1). carcinoma R12 (\u2191) Consider the risk factors for the patient and the marStandard surgical excision gin, site and tumour stage in people with cSCC with one or R5 (\u2191\u2191) Offer* standard surgical excision as the first-line more clear-but-close margins (< 1 mm). Consider observation in immunocompetent people with cSCC with a low-risk treatment option topeople withresectableprimary cSCC. tumour (Figure 1). R6 (\u2191\u2191) Peripheral tumour margins should be determined R13 (\u2191\u2191) Offer further wide local excision (with likely under bright lighting and magnification or dermoscopy. Excise*with aclinicalperipheral surgical margin of delayed reconstruction), Mohs micrographic surgery, or adjuvant radiotherapy to people with cSCC with one or more (cid:129) \u22654mm foralow-risk cSCCtumour, involved margins, or close margins (< 1 mm), where patient (cid:129) \u22656mm forahigh-risk cSCCtumour, or tumour factorsconfer higher risk. (cid:129) \u226510mm foravery high-risk cSCCtumour. R14 (GPP) Offer active treatment to immunosuppressed peoFordefinition ofthelevels ofrisk seeFigure 1.13\u201318 ple with cSCC with one or more clear-but-close (< 1 mm) or R7 (\u2191\u2191) Ensure at least a 1-mm histological clearance of cSCC involved margins withstructured follow-up andsurveillance. excisions at all margins by including sufficient peripheral and R15 (\u2191\u2191) Discuss at an SSMDT people with cSCC with sympdeep tissues (see R6 for appropriate standard surgical excision tomatic perineural invasion and/or radiological evidence of margins). perineural invasion. If discussed at a skin MDT, skull base or (cid:129) head and neck MDT opinion may be required.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 6}, {"text": "at a skin MDT, skull base or (cid:129) head and neck MDT opinion may be required. Aggressive surFor mobile lesions the deep margin should be within the gical excision of the involved nerve should be the first step, next clear surgical plane, and on the scalp the excision where technically possible, followed by consideration of adjushouldinclude thegalea. (cid:129) vant radiotherapy. For deeply infiltrating or fixed lesions at any site, achieving an uninvolved deep histological margin may require inclusion of one or more of the following \u2013 fascia, musMohs micrographic surgery cle, bone or other underlying structure \u2013 which may be determinedclinically or by imaging, or both. R16 (\u2191) Consider Mohs micrographic surgery in selected peo- (cid:129) Consideration should be given to excision of a further, ple with cSCC following SSMDT discussion, particularly where orientated, deep-margin specimen where possible, if there tumour margins are difficult to delineate or in sites where tisis clinical concern at the time of resection that the resecsue conservation is importantfor function. tion is closeor incomplete. (cid:129) Whenever possible confirm uninvolved histological marRadiotherapy: primary andpostoperative (adjuvant gins by paraffin section analysis prior to reconstruction radiotherapy) involving complex tissue rearrangement where dressings or temporizing cover can reasonably be achieved. HowR17 (\u2191\u2191) Discuss people with histologically proven cSCC ever, in the context of extensive ablative resections (e.g. being considered for radiotherapy at an MDT (LSMDT or scalp into the calvarium or abutting dura, ear\u2013parotid\u2013 SSMDT)withaclinical oncologist present. temporal bone, composite maxillofacial resections etc.) R18(\u2191\u2191)Offer primary radiotherapy this approach is unlikely to be feasible due to immediate (cid:129) to selected people with cSCC as a treatment option followreconstructive requirements. (cid:129) ing appropriate discussion at the appropriate skin MDT Where there is extensive disease, and/or involvement of and/or with a clinical or radiation oncologist, factoring in specific anatomical areas, consider liaising with one or patientpreference, and moreadditional MDTdepending on thesite ofthecSCC. (cid:129) topeoplewithcSCCwhensurgeryisnotfeasibleorwould R8 (\u2191\u2191) Manage and report excised cSCC specimens according be challenging or likely to result in an unacceptable functotheRoyalCollege ofPathologists dataset.8 tional oraesthetic outcome. BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 6}, {"text": "Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 2, "page": 6}, {"text": "BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. 407 R19 (\u2191)Consider adjuvantradiotherapy inpeople withcSCC (cid:129) who are immunocompromised and with locally advanced (cid:129) if pathological excision margins are clear but close (< 1 and/or metastaticcSCC, mm) following discussion at an appropriate skin MDT, (cid:129) within transit metastases fromcSCC, and where aclinical oncologist is present,and (cid:129) with metastatic cSCC who have had further locoregional (cid:129) withcompletelyexcisedT3tumours,wheretherearemulrelapse followinglymphadenectomy. tiple high-risk factors, including those > 6 mm in thickness(depth) andinvasion beyond subcutaneous fat. R28 (GPP) Where assessment of the anatomical extent of a primary cSCC warrants imaging, consider including regional R20 (\u2191\u2191) Offer adjuvant radiotherapy to people with incomlymph nodesin thescan. pletely excised cSCC, where further surgery is not possible (or is not chosen by the patient) and in those at high risk of local R29 (GPP) Only consider sentinel lymph node biopsy for recurrence specific, high-risk cases of primary cSCC in the context of a (cid:129) inthecaseofperineuralinvasion(multifocal,namednerve clinical trialor SSMDTdiscussion.3 and/ordiameterofnerve>0(cid:1)1mm,belowthedermis), R30 (GPP) Offer ultrasound-guided fine-needle aspiration (cid:129) in recurrent disease, and cytologytopeoplewithcSCCwithclinicallysuspiciousnodes.If (cid:129) in thosewho are immunocompromised (see R21). they are negative and suspicion remains, this can be repeated, R21 (\u2193\u2193) Do not offer postoperative radiotherapy to people althoughcoreoropen-biopsyhistologymayberequired. with completely excised T1 or T2 cSCC and with microscopic, R31 (GPP) Undertake high-resolution magnetic resonance dermal-only, nerve diameter< 0(cid:1)1mmperineural invasion. imaging (MRI) of the involved area in people with cSCC with R22 (\u2191) Consider conformal radiotherapy including the entire in transit metastasis or regional perineural invasion of named course of the involved nerve in people with cSCC with sympnerves. Discuss with a radiologist if MRI is contraindicated. tomatic perineural invasion and/or radiological evidence of (In transit metastasis is a type of metastasis in which skin canperineural invasion when surgery is inappropriate, after carecer spreads through a lymph vessel and begins to grow fully weighing the benefits and side-effects from radiotherapy between theareaofprevious treatment andthenodalbasin.) tosuch an extensive radiotherapy treatment field. R32(\u2191\u2191)OffertherapeuticregionallymphadenectomytopeoR23 (GPP) Inform younger people with cSCC (age < 60 ple with head and neck cSCC with regional lymph node years), especially if they are an organ transplant recipient, of metastasis. (Regionallymphadenectomy isasurgical procedure the very low risk of radiation-induced, in-field malignancy in in which the lymph nodes that drain the site of the tumour the future.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 7}, {"text": "an organ transplant recipient, of metastasis. (Regionallymphadenectomy isasurgical procedure the very low risk of radiation-induced, in-field malignancy in in which the lymph nodes that drain the site of the tumour the future. Take this risk into account when making any treatare removedtoanextentthat hastherapeutic rather thandiagment decision. nostic or palliative intent. The tissue is subsequently checked underthemicroscopeforsignsofcancer.)Imagingisrequired preoperatively to define the extent of locoregional relapse, and Curettage andcautery to identify distant metastatic disease (also see R36). The head R24 (\u2191) Consider curettage and cautery with curative intent and neck imaging should include locoregional MRI or comin immunocompetent people with small (< 1 cm), well-deputed tomography (CT), and CT imaging of the chest as a fined, nonrecurrent, clinically low-risk cSCC. minimum. The surgery should be performed by a designated surgeon who is a core member of the SSMDT pathway and R25 (GPP) Review the histology of cSCC removed by curetcompliant withprevailing multispecialtyguidance. tage and cautery to identify high-risk or very high-risk fea- (cid:129) Where the parotid gland has proven nodal metastasis and tures. Ifthese are identified, thecaseshould bediscussed atan the neck is cN0, a therapeutic parotidectomy, usually the appropriate MDTregarding further management. superficial lobe alone, should be combined with an elective selective neck dissection of levels I\u2013III. If an anterior Locally advanced, recurrentandmetastatic cutaneous scalp or temple primary site has proven neck nodal metassquamous cellcarcinoma tasis, consideration should be given to an elective superficial parotidectomy at the time of therapeutic neck nodal R26 (GPP) Do not routinely offer imaging of the draining dissection. nodal basin to people with cSCC in the absence of suspected (cid:129) Wheretheneckhasprovennodalmetastasis,thetherapeutic or clinically detectable regional nodal involvement. Very highneckdissectionshouldincludelevelsandstructurestomaxirisk lesions, such as pT2 or greater lip cSCC, carry a high risk mizetumourclearance,whileminimizingunnecessarymorof occult metastasis and consideration can be given to highbidity. It may be appropriate to preserve a clinically and resolution ultrasound scan of the regional nodes in the cliniradiologicallyuninvolvedlevelIwheretheprimarytumour cally N0setting. wasposterior,thustocarryoutaposterolateralneckdissecR27 (\u2191\u2191) Initiate an individualized SSMDT, multimodality and tionoflevelsII\u2013V.Considerationcanalsobegiventopreserimaging treatment plan forpeople vationofanuninvolved,levelVwheretheprimarytumour (cid:129) withregional lymphnode metastasis, sitewasinthecentrallowerface. \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 7}, {"text": "by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 2, "page": 7}, {"text": "408 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. (cid:129) consideration for best supportive care should be made. EGFR Nodes in the superficial system, such as the occipital inhibitors are unlicensed forcSCCin theUK. nodes, or external jugular node should also be included in a dissection, according to the primary site, and the identiR39 (GPP) Consider electrochemotherapy in people with fiedsitesofmetastasis. locally advanced cSCC in palliative settings if other local or R33(\u2191\u2191)Offertherapeuticregionallymphadenectomytopeosystemictherapies arenot appropriate. ple with non-head and neck cSCC with regional lymph node metastases in axillary, inguinofemoral or other peripheral Follow-up draining nodes. Imaging is required preoperatively to define R40 (\u2191\u2191) Offer access to a key worker to people with cSCC, the extent of locoregional relapse, and to identify distant ideally a clinical nurse specialist, as part of an ongoing treatmetastatic disease (also see R36). In the axilla, CT imaging ment prevention package.19 Provide information on the diagshould include the neck, chest and axilla as a minimum and the surgery should include levels I\u2013III. In the inguinofemoral nosisandmanagement ofcSCC. region CT imaging should include the chest\u2013abdomen\u2013pelvis R41 (GPP) Follow up people with cSCC by examining the and to midthigh level and the surgery should include superfiskin and lymph node basins and with any other appropriate cial anddeeplevels. clinicalexamination. (cid:129) Therapeutic extended ilio-inguinofemoral lymphadenecR42 (GPP) Educate people with cSCC on self-examination tomy is indicated in those with additional iliac nodal cSCC (skin and lymph nodes) and sun protection by providing onimaging or cytology. (cid:129) appropriate verbal and written information (e.g. www.bad. Elective extended ilio-inguinofemoral lymphadenectomy org.uk/leaflets). should also be considered, at the SSMDT, for people with extensive inguinofemoral relapse (multiple nodes, any > 3 R43(GPP)Offerpeoplewithlow-riskcSCCasinglepost-treatcm, plus or minus extranodal extension) who do not have mentappointment,whereappropriate,tocheckhistopathology concurrent evidence of iliac relapse on imaging or cytolresults,conductskinandnodalsurveillanceandfacilitatepatient ogy but are deemed to be at high risk of microscopic diseducationonself-examinationandsurveillanceofpatients\u2019own easein theextended basin. digitalphotographs(patienteducationcouldhavealreadytaken (cid:129) Nodaldisease atother ectopicsites should haveindividualplaceatthepretreatmentappointment).Provideinformationon izedimagingunder guidance fromtheSSMDT. the5-yearriskofdevelopingfurthercSCCandonhowtoaccess (cid:129) The surgery should be performed by a designated surgeon areferral,includingthe2-week-waitpathwaybackintothesysof the SSMDT pathway who is compliant with prevailing temiftheysuspectanewlesion. multispecialtyguidance. R44 (GPP) Offer people with high-risk cSCC (especially R34 (\u2191\u2191) Offer adjuvant radiotherapy following therapeutic when several risk factors apply) post-treatment follow-up regional lymphadenectomy to people with cSCC with highappointments at 4-monthly intervals for 12 months, then at risk pathology (e.g.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 8}, {"text": "with high-risk cSCC (especially R34 (\u2191\u2191) Offer adjuvant radiotherapy following therapeutic when several risk factors apply) post-treatment follow-up regional lymphadenectomy to people with cSCC with highappointments at 4-monthly intervals for 12 months, then at risk pathology (e.g. two or more nodes, large nodes and 6-monthy intervals for a further 12 months. The initial folextracapsular extension), definedby UICC8as\u2265 pN1. low-up should be with secondary-care clinicians to facilitate skin surveillance and patient education on self-examination. R35 (GPP) Consider surgical resection (with or without adjuLaterappointmentsmaybewithotherclinicians abletorecogvant radiotherapy) or primary radiotherapy in people with nize recurrences and new skin cancers according to local locally recurrent cSCC. arrangements approvedby theappropriateskin MDT. R36 (GPP) Consider regional lymphadenectomy or regional R45 (GPP) Offer people with very high-risk cSCC post-treatlymph node basin irradiation in selected people with cSCC ment follow-up appointments at 4-monthly intervals for 24 for disease control even in the presence of distant metasmonths, then at 6-monthly intervals for a further 12 months. tases, especially in those undergoing multimodality treatThe initial follow-up should be with secondary-care clinicians ment. to facilitate skin surveillance and patient education on self-exR37 (\u2191) Consider immune checkpoint inhibitor treatment in amination. Later appointments may be made with other clinipeople with locally advanced cSCC where curative surgery or cians able to recognize recurrences and new skin cancers radiotherapy is not reasonable, or those with metastatic cSCC, according to local arrangements approved by the appropriate except patients with organ transplants or those who have sigskin MDT. People who have a high risk of developing further nificant autoimmune conditions. high-risk, primary cSCC, such as organ transplant recipients, should remain under lifelongskin surveillance. R38 (\u2191) Consider systemic chemotherapy or epidermal growth factor receptor (EGFR) inhibitors in people with metaR46 (GPP) Offer people with metastatic cSCC post-treatment static cSCC with contraindications to immune checkpoint inhifollow-up appointments at 3-monthlyintervals for24 months, bitors. Responses are generally short lived and chemotherapy then at 6-monthy intervals for a further 36 months, with is poorly tolerated in elderly and frail people, and potential longer-term review dependent on patient factors. BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 8}, {"text": "\u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 2, "page": 8}, {"text": "BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. 409 Imaging should be performed on the basis of clinical findings, experience were used to inform the algorithm and pathway of with SSMDTdiscussion ifappropriate. care(Figures 2and3). Background Insufficient evidence to support anyrecommendation \u0398 There is insufficient evidence to support any recommendaDefinition tion for cryotherapy, CO laser or topical therapies in the 2 Primarycutaneoussquamouscellcarcinoma(cSCC)isamaligtreatment of cSCC. nant tumour that arises from the keratinocytes of the epidermis or its hair follicles. It is locally invasive and has the List ofkeyfutureresearch recommendations potential tometastasize.20 The following list outlines future research recommendations (FRRs). Incidence andaetiology FRR1 Research should identify which clinicopathological or Therateofnonmelanomaskincancerisatleast2(cid:1)4timeshigher molecular factorspredict pooroutcome, which might facilitate ascoring system (1\u20135)for risk. thanthatofthenextmostcommontumourintheUK,whichis breast cancer.21 Recent evidence suggests that this is still an FRR2 Future cancer-related RCTs need to include more people underestimateforskincancerduetounder-reporting.22cSCCis with cSCC,with stratification oftheresults byrisk factors. thesixthmostcommoncancerintheUK21,22anditsincidence FRR3 Future skin cancer clinical studies need to differentiate continues to rise, not only in the UK but also in many other outcomes clearly by histopathology (i.e. SCC or basal cell carcountries.22\u201324Thiswillhaveanincreasingimpactonplanning cinoma) andstage. forNHSservicesandonhistopathologyservices.22,25 FRR4 Prospective, head-to-head RCTs for primary cSCC Its occurrence is usually related to chronic ultraviolet (UV) reporting (i) 5-year recurrence rates, (ii) quality of life and exposure and is therefore especially common in people with (iii) longand short-term adverse effects, including pain, sun-damaged skin, fair skin, albinism and xeroderma pigmenfunction andcosmetic appearance (cid:129) tosum. Additionally, increasing longevity may also be responcomparing surgical interventions with modern standardsible for the increasing incidence of these tumours. It may izedtwo-dimensional histopathology, (cid:129) develop de novo \u2013 as a result of previous exposure to UV and evaluating the role of adjuvant radiotherapy in resected ionizing radiation, or chemicals such as pesticides, herbicides primary cSCC, (cid:129) or arsenic; within chronic wounds, scars, burns, ulcers or comparing further surgery vs. radiotherapy in incomsinus tracts; or from pre-existing lesions such as SCC in situ pletelyresected primary cSCC,and (cid:129) (Bowen disease).23,24 A high incidence of aggressive cSCC is comparing adjuvant radiotherapy (margins, techniques) found in individuals with recessive dystrophic epidermolysis aftersurgical excision ofhigher-risk cSCC. bullosa (RDEB), where it is a major cause of death. In RDEB, FRR5 All future RCTs involving cSCC need to report standardthe aetiology of cSCC is chronic wounding, not UV exposure. ized outcome measures (e.g.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 9}, {"text": "cSCC. bullosa (RDEB), where it is a major cause of death. In RDEB, FRR5 All future RCTs involving cSCC need to report standardthe aetiology of cSCC is chronic wounding, not UV exposure. ized outcome measures (e.g. time to recurrence, standardized Individuals with impaired immune function, for example quality-of-life scales) to facilitate comparisons and pooling of those receiving immunosuppressive drugs following allogeneic data across studies. organ transplantation or for inflammatory disease, and those FRR6 A study evaluating the cost and resource implications of with lymphoma or leukaemia, are at increased risk of this different treatment options for people with cSCC in the UK tumour. Some cSCCs are associated with human papilloNHS healthcare setting. mavirus infection.26 The risk of cSCC with the \u2018biologic\u2019 therFRR7 Alternative immunotherapy strategies suitable for people apies (for inflammatory or haematological disease) has yet to withinoperable,locallyadvancedcSCC,not amenabletoradibeaccurately quantified.27,28 cal radiotherapy, or metastatic cSCC in whom immune checkThere is good evidence linking cSCCs with chronic actinic point inhibitors are contraindicated. damage(includingthatfromtheuseoftanningdevices)29and FRR8 There is a need for a review of the treatments of cSCC to support sun avoidance, use of protective clothing and effecin those who are at increased risk of developing SCC (e.g. tive sun blocks30 in the prevention of actinic keratoses and those withimpaired immunity or genetic conditions). cSCCs. These measures are particularly important for people FRR9 The role of sentinel lymph node biopsy in the staging receiving long-term immunosuppressive medication.31 People of very high-risk cSCC given the propensity of these tumours who have had psoralen\u2013UVA therapy for skin conditions may tometastasize. also be at higher risk.32 cSCC may also occur in patients who arebeingtreatedwithBRAFinhibitorsformelanoma.33 Algorithms People with organ transplants are at high risk of developing cSCC. Skin surveillance to allow early detection and treatment, The recommendations, discussions in the LETRs (Appendix D; and measures to prevent cSCC, should be part of their routine see Supplementary Information) and consensus specialist care. In patients with multiple, frequent or high-risk cSCCs \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 9}, {"text": "410 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. Figure2 Staging and management pathway of primary cutaneous squamous cell carcinoma (cSCC). FNAB, fine-needle aspiration biopsy; FNAC, fine-needle aspiration cytology; LSMDT, local skin cancer multidisciplinary team; SSMDT, specialist skin cancer multidisciplinary team; USS, ultrasoundscan.[Colourfigurecanbeviewedatwileyonlinelibrary.com] BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 10}, {"text": "llecsuomauqscitatsatem,CCSm;amonicracllecsuomauqsdecnavdayllacol,CCSal;yparehtoidartnavujda,TRA.stludani)CCSc(amonicracllecsuomauqssuoenatucyramirprofyawhtaptnemtaerT 3erugiF ]moc.yrarbilenilnoyeliwtadeweivebnacerugfiruoloC[.maetyranilpicsiditlumrecnacnikstsilaiceps,TDMSS;amonicrac BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. 411 \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 11}, {"text": "412 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. consideration should be given to modifying immunosuppresb The anatomicaldescription ofthedeepmargin? sive regimens34,35 and the prophylactic use of systemic retinoids,36\u201338 which may also be valuable in other high-risk 10 Histological margins in all planes following standard surgical excision? Note: these are defined as clear (\u2265 1 groups.39 Nicotinamide should also be considered in this situmm), clearbut close(< 1 mm)orinvolved (0mm). ation.40 Therapies such as topical 5-fluorouracil41 and imiqui11 Appropriate follow-up protocols (R43, R45, R46 and mod,42 and photodynamic therapy43 may have useful roles in see below) by different members of the MDT, including preventing skin dysplasia and therefore decreasing the risk of clinical nurse specialists? Note: follow-up schedules are skin cancers in high-risk renal transplant recipients, but sublow-risk: one appointment for diagnosis and educastantive evidenceis awaited. tion; high-risk: a follow-up every 4 months in the first year then every 6 months in the second year; Diagnosis and investigation and very high-risk: a follow-up every 4 months in the first and second years, then every 6 months in Clinicalpresentation the third year. 12 Recording and review of histologically proven recurrence SCC usually presents as an indurated nodular keratinizing or of cSCC during follow-up periods following both surgical crusted tumour that may ulcerate, or it may present as an andnonsurgical treatments? ulcer without evidence of keratinization. All patients in whom there is a possibility of a cSCC should be referred urgently to The audit recommendation of 20 cases per department is to an appropriately trained specialist who is attached to an reduce variation in the results due to a single patient and LSMDT, usually in their local dermatology department\u2019s rapidallow benchmarking between different units (Appendix L; see access skincancer clinic.44 Supporting Information). Diagnosis andstaging Stakeholder involvement and peer review The handling of skin cancer specimens and their histopathoThe draft document and Supporting Information were made logical diagnosis and reporting should conform to the Royal available to the BAD membership, the Royal College of GenCollege of Pathologists dataset for primary cSCC.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 12}, {"text": "of Pathologists College of Pathologists and Public Health England have (RCPath), the Royal College of Radiologists (RCR), the British adopted UICC8 TNM9 for the staging of melanoma and nonAssociation of Oral and Maxillofacial Surgeons (BAOMS), the melanoma skin cancer. British Association of Head and Neck Oncologists (BAHNO), the British Association of Plastic Reconstructive and Aesthetic Recommended audit points Surgeons (BAPRAS), the British Society for Dermatological Surgery (BSDS), the British Dermatological Nursing Group In the last 20 consecutive patients with cSCC is there clear (BDNG), the British Association of Skin Cancer Nurse Specialdocumentation foror evidenceofthe ists (BASCNS) and the Primary Care Dermatological Society 1 Name and grade of the surgeon who carried out the sur- (PCDS). The comments received were actively considered by gery? the GDG. Following further review, the finalized version was 2 Patient being instructed in self-examination and provided sent for peer review by the Clinical Standards Unit of the BAD with written patient information (e.g. www.bad.org.uk/ (made up of the Therapy & Guidelines Subcommittee) prior leaflets)? tosubmission for publication. 3 Site and maximum dimension (usually diameter) of the lesion? 4 Lesion being fixed or mobile beneath the skin (head, Limitations of the guideline neck, trunk andlimbs)? This document has been prepared on behalf of the BAD and is 5 Lesion having tarsal plate or lid margin involvement, or based on the best data available when the document was prenot(eyelid)? pared. It is recognized that under certain conditions it may be 6 Immunosuppressive status ofthepatient? necessary todeviate from the guidelines and that the results of 7 Risk status of the lesion (low risk, high risk or very high future studies may require some of the recommendations risk)? herein to be changed. Failure to adhere to these guidelines 8 Lesion having associated clinically detectable nodes, or should not necessarily be considered negligent, nor should being clinically N0? adherence to these recommendations constitute a defence 9 Standard surgical excision, detailing against a claim of negligence. Limiting the review to Englisha The surgical margins of excision (R6; and see below)? and German-language references was a pragmatic decision but Note: these are \u2265 4 mm for low-risk, \u2265 6 mm for the authors recognize this may exclude some important inforhigh-risk and\u226510 mmfor very high-risk cSCC. mationpublished in otherlanguages.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 12}, {"text": "and German-language references was a pragmatic decision but Note: these are \u2265 4 mm for low-risk, \u2265 6 mm for the authors recognize this may exclude some important inforhigh-risk and\u226510 mmfor very high-risk cSCC. mationpublished in otherlanguages. BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 2, "page": 12}, {"text": "BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. 413 12 Motley RJ, Preston PW, Lawrence CM. Multi-professional guideliPlans for guideline revision nes for the management of the patient with primary cutaneous squamous cell carcinoma. Available at: http://www.bad.org.uk/ The proposed revision date for this set of recommendations is shared/get-file.ashx?id=59&itemtype=document (last accessed 20 scheduled for 2025; where necessary, important interim October2020). changes willbeupdated ontheBAD website. 13 Eigentler TK, Leiter U, H\u20acafner HM et al. Survival of patients with cutaneous squamous cell carcinoma: results of a prospective cohortstudy.JInvestDermatol2017;137:2309\u201315. Acknowledgments 14 Rose AM, Nicoll KJ, Moinie A et al. Patients with low-risk cutaWeareverygratefultoProfessorFionaBath-Hextallforheradvice neous squamous cell carcinoma do not require extended out-patientfollow-up.JPlastReconstrAesthetSurg2017;70:852\u20135. on formulating the protocols, and Dr Stephen Kownacki (PCDS), 15 Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurDrVirginiaWolstenholme(RCR),MsLizFreeman(BDNG)andDr rence,metastasis,andsurvivalratesinsquamouscellcarcinomaof RobertHerdfortheircontributionattheinceptionoftheseguidethe skin, ear, and lip. Implications for treatment modality seleclines.WethankthepatientrepresentativesMsPatriciaFairbrother tion.JAmAcadDermatol1992;26:976\u201390. and Mr Paul Buckley for their input in formulating the clinical 16 Ruiz ES, Karia PS, Besaw R et al. Performance of the American Joint questions, ranking of the outcomes, reviewing the evidence and CommitteeonCancerStagingManual,8thEditionversustheBrigham formulating the recommendations, as well as all of those who and Women\u2019s Hospital Tumor Classification System for Cutaneous SquamousCellCarcinoma.JAMADermatol2019;155:819\u201325. commentedonthedraftduringtheconsultationperiod. 17 Jambusaria-Pahlajani A, Kanetsky PA, Karia PS et al. Evaluation of AJCCtumorstagingforcutaneoussquamouscellcarcinomaand a proposed alternative tumor staging system. JAMA Dermatol 2013; References 149:402\u201310. 1 National Institute for Health and Care Excellence. Improving out18 Wehner MR, Linos E, Parvataneni R et al. Timing of subsequent comes for people with skin tumours including melanoma. Availnew tumors in patients who present with basal cell carcinoma or able at: https://www.nice.org.uk/guidance/csg8/evidence/fullcutaneous squamous cell carcinoma. JAMA Dermatol 2015; guideline-2006-pdf-2191950685(lastaccessed20October2020). 151:382\u20138. 2 Morton CA, Birnie AJ, Eedy DJ. British Association of Dermatolo19 National Institute for Health and Care Excellence. Skin cancer. gists\u2019 guidelines for the management of squamous cell carcinoma Quality standard QS130. Available at: https://www.nice.org.uk/ insitu(Bowen\u2019sdisease)2014.BrJDermatol2014;170:245\u201360. guidance/qs130(lastaccessed20October2020). 3 National Comprehensive Cancer Network. NCCN Guidelines: squa20 KwaRE,CampanaK,MoyRL.Biologyofcutaneoussquamouscell mouscellskincancer.Availableat:https://www.nccn.org/professiona carcinoma.JAmAcadDermatol1992;26:1\u201326. ls/physician_gls/pdf/squamous.pdf(lastaccessed20October2020). 21 Cancer ResearchUK. Non-melanomaskin cancer incidence.Avail4 Lopez AT, Carvajal RD, Geskin L. Secondary prevention strategies able at: https://www.cancerresearchuk.org/health-professional/ca for nonmelanoma skin cancer. Oncology (Williston Park) 2018; ncer-statistics/statistics-by-cancer-type/non-melanoma-skin-cance 32:195\u2013200. r#heading-zero(lastaccessed20October2020). 5 Mohd Mustapa MF, Exton LS, Bell HK et al. Updated guidance for 22 VenablesZC,NijstenT,WongKFetal.Epidemiologyofbasaland writing a British Association of Dermatologists clinical guideline: cutaneous squamous cellcarcinoma in the UK 2013\u201315: a cohort theadoptionoftheGRADEmethodology2016.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 13}, {"text": "2018; ncer-statistics/statistics-by-cancer-type/non-melanoma-skin-cance 32:195\u2013200. r#heading-zero(lastaccessed20October2020). 5 Mohd Mustapa MF, Exton LS, Bell HK et al. Updated guidance for 22 VenablesZC,NijstenT,WongKFetal.Epidemiologyofbasaland writing a British Association of Dermatologists clinical guideline: cutaneous squamous cellcarcinoma in the UK 2013\u201315: a cohort theadoptionoftheGRADEmethodology2016.BrJDermatol2017; study.BrJDermatol2019;181:474\u201382. 176:44\u201351. 23 QueSKT,ZwaldFO,SchmultsCD.Cutaneoussquamouscellcarci6 Brouwers M, Kho ME, Browman GP et al. AGREE II: advancing noma:incidence,riskfactors,diagnosis,andstaging.JAmAcadDerguideline development, reporting and evaluation in healthcare. matol2018;78:237\u201347. CMAJ2010;182:E839\u201342. 24 GreenAC,OlsenCM.Cutaneoussquamouscellcarcinoma:anepi7 GuyattGH,OxmanAD,VistGEetal.GRADE:anemergingconsendemiologicalreview.BrJDermatol2017;177:373\u201381. sus on rating quality of evidence and strength of recommenda25 GoonPK,GreenbergDC,IgaliLetal.Squamouscellcarcinomaof tions.BMJ2008;336:924\u20136. the skin has more than doubled over the last decade in the UK. 8 Slater DN, Barrett P. Dataset for the histological reporting of priActaDermVenereol2016;96:820\u20131. mary cutaneous squamous cell carcinoma and regional lymph 26 Tommasino M. HPV and skin carcinogenesis. Papillomavirus Res nodes. Available at: https://www.rcpath.org/uploads/assets/9c1d 2019;7:129\u201331. 8f71-5d3b-4508-8e6200f11e1f4a39/Dataset-for-histopathological27 Scott FI, Mamtani R, Brensinger CM et al. Risk of nonmelanoma reporting-of-primary-invasive-cutaneous-squamous-cell-carcinomaskin cancer associated with the use of immunosuppressant and and-regional-lymph-nodes.pdf(lastaccessed20October2020). biologic agents in patients with a history of autoimmune disease 9 Brierley JD, Gospodarowicz MK, Wittekind C. Skin tumours. In: andnonmelanomaskincancer.JAMADermatol2016;152:164\u201372. TNM Classification Of Malignant Tumours, 8th edn (Brierley JD, Gospo28 Patel RV, Clark LN, Lebwohl M et al. Treatments for psoriasis and darowiczMK,WittekindC,eds),Chichester:JohnWileyandSons, theriskofmalignancy.JAmAcadDermatol2009;60:1001\u201317. 2017,131\u201349. 29 Karagas MR, Stannard VA, Mott LA et al. Use of tanning devices 10 Califano JA, Lydiatt WM, Nehal KS et al. Cutaneous squamous cell and risk of basal cell and squamous cell skin cancers. J Natl Cancer carcinomaoftheheadand neck.In:AJCCCancerStagingManual,8th Inst2002;94:224\u20136. edn(AminMB,EdgeSB,GreeneFL,ByrdDR,BrooklandRKetal., 30 vanderPolsJC,WilliamsGM,PandeyaNetal.Prolongedpreveneds).NewYork:Springer,2017;171\u201381. tion of squamous cell carcinoma of the skin by regular sunscreen 11 Motley R, Kersey P, Lawrence C. Multiprofessional guidelines for use.CancerEpidemiolBiomarkersPrev2006;15:2546\u20138. the management ofthepatient withprimary cutaneous squamous 31 UlrichC,JurgensenJS,DegenAetal.Preventionofnon-melanoma cellcarcinoma.BrJDermatol2002;146:18\u201325. skin cancer in organ transplant patients by regular use of a \u00a92020BritishAssociationofDermatologists BritishJournalofDermatology(2021)184,pp401\u2013414 Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 13}, {"text": "414 BADguidelinesformanagementofpeoplewithSCC2020, S.G.Keohaneetal. sunscreen: a 24 months, prospective, case\u2013control study. Br J DerCentral(demitted2016),DeputyChairTVCNSkinCancerTSSG matol2009;161(Suppl.3):78\u201384. (demitted 2020) (specific). K.F.: (i) advisory boards \u2013 ESAI, 32 Stern RS, PUVA Follow-Up Study. The risk of squamous cell and IPSEN, Roche, Novartis, Merck, Pfizer and Eusa (specific); (ii) basalcellcancerassociatedwithpsoralenandultravioletAtherapy: speaker fees and consultancy \u2013 BMS, Pfizer, MSD (non-specia30-yearprospectivestudy.JAmAcadDermatol2012;66:553\u201362. fic); (iii) conference hospitality \u2013 Novartis, Ipsen (specific); 33 GibneyGT,MessinaJL,FedorenkoIVetal.Paradoxicaloncogenesis \u2013 the long-term effects of BRAF inhibition in melanoma. Nat Rev (iv) institutional research funding \u2013 Roche, MSD, Exelixis ClinOncol2013;10:390\u20139. (specific). C.A.H.: (i) speaker and honoraria for Sanofi (speci34 Mittal A, Colegio OR. Skin cancers in organ transplant recipients. fic); (ii) member of the NCRI Skin Group (specific) and memAmJTransplant2017;17:2509\u201330. ber of the EADO guidelines development group for cSCC 35 CollinsL,QuinnA,StaskoT.Skincancerandimmunosuppression. (specific). J.R.M.: member of the NCRI non-melanoma skin DermatolClin2019;37:83\u201394. cancersubgroup(specific).C.N.: (i)memberoftheNCRInon36 Otley CC, Stasko T, Tope WD et al. Chemoprevention of nonmelanoma skin cancer subgroup (specific); (ii) has shares in a melanoma skin cancer with systemic retinoids: practical dosing andmanagementofadverseeffects.DermatolSurg2006;32:562\u20138. private general practitioner web-based company (non-specific). 37 Herold M, Good AJ, Nielson CB et al. Use of topical and systemic C.P.: (i) Chair of the Scottish Dermatological Society Skin Canretinoids in solid organ transplant recipients: update and review cer Group (specific); (ii) member of the NCRI Skin Group ofthecurrentliterature.DermatolSurg2019;45:1442\u20139. (specific); (iii) member of the NCRI non-melanoma skin can38 QueSKT,ZwaldFO,SchmultsCD.Cutaneoussquamouscellcarcicer subgroup (specific); (iv) clinical expert for appraisal of noma:management ofadvancedandhigh-stagetumors.JAmAcad cemiplimabforcSCCforNICE(April2019)(specific).A.R.: (i) Dermatol2018;78:249\u201361. memberoftheNCRISkinGroup (specific);(ii)memberofthe 39 NijstenTE,SternRS.Oralretinoidusereducescutaneoussquamous NCRI non-melanoma skin cancer subgroup (specific); (iii) cellcarcinomariskinpatientswithpsoriasistreatedwithpsoralenUVA:anestedcohortstudy.JAmAcadDermatol2003;49:644\u201350. Non-Melanoma Skin Cancer Advisory Board prior to ESMO 40 Chen AC, Martin AJ, Choy B et al. A phase 3 randomized trial of 2018oncemiplimabforSanofi(specific).D.N.S.:RoyalCollege nicotinamide forskin-cancer chemoprevention.N Engl J Med2015; of Pathologists Lead on Skin Cancer Datasets (specific). S.G.K., 373:1618\u201326. J.B., O.M.D., R.M., R.J.M., C.N., J.A.S., P.B., P.F., M.H., 41 Weinstock MA, Thwin SS, Siegel JA et al. Chemoprevention of M.F.M.M.andL.S.E.declaretheyhavenoconflictsofinterest. basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: a randomized clinical trial. JAMA Dermatol 2018;154:167\u201374. Supporting Information 42 BrownVL,AtkinsCL,GhaliLetal.Safetyand efficacyof5%imiquimod cream for the treatment of skin dysplasia in high-risk AdditionalSupportingInformationmaybefoundintheonline renal transplant recipients: randomized, double-blind, placebocontrolledtrial.ArchDermatol2005;141:985\u201393. version ofthis articleat thepublisher\u2019s website: 43 Togsverd-Bo K, Omland SH, Wulf HC et al. Primary prevention of skindysplasiainrenaltransplantrecipientswithphotodynamictherAppendix AReviewprotocol. apy:arandomizedcontrolledtrial.AmJTransplant2015;15:2986\u201390. Appendix BForest plots.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 14}, {"text": "treatment of skin dysplasia in high-risk AdditionalSupportingInformationmaybefoundintheonline renal transplant recipients: randomized, double-blind, placebocontrolledtrial.ArchDermatol2005;141:985\u201393. version ofthis articleat thepublisher\u2019s website: 43 Togsverd-Bo K, Omland SH, Wulf HC et al. Primary prevention of skindysplasiainrenaltransplantrecipientswithphotodynamictherAppendix AReviewprotocol. apy:arandomizedcontrolledtrial.AmJTransplant2015;15:2986\u201390. Appendix BForest plots. 44 National Institute for Health and Care Excellence. Suspected canAppendix CClinical evidencesummary. cer:recognitionandreferral.NICEclinicalguidelineNG12.AvailAppendix DLinkingEvidenceToRecommendations(LETR). able at: https://www.nice.org.uk/guidance/ng12 (last accessed Appendix EGRADE evidencetables. 20October2020). Appendix FSummary ofincluded studies. Appendix GNarrativefindingsfornon-comparativestudies. Appendix Appendix HPRISMAdiagram:study selection. Appendix IPapers excluded fromquantitative analysis. Appendix JMethodology. Conflicts of interest Appendix KSearch strategy. The following interests were declared over the duration of the Appendix L Audit standards, data items and data collection guideline development. P.G.B.: RCSEng RSPA Plastics South methodology. BritishJournalofDermatology(2021)184,pp401\u2013414 \u00a92020BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/184/3/401/6702204 by guest on 23 February 2026", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 14}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "cutaneous SCC guideline.pdf", "chunk_id": 0, "page": 15}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "cutaneous SCC guideline.pdf", "chunk_id": 1, "page": 15}, {"text": "BJD GUIDELINE British Journal of Dermatology British Association of Dermatologists guidelines for the management of lichen sclerosus, 2018* F.M. Lewis iD,1,2 F.M. Tatnall,3 S.S. Velangi,4 C.B. Bunker,5,6 A. Kumar,7 F. Brackenbury,8 M.F. Mohd Mustapa9 and L.S. Exton9 1Frimley HealthNHS Foundation Trust,Slough SL24HL, U.K. 2StJohn\u2019s Institute of Dermatology, Guy\u2019s &StThomas\u2019 NHSFoundation Trust, London SE19RT, U.K. 3West Hertfordshire NHSTrust, Watford WD180HB, U.K. 4University Hospitals Birmingham NHS FoundationTrust, Birmingham B15 2TH, U.K. 5University CollegeLondon Hospitals NHSFoundation Trust, University CollegeHospital,London NW12BU, U.K. 6Chelsea &Westminster NHS Foundation Trust, LondonSW10 9NH,U.K. 7King\u2019s CollegeLondon, LondonSE1 3ER, U.K. 8Association forLichenSclerosus and Vulval Health,Brighton, U.K. 9British Association of Dermatologists, WillanHouse, 4 Fitzroy Square, LondonW1T 5HQ, U.K. Linked Editorial: AkelandFuller.BrJDermatol2018;178: 823\u2013824. Correspondence FionaLewis. 1.0 Purpose and scope E-mail:fiona.lewis@gstt.nhs.uk;guidelines@bad.org.uk The overall objective of the guideline is to provide up-to-date, Accepted forpublication evidence-based recommendations for the management of 6December2017 lichen sclerosus (LS) in adults (\u2265 18 years), children (0\u2013 12 years) and young people (13\u201317 years). The document Funding sources aims to: None. (cid:129) Offer an appraisal of all relevant literature up to July 2017, focusingon any keydevelopments. Conflicts ofinterest (cid:129) Address important, practical clinical questions relating to F.M.L.wassecretaryoftheEuropeanCollegeforStudyofVulvalDisease(2008-16) (specific).C.B.B.isprincipalinvestigatorandresearchgrantholderforinvestigation theprimary guideline objective. (cid:129) intomalegenitallichensclerosus,humanpapillomavirusandpeniscancer\u2013SirJohn Provide guideline recommendations and, if appropriate, FisherFoundation,SkinTreatmentandResearchTrust(START)andEuropeanAcademy research recommendations. ofDermatologyandVenereology. The guideline is presented as a detailed review with highThisisanupdatedguidelinepreparedfortheBADClinicalStandardsUnit,which lighted recommendations for practical use in primary care and includestheTherapy&Guidelinessubcommittee.MembersoftheClinicalStandards in secondary-care clinics, in addition to an updated patient UnitwhohavebeeninvolvedareP.M.McHenry(ChairmanTherapy&Guidelines), information leaflet[available on theBritish Association ofDerT.A.Leslie,S.Wakelin,R.Y.P.Hunasehally,M.Cork,G.A.Johnston,N.Chiang, matologists (BAD) website, http://www.bad.org.uk/for-theF.S.Worsnop,D.Buckley,G.Petrof,A.Salin,N.Callachand(BritishNationalForpublic/patient-information-leaflets]. mulary),C.Saunders(BDNG),A.A.Salad(BADScientificAdministrator),L.S.Exton (BADGuidelineResearchFellow)andM.F.MohdMustapa(BADClinicalStandards Manager). 1.1 Exclusions The guideline does not cover complex surgical techniques Producedin2002bytheBritishAssociationofDermatologists.Reviewedandupdated used in the management of selected cases of LS or the man2010,2018 agementof squamouscell carcinoma (SCC) inLS. DOI10.1111/bjd.16241 2.0 Methodology NICEhasaccreditedtheprocessusedbytheBritishAssociationof Dermatologiststoproduceclinicalguidelines.Therenewedaccreditationisvaliduntil31May2021andappliestoguidanceproThissetofguidelineshasbeendevelopedusingtheBAD\u2019srecomducedusingtheprocessdescribedintheupdatedguidancefor writingaBritishAssociationofDermatologistsclinicalguideline\u2013 mended methodology1 (Appendix K; see Supporting InformatheadoptionoftheGRADEmethodology2016.Theoriginal accreditationtermbeganon12May2010.Moreinformationon tion)withreferencetotheAppraisalofGuidelinesResearchand accreditationcanbeviewedatwww.nice.org.uk/accreditation. Evaluation (AGREE II) instrument (www.agreetrust.org)2 and theGradingofRecommendationsAssessment,Developmentand *Plainlanguagesummaryavailableonline Evaluation (GRADE; http://www.gradeworkinggroup.org).3 \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 839 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 1}, {"text": "840 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. Recommendations were developed for implementation in the (cid:129) Topical calcineurin inhibitors U.K.NationalHealthService. (cid:129) Testosterone andotherhormonal treatments The Guideline Development Group (GDG), which consisted (cid:129) Surgery of consultant dermatologists, patient representatives and a (cid:129) Cryotherapy technical team (consisting of a guideline research fellow and (cid:129) Photodynamic therapy project manager providing methodological and technical sup- (cid:129) Phototherapy port) established several clinical questions pertinent to the (cid:129) Laser scope of the guideline and a set of outcome measures of (cid:129) Systemictherapies importance to patients, ranked according to the GRADE methodology (see Section 2.1). Additionally, the GDG also aims to answer the following A systematic literature search of the PubMed, MEDLINE, questions based ontheevidence, if possible,or on consensus: Embase,CochraneandAMEDdatabaseswasconductedtoiden1 Whatis themostappropriate treatment regimen? tify key articles on LS up to July 2017; the search terms and 2 Ismaintenance treatment required? strategies are detailed in the Supporting Information 3 Whatfollow-up protocols are needed? (Appendix L). Additional references relevant to the topic were alsoobtainedfromcitationsinthereviewedliterature.Evidence The GDG also established two sets of outcome measures from the included studies was graded according to the GRADE of importance to patients (treatment), which were agreed system(high,moderate,loworverylowquality).Recommenupon by the patient representatives, one for female dationsarebasedonevidencedrawnfromsystematicreviewsof patients and one for male patients, ranked according to the theliteraturepertainingtotheclinicalquestionsidentified.The GRADE methodology (Table 2).3 The data were extracted summary of findings with forest plots (Appendix D), GRADE from the included studies (Appendix K; see Supporting evidence profiles indicating the quality of evidence Information). (Appendix E), clinical evidence summary (Appendix B), summary of included studies (Appendix F), narrative findings for 3.0 Summary of recommendations noncomparativestudies(Appendix G),summaryoftopicalsteroids (Appendix H), tables linking the evidence to the recomThere are few randomized controlled trials to support the folmendations(Appendix C),PRISMAflowdiagram(Appendix I) lowing guidelines for the management of LS. The following and list of excluded studies (Appendix J) are detailed in the recommendations and ratings were agreed upon unanimously Supporting Information. The strength of recommendation is by the core members of the GDG and patient representatives. expressedbythewordingandsymbolsshowninTable 1. For further information on the wording used for the recommendations and strength of recommendation ratings see Table 1. Good practice point (GPP) recommendations are 2.1 Clinical questions andoutcomes derived from informalconsensus.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 2}, {"text": "recommendations and strength of recommendation ratings see Table 1. Good practice point (GPP) recommendations are 2.1 Clinical questions andoutcomes derived from informalconsensus. The GDG established a clinical question pertinent to the scope The GDG is aware of the lack of high-quality evidence for of the guideline (see Appendix A in the Supporting Informathese recommendations; therefore, strong recommendations tion for thefull reviewprotocol). with an asterisk (*) are based on the available evidence, as In patients with LS, what are the clinical outcomes and well as consensus and specialist experience. Further informacost-effectiveness oftherapies? tion about other therapies where there is less evidence are dis- (cid:129) Topical corticosteroids cussedin theSupporting Information. Table1 Strengthofrecommendationratings Strength Wording Symbols Definition Strongrecommendationfor \u2018Offer\u2019(orsimilar,e.g. Benefitsoftheinterventionoutweightherisks;mostpatientswould theuseofanintervention \u2018use\u2019,\u2018provide\u2019,\u2018take\u2019, choosetheinterventionwhileonlyasmallproportionwouldnot; \u2018investigate\u2019etc.) forclinicians,mostoftheirpatientswouldreceivetheintervention; forpolicymakers,itwouldbeausefulperformanceindicator Weakrecommendationforthe \u2018Consider\u2019 Risksandbenefitsoftheinterventionarefinelybalanced;most useofanintervention patientswouldchoosetheinterventionbutmanywouldnot; clinicianswouldneedtoconsidertheprosandconsforthepatient inthecontextoftheevidence;forpolicymakers,itwouldbeapoor performanceindicatorwherevariabilityinpracticeisexpected Norecommendation \u0398 Insufficientevidencetosupportanyrecommendation Strongrecommendationagainst \u2018Donotoffer\u2019 Risksoftheinterventionoutweighthebenefits;mostpatientswould theuseofanintervention notchoosetheinterventionwhileonlyasmallproportionwould;for clinicians,mostoftheirpatientswouldnotreceivetheintervention BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 2}, {"text": "BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 841 Table2 Importantoutcomemeasuresforfemaleandmalepatients Female Male Qualityoflife(improvementofsymptoms) 9 Qualityoflife(improvementofsymptoms) 9 Restorationofsexualfunctiona 9 Restorationofsexualfunctiona 9 Abolitionofriskofvulvalcancera 9 Abolitionofriskofpenilecancera 9 Seriousadverseevents 8 Seriousadverseevents 8 Physician\u2019sGlobalAssessment 6 Restorationofurinaryfunction 7 Patient\u2019sGlobalAssessment 5 Physician\u2019sGlobalAssessment 6 Minoradverseevents 4 Patient\u2019sGlobalAssessment 5 Minoradverseevents 4 Outcomesranked7,8or9arecriticalfordecisionmaking;thoseranked4,5or6areimportantbutnotcriticalfordecisionmaking.aAdults andyoungpeopleonly. R11 (GPP) Consider referral to a specialist vulval clinic in all All people(children, young peopleandadults;male and female patients (including children and young people) with female) LS not responding to a topical steroid, or if surgical manageR1 (GPP) All people with LS should be managed by a healthment is being considered. care professional experienced in treating the condition (secR12 ( ) Consider intralesional triamcinolone (10\u201320 mg) in ondary-care specialist or general practitioner with specific female patients with LS with topical steroid-resistant, hypertraining). keratotic areas after intraepithelial neoplasia or malignancy has R2 (GPP) Commence treatment of LS following a firm clinical been excluded bybiopsy. diagnosis or withhistological confirmation, where necessary. R3 (GPP) Undertake a full history for all people with LS, Adult male including dyspareunia and psychosexual issues. Document urinary symptoms. Perform a detailed examination documenting R13 ( ) Offer* all male patients with genital LS CP 0(cid:1)05% architectural changes at baseline (using a diagram or phoointment once daily for 1\u20133 months with an emollient as a tograph, according topatientpreference). soap substitute andasabarrier preparation. R4 (GPP) Advise all people with LS to avoid all irritant and R14 (GPP) Discuss the amount of topical treatment to be fragranced products. used, the site of application and the safe use of an ultrapotent R5 (GPP) Provide all people with LS up-to-date patient infortopical steroidwith thepatient. mation on the condition (http://www.bad.org.uk/for-theR15 (GPP) Consider a repeat course of topical treatment for public/patient-information-leaflets). 1\u20133 months in thosewho relapse. R6 (GPP) All people treated for LS should be followed up R16 ( ) Consider intralesional triamcinolone in male patients (see algorithms in Figs 1 and 2) to assess response to treatwithLSwithtopicalsteroid-resistant,hyperkeratoticareasfollowment andtoadvise on long-term control. ingbiopsytoensurenointraepithelialneoplasiaormalignancy. R17 ( ) Offer*allmalepatientswithphimosiscausedbyLS who do not respond to an ultrapotent topical steroid after 1\u2013 Adult female 3 monthsreferraltoanexperiencedurologistforcircumcision.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 3}, {"text": "Offer* all female patients with anogenital LS clobeR18 (GPP) Offer male patients with urinary symptoms due to tasol propionate (CP) 0(cid:1)05% ointment on a regimen for LS referral for a urology opinion and further investigation and 3 months (once a day for a month, alternative days for a management oflower urinary tract symptoms. month, twice weekly for a month), combined with a soap R19 (GPP) Offer treatment for meatal involvement by LS with substitute andabarrier preparation. CP 0(cid:1)05% ointment applied once daily via cotton wool bud or R8 (GPP) Discuss the amount of topical treatment to be used, meatal dilator for 1\u20133 months prior to referral to a urologist the site of application and the safe use of an ultrapotent topispecialized in themanagementofLS. cal steroid withthepatient. R20 (GPP) Offer all male patients with a urethral stricture R9 ( ) Offer* continued use of CP 0(cid:1)05% for ongoing due toLS referraltoaurologist specialized inthemanagement active LS disease(see algorithmsin Figs 1and2). of LS. A urologist may consider treatment for a urethral stricR10 ( ) Consider an individualized treatment regimen of ture with CP introduced into the urethra via a urinary catheter topical steroid tomaintain diseasecontrol andprevent scarring or meatal dilator, depending on stricture length, before proin female patients with ongoing active LS disease despite good ceeding tosurgical treatment options. compliance. Treatment should be titrated to maintain sympR21 ( ) Offer all male patients with LS who have failed to toms and resolution of skin thickening and ecchymosis, respond to topical steroids and/or circumcision referral for a although pallormay notcompletely resolve. specialist urology opinion on other surgical treatment options, \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 3}, {"text": ".amonicracllecsuomauqs,CCS;renoititcarplareneg,PG.yawhtaptnemeganam)SL(susorelcsnehcilelamtludA .1giF 842 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 4}, {"text": ".amonicracllecsuomauqs,CCS.yawhtaptnemeganam)SL(susorelcsnehcilelameftludA .2giF BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 843 \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 5}, {"text": "844 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. for example total or partial glans resurfacing and split-skin FRR2 What is the role of topical steroids in preventing maliggrafting. nancy in genital LSin femalepatients? R22 (GPP) Advise obese male patients with LS and a buried FRR3 What is the course of LS after puberty in female penis to lose weight. Further referral to a specialist urologist patients? andbariatric services may berequired. FRR4 What is the optimal surgical management of female patients withfusion overtheclitoris? FRR5 Would acitretin in combination with atopical steroid be Childrenandyoung people-female moreeffectivethanmonotherapyintreatingpeoplewithresisR23 (GPP) Refer female children and young people with LS tantLS? to specialized vulval services (vulval clinic, paediatric dermaFRR6 What are the safety and efficacy of adalimumab in male tologist or urologist experienced in managingLS). patients withurethral stenosis causedbyLS? R24 (GPP) Consider referral to a specialist vulval clinic in FRR7 Set up a national registry for extensive extragenital LS to female patients (also adults) with LS not responding to topical identify thetreatments involved andoutcomes achieved steroids, orif surgical managementis being considered. FRR8 What is the role of urine in the pathogenesis of genital R25 ( ) Offer* all female patients with anogenital LS CP LSandpaediatric genital LS? 0(cid:1)05% ointment on a regimen for 3 months (once a day for a FRR9 Isthere arole forsystemic therapyin genital LS? month,alternativedaysforamonth,twiceweeklyforamonth) FRR10 Whatproportion ofpatients withLS remitcompletely? withanemollientasasoapsubstituteandasabarrierpreparation. R26 (GPP) Discuss the amount of topical treatment to be 4.0 Algorithm used, the site of application and the safe use of an ultrapotent topicalsteroid withthe patient. The recommendations and discussions in the \u2018linking evidence R27( )Consideranindividualizedtreatmentregimenoftopical torecommendations\u2019 table(Appendix C; seeSupporting Inforsteroidtomaintaindiseasecontrolandpreventscarringinfemale mation) and consensus specialist experience were used to propatientswithongoingactiveLSdiseasedespitegoodcompliance. duce management pathways for adult patients (Figs 1 and 2). Similar algorithmshave been published elsewhere.4 Childrenandyoung people\u2013 male 5.0 Introduction R28 ( ) Offer* a trial of an ultrapotent topical steroid applied once daily for 1\u20133 months combined with emollients 5.1 Definition andbarrier preparations toallmalechildrenandyoungpeople withphimosis causedby LS. LS is an inflammatory scarring dermatosis, characterized by a R29 ( ) Offer all male children with phimosis caused by lymphocytic response, that has a predilection for the genital LS who do not respond to topical steroids after 1\u20133 months skin in both sexes.5\u20137 referral to a paediatric urologist for circumcision.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 6}, {"text": "phimosis caused by lymphocytic response, that has a predilection for the genital LS who do not respond to topical steroids after 1\u20133 months skin in both sexes.5\u20137 referral to a paediatric urologist for circumcision. Disease of The old terms \u2018balanitis xerotica obliterans\u2019 and \u2018kraurosis the glans unmasked by circumcision should be treated with a vulvae\u2019 are synonymous terms for LS and should not be used. potent topicalsteroid once dailyfor1\u20133 months. The suffix\u2018et atrophicus\u2019has beendropped,as it is recognized R30 (GPP) Send* all circumcision specimens in male patients thatsomecasesofLSareassociatedwithahypertrophic,rather withLS forhistological examination. than atrophic, epithelium. The term \u2018leukoplakia\u2019 (meaning whiteplaque)isnotadiagnosticentityandisdescriptiveonly, as many conditions may present with white plaques. There are Extragenital disease instanceswhenitcanbedifficulttodifferentiatebetweenLSand R31( )Considerpotenttopicalsteroids,acitretin,methotrexlichen planus (LP) on the basis of the clinical and histological ateandphototherapyforpeoplewithextragenitalLS. features,8 and these cases appear to constitute an overlap syndrome. Clinically, these cases can be associated with hyperkeratosisandapoorresponsetoultrapotenttopicalcorticosteroids. Insufficient evidence tosupport any recommendation \u0398 Currently there is insufficient evidence to recommend the 5.2 Aetiology following interventions for peoplewith LS: (cid:129) Topical calcineurin inhibitors The aetiology of LS is contested. There is evidence to suggest (cid:129) Systemicretinoids. that autoimmune mechanisms are involved in its pathogenesis.9\u201312Anincreasedincidenceoftissue-specificantibodies13 and associations with other autoimmune diseases, especially thyroid disease, have been documented in women Listofkeyfuture research recommendations (FRRs) withLS,14\u201316butthisisnotthecaseinmen.17,18ThetranscripFRR1 What is the role of topical calcineurin inhibitors in tosome of male genital LS shows no evidence of patterns of treatingpeople withLS? gene expression associated with autoimmune diseases or BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 6}, {"text": "BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 845 infectious diseases.19 The presence of circulating extracellular maybeprominent,andoccasionallyhyperkeratosisisapromimatrix protein antibodies has been demonstrated in both nent feature. The characteristic sites are the interlabial sulci, sexes.20,21 labia minora, clitoral hood, clitoris and perineal body. LS is a InmalepatientsLSisassociatedwithanincreasedbodymass scarring dermatosis and may cause resorption of the labia index22,23andhasbeenassociatedwithcoronaryarterydisease, minora, sealing of the clitoral hood and covering of the clidiabetes mellitus and tobacco use.23 Crucially in male patients, toris. The vagina and cervix are not involved (in contrast to LSisassociatedwithurinaryocclusionbecauseofmicroincontiLP), unless there is a significant vaginal prolapse, when the nence created by the dysfunctional performance of the navicumucosa may become keratinized and develop the disease.47,48 lomeatal fossa and meatal lips as a low-pressure valve.24 LS Perianal lesions occur in women in 30% of cases. There may rarelyoccursinboyscircumcisedatbirth,andthismaysupport beextension tothebuttocks andgenitocrural folds. theconceptthatamoistenvironmentundertheforeskinpredisposes to LS.17 The association of LS with urostomy and ileos5.4.2 Lichensclerosus inpregnancy tomy suggests that moisture and irritation may play a role in theaetiologyofLS.25UrinecontactmayberelevanttotheassoLS can Koebnerize and may first arise in obstetric scars. ciation of LS with hypospadias,26 and hypospadias repair in There are few reports of the effects of pregnancy on LS, but cases without prior LS can be complicated by LS. Trauma is clinical experience suggests that it does improve, with less known to predispose to LS and it may appear in surgical treatment required. However, topical steroids can be safely woundsandfollowingradiotherapyandsunburn.27\u201329 continued during pregnancy and in the postdelivery period, Genetic associations and associations with human leucocyte if needed. If the LS is well controlled, without significant antigen class II antigens are seen in patients of both scarring, vaginal delivery is not contraindicated and a consexes.19,30\u201332 A family history is reported in 12% of patients trolled delivery can be performed by an experienced midwife with LS.33 Vulval LS is associated with epigenetic alterations in with early episiotomy to prevent tearing. The preferred mode expression of isocitrate dehydrogenase enzymes and hydroxyof delivery should be discussed with the patient and their methylation.34Controversy remains regardingtherole ofBorreobstetrician. lia infection as an aetiological agent; although several studies have shown that this association does not occur in the U.S.A., 5.4.3 Childfemale anogenital some doubt still remains in Europe.35 There is no evidence for a link between LS and Borrelia burgdorferi in the U.K.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 7}, {"text": "shown that this association does not occur in the U.S.A., 5.4.3 Childfemale anogenital some doubt still remains in Europe.35 There is no evidence for a link between LS and Borrelia burgdorferi in the U.K.36 The Thelesionsaresimilartothoseinadultwomen,butecchymosis role for tumour necrosis factor-a in the pathogenesis of LS maybeverystrikingandpotentiallymistakenasevidenceofsexhas been reported, and early reports suggest promising outualabuse.However,thetwoarenotmutuallyexclusiveassome comes fortreatment ofmaleLS withadalimumab.37,38 casesofLSmaypossiblybecausedoraggravatedbysexualabuse through Koebnerization.49 Features that should arouse suspicion ofthisincludeLSarisinginolderprepubertalgirls,poorresponse 5.3 Incidence andpatterns to treatment, the presence of associated sexually transmitted The true incidence of LS is unknown, and probably underestiinfectionorothersymptomsorsignsofabuse. mated as it is either asymptomatic or under-recognized.39 The Perianal involvement is a frequent finding in young girls, estimated prevalence in adult female patients is up to 3%,40 who may present with constipation because of painful fissurand 0(cid:1)07% in men.41 Genital LS in female patients has two ing in thisarea. Dysuriacan alsoresult fromfissuring. peak ages of presentation \u2013 in the prepubertal and postAlthough childhood LS often improves at puberty, there menopausal years.42 There is also a bimodal onset in male may be cases that persist into adulthood50 and the patient patients, withage peaks in youngboys andin adultmen.17,43 should be made aware of this. Long-term follow-up may be needed for those patients with ongoing disease activity. Malignancy has notbeen reported in girls, butscarring canoccur. 5.4 Clinicalfeatures 5.4.1 Adult female anogenital 5.4.4 Adult malegenital Itchisthemainsymptom,butpainmaybeaconsequenceoferoThe common sites of involvement of LS in adult men are the sionsorfissures.Rarely LSmay beasymptomaticandisaninciglanspenis,coronalsulcus,frenulumandprepuce.Perianaldisdental finding on examination. In those with itch, this is often easeisrarely,ifever,seeninmen.Thepresentingcomplaintis worse at night and may be sufficiently severe to disturb sleep. often difficulty with sexual intercourse (male dyspareunia).17 Dyspareuniaoccursinthepresenceoferosions,fissuresorintroiTightening of the foreskin (constrictive posthitis) may lead to tal narrowing. Urinary symptoms and urinary incontinence are paraphimosis,phimosisandpainfulerections.OnereportdocureportedbywomenwithLS,44,45buthavebeenshowntobeless ments that 30% of phimosis occurring in adults was due to commonthaninthegeneralpopulationinanotherstudy.45,46 LS,51althoughanotherstudyof75patientswithseverephimoThe typical lesions are porcelain-white papules and plaques, sisidentifiedLSinonly11%.52Otherpresentingcomplaintsare often associated with areas of ecchymosis. Follicular delling due to the appearance of lesions or changes in urinary stream, \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 7}, {"text": "846 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. butitchisnotaprominentsymptom.Urologicalsymptomsare pathologist is vital, particularly in relation to the diagnosis of reportedin10%ofpatients.17Inaurologicalpractice,urethral differentiated intraepithelial neoplasia. diseasewasreportedtooccurin20%ofpatientsandmeataldisAbiopsy must alwaysbeconsidered in patients if: easein4%.53Theperimeatalareamaybeinvolvedandpostinflammatory scarring may lead to stenosis and obstruction. 1 There is a suspicion of neoplastic change, with a persisInitialmeataldiseasemayleadtoproblematicvoidingwithsubtent area of hyperkeratosis, erosion or erythema, or new sequent progression to urethral disease,6 and the extent of warty or papular lesions. Several mapping biopsies may involvementranges frompurelymeataltopanurethral.54Ithas be required if there is extensive abnormality. If there are been suggested that early treatment ofmeatal disease may preany lesions highly suspicious of an SCC, the patient vent progression to urethral involvement and urethral stricshould be referred urgently to a gynaeoncologist, or spetures.55 These complications may require a multidisciplinary cialist urologist in male patients, for excision of the approachwithinputfrombothadermatologistandaurologist. whole lesion foradequate staging. 2 The diseasefailstorespond toadequate treatment. 3 Circumcision is performed: the foreskin should always be 5.4.5 Childmalegenital sent for histology to exclude penile intraepithelial neoplasia (PeIN) and confirm the diagnosis, but nonspecific The most frequent presentation is phimosis. The reported features do not exclude LS. Although an obligate factor in incidence of LS in boys with phimosis ranges from 12% to 100%.56\u201359 Involvement of the glans has been reported to the pathogenesis of LS, the foreskin is not always the seat occur in 56% of boys and meatal involvement in 37%.60 Perior asite ofdisease. 4 There is extragenital LS, which has features mimicking anal involvement, as in adult men, is extremely rare. There is morphoea. a report of a rare complication of renal failure following meatal obstruction.61 Phimosis caused by LS may be complicated 5 There are pigmented areas, to exclude an abnormal melaby preputialstones.62 nocytic proliferation. 6 Alternative or additional therapy to a potent topical steroid is tobeused. 5.4.6 Male,female andchildextragenital 7 Urological surgery is being considered for urethral disease forconfirmation ofLS.69 The classical sites for extragenital lesions are the upper trunk, axillae,buttocksandlateralthighs,andtheseareinvolvedmost frequentlyinadultwomen.Rarersitesincludethemouth,face, 5.5.2 Immunology scalp, hands, feet and nails.63,64 The typical lesions are porcelain-whiteplaques,whichmayhavefolliculardellsandareasof An autoantibody screen to look for associated autoimmune ecchymosis,similarlytothegenitallesions.Theremaybediffidiseaseis usefulonly if there are clinicalfeatures tosuggest an cultyindistinguishingthelesionsfromthoseofmorphoea.The autoimmune disorder. clinical types of extragenital LS include an extensive bullous form65,66 and annular, Blaschkoid and keratotic variants.67 5.5.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 8}, {"text": "usefulonly if there are clinicalfeatures tosuggest an cultyindistinguishingthelesionsfromthoseofmorphoea.The autoimmune disorder. clinical types of extragenital LS include an extensive bullous form65,66 and annular, Blaschkoid and keratotic variants.67 5.5.3 Microbiology Koebnerization is very common at extragenital sites, arising at pressurepoints,oldsurgicalandradiotherapyscars,andsitesof Swabs are not required routinely but may be indicated in erotraumaincludingurostomies.25,68 sive or topical steroid-resistant disease to exclude herpes simplex orCandida asadditional complicating problems. 5.5 Assessment andinvestigations 5.6 Complications 5.5.1 Biopsy 5.6.1 Malignancy LS is a clinical diagnosis and a confirmatory biopsy is not always necessary when the typical clinical features are present. SCChasbeendescribedingenitalLSoftheusualandverrucous This is particularly true in children and men. However, histohistologicalsubtypes.70\u201372SCCisnotassociatedwithextragenital logical examination is recommended if there are atypical feaLS. Melanoma, basal cell carcinoma and Merkel cell carcinoma tures or diagnostic uncertainty, and it is essential if there is haveallbeenreportedinpatientswithvulvalLS,andmelanoma any suspicion of neoplastic change. As LS is less common in in male genital LS,73 but no studies prove that there is an young adult female patients presenting in the reproductive increased frequency of these tumours. There appear to be two years, a biopsy should be considered to confirm the diagnosis pathogeneticmechanismsforgenitalSCC:firstly,SCCinyounger beforestarting treatment. patientsisassociatedwiththeoncogenictypesofhumanpapilloThe site of the biopsy is important, and it should be taken mavirus (HPV, specifically high-risk HPV16 and HPV18); and from the most active sclerotic area. Good clinicopathological secondly,inolderpatients,theassociationiswithachronicscarcorrelation with active discussion between clinician and ringdermatosis suchasLS(orLP)withlittleevidenceofa link BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 8}, {"text": "BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 847 with HPV.74\u201376 Differentiated vulval intraepithelial neoplasia Phimosis Phimosis is due to preputial scarring. Phimosis can (VIN)orPeINassociatedwithadermatosisisaprecursorofSCC make a topical steroid difficult to apply to the diseased inner butcanbechallengingtodiagnosehistologically.77Localrecuraspect of the foreskin, and methods of applying the topical renceofavulvalSCCisgreaterinthosewithLS.78 steroid should be reviewed. One option is to introduce the topical steroid using a cotton wool bud. If the phimosis has Squamous cellcarcinoma infemalepatientswithgenital lichensclerosus This failed to respond to a potent topical steroid the patient should risk of developing malignancy is approximately 3(cid:1)5\u20135%.6,42,79 be referred for circumcision. If the disease is still active at the However, histopathological examination of vulval SCCs inditime of surgery it is important to continue topical steroids to cates that about 60% occur on a background of LS.80\u201382 LS prevent Koebnerization and further scarring, particularly may act as both an initiator and a promoter of carcinogenesis around thecoronal sulcus. by mechanisms that seem to be independent of HPV. However, HPVmay befound in VINassociatedwith LS.83 Adhesions and frenulum disease Adhesions may be transcoronal or SCC of the vulva should be managed by gynaecological subcoronal. Often there is a mixed presentation. They may be oncologistsassurgeryhastobeindividualizedaccordingtothe reduced manually by the patient during treatment with ultratumoursizeandlocation,particularlyinearlyinvasivedisease. potent topical steroids or they may require surgical reduction usually duringcircumcision. Squamous cell carcinoma in men with genital lichen sclerosus An associaFrenulum scarring may be the cause of significant sexual tion between LS and penile SCC has also been morbidity and has a variable response to topical steroids. reported.53,70,84,85 The maximum rate is 12(cid:1)5% and the miniFrenuloplasty may be necessary, usually in the context of mum is 0%.17,86 The overall rate is probably 4\u20135% as in complete circumcision. women.42 Histological evidence of LS can be found in about 23\u201340% of penile carcinomas.85,87,88 In a 10-year multicentre Meatal stenosis in male patients Ifthisresultsinanimpairedurinary cohort of 130 male patients with genital LS, histological stream,referralforurologicalassessmentisadvisable.Beforereferchanges of SCC were found in eight, verrucous carcinoma in ral a meatal stenosis can be treated with a topical steroid introtwo andPeIN in one.89 ducedviacottonwoolbudormeataldilatorfor1\u20133 months. Rarely, chronic LS-related urethral stricture disease is associated withan SCC oftheurethra. Urethralstricture Although LS may startatthe meatus,thecondiThe role of HPV in penile LS-associated SCC has also been tion may spread proximally to involve the penile and bulbar debated.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 9}, {"text": "LS-related urethral stricture disease is associated withan SCC oftheurethra. Urethralstricture Although LS may startatthe meatus,thecondiThe role of HPV in penile LS-associated SCC has also been tion may spread proximally to involve the penile and bulbar debated. Some studies using polymerase chain reaction have urethra.53 Urethral involvement is reported to occur in 20% documentedanegligiblefrequencyofHPVinLS,90,91butother of male patients with LS.53 All male patients with LS should studieshavesuggestedafrequencyofupto33%.92,93Anaddibe questioned about urinary symptoms. If they are present, tionalfeaturethathasbeenlinkedwithpenileLS-associatedSCC referral to a specialist urologist for further investigation is is the occurrence of a prominent lichenoid infiltrate on longneeded. Prior to invasive surgery for a urethral stricture, a standing,chronicLS,suggestingdiseasereactivation.94 urologist mayconsidertreatmentwithatopicalsteroidapplied to the urethra via a urinary catheter or meatal dilator, depending onthelength ofthestricture.69 5.6.2 Scarring Introital narrowing Anterior and/or posterior fusion of the labia 5.6.3 Sensory abnormalities can lead to a narrowing of the introitus. If this is significant and causes dyspareunia or difficulty with micturition, surVulvodynia Vulvodynia may occur after any inflammatory congery may need to be considered, using part of the posterior dition of the vulva or vestibule. Typically, the patient remains vaginal wall in the reconstruction to prevent further adhesymptomatic despite objective clinical improvement or resolusions and stenosis due to Koebnerization.95,96 Topical stertion of the skin lesions. Neuropathic pain does not respond to oids, together with the use of vaginal dilators, must be topical corticosteroids, and treatment must be directed to this used postoperatively to prevent readhesion.97 The topical entity. steroid can be started 48 h postoperatively once daily until the area is fully epithelialized and then reduced in frePenile dysaesthesia Men may develop a similar problem, with an quency on an individual basis to maintain control of sympabnormal burning sensation on the glans or around the uretoms and signs. thral meatus. The managementis asfor femalepatients. Pseudocyst of the clitoris Occasionally, clitoral hood adhesions seal 5.6.4 Psychosexual problems over the clitoris, and keratinous debris builds up underneath forming a painful pseudocyst. These patients should be LS has a significant impact on quality of life,100\u2013102 particureviewed with a gynaecologist with a special interest in vulval larly on sexual functioning.103 Psychosexual issues are comdisease. Division of adhesions may be needed if symptomatic mon and may persist after successful treatment.104 Patients or recurrently infected.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 9}, {"text": "special interest in vulval larly on sexual functioning.103 Psychosexual issues are comdisease. Division of adhesions may be needed if symptomatic mon and may persist after successful treatment.104 Patients or recurrently infected.98,99 who have any chronic genital disorder will often lose their \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 2, "page": 9}, {"text": "848 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. interest in sexual activity, leading to problems with sexual the patient may require penile reconstruction110 combined dysfunction.105,106 It is important to give the patient the withremovalofthesuprapubicandlateralfatpads.111 opportunity to express their concerns about their sexual function, and to offer a referral to someone with the necessary expertise to address these problems. Menopause may also have 7.0 Follow-up an effect on sexual function, which may be helped by horFollow-up is needed for patients with LS to assess response to monereplacement. treatment,toconfirmgoodcontrol ofthediseaseandtocheck for complications. It is also an opportunity to provide patient 6.0 Treatment failure education and to ensure that patients know how to manage their disease well. The frequency and length of follow-up If treatment with topical corticosteroids appears to fail to must betailored tothepatient. bringLSundercontrolthenitisimportanttoconsiderthefollowing. (cid:129) Is noncompliance an issue? Sometimes patients may be 7.1 Adult female patients alarmed at the contents of the package information insert Those patients with uncomplicated disease that responds well warning against the use of topical corticosteroids in the to topical treatment need limited follow-up. Two follow-up anogenital area. Patients with poor eyesight and/or limited visits after the initial consultation are suggested: one at mobility or flexibility may not be able to apply the medi3 months to assess response to treatment and to check that cation appropriately. It is also important to ensure that the the patient is using the topical corticosteroid appropriately, treatment is being applied in an adequate amount and to and a second assessment 6 months later to ensure that the thecorrectsite. (cid:129) patient is confident in treating their problem and to take the Has the correct diagnosis been made? If a biopsy was not opportunity to discuss any residual problems before dischargdone previously, it should be considered to exclude differing to the care of their primary physician. Emollients should ential diagnoses including LP, mucous membrane pembe continued, and if the patient needs to apply a topical sterphigoid or genital intraepithelial neoplasia. Another oid regularly, it is suggested that they see their primary-care differential diagnosis is vitiligo, but this does not cause physician once a year. However, as over half of women disany architectural change and is asymptomatic; however, chargedfromU.K.vulvalclinicsarenotsubsequentlyfollowed vitiligo may coexist withLS.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 10}, {"text": "but this does not cause physician once a year. However, as over half of women disany architectural change and is asymptomatic; however, chargedfromU.K.vulvalclinicsarenotsubsequentlyfollowed vitiligo may coexist withLS. (cid:129) up in primary care appropriately,112 it is important that Is there an additional superimposed problem such as the instructions for self-monitoring are fullyunderstood. development of a contact allergy to the medication (refer The risk of malignancy in uncomplicated genital LS that has for patch testing), urinary incontinence (refer for urologibeendiagnosedandtreatedappropriatelyissmall,andinfemale cal advice), herpes simplex infection or candidiasis (treat patients there is growing evidence that LS under good control infection appropriately)? Some patients can have LS and has a reduced risk of scarring and malignancy.113 Written psoriasis together, which may be more difficult to coninstructions should be given to the patient at the time of their trol.107,108 (cid:129) discharge from the clinic explaining that any change of sympThose patients with hyperkeratotic LS often require further toms, lack of response to topical treatment, new areas of erotreatment and should be referred to a specialist clinic. Syssion, ulceration or the development of any lumps must be temicretinoids may beconsidered in this group. (cid:129) reported to their family practitioner straight away, who will Has the patient developed vulvodynia/penodynia? If the LS thenmakeanurgentreferralbacktoanappropriatespecialist. has been successfully treated but the patient remains Long-term follow-up in a secondary-care specialist clinic is symptomatic, often with burning or soreness being a preappropriate for female patients with anogenital LS associated dominant symptom rather than itch, always consider vulwith ongoing troublesome symptoms, atypical disease, previvodynia/penodynia. (cid:129) ous cancer or any type of VIN, or pathological uncertainty Has the patient presented with a tight phimosis? Phimosis about intraepithelial neoplasia.114 Biopsies of persistent erocan make a topical steroid difficult toapply to the diseased sions, ulcers, and hyperkeratotic and fixed erythematous areas inner aspect of the foreskin, and methods of applying the should excludeintraepithelial neoplasia or invasive SCC. topical steroid should be reviewed. One option is to introFemale patients who require surgery for severe fusion leadduce the topical steroid using a cotton wool bud.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 10}, {"text": "If the ing to functional difficulties need close follow-up postoperaphimosis is sufficiently tight that the application of a topitively with intensive topical steroid treatment to prevent cal steroid is impossible, the patient should be referred to recurrence offusion. aurologist for acircumcision. (cid:129) Hastopicaltreatmentfailedinanobesemalepatient?These patients may find topical treatment difficult to apply as the 7.1.1 Children andyoungpeople \u2013 female penisbecomesburied.Treatmentshouldbedirectedatcorrecting obesity, and this may involve bariatric surgery if GirlswithLSshouldbeseenat3 monthsaftertheinitialconsulconservative methods of weight loss fail.109 Subsequently tation and then 6 months later. Emollients can be continued, BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 2, "page": 10}, {"text": "BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 849 and maintenance treatment with a topical steroid may be the meatus118 and toreview thehistopathology of thecircumrequired.115Follow-upshouldcontinueuntilatleastpubertyin cision specimen. Topical steroid therapy should be initiated to allcases,butanychildwithatypicalorpoorlyresponsivedisease remaining active areas of LS. As in men, any child with shouldbeunderlong-termfollow-upinaspecializedclinic. ongoing active disease should remain under review. Obese children and those who have had surgical interventions, including a hypospadias repair, are at a greater risk of 7.2 Adult male patients persistent disease.60,119 Follow-up should occur at 3 months after diagnosis and the initial courseoftopicalsteroid. Symptomsshould berecorded, 7.3 Extragenital lichensclerosus particularly those relating to sexual and urinary function. If the disease has responded well to topical steroids a further Patients with extragenital disease do not need prolonged folreview 6 months later is recommended. At this stage, if dislow-up unless they are on systemic agents, where follow-up ease remission has continued, the patient can be discharged. It should adhere to relevant guidance on drug monitoring. If is essential that written information is provided outlining they have had phototherapy, a follow-up visit would be symptoms and signs that may suggest disease relapse, and neededtoassess response totreatment. those that may be related to malignant change. As in female patients, male patients should see their general practitioner, who will referbacktosecondary care forfurther assessment. 8.0 Recommended audit points Those men who require circumcision at 3 months because In the last 20 consecutive patients have the following points of persistent disease unresponsive to topical steroids should be been met? reviewed after surgery. Circumcision following a tight phimo1 Is there documentation of the history, including urinary sis may reveal active disease on the glans and in the coronal symptoms andsexual andpsychosexual symptoms? sulcus, which will require further treatment with a topical 2 Has a biopsy been performed in patients with clinically steroid. The results of biopsies taken during surgery must be active LS that has not responded to treatment in female reviewed, as they may confirm the clinical diagnosis of LS; patients? biopsies from suspicious areas suggestive of PeIN or SCC must 3 Has a topical steroid of adequate potency and duration be reviewed and appropriate treatment instigated.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 11}, {"text": "topical steroid of adequate potency and duration be reviewed and appropriate treatment instigated. For many been used prior to circumcision in male patients with patients, circumcision may cure their disease and they can be symptomatic LS? discharged afterthepostoperative follow-up visit. 4 Are all circumcision specimens sent for histology to conPatients with active ongoing disease will require long-term firm the diagnosis of LS and to exclude PeIN, which will follow-up. At each review, symptoms, particularly urinary and aid in thefuturemanagement ofthepatient? sexual, should be assessed and any changes suggestive of PeIN 5 Have patients discharged from the clinic been given or SCC (persistent area of well-defined erythema, erosion, advice on when to seek advice if further symptoms ulceration,papuleornodule)shouldbebiopsied.Patientswith occur? urinarysymptomsshouldbereferredtoaurologistforflowrate andpostvoidresidualvolumemeasurementtoidentifyurethral The audit recommendation of 20 cases per department is to involvement by LS; ultimately, referral to a specialist urologist reduce variation in the results due to a single patient, and to for management of a urethral stricture or meatal stenosis may allow benchmarking between different units. However, beneeded.Wheremedicaltreatmenthasfailed,patientsshould departments unable to achieve this recommendation may be offered referral to discuss other surgical treatment options choose toauditallcases seenin thepreceding12 months. such as division of coronal adhesions, frenuloplasty and glans resurfacingwithsplit-skingrafting.Followingsurgery,patients 9.0 Stakeholder involvement and peer review should continue under review as LS may recur after surgical treatment, and follow-up treatment with topical steroids may The draft document and supporting information were made berequired.Menwhoaredischargedbecausetheirdiseaseisin available to the BAD membership, the British Dermatological remissionshouldbeawarethatLScanrecuraftermanyyears116 Nursing Group (BDNG), Primary Care Dermatological Society and that they should seek referral to specialist services if there (PCDS), British Society for Paediatric Dermatology (BSPD), aresignsofdiseaserecurrence. British Society for the Study of Vulval Disease (BSSVD), British Association of Sexual Health and HIV (BASHH), Royal College of Obstetrics & Gynaecology (RCOG), Royal College 7.2.1 Children andyoungpeople \u2013 male of General Practitioners (RCGP), Royal College of Paediatrics A proportion of boys presenting with phimosis due to LS will & Child Health (RCPCH), British Association of Urological respond to topical steroids.117 Children with phimosis unreSurgeons, British Association of Paediatric Urologists (BAPU), sponsive to topical steroids are referred to a urologist for cirBritish Association of Urological Nurses (BAUN), British cumcision.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 11}, {"text": "(BAPU), sponsive to topical steroids are referred to a urologist for cirBritish Association of Urological Nurses (BAUN), British cumcision. Following surgery, the boys should be reviewed to Association of Urological Pathologists (BAUP) and urology assess residual disease that may be present in the glans and/or and gynaecology colleagues for comments, which were \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 2, "page": 11}, {"text": "850 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. actively considered by the GDG. Following further review, 7 Fistarol SK, Itin PH. Diagnosis and treatment of lichen sclerosus: the finalized version was sent for peer review by the Clinical anupdate.AmJClinDermatol2013;14:27\u201347. Standards Unit of the BAD, made up of the Therapy & 8 Day T, Moore S, Bohl TG etal. Comorbid vulvar lichen planus andlichensclerosus.JLowGenitTractDis2017;21:204\u20138. Guidelines subcommittee, prior to submission for 9 Dickie RJ, Horne CH, Sutherland HW etal. Direct evidence of publication. localised immunological damage in vulvar lichen sclerosus et atrophicus.JClinPathol1982;35:1395\u20137. 10.0 Limitations of the guideline 10 CarliP,CattaneoA,PimpinelliNetal.Immunohistochemicalevidence of skin immune system involvement in vulvar lichen scleThis document has been prepared on behalf of the BAD and is rosusetatrophicus.Dermatologica1991;182:18\u201322. based on the best data available when the document was pre11 Farrell AM, Marren P, Dean D etal. Lichen sclerosus: evidence that immunological changes occur at all levels of the skin. Br J pared. It is recognized that under certain conditions it may be Dermatol1999;140:1087\u201392. necessary todeviate from the guidelines and that the results of 12 Terlou A, Santegoets LA, van der Meijden WI etal. An autoimfuture studies may require some of the recommendations mune phenotype in vulvar lichen sclerosus and lichen planus: a herein to be changed. Failure to adhere to these guidelines Th1 response and high levels of microRNA-155. J Invest Dermatol should not necessarily be considered negligent, nor should 2012;132:658\u201366. adherence to these recommendations constitute a defence 13 Cooper SM, Ali I, Baldo M etal. The association of lichen scleagainst aclaimofnegligence. rosus and erosive lichen planus of the vulva with autoimmune disease: a case\u2013control study. Arch Dermatol 2008; 144: 1432\u20135. 11.0 Plans for guideline revision 14 Harrington CI, Dunsmore IR. An investigation into the incidence of auto-immune disorders in patients with lichen sclerosus and The proposed revision date for this set of recommendations is atrophicus.BrJDermatol1981;104:563\u20136. scheduled for 2023; where necessary, important interim 15 Meyrick Thomas RH, Ridley CM, Black MM. The association of changes will beupdatedon theBAD website. lichen sclerosus et atrophicus and autoimmune-related disease in males.BrJDermatol1983;109:661\u20134. 16 Birenbaum DL, Young RC. High prevalence of thyroid disease in Acknowledgments patientswithlichensclerosus.JReprodMed2007;52:28\u201330. 17 Edmonds EV, Hunt S, Hawkins D etal.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 12}, {"text": "High prevalence of thyroid disease in Acknowledgments patientswithlichensclerosus.JReprodMed2007;52:28\u201330. 17 Edmonds EV, Hunt S, Hawkins D etal. Clinical parameters in We are very grateful to both patient representatives for their male genital lichen sclerosus: a case series of 329 patients. J Eur input in formulating the clinical question, ranking of the outAcadDermatolVenereol2012;26:730\u20137. comes, reviewing of the evidence and formulating the recom18 Kantere D, Alvergren G, Gillstedt M etal. Clinical features, commendations and subsequent draft guideline; to Mr Asif plications and autoimmunity in male lichen sclerosus. Acta Derm Muneer, Consultant Urological Surgeon and Andrologist Venereol2017;97:365\u20139. 19 Edmonds E, Barton G, Buisson S etal. Gene expression profiling (University College Hospital NHS Foundation Trust) for his inmalegenitallichensclerosus.IntJExpPathol2011;92:320\u20135. advice and input; and to all those who commented on the 20 ChanI,OyamaN,NeillSMetal.CharacterizationofIgGautoantidraftduring theconsultation period. bodies to extracellular matrix protein 1 in lichen sclerosus. Clin ExpDermatol2004;29:499\u2013504. References 21 Edmonds EV, Oyama N, Chan I etal. Extracellular matrix protein 1 autoantibodies in male genital lichen sclerosus. Br J Dermatol 1 MohdMustapaMF,ExtonLS,BellHKetal.Updatedguidancefor 2011;165:218\u201319. writing a British Association of Dermatologists clinical guideline: 22 Kirk PS, Yi Y, Hadj-Moussa M etal. Diversity of patient profile, the adoption of the GRADE methodology 2016. Br J Dermatol urethral stricture, and other disease manifestations in a cohort 2017;176:44\u201351. of adult men with lichen sclerosus. Investig Clin Urol 2016; 2 Brouwers MC, Kho ME, Browman GP etal. AGREE II: advancing 57:202\u20137. guideline development, reporting and evaluation in health care. 23 Hofer MD, Meeks JJ, Mehdiratta N etal. Lichen sclerosus in men CMAJ2010;182:E839\u201342. is associated with elevated body mass index, diabetes mellitus, 3 Guyatt GH, Oxman AD, Vist GE etal. GRADE: an emerging concoronary artery disease and smoking. World J Urol 2014; 32:105\u2013 sensus on rating quality of evidence and strength of recommen8. dations.BMJ2008;336:924\u20136. 24 Bunker CB, Patel N, Shim TN. Urinary voiding symptomatology 4 British Society for the Study of Vulval Disease. Vulval lichen (micro-incontinence) in male genital lichen sclerosus. Acta Derm sclerosus \u2013 guidance for health care professionals (hospital team Venereol2013;93:246\u20138. or GP special interest). Available at: https://bssvd.org/edu 25 Al-Niaimi F, Lyon C. Peristomal lichen sclerosus: the role of cation-and-training/guidelines-and-clinical-standards/documents/ occlusionandurineexposure?BrJDermatol2013;168:643\u20136. Lichen-Sclerosus-management.pdf (last accessed 8 January 26 Uemura S, Hutson JM, Woodward AA etal. Balanitis xerotica 2018). obliterans with urethral stricture after hypospadias repair.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 12}, {"text": "C. Peristomal lichen sclerosus: the role of cation-and-training/guidelines-and-clinical-standards/documents/ occlusionandurineexposure?BrJDermatol2013;168:643\u20136. Lichen-Sclerosus-management.pdf (last accessed 8 January 26 Uemura S, Hutson JM, Woodward AA etal. Balanitis xerotica 2018). obliterans with urethral stricture after hypospadias repair. Pediatr 5 Smith YR, Haefner HK. Vulvar lichen sclerosus: pathophysiology SurgInt2000;16:144\u20135. andtreatment.AmJClinDermatol2004;5:105\u201325. 27 Pass CJ. An unusual variant of lichen sclerosus et atrophicus: 6 Pugliese JM, Morey AF, Peterson AC. Lichen sclerosus: review of delayedappearanceinasurgicalscar.Cutis1984;33:405,408. the literature and current recommendations for management. J 28 YatesVM,KingCM,DaveVK.LichensclerosusetatrophicusfolUrol2007;178:2268\u201376. lowingradiationtherapy.ArchDermatol1985;121:1044\u20137. BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 2, "page": 12}, {"text": "BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 851 29 Milligan A, Graham-Brown RA, Burns DA. Lichen sclerosus et 51 Aynaud O, Piron D, Casanova JM. Incidence of preputial lichen atrophicusfollowingsunburn.ClinExpDermatol1988;13:36\u20137. sclerosus in adults: histologic study of circumcision specimens. J 30 Marren P, Yell J, Charnock FM etal. The association between AmAcadDermatol1999;41:923\u20136. lichen sclerosus and antigens of the HLA system. Br J Dermatol 52 Liatsikos EN, Perimenis P, Dandinis K etal. Lichen sclerosus et 1995;132:197\u2013203. atrophicus. Findings after complete circumcision. Scand J Urol 31 Azurdia RM, Luzzi GA, Byren I etal. Lichen sclerosus in adult Nephrol1997;31:453\u20136. men: a study of HLA associations and susceptibility to autoim53 DepasqualeI,ParkAJ,BrackaA.Thetreatmentofbalanitisxerotmunedisease.BrJDermatol1999;140:79\u201383. icaobliterans.BJUInt2000;86:459\u201365. 32 Powell J, Wojnarowska F, Winsey S etal. Lichen sclerosus pre54 Granieri MA, Peterson AC, Madden-Fuentes RJ. Effect of lichen menarche: autoimmunity and immunogenetics. Br J Dermatol sclerosis on success of urethroplasty. Urol Clin North Am 2017; 2000;142:481\u20134. 44:77\u201386. 33 ShermanV,McPhersonT,BaldoMetal.Thehighrateoffamilial 55 Tausch TJ, Peterson AC. Early aggressive treatment of lichen lichen sclerosus suggests a genetic contribution: an observational sclerosus may prevent disease progression. J Urol 2012; cohortstudy.JEurAcadDermatolVenereol2010;24:1031\u20134. 187:2101\u20135. 34 Gambichler T,Terras S,Kreuter A etal. Altered global methylation 56 Chalmers RJ, Burton PA, Bennett RF etal. Lichen sclerosus et and hydroxymethylation status in vulvar lichen sclerosus: further atrophicus.Acommonanddistinctivecauseofphimosisinboys. supportforepigeneticmechanisms.BrJDermatol2014;170:687\u201393. ArchDermatol1984;120:1025\u20137. 35 Eisendle K, Grabner T, Kutzner H etal. Possible role of Borrelia 57 Meuli M, Briner J, Hanimann B etal. Lichen sclerosus et burgdorferi sensu lato infection in lichen sclerosus. Arch Dermatol atrophicuscausingphimosisinboys:aprospectivestudywith52008;144:591\u20138. year followup after complete circumcision. J Urol 1994; 36 EdmondsE, MavinS, FrancisN etal.Borreliaburgdorferiisnotasso152:987\u20139. ciated with genital lichen sclerosus in men. Br J Dermatol 2009; 58 KissA,KiralyL,KutasyBetal.Highincidenceofbalanitisxerot160:459\u201360. ica obliterans in boys with phimosis: prospective 10-year study. 37 Feig JL, Gribetz ME, Lebwohl MG. Chronic lichen sclerosus sucPediatrDermatol2005;22:305\u20138. cessfully treated with intralesional adalimumab. Br J Dermatol 59 YardleyIE,CosgroveC,LambertAW.Paediatricpreputialpathol2016;174:687\u20139. ogy: are we circumcising enough? Ann R Coll Surg Engl 2007; 38 Lowenstein EB, Zeichner JA. Intralesional adalimumab for the 89:62\u20135. treatment of refractory balanitis xerotica obliterans. JAMA Dermatol 60 Gargollo PC, Kozakewich HP, Bauer SB etal. Balanitis xerotica 2013;149:23\u20134. obliteransinboys.JUrol2005;174:1409\u201312. 39 GoldsteinAT,MarinoffSC,ChristopherKetal.Prevalenceofvul61 Christman MS, Chen JT, Holmes NM. Obstructive complications var lichen sclerosus in a general gynecology practice. J Reprod Med oflichensclerosus.JPediatrUrol2009;5:165\u20139. 2005;50:477\u201380. 62 KekreGA,KothariPR,GuptaARetal.Ararecaseofpreputialcal40 LeibovitzA,KaplunVV,SaposhnicovNetal.Vulvovaginalexamiculiin achild withbalanitis xeroticaobliterans:a short communations in elderly nursing home women residents. Arch Gerontol nication.AfrJUrol2016;22:227\u20139. Geriatr2000;31:1\u20134. 63 Ramrakha-JonesVS,PaulM,McHenryPetal.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 13}, {"text": "Holmes NM. Obstructive complications var lichen sclerosus in a general gynecology practice. J Reprod Med oflichensclerosus.JPediatrUrol2009;5:165\u20139. 2005;50:477\u201380. 62 KekreGA,KothariPR,GuptaARetal.Ararecaseofpreputialcal40 LeibovitzA,KaplunVV,SaposhnicovNetal.Vulvovaginalexamiculiin achild withbalanitis xeroticaobliterans:a short communations in elderly nursing home women residents. Arch Gerontol nication.AfrJUrol2016;22:227\u20139. Geriatr2000;31:1\u20134. 63 Ramrakha-JonesVS,PaulM,McHenryPetal.Naildystrophydue 41 Kizer WS, Prarie T, Morey AF. Balanitis xerotica obliterans: epitolichensclerosus?ClinExpDermatol2001;26:507\u20139. demiologic distribution in an equal access health care system. 64 Marangon Ju(cid:1)nior H, Souza PEA, Soares RV etal. Oral lichen scleSouthMedJ2003;96:9\u201311. rosus: a rare case report and review of the literature. Head Neck 42 Wallace HJ. Lichen sclerosus et atrophicus. Trans St Johns Hosp DerPathol2017;11:212\u201318. matolSoc1971;57:9\u201330. 65 Madan V, Cox NH. Extensive bullous lichen sclerosus with scar43 Lipscombe TK, Wayte J, Wojnarowska F etal. A study of clinical ringalopecia.ClinExpDermatol2009;34:360\u20132. andaetiologicalfactorsand possibleassociationsoflichensclero66 Ballester I, Ban~uls J, P(cid:1)erez-Crespo M etal. Extragenital bullous susinmales.AustralasJDermatol1997;38:132\u20136. lichensclerosusatrophicus.DermatolOnlineJ2009;15:6. 44 Christmann-Schmid C, Hediger M, Groger S etal. Vulvar lichen 67 Criado PR, Lima FH, Miguel DS etal. Lichen sclerosus \u2013 a kerasclerosus in women is associated with lower urinary tract symptoticvariant.JEurAcadDermatolVenereol2002;16:504\u20135. toms.IntUrogynecolJ2018;29:217\u201321. 68 WengAA,Charles-HolmesR.Peristomallichensclerosusaffecting 45 Berger MB, Damico NJ, Menees SB etal. Rates of self-reported colostomysites.BrJDermatol2000;142:177\u20138. urinary, gastrointestinal, and pain comorbidities in women with 69 Potts BA, Belsante MJ, Peterson AC. Intraurethral steroids are a vulvarlichensclerosus.JLowGenitTractDis2012;16:285\u20139. safe and effective treatment for stricture disease in patients with 46 Kennedy CM, Nygaard IE, Bradley CS etal. Bladder and bowel biopsyprovenlichensclerosus.JUrol2016;195:1790\u20136. symptomsamongwomenwithvulvardisease:aretheyuniversal? 70 Bunker CB, Porter WM. Dermatoses of the male genitalia: squaJReprodMed2007;52:1073\u20138. mous carcinoma and other malignant neoplasms. In: Rook\u2019s Text47 Bhargava K, Lewis FM. Lichen sclerosus occurring on vaginal bookof Dermatology(GriffithsCEM,Barker J,BleikerT,ChalmersR, mucosa secondary to uterine prolapse. J Obstet Gynaecol 2013; CreamerD,eds),9thedn,vol.3.Chichester:JohnWiley&Sons, 33:319\u201320. 2016;111.29\u201331. 48 ZendellK,EdwardsL.Lichensclerosuswithvaginalinvolvement: 71 Lewis F. Dermatoses of the female genitalia: inflammatory derreportof2casesandreviewoftheliterature.JAMADermatol2013; matoses of the vulva: lichen sclerosus. In: Rook\u2019s Textbook of Derma149:1199\u2013202. tology(GriffithsCEM,BarkerJ,BleikerT,ChalmersR,CreamerD, 49 Warrington SA, de San Lazaro C. Lichen sclerosus et atrophicus eds), 9th edn, vol. 3. Chichester: John Wiley & Sons, 2016; andsexualabuse.ArchDisChild1996;75:512\u201316. 112.6\u20139. 50 PowellJ,WojnarowskaF.Childhoodvulvarlichensclerosus.The 72 Calonje E, Neill S, Bunker C etal. Diseases of the ano-genital courseafterpuberty.JReprodMed2002;47:706\u20139. skin. In: McKee\u2019s Pathology of the Skin (Calonje JE, Brenn T, Lazar \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 13}, {"text": "Lazar \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 2, "page": 13}, {"text": "852 BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. AJ, McKee PH, eds), 4th edn. Philadelphia: Elsevier, 2011; verrucous and invasive carcinoma of the penis. J Urol 1995; 492\u2013501. 154:1024\u20139. 73 TurnbullN,ShimT,PatelNetal.Primarymelanomaofthepenis 91 Lau PW, Cook N, Andrews H etal. Detection of human papilloin3patientswithlichensclerosus.JAMADermatol2016;152:226\u2013 mavirus types in balanitis xerotica obliterans and other penile 7. conditions.GenitourinMed1995;71:228\u201330. 74 van de Nieuwenhof HP, van Kempen LC, de Hullu JA etal. The 92 Nasca MR, Innocenzi D, Micali G. Association of penile lichen etiologic role of HPV in vulvar squamous cell carcinoma fine sclerosus and oncogenic human papillomavirus infection. Int J tuned.CancerEpidemiolBiomarkersPrev2009;18:2061\u20137. Dermatol2006;45:681\u20133. 75 Mannweiler S, Sygulla S, Winter E etal. Two major pathways of 93 Prowse DM, Ktori EN, Chandrasekaran D etal. Human papillopenile carcinogenesis: HPV-induced penile cancers overexpress mavirus-associated increase in p16INK4A expression in penile p16ink4a, HPV-negative cancers associated with dermatoses lichensclerosusandsquamouscellcarcinoma.BrJDermatol2008; expressp53,butlackp16ink4aoverexpression.JAmAcadDermatol 158:261\u20135. 2013;69:73\u201381. 94 Innocenzi D, Nasca MR, Skroza N etal. Penile lichen sclerosus: 76 Shim TN, Andrich DE, Mundy AR etal. Lichen sclerosus correlation between histopathologic features and risk of cancer. associated with perineal urethrostomy. Br J Dermatol 2014; ActaDermatovenerolCroat2006;14:225\u20139. 170:222\u20133. 95 PanielBJ,TrucJB,deMargerieVetal.[Vulvo-perinealsurgery].J 77 Bigby SM, Eva LJ, Fong KL etal. The natural history of vulvar GynecolObstetBiolReprod(Paris)1984;13:91\u2013100.(inFrench). intraepithelialneoplasia,differentiatedtype:evidenceforprogres96 RouzierR,HaddadB,DeyrolleCetal.Perineoplastyforthetreatsion and diagnostic challenges. Int J Gynecol Pathol 2016; 35:574\u2013 ment of introital stenosis related to vulvar lichen sclerosus. Am J 84. ObstetGynecol2002;186:49\u201352. 78 Yap JK, Fox R, Leonard S etal. Adjacent lichen sclerosis predicts 97 BradfordJ,FischerG.Surgicaldivisionoflabialadhesionsinvullocal recurrence and second field tumour in women with vulvar var lichen sclerosus and lichen planus. J Low Genit Tract Dis 2013; squamouscellcarcinoma.GynecolOncol2016;142:420\u20136. 17:48\u201350. 79 Micheletti L, Preti M, Radici G etal. Vulvar lichen sclerosus and 98 Paniel BJ, Rouzier R. Surgical procedures in benign disease. In: neoplastic transformation: a retrospective study of 976 cases. J Ridley\u2019sTheVulva(NeillSM,LewisFM,eds).London:Wiley-BlackLowGenitTractDis2016;20:180\u20133. well,2009;236. 80 LeibowitchM,NeillS,PelisseMetal.Theepithelialchangesasso99 Goldstein AT, Burrows LJ. Surgical treatment of clitoral phimosis ciated with squamous cell carcinoma of the vulva: a review of causedbylichensclerosus.AmJObstetGynecol2007;196:126. the clinical, histological and viral findings in 78 women. Br J 100 Rajagopalan R, Anderson RT, Sherertz EF etal. Quality of life ObstetGynaecol1990;97:1135\u20139. evaluationinchroniclichensclerosusforimprovedmedicalcare. 81 WalkdenV,ChiaY,WojnarowskaF.Theassociationofsquamous DrugInfJ1999;33:577\u201384. cell carcinomaof the vulva and lichensclerosus: implicationsfor 101 LansdorpCA,vandenHondelKE,KorfageIJetal.Qualityoflife managementandfollowup.JObstetGynaecol1997;17:551\u20133. in Dutch women with lichen sclerosus. Br J Dermatol 2013; 82 VilmerC,Cavelier-BalloyB,NoguesCetal.Analysisofalterations 168:787\u201393.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 14}, {"text": "carcinomaof the vulva and lichensclerosus: implicationsfor 101 LansdorpCA,vandenHondelKE,KorfageIJetal.Qualityoflife managementandfollowup.JObstetGynaecol1997;17:551\u20133. in Dutch women with lichen sclerosus. Br J Dermatol 2013; 82 VilmerC,Cavelier-BalloyB,NoguesCetal.Analysisofalterations 168:787\u201393. adjacent to invasive vulvar carcinoma and their relationship with 102 van Cranenburgh OD, Nijland SBW, Lindeboom R etal. Patients the associated carcinoma: a study of 67 cases. Eur J Gynaecol Oncol withlichensclerosusexperience moderatesatisfactionwithtreat1998;19:25\u201331. ment and impairment of quality of life: results of a cross-sec83 van SetersM,tenKateFJ, vanBeurdenM etal.Inthe absenceof tionalstudy.BrJDermatol2017;176:1508\u201315. (early) invasive carcinoma, vulvar intraepithelial neoplasia 103 Van De Nieuwenhof HP, Meeuwis KAP, Nieboer TE etal. The associated with lichen sclerosus is mainly of undifferentiated effect of vulvar lichen sclerosus on quality of life and sexual type: new insights in histology and aetiology. J Clin Pathol 2007; functioning.JPsychosomObstetGynecol2010;31:279\u201384. 60:504\u20139. 104 Burrows LJ, Creasey A, Goldstein AT. The treatment of vulvar 84 Nasca MR, Innocenzi D, Micali G. Penile cancer among lichen sclerosus and female sexual dysfunction. J Sex Med 2011; patients with genital lichen sclerosus. J Am Acad Dermatol 1999; 8:219\u201322. 41:911\u201314. 105 Dalziel KL. Effect of lichen sclerosus on sexual function and par85 Powell J, Robson A, Cranston D etal. High incidence of lichen turition.JReprodMed1995;40:351\u20134. sclerosus in patients with squamous cell carcinoma of the penis. 106 Marin MG, King R, Dennerstein GJ etal. Dyspareunia and vulvar BrJDermatol2001;145:85\u20139. disease.JReprodMed1998;43:952\u20138. 86 KravvasG,ShimTN,DoironPRetal.Thediagnosisandmanage107 EberzB, BergholdA, RegauerS.High prevalenceofconcomitant ment of male genital lichen sclerosus: a retrospective review of anogenital lichen sclerosus and extragenital psoriasis in adult 301patients.JEurAcadDermatolVenereol2018;32:91\u20135. women.ObstetGynecol2008;111:1143\u20137. 87 Pietrzak P, Hadway P, Corbishley CM etal. Is the association 108 Simpkin S, Oakley A. Clinical review of 202 patients with vulval betweenbalanitisxeroticaobliteransandpenilecarcinomaunderlichen sclerosus: a possible association with psoriasis. Australas J estimated?BJUInt2006;98:74\u20136. Dermatol2007;48:28\u201331. 88 Philippou P, Shabbir M, Ralph DJ etal. Genital lichen sclerosus/ 109 NationalInstituteforHealthandCareExcellence.Obesity:identibalanitisxeroticaobliteransinmenwithpenilecarcinoma:acritfication, assessment and management. Clinical guideline CG189. icalanalysis.BJUInt2013;111:970\u20136. Available at: https://www.nice.org.uk/guidance/cg189 (last 89 Barbagli G, Palminteri E, Mirri F etal. Penile carcinoma in accessed8January2018). patients with genital lichen sclerosus: a multicenter survey. J Urol 110 FiglerBD,CheryL,FriedrichJBetal.Limitedpanniculectomyfor 2006;175:1359\u201363. adultburiedpenisrepair.PlastReconstrSurg2015;136:1090\u20132. 90 Cupp MR, Malek RS, Goellner JR etal. The detection of human 111 DoironPR,BunkerCB.Obesity-relatedmalegenitallichenscleropapillomavirus deoxyribonucleic acid in intraepithelial, in situ, sus.JEurAcadDermatolVenereol2017;31:876\u20139. BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 14}, {"text": "intraepithelial, in situ, sus.JEurAcadDermatolVenereol2017;31:876\u20139. BritishJournalofDermatology(2018)178,pp839\u2013853 \u00a92018BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 2, "page": 14}, {"text": "BADguidelinesforthemanagementoflichensclerosus,2018, F.M.Lewisetal. 853 112 Balasubramaniam P, Lewis FM. Long-term follow-up of patients Supporting Information withlichensclerosus:doesitreallyhappen?JObstetGynaecol2007; 27:282. AdditionalSupportingInformationmaybefoundintheonline 113 Lee A, Bradford J, Fischer G. Long-term management of adult version ofthis article atthepublisher\u2019s website: vulvar lichen sclerosus: a prospective cohort study of 507 women.JAMADermatol2015;151:1061\u20137. Appendix AReview protocol. 114 Jones RW, Scurry J, Neill S etal. Guidelines for the follow-up of Appendix B Clinical evidencesummary. women with vulvar lichen sclerosus in specialist clinics. Am J Appendix CLinking evidencetorecommendations. ObstetGynecol2008;198:496. Appendix D Forestplots. 115 Ellis E, Fischer G. Prepubertal-onset vulvar lichen sclerosus: the Appendix E GRADE evidencetables. importance of maintenance therapy in long-term outcomes. PediAppendix F Summary ofincluded studies. atrDermatol2015;32:461\u20137. Appendix G Narrative findingsfor noncomparative studies. 116 Mangera A, Osman N, Chapple C. Recent advances in understandingurethrallichensclerosus.F1000Res2016;5:96. Appendix H Summary of topical steroids case series and 117 Kiss A, Csontai A, Piro(cid:1)t L etal. The responseof balanitis xerotica casereports. obliterans to local steroid application compared with placebo in Appendix I PRISMAdiagram\u2013 study selection. children.JUrol2001;165:219\u201320. Appendix J Papers excludedfromquantitative analysis. 118 Ebert AK, R\u20acosch WH, Vogt T. Safety and tolerability of adjuvant Appendix K Methodology. topical tacrolimus treatment in boys with lichen sclerosus: a Appendix L Search strategy. prospectivephase2study.EurUrol2008;54:932\u20137. 119 BeckerK.Lichensclerosusinboys.DtschArzteblInt2011;108:53\u2013 Author S1 Video. Powerpoint S1 Journal ClubSlide Set. 8. \u00a92018BritishAssociationofDermatologists BritishJournalofDermatology(2018)178,pp839\u2013853 Downloaded from https://academic.oup.com/bjd/article/178/4/839/6602656 by guest on 23 February 2026", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 15}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "lichen sclerosis guidline.pdf", "chunk_id": 0, "page": 16}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "lichen sclerosis guidline.pdf", "chunk_id": 1, "page": 16}, {"text": "BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists guidelines for the management of adults with basal cell carcinoma 2021* I. Nasr iD,1 E.J. McGrath,2 C.A. Harwood iD,3,4 J. Botting,5 P. Buckley,6 P.G. Budny,7,8 P. Fairbrother,6 K. Fife iD,9,10 G. Gupta iD,11 M. Hashme,1 S. Hoey,12 J.T. Lear,13,14,15 R. Mallipeddi,16,17 E. Mallon,18 R.J. Motley iD,19 C. Newlands,20,21 J. Newman,22,23 E.V. Pynn,24 N. Shroff,25 D.N. Slater iD,26 L.S. Exton iD,1 M.F. Mohd Mustapa iD,1 M.C. Ezejimofor iD 1 on behalf of the British Association of Dermatologists\u2019 Clinical Standards Unit Correspondence Linked Comment: M.D. Moncrieff and J.P. Nobes. Br J Derma IbrahimNasr. tol 2021;185:877. Email:ibrahim.nasr@outlook.com;guidelines@bad.org.uk ThisisanupdatedguidelinepreparedfortheBritishAssociation Accepted forpublication ofDermatologists(BAD)ClinicalStandardsUnit,whichincludes 26May2021 theTherapy&Guidelines(T&G)subcommittee.Membersofthe Clinical Standards Unit who have been involved are N.J. Levell TheauthoraffiliationscanbefoundintheAppendix. (Chairman T&G), B. McDonald (Assistant Honorary Secretary), F.S. Worsnop, P. Rakvit, S.L. Chua, P. Laws, A. Bardhan, L.S. Funding sources Exton(BADGuidelineResearchFellow),M.Hashme(BADInforNone. mationScientist),M.C.Ezejimofor(BADGuidelineResearchFellow)andM.F.MohdMustapa(BADClinicalStandardsManager). Conflicts ofinterest C.A.H.hasreceivedhonorariaasanadvisoryboardmemberandspeakerforRoche, LEOPharmaandNovartis(specific)andforSanofi,Merck(nonspecific);andhasacted 1. Purpose and scope asaclinicaltrialinvestigatorforPellePharmInc.(specific)andNovartis,LEOPharma andMeda(nonspecific).P.B.wasemployedwithinthehealthcareindustry(2003\u2013 The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of basal 2013;specific).P.G.B.isDeputyChairoftheTVCNSkinCancerTSSG(specific). K.F.hasreceivedhonorariaasanadvisoryboardmemberandspeakerforRoche(specicell carcinoma (BCC).The document aims to: fic)andsponsorshiptoattendameetingfromRoche(specific).G.G.hasreceivedhono- (cid:129) Offer an appraisal of all relevant literature up to 24 JanrariaasanadvisoryboardmemberandspeakerforAlmirall,LEOPharmaandMeda uary 2020,focusing on anykey developments. (specific)andfromNovartis(nonspecific);andresearchsupportfromBiofrontera(speci- (cid:129) Address important, practical clinical questions relating to fic)andLEOPharmaandMeda(nonspecific).S.H.hasreceivedhonorariaasanadvitheprimary guideline objective. soryboardmemberandspeakerfromAbbVieandJanssen(nonspecific).J.T.L.has (cid:129) receivedhonorariaasanadvisoryboardmemberandspeakerfromLEOPharma,Meda, Provide guideline recommendations and, if appropriate, NovartisandRoche(specific).E.M.hasreceivedsponsorshiptoattendameetingfrom research recommendations. LEOPharma(specific).C.N.isaninvestorinaprivateGPweb-basedcompany(nonThe guideline is presented as a detailed review with highspecific).E.V.P.hasreceivededucationsponsorshiptoattendadermatologycoursefrom lighted recommendations for practical use in primary care [all LEOPharma(specific).D.N.S.isaleadonaskincancerdataset(specific).Allother general practitioners (GPs)], intermediary care [accredited authorsdeclaretheyhavenoconflictsofinterest. GPs, currently known as a GPs with extended role (GPwERs)] Producedin1999bytheBritishAssociationofDermatologists. and secondary care (see section 3.0), in addition to an updatedpatientinformationleaflet(availableontheBADweb- *Plainlanguagesummaryavailableonline site, www.skinhealthinfo.org.uk/a-z-conditions-treatments). Reviewedandupdated2008,2021. 1.1. Keyexclusions DOI10.1111/bjd.20524 BCC involving the eyelid has been excluded from this guideNICEhasaccreditedtheprocessusedbytheBritishAssociation ofDermatologiststoproduceclinicalguidelines.Therenewed line (see section 6.3). accreditationisvaliduntil31May2026andappliestoguidance producedusingtheprocessdescribedinupdatedguidanceforwriting aBritishAssociationofDermatologistsclinicalguidance\u2013the adoptionoftheGRADEmethodology2016.Theoriginalaccredi2. Methodology tationtermbeganon12May2010.Moreinformationonaccreditationcanbeviewedatwww.nice.org.uk/accreditation. This setofguidelines hasbeen developed using theBAD\u2019srecommended methodology1 (Appendix J; see Supporting Information) with reference to the AGREE II instrument2 and GRADE.3 Recommendations were developed for implementation in theUK NationalHealth Service(NHS). \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 899 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 1}, {"text": "900 BADguidelinesforadultswithBCC2021, I.Nasretal. TheGuidelineDevelopmentGroup(GDG)consistsof10conComprehensiveCancerNetwork(NCCN)guidelines7gavemore sultantdermatologists(representingEngland,NorthernIreland, preciseclinicalcriteriaforclinicallow-riskandhigh-riskBCC.As ScotlandandWales;threeofwhomarealsoMohssurgeons),a theUnionforInternationalCancerControl8thedition(UICC8)8 consultant plastic surgeon, a consultant oral and maxillofacial versionofTNM8(tumour\u2013nodes\u2013metastasis)hasbeenendorsed surgeon, a clinical oncologist, a pathologist, two primary care foruseintheUK,andasNCCNusestheAmericanJointCommitphysicians,aclinicalnursespecialist,twopatientrepresentatives tee on Cancer 8th edition cancer staging manual (AJCC8),9 the andatechnicalteam(consistingofaninformationscientist,two NCCN table on low-risk and high-risk BCC criteria has been guideline research fellows and a project manager providing adaptedheretoequatetotheUICC8andRCPathdataset. methodological and technical support). The GDG established The GDG\u2019s adopted definition of criteria for low-risk and severalclinicalquestionspertinenttothescopeoftheguideline high-risk BCC is provided inTable 2. andasetofoutcomemeasuresofimportancetopatients,ranked The GDG identified a paper that provided a definition for according to the GRADE methodology (section 2.1 and advanced BCC,10 but it was dependent on the AJCC7 risk criAppendix A;seeSupportingInformation). teria. The GDG adopted the definition with some adaptation A systematic literature search of the PubMed, MEDLINE, tobeusedin this guideline, as follows: Embase and Cochrane databases was conducted to identify key \u2018An advanced BCC is a BCC that is either (i) metastatic articles on BCC published from 1 January 2007 to 24 January (mBCC) or (ii) locally advanced (laBCC) with one or 2020 (publications already included in the 2008 guideline4 more high-risk factors, in which current treatment were evaluated for inclusion). Search terms and strategies can modalities are considered potentially contraindicated by be found in Appendix K (see Supporting Information). Additumour orpatient factors\u2019. tional references relevant to the topic were also extracted from citationsinthereviewedliterature,and,whereidentified,releClinical tumour factors that may contribute individually or in vant articles published after May 2017 were included. Evicombination to a BCC being regarded as locally advanced dence from the included studies was graded according to the include: GRADE system (high, moderate, low, or very low certainty). (cid:129) Tumour size and location, and cosmetic and functional Recommendations were based on evidence drawn from sysconsequences of treatment (e.g. \u2018giant\u2019 BCC, which is > tematic reviews of the literature pertaining to the clinical 5 cm and/or would require extensive surgery such as questions identified. The Supporting Information includes the amputation; andH-zone tumours; Figure 1). summary of findings with forest plots (Appendices B and C; (cid:129) Largenumbers ofcoexisting tumours. see Supporting Information), tables Linking the Evidence To (cid:129) Tumour subtype (e.g. infiltrative tumours with poorly the Recommendations (LETR) (Appendix D; see Supporting definedmargins).", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 2}, {"text": "tumours. see Supporting Information), tables Linking the Evidence To (cid:129) Tumour subtype (e.g. infiltrative tumours with poorly the Recommendations (LETR) (Appendix D; see Supporting definedmargins). Information), GRADE evidence profiles indicating the certainty (cid:129) Likelihood of successful treatment compromised by previof the evidence (Appendix E; see Supporting Information), a ous treatment (e.g. multiple recurrences of BCC after sursummary of included comparative studies (Appendix F; see geryor previous radiotherapy). Supporting Information), narrative findings for noncomparative studies (Appendix G; see Supporting Information), a Patient-driven factors that may contribute individually or in PRISMA flow diagram (Appendix H; see Supporting Informacombination to a BCC being regarded as locally advanced tion) and lists of studies excluded from quantitative analyses include: with reasons for exclusion (Appendix I; see Supporting Infor- (cid:129) Patient performance status (e.g. compromised due to age mation). The strength of recommendation is expressed by the orfrailty). wording andsymbolsshown in Table 1. (cid:129) Presence of patient comorbidities potentially interfering withsurgery (e.g.unsuitability forgeneral anaesthetic). (cid:129) 2.1. Low-risk andhigh-risk basal cellcarcinoma criteria Presence of patient factors potentially interfering with radiotherapy (e.g. contraindicated in Gorlin syndrome and FollowingreviewoftheliteraturetheGDGagreedtoadoptthe relativelycontraindicated in younger patients). Royal College of Pathologists (RCPath) dataset.5 The dataset (cid:129) Patient opinions and beliefs regarding treatment and/or defines pathological low-risk and high-risk BCC based on their impact on quality of life [e.g. unwilling or reluctant increasedriskforlocalrecurrenceandveryoccasionallymetastato accept consequences of surgery such as poor cosmetic sis,especiallyifthereisperineuralinvasioninanytypeofBCC outcomeor adverseeffects (AEs) ofradiotherapy]. and/or lymphovascular invasion in basosquamous carcinoma. Clinicalfactorsthatconferlow-riskvs.high-riskBCCaredefined as per the National Institute for Health and Care Excellence 2.2. Clinicalquestions andoutcomes (NICE), based on reducing the risks of incomplete excision, recurrence following surgery, and damaging important, proxiTheGDGestablishedanumberofclinicalquestionspertinentto mate anatomical features, to achieve good cosmetic results and the scope of the guideline (Appendix A; see Supporting Inforreduce postsurgical complications.6 NICE also considered the mation).TheGDGalsoestablishedasetofoutcomemeasuresof skills and training of the surgical operator. The National importancetopatientsforeachclinicalquestion;theseoutcomes BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 2}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 901 Table1 Strengthofrecommendationratings Strength Wording Symbol Definition Strongrecommendationforthe \u2018Offer\u2019(orsimilar, \u2191\u2191 Benefitsoftheinterventionoutweightherisks;mostpatientswould useofanintervention e.g.\u2018use\u2019,\u2018provide\u2019, choosetheinterventionwhileonlyasmallproportionwouldnot; \u2018take\u2019,\u2018investigate\u2019etc.) forclinicians,mostoftheirpatientswouldreceivetheintervention; forpolicymakers,itwouldbeausefulperformanceindicator Weakrecommendationforthe \u2018Consider\u2019 \u2191 Risksandbenefitsoftheinterventionarefinelybalanced;many useofanintervention patientswouldchoosetheintervention,butmanywouldnot; clinicianswouldneedtoconsidertheprosandconsforthepatient inthecontextoftheevidence;forpolicymakersitwouldbeapoor performanceindicatorwherevariabilityinpracticeisexpected Norecommendation \u0398 Insufficientevidencetosupportanyrecommendation Strongrecommendationagainst \u2018Donotoffer\u2019 \u2193\u2193 Risksoftheinterventionoutweighthebenefits;mostpatientswould theuseofanintervention notchoosetheinterventionwhileonlyasmallproportionwould;for clinicians,mostoftheirpatientswouldnotreceivetheintervention Table2 Criteriaforlow-riskandhigh-riskbasalcellcarcinoma(BCC) Lowrisk Highriska Clinicalcriteria Locationandsize AreaLb\u226420mm(maximumclinicaldiameter) AreaLb>20mm(maximumclinicaldiameter) AreaMc\u226410mm(maximumclinicaldiameter) AreaMc>10mm(maximumclinicaldiameter) AreaHd Borders Welldefined Poorlydefined Primaryvs.recurrent Primary Recurrent Immunosuppression No Yes Siteofpriorradiotherapy No Yes Pathologicalcriteria BCCandstage Growthpattern Nodularorsuperficial Infiltrative(infiltrating,morphoeic,micronodular) Differentiation:basosquamous Absent Present(withorwithoutlymphovascularinvasion) Levelofinvasion Dermis,subcutaneousfat Beyondsubcutaneousfat Depth(thickness) \u22646mm >6mm Perineuralinvasione Absent Present PathologicalTNMstage pT1\u226420mm(maximumdiameter) pT2>20mmbut\u226440mm(maximumdiameter) pT3>40mm(maximumdiameter),or upstagedfpT1orpT2,orminorboneinvasion pT4majorboneinvasion Margins Histologicalmargins Notinvolved(\u22651mm) Involved(0mm)orhistologicallyclose(<1mm) TNM,Tumour\u2013Nodes\u2013Metastasis.aOneormorecriteriaequalshighrisk,unlessstateddifferentlyinthesummaryoftherecommendations, orinanexplanatorynote.bAreaL=trunkandextremitiesbutexcludinghands,nailunits,genitals,pretibia,anklesandfeet.cAreaM(see Figure1)=cheeks,forehead,scalp,neckandpretibia.dAreaH(seeFigure1)=\u2018maskareas\u2019offace[centralface,eyebrows,periorbital, nose,lips(cutaneousandvermilion),chin,mandible,preauricular,postauricular,temple,ears];genitalareas;hands,nailunits,ankles andfeet,butexcludingtheeyelid.Fortumours<6mminsizewithoutotherhigh-riskfeatures,standardsurgicalexcisionmaybeconsidered ifa\u22654mmclinicalsurgicalmargincanbeobtainedwithoutsignificantanatomicalorfunctionaldistortions.eAnamednerveoradiameter \u22650(cid:1)1mmorbeyondthedermis.fT1andT2canbeupstagedtoT3bythepresenceofoneormorehigh-riskclinicalorpathologicalfactors comprisingspecificallydefinedperineuralinvasionordeepinvasionrepresentingeitheratumourthicknessordepth>6mmand/orinvasionbeyondorfurtherthanthesubcutaneousfat. were ranked by the patient representatives according to the Review question 1:treatment forhigh-risk BCC GRADEmethodologyfrom1to9.3Outcomesranked7,8or9 In people with high-risk BCC, what are the clinical effecwere critical for decision making; those ranked 4, 5 or 6 were tiveness and cost-effectiveness of surgical (standard and important but not critical for decision making. Data on these Mohs) and nonsurgical techniques [topical therapies, photooutcome measures were extracted from the included studies dynamic therapy (PDT), radiotherapy and biologic therapies] (AppendicesB,C,E,FandG;seeSupportingInformation).The compared with each other or with no treatment (observaoutcomesaregivenalongwiththeirrankingscore. tion)? \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 3}, {"text": "902 BADguidelinesforadultswithBCC2021, I.Nasretal. Figure1 AreasH(darkershade)andM (lightershade)ontheheadandneck (cid:129) multidisciplinary (MDT)] lead to a decreased chance of having Complete responseor clearance (9). (cid:129) toundergo re-excision? Recurrence rate(above clavicle)(9). (cid:129) Treatment-related serious AEs (nonsurgical) or complica- (cid:129) Recurrence rate(9). tions(surgery) (8). (cid:129) Incompleteexcision (9). (cid:129) Functional outcome (physicalor social functioning) (8). (cid:129) Cosmesis(7). (cid:129) Convenience oftreatment andpatientchoice (7). 3. Summary of recommendations (cid:129) Partial(>50%) response or clearance (6). The majority of the recommendations and ratings were Review question 2:treatment for low-riskBCC agreed upon unanimously by the core members of the GDG In people with low-risk BCC, what are the clinical effectiveand patient representatives following extensive discussions. ness and cost-effectiveness of surgical (standard and Mohs) Where the GDG disagreed on specific issues, votes were cast and nonsurgical techniques (topical therapies, PDT, radiotheron all options put forward, and the simple-majority results apy and biologic therapies) compared with each other or with were featured as the final decision. (For further information no treatment (observation)? on the wording used for recommendations and strength of (cid:129) recommendation ratings, see Table 1.) The GDG is aware of Complete responseor clearance (9). (cid:129) the lack of high-certainty evidence for some recommendaConvenience oftreatment (9). (cid:129) tions, therefore, strong recommendations with an asterisk Treatment-related serious AEs (nonsurgical) or complica- (*) are based on available evidence, as well as informal contions(surgery) (8). (cid:129) sensus and specialist experience amongst GDG members. Cosmesis(7). (cid:129) Good practice point (GPP) recommendations are derived Recurrence rate(below clavicle)(6). (cid:129) Partial(>50%) response or clearance (6). from informal consensus among GDG members. In general, patient choice should be factored into the decision-making Review question 3:surgical margins process in applying all the recommendations listed below. In people with BCC who undergo standard surgical exciFor the relevant recommendations listed below, see \u2020 \u00b6 sion,what surgical margins should beused? Table 2 for the criteria for low-risk and high-risk BCC, sec- \u00a5 (cid:129) tion 2.1 for the definition of advanced BCC, and Table 3 for Recurrence rate(9). \u00a7 (cid:129) levels of community skin cancer services. Where a patient Incompleteexcision (7). declines treatment this could also be the patient\u2019s representaReview question 4:follow-up tivewith power ofattorney.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 4}, {"text": "could also be the patient\u2019s representaReview question 4:follow-up tivewith power ofattorney. In people with high-risk BCC, what is the appropriate folGeneral low-up period following treatment, including surgical (stanR1 \u2191\u2191 Offer* verbal and written information about BCC to dard and Mohs) and nonsurgical techniques (topical therapies, all adults with BCC, including the nature and prognosis of PDT, radiotherapy andbiologic therapies) orno treatment? BCC, available treatment options and the ongoing need for (cid:129) sun protection and self-surveillance of their skin as part of Recurrence rate(9). prevention or early detectionoffuture skin tumours. Review question 5:clinicalsettings Referral fromprimary care In people with a high-risk BCC, would referral to the \u2018next R2 \u2191\u2191 Refer* to a local skin multidisciplinary team care level\u2019 [primary to secondary or secondary to (LSMDT) or a specialized skin cancer multidisciplinary team BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 4}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 903 (SSMDT) member all adults with high-risk \u2020 BCC, and all (cid:129) anexcised BCC with involved margins \u2020 \u00a5 adults with low-risk BCC in the absence of an accredited General Practitioner with Enhanced Role (GPwER) or if the R16 \u2193\u2193 Do not offer* radiotherapy as a treatment option to \u00a7 primary care facility is not suitable for surgery. See Table 3 adults with BCC who are unsuitable for or decline Mohs for levels ofcommunity skincancer services. micrographic surgery or standard surgical excision, and in Surgical treatment whom thelesion is: R3 \u2191\u2191 Offer* standard surgical excision as a first-line treat- (cid:129) arecurrent BCC following previous radiotherapy ment option toadultswithlow-risk \u2020 BCC. (cid:129) associated with certain genetic syndromes predisposing to R4 \u2191\u2191 Offer* standard surgical excision with immediate skin cancers, for example Gorlin syndrome or xeroderma reconstruction as a first-line treatment option to adults with pigmentosum \u2020 primaryBCCwithahigh-riskfactor, iftheBCChaswell-defined clinical margins under bright lighting and magnification Discuss alternative treatment modalities at an MDT (see R1, or dermoscopy. R3\u20135,R9\u201314andR18\u201323). R5 \u2191\u2191 Offer* standard surgical excision with delayed R17 \u2193\u2193 Do not routinely offer* radiotherapy as a treatment \u00a7 definitive reconstruction, or Mohs micrographic surgery, as option to adults with BCC who are unsuitable for or decline the first-line treatment option to adults with high-risk \u2020 BCC Mohs micrographic surgery or standard surgical excision, and within a high-risk anatomical site if the BCC has poorly in whom thelesion is: defined clinical margins under bright lighting and magnifica- (cid:129) on areasofpoor bloodsupply(e.g.the lowerlimbs) tion or dermoscopy. (cid:129) in younger patients in whom the late effects of radiotherR6\u2191\u2191 Excise* low-risk \u2020 BCC using a4mmperipheral cliniapy couldbeanissue (suggested age<60 years) cal surgical margin. (cid:129) aBCC invading bone or cartilage R7\u2191\u2191 Excise* primary BCC with ahigh-risk factor \u2020 using at least a 5 mm peripheral clinical surgical margin (see also R4 Discuss alternative treatment modalities at an MDT (see R1, andR5). R3\u20135,R9\u201314andR18\u201323). R8 \u2191\u2191 Excise* BCC by ensuring adequate excision at the Other treatment options deep margin to a clear plane, including a fat layer where preR18 \u2191\u2191 Offer* topical imiquimod, topical 5-fluorouracil, sent, andotherdeeper structuresifneeded.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 5}, {"text": "layer where preR18 \u2191\u2191 Offer* topical imiquimod, topical 5-fluorouracil, sent, andotherdeeper structuresifneeded. cryosurgery or topical PDT as treatment options to adults with \u2020 \u00a7 R9 \u2191 Consider Mohs micrographic surgery in adults with low-risk BCCwhoare unsuitableforordecline standardsurprimary BCC withatleast one high-riskfactor. \u2020 gical excision. R10\u2191\u2191Offer*Mohsmicrographicsurgeryasafirst-linetreatR19 \u2193\u2193 Do not offer* topical imiquimod, topical 5-fluomentoptiontoadultswithrecurrentBCCwithatleastoneother rouracil, cryosurgery, curettage and cautery, or topical PDT as high-riskfactor, \u2020 especiallyifthetumourisatahigh-risksite. treatment options to adults with high-risk \u2020 BCC who are \u00a7 R11 \u2191 Following discussion at an MDT, consider standard unsuitable for or decline Mohs micrographic surgery or stansurgical excision with at least a 5 mm margin and delayed dard surgical excision. definitive reconstruction as a treatment option to adults with R20 \u2193\u2193 Do not offer* topical imiquimod, topical 5-fluorecurrent BCC withatleast one otherhigh-riskfactor. \u2020 rouracil, cryosurgery or topical PDT as a treatment option to \u00b6 R12\u2191\u2191Offer*standardsurgicalexcisionorradiotherapyasa adults with advanced BCC unless for palliation of symptoms, treatmentoptiontoadultswithadvanced \u00b6 BCC(seealsoR14). following discussion atanMDT. R13 \u2191 Consider Mohs micrographic surgery as a treatment R21 \u2191\u2191 Advise* adults with BCC who decline \u00a7 all treatoption toadultswithadvanced \u00b6 BCC. ments that the risk of significant progression of the tumour is Systemictherapy at least 25%over2\u20135 years. R14\u2191\u2191 Offer* vismodegib, subject toavailability, asatreat\u03981 There is insufficient evidence to support any recomment optiontoadultswithadvanced \u00b6 BCC whoareunsuitable mendation for the following interventions for low-risk (in- \u2020 for Mohs micrographic surgery, standard surgical excision or cluding recurrent,low-risk) BCC: radiotherapy, including patients with Gorlin syndrome, fol- (cid:129) Mohs micrographic surgery lowing discussion atanMDT(see also R12andR13). (cid:129) vismodegib Radiotherapy R15 \u2191\u2191 Offer* radiotherapy as a treatment option to adults \u03982 There is insufficient evidence to support any recom- (suggested age \u2265 60 years) with low-risk and high-risk BCC mendation for thefollowinginterventions forBCC: who are unsuitable for or decline \u00a7 Mohs micrographic surgery (cid:129) topicalingenol mebutate gel. or standard surgical excision and who express a preference for (cid:129) topicalCuraderm-BEC5 cream. radiotherapy, andin whom thelesion is: (cid:129) electrochemotherapy (ECT). (cid:129) anodular BCC (cid:129) CO 2 laser. (cid:129) an infiltrative subtype of BCC, provided a sufficient plan- (cid:129) pulsed-dye laser. (cid:129) ning marginis used combinations of: \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 5}, {"text": "(cid:129) pulsed-dye laser. (cid:129) ning marginis used combinations of: \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 5}, {"text": "904 BADguidelinesforadultswithBCC2021, I.Nasretal. Table3 Levelsofcommunityskincancerservices GroupofGPwER Status Rangeofactivitya Group1:GPwERingeneral AGPwhohassuitabletrainingandhas Diagnosisandmanagementofinflammatoryskindisease; dermatology(nonsurgical) demonstratedcompetencyingeneral diagnosisofskinlesionsandtheirnonsurgicalmanagement, dermatology includingtopicaltherapyandPDT;andnonexcisionalsurgical procedures,includingcryosurgeryandcurettageandcautery, dependingontheirtraininglevelandavailabilityof treatment,forlow-riskBCCandalsoprecancerouslesions, e.g.actinickeratosesandSCCinsitu(Bowendisease) Group2:GPwERinskinlesion AGPwhohassuitabletrainingandhas Diagnosisandmanagementofskinlesions,includinglow-risk management demonstratedcompetencyinskin BCC[well-definedborderedprimarynodularorsuperficial lesionmanagement BCConareaLb\u226420mm(maximumclinicaldiameter)and onareaMc\u226410mm(maximumclinicaldiameter)],using bothsurgicalandnonsurgicaltechniques,relevanttotheir clinicaltraining.Inaddition,group2and3GPwERsare expectedtofollowthoseaspectsoftheNICE recommendationserelevanttotheiragreedscopeofpractice Group3:GPwERingeneral AGPwhohassuitabletrainingandhas Thisgroupcombinesgroups1and2 dermatologyandskinlesion demonstratedcompetencyingeneral management dermatologyandskinlesion management Model2practitioner AskinsurgeonwhomightbeaGP, ManagementofskinlesionsdiscussedwithacoreLSMDT nursespecialistorsecondarycare memberandwithinthepractitioner\u2019scompetencies specialistworkinginthecommunity recognizedbytheLSMDT underthegovernanceofanacutetrust BCC,basalcellcarcinoma;GP,generalpractitioner;GPwER,GPwithEnhancedRole;LSMDT,LocalSkinMultidisciplinaryTeam;NICE, NationalInstituteforHealthandCareExcellence.aNocommunitypractitionershouldknowinglytreathigh-riskBCC,especiallyonareasMc orHd;recurrentBCC;orBCCwithhigh-riskpathologicalcriteria,exceptafterdiscussingitwiththeLSMDT.bAreaL=trunkandextremities butexcludinghands,nailunits,genitals,pretibia,anklesandfeet.cAreaM=cheeks,forehead,scalp,neckandpretibia.dAreaH=\u201cmask areas\u201dofface(centralface,eyebrows,periorbital,nose,lips(cutaneousandvermilion),chin,mandible,preauricular,postauricular,temple, ears);genitalareas;hands,nailunits,anklesandfeet,butexcludingtheeyelid.eNICE6recommendsthat,forallgroupsofGPsmanagingBCCin thecommunity,thepatientisnotaged24yearsoryounger,isnotimmunosuppressedanddoesnothaveGorlinsyndrome,andalsothat thelesion(i)islocatedbelowtheclavicle(areaL),(ii)is<1cmindiameterwithclearlydefinedmargins,(iii)isnotarecurrentBCCfollowingincompleteexcision,(iv)isnotapersistentBCCthathasbeenincompletelyexcisedaccordingtohistology,(v)isnotmorphoeic, infiltrativeorbasosquamousinappearanceand(vi)isnotlocated(A)overimportantunderlyinganatomicalstructures(e.g.majorvesselsor nerves),(B)inanareawhereprimarysurgicalclosuremaybedifficult(e.g.digitsorfrontofshin),(C)inanareawheredifficultexcision mayleadtoapoorcosmeticresult,or(D)atahighlyvisibleanatomicalsite(e.g.anteriorchestorshoulders)whereagoodcosmeticresult isimportanttothepatient.IfthelesionisthoughttobeasuperficialBCCtheGPshouldensurethatthepatientisofferedthefullrangeof medicaltreatments(includingtopicaltherapyandPDT)andnonexcisionalsurgicalprocedures,includingcryosurgeryandcurettageandcautery, whichmayrequirereferraltoamemberoftheLSMDT. \u25cb Topical diclofenac + calcitriol. R23 GPP Refer all adults with excised high-risk \u2020 BCC with \u25cb Topical imiquimod +Mohs micrographic surgery. a close histological margin (< 1 mm) for MDT discussion of \u25cb Intralesional interferon-a+ standard surgical excision. management options. These may include surgical re-excision, \u25cb Topical PDT +Mohs micrographic surgery. Mohs micrographic surgery, radiotherapy or monitoring. \u25cb Laser therapy+ topical PDT. Patient choice should especially be factored into the decision\u03983 There is insufficient evidence to recommend \u2018no treatmaking process in such asituation. ment\u2019as anoption foradultswith: R24 \u2193\u2193 Do not routinely offer* follow-up to patients with adequately treated isolated BCC, unless for a postoperative (cid:129) recurrent BCC withat least oneotherhigh-risk factor. review (seealso R25andR26). (cid:129) \u00a7 advanced BCC who are not suitable for or decline Mohs R25 GPP Offer, if possible, a postoperative review of adults micrographic surgery or standard surgical excision. with adequately treated BCC by an appropriate healthcare proManagement following primarytreatment fessional, in either secondary or primary care. R22 \u2191\u2191 Following discussion at an MDT, offer* further R26 GPP Offer, if possible, at least yearly follow-up to standard surgical re-excision to adults with excised high-risk \u2020 adults with a history of multiple BCCs who are likely to BCC with involved histological margin unless there is a condevelopfurther tumours or recurrence within12 months. traindication (see also R4,R5,R7\u201321,\u03981,\u03982 and\u03983). Summaryof future research recommendations BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 6}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 905 The following list outlines future research recommendations 5. Background (FRRs). FRR1 Randomized controlled trials (RCTs) comparing stan5.1. Definition dard surgical re-excision of high-risk BCC excised with close (< 1 mm) or involved histological margin vs. Mohs microBCC is the most common keratinocyte cancer (KC)/nongraphic surgery, radiotherapy or no treatment. Primary outmelanoma skin cancer (NMSC).11\u201315 It is a slow-growing, comes shouldinclude recurrencerate overatleast 5 years. locally invasive malignancy that very rarely metastasizes.7,10,14 FRR2 RCTs directly comparing various treatment modalities Usually it develops on sun-exposed areas such as the head and with primary outcomes to include UK health economic assessneck,13,14 although potentially any cutaneous site can be ment (including treatment of recurrences) and patient-reaffected. Clinically and pathologically, BCC is heterogeneous. ported outcomemeasures. The most common subtype is nodular BCC (> 60%),10 and FRR3 RCTs comparing standard surgical excision vs. Mohs other variants include superficial, infiltrative (morphoeic, sclemicrographic surgery for high-risk BCC, with longer followrosing, micronodular), keratotic and pigmented are also up periods ofatleast 5 years. described, with frequent histological overlap between types.11 The basosquamous variant is the most aggressive type. It has a 4. Algorithm tendency for lymphovascular or perineural invasion, and can rarely metastasize.7,11 BCC usually develops as a sporadic The recommendations, discussions in the LETR sections tumour but rarely it can develop in chronic scars16 or be part (Appendix D; see Supporting Information) and consensus speof a genodermatosis, for example Gorlin syndrome, xerocialist experience were used to producemanagement pathways derma pigmentosum, Bazex\u2013Dupr(cid:1)e\u2013Christol syndrome and for adultswith BCC \u2013seeFigure 2and Tables 4\u20138. Rombo syndrome.10,11,13 Figure2 Basal cell carcinoma management pathway in primary, secondary and tertiary care. BCC, basal cell carcinoma; GP, general practitioner; GPwER,GPwithExtendedRole;GPwSI,GPwithSpecialInterest;LSMDT,LocalSkinMDT;MDT,MultidisciplinaryTeam;NICE,NationalInstitute forHealthandCareExcellence;SMC,ScottishMedicinesConsortium;SSMDT,SpecialistSkinCancerMDT \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 7}, {"text": "906 BADguidelinesforadultswithBCC2021, I.Nasretal. Table4 Primarybasalcellcarcinoma(BCC)suitableforsurgery:influence Table7 Recurrentbasalcellcarcinoma(BCC)notsuitablefororpatient oftumourriskontheselectionoftreatment declinessurgery:influenceoftumourriskontheselectionoftreatment Strengthofrecommendation Strengthofrecommendation Treatment Low-riskBCC High-riskBCC Treatment Low-riskBCC High-riskBCC Excisionalsurgery \u2191\u2191 \u2191\u2191a Radiotherapy \u2191\u2191a \u2191\u2191a Mohsmicrographicsurgery \u0398 \u2191\u2191 Vismodegib \u0398 \u2191 Topicalagents \u2191 \u2193\u2193 aPleaserefertosummaryofrecommendationsR4,R5,R7and (imiquimodor5-fluorouracil) R8fordetails. Cryosurgery \u2191 \u2193\u2193 Curettageandcautery \u2191 \u2193\u2193 withoutsubsequentsurgery Table5 Primarybasalcellcarcinoma(BCC)notsuitablefororpatient Photodynamictherapy \u2191 \u2193\u2193 declinessurgery:influenceoftumourriskontheselectionoftreatment Notreatment(patientb \u2191 \u0398c declinestreatment) Strengthofrecommendation aPleaserefertosummaryofrecommendationsR15\u2013R17for Treatment Low-riskBCC Highrisk-BCC details.bOrpatient\u2019srepresentativewithpowerofattorney.c Radiotherapy \u2191\u2191a \u2191\u2191a PleaserefertosummaryofrecommendationsR21and\u03983for Vismodegib \u0398 \u2191b details. Topicalagents \u2191\u2191 \u2193\u2193 (imiquimodor5-fluorouracil) Cryosurgery \u2191\u2191 \u2193\u2193 Table8 Advancedbasalcellcarcinoma(metastaticorlocally Curettageandcautery \u2191\u2191 \u2193\u2193 advanced):strengthofrecommendationfortreatments withoutsubsequentsurgery Photodynamictherapy \u2191\u2191 \u2193\u2193 Strengthof Notreatment(patientc \u2191 \u0398d Treatment recommendation declinestreatment) Excisionalsurgery \u2191\u2191 aPleaserefertosummaryofrecommendationsR15\u2013R17for Mohsmicrographicsurgery \u2191 details.bPleaserefertosummaryofrecommendationsR14for Radiotherapy \u2191\u2191 details.cOrpatient\u2019srepresentativewithpowerofattorney.d Vismodegib \u2191\u2191 PleaserefertosummaryofrecommendationsR21fordetails. Topicalagents \u2193\u2193 (imiquimodor5-fluorouracil) Cryosurgery \u2193\u2193 Table6 Recurrentbasalcellcarcinoma(BCC)suitableforsurgery: Curettageandcautery \u2193\u2193 influenceoftumourriskontheselectionoftreatment withoutsubsequentsurgery Photodynamictherapy \u2193\u2193 Strengthofrecommendation Notreatment(patienta \u0398b declinestreatment) Treatment Low-riskBCC High-riskBCC Excisionalsurgery \u2191\u2191 \u2191a aOrpatient\u2019srepresentativewithpowerofattorney.bPleaserefer Mohsmicrographicsurgery \u0398 \u2191\u2191 tosummaryofrecommendationsR21and\u03983fordetails. aPleaserefertosummaryofrecommendationsR4,R5andR7\u2013 R11fordetails. exposuretoultravioletradiation,andtheriskisincreasedinthe contextofimmunosuppression,forexampleorgantransplanta5.2. Incidence andaetiology tion,19 HIV20 and haematological malignancy.11,13 The hedgeThe exact incidence of BCC globally is not accurately known hogintracellularsignallingpathwayiscriticalfortheregulation because it is not included in cancer registries in most counof cell growth and differentiation in embryonic development. tries.13\u201315 However, recent improvements to registry data colDevelopment of BCC is associated in most cases with loss of lection in England have enabled more accurate analysis, which inhibitionofhedgehogsignalling.Thisistheresultofinactivathas confirmed a rise in incidence of the first BCC per person ingmutationsinthetumour-suppressorproteinpatchedhomoper year from 268 565 in 2013 to 410 716 in 2015.15 Incilogue 1 gene (PTCH1) in 90% of sporadic BCC and activating denceincreases withage andBCC is morecommonin men.15 mutations in the smoothened transmembrane protein gene BCC is an epidermal KC. The exact cell of origin is not (SMO)in 10%ofcases,withgermline mutations inPTCH1and known, although itis considered tooriginate from pluripotent occasionally PTCH2,SMO andsuppressor of fused(SUFU)genes cells in the interfollicular epidermis and infundibulum of the in Gorlin syndrome. The importance of this pathway is highhair follicle distributed along the basal layer.17,18 It is believed lighted by the successful use in advanced BCC of hedgehog to be caused by a combination of genetic predisposition and pathwayinhibitors(e.g.vismodegib).10,11,14,18 BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 8}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 907 and proximity to or involvement of important structures 6. Diagnosis and investigation such astheeye andbony orifices) (cid:129) presence of comorbidities, including serious, life-limiting 6.1. Diagnosis conditions (cid:129) Dermatologists and other skin cancer specialists can usually presenceof genodermatoses(e.g. Gorlinsyndrome) (cid:129) diagnose BCCclinically,without theneed forbiopsy.Diagnospresenceof compromisedimmune status (cid:129) tic accuracy is enhanced by good lighting, the skin stretch regular medications taken by the patient, especially anticotest21 and dermoscopy.22,23 Specialist noninvasive skin imagagulants andthosethatadversely modify woundhealing (cid:129) ing tools, including reflectance confocal microscopy and optirisk of morbidity or mortality associated with treatment of cal coherence tomography, may also help in diagnosis of theBCC difficult cases, although these are notwidelyavailable.24\u201326 (cid:129) thelikelihood oftreatment success (cid:129) Biopsy is indicated if there is clinical doubt about the diagwhetherthepatient hasan implanted cardiacdevice nosis, for potentially high-risk types (e.g. based on clinical As BCC is a slow-growing, often asymptomatic tumour that risk factors of size and/or location), if the treatment will be rarely metastasizes, in certain circumstances the option of \u2018no influenced by histological subtype (e.g. infiltrative vs. superfitreatment\u2019 arises. This may seem an attractive option if the cial) and to confirm recurrences after treatment.7,11,12,14 In patient has a short life expectancy, but the healthcare provider most cases, shave or curette biopsy should be sufficient to needs to ensure that the patient fully understands the risks of make a positive diagnosis of BCC.11 If the histological subtype locally advanced disease.10,12 Acaseseries offivepatients with is in doubt, a deep incisional or excisional biopsy (to include low-risk BCC demonstrated that they progressed to advanced thedermis or fat,if possible) isrecommended.12,14 BCC within 2 years.28 Retrospective studies of patients who If there is clinical suspicion that the tumour is attached to did not have re-excision for incompletely excised BCCs or extends deep into the underlying deep fascia, and/or if showed recurrencerates ofat least25% over5 years.29,30 there is suspected involvement of muscle, large nerves, blood vessels or bone, then cross-sectional imaging of the area using either computed tomography (CT) scanning or magnetic reso6.3. Eyelid nance imaging (MRI) should be considered, and the case For several editions of TNM, staging of the eyelid has been should be discussed at an SSMDT meeting prior to treatspecifically excluded from staging of BCC of the entire skin. ment.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 9}, {"text": "be considered, and the case For several editions of TNM, staging of the eyelid has been should be discussed at an SSMDT meeting prior to treatspecifically excluded from staging of BCC of the entire skin. ment.7,12,14 In the case of involvement of deeper structures of The eyelid has been allocated its own specific and different the head and neck area, referral to the head and neck MDT staging system for the primary tumour and lymph nodes. For may beconsidered.7,12,14 many reasons (including clinical, pathological and cancer registration) it is essential that this different system for the eyelid 6.2. Low-risk andhigh-risk tumours,patient factorsand is better recognized and used by clinicians, pathologists and treatment selection skin cancer MDTs. Regarding its management, a BCC of the eyelid of combined lowest pT1 stage and low-risk histological The management of BCC depends on a number of factors status still constitutes a high-risk BCC as it is situated in area including the size, site and histological subtype of the tumour H. This would mandate management considerations similar to (Table 2), patient comorbidities, previous treatment history all high-risk BCCs in area H, namely with either Mohs microand patient preference.10 It is also important to consider graphic surgery or standard surgical excision with delayed whether the intention of treatment is curative or palliative, definitive reconstruction \u2013 seeR4, R5,R9\u201321 and\u03983. where and by whom treatment should be delivered to ensure the best possible outcome (see section 7), and the availability of treatment withinthetreating healthcareprovider\u2019s service. 6.4. Digital photography The GDG identified only one publication27 that addresses The diagnosis and management of skin disorders can be aided the needs and preferences of patients regarding BCC and squaby digital photography for clear documentation, and to monimous cell carcinoma (SCC) treatment. This qualitative study tor treatment response.31 BCC is no exception to this, where found that of particular importance to patients with BCC were healthcare professionals can utilize it with or without digital to receive relevant information tailored to their specific situadermoscopy photography. Digital photography is also useful tion, to be seen by the same physician during treatment and in helping patients with regular self-examination of their follow-up, to have a full-body skin examination during folskin.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 9}, {"text": "be seen by the same physician during treatment and in helping patients with regular self-examination of their follow-up, to have a full-body skin examination during folskin.32 Total-body digital photography can be available for use low-up, andtoparticipate in shareddecision making. in clinic, while patients can use digital applications to store Factorsthatshould beconsidered inmaking ajoint decision these photographs on theirpersonal devices.33 regarding treatment include: However, some limitations and challenges have been (cid:129) performancestatus of thepatient reported, such as the lack of standardization in ensuring the (cid:129) riskoftheparticulartumourincausingharmifnottreated same position, imaging angle and lighting every time, highly (e.g. the presence of ulceration, bleeding, rapid growth, expensivedevicesandequipment,andthetimeneededtohave \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 9}, {"text": "908 BADguidelinesforadultswithBCC2021, I.Nasretal. the photographs taken.34 It is envisaged that in the future, andtreatmentoptionsforBCC,predisposing factors(especially advancesintechnologymightmakedigitalphotographyforskin sun exposure), advice on photoprotection (with accompanycancer,includingBCC,moreefficientandcheaper.34 ing advice on implications of photoprotection for vitamin D The GDG agrees with the utility of digital photography, status), risk of recurrence or development of new primary where possible, in the management of BCC, and highlights skin cancers, and the importance of early detection of recurthefollowing: rence or new tumours by self-skin examination. All patients (cid:129) should be directed as to how to access clinical assessment No image should be kept without the patient\u2019s express rapidly should asuspicious lesion arise. consent, and in line with the NHS data protection and information governance requirements. (cid:129) Asremoteconsultations(e.g.teledermatology)increasingly 7.2. Considerations: theclinical practitioner become the new norm, even prior to the COVID-19 panOne important issue in management of BCC in the UK is that demic, patients should be informed of the risks associated not all clinicians involved in providing treatment have the with forwarding of digital images. Information governance same specific skills. For example, some are competent in treatand data protection rules do not apply until the images ing low-risk BCC in the primary care setting, while others in havereached thehealthcare provider.35 (cid:129) the secondary care setting have advanced surgical skills either Imagesshouldbecomepartofthepatient\u2019slifelongclinical for all anatomical areas affected (L, M, H) or for particular records. (cid:129) areas only, for example areas L and M (Table 2). Others are Images should demonstrate both anatomical location and clinical or medical oncologists who treat advanced BCC with close-to-detail features (plus dermoscopic detail, if availradiotherapy and/or systemic agents,respectively. able). (cid:129) Primary care/community-based practitioners can choose to Where multiple lesions exist, each should be annotated develop the necessary knowledge and skills to undertake skin separately. cancer diagnosis and treatment. All GPs providing skin cancer treatment should demonstrate the necessary knowledge and skills commensurate with their level of activity. Those cur7. Management rently known as a GPwER are accredited by a team appointed Overview by the Royal College of General Practitioners (RCGP) to meet In most cases of primary BCC, surgery is the recommended the skills described in the current NICE guidance 20106 and treatment modality.11 \u2018Surgery\u2019 includes those forms of surgitheRCGP framework 2018 (seeTable 3).", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 10}, {"text": "most cases of primary BCC, surgery is the recommended the skills described in the current NICE guidance 20106 and treatment modality.11 \u2018Surgery\u2019 includes those forms of surgitheRCGP framework 2018 (seeTable 3).36 cal treatment with postoperative margin assessment such as standard surgical excision and Mohs micrographic surgery, 7.3. Multidisciplinary team and those without postoperative margin assessment, such as curettage and cautery, cryosurgery and laser therapy.11,12,14 One of the main service provisions for management of skin Each surgical technique has its own indications and concancers, including BCC, in the UK is the MDT. It was first rectraindications (see sections 7.4, 7.5, 7.6 and 7.7). Other treatommended by NICE in 200637 to be in two forms: the ment modalities such as radiotherapy, topical therapies and LSMDT and the SSMDT. NICE described in the guidance the PDT may be offered if the patient is not suitable for or declitypes of patients to be referred toeach level of MDT, the roles nes surgery; selection of each modality depends on the precise required from the MDT, and the core and the extended memclinical scenario. In advanced BCC (mBCC and laBCC), surgery bership of each MDT. This guidance was updated in 20106 may not be feasible, and alternative options include radiother- (and is currently under review), the referral process was apy andhedgehog pathwayinhibitors. reviewed in 2015 and the quality standard was published in 2016.38 A report was published in 2018 by the BAD39 in response to the NHS England reform of cancer MDT meet7.1. Considerations: thepatient ings.40 The patient, or the person with the power of attorney for Themain pointsthattheseguidancedocuments recommend health matters, should be counselled sufficiently on all aspects for BCCare: of the treatment approach being considered and post-treat- (cid:129) Toreferfor discussion atanLSMDT meeting ment care, especially with respect to the possibility of developing a scar. Patients should be informed of methods to \u25cb All patients with high-risk BCCs that involve the exciimprove cosmetic outcome following primary treatment. If sion margins or are recurrent. psychological need has been identified, a referral should be \u25cb Patients suitable for Mohs micrographicsurgery. made to appropriate services and a key worker should be \u25cb Immunocompromised patients (e.g. organ transplant identified tosupportthepatientduring this process.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 10}, {"text": "Patients suitable for Mohs micrographicsurgery. made to appropriate services and a key worker should be \u25cb Immunocompromised patients (e.g. organ transplant identified tosupportthepatientduring this process. recipients, patients with haematological malignancy or At diagnosis, all patients with BCC should be given tailored HIV/AIDS) with skin cancers and patients who have advice in the forms of verbal and written information. This Gorlin syndrome or other genetic conditions in which should include information regarding the nature, prognosis predisposition occurs. BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 10}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 909 \u25cb All patients with low-risk BCCs that should not be treaExpertly performed, definitive standard surgical excision can tedin primary care, asperTable 3. thereforehave lowrecurrence rates.Evidence forclinically sig- (cid:129) Torefer fordiscussion at anSSMDTmeeting nificant sparing of tissue, which thereby enables less extensive reconstruction by using complex margin-controlled tech- \u25cb Patients withmetastaticBCCs. niques, is limited. \u25cb For periodic review, patients developing skin cancers Evidence from case series involving standard excision marwho are immunocompromised, have Gorlin syndrome gins of 4\u20135 mm in high-risk BCC (head and neck) reports orhave othergenetic predisposition syndromes. lower incomplete excision rates (3(cid:1)74%) compared with exci- \u25cb Patients who may be eligible for entry into clinical trision margins of 3\u20134 mm (4(cid:1)10%) or < 4 mm (11(cid:1)31%) als. (Appendices C and D for proportional meta-analysis forest \u25cb Patients who require adjuvant treatment (where this is plots and LETR discussions, respectively; see Supporting Inforshowntobebeneficial). mation). Similarly, evidence from case series involving stanAdditionally, the GDG recommends that the following cases dard excision margins of 4\u20135 mm in high-risk BCC (whole bereferred toanLSMDT member: body) reports lower incomplete excision rates (3(cid:1)66%) compared with excision margins of 3\u20134 mm (4(cid:1)49%) or < 4 mm (cid:129) Low-risk BCC in the absence of a competent GPwER or if (9(cid:1)72%). Dhepnorrarat et al.49 reported a very high volume theprimarycarefacilityisnotsuitableforsurgery(seeR2). (21 677) of BCCs excised; data were collected prospectively (cid:129) Recurrent BCC with high-risk factors when Mohs microover a period of 6 years by a defined group of 25 plastic surgraphic surgery is not appropriate, or the patient or the geons in Western Australia which showed an incomplete excipatient\u2019s representative with power of attorney declines it sion rate of 4(cid:1)01%, although no reference was made to the (see R11). margins involved. (cid:129) Patients unsuitable for Mohs micrographic surgery or stanStandard surgical excision consists of three stages: (i) excidard surgical excision but suitable for radiotherapy, and sion of the tumour with a predetermined margin of normalpatients who may prefer radiotherapy as an alternative appearing skin beyond the visible edge of the tumour; (ii) treatment option (seeR15, R16andR17). surgical repair of the wound; and (iii) subsequent histological (cid:129) Excised high-risk BCC with a close histological margin (< analysis oftheexcised tissue. 1 mm;seeR23).", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 11}, {"text": "treatment option (seeR15, R16andR17). surgical repair of the wound; and (iii) subsequent histological (cid:129) Excised high-risk BCC with a close histological margin (< analysis oftheexcised tissue. 1 mm;seeR23). For a list of good surgical practice points please refer to the (cid:129) If deep extension of BCC to underlying tissue (e.g. named \u2018other considerations\u2019 section in Appendix D1.1 (LETR, pp nerve,muscleorbone)issuspected,followingaCTscanor 78\u201382; seeSupporting Information). MRI. In advanced cases of BCC, consider referral to one or more 7.4.2. Mohs micrographic surgery other MDTs,as clinically appropriate. For the indications for Mohs micrographic surgery please refer to the recommendations R5, R9, R10, R13 and \u03981. For a 7.4. Excisiontechniques withpostoperative margin more detailed discussion on the evidence that underpins these assessment recommendations please refer to Appendix D1 (LETR, pp 62\u2013 4; seeSupporting Information). 7.4.1. Standard surgical excision withpredetermined All the general good medical advice for standard surgical margins excision still applies to Mohs micrographic surgery, namely For the indications for standard surgical excision with predethe operator should be qualified and working in an accredited termined surgical margins, please refer to recommendations centreforsuchsurgery,withsufficienttimeallocation,high-sR3\u20138, R11, R12, R22 andR23. Fora moredetailed discussion tandard (theatre) lighting, and patient counselling for on the evidence that underpins these recommendations please informed consent. Recently, the BAD published service guidrefer to Appendices D1 and D2 (LETR, pp 62\u201377 and 84\u20137; ance and standards for Mohs micrographic surgery performed see SupportingInformation). in theUK.50 Standard surgical excision is an empirical treatment suitable For key features of Mohs micrographic surgery and the diffor the majority of primary BCCs, with reported 5-year recurferences in technique from standard surgical excision please rence rates of 3\u20138%;41\u201343 higher recurrence rates have been refer to the \u2018other considerations\u2019 section in Appendix D1.1 reported in more historical papers.30,44 Standard surgical exci- (LETR, pp78\u201382; seeSupporting Information). sion with complete margin control showed 0(cid:1)5% recurrence OnlyoneRCTtodatehascomparedMohsmicrographicsurat 5 years for primary tumours and 2(cid:1)9% at 5 years for recurgery against standard surgical excision, with only 3 mm marrent tumours in a single study.45 For Mohs micrographic surginsbeingusedforthelatterinthestudy.Thesubsequenttwo gery, recurrence rates for primary tumours of the head and publications for the RCT showed the recurrence rates with neck range from 0(cid:1)3% to 6(cid:1)5%.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 11}, {"text": "tumours of the head and publications for the RCT showed the recurrence rates with neck range from 0(cid:1)3% to 6(cid:1)5%.42,46\u201348 Treating already recurMohsmicrographicsurgerytobeloweratboth5-yearand10rent tumours is associated with higher subsequent recurrent year follow-ups; however, this was not statistically significant rates, rangingfrom 4%to10%.42,47,48 (P > 0(cid:1)05) for primary, high-risk BCC43 (after 5 years: Mohs \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 11}, {"text": "910 BADguidelinesforadultswithBCC2021, I.Nasretal. micrographicsurgeryrecurrencerate2(cid:1)5%vs.standardsurgical Inretrospectivecaseseries,5-yearand10-yearlocalrecurrence excision 4(cid:1)1%;51 after 10 years: 4(cid:1)4%vs. 12(cid:1)2%, respectively). ratesof4%and6%,respectively,werereportedinaseriesof720 With regard to recurrent BCC, the same publications showed head and neck BCCs,56 with a 5-year recurrence rate of 4(cid:1)2% thattherecurrencerateforMohsmicrographicsurgerywasstareportedinanotherseriesof712patients.57Inasystematicreview tisticallysignificantlybetter(P < 0(cid:1)05)thanforstandardsurgiofpatientswithNMSCtreatedwithhypofractionatedradiotherapy cal excision (after 5 years: Mohs micrographic surgery (i.e.fractionsize>2 Gy),thelocalrecurrenceratedidnotexceed recurrencerate2(cid:1)4%vs.standardsurgicalexcision12(cid:1)1%;after 7(cid:1)9% in 33 of 36 studies with follow-up ranging from 2 to 10 years:3(cid:1)9%vs.13(cid:1)5%,respectively).43,51 77 months.57 However, an older retrospective study of 148 Mohs micrographic surgery can be considered for all highpatients with 175 BCCs of different subtypes treated with radiorisk primary BCCs, and offered for recurrent, high-risk BCC. therapyfoundanoverall5-yearrecurrencerateof15(cid:1)8%;86(cid:1)4% In such cases, either Mohs micrographic surgery is offered or ofallrecurrencesappearedwithin3 yearsfollowingtreatment.58 the wound from standard surgical excision should be kept Inthesamestudy,comparedwithnodularBCC,sclerosing(moropen for delayed reconstruction until the margins are conphoeicorinfiltrative)BCCwasasignificantriskfactorforrecurfirmedclear,by paraffinsections. renceafterradiotherapy;therefore,surgeryisgenerallypreferable for these subtypes.58 If radiotherapy is used for poorly defined BCCs,thenawiderplanningmarginisadvised.58Surgeryisalso 7.5. Radiotherapy preferredtoradiotherapyinareasofpotentialpoorhealing,particFor the indications for radiotherapy please refer to recommenularlytheleg,59andforBCCinvadingboneorcartilageandrecurdations R15\u2013R17. For a more detailed discussion on the evirentBCCsthathaverecurredfollowingradiotherapy.7,12,14 dence that underpins these recommendations please refer to Theacutecomplicationsofradiotherapyincludemoistanddry Appendix D1 (LETR,pp 64\u20136; seeSupporting Information). desquamation, and acute/erosive dermatitis. The longer-term, Primary treatment of BCC with radiotherapy is a well-estabcosmetic effects of radiotherapy (e.g. hypopigmentation, telanglished, definitive treatment. It is considered an acceptable iectasia,fibrosis;and,rarely,skin,cartilageorboneradionecrosis) modality in the previous iteration of the BAD guidelines,4 as mayworsenovertime,andarelikelytobeworsewithahigher well as in international guidelines such as those of the Eurodose per fraction.60 However, there is growing clinical evidence pean Dermatology Forum 2019,14 the US NCCN 2019,7 and that hypofractionation (larger than the standard 2\u20132(cid:1)5 Gy per theAmericanAcademy ofDermatology 2018.12,52 fraction) does not compromise cosmesis and is particularly Standard surgical excision or Mohs micrographic surgery is appealing to older or frail patients, as fewer treatments are theusualprimarytreatmentforBCC;however,radiotherapycan required. Most guidelines therefore recommend reserving radiobe considered on an individual patient basis, especially when therapyforpatientsaged60 yearsorover.7Radiotherapyshould older patients may prefer radiotherapy as an alternative treatalsonotbeusedingeneticsyndromespredisposingtoskincancers ment option, usually after MDT discussion for high-risk BCCs suchasGorlinsyndromeandxerodermapigmentosum,asitcan and usually with a diagnostic biopsy. There is evidence for its predisposetosecondarycarcinomas.7,61\u201364 role as an alternative primary treatment modality for nodular For discussions on radiotherapy regimens please refer to the BCC,particularlyinolderpatientswithpoorerperformancesta- \u2018other considerations\u2019 section in Appendix D1.1 (LETR, p 82; tus, in those (or their representative with power of attorney) seeSupporting Information).", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 12}, {"text": "modality for nodular For discussions on radiotherapy regimens please refer to the BCC,particularlyinolderpatientswithpoorerperformancesta- \u2018other considerations\u2019 section in Appendix D1.1 (LETR, p 82; tus, in those (or their representative with power of attorney) seeSupporting Information). who decline surgery, in patients for whom surgery may result insignificantlyadversecosmeticorfunctionaloutcomes,andin 7.6. Other surgicaltechniques without postoperative patientswhomaypreferradiotherapyasanalternativetreatment margin assessment option. It may be an effective postoperative treatment for BCC with involved (microscopic or macroscopic) histological marFor the indications for other surgical techniques without postginsforwhichfurthersurgeryisinappropriate.14,53 operative margin assessment, please refer to recommendations When managing BCC with perineural invasion (PNI), an R18\u2013R20 and \u03982. For a more detailed discussion on the eviMDT team including a cutaneous surgeon and a radiation dence that underpins these recommendations please refer to oncologist familiar with PNI is recommended. Where there is Appendix D1 (seeSupporting Information). one or more close or involved margin and PNI, further excision shouldbeoffered,or radiotherapy ifexcision isnotfeasi7.6.1. Curettageandcautery ble. The evidence for the role of adjuvant radiotherapy in a completely excised BCC withPNI isweak.14,53 Curettage, in combination with cautery or electrodesiccation, There is a single randomized trial evaluating standard surgical up to three cycles has been used as a treatment modality for excisionvs.radiotherapyforfacialBCCs<4 cm,in347patients. many years for BCC.7,12,14 Although it is an expedient and The4-yearactuarialfailureratewas0(cid:1)7%(95%confidenceintercost-effective technique for superficial lesions, it does not val 0(cid:1)1\u20133(cid:1)9%) for surgery, and 7(cid:1)5% (95% confidence interval allow histological marginassessment.7 4(cid:1)2\u201313(cid:1)1%)forradiotherapy(P = 0(cid:1)003).Patientswereassessed Curettage andcautery undertaken by experienced practitionforcosmeticresultat4 years,whichwasratedas\u2018good\u2019in87% ers for well-defined, low-risk nodular and superficial BCCs ofthosehavingundergonesurgeryand69%forradiotherapy.54,55 produces 5-year recurrence rates of 4\u20138%.65,66 If it is used for BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 12}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 911 high-risk BCC it was reported to have a recurrence rate of 7.7.1. Topical therapy 19%,41 which carries significant morbidity to patients and may make subsequent treatment more complicated and cure Two topical agents are licensed for BCC, namely imiquimod more difficulttoachieve. and5-fluorouracil (5-FU). Curettage may be used prior tostandard surgical excision to define the extent of tumour margins more accurately67 (see Imiquimod. Imiquimod is a toll-like receptor 7 agonist that section 7.4.1), prior to Mohs micrographic surgery48 (see secinduces a tumour-directed cellular immune response.75 Several tion 7.4.2), prior to cryosurgery12 (see section 7.6.2) or prior studies support its use in superficial BCC,72,76\u201378 and it is toPDT68(see section 7.7.2). licensed in a regimen of 5 days per week over 6 weeks. Many In the event that the curette enters the subcutaneous fat, studies support its efficacy in treating single or multiple small, curettage should be abandoned, and the wound excised surgisuperficial, low-risk BCCs, particularly those on the trunk and cally.7,12,14 limbs, with two noninferiority RCTs comparing imiquimod to standard surgical excisioninlow-risk BCC79,80 andtoPDTand topical 5-FU 5% cream.81,82 In these RCTs, topical imiquimod 7.6.2. Cryosurgery was inferior to standard surgical excision:79 3-year follow-up Although \u2018cryotherapy\u2019 is a common synonym for \u2018cryosurcure rates were 84% with imiquimod and 98% with standard gery\u2019, the GDG agreed to use the latter term because in the surgical excision (P < 0(cid:1)001), with comparable data at UK, the term \u2018cryotherapy\u2019 often refers to cold therapy for 5 years:80 82(cid:1)5% for imiquimod and 97(cid:1)7% for surgery destructive and nondestructive purposes. The term \u2018cryosur- (P < 0(cid:1)001).However,imiquimod wassuperiortobothMALgery\u2019 refers to the destruction of BCC using liquid nitrogen PDT and topical 5-FU:81 1-year follow-up cure rates were specifically. 83(cid:1)4% with imiquimod, 72(cid:1)8% with PDT and 80(cid:1)1% with 5Cryosurgerywithliquidnitrogensprayinfreeze\u2013thawcyclesis FU, indicating that topical imiquimod was superior to MALan effective treatment for selected low-risk, well-defined PDT and that 5-FU was noninferior to MAL-PDT for treatment BCCs.7,12,14 However, the reported 5-year recurrence rates vary of superficial BCC.79,81 Five-year follow-up data confirmed the significantly, ranging from 7(cid:1)5%65 to 20%.69 This variability superiority of imiquimod over both MAL-PDT and 5-FU, with mightbearesultofwrongpatientselection,differenttechniques 5-yearBCC-freesurvivalratesof80(cid:1)5%forimiquimod,70(cid:1)0% anddifferentclinicianskills,asreportedbyasingleclinicianwho for5-FU5%,and62(cid:1)7%forMAL-PDT.82 treated 7338 patients (primary and recurrent BCC and SCC) by Arits et al.81 noted that topical treatments are associated cryosurgeryover30 yearswithatotalrecurrencerateof1%.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 13}, {"text": "This variability superiority of imiquimod over both MAL-PDT and 5-FU, with mightbearesultofwrongpatientselection,differenttechniques 5-yearBCC-freesurvivalratesof80(cid:1)5%forimiquimod,70(cid:1)0% anddifferentclinicianskills,asreportedbyasingleclinicianwho for5-FU5%,and62(cid:1)7%forMAL-PDT.82 treated 7338 patients (primary and recurrent BCC and SCC) by Arits et al.81 noted that topical treatments are associated cryosurgeryover30 yearswithatotalrecurrencerateof1%.70 with very high rates of local AEs, with up to 56% of patients Thissen et al.71 compared the cosmetic outcome of cryosurexperiencing severe local skin reactions and discomfort. This gery with that of standard surgical excision of superficial BCC is variable between patients and may necessitate alterations to and reported that both clinicians and patients were in favour treatment regimens to achieve maximal efficacy without of standard surgical excision over cryosurgery. Similarly, in an unacceptable side-effects. Around 5% of patients treated with RCT comparing cryotherapy against methylaminolaevulinate topical imiquimod also experienced systemic flu-like symp- (MAL)-PDT, recurrence rates at 5 years were similar, but costoms.81 metic outcomes weresignificantly better with MAL-PDT.69 In terms of cosmesis, if the BCC does not recur, then topical therapy is associated with comparable or superior cosmetic outcomes to standard surgical excision at 3 years.79 7.6.3. Lasertherapy Laser destruction of low-risk superficial or thin nodular BCCs 5-Fluorouracil cream. 5-FU, a topical chemotherapeutic agent, is has been employed using several different laser types, includlicensed for treatment of superficial BCC in a treatment regiing pulsed dye72,73 and CO laser.74 The latter study randommen of once or twice daily for 3\u20134 weeks.83 As mentioned 2 ized patients to CO laser, standard surgical excision or above, 5-FU is inferior to imiquimod but is noninferior to 2 cryosurgery. Complete remission with CO laser was similar MAL-PDT.79\u201382 Rates of local AEs are similar to those seen 2 to that with cryosurgery but significantly lower than for surwith imiquimod, but flu-like systemic symptoms were not gery, although these data were reported after a follow-up perseen with use of 5-FU in one study.81 One study suggested iod of only 3 months and so are not sufficient to determine that 5-FU treatment was associated with higher rates of efficiency adequately. wound infection thanimiquimod treatment.81 Other agents. A low-certainty, randomized, vehicle-controlled 7.7. Nonsurgical clinical study involving 94 participants, of whom 62 For the indications for nonsurgical treatments please refer to patients with superficial, nodular, cystic and pigmented BCCs recommendations R14, R18\u2013R20, \u03981 and \u03982.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 13}, {"text": "randomized, vehicle-controlled 7.7. Nonsurgical clinical study involving 94 participants, of whom 62 For the indications for nonsurgical treatments please refer to patients with superficial, nodular, cystic and pigmented BCCs recommendations R14, R18\u2013R20, \u03981 and \u03982. For a more were treated with solasodine glycoalkaloids. This study detailed discussion on the evidence that underpins these recreported 66% efficacy with solasodine glycoalkaloids, comommendations please refer to Appendix D1 (LETR, pp 68\u201372; pared with 25% for the vehicle group at the end of an 8see SupportingInformation). week treatment period, which was reduced to 47% by the \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 13}, {"text": "912 BADguidelinesforadultswithBCC2021, I.Nasretal. end of the year.84 The results in this single study are not (mBCC)and26(cid:1)2 months(laBCC).94\u201396Duringtreatment,classsufficient to determine the safety and efficacy of the studied specificAEswerecommonandincludedmusclespasm,tastealtercream compared with more established topical agents. ations, hair loss, fatigue and weight loss. These AEs appeared in the majority of patients and led to treatment discontinuation in 21% of all treated patients. In the primary analysis of STEVIE, 7.7.2. Photodynamic therapy 1215recruitedpatientswereevaluable(1119laBCC,96mBCC). Topical PDT is a widely studied treatment option for low-risk, Investigator-assessed response rates were 68(cid:1)5% for laBCC and superficial BCC.69,81,82,85\u201387 In these studies, PDT was com36(cid:1)9%formBCC,andtheAEswereconsistentwiththoseidentipared with cryosurgery,87 standard surgical excision86 and fied in ERIVANCE.97,98 Treatment was associated with improvetopical therapy (imiquimod or 5-FU).81,82,85 The studies mentinhealth-relatedqualityoflife.101 showed that PDT was not inferior to cryosurgery, standard InpatientswithGorlinsyndrome,arandomized,placebo-consurgical excision or 5-FU, while imiquimod was superior to trolledtrialshowedasignificantreductioninthenumberofnew, PDT.ThecosmeticoutcomeofPDTwasbetterthanwithcryosurgicallyeligibleBCCsontreatmentwithvismodegibcompared surgery and standard surgical excision but was equalto that of withplacebo(2vs.29casespergroupperyear,P < 0(cid:1)001).99,100 imiquimod or 5-FU.69,81,82,85,86 The MIKIE study showed that two intermittent dosing regiPDTisassociatedwithfewAEs,ofwhichsomeareexpected mens of vismodegib were effective in the control of patients (e.g. pain during and after treatment and an acute local reacwith multiple BCCs, including Gorlin syndrome. The regimen tion) and some are unexpected, (e.g. urticaria in the treated with a shorter induction period of 12 weeks (followed by area, hyperand hypopigmentation, and rarely, scarring and 8 weeks of placebo alternating with 12 weeks of treatment) contactsensitization).88 showed a similar AE profile to that in the group with a 24Some studies indicate a possible role for PDT in treating week induction period (followed by 8 weeks of placebo alternodular BCC, although 5-year follow-up studies indicate effinatingwith 8 weeks oftreatment).102 cacy rates of no more than 76% at best:89 2-year cure rate of Studies of neoadjuvant vismodegib in patients with laBCC 94% for standard surgical excision and 74% for PDT;90 5-year are promising, especially in the periocular andorbital areafolcure rates of 96% and 76%, respectively;89 12-month cure lowedby Mohs micrographicsurgery.103\u2013105 rates of 79% and 62%, respectively;68 3-year cure rates of Sonidegib, the other smoothened inhibitor, was also shown to 97(cid:1)7% and 69(cid:1)7%, respectively;91 and 5-year cure rates of beclinicallyeffectivein apivotalprospective randomized dou98%and72% forPDT, respectively.92 ble-blinded clinicaltrial(BOLT).106,107 Guidelines regarding use of PDT in BCC can be found in theBADandBritish PhotodermatologyGroup updatedguideli7.7.4. Electrochemotherapy nes for topicalPDT.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 14}, {"text": "97(cid:1)7% and 69(cid:1)7%, respectively;91 and 5-year cure rates of beclinicallyeffectivein apivotalprospective randomized dou98%and72% forPDT, respectively.92 ble-blinded clinicaltrial(BOLT).106,107 Guidelines regarding use of PDT in BCC can be found in theBADandBritish PhotodermatologyGroup updatedguideli7.7.4. Electrochemotherapy nes for topicalPDT.93 NICE recognizedECT asanablative treatment formetastases in theskinfromtumoursofnonskinoriginandmelanoma,108and 7.7.3. Hedgehog pathway inhibition in2014producedaguidanceonECTforprimaryBCCandpriFor a more detailed discussion on the evidence that underpins mary SCC.109 With regard to primary BCC, NICE advised that theserecommendationspleaserefertoAppendixD1(LETR,pp67; \u2018evidenceonitsefficacyislimitedinquantityandquality\u2019,andthattheclinseeSupportingInformation). icianshould\u2018ensurethatpatientsunderstandtheuncertaintyabouttheproceVismodegib and sonidegib are hedgehog pathway inhibidure\u2019sefficacyandwhyitisbeingofferedasanalternativetootherestablished tors and specifically target oncogenic smoothened receptors. methodsoftreatment\u2019.109Sincethen,fournonrandomizedcomparaBoth vismodegib and sonidegib are approved by the Eurotiveandnoncomparative studies, andoneRCThave been pubpean Medicines Agency and the US Food and Drug Adminlished.110\u2013114 The certainty of these studies are generally very istration for treatment of adults with laBCC who are not low,andnoneprovidedadditionalevidencetoupdatetheNICE candidates for surgery or radiotherapy, while vismodegib is recommendationsinitsguidancefortreatingprimaryBCC. also approved for patients with mBCC. Currently in the UK, Campana et al.115 and Gehl et al.116 produced recommendavismodegib has a marketing authorization but did not attain tions and minimal requirements for reporting clinical data on NICE approval for treating symptomatic metastatic BCC in ECT and updated the standard operating procedures for ECT, the NHS, whereas sonidegib does not have a marketing which, if future trials followed these, would help provide furauthorization. ther evidence for clinical practice. For a more detailed discusVismodegib demonstrated efficacy in patients with laBCC and sion on the GDG\u2019s decision not to recommend ECT for mBCC in the pivotal ERIVANCE clinical trial.94\u201396 Efficacy was treating BCC, please refer to Appendix D1 (LETR, pp 73\u20134; confirmed in a subsequent global safety study (STEVIE clinical seeSupporting Information). trial),97,98 and was also demonstrated in a separate RCT in patients withGorlinsyndrome.99,100 7.7.5. Othertreatments Intotal,104patientsweretreatedinERIVANCE.At39 months, responserateswere60(cid:1)3%(laBCC)and48(cid:1)5%(mBCC,allpartial Thereareothertreatmentsthathavebeenreportedintheliterresponses), and median response durations were 14(cid:1)8 months ature to treat BCC, but they are either historical or currently BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 14}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 913 have insufficient evidence to recommend their use for treating important, so for children with a high risk of BCC, education BCC. on skin surveillance and regular follow-up with a dermatologist are recommended.14,130\u2013132 Chemotherapy. Literature on chemotherapy for BCC is old and limited to case reports7 that would not comply with the 8. Follow-up guideline\u2019s inclusion criteria. Moreover, since the introduction of hedgehog inhibitors, chemotherapy has rarely been used in Please refer to recommendations R24\u2013R26 and Appendix D3 practice (personal communications). (pp 87\u201390; see Supporting Information) . R24 is underpinned by higher-certainty evidence against routinely followSystemic immunotherapy. Literature on systemic immunotherapy ing up adequately treated BCC, whereas R25 and R26 are is fairly new but still limited to a phase II study and case recommendations based on GPP. There are many specialties reports. These reports indicate that anti-programmed death-1 that treat BCCs and other skin cancers, and each specialty (anti-PD-1) drugs, namely pembrolizumab117,118 and nivoluwill have their own clinics and policies to govern the folmab,119,120 might be promising agents to treat advanced BCC, low-up process. although one120 of the two reports on nivolumab showed that Thepossiblereasonsforfollow-upafterinitialdiagnosisand new superficial and nodular BCCs appeared during successful treatment include(i) detection oflocal recurrencefor tumours treatment of ametastatictumour. at high risk for recurrence, (ii) monitoring of advanced BCC following conservative or palliative treatment,(iii) surveillance Combination therapy. There were few studies, and of very low for subsequent development of new BCCs and/or other skin certainty, evaluating a number of different combination theracancers and (iv) repeating the advice on BCC verbally and in pies to treat nodular BCC, such as combinations of diclofenac writtenformat(asmentionedinsection 7.1). + calcitriol,121 imiquimod + Mohs micrographic surAt present there is no evidence that follow-up is required gery,122,123 interferon-a + standard surgical excision,124 topifor patients with a single, adequately treated low-risk BCC. cal PDT + Mohs micrographic surgery125 and lasers + topical However, for patients with inadequately treated BCC at high PDT.126\u2013128 In order to assess such combination therapies, risk of recurrence, for patients with a past history of multiple they needtobefollowedup for atleast 5 years. primary or recurrent BCCs, or for those who are at high risk of developing multiple BCCs (e.g. in the setting of Gorlin syndrome or immunosuppression), then long-term follow-up 7.8.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 15}, {"text": "multiple they needtobefollowedup for atleast 5 years. primary or recurrent BCCs, or for those who are at high risk of developing multiple BCCs (e.g. in the setting of Gorlin syndrome or immunosuppression), then long-term follow-up 7.8. Basal cellcarcinoma inchildren andyoung people may be justified. There is no evidence to support how often BCC is extremely rare in children under 15 years of age,129 this should be, but 6-monthly follow-up for the first year, and when seen is generally in the context of inherited condithen annually for at least 5 years and possibly up to 10 years tions such as Gorlin syndrome (prevalence 1 per 40 000\u2013 or longer may be appropriate. This may need to be more fre60 000).130 Childhood BCC may also be seen in association quent in selected high-risk patients such as those with Gorlin with xeroderma pigmentosum, Bazex syndrome, Rombo synsyndrome or immunosuppressed organ transplant recipients. drome, albinism, previous radiotherapy and naevus sebaFor patients with advanced BCC, follow-up is likely to be ceous.11,129,131 Sporadic idiopathic BCC in childhood is also required andshouldbedecidedaspartofmanagementdiscusreported in the literature, with a total of 107 cases reported sions withintheSSMDT andon acase-by-case basis. worldwide.129,131 All childhood BCC should be managed within the context of a specialist MDT including specialists 9. Prevention experienced intreating skin cancerin children.130,132 The first-line treatment option for childhood BCC is surPatients with a history of BCC have an increased risk of develgery, with either standard surgical excision or Mohs microoping further skin cancers of all types.133\u2013135 For this reason, graphic surgery.129\u2013132 Other treatments described for treating advice regarding the avoidance of excessive exposure to ultrachildhood BCC include radiotherapy (contraindicated in inherviolet radiation, including from sunbeds, and regular skin ited BCC syndromes),14,62,132 topical therapy, curettage and surveillance is recommended for all patients with BCC. Practicautery, PDT and cryosurgery.129\u2013132 However, in view of the cal guidance in this regard, including on vitamin D supplehigh recurrence rates for childhood BCC (18% overall),131 mentation, is well described in the NICE guidance \u2018Sunlight these treatment options are notrecommended. exposure: risks and benefits\u2019136 and in conjunction with Vismodegib has proven efficacy in treating BCCs associated another NICE guidance on \u2018Vitamin D: supplement use in withGorlinsyndrome,butitsuseinchildrenislimitedbysidespecific population groups\u2019.137 effects,ahighrecurrencerateandincidenceofnewtumourson Although excessive ultraviolet radiation exposure is strongly cessationoftreatment.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 15}, {"text": "and in conjunction with Vismodegib has proven efficacy in treating BCCs associated another NICE guidance on \u2018Vitamin D: supplement use in withGorlinsyndrome,butitsuseinchildrenislimitedbysidespecific population groups\u2019.137 effects,ahighrecurrencerateandincidenceofnewtumourson Although excessive ultraviolet radiation exposure is strongly cessationoftreatment.Inaddition,vismodegibiscurrentlynot associated with the development of BCCs, there is no good recommendedbyNICEguidanceintheUK.130,132 evidence for the benefit of sunscreens in preventing further Reducing the risk of future development of BCC should BCC (in contrast to actinic keratosis and cutaneous SCC).138 start in childhood with ultraviolet protection, particularly in Despite the lack of firm evidence for the role of sunscreens in those with predisposing conditions. Early detection is preventing BCC, it is still considered an important part of \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 15}, {"text": "914 BADguidelinesforadultswithBCC2021, I.Nasretal. general advice on sun protection. Specific agents that have org.uk/clinical-and-research/our-programmes/qualitybeen studied for the chemoprevention of BCC are described improvement/community-based-surgery-audit.aspx), to docbelow. umentallsurgicallytreatedcasesofNMSCincludingBCC. (cid:129) Nonsteroidal anti-inflammatory drugs (NSAIDs; other Other secondary care specialists may have alternative than aspirin): a large RCT found that oral celecoxib 200 mg arrangementsfor auditing theirpractice. twice daily significantly reduced the mean number of BCCs in Thesetoolscalculatethestatisticswhileaddingthehistology a high-risk population.139 However, there is a known risk of results. They present the results for the whole department or cardiovascular events with long-term use of cyclooxygenase-2 for theindividual surgical operators in thedepartment. (COX-2) inhibitors, and therefore routine use in the prevenFor all cases of BCC, is there documentation of the followtion setting is notcurrently recommended. ing(modified BSDS audit tool)? Oral retinoids: acitretin has long been used in transplant/ (cid:129) immunocompromised patients with a high keratinocyte Surgeonidentity (cid:129) tumour burden. Its use is limited due to a high rate of mucoPatient identity without any identifiable personal data cutaneous side-effects and hyperlipidaemia. No large RCTs entry (cid:129) have been carried out in the nonimmunosuppressed populaSiteof lesion (cid:129) tion, although a small study demonstrated that acitretin Primaryvs. recurrent lesion (cid:129) 25 mg once daily was associated with 25% fewer keratinocyte Typeofsurgery (cid:129) cancers (both BCC and SCC) compared with placebo.140 HowClinical surgical margins (cid:129) ever, the results lacked statistical significance for the study size Closure (cid:129) (designed topick upadifference of33%or more). Growth pattern, deep invasion, perineural invasion and Oral nicotinamide: anRCTinvolvingnicotinamide500 mg TNM stage (cid:129) twicedailyinpatientswithahistoryofNMSCshowedarelative Histological marginclearance (cid:129) reductioninBCCincidenceof20%at12 months.141Thisresult Complications (cid:129) wasmodestandnotstatisticallysignificant,andthereductionin Follow-upplan BCC incidence wasnotmaintainedupon cessationofthedrug. For all cases of BCC managed in primary care, is there docAclinicianwishingtoadviseonoralnicotinamideshouldhighumentation ofthefollowing (CBSA audit tool)? light to their patients that it gives no more than 20% relative (cid:129) reduction in thenumber ofBCCs, theeffectis notlong-lasting Surgeon (cid:129) followingtreatmentcessation,andtheevidenceisbasedononly Patient (cid:129) onetrialthathasnotbeenrepeated. Proceduretype Other oral agents: both a-difluoromethylornithine142 and (cid:129) Locationof lesion (cid:129) selenium143 have been studied for effects on BCC prevention, Closure (cid:129) butno significant risk reduction has beenfound. Histology serviceusage (cid:129) Topical retinoids: neither tazarotene144 nor tretinoin145 Histological diagnoses (cid:129) has been showntosignificantly reduce therisk ofBCC. Comparisonof clinicalandhistological diagnoses (cid:129) Inconclusion,asidefromsunprotection146andregularskin Histological margincompleteness (cid:129) self-surveillance,whichshouldberecommendedforallpatients Complications (cid:129) followingadiagnosisofBCC,thereissomeevidenceforasmall Managementinformation preventative effect of oral acitretin, nicotinamide and non- \u25cb Waiting timefor surgery aspirinNSAIDs.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 16}, {"text": "Histological diagnoses (cid:129) has been showntosignificantly reduce therisk ofBCC. Comparisonof clinicalandhistological diagnoses (cid:129) Inconclusion,asidefromsunprotection146andregularskin Histological margincompleteness (cid:129) self-surveillance,whichshouldberecommendedforallpatients Complications (cid:129) followingadiagnosisofBCC,thereissomeevidenceforasmall Managementinformation preventative effect of oral acitretin, nicotinamide and non- \u25cb Waiting timefor surgery aspirinNSAIDs.Duetothecommitmentoflifelongmedication \u25cb Waiting timefor histology results and the potential for side-effects, these are likely to be recom- \u25cb Consent forsurgery mendedonlyforthosewithahistoryofmultipleBCCs. \u25cb Postoperative information \u25cb Onward referral 10. Recommended audit points Individual operators and units should regularly audit their outcomes, with a target of \u2265 95% complete excision rate All clinicians treating skin cancer should audit their histologibeing definedasacceptable.147,148 cal concordance and complete excision rate (Appendix L; see Supporting Information). Current examples available for use include: 11. Stakeholder involvement and peer review (cid:129) For dermatologists who are core MDT members: the BriThe GDG consisted of representatives from the National Cantish Society for Dermatological Surgery (BSDS) audit tool cer Research Institute (NCRI) Skin Cancer Clinical Studies (https://bsds2020.wpengine.com/wp-content/uploads/ Group and nonmelanoma skin cancer subgroup (C.A.H.), the 2020/10/Dr-Brays-Surgical-Log-Book.zip). RCGP (J.B.), the RCPath (D.N.S.), the Royal College of Radiol- (cid:129) For primary care clinicians involved in skin cancer surgery: ogists (RCR) (K.F.), the British Association of Oral and MaxtheCommunityBasedSurgeryAudit(CBSA)tool(www.rcgp. illofacial Surgeons (BAOMS) (C.N.), the British Association of BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 16}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 915 Plastic Reconstructive and Aesthetic Surgeons (BAPRAS) 3 Guyatt GH, Oxman AD, Vist GE et al. GRADE: an emerging con- (P.G.B.), the British Society for Dermatological Surgery (BSDS) sensus on rating quality of evidence and strength of recommen- (R.J.M.), the British Society for Skin Care in Immunosupdations.BMJ2008;336:924\u20136. 4 TelferN,ColverG,MortonC.Guidelinesforthemanagementof pressedIndividuals(BSSCII)(J.T.L.),theBritishDermatological basalcellcarcinoma.BrJDermatol2008;159:35\u201348. Nursing Group (BDNG) (J.N.) and the Primary Care Dermato5 SlaterD,BarrettP,DurhamC.Standardsanddatasetsforreporting logical Society (PCDS) (N.S.). The draft document and supcancers.Datasetforhistopathologicalreportingofprimaryinvasive porting information were made available to the BAD cutaneous squamous cell carcinoma and regional lymph nodes. membership, the RCGP, RCPath, RCR, BAOMS, BAPRAS, BSDS, Available at: https://www.rcpath.org/uploads/assets/9c1d8f71BSSCII, BDNG, PCDS and British Association of Head & Neck 5d3b-4508-8e6200f11e1f4a39/Dataset-for-histopathological-re Oncologists (BAHNO), whose feedback was actively considporting-of-primary-invasive-cutaneous-squamous-cell-carcinomaand-regional-lymph-nodes.pdf(lastaccessed2June2021). ered by the GDG. Following further review, the finalized ver6 National Institute for Health and Care Excellence. Improving outsion wassentfor peerreview bytheClinical StandardsUnitof comesforpeoplewithskintumoursincludingmelanoma(update). theBAD,madeup oftheT&Gsubcommittee, priortosubmisThemanagementoflow-riskbasalcellcarcinomasinthecommusion forpublication. nity. Available at: https://www.nice.org.uk/guidance/csg8/evide nce/2010-update-the-management-of-lowrisk-basal-cell-carcinoma 12. Limitations of the guideline s-in-the-community-updated-recommendations-and-evidence-onthis-topic-only-pdf-7022614429(lastaccessed2June2021). This document has been prepared on behalf of the BAD and is 7 National Comprehensive Cancer network (NCCN). NCCN Guidelines. Basal cell skin cancer. Available at: https://www.nccn.org/ based on the best data available when the document was preguidelines/guidelines-detail?category=1&id=1416(lastaccessed2 pared. It is recognized that under certain conditions it may be June2021). necessary to deviate from the guidelines and that the results of 8 Gospodarowicz MK, Brierley JD, Wittekind C. TNM Classification of future studies may require some of the recommendations MalignantTumours.Chichester:JohnWiley&Sons,2017. hereintobechanged.Additionally,itisacknowledgedthatlim9 Califano J, Lydiatt WM, Nehal KS et al. Cutaneous squamous cell ited cost-effectiveness data in the context of the UK healthcare carcinomaoftheheadandneck.In:AJCCCancerStagingManual(Amin settingmayimpactontheavailabilityofagiventherapywithin MB,EdeS,GreeneF,etal.,eds),Berlin:Springer,2017;171\u201381. 10 Lear JT, Corner C, Dziewulski P et al. Challenges and new horitheNHS,despiteevidenceofefficacy.Failuretoadheretothese zons in the management of advanced basal cell carcinoma: a UK guidelines should not necessarily be considered negligent, nor perspective.BrJCancer2014;111:1476\u201381. should adherence to these recommendations constitute a 11 DikaE,Scarf(cid:3)\u0131F,FerracinMetal.Basalcellcarcinoma:acompredefence against a claim of negligence. Limiting the review to hensivereview.IntJMolSci2020;21:5572. English-language references was a pragmatic decision but the 12 Bichakjian C, Armstrong A, Baum C et al. Guidelines of care for authors recognize this may exclude some important informathemanagementofbasalcellcarcinoma.JAmAcadDermatol2018; tionpublishedinotherlanguages. 78:540\u201359. 13 ReinauD,SurberC,JickSSetal.Epidemiologyofbasalcellcarcinoma in the UK: incidence, lifestyle factors, and comorbidities. 13. Plans for guideline revision BrJCancer2014;111:203\u20136. 14 Peris K, Fargnoli MC, Garbe C et al.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 17}, {"text": "some important informathemanagementofbasalcellcarcinoma.JAmAcadDermatol2018; tionpublishedinotherlanguages. 78:540\u201359. 13 ReinauD,SurberC,JickSSetal.Epidemiologyofbasalcellcarcinoma in the UK: incidence, lifestyle factors, and comorbidities. 13. Plans for guideline revision BrJCancer2014;111:203\u20136. 14 Peris K, Fargnoli MC, Garbe C et al. Diagnosis and treatment of The proposed revision for this set of recommendations is basal cell carcinoma: European consensus-based interdisciplinary scheduled for 2026; where necessary, important interim guidelines.EurJCancerCare2019;118:10\u201334. changes willbeupdated ontheBAD website. 15 Venables Z, Nijsten T, Wong K et al. Epidemiology of basal and cutaneoussquamouscellcarcinomaintheUK2013\u201315:acohort study.BrJDermatol2019;181:474\u201382. Acknowledgements 16 Kowal-Vern A, Criswell BK. Burn scar neoplasms: a literature reviewandstatisticalanalysis.Burns2005;31:403\u201313. We are very grateful to the patient representatives for their 17 Tan ST, GhaznawieM,HeenanPJ, DosanR. Basalcell carcinoma input in formulating the clinical questions, ranking of the arises from interfollicular layer of epidermis. J Oncol 2018; outcomes, reviewing the evidence and subsequent draft 2018:3098940. guideline; to clinical oncologist Agata Rembielak; and to all 18 Sehgal VN, Chatterjee K, Pandhi D et al. Basal cell carcinoma: those who commented on the draft during the consultation pathophysiology.Skinmed2014;12:176\u201381. period. 19 Matinfar M, Shahidi S, Feizi A. Incidence of nonmelanoma skin cancer in renal transplant recipients: a systematic review and References meta-analysis.JResMedSci2018;23:14. 20 OmlandSH,AhlstromMG,GerstoftJetal.Riskofskincancerin 1 Mohd Mustapa M, Exton L, Bell H et al. Updated guidance for patients with HIV: a Danish nationwide cohort study. J Am Acad writing a British Association of Dermatologists clinical guideline: Dermatol2018;79:689\u201395. the adoption of the GRADE methodology 2016. Br J Dermatol 21 Mellor RH, Bulstrode N, Withey S et al. The stretch test in basal 2017;176:44\u201351. cellcarcinoma:aclinicalindicatoroftumour.BrJPlastSurg2002; 2 Brouwers MC, Kho ME, Browman GP et al. AGREE II: advancing 55:594\u20135. guideline development, reporting and evaluation in health care. 22 Carducci M, Bozzetti M, De Marco G et al. Usefulness of marCanMedAssocJ2010;182:E839\u2013E842. gin detection by digital dermoscopy in the traditional surgical \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 17}, {"text": "916 BADguidelinesforadultswithBCC2021, I.Nasretal. excision of basal cell carcinomas of the head and neck 41 Thissen MR, Neumann MH, Schouten LJ. A systematic review of including infiltrative/morpheaform type. J Dermatol 2012; treatment modalities for primary basal cell carcinomas. Arch Der39:326\u201330. matol1999;135:1177\u201383. 23 Caresana G, Giardini R. Dermoscopy-guided surgery in basal cell 42 SmeetsNW,KrekelsGA,OstertagJUetal.Surgicalexcisionversus carcinoma.JEurAcadDermatolVenereol2010;24:1395\u20139. Mohs\u2019 micrographic surgery for basal-cell carcinoma of the face: 24 KadouchDJ,LeeflangMM,ElshotYSetal.Diagnosticaccuracyof randomisedcontrolledtrial.Lancet2004;364:1766\u201372. confocalmicroscopyimagingversuspunchbiopsyfordiagnosing 43 MosterdK, KrekelsGA,NiemanFHetal.Surgicalexcisionversus and subtyping basal cell carcinoma. J Eur Acad Dermatol Venereol Mohs\u2019 micrographic surgery for primary and recurrent basal-cell 2017;31:1641\u20138. carcinoma of the face: a prospective randomised controlled trial 25 Yucel D, Themstrup L, Manfredi M et al. Optical coherence with5-years\u2019follow-up.LancetOncol2008;9:1149\u201356. tomography of basal cell carcinoma: density and signal attenua44 Griffiths R, Suvarna S, Stone J. Do basal cell carcinomas recur tion.SkinResTechnol2016;22:497\u2013504. aftercompleteconventionalsurgicalexcision?BrJPlastSurg2005; 26 IftimiaN,PetersonG,ChangEWetal.Combinedreflectancecon58:795\u2013805. focal microscopy\u2013optical coherence tomography for delineation 45 Wetzig T, Woitek M, Eichhorn K et al. Surgical excision of basal of basal cell carcinoma margins: an ex vivo study. J Biomed Opt cell carcinomawith completemargin control: outcome at 5-year 2016;21:16006. follow-up.Dermatology2010;220:363\u20139. 27 vanEgmondS,WakkeeM,DrogerMetal.Needsandpreferences 46 Macfarlane L, Waters A, Evans A et al. Seven years\u2019 experience of of patients regarding basal cell carcinoma and cutaneous squaMohs micrographic surgery in a UK centre, and development of mous cell carcinoma care: a qualitative focus group study. Br J a UK minimum dataset and audit standards. Clin Exp Dermatol Dermatol2019;180:122\u20139. 2013;38:262\u20139. 28 Varga E, Korom I, Rasko Z et al. Neglected basal cell carcinomas 47 LeibovitchI,HuilgolSC,SelvaDetal.Basalcellcarcinomatreated inthe21stcentury.JSkinCancer2011;2011:392151. with Mohs surgery in Australia II. Outcomeat 5-year follow-up. 29 Sherry K, Reid L, Wilmshurst A. A five year review of basal cell JAmAcadDermatol2005;53:452\u20137. carcinomaexcisions.JPlastReconstrAesthetSurg2010;63:1485\u20139. 48 Wennberg AM, Larko O, Stenquist B. Five-year results of Mohs\u2019 30 Codazzi D, Van Der Velden J, Carminati M et al. Positive commicrographicsurgeryforaggressivefacialbasalcellcarcinomain paredwithnegativemarginsinasingle-centreretrospectivestudy Sweden.ActaDermVenereol1999;79:370\u20132. on 3957 consecutive excisions of basal cell carcinomas. Associ49 Dhepnorrarat RC, Lee MA, Mountain JA. Incompletely excised ated risk factors and preferred surgical management. J Plast Surg skincancerrates:aprospectivestudyof31731skincancerexciHandSurg2014;48:38\u201343. sionsbytheWesternAustralianSocietyofPlasticSurgeons.JPlast 31 GiuffridaR,ConfortiC,DiMeoNetal.Useofnoninvasiveimaging ReconstrAesthetSurg2009;62:1281\u20135. inthemanagementofskincancer.CurrOpinOncol2020;32:98\u2013105. 50 British Association of Dermatologists. Service guidance and stan32 Marek AJ, Chu EY, Ming ME et al. Piloting the use of smartdards for Mohs micrographic surgery (MMS). Available at: phones, reminders, and accountability partners to promote skin https://www.bad.org.uk/shared/get-file.ashx?itemtype=docume self-examinationsinpatientswithtotalbodyphotography:arannt&id=6346(lastaccessed2June2021). domizedcontrolledtrial.AmJClinDermatol2018;19:779\u201385.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 18}, {"text": "Marek AJ, Chu EY, Ming ME et al. Piloting the use of smartdards for Mohs micrographic surgery (MMS). Available at: phones, reminders, and accountability partners to promote skin https://www.bad.org.uk/shared/get-file.ashx?itemtype=docume self-examinationsinpatientswithtotalbodyphotography:arannt&id=6346(lastaccessed2June2021). domizedcontrolledtrial.AmJClinDermatol2018;19:779\u201385. 51 van Loo E, Mosterd K, Krekels GA et al. Surgical excision versus 33 Schneider SL, Kohli I, Hamzavi IH et al. Emerging imaging techMohs\u2019 micrographic surgery for basal cell carcinoma of the face: nologiesindermatology.PartI.Basicprinciples.JAmAcadDermatol a randomised clinical trial with 10 year follow-up. Eur J Cancer 2019;80:1114\u201320. 2014;50:3011\u201320. 34 Schneider SL, Kohli I, Hamzavi IH et al. Emerging imaging tech52 LikhachevaA,AwanM,BarkerCAetal.Definitiveandpostoperanologies in dermatology. Part II. Applications and limitations. J tive radiation therapy for basal and squamous cell cancers of the AmAcadDermatol2019;80:1121\u201331. skin:anASTROclinicalpracticeguideline.PractRadiatOncol2020; 35 Rimmer A. Can I receive and store images sent from patients 10:8\u201320. duringremoteconsultations?BMJ2020;370:m2675. 53 Jackson JE, Dickie GJ, Wiltshire KL et al. Radiotherapy for per36 Cunliffe T, Schofield J. Guidance and competences for GPs with ineural invasion in cutaneous head and neck carcinomas: toward extended roles in dermatology and skin surgery. Available at: arisk-adaptedtreatmentapproach.HeadNeck2009;31:604\u201310. https://www.rcgp.org.uk/training-exams/practice/guidance-and54 AvrilMF,AuperinA,MargulisAetal.Basalcellcarcinomaofthe competences-for-gps-with-extended-roles-in-dermatology-andface:surgeryorradiotherapy?Resultsofarandomizedstudy.BrJ skin-surgery.aspx(lastaccessed2June2021). Cancer1997;76:100\u20136. 37 NationalInstituteforHealthandCareExcellence.Improvingoutcomes 55 Bath-Hextall FJ, Perkins W, Bong J et al. Interventions for basal for people with skin tumours including melanoma. Available at: cell carcinoma of the skin. Cochrane Database Syst Rev 2007; 1: https://www.nice.org.uk/guidance/csg8(lastaccessed2June2021). CD003412. 38 National Institute for Health and Care Excellence. Skin cancer. 56 Marconi DG, Da Costa Resende B, Rauber E et al. Head and neck Available at: https://www.nice.org.uk/guidance/qs130 (last non-melanoma skin cancer treated by superficial X-ray therapy: accessed2June2021). ananalysisof1021cases.PLoSOne2016;11:e0156544. 39 British Association of Dermatologists. National reform of cancer 57 GunaratneDA,VenessMJ.EfficacyofhypofractionatedradiotherMDTmeetings.Availableat:https://www.bad.org.uk/healthcareapy in patientswith non-melanoma skincancer: resultsofa sysprofessionals/clinical-services/national-reform-of-cancer-mdt-mee tematicreview.JMedImagingRadiatOncol2018;62:401\u201311. tings(lastaccessed2June2021). 58 ZagrodnikB,KempfW,SeifertBetal.Superficialradiotherapyfor 40 Gore M. Transforming multidisciplinary team meetings patientswithbasalcellcarcinoma:recurrencerates,histologicsub- (MDTMs). Available at: https://www.england.nhs.uk/south/wptypes,andexpressionofp53andBcl-2.Cancer2003;98:2708\u201314. content/uploads/sites/6/2018/10/Transforming-MDTM-Martin59 Podd T. Treatment of lower limb basal cell and squamous cell Gore-August-2017.pdf(lastaccessed2June2021). carcinomaswithradiotherapy.ClinOncol1992;4:44\u20135. BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 18}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 917 60 Pampena R, Palmieri T, Kyrgidis A et al. Orthovoltage radiothercream 5%: results of a prospective 5-year study. Cutis 2010; apyfor nonmelanoma skin cancer (NMSC): comparison between 85:318\u201324. 2differentschedules.JAmAcadDermatol2016;74:341\u20137. 79 Bath-Hextall F, Ozolins M, Armstrong SJ et al. Surgical excision 61 CooperJS.Radiotherapyinthetreatmentofskincancers.In:Canversusimiquimod5%creamfornodularandsuperficialbasal-cell ceroftheSkin(FriedmanRJ,RigelDS,KopfAW,HarrisMN,Baker carcinoma (SINS): a multicentre, non-inferiority, randomised D,eds),Philadelphia:WBSaunders,1991;553\u201368. controlledtrial.LancetOncol2014;15:96\u2013105. 62 Silverman MK, Kopf AW, Gladstein AH et al. Recurrence rates of 80 Williams HC, Bath-Hextall F, Ozolins M et al. Surgery versus 5% treatedbasalcellcarcinomas.Part4:X-raytherapy.JDermatolSurg imiquimod for nodular and superficial basal cell carcinoma: 5Oncol1992;18:549\u201354. yearresultsoftheSINSrandomizedcontrolledtrial.JInvestDerma63 Smith SP, Foley EH, Grande DJ. Use of Mohs micrographic surtol2017;137:614\u20139. gery to establish quantitative proof of heightened tumor spread 81 AritsAH,MosterdK,EssersBAetal.Photodynamictherapyversus inbasalcellcarcinomarecurrentfollowingradiotherapy. JDermatopical imiquimod versus topical fluorouracil for treatment of tolSurgOncol1990;16:1012\u20136. superficial basal-cell carcinoma: a single blind, non-inferiority, 64 Smith SP, Grande DJ. Basal cell carcinoma recurring after radiorandomisedcontrolledtrial.LancetOncol2013;14:647\u201354. therapy: a unique, difficult treatment subclass of recurrent basal 82 Jansen MHE, Mosterd K, Arits A et al. Five-year results of a rancellcarcinoma.JDermatolSurgOncol1991;17:26\u201330. domized controlled trial comparing effectiveness of photody65 Rowe DE, Carroll RJ, Day CL Jr. Long-term recurrence rates in namic therapy, topical imiquimod and topical 5-fluorouracil in previously untreated (primary) basal cell carcinoma: implicapatients with superficial basal cell carcinoma. J Invest Dermatol tions for patient follow-up. J Dermatol Surg Oncol 1989; 15:315\u2013 2018;138:527\u201333. 28. 83 MylanProductsLtd.Efudix5%cream[packageleaflet].Available 66 Barlow JO, Zalla MJ, Kyle A et al. Treatment of basal cell carciat: https://www.medicines.org.uk/emc/files/pil.9260.pdf (last nomawithcurettagealone.JAmAcadDermatol2006;54:1039\u201345. accessed2June2021). 67 Chiller K, Passaro D, McCalmont T et al. Efficacy of curettage 84 Punjabi S, Cook LJ, Kersey P et al. Solasodine glycoalkaloids: a before excision in clearing surgical margins of nonmelanoma novel topical therapy for basal cell carcinoma. A double-blind, skincancer.ArchDermatol2000;136:1327\u201332. randomized, placebo-controlled, parallel group, multicenter 68 BerroetaL,ClarkC,DaweRetal.Arandomizedstudyofminimal study.IntJDermatol2008;47:78\u201382. curettage followed by topical photodynamic therapy compared 85 Roozeboom MH, Arits A, Mosterd K et al. Three-year follow-up with surgical excision for low-risk nodular basal cell carcinoma. results of photodynamic therapy vs. imiquimod vs. fluorouracil BrJDermatol2007;157:401\u20133. for treatment of superficial basal cell carcinoma: a single-blind, 69 Basset-Seguin N, Ibbotson SH, Emtestam L et al. Topical methyl noninferiority, randomized controlled trial. J Invest Dermatol 2016; aminolaevulinate photodynamic therapy versus cryotherapy for 136:1568\u201374. superficial basal cell carcinoma: a 5 year randomized trial. Eur J 86 SzeimiesRM,IbbotsonS,MurrellDFetal.AclinicalstudycomparDermatol2008;18:547\u201353. ingmethylaminolevulinatephotodynamictherapyandsurgeryin 70 Kuflik EG.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 19}, {"text": "al. Topical methyl noninferiority, randomized controlled trial. J Invest Dermatol 2016; aminolaevulinate photodynamic therapy versus cryotherapy for 136:1568\u201374. superficial basal cell carcinoma: a 5 year randomized trial. Eur J 86 SzeimiesRM,IbbotsonS,MurrellDFetal.AclinicalstudycomparDermatol2008;18:547\u201353. ingmethylaminolevulinatephotodynamictherapyandsurgeryin 70 Kuflik EG. Cryosurgery for skin cancer: 30-year experience and small superficial basal cell carcinoma (8\u201320 mm), with a 12curerates.DermatolSurg2004;30:297\u2013300. monthfollow-up.JEurAcadDermatolVenereol2008;22:1302\u201311. 71 Thissen MR, Nieman FH, Ideler AH et al. Cosmetic results of 87 Basset-Seguin N. Topical photodynamic therapy for superficial cryosurgery versus surgical excision for primary uncomplicated and nodular basal cell carcinoma. Expert Rev Dermatol 2010; 5:61\u2013 basal cell carcinomas of the head and neck. Dermatol Surg 2000; 6. 26:759\u201364. 88 IbbotsonSH,WongTH,MortonCAetal.Adverseeffectsoftopi72 Roozeboom MH, Arits AH, Nelemans PJ et al. Overall treatment cal photodynamic therapy: a consensus review and approach to successaftertreatmentofprimarysuperficialbasalcellcarcinoma: management.BrJDermatol2019;180:715\u201329. a systematic review and meta-analysis of randomized and non89 Rhodes LE, de Rie MA, Leifsdottir R et al. Five-year follow-up of randomizedtrials.BrJDermatol2012;167:733\u201356. arandomized,prospectivetrialoftopicalmethylaminolevulinate 73 TranHT,LeeRA,OganesyanGetal.Singletreatmentofnon-mephotodynamictherapyversussurgeryfornodularbasalcellcarcilanomaskincancersusingapulsed-dyelaserwithstackedpulses. noma.ArchDermatol2007;143:1131\u20136. LasersSurgMed2012;44:459\u201367. 90 Rhodes LE, de Rie M, Enstrom Y et al. Photodynamic therapy 74 Zane C, Facchinetti E, Arisi M et al. Pulsed CO laser ablation of using topical methyl aminolevulinate versus surgery for nodular 2 superficial basal cell of limbs and trunk: a comparative randombasal cell carcinoma: results of a multicenter randomized ized clinical trial with cryotherapy and surgical ablation. Dermatol prospectivetrial.ArchDermatol2004;140:17\u201323. Surg2017;43:920\u20137. 91 Mosterd K, Thissen MR, Nelemans P et al. Fractionated 5-amino75 Scho\u20acn M, Sch\u20acon M. Imiquimod: mode of action. Br J Dermatol laevulinic acid-photodynamic therapy vs. surgical excision in the 2007;157:8\u201313. treatment of nodular basal cell carcinoma: results of a random76 Geisse J, Caro I, Lindholm J et al. Imiquimod 5% cream for the izedcontrolledtrial.BrJDermatol2008;159:864\u201370. treatment of superficial basal cell carcinoma: results from two 92 Roozeboom MH, Aardoom MA, Nelemans PJ et al. Fractionated phaseIII,randomized,vehicle-controlledstudies.JAmAcadDerma5-aminolevulinicacidphotodynamictherapyafterpartialdebulktol2004;50:722\u201333. ing versus surgical excision for nodular basal cell carcinoma: a 77 GollnickH,BaronaCG,FrankRGetal.Recurrencerateofsuperfirandomized controlled trial with at least 5-year follow-up. J Am cialbasalcellcarcinomafollowingtreatmentwithimiquimod5% AcadDermatol2013;69:280\u20137. cream:conclusionofa5-yearlong-termfollow-upstudyinEur93 WongTH,MortonCA,CollierNetal.BritishAssociationofDerope.EurJDermatol2008;18:677\u201382. matologists and British Photodermatology Group guidelines for 78 Quirk C, Gebauer K, De\u2019Ambrosis B et al. Sustained clearance topical photodynamic therapy 2018. Br J Dermatol 2019; of superficial basal cell carcinomas treated with imiquimod 180:730\u20139. \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 19}, {"text": "Br J Dermatol 2019; of superficial basal cell carcinomas treated with imiquimod 180:730\u20139. \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 19}, {"text": "918 BADguidelinesforadultswithBCC2021, I.Nasretal. 94 Sekulic A, Migden MR, Oro AE et al. Efficacy and safety of vis111 CampanaLG,MarconatoR,ValpioneSetal.Basalcellcarcinoma: modegib in advanced basal-cell carcinoma. N Engl J Med 2012; 10-year experience with electrochemotherapy. J Transl Med 2017; 366:2171\u20139. 15:122. 95 SekulicA,MigdenMR,LewisKetal.PivotalERIVANCEbasalcell 112 Kristiansson S, Reizenstein J, von Beckerath M et al. Long-term carcinoma (BCC) study: 12-month update of efficacy and safety follow-up in patients treated with electrochemotherapy for nonof vismodegib in advanced BCC. J Am Acad Dermatol 2015; melanoma skin cancer in the head and neck area. Acta Otolaryngol 72:1021\u20136. 2019;139:195\u2013200. 96 Sekulic A, Migden MR, Basset-Seguin N et al. Long-term safety 113 RotunnoR,CampanaL,QuaglinoPetal.Electrochemotherapyof and efficacy of vismodegib in patients with advanced basal cell unresectable cutaneous tumours with reduced dosages of intracarcinoma:finalupdateofthepivotalERIVANCEBCCstudy.BMC venous bleomycin:analysis of57 patients fromthe International Cancer2017;17:332. Network for Sharing Practices of Electrochemotherapy registry. J 97 Basset-Seguin N, Hauschild A, Grob JJ et al. Vismodegib in EurAcadDermatolVenereol2018;32:1147\u201354. patients with advanced basal cell carcinoma (STEVIE): a pre114 Clover AJP, Salwa SP, Bourke MG et al. Electrochemotherapy for plannedinterimanalysisofaninternational,open-labeltrial.Lanthetreatmentofprimarybasalcellcarcinoma;arandomisedconcetOncol2015;16:729\u201336. trol trial comparing electrochemotherapy and surgery with five 98 Basset-Seguin N, Hauschild A, Kunstfeld R et al. Vismodegib in yearfollowup.EurJSurgOncol2020;46:847\u201354. patients with advanced basal cell carcinoma: primary analysis of 115 Campana LG, Clover AJ, Valpione S et al. Recommendations for STEVIE, an international, open-label trial. Eur J Cancer 2017; improving the quality of reporting clinical electrochemotherapy 86:334\u201348. studies based on qualitative systematic review. Radiol Oncol 2016; 99 Tang JY, Mackay-Wiggan JM, Aszterbaum M et al. Inhibiting the 50:1\u201313. hedgehog pathway in patients with the basal-cell nevus syn116 GehlJ,SersaG,MatthiessenLWetal.Updatedstandardoperating drome.NEnglJMed2012;366:2180\u20138. procedures for electrochemotherapy of cutaneous tumours and 100 Tang JY, Ally MS, Chanana AM et al. Inhibition of the hedgehog skinmetastases.ActaOncol2018;57:874\u201382. pathway in patients with basal-cell nevus syndrome: final results 117 Lipson EJ, Lilo MT, Ogurtsova A et al. Basal cell carcinoma: PDfrom the multicentre, randomised, double-blind, placebo-conL1/PD-1 checkpoint expression and tumor regression after PD-1 trolled,phase2trial.LancetOncol2016;17:1720\u201331. blockade.JImmunotherCancer2017;5:23. 101 HanssonJ,BartleyK,KaragiannisTetal.Assessmentofqualityof 118 Chang ALS, Tran DC, Cannon JGD et al. Pembrolizumab for life using Skindex-16 in patients with advanced basal cell carciadvancedbasalcellcarcinoma:aninvestigator-initiated,proof-ofnomatreatedwithvismodegibintheSTEVIEstudy.EurJDermatol conceptstudy.JAmAcadDermatol2019;80:564\u20136. 2018;28:775\u201383. 119 Sabbatino F, Marra A, Liguori L et al. Resistance to anti-PD-1102 Dreno B, Kunstfeld R, Hauschild A et al.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 20}, {"text": "2018;28:775\u201383. 119 Sabbatino F, Marra A, Liguori L et al. Resistance to anti-PD-1102 Dreno B, Kunstfeld R, Hauschild A et al. Two intermittent visbased immunotherapy in basal cell carcinoma: a case report and modegib dosing regimens in patients with multiple basal-cell reviewoftheliterature.JImmunotherCancer2018;6:126. carcinomas (MIKIE): a randomised, regimen-controlled, double120 Cohen PR, Kato S, Goodman AM et al. Appearance of new cutablind,phase2trial.LancetOncol2017;18:404\u201312. neous superficial basal cell carcinomas during successful nivolu103 GonzalezA.Neoadjuvantvismodegibforthetreatmentofperiocumab treatment of refractory metastatic disease: implications for larbasalcellcarcinoma.AnnSurgOncol2018;25(1Suppl.):S181. immunotherapy in early versus late disease. Int J Mol Sci 2017; 104 Sagiv O, Nagarajan P, Ferrarotto R et al. Ocular preservation 18:1663. with neoadjuvant vismodegib in patients with locally advanced 121 BrinkhuizenT,FrenckenK,NelemansPetal.Theeffectoftopical periocular basal cell carcinoma. Br J Ophthalmol 2019; 103:775\u2013 diclofenac3%andcalcitriol3lg/gonsuperficialbasalcellcarci80. noma (sBCC) and nodular basal cell carcinoma (nBCC): a phase 105 Wong KY, Fife K, Lear JT et al. Vismodegib for locally advanced II, randomized controlledtrial. J Am Acad Dermatol 2016; 75:126\u2013 periocular and orbital basal cell carcinoma: a review of 15 con34. secutivecases.PlastReconstrSurgGlobOpen2017;5:e1424. 122 Butler DF, Parekh PK, Lenis A. Imiquimod 5% cream as adjunc106 ChenL,AriaAB,SilapuntSetal.Treatmentofadvancedbasalcell tive therapy for primary, solitary, nodular nasal basal cell carcicarcinoma with sonidegib: perspective from the 30-month nomasbeforeMohsmicrographicsurgery:arandomized,double updateoftheBOLTtrial.FutureOncol2018;14:515\u201325. blind,vehicle-controlledstudy.DermatolSurg2009;35:24\u20139. 107 Lear JT, Migden MR, Lewis KD et al. Long-term efficacy and 123 vanderGeerS,MartensJ,vanRoijJetal.Imiquimod5%cream safety of sonidegib in patients with locally advanced and metaas pretreatment of Mohs micrographic surgery for nodular basal staticbasalcellcarcinoma:30-monthanalysisofthe randomized cell carcinoma in the face: a prospective randomized controlled phase 2 BOLT study. J Eur Acad Dermatol Venereol 2018; 32:372\u2013 study.BrJDermatol2012;167:110\u20135. 81. 124 WettsteinR,ErbaP,ItinPetal.Treatmentofbasalcellcarcinoma 108 National Institute for Health and Care Excellence. Elecwith surgical excision and perilesional interferon-alpha. J Plast trochemotherapy for metastases in the skin from tumours of ReconstrAesthetSurg2013;66:912\u20136. non-skin origin and melanoma. Available at: https://www.nice. 125 Al-NiaimiF,ShethN,KurwaHAetal.Photodynamictherapyfolorg.uk/guidance/ipg446(lastaccessed2June2021). lowedbyMohs micrographicsurgery comparedtoMohs micro109 National Institute for Health and Care Excellence. Elecgraphic surgery alone for the treatment of basal cell carcinoma: trochemotherapy for primary basal cell carcinoma and primary results of a pilot single-blinded randomised controlled trial. J squamous cell carcinoma. Available at: https://www.nice.org. CutanAesthetSurg2015;8:88\u201391. uk/guidance/ipg478(lastaccessed2June2021). 126 CarijaA,Puizina-IvicN,VukovicDetal.Singletreatmentoflow110 BertinoG,SersaG,DeTerlizziFetal.EuropeanResearchonElecrisk basal cell carcinomaswith pulsed dye laser-mediated phototrochemotherapy in Head and Neck Cancer (EURECA) project: dynamic therapy (PDL-PDT) compared with photodynamic therresults of the treatment of skin cancer.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 20}, {"text": "basal cell carcinomaswith pulsed dye laser-mediated phototrochemotherapy in Head and Neck Cancer (EURECA) project: dynamic therapy (PDL-PDT) compared with photodynamic therresults of the treatment of skin cancer. Eur J Cancer 2016; 63: apy (PDT): a controlled, investigator-blinded, intra-individual 41\u201352. prospectivestudy.PhotodiagnosisPhotodynTher2016;16:60\u20135. BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 2, "page": 20}, {"text": "BADguidelinesforadultswithBCC2021, I.Nasretal. 919 127 Haak CS, Togsverd-Bo K, Thaysen-Petersen D et al. Fractional 147 Keith D, Bray A, Brain A et al. British Association of Dermatololaser-mediated photodynamic therapy of high-risk basal cell cargists(BAD)nationalauditonnon-melanomaskincancerexcision cinomas \u2013 a randomized clinical trial. Br J Dermatol 2015; 2016incollaborationwiththeRoyalCollegeofPathologists.Clin 172:215\u201322. ExpDermatol2020;45:48\u201355. 128 Smucler R, Vlk M. Combination of Er:YAG laser and photody148 Keith D, de Berker D, Bray A et al. British Association of Dermanamic therapy in the treatment of nodular basal cell carcinoma. tologists\u2019 national audit on nonmelanoma skin cancer excision, LasersSurgMed2008;40:153\u20138. 2014.ClinExpDermatol2017;42:46\u201353. 129 KuvatSV,Gu\u20accinZ,KeklikBetal.Basalcellcarcinomainachild. JSkinCancer2011;2011:752901. Supporting Information 130 Spiker AM, Troxell T, Ramsey ML. Gorlin syndrome. Available at: https://www.statpearls.com/articlelibrary/viewarticle/22375 AdditionalSupportingInformationmaybefoundintheonline (lastaccessed2June2021). version ofthis article atthepublisher\u2019s website: 131 Griffin JR, Cohen PR, Tschen JA et al. Basal cell carcinoma in childhood: case report and literature review. J Am Acad Dermatol 2007;57(5Suppl.):S97\u2013102. Appendix ASystematic review protocols. 132 Evans DGF, Farndon PA. Nevoid Basal Cell Carcinoma Syndrome. AvailAppendix BForest plots forcomparative studies. able at: https://www.ncbi.nlm.nih.gov/sites/books/NBK1151 Appendix CForest plotsfor noncomparative studies. (lastaccessed2June2021). Appendix DLinking Evidence ToRecommendations. 133 Cameron MC, Lee E, Hibler BP et al. Basal cell carcinoma: conAppendix E GRADEevidence tables. temporary approaches to diagnosis, treatment, and prevention. J Appendix F Summaryofincluded comparative studies. AmAcadDermatol2019;80:321\u201339. Appendix GNarrative findings fornoncomparative studies. 134 Marcil I, Stern RS. Risk of developing a subsequent nonAppendix HPRISMAdiagram \u2013study selection. melanomaskincancerinpatientswithahistoryofnonmelanoma skin cancer: a critical review of the literature and meta-analysis. Appendix I Papers excludedfromquantitative analysis. ArchDermatol2000;136:1524\u201330. Appendix JMethodology. 135 Kiiski V, de Vries E, Flohil SC et al. Risk factors for single and Appendix K Searchstrategy. multiplebasalcellcarcinomas.ArchDermatol2010;146:848\u201355. Appendix L Audit standards, data items and data collection 136 National institute for Health and Care Excellence. Sunlight expomethodology. sure: risks and benefits. Available at: https://www.nice.org.uk/ Powerpoint S1 Journal ClubSlideSet. guidance/ng34(lastaccessed2June2021). 137 NationalInstituteforHealthandCareExcellence.VitaminD:supplement use in specific population groups. Available at: https:// Appendix www.nice.org.uk/guidance/ph56(lastaccessed2June2021). Author affiliations 138 GreenA,WilliamsG,NealeRetal.Dailysunscreenapplicationand beta-carotenesupplementationinpreventionofBCCandSCCofthe 1British Association of Dermatologists WillanHouse 4 Fitzroy Square, skin:arandomisedcontrolledtrial.Lancet1999;354:723\u20139. London W1T 5HQ, UK 139 Elmets CA, Viner JL, Pentland AP et al. Chemoprevention of non2RoyalDevon andExeter NHSFoundation Trust, ExeterEX2 5DW, UK melanomaskincancerwithcelecoxib:arandomized,double-blind, placebo-controlledtrial.JNatlCancerInst2010;102:1835\u201344. 3BartsHealth NHSTrust, London E11BB, UK 140 Kadakia KC, Barton DL, Loprinzi CL et al.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 21}, {"text": "NHSTrust, London E11BB, UK 140 Kadakia KC, Barton DL, Loprinzi CL et al. Randomized con4NationalCancer ResearchInstitute\u2019s SkinCancer Clinical StudiesGroup and trolled trial of acitretin versus placebo in patients at high-risk Non-Melanoma Skin CancerSubgroup, London,UK for basal cell or squamous cell carcinoma of the skin (North 5RoyalCollege of GeneralPractitioners, London,UK Central Cancer Treatment Group Study 969251). Cancer 2012; 6Independent CancerPatients\u2019 Voice, London,UK 118:2128\u201337. 7British Association of PlasticReconstructive &Aesthetic Surgeons,London, 141 ChenAC,MartinAJ,ChoyBet al.Aphase3randomizedtrialof UK nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015;373:1618\u201326. 8Buckinghamshire HealthcareNHS Trust,Aylesbury HP21 8AL,UK 142 KreulSM,HavighurstT,KimKetal.AphaseIIIskincancerchemo9RoyalCollege of Radiologists, London,UK prevention study of DFMO: long-term follow-up of skin cancer 10CambridgeUniversity Hospitals NHSFoundation Trust, CambridgeCB2 eventsandtoxicity.CancerPrevRes(Phila)2012;5:1368\u201374. 0QQ, UK 143 Duffield-Lillico AJ,Slate EH, Reid MEet al. Seleniumsupplemen11NHSLothian Lauriston Building, Edinburgh EH39EN,UK tation and secondary prevention of nonmelanoma skin cancer in 12RoyalVictoriaHospital, Belfast BT126BA, UK arandomizedtrial.JNatlCancerInst2003;95:1477\u201381. 13British Societyfor SkinCare inImmunosuppressed Individuals,London, UK 144 Tang JY, Chiou AS, Mackay-Wiggan JM et al. Tazarotene: randomized, double-blind, vehicle-controlled, and open-label con14SalfordRoyal NHSFoundation Hospital,Salford M68HD,UK current trials for basal cell carcinoma prevention and therapy in 15Manchester AcademicHealth Science Centre,Manchester M202LR, UK patients with basal cell nevus syndrome. Cancer Prev Res (Phila) 16British Societyfor Dermatological Surgery,London, UK 2014;7:292\u20139. 17StJohn\u2019s Institute of Dermatology Guy\u2019s andStThomas\u2019 NHS Foundation 145 Weinstock MA, Bingham SF, DiGiovanna JJ et al. Tretinoin and Trust, London SE19RT, UK the prevention of keratinocyte carcinoma (basal and squamous 18StMary\u2019s Hospital Imperial CollegeHealthcareNHS Trust, LondonW2 cell carcinoma of the skin): a Veterans Affairs randomized chemopreventiontrial.JInvestDermatol2012;132:1583\u201390. 1NY, UK 146 Olsen C. Chemoprevention of keratinocyte cancers. Br J Dermatol 19University Hospitalof Wales, Cardiff CF144XW, UK 2018;179:233\u20134. 20British Associationof Oral and Maxillofacial Surgeons, London,UK \u00a92021BritishAssociationofDermatologists BritishJournalofDermatology(2021)185,pp899\u2013920 Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 21}, {"text": "920 BADguidelinesforadultswithBCC2021, I.Nasretal. 21RoyalSurreyCountyHospitalNHSFoundationTrust,GuildfordGU27XX,UK 24Nevill Hall Hospital,Abergavenny NP77EG, UK 22British Dermatological Nursing Group,Belfast Ireland 25Primary Care Dermatology Society, Rickmansworth, UK 23King\u2019s CollegeHospital NHSFoundation Trust, London SE59RS, UK 26Royal Collegeof Pathologists, London,UK BritishJournalofDermatology(2021)185,pp899\u2013920 \u00a92021BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/185/5/899/6599942 by guest on 23 February 2026", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 22}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 0, "page": 23}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "Basal cell carcinoma guidelines.pdf", "chunk_id": 1, "page": 23}, {"text": "BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists\u2019 guidelines for the care of patients with actinic keratosis 2017 D. de Berker,1 J.M. McGregor,2 M.F. Mohd Mustapa,3 L.S. Exton3 and B.R. Hughes4 1Bristol Dermatology Centre, University HospitalsBristol, Bristol BS2 8HW,U.K. 2Departmentof Dermatology, BartsHealth NHS Trust, LondonE11BB, U.K. 3British Associationof Dermatologists, WillanHouse, 4 Fitzroy Square,London W1T 5HQ, U.K. 4PortsmouthDermatology Centre, PortsmouthHospitals NHSTrust, PortsmouthPO3 6AD, U.K. Correspondence DaviddeBerker. 1.0 Purpose and scope E-mail:guidelines@bad.org.uk The overall objective of the guideline is to provide up-to-date, Acceptedfor publication evidence-based recommendations for the management of acti7September2016 nickeratosis (AK). The document aims (i) to offer an appraisal of all relevant Fundingsources literature up to February 2016, focusing on any key developNone. ments; (ii) to address important, practical clinical questions relating to the primary guideline objective, including accurate Conflictsof interest diagnosis and suitable treatment; (iii) to provide guideline Nonedeclared. recommendations and, where appropriate, some health ecoD.deB.,J.M.M.andB.R.H.aremembersoftheGuidelineDevelopmentGroup,with nomicimplications; and(iv)todiscuss potentialdevelopments technicalsupportfromL.S.E.andM.F.M.M. andfuture directions. The guideline is presented as a detailed review with highThisisanupdatedguidelinepreparedfortheBritishAssociationofDermatologists lighted recommendations for practical use in the clinic (see (BAD)ClinicalStandardsUnit,whichincludestheTherapy&Guidelines(T&G)SubSection 13.0), in addition to an updated patient information committee.MembersoftheClinicalStandardsUnitwhohavebeeninvolvedareP.M. leaflet (PIL), available at the British Association of DermatoloMcHenry(ChairmanT&G),K.Gibbon,D.A.Buckley,I.Nasr,C.E.DuarteWilgists (BAD) website (http://www.bad.org.uk/for-the-public/ liamson,V.J.Swale,T.A.Leslie,E.C.Mallon,S.Wakelin,S.Ungureanu,R.Y.P. patient-information-leaflets). Hunasehally,M.Cork,G.A.Johnston,J.Natkunarajah,F.S.Worsnop,N.Chiang,J. Donnelly(BritishNationalFormulary),C.Saunders(BritishDermatologicalNursing Group),A.G.Brian(BADScientificAdministrator),L.S.Exton(BADInformation 1.1 Exclusions Scientist)andM.F.MohdMustapa(BADClinicalStandardsManager). This guideline does not cover bowenoid AK or actinic Guidelinesproducedin2007bytheBritishAssociationofDermatologists;reviewedand cheilitis. updated,2016. 2.0 Stakeholder involvement and peer review DOI10.1111/bjd.15107 NICEhasrenewedaccreditationoftheprocessusedbytheBritishAssociaTheGuidelineDevelopmentGroup(GDG)consistedofconsultionofDermatologiststoproduceclinicalguidelines.Therenewedaccreditationisvaliduntil31May2021andappliestoguidanceproducedusing tant dermatologists. The draft document was circulated to the theprocessesdescribedinUpdatedguidanceforwritingaBritishAssociationofDermatologistsclinicalguideline\u2013theadoptionoftheGRADE BAD membership, the British Dermatological Nursing Group, methodology2016.Theoriginalaccreditationtermbeganon12May 2010.Moreinformationonaccreditationcanbeviewedatwww.nice. the Primary Care Dermatological Society, the British Society org.uk/accreditation. for Skin Care in Immunosuppressed Individuals, and Age U.K. for comments. These comments were actively considered by the GDG, and peer reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy & Guidelines Subcommittee) priortopublication. 3.0 Methodology This set of guidelines has been developed using the BAD recommended methodology,1 with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument 20 BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 1}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 21 (www.agreetrust.org).2 Recommendations were developed for feature of an AK is epithelial dysplasia. This may be restricted implementation in the National Health Service (NHS) using a to the basal layer or may extend to full-thickness atypia, at process of considered judgement based on the evidence. The which point the lesion is known as SCC in situ (Bowen disPubMed, MEDLINE and EMBASE databases were searched for ease). There is disorderly arrangement and maturation of meta-analyses, randomized and nonrandomized controlled epithelial cells. Multiple buds of epithelial cells may occur at clinical trials, case series, case reports and open studies involvthemembranezone, but noinvasion is seen.Histological variing AK published in the English language from January 2004 ants of AK have been described, including hypertrophic, to February 2016; the search terms and strategies are detailed bowenoid, lichenoid, acantholytic andpigmented. in Appendix S1 (see Supporting Information). Additional releActinic keratoses are generally considered to be premaligvant references were also isolated from citations in the nant lesions with low individual potential for invasive maligreviewed literature, as well as specific targeted searches for nancy andpotential for spontaneous regression. AKs present as systemic treatments and AK developing into squamous cell discrete, sometimes confluent, patchesoferythema andscaling carcinoma (SCC) asaresult ofspecific newtreatments. on predominantly sun-exposed skin, usually in middle-aged All identified titles were screened, and those relevant for and elderly individuals. Clinically, they are graded on a threefirst-round inclusion were selected for further scrutiny. The point scale according to magnitude. Field change might abstracts for the shortlisted references were then reviewed by include any or all of these lesions (Table 1).3 At grade 1 the the GDG, with a third round of review and selection for pholesion is just visible and palpable (gritty to feel and difficult to todynamic therapy (PDT) publications given their number and see), grade 2 lesions are usually red and scaly (easily felt and complexity.Disagreementsinthefinalselectionswereresolved seen), and grade 3 corresponds to thicker, hyperkeratotic by discussion with the entire GDG. The full papers of relevant lesions. Grade 3 AKs can be difficult to differentiate from material were obtained. The structure of the 2007 guidelines small, early SCCs, which, if excised, may be reported to have was then discussed and re-evaluated, with headings and subearly or equivocalinvasion.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 2}, {"text": "material were obtained. The structure of the 2007 guidelines small, early SCCs, which, if excised, may be reported to have was then discussed and re-evaluated, with headings and subearly or equivocalinvasion. headings decided; different coauthors were allocated separate They are often asymptomatic but may occasionally be sore subsections. Each coauthor then performed a detailed appraisal or itch; lesions may be single or multiple. When multiple, the of the selected literature with discussions within the GDG to concept of \u2018field change\u2019 is used to describe an area of skin resolve any issues. All subsections were subsequently collated that is involved extensively with actinic damage.4 The epiandedited toproducethefinal guideline. demiology, risk factors, disease associations and demographics of the \u2018at-risk\u2019 population are all pertinent to patient management. They are discussed together with the available treatment 4.0 Limitations of the guideline options. This document has been prepared on behalf of the BAD and is based on the best data available when the document was pre6.1 Aetiology pared. It is recognized that under certain conditions it may be necessary to deviate from the guidelines, and that the results Actinic keratosesaretheresultofchronicexposuretoultravioof future studies may require some of the recommendations let (UV) radiation, predominantly on skin of the head and herein to be changed. Failure to adhere to these guidelines dorsa of the hands, in fair-skinned individuals.5 In addition, should not necessarily be considered negligent, nor should UVB-specific p53 mutations have been demonstrated in AKs, adherence to these recommendations constitute a defence providing molecular evidence in support of a role for sunagainst a claim of negligence. Limiting the review to Englishlight.6 There is a high prevalence of keratinocyte cancer, language references was a pragmatic decision, but the authors including AKs,in thosereceiving chronicimmunosuppression, recognize this may exclude some important information pubparticularly organ transplant recipients,7 but also patients on lished in otherlanguages. long-term treatment for inflammatory bowel and rheumatological disease, although this is not as well documented. Other possible risk factors include exposure to arsenic8,9 and chronic 5.0 Plans for guideline revision sunbed use.10\u201312 The proposed revision of this set of recommendations is scheduled for 2021; where necessary, important interim Table1 Gradesofactinickeratosis(AK)3 changes willbeupdated ontheBAD website. Grade1 Mild;pinkorgreymarkswithslightscaleorgritty 6.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 2}, {"text": "of this set of recommendations is scheduled for 2021; where necessary, important interim Table1 Gradesofactinickeratosis(AK)3 changes willbeupdated ontheBAD website. Grade1 Mild;pinkorgreymarkswithslightscaleorgritty 6.0 Background totouch Grade2 Moderate;thickerhyperkeratosisandeasilydetected Actinic keratoses (synonymous with solar keratoses) are keraGrade3 Severe;hypertrophic,thickkeratin totic lesions occurring on chronically light-exposed adult skin. Fieldchange Confluentareasofseveralcentimetresormorewith They represent focal areas of abnormal keratinocyte proliferaarangeoffeaturesmatchinganyorallofthe gradesofAK tion and differentiation that carry a low risk of progression to invasive SCC. A spectrum of histology is seen, but the cardinal \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 2}, {"text": "22 Guidelinesforactinickeratosis2017, D.deBerkeretal. prospective photographic monitoring study over 5 years, it 6.2 Incidence andprevalence appeared that 65% of SCCs arose at a site of previously docuIt is likely that the incidence of AKs is underestimated. It is mented AK.20 A recent systematic review of 24 eligible studies difficult to measure the burden of AKs reliably in individuals examining the natural history of AKs concluded that there andin populations.13 were no reliable estimates concerning the frequency of AKs In prevalence studies in Galway, South Wales and developing into invasive carcinoma.26 Merseyside, 19\u201324% of individuals aged > 60 had at least one In summary, combined data suggest the possibility of AK.14\u201316 AKs were also present in 3(cid:1)6% of men aged regression and a low risk of malignant progression for any 40\u201349 years.16 A linear increase in prevalence was found with given AK. The presence of AK (particularly in high-risk age (from 60 to 80 years) in men but not in women in patients\u2013seeSection 7.6\u2013withmultipleAKsorfieldchange) another U.K. study, and the rate of new AKs was estimated to predicts an excess risk for subsequently developing an NMSC be 149 per 1000 person-years.15 Over 30% of those attending or melanoma compared withamatchedpopulation. a dermatology clinic (mean age of attendance 61 years) in Austria had AK. By the age of 70 years, > 70% of those 6.4 Investigation anddiagnosis attending had AK, with the majority (70%) on the head and neck.17 A Rotterdam prevalence study of > 2000 Dutch men Diagnosis of AK may be made in primary or secondary care and women, mean age 72 years, found AK in 49% of men and as part of a general skin examination associated with and28%of women.18 assessment of sun damage, focal keratotic lesions or skin cancer. Teledermatology has been cited as an effective means of diagnosis.27 Dermoscopy can be employed with a range of 6.3 Natural history: spontaneousregression and defined dermoscopic features.28 People with chronic fluctuatmalignant transformation ing disease may learn self-diagnosis but are advised to corrobPatientswithAKhaveachronicdisease.Thepresenceofasinorate their assessment with a healthcare professional. Such gle lesion is a marker of excessive sun exposure and is associmodels of patient-led monitoring and action are advocated in ated with the development of further lesions.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 3}, {"text": "lesion is a marker of excessive sun exposure and is associmodels of patient-led monitoring and action are advocated in ated with the development of further lesions. Point-prevalence otherchronicdiseasessuchasdiabetesmellitus,29wheremotistudies demonstrate that lesions regress and relapse over time vated self-management is a significant element in improved (thisisprobablyrelevantinthecaseofgrade1and2lesions). outcome.30 Diagnosis is typically on clinical grounds. UncerFigures range between 25% and 70% for apparent resolution tainty may arise in distinguishing AKs from superficial BCC, of AKs over a period of 1\u20134 years.15,19,20 Prospective evaluaSCC in situ, invasive SCC and even amelanotic melanoma, tion demonstrates a low rate of malignant transformation, where a skin biopsy or excision for histological examination with less than one in 1000 AKs developing into SCC per may be indicated. Where invasive malignancy is in the differannum.21 In a US study, 0(cid:1)6% of patients developed an SCC ential, the patient care should be shared with a member of a in the AK field within the first year \u2013 rising to 2(cid:1)57% at skin cancer multidisciplinary team. At the diagnosis of AK, the 4 years.20 The higher rate of apparent transformation in the location and thickness (e.g. grade 1, 2 or 3)3 should be docuUS study probably reflects the higher risk status of this premented; locationis best recorded on adiagram. dominantly maleveteran population. Nonetheless, there is evidence that AKs are a marker of 6.5 Shouldactinic keratoses be treated? excess risk for nonmelanoma skin cancer (NMSC). Mathematical models derived from the study undertaken by Marks et al. The natural history of individual lesions suggests that treatpredict that for an individual with an average of 7(cid:1)7 AKs, the ment is not universally required on the basis of preventing probability of developing an SCC within a 10-year period is progression into SCC.15 An indirect benefit of treatment is the approximately 10%.22 demonstration of lesions not responding to normal therapy, When 918 adults (mean age 61 years) with AKs but no which may represent a subgroup with higher malignant previous history of skin cancer were followed prospectively potential.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 3}, {"text": "opinion that believes for 5 years, the incidence rates for basal cell carcinoma (BCC) AKs are part of a spectrum that includes SCC in situ, and that and SCC were estimated at 4106 and 3198 per 100 000 perprevention of SCC is therefore the reason for therapy.31 A son-years, respectively, representing an excess risk compared Cochrane review of treatment of AK did not find any evidence with the general population.23 A sixfold excess risk for NMSC that treatment of AK resulted in reduction in presentation of or melanoma was found in a representative sample of the US invasive SCC.32 There is inadequate evidence to justify treatMedicare population with AKs compared with those without ment ofallAKs totry toprevent malignant change. (P < 0(cid:1)001).24 The most appropriate management plan should be deterDespite the proximity of AKs and SCC when they occur on mined by the patient\u2019s preferences and clinical circumstances, chronically sun-damaged skin, and the histological and molecwhich should take into account the extent, duration and presular similarities between them,25 debate continues concerning ence of symptoms, severity of lesions and other associated risk whether they are separate but similar pathologies developing factors for skin cancer, in addition to the patient\u2019s general in tandem or whether one leads directly to the other. In one healthandwell-being.Aquality-of-life questionnaire(AKQoL) BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 3}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 23 has been established and validated.33 In particular, patients 7.1 Notreatment (strength ofrecommendation A, quality express concern with respect to (i) the disease itself, (ii) sideofevidence 2++) effects and difficulties with treatment, (iii) association with the term cancer where AK is a risk factor for SCC, and (iv) Summaries of the levels of evidence and strengths of recomthe need to adjust sunshine behaviour on a background of mendation are given inAppendices 1and2. long-acquired habits andpreferences.34 Any perspective on nontreatment should be based on a whole-patient assessment,risks,comorbidities andpreferences. The fact that many AKs remit does not diminish the counter7.0 Management balancing point that they are associated with UV exposure and Many options are available for the treatment of AKs. The the development of melanoma, SCC and BCC. All patients main patient-centred considerations are the symptoms and need clear information on this risk and their own risk of SCC cosmetic burden of the AK, the efficacy and burden of treatin general so that, irrespective of the diagnosis of AK, they ment, and the threat of evolution of the AK into a more know to present early for assessment if a lesion bleeds, is bulky lesion or invasive SCC. Healthcare professional considpainful, grows significantly or becomes protuberant. All erations overlap with these, but include others such as effipatients should beadvised regarding sunprotection. cacy, a flexible regimen, availability in primary and secondary care and cost. An additional aspect of management 7.2 Primary care is consideration of the patient\u2019s overall risk of skin cancer and the wider skin examination. In the Rotterdam study on Patients with AK will ask their general practitioner (GP) for the prevalence of AK in the general population, participants diagnosis and treatment advice. Most AKs can be diagnosed with \u2265 10 AKs (13(cid:1)6%) had a threefold higher risk for havand treated in primary care.41 In healthcare systems with a ing a history of SCC compared with participants with four to primary-care physician as the first contact, skin monitoring of nine (4(cid:1)0%).18 Full-body skin examination revealed a skin sun-exposed surfaces of the head and neck and dorsa of hands cancer (BCC, SCC or melanoma) in 4%.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 4}, {"text": "sun-exposed surfaces of the head and neck and dorsa of hands cancer (BCC, SCC or melanoma) in 4%. The correlation is possible on an opportunistic basis and can be coupled with between skin cancer and number of AKs led the Dutch relevant prevention and self-care advice.42 Specialist dermatolgroup to advocate shorter follow-up intervals and more ogy nurses can play a similar role and are able to prescribe active treatment in those with \u2265 10 AKs, while not defining treatment in some healthcare systems.43 The Primary Care an interval and acknowledging the resource implications for Dermatology Society has developed guidance on the managethis 5% of the population. ment of AK in primary care in the U.K.44,45 Teledermatology At the outset of management, the location and grade has been used to support the diagnosis and management of (Table 1) of the AKs should be defined to enable monitoring, AK in primary care with specialist guidance.27 AKs are part of response to treatment or evolution. This can be done using the spectrum of actinic damage, which, once present, is mandrawings, body maps and photography, often with lesions aged rather thancured. numbered. Consider referral forspecialist care when: Management can be directed at individual lesions or over a (cid:129) AK failstorespondtostandard treatments; wider area (Fig. 1). This distinction represents lesion vs. field (cid:129) multiple or relapsing AKs represent a management chaltreatment. Field-based treatment can act to manage a range of lenge; actinic changes in a zone such as theforehead, scalp or central (cid:129) AK occurs inthelong-term immunosuppressed; face, and may provide some benefit in reduction of onset of (cid:129) new lesions.35 Topical therapies, skin peels36\u201339 and PDT are lesions are likely to be AK, but there is concern that they might be SCC (use the 2-week-wait route for possuitable. Usually, focal destructive therapies such as curettage sible skin cancer), for example when they are (i) bleedand cautery or cryotherapy are limited to lesion treatment ing, (ii) painful or (iii) thickened with substance when (Table 2). held between fingerandthumb. AEuropeanAK guideline achieved consensus through avoting and weighting method with advice grouped according to the isolated, field-associated or skin-cancer-associated distribu7.3 Secondary care tion of the AKs. There remained a preference for cryosurgery for isolated lesions and curettage for larger ones.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 4}, {"text": "avoting and weighting method with advice grouped according to the isolated, field-associated or skin-cancer-associated distribu7.3 Secondary care tion of the AKs. There remained a preference for cryosurgery for isolated lesions and curettage for larger ones. Otherwise, Secondary-care referral is required for diagnosis and/or manpreferences revolved largely around different strengths of the agement if the lesion might represent an invasive SCC.41 All common main agents, namely 5-fluorouracil (5-FU), imiquiregions of the U.K. have dedicated 2-week-wait or \u2018urgent mod, ingenol mebutate and variants of PDT. Diclofenac in cancer\u2019 pathways. In addition, if treatment in primary care for hyaluronic acid and imiquimod at 2(cid:1)5% were not favoured. In AK is unsuccessful, then referral is warranted for management immunosuppressed patients there was a preference for the alone. This includes patients with extensive disease or who are stronger formulations of all products. Laser was not considimmunosuppressed (see bulletpoints above). ered a good choice for any circumstance other than treatment Following diagnosisinsecondary care,treatmentcanbeiniof fielddisease.40 tiated with a future management plan for continued patient \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 4}, {"text": "24 Guidelinesforactinickeratosis2017, D.deBerkeretal. Fig1. Venndiagramillustratingtheoverlappingnatureoflesion-andfield-basedtreatmentsforactinickeratosis(AK). self-care (see Section 7.4) in collaboration with the GP. Histoof further lesions and relapse. They may also develop related logical diagnosis can be provided through a range of surgical pathology such as solar lentigo, lentigo simplex, SCC in situ procedures (see Sections 8.3 and 8.4) determined by lesion andNMSC. and circumstance. Follow-up in secondary care can be warPatient education is important in enabling self-care, with ranted to assess outcomes of treatment, extensive disease, early self-diagnosis, ongoing intermittent treatment and patients with associated skin cancers, or those with other conawareness of the risk of skin cancer and how to minimize this siderations such as immunosuppression. Nurse clinicians may risk (see the AK PIL available at http://www.bad.org.uk/forcontribute tothecarepathway. the-public/patient-information-leaflets). Most patients with mild AK will be seen in primary care and can manage their disease with topical therapy. Corroboration of diagnosis with 7.4 Self-care the GP is advisable before treatment of new lesions. ShortActinic keratosis is a chronic disease. Once patients have the term therapies (e.g. 4 weeks) may need renewal of prescripdiagnosis of AK, it is usually the start of a continued process tion when expired to ensure maintained efficacy. 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.tnemtaert .noitpircserp .stnemtaert .snoiselrekciht lacidem tub,rebmemer laitnatsbusfo dicacilycilaS -flesrofdooG seriuqeR salacitcarptoN fonoisivorp secuder stceffe-edis ylbaborp eracdetcerid detacided enituor ;tnemtaert roytilibixefl sesaercni dnatnempiuqe ,tnemtaert -flessevomer rofytiliba rofytilibatius erac-yradnoces sracssevael nacdnaerac ottneitap denekciht ninoisivorp seriuqerdna gnirracsesuac yfidom snoisel secnatsnitsom lacol otgnidrocca citehtseana stceffe-edis nidesuylerar(cid:129);secnatsmucricnognidnepeddesuebnac(cid:129)(cid:129);tnemtaertriaf(cid:129)(cid:129)(cid:129);tnemtaertdooG(cid:129)(cid:129)(cid:129)(cid:129).yparehtcimanydotohpetaniluvealonimalyhtem,TDP-LAM;licaruoroufl,UF;sisotarekcinitca,KA .knurtdnasbmilehtno1(cid:3)ggl005dnaecafehtno1(cid:3)ggl051tadesoDa.secnatsmucriceseht 26 Guidelinesforactinickeratosis2017, D.deBerkeretal. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 7}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 27 important part of patient education is awareness of the side8.0 Treatment effects of treatment before they start therapy. Many cause short-term redness, soreness and sometimes crusting or oozTreatment needs to address a wide range of variables including. If this is not anticipated it can cause distress and abaning thenature oftheAK,thebody site, patientpreference, the donment of treatment, where a pause would have been more premorbid state of the patient and previous treatments tried. appropriate. Added to this is the large number of therapeutic agents, their modes of application andtheflexibility with which eachagent can be used. Given this backdrop, it is to be expected that 7.5 Prevention there is variation in clinical practice. Table 2 attempts to bring There have been three randomized controlled trials (RCTs) a broad perspective to the options. In some instances it might (twoin Australia andoneintheU.S.A.)in patients> 50 years be viewed in combination with Table 3, which is an approxiold, many of whom had a history of AKs, to show that sunmationof asimplified cost\u2013benefit analysis. screen, used to prevent unintentional sun exposure, is associated with a small decrease in the incidence of SCCs and AKs (but notBCCs) over ashort follow-up period.46\u201348 8.1 General More active treatment with a 4-week course of 5-FU, 5% Lifestyle, dietary fat,56 workplace and genetics are likely to twice daily to a field of involved skin can reduce the rate of make a difference to the risk of getting AK, mainly relating to onset of new AKs in that area over the subsequent 18 months thelevels of UVradiation exposure. when compared with placebo.35 There are no studies to show that sun avoidance reduces 8.1.1 Emollient (strength ofrecommendation B, levelof the risk of development of AKs and skin cancer in a popuevidence 2+) lation without AKs. Nonetheless, it is reasonable to hope that the effect of public health campaigns over the last few Elderly, sun-damaged skin is often dry, and emollient can be decades will have an impact on this risk. Such practices part of a management regimen. The direct effect of emollient may have a bearing on vitamin D levels, which warrant on AKs is not clear.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 8}, {"text": "effect of emollient may have a bearing on vitamin D levels, which warrant on AKs is not clear. Additives such as urea or salicylic acid review in those patients subject to high levels of sun avoidmay provide benefit. There are no trials dedicated to the study ance or who have other risk factors for diseases related to of palliative therapy of AKs, but emollient or gel vehicle has low vitamin D.49 been employed in the placebo arm of many trials. The vehicle limb of an RCT of diclofenac gel in hyaluronan vehicle described clearance of the target lesion in 44% of patients 7.6 High-risk cases using the vehicle after 60 days.57 Less dramatic results were Are there high-risk groupsandis their managementdifferent? seen with the cream vehicle used in trials of imiquimod Patients with multiple and confluent AKs are likely to be at applied two or three times a week for 4 weeks, reporting higher risk of NMSC than those with single lesions. Patients complete clearance of treated AKs in 0%,58 2(cid:1)4%59 and on chronic immunosuppressive therapy are at increased risk 14(cid:1)1%,60 with the latter treated three times a week for for skin cancer. Organ transplant recipients are reported as 8 weeks. having 50\u2013100 times the skin cancer risk of an ageand sexmatched control population.50,51 It is recommended that 8.1.2 Sunprotection andsunscreen (strength of high-risk patients have closer follow-up52 and more rigorous recommendation A,levelof evidence1++) treatment40 for premalignant lesions, including SCC in situ and AK, together with a lower index of suspicion for skin biopsy There is no specific information or evidence on sun protection to exclude malignancy. Nonetheless, there is no evidence that other than through studies on sunscreen. Sunscreen has a such measures reduce the risk of new skin cancers, although combined emollient andphotoprotective effect.Arandomized, they may reduce morbidity from surgery and minimize the placebo-controlled trial of sunscreen with sun protection facrisk ofrecurrence. tor (SPF) 17 applied twice daily to the face for 7 months Treatment for AKs in transplant patients may be less effecshowed sunscreen to be more effective than emollient in tive than in the general population.53 Outcomes may be conterms of the total number of AKs and new lesions.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 8}, {"text": "be more effective than emollient in tive than in the general population.53 Outcomes may be conterms of the total number of AKs and new lesions.46 A single, founded by the large number of proliferative and daily application of sunscreen with SPF 16 in Queensland, hyperkeratotic lesions in this group. Studies have not found a Australia, also showed it to be more effective than discrereduction in subsequent skin cancers in areas previously treationary use of the same sunscreen over a 2-year period in the ted for AKs with PDT.51 Oral retinoids have been used to reduction of AKs.61 A similar approach in the same setting reduce the risk of SCC in transplant patients at high risk of also reduced the incidence of cutaneous SCC.48 A 24-month getting skincancer,but theeffecton AKsis not reported. study of daily use of sunscreen (SPF > 50, high UVA absorpA single study reported that capecitabine, used in 15 tion) in 120 case-controlled organ transplant recipients patients, reduced the risk of SCC,54 BCC and AKs in organ showedsignificantreductioninAKsandNMSCsarisingduring transplant recipients, buttoxicityis likely tolimititsuse.55 thestudy.49 \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 8}, {"text": "ecnedivefoslevelehT.serusaememoctuodnagnilpmasralimisnodesabsyawlatoneraspuorgtnemtaertneewtebataD.KAnisnoitpotnemtaertniamehtfognittesdnaytilibixefl,ycacfife,tsoC 3elbaT 4ot++1morfegnarelbatsihtotgnitubirtnoc ninoitcudeR nodesabsKA ffatsfotsocno-ddA lanoitavresboa .tnempiuqeroemit rosTCRb,seiduts roeracyramirP sisylana-atemc otelbanemA .]eracyradnoces[ tonodseulav( noitaulavefodoireP elbanemA eracdetcerid-tneitap elbixelF seriuqeryllacipyTd ssecxetcefler nahtregnol( eracyramirpot gnirotinomdna snemiger stisiv2 metidesnepsiD metirepegnartsoC )lortnocrevo )tnemtaertevitca (cid:129)(cid:129)(cid:129) (cid:129) (cid:129) 0 \u2666 51,a%12otpU etinfiedni,cidoireP tnemtaertoN (cid:129)(cid:129)(cid:129) (cid:129) (cid:129) 0 \u2666 06,75,b%44\u20130 etinfiedni,cidoireP elcihevrotneillomE (cid:129)(cid:129)(cid:129) (cid:129) (cid:129) ]\u2666\u2666[\u2666 Lm005 \u2666 74,64,b%63\u201371 etinfiedni,cidoireP /3AVU(neercsnuS )05\u201371FPS (cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 g04 \u2666 66,63,b%87\u201307 shtnom4\u20132 %5licaruoroulF-5 (cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 stehcas42\u201321 \u2666\u2666/\u2666 57,47,b%48otc%05 shtnom4\u20132 %5domiuqimI (cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 stehcas65\u201382 \u2666\u2666\u2666\u2666/\u2666\u2666\u2666 58,b%63\u201343 shtnom4\u20133 %57(cid:1)3domiuqimI (cid:129)(cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 g001\u201305 \u2666\u2666/\u2666 09,75,b%07\u201391 shtnom4\u20132 %3legcanefolciD (cid:129)(cid:129) \u274d (cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 noitacilppa-elgnis3\u20132 \u2666\u2666 39,29,b%24\u201343 shtnom2\u20131 etatubemlonegnI sebutg-74(cid:1)0 ,ecaf1(cid:3)ggl051( sbmil1(cid:3)ggl005 )knurtdna \u274d \u274d (cid:129)(cid:129) 771829\u00a3\u2013724\u00a3 ebuttnemtaertelgniS \u2666\u2666\u2666 671,721,911,701,b%39\u201396 shtnom2\u20131 TDP-LAM (cid:129) \u274d (cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 elbacilppatoN nwonktoN 601,301,a%88\u201393 shtnom2\u20131 yregrusoyrC seiparehtnoitanibmoC (cid:129)(cid:129)(cid:129) (cid:129)(cid:129) (cid:129)(cid:129) ]\u2666\u2666[\u2666 Lm52 \u2666 27,17,b%77ota%55 shtnom4\u20132 %5(cid:1)0 licaruoroulF-5 dicacilycilasdna %01 (cid:129) (cid:129) (cid:129)(cid:129) ]\u2666\u2666[\u2666 g001\u201305 \u2666\u2666/\u2666 751,651,a%001\u201364 shtnom4\u20132 dnalegcanefolciD yregrusoyrc (cid:129) (cid:129) (cid:129)(cid:129) d]\u2666\u2666\u2666\u2666[\u2666\u2666 stehcas42\u201321 \u2666\u2666/\u2666 68,a%5(cid:1)95 shtnom4\u20132 dnadomiuqimI yregrusoyrc \u274d (cid:129) (cid:129)(cid:129) sulpd]\u2666\u2666\u2666\u2666[\u2666\u2666 sulpstehcas42\u201321 \u2666\u2666/\u2666 061,a%98 shtnom4\u20132 dnadomiuqimI 829\u00a3\u2013724\u00a3 ebuttnemtaertelgnis TDP-LAM morfnwardstsoC egakcapdradnatS stnemmoC snoitacilbupSHN esruocroezis :tnemtaertfo 66noitide,4102FNB noitcetorpnus,FPS;lairtdellortnocdezimodnar,TCR;yparehtcimanydotohpetaniluvealonimalyhtem,TDP-LAM;ecivreShtlaeHlanoitaN,SHN;yralumroFlanoitaNhsitirB,FNB;sisotarekcinitca,KA ;ytilibanema/ytilibixefletaredom(cid:129)(cid:129);ytilibanema/ytilibixeflemos(cid:129);elbixeflroelbanematon\u274d:yekeraC.002\u2013051\u00a3\u2666\u2666\u2666\u2666;051\u2013101\u00a3\u2666\u2666\u2666;001\u201315\u00a3\u2666\u2666;05\u20130\u00a3\u2666:yektsoC.Ateloivartlu,AVU;rotcaf 971.44\u00a3:tisivPG.86\u00a3:ecnadnettapu-wolloflatipsoH871.401\u00a3:51\u20134102ffiratSHNecnadnettacinilclatipsohtsriF.elbanema/elbixeflyrev(cid:129)(cid:129)(cid:129) 28 Guidelinesforactinickeratosis2017, D.deBerkeretal. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 9}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 29 A Cochrane review with subsequent meta-analysis of complete 8.2 Active treatments clearance results ranked the efficacy of all of the main treatAll topical therapies for AK may result in side-effects of irritaments andput5-FU atthetop.65 tion. Some AKs proceed to ooze, crusting and soreness with Nine of the trials were controlled; a right\u2013left comparison local swelling. Details are cited in this guideline for the indi- (n = 6)wasthemostcommondesign,butonlyfivewereranvidual treatments and are included in the relevant PILs. It is domized. Numbers in the studies were generally small, with a important that the patient understands the extent of the area mean of 26 patients per trial and fewer than 15 patients in to be treated and anticipates the side-effects. The size of area 50% of the trials. The minimum follow-up was \u2265 12 months will depend on a range of factors including the therapy, focal in only two studies. Many open studies appeared to demonor scattered pathology and the conceptual model (fieldor strate the efficacy of 5-FU in a range of potencies and differlesion-basedtreatment).Wheremorbidityisanascendantconent vehicles in the treatment of AKs when used on the face cern, treatment should be initiated over a small area such as twice daily for 3 weeks. Only two trials studied the use of 54\u201310 cm2 with flexible frequency to establish tolerance and FU in the currently available formulation of a 5% cream in a confidence. Some treatments define a ceiling of surface area well-constructed, controlled manner.36,66 Kurwa et al. exambased on the aliquot of prescribed item, for example one tube ined the lesional area of AKs on the back of the hands before of ingenol mebutate is a single dose for 25 cm2. Imiquimod and after treatment with 5-FU 5% cream twice daily for 5% is issued in 250-mg sachets where directions include \u2018one 3 weeks in a randomized right\u2013left comparison with a single sachet only\u2019 and to \u2018cover the area\u2019 typically with a centimetre treatment with PDT.66 Of the 14 patients evaluable at margin around any pathology. Others recommend a maxi6 months, there was a mean reduction in lesional area of 70% mum basedon toxicity, such as500 cm2for 5-FU 5%. (5-FU) and 73% (PDT), with no statistically significant differPatients should be provided with advice on how to manage encebetweenthem.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 10}, {"text": "there was a mean reduction in lesional area of 70% mum basedon toxicity, such as500 cm2for 5-FU 5%. (5-FU) and 73% (PDT), with no statistically significant differPatients should be provided with advice on how to manage encebetweenthem.Openstudieshavesuggestedthatthisregside-effects, with strategies including a break in treatment, imen is not sufficiently long for effective treatment of AKs on altering the frequency of application, use of emollient and in thehands,67but is adequatefor thoseon theface.36 some instances application oftopicalsteroid. Witheiler et al. used 5-FU 5% cream on the face as the control in a right\u2013left comparison with a single application of Jessner\u2019s solution (14% lactic acid, 14% salicylic acid, 14% 8.2.1 5-Fluorouracil (strength ofrecommendation A, level resorcinol in ethanol) followed by a trichloroacetic acid (TCA) of evidence1++) 35% peel.36 There was a mean reduction in AKs on both sides The majority of the data on topical therapies relate to the 5% of the face from 18 to four (78% reduction with 5-FU and concentration of 5-FU cream. 5-FU works by the inhibition of 79% reduction with TCA). This benefit was sustained for thymidylate synthetase, which is needed for DNA synthesis. It 12 months. The third follow-up at 32 months demonstrated may also interfere with the formation and function of RNA.62 that the number of AKs had risen again to 10 (5-FU) and 15 It is a widely used, flexible and low-cost treatment.63 It can (TCA) in the eight evaluable patients; these differences were be used either as lesional treatment or as part of field treatnot statistically significant. ment. The side-effects with the latter can be substantial, and it The results of using the same formulation of 5-FU less freis important that the patient is counselled about them, includquently, but for prolonged periods, are conflicting. An open ing soreness, redness and possible crusting. All of these can be trial of 10 patients reported clearance of 96% of AKs after a minimized through reduction in the frequency of application mean of 6(cid:1)7 weeks applying treatment twice daily, once or or short breaks in a course of therapy. It is permitted to wash twice per week.68 Six patients were followed for 9 months the area and apply thin emollient. If the reaction is excessive, and showed an 86% clearance rate that was maintained.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 10}, {"text": "of therapy. It is permitted to wash twice per week.68 Six patients were followed for 9 months the area and apply thin emollient. If the reaction is excessive, and showed an 86% clearance rate that was maintained. weak steroid can be applied. It is important that the patient is Epstein followed this study with a similar protocol and sample enabled to learn how to use the treatment, as it is one they size, except that evaluation was done by dermatologists given mayrequireintermittentlyinthefutureandabadinitialexpea series of photographs and blinded to the sequence.69 Eight rience canlimit further use. of 13 patients failed to show any improvement, with the conMany regimens cite twice-daily application over 4 weeks, clusion that pulsing 5-FU over a period < 10 weeks is not but less frequent initial use may enable titration of the freeffective. A comparison of use twice daily for 3 weeks against quency of application against reaction, tolerance and efficacy. twice daily for 1 day a week for 12 weeks showed the infreUse at poor healing sites such as the lower leg should always quent regimen to be 80% as effective when evaluated at the be undertaken with caution and may need supervision. More final assessment at 52 weeks.70 recently, 5-FU 0(cid:1)5% in 10% salicylic acid has been evaluated The mixed quality and size of these studies mean it is diffiand can be prescribed.64 A wide range of open trials, dosecult to provide a firm interpretation, but the indication is that ranging studies and manipulations of the vehicle have been pulsed therapy may work for some patients and enable more reported over the last 45 years, as well as two RCTs, confirmprotracted therapy with reduced morbidity. Such an approach ing efficacy. A large,placebo-controlled RCT showed 5-FU 5% can be useful for sensitive areas or people reluctant to use to be more effective than placebo in AK clearance and the treatments that provoke redness and crusting. However, for reduction of follow-up cryosurgery treatments at 6 months.35 some people it may fail to show benefit, and increased \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 10}, {"text": "increased \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 3, "page": 10}, {"text": "30 Guidelinesforactinickeratosis2017, D.deBerkeretal. frequency of use or an alternative treatment may need to be periods. After a further 24 weeks, these figures changed to employed. 45%, 0% and 14(cid:1)3%, respectively, illustrating that improve5-FU 0(cid:1)5% in 10% salicylic acid has been assessed, where mentcontinuestoprogressaftertheconclusionofimiquimod, salicylic acid may be acting as a keratolytic to enhance the in contrast to other treatments.58 Similar results were reported efficacy of5-FU. Intheinitial opentrial, statistics wereunderfor imiquimod 5% used three times a week for 4 weeks in taken per AK rather than per patient.71 In this framework, itis 126 patients, andrepeated for afurther 4 weeksa monthlater not possible to report the complete cure of any single patient. in 79 of them and compared with cream vehicle. The global However, the clinical clearance rate for individual AKs was complete response in the combined groups was 55%, com77%, with no control or blinding. Subsequent evaluation paredwith2(cid:1)3%forvehicle,illustratingthatpersonalvariation against salicylic acid vehicle and diclofenac 3% in hyaluronic makes it possible to tailor the duration of the regimen to the gel has been undertaken.64 Daily application with a brush for individual.77 An RCT comparing imiquimod 5% cream on the 6\u201312 weeks or the point of clearance was compared with face [three times a week for 4 (40%) or 8 (60%) weeks twice-daily diclofenac gel over the same period. Eight weeks depending on response] with liquid nitrogen spray (10-s post-treatment, complete clearance was determined to be freeze to commencement of thawing) favoured liquid nitroachieved in 55(cid:1)4%, 32% and 15(cid:1)1% of the patients using the gen, with complete clearance in 88% vs. 66(cid:1)9%. However, the study product, diclofenac and vehicle, respectively; the AKs cryosurgery resulted in a higher number of pigmentary were grades 1 and 2. A follow-up phase of the same study changes.78 measured the rate of relapse of individual lesions rather than The side-effects of imiquimod are similar to those of 5-FU, relapse from complete clearance.72 With this measure, the rate with severe erythema (30(cid:1)6%), scabbing andcrusting (29(cid:1)9%) of relapse measured per lesion was less at 12 months with 5and erosions or ulceration (10(cid:1)2%). Flu-like symptoms can FU 0(cid:1)5% in 10% salicylic acid (14(cid:1)2%) thandiclofenac 3% gel also arise and are more likely if multiple sachets are used at (19%) (P = 0(cid:1)02%).", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 11}, {"text": "erosions or ulceration (10(cid:1)2%). Flu-like symptoms can FU 0(cid:1)5% in 10% salicylic acid (14(cid:1)2%) thandiclofenac 3% gel also arise and are more likely if multiple sachets are used at (19%) (P = 0(cid:1)02%).72 The nature of the application makes it each treatment or if it is being used for superficial BCC with suitable for lesion-directed therapy rather than field therapy. more frequent applications than is typically the case for AK.59 The license highlights the benefit of the salicylic acid vehicle An instance of post-treatment eruptive keratoacanthomas has as a means of addressing more keratotic AKs. About 50% of been reported.79 The extent of side-effects is not wholly prepatients discontinue treatment at 6 weeks due to disappeardictable, with some patients manifesting an extreme reaction anceoftheAK.73 and others very little. The clinical response is largely in proportion to the side-effects, and those terminating treatment early due to extreme soreness may still get a good response. 8.2.2 Imiquimod5% cream(strength of recommendation Side-effects are generally well tolerated, but it is important to A,levelof evidence1++) counsel the patient carefully in order to anticipate those who Imiquimod is a topical immune-response modifier. It is availhave moreextremeclinicalreactions.80 able as a 5% and a 3(cid:1)75% cream. Most of the data on treatThere are limited long-term data on relapse after treatment, ment response pertain to the 5% cream and are considered but in a three-armed RCT between cryosurgery, 5-FU 5% and first.IntheU.K.itislicensedforuseinclinicallytypical,nonimiquimod, the proportions of the intention-to-treat populahyperkeratotic, nonhypertrophic AKs on the face or scalp in tion maintaining clearance at 12 months were 1%, 33% and immunocompetent adults, when the size or number of lesions 76%, respectively.81 The cryosurgery treatments were 20\u201340 s limits the efficacy and/or acceptability of cryotherapy, and in duration, which is a dose at which scarring might be other topical treatment options are contraindicated or less expected. This observation poses questions about this limb of appropriate. It isapplied atnight andwashed offin themornthe study. In an observational, 16-month follow-up study, ing 8 h later. Courses are three times a week for 4 weeks, 75(cid:1)3% of those receiving treatment three times a week over whichcan berepeated forafurther 4 weeksifneeded.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 11}, {"text": "of those receiving treatment three times a week over whichcan berepeated forafurther 4 weeksifneeded. 8 weeks were clear at 16 months, in comparison with 57(cid:1)4% A meta-analysis of the use of imiquimod 5% cream from receiving thesametreatment twice aweek.82 five RCTs using it two or three times a week for 12\u201316 weeks There is a small number of studies on imiquimod 3(cid:1)75% demonstrated a 50% complete clearance rate. This is similar to cream (strength of recommendation B, level of evidence 1+), more brief and flexible regimens as per the license.74 A small which is licensed for treatment of AKs of the head and scalp RCT against vehicle placebo showed clearance rates of 84% with application once daily for two, 2-week periods separated when used up to three times per week for 12 weeks.75 Two by 2 weeks. Early studies had longer courses, applied once RCTs with regimens of three times per week for 16 weeks daily for two periods of 3 weeks separated by 3 weeks, over a and follow-up 8 weeks later gave 47% of subjects with com9-week course. Comparison with placebo vehicle 8 weeks plete clearance (vs. 7(cid:1)2% with placebo)76 and 57(cid:1)1% (vs. after conclusion of treatment showed complete clearance rates 2(cid:1)2%for placebo).59 of 5(cid:1)5% (placebo) and 34%.83 Where AKs responded they A head-to-head open trial between imiquimod 5% (twice recurred in 60% of patients within 14 months.84 Where treatper week for 16 weeks), its cream vehicle and diclofenac 3% ment was given as per the licence at weeks 1 and 2, then 5 gel (twice daily for 90 days) showed complete clearance of and 6, complete clearance was seen in 6(cid:1)3% and 35(cid:1)6% for 19(cid:1)1%, 0% and 20% at the end of the respective treatment emollient and imiquimod, respectively.85 Where the BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 11}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 31 comparator wascryosurgery andemollient vehicle, imiquimod the disruption of mitochondrial membranes resulting in dam3(cid:1)75%following cryosurgery resulted in complete clearance in age anddeath of host cells and promotion ofcell-specific anti59(cid:1)5%ofpatients.86 bodies with consequent antibody-dependent, cell-medicated Imiquimod3(cid:1)75%hasalsobeenusedfollowingcryosurgery cellular cytotoxicity. It is licensed for the treatment of nonkerasasupplementarytreatment,improvingtheresultoftreatment atotic, nonhypertrophic AK in adults (grade 1 and 2). It is ofhypertrophicAKsontheforearmanddorsaofthehandsover sold in two strengths (150 and 500 lg g (cid:3)1), with the weaker cryosurgery alone.87 It is possible that the adverse side-effects one applied 3 days in succession to the chosen area on the associated with imiquimod 5% cream are less with the 3(cid:1)75% face and scalp and the stronger one applied 2 days in succesformulation, and this might enable more field-based treatment sion to other sites. Each application is dispensed as a single overlesiontherapyandimprovepatienttolerance. tube of cream (three tubes for the face and scalp or two tubes for other sites) with scope to cover a field 5 9 5 cm. Use of the 150-lg g (cid:3)1 preparation on the face and scalp over 3 days 8.2.3 Diclofenac gel(strength of recommendation A,level resulted in a complete cure rate of 40% vs. 11(cid:1)7% for vehicle of evidence1+) 60 days after starting the treatment in one RCT,92 and 42(cid:1)2% Diclofenac3%ina2(cid:1)5%hyaluronicgelislicensedforapplicavs. 3(cid:1)7%forvehicle in another ofsimilar size.93 tion twice daily for 60\u201390 days and can be applied as a Pooled data from two trials of this treatment regimen follesionor field-based treatment. Its mechanism of action for lowed successfully treated patients for 12 months. There was AK is not known, but may be related to inhibition of the relapse on the head and neck in just over half of the patients cyclooxygenase pathway leading to reduced prostaglandin E2 in the following year.94 If residual lesions are re-treated at synthesis. Diclofenac gel usually causes less intense local skin 8 weeks, clearance at 12 months increases from 27% to reaction than 5-FU or imiquimod 5% cream.88 The reduction 50%.95 Clearance on other body sites is less, at 34(cid:1)1% vs. ofside-effectsismatchedbyreduced efficacywherediclofenac 4(cid:1)7%for vehicle after application of the500-lg g (cid:3)1 cream on gel and 5-FU 5% are compared, but both achieve high levels two consecutive days, with relapse in just over half of the (73% vs. 77%) ofpatientsatisfaction.89 patients at 12 months.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 12}, {"text": "the500-lg g (cid:3)1 cream on gel and 5-FU 5% are compared, but both achieve high levels two consecutive days, with relapse in just over half of the (73% vs. 77%) ofpatientsatisfaction.89 patients at 12 months. Specific sites such as the back of the There are three vehicle-controlled studies in the treatment hand are less likely to clear completely, with 18(cid:1)5% vs. 0% of mild AKs. In the first, patients were treated for a mean of for placebo.96 60 days, with aclearance of 70%of target lesionsin the treatSide-effects peak at 4 days, which is after completion of the ment group compared with 44% in those using the vehicle.57 application of treatment. Common effects are redness, scabIn the second study, treatment was for 90 days; 50% achieved bing, pain and pustules, with most side-effects settling within complete clearance vs. 20% of those treated with vehicle alone 28 days.93,94 (P < 0(cid:1)001).90 In a three-armed RCT comparing diclofenac A 2015 update from the US Food and Drug Administration 3%, imiquimod 5% cream and base cream, the rates of comhighlights the risks of severe adverse reactions, with local and plete clearance at the end of treatment were 19(cid:1)1%, 20% and systemic allergic features and herpes zoster infection. Within 0%. the update they emphasize the need \u2018to avoid applying the gel In summary, these three different studies with diclofenac in, near, and around the mouth, lips and eye area\u2019.97 Extendgel show 26%, 30% and 19(cid:1)1% benefit over vehicle gel or ing the area of treatment of ingenol mebutate to 100 cm2 base cream, respectively.58 Extending treatment from 90 to resulted in no increase in treatment-related adverse events 180 days gave an additional 5% complete clearance without a compared with 25 cm2.98 Clobetasol propionate, used twice significant change in adverse effects.91 Follow-up assessment daily for 4 days post-treatment, did not alleviate the sympwas limited to 30 days post-treatment in the first two studies. toms or efficacy of ingenol mebutate.99 This may be relevant In the third, clearance dropped to 14(cid:1)3% at 24 weeks\u2019 followtoothertreatments causingsoreness. up. Diclofenac 3% gel used as part of a three-armed study with 5-FU 0(cid:1)5% in 10% salicylic acid and vehicle resulted in a 8.2.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 12}, {"text": "causingsoreness. up. Diclofenac 3% gel used as part of a three-armed study with 5-FU 0(cid:1)5% in 10% salicylic acid and vehicle resulted in a 8.2.5 Topicalretinoids (strength ofrecommendation B, 32% rate (17% over vehicle)64 of complete clearance, and a level ofevidence1+) relapse rate of 19% at 12 months.72 These data indicate moderate efficacy with low morbidity in mild AKs. Treatment was A range of older trials demonstrate a modest benefit with the well tolerated and reported side-effects were mainly pruritus use of topical retinoids in AK.100 They may lend some addi- (41% estimated after 30 days\u2019 treatment) and rash (40% estitional benefit with respect to improvement in lentigines and mated after60 days).57 reduced wrinkles. Their use is usually sustained rather than based on a limited course of treatment. Products include ada8.2.4 Ingenol mebutate cream(150 lgg(cid:3)1faceandscalp, palene 0(cid:1)3%, tretinoin 0(cid:1)1% and 0(cid:1)05% and topical isotreti500 lgg(cid:3)1limbsand trunk)(strength ofrecommendation noin 0(cid:1)1%. Where adapalene 0(cid:1)1% was compared with 0(cid:1)3%, the latter was significantly more efficacious in achieving AK A, levelofevidence 1+) count reduction after 9 months.101 Currently, tretinoin and Ingenol mebutate is a diterpene ester extracted from the plant isotretinoin are prescribable in the U.K. only in 0(cid:1)025% and Euphorbia peplus. At a cellular level it appears to work through 0(cid:1)05% concentrations, respectively, as topical antibiotic \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 12}, {"text": "32 Guidelinesforactinickeratosis2017, D.deBerkeretal. combinations licensed for use in acne. A Veterans Association rate of 88% as judged at 24 weeks.106 In a right\u2013left, splitRCT exploring topical retinoid for chemoprevention of skin face study comparing MAL-PDT with a cryosurgery double cancerwasstoppedearlybecauseofexcessiveall-causemortalfreeze\u2013thaw cycle retreated at 12 weeks as needed, MAL-PDT ityin thetreatment groupat interim analysis.102 showed 89(cid:1)1% cured lesions vs. 86(cid:1)1% for cryosurgery, with Keyrecommendations: topical therapies no significant difference between them. Patient and clinician (cid:129) assessment of cosmetic outcome were in favour of MALEmollient and sunscreen with advice on sun protection PDT.107 might be a satisfactory treatment for people with fluctuExtensive cryosurgery over large areas has been referred to ating grade 1AKs. (cid:129) as cryopeeling, and can be used to treat fields of AKs and Education at the outset of using active topical therapies background damage.108 Cryosurgery has been described in is important to ensure a full understanding of how to combination with topical 5-FU, where the duration of treatapplytreatmentandthenatureoftheside-effects,which ment and consequent side-effects of both modalities could be canbemarked. (cid:129) reduced while maintaining efficacy.109 The pretreatment of AK Active topical therapy is suited to use in primary and with 5-FU 0(cid:1)5%for 1 week, prior totreatment of theremainsecondary care. Where possible, a management plan ing lesions with cryosurgery at the 1-month follow-up, may should be formulated that enables the patient to be decrease the AK count at 6 months when compared with managed in primary care. (cid:129) cryosurgery and vehicle pretreatment (reduced to 33% vs. Topical therapy is suited to use as lesionand field55%, P = 0(cid:1)01).110 basedtreatment.Whereusedforfieldtreatment,thesize Cryosurgery is a flexible therapy that requires skill in of the field needs to be defined with the patient to administration. With larger doses it is likely to result in loss ensure anticipation andtolerance ofside-effects. (cid:129) of pigment and scarring. Patient counselling is important conFailure of an individual lesion to respond to topical cerning the shortand long-term side-effects. In particular, therapyindicates aneedfor furtherevaluation. Thismay patients should be aware of blistering, oedema, crusting and include referral from primary care to secondary care or soreness. Doses appropriate for AK are usually < 10 s, but still surgerytoobtainhistology andextendtreatment. carry some risk of damage to underlying structures such as tendons and nerves if applied on the back of the hands.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 13}, {"text": "or soreness. Doses appropriate for AK are usually < 10 s, but still surgerytoobtainhistology andextendtreatment. carry some risk of damage to underlying structures such as tendons and nerves if applied on the back of the hands. Below the knee, slow healing can be a problem, particularly in the 8.3 Cryosurgery(strength ofrecommendation A,level of older patientgrouppresenting withAK. evidence 1++) Cryosurgery is a long-established treatment for AKs requiring 8.4 Surgery a cryospray (or cotton wool and orange sticks) and a supply of liquid nitrogen. Complete clearance rates vary according to There are no trials of surgery for AKs. The nature of the the duration of freeze and the number of treatments, usually pathology makes it likely that a surgical procedure able to separated by 6\u201312 weeks. The relationship between duration remove an area of diseased skin represents an effective therof freeze and clearance was examined in a three-dose study apy. Histological information can be useful in management of with 12-month follow-up after cryosurgery. A duration < 5 s AK. It is unlikely that this would be a first-line treatment showed 39% cure, 5\u201320 s, 69% cure and > 20 s, 83% cure unless there was diagnostic uncertainty. Surgery addresses a on the scalp and face.103 Many more recent studies are based focal lesion, and where AK presents in a field of actinic damon head-to-head trials with PDT. A randomized study comparage, it does not address this. A curettage specimen may make ing cryosurgery with PDT in 193 patients indicated an overall it difficult to determine whether a lesion has an element of 75% complete response rate for cryosurgery in contrast to dermal invasion. In some instances a deep shave or formal 69% in those treated with PDT at 3 months.104 The differenexcision with histological examination might be preferred. If tial success of the two therapies was more marked for thick curettage is used for a hyperkeratotic AK where SCC is a diflesions, with 69% showing complete response to cryosurgery ferential diagnosis, it may be warranted to employ two or vs. 52% to PDT. A double freeze\u2013thaw cycle was used in this three cycles oftherapy.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 13}, {"text": "52% to PDT. A double freeze\u2013thaw cycle was used in this three cycles oftherapy. This will ensure that if the histology is study in contrast to a single cycle, which, when used in a difthat of invasive SCC, or if it is equivocal, the curettage is still ferent study, yielded a68%response.105 likely to represent adequate treatment. Exceptions would be A more recent head-to-head study with methyl aminolaewhere the size, histological type or location of an SCC would vulinate (MAL)-PDT employed cryosurgery (1 9 10-s freeze) make curettageanunacceptable treatment.111 as needed every 3 months for up to four visits with assessment at 12 months. It reported a complete response rate of 8.5 Systemic therapy (strength ofrecommendation C, 85%, with 77% needing only one treatment. Side-effects of level ofevidence 2+) cryosurgery of soreness, blistering, pigmentary change and scarring contributed to an overall patient preference for Systemic retinoids have been assessed for their potential role PDT.78 Inanother study, adoublefreeze\u2013thaw cycle given just in suppression or treatment of multiple AKs. Early studies once with no defined duration provided a complete clearance employing etretinate showed the efficacy of this drug in BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 13}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 33 double-blind, crossover trials.112 Anecdotal evidence over the photosensitizing cream, then the agent is applied under occlulast 20 years suggests that there can be some considerable sion for 3 h prior to irradiation. Surface fluorescence with a morbidity in employing this treatment. In addition, there may Wood\u2019s lamp can help delineate lesions and identify persistent be a rebound effect once the systemic therapy is stopped. disease. Treatment can be painful but can be managed with However, these effects were not observed at the 4-month folcold-air analgesia or nerve blocks.121,122 Erythema and crustlow-up in theone availablereport on thissubject.113 ing often occur but can be reduced by the use of plaster or Use of systemic retinoids may be justified in very high-risk physical sunscreens.123 patients, such as organ transplant recipients, where there is a Four studies report PDT to be more effective than plapresumed increased risk of progression from AK to SCC.54 cebo.105,107,124,125 Three were randomized and one double Renal transplant patients given oral acitretin 0(cid:1)4 mg kg (cid:3)1 blinded, with 80\u2013211 subjects. Efficacy rates appear better for showed some immunohistochemical normalization of keratin the face and scalp than the forearm and hands,126 but there expression patterns, butaresidue ofhistological dysplasia sugare no studies comparing the two sites. Response rates in the gests potential for relapse when the drug is stopped.114 Lowface and scalp range from 69% to 93%. Follow-up reported dose acitretin is currently given as a treatment option in the up to24%recurrence at12 months in anopen-label study.127 \u2018European best practice guidelines\u2019 for renal transplant patients There may be an increased response of PDT with fractionwith multipledysplastic skin lesions.115 ated light128 and pretreatment with laser.129 Both claimed betAn international survey of 28 dermatologists managing skin ter responses, but patient numbers were small and the sidedisease in organ transplant recipients looked at the use of syseffects greater with laser pretreatment. In a side-to-side comtemic retinoid.116 In the setting of AK alone, only where the parative study of PDT vs. CO laser treatment they were of 2 AK was extensive did the majority (56%) advocate systemic equalefficacy but patientpreferencewas forPDT.130 retinoid. Once patients start getting multiple (more than five) Three open-label RCTs compared MAL-PDT with cryosurSCCs in addition to AK, the rate of prescribing increased to gery.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 14}, {"text": "did the majority (56%) advocate systemic equalefficacy but patientpreferencewas forPDT.130 retinoid. Once patients start getting multiple (more than five) Three open-label RCTs compared MAL-PDT with cryosurSCCs in addition to AK, the rate of prescribing increased to gery. Two freeze\u2013thaw cycles were comparable in one between 74% and 81% depending on whether the SCCs were study104 and inferior in terms of relapse in another.107 A sinhigh risk. Acitretin was the most common drug, at a starting gle cycle was inferior in the third study.105 The efficacy of dose of 10 mg (42%) or 25 mg (58%); 12% of respondents PDT was confirmed in a meta-analysis in 2014.131 PDT has used isotretinoin. also been compared side to side in trials with 5-FU.66 A There is little literature on the use of systemic cytotoxic right\u2013left comparison of AK treatment on the backs of the agents in the immunosuppressed, mainly for the treatment of hands showed a similar response for PDT and 5-FU, clearing SCC but in the setting of extensive AK. Capecitabine given to lesions in 73% and 70% of cases, respectively. Three studies 15 organ transplant recipients with frequent SCC, BCC and AK showed nodifference between PDTandimiquimod.132\u2013134 showed reductions in monthly incidence to 22%, 33% and In a randomized study of 30 patients given up to two treat45% of pretreatment levels, respectively.55 Side-effects resulted ments with ALA-PDT or one to two courses of imiquimod in 33% ofpatients stopping after1 year. (three times a week for 4 weeks), equivalent responses were The cyclooxygenase-2 inhibitor, celecoxib, taken for seen 6 months after completion of treatment (65% vs. 9 months can reduce the number of BCCs and SCCs over an 55%).134 PDTwasmoreeffectivefor grade 2lesions. 11-month period, but does not appear to alter the number of A thin, self-adhesive patch has been developed for selfAKs.117 Overall, it may have a role in high-risk patients with application.135,136 In a multicentre RCT involving 449 multiple NMSCs, but it does not have evidence of a role for patients, efficacy with active treatment was 82% after AK.118 12 weeks compared with 19% for placebo and 77% for cryosurgery. It is advocated as allowing self-application and avoiding theneed forpretreatment curettage. 8.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 14}, {"text": "weeks compared with 19% for placebo and 77% for cryosurgery. It is advocated as allowing self-application and avoiding theneed forpretreatment curettage. 8.6 Photodynamic therapy (strength ofrecommendation Daylight PDT involves the application of MAL to the skin A, level ofevidence 1+) without occlusion and subsequent exposure to ambient dayPhotodynamic therapy combines a dedicated light source of light. A high-SPF sunscreen without mineral filters is applied appropriate wavelengths with the application of a photosensi15 min before the photosensitizing cream. Thirty minutes tizing cream to produce apoptosis and necrosis of the target later thepatient spends2 houtdoors. tissue. Photosensitizing agents include 5-aminolaevulinic acid Five RCTs in Europe and Australia have confirmed the effi- (5-ALA) and the methyl ester of 5-ALA, 5-MAL. BF-200ALA cacy of daylight PDT compared with conventional PDT.137\u2013141 was recently used, showing increased stability and penetraThis was in mild (grade 1) to moderate (grade 2) lesions on tion.119,120 the face and scalp. Clearance rates of 70\u201389% were reported. A range of light sources can be used.121 Red narrow-specIn European studies daylight PDT can be performed in all trum light sources permit shorter illumination times and weather conditions,141 but temperatures > 10 \u00b0C are advised appear to give higher response rates.119,120 Current knowledge for patient comfort. Consensus guidelines have also been proof photosensitizers and light sources are detailed in the 2013 duced.142\u2013144 European Guidelines for PDT.121 In most situations superficial One comparative study was a right\u2013left comparison of PDT crust or keratin is first removed with light curettage and with ingenol mebutate in grade 1 and 2 lesions (27 patients). \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 14}, {"text": "34 Guidelinesforactinickeratosis2017, D.deBerkeretal. In both there was a 40% complete response rate, but PDT was product with two active ingredients where, for instance, salibetter tolerated.145 cylic acid 10% may break down surface keratin and improve penetration and hence the efficacy of 5-FU 0(cid:1)5% (see Section 8.2.1). 8.7 Laser therapy (strength ofrecommendation B, level Salicylic acid ointment is sometimes used as a preliminary ofevidence 1+) to topical 5-FU to remove overlying keratin. Salicylic acid In principal, dermabrasion, chemical peels and laser treatment 50% in croton oil has been described as a treatment for AKs should treat AKs, as skin is destroyed to a controlled depth. when used in combination with TCA 20% and pretreatment The majority of studies treat field change as well as individual with topical tretinoin as a serial regimen for facial peel.39 The lesions. These physical therapies come with significant risk of ointment base may be acting as an emollient, with some level long-term side-effects including hypopigmentation and persisofsuccess for grade 1AK3,57 (seeSection 8.1.1). tent erythema and scarring. The risk of such problems is In a case series, patients were pretreated with diclofenac 3% greater with ablative rather than nonablative laser techniques, gel for 12 weeks followed by cryosurgery for the 29% with whichalso requireanti-infective prophylaxis.146 residual lesions. This demonstrated an overall effective There are no studies comparing laser treatment with no response to this combined management approach, with comtreatment or placebo. plete clearance maintained for6\u201320 months (mean10).156 An A good-quality, prospective, randomized study of 5-FU open-label multicentre trial of cryosurgery (freeze time of 4\u2013 (twice daily for 4 weeks) vs. erbium-doped yttrium alu10 s) followed by diclofenac 3%gel 15 days later for the next minium garnet (Er:YAG) laser in 55 patients demonstrated 3 months vs. cryosurgery alone found that complete clearance significantly fewer recurrences in the laser group at 6 and increased from 21% to 46% with the addition of diclofenac. 12 months, but more erythema and hypopigmentation in the The clearance rates for a target lesion were greater at 32% vs. long term. No data were reported on clearance at completion 64%.157 A small, right\u2013left-hand study with 4 weeks\u2019 pretreatoftreatment.147 ment using diclofenac 3% gel and PDT compared with plaA second prospective randomized trial of CO laser vs.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 15}, {"text": "data were reported on clearance at completion 64%.157 A small, right\u2013left-hand study with 4 weeks\u2019 pretreatoftreatment.147 ment using diclofenac 3% gel and PDT compared with plaA second prospective randomized trial of CO laser vs. TCA cebo gel and PDT demonstrated a greater decrease in the 2 30% vs. 5-FU (twice daily for 3 weeks) with small patient number and thickness of AKs on the side with diclofenac prenumbers showed a significant clearance of lesions with all treatment,at 12 months.158 interventions at 3 months. The authors also claimed a delayed Diclofenac 3% as pretreatment for 5-FU 0(cid:1)5% in 10% salitime to recurrence of NMSC compared with controls, but the cylic acid is also reported as an effective sequential regicontrolswere thedropouts fromthestudy.148 men.156 There are reports of 5\u20137 days of 5-FU 5% Three retrospective case studies of CO with or without Er: pretreatment also being safe and effective in combination with 2 YAG lasers show clearance and reduced AKs at follow-up.149 cryosurgery110 or PDT159 or, alternatively, in combination Two of these studies demonstrate 80% and 87% clearance at with glycolic peels.38 PDT followed by imiquimod twice a 12 months.150,151 A split-face study of ablative, fractionated week for 16 weeks was beneficial over PDT and subsequent (i.e. multiple pinpoint treatments) CO laser treatment vehicle cream alone when undertaken in a split-face study.160 2 demonstrated only a short-term reduction in the number of Thecompleteclearanceratewasnotreported,butthepercentAKs, not sustained over 3 months.152 One pilot study of nonage reduction in count was significant at 89(cid:1)9% in the comablative fractional laser in 10 patients reported 46% clearance bined treatment side vs. 74(cid:1)5% on the side treated with PDT at 6 months and claimed minimal acute and long-term sidealone. With PDT as the variable rather than imiquimod, PDT effects.153 did not appear to improve the efficacy of imiquimod alone, Dermabrasion in open studies clears AKs on the face and although the study was small. Similarly, adding imiquimod scalp. Coleman et al. treated 23 patients, 96% of whom were 5% two times a week for 8 weeks to cryosurgery does not clear at 6 months and 54% at 5 years.154 Winton and Salasche appeartoimprove on cryosurgery alone. treated fivepatients successfully, withcompleteclearance.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 15}, {"text": "does not clear at 6 months and 54% at 5 years.154 Winton and Salasche appeartoimprove on cryosurgery alone. treated fivepatients successfully, withcompleteclearance.155 An alternative regimen has been studied for hypertrophic A simple, prospective case series describing treatment of AKs on the forearms and the dorsa of the hands. Imiquimod individual AKs with phenol 100% applied once a month for 3(cid:1)75% was used following a double, 5-s freeze\u2013thaw cycle, up to a maximum of 8 months in 32 patients reported no randomized to the right or left arm and applied in up to two recurrence at12 months.37 sachets per night for 2 weeks, followed by a 2-week break and a further 2 weeks. The comparison was cryosurgery alone on the other arm. Complete cure was not an end point, but 8.8 Combination treatment there was a greater level of clearance in the combination arm There are many trials of combination therapy in the treatment (76%) than the control arm (38%). This difference did not of AK; they are of two kinds. The first is a serial approach emerge until 10 weeks after cryosurgery (4 weeks after comwhere one treatment is advocated to follow the other dependpletion of imiquimod), and maximized at the end of assessing on outcome, or as a specific regimen of pretreatment with ment at 14 weeks.87 Randomizing to 5-FU 0(cid:1)5%, 1 week the possibility that the effects of one treatment will maximize, after cryosurgery resulted in nonsignificant improvement over or consolidate, the response. The second approach is to use a cryosurgery alone.161 BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 15}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 35 Keyrecommendations: physicalandsystemic therapies Studies undertaken in ophthalmology suggest that treatment (cid:129) is possible with close supervision. Treatment can be combined Education at the outset of using physical therapies is with care of the eye. In a case series of 14 patients treating important to ensure a full understanding of the sideperiocular skin with 5-FU 5% twice daily for 2 weeks, antibieffects, which can be marked and include scarring and otic ointment was coprescribed and used until the area had alteredpigmentation. (cid:129) healed.163 Six of the 14 AKs were on the upper eyelid and Cryosurgery is a flexible and effective form of lesionnine abutted a lid margin. Five patients required a second based physical therapy that removes the patient involvecourse of treatment, but overall clearance was complete in all ment in their own care and requires administration in a cases and remained so for a mean follow-up period of servicewith cryosurgery. (cid:129) 38 months. Two patients had transient inflammatory sideCurettage can be warranted for thicker (grade 3) AKs, effects affecting the eye. The potential precision of application wheretheyareresistanttotopicaltherapyandwherethere of 5-FU 0(cid:1)5% in 10% salicylic acid in a collodion base might is suspicion that they may representearly SCC. Histology make it a useful alternative to cream formulation, but there mustalwaysbeobtained.Diagnosticbiopsymaybewarare no dataon this. rantedonthesamebasis,butissubjecttosamplingerror. (cid:129) A retrospective study of the use of imiquimod 5% cream PDT is an effective treatment for confluent AKs, such as for a range of periocular actinic lesions identified 47 patients on the scalp, which are difficult to manage or resistant mainly with AK, mainly on the lower lid.164 Conjunctivitis totreatment in theabsence ofinvasive disease. (cid:129) occurred in 15 and six had ocular stinging, with conjunctivitis PDT has low scarring potential and less risk of poor in three for over 2 weeks. Antibiotics were needed in three, healing in comparison with other physical therapies at for preseptal cellulitis in two of them. Nine patients discontinvulnerable sitessuch asthelower leg. (cid:129) ued imiquimod due to ocular irritation and conjunctivitis, of Pretreatment with topical therapy can increase the effiwhom four patients recommenced and finished the treatment cacy ofphysical therapies. (cid:129) after a rest period.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 16}, {"text": "increase the effiwhom four patients recommenced and finished the treatment cacy ofphysical therapies. (cid:129) after a rest period. At a mean follow-up of 16 weeks, 34 Failure of an individual lesion to respond to physical (72%) patients had clinical clearance of the periocular lesions therapy indicates a need for further evaluation. This and no patient had any residual ophthalmic side-effects from couldinclude formalexcision. (cid:129) imiquimod. Systemic therapy is usually given in the context of mulThere is no good literature on diclofenac gel or ingenol tiple grade 3 AKs, a history of serial SCCs and immunomebutate, but both the PIL and product licence emphasize the suppression. Therapy might be preventive with a importance of avoidingcontact oftheproductwiththeeyes. retinoid and should be undertaken as part of a multidisciplinarydecision,whichmightincludealternatives such asthereduction ofimmunosuppression. 9.1.2 Ears The ear is a common site for the presentation of AK and SCC. The risk of metastasis is higher when SCC arises on 9.0 Special considerations the ear. This means that the context of treatment is slightly different at this site than at others. The wish to treat AK 9.1 Bodysites (strengthof recommendation C, levelof with a view to avoiding evolution to SCC may be a greater evidence 2+) priority. Histological diagnosis of any thicker AKs to Thedatafromavailabletreatmentsindicatethatsometreatments differentiate them from invasive SCC by shave biopsy or are more adaptable than others and that morbidity varies with excision is recommended. These interventions may represent location. The balance ofissues determined by location,charactreatment of such AKs or a preliminary to treatment of teristicsoftheAKsandnatureofthepatientaresummarizedin SCC. Table 3.Thescoringisbasedontheauthors\u2019evaluationofefficacy,easeofuse,morbidityandcost-benefit. 9.1.3 Forearm andhands Actinickeratosesonthedorsumofthehandareoftenmultiple 9.1.1 Periocular and hyperkeratotic. Early management with topical therapy or The main consideration for treatment of periocular AK is the PDT may reduce the need for surgical interventions later. The risk of adverse events involving the eye. All products licensed skin is more tolerant of the side-effects of inflammatory treatfor treatment of AK have cautions in the PIL and/or summary ments and hence permits prolongation of the course of treatof product characteristics concerning getting treatment in the ment in some instances. This may be required due to the eye.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 16}, {"text": "instances. This may be required due to the eye. Creams used near the eye can smear into it, and inflamthicker skin or hindrance to treatment penetration by keratin mation caused by local destructive or inflammatory treatments in thicker AKs. Combinations of salicylic acid and 5-FU or such as cryosurgery may impinge upon the eye either directly curettage can be useful elements of treatment for the grade 3 or indirectly. Typically, liquid nitrogen is used with a contact AKs found on the forearm and back of hands (see Secprobe, ensuring thatcold vapour doesnotdamage theeye.162 tion 8.8) \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 16}, {"text": "36 Guidelinesforactinickeratosis2017, D.deBerkeretal. Anecdotal and limited trial data suggest that treatments for 9.1.4 Below theknee AKs in transplant patients are less effective than in the general Actinic keratosis below the knee are often mixed with SCC population,53 perhaps because AKs are more proliferative and in situ, a disposition to NMSC, including atypical BCCs and hyperkeratotic in this group or because new lesions appear other actinic changes. They are a feature of elderly sunrapidly in the treated site. One study in transplant recipients exposed legs and often coincide with decreasing ability to failed to demonstrate a reduction in the development of subheal. Treatments need to find the right balance between sequent skin cancers in those areas of skin previously treated managing the disease and causing complications, which for AKs with PDT.51 Where safety studies are undertaken in include nonhealing and soft-tissue infection. Treatment is transplantpatientstheyappeartodemonstratereactionssimilar likely to be intermittent, low intensity and chronic; most tothosein nontransplant patients.167 reports are case series with small numbers. Infrequent or pulsed application of 5-FU has been employed,68 as has more 9.3 Follow-up intensive treatment using 5-FU chemowraps.165 This entails the application of 5-FU 5% once a week under an occlusive There are no data concerning the benefit of follow-up in bandage for 7 days over a period of 4\u20138 weeks. Gaps in treatpatients with AKs. Patients and their carers should be educated ment canbeneeded whereskin breakagedevelops. regarding changes that suggest malignancy. Those at high risk Diclofenac 3% gel might be employed with the expectation of NMSC, such as organ transplant recipients, may warrant of fewer side-effects, but possibly less benefit. PDT is used on follow-up; the presence of at least 10 AKs is an indicator of thelower legs,particularly wherethere may beproblems with this risk.18 healing. Where treatments are likely to require evaluation and Keyrecommendations: special sites (Table 2) adjustment, follow-up in primary, intermediate or secondary (cid:129) care is needed. This could be by any member of the healthPoor healing sites such as below the knee in the elderly careteamwithvalidatedcompetenciesinthesafeandeffective require flexible regimens, heightened supervision and management of AK. Current NHS guidance suggests that consideration ofless destructive treatments such asPDT. (cid:129) patients with AK should be managed in primary care.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 17}, {"text": "supervision and management of AK. Current NHS guidance suggests that consideration ofless destructive treatments such asPDT. (cid:129) patients with AK should be managed in primary care. Where The ears are commonly affected by AK and require this is a sole pathology and not complicated by NMSC or attention early in respect to all modalities of treatment, other factors, the patient should be provided with information including preventive action with a broad-brimmed hat toenableongoing diagnosis and care. andsunscreen. (cid:129) Grade 3 AKs on the ear may warrant curettage early to obtain histology andavoid missedearly SCC. 9.4 Treatment failure (cid:129) The skin of the dorsum of the hands can be more resisAll treatments have some risk of failing to achieve clearance of tant to treatment than the head and neck, and warrants anindividuallesion.Wherethisisthecase,thereasonforfailextendedperiods oftopical therapy. (cid:129) ure needs assessment, where one of the possible explanations All licensed treatments include warnings about use near might be that the diagnosis is incorrect. Lesions within the the eye. Periocular AK needs careful assessment in secdifferential diagnosis of AK include SCC in situ, invasive SCC, ondary care. Topical treatments may be possible, but seborrhoeic keratosis, actinic porokeratosis, viral wart and clearguidance andsupervision areneeded. others. Depending on the outcome of this clinical assessment, treatment might be escalated in intensity, duration or type, or thelesion might bebiopsied or treated surgically. 9.2 Immunosuppressed patients An alternative interpretation of failure is that the patient Data on the epidemiology and natural progression of AK in continues to get new AKs. This is not true failure, but more the immunosuppressed are less detailed than in the normal an illustration of the nature of the disease. Once someone is population. The risk of progression to SCC is likely to be diagnosed with AK, they are likely to need intermittent, lifehigher, and therefore there is a greater need for treatment of long treatment. AK. Wallingford et al. highlighted the need to monitor transplant patients with field-change AK disease.166 Within a large 10.0 Economic considerations cohort of renal transplant patients, nearly one-third were found to have AKs. Of these, half were isolated AKs and half Table 3summarizes thecost-effectiveness of therapy. were AKs within a field of AK and actinic change.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 17}, {"text": "found to have AKs. Of these, half were isolated AKs and half Table 3summarizes thecost-effectiveness of therapy. were AKs within a field of AK and actinic change. In the subIt is likely that the number of treatment episodes for AK sequent year, the rate of development of SCC associated with will increase. Australian Medicare data demonstrate an increase the isolated AK was 7%, in comparison with 21% of those of 160% between 1994 and 2012 in claims for use of cryowith field change, most of which (11 of 15) arose within the surgery to treat 10 or more AKs. Many studies have tried to field. Other differences between the two groups were that the assess the cost-effectiveness of treatment for AK.168\u2013171 Howpatients with isolated AKs tended to be transplanted later in ever, the methods of calculation and the different healthcare lifeandhadashorter duration ofimmunosuppression.166 systems andtheirwaysof fundingprevent comparison. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 17}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 37 Two nonindustry studies have been published from the quantitative assessment. Examples of all this are found in the U.K. Wilsontried tocomparethecostofPDTandimiquimod, studies referencedin this guideline. taking into account quality of life.172 The author comments Areas of uncertainty in thetreatment of AK that requirefurthat a head-to-head study of imiquimod vs. PDT was required ther studies include (i) measurement and relevance of vitamin to enable more accurate calculations. Muston et al. used effiD and (ii) prospective studies looking at the effect of treatcacy data from the literature to assess the cost\u2013benefit ratio ment ofAKs on subsequent SCCreduction. and reported that the costs and effectiveness of PDT compare well withothertreatmentsfor AK.173 12.0 Recommended audit points At a practical local level, prescriptions that enable the patient tore-treat, extend treatment or treat new areas have an Inthelast20consecutive patients withAKis there cleardocuinherent economic value and enable the patient to exercise mentation of: their judgement. Imiquimod and ingenol mebutate are dis- (cid:129) the location of the AKs indicated on a drawing or a pensed in aliquot packages that are single-treatment doses and head andneckor body map; provided in a number to complete a course of treatment. This (cid:129) the grade or bulk of the AKs (e.g. grade 1, 2, 3 or tightly defines the cost per course of treatment and the terridescriptive; seeTable 1); tory that can be treated. By contrast, Gibbs and Davis noted (cid:129) treatment modality anddosage; that patients used only 31% of the content of a tube of 5-FU (cid:129) information (e.g. a PIL or other suitable source of infor5% in a single course of treatment, which enables substantial mation) provided to the patient on side-effects of treatflexibility in thecourseandterritory oftreatment.174,175 ment,where relevant; (cid:129) the patient having received information on the name 11.0 Future directions andnature oftheir diagnosis; (cid:129) information provided for the GP in diagnosis and future Future directions need to address the human element of bearmanagement, in primary carewhere relevant. ing thelong-term diagnosis of AKand thetechnical challenges of treating AK effectively with low morbidity and acceptable The audit recommendation of 20 cases per department is to cost. The clinical challenge comprises an ageing person with reduce variation in the results due to a single patient, and to barely symptomatic dry areas of skin.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 18}, {"text": "audit recommendation of 20 cases per department is to cost. The clinical challenge comprises an ageing person with reduce variation in the results due to a single patient, and to barely symptomatic dry areas of skin. Education, prevention allow benchmarking between different units. However, and empowerment at this stage may help avoid the situation departments unable to achieve this recommendation may in 10\u201320 years where multiple untreated AKs accumulate and choose toauditallcases seenin thepreceding12 months. the patient presents with advanced AKs mingled with possible SCCs. The earliest stage in the prevention strategy shares 13.0 Summary ground with strategies for the avoidance of skin cancer, and equally shares its concerns of compromised vitamin D levels The findings are summarized in Table 2. See the text for and loss of the indirect benefits of UV exposure. Collaborative details ofevidence. work between patient groups and primary and secondary care Actinic keratoses are a multifocal manifestation of sun damshould aim to find a suitable balanced approach to global care age, comprising a spectrum of clinical complaint and patholof patientswith thisdiagnosis. ogy. They are relapsing and remitting and constitute a chronic Technical assessment of the efficacy of treatments should disease. Most patients can be diagnosed and managed in pricontinue, but usingastandardized modelofreporting. Review mary care. In many instances, management may entail little or of data of AK treatment illustrates the variety of end points in no medical treatment other than advice on sun avoidance and studies, which makes comparison between them difficult. self-monitoring. Where there is clinical concern or the patient These include percentage clearance of lesion number within a specifically wants treatment, therapy can be employed taking person, percentage of people within a study having complete into consideration the specifics of the situation. If there is clearance, percentage of target lesions clearing, and mathematdiagnostic concern or failure torespond tofirst-line treatment, ical models with projected AK behaviour based on withina histological specimen, such as obtained at curettage, shave study data. or formal excision, may be diagnostic and curative. Where The time points at which these measures are defined also AKs are multiple or confluent, at sites of poor healing or with vary and have the scope to alter the result greatly. Treatments poorresponsetostandardtherapies, PDTmay behelpful.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 18}, {"text": "which these measures are defined also AKs are multiple or confluent, at sites of poor healing or with vary and have the scope to alter the result greatly. Treatments poorresponsetostandardtherapies, PDTmay behelpful. Such have optimum times when their outcome is at its best, which patients may also warrant long-term follow-up for the assocican be up to 10 weeks after completion of treatment in the ated increased risk ofNMSC. case of imiquimod. Equally, in the setting of a chronic relapsing and remitting disease, 12and 24-month evaluation Acknowledgments points are relevant. As AK is a multifocal manifestation of sun damage, AKs within a zone at 12 months may represent a We are very grateful to everyone who commented on the mix of relapse and new lesions, which can further complicate draft duringtheconsultation period. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 18}, {"text": "38 Guidelinesforactinickeratosis2017, D.deBerkeretal. References 22 Dodson JM, DeSpain J, Hewett JE etal. Malignant potential of actinic keratoses and the controversy over treatment. A patient1 BellHK,OrmerodAD.WritingaBritishAssociationofDermatolorientedperspective.ArchDermatol1991;127:1029\u201331. ogists clinical guideline: an update on the process and guidance 23 Foote JA, Harris RB, Giuliano AR etal. Predictors for cutaneous forauthors.BrJDermatol2009;160:725\u20138. basaland squamous-cell carcinoma among actinically damaged 2 Brouwers MC, Kho ME, Browman GP etal. AGREE II: advancing adults.IntJCancer2001;95:7\u201311. guideline development, reporting and evaluation in health care. 24 Chen GJ, Feldman SR, Williford PM etal. Clinical diagnosis of CMAJ2010;182:E839\u201342. actinic keratosis identifies an elderly population at high risk of 3 Olsen EA, Abernethy ML, Kulp-Shorten C etal. A double-blind, developingskincancer.DermatolSurg2005;31:43\u20137. vehicle-controlled study evaluating masoprocol cream in the 25 LambertSR,MladkovaN,GulatiAetal.Keydifferencesidentified treatment of actinic keratoses on the head and neck. J Am Acad betweenactinickeratosisandcutaneoussquamouscellcarcinoma Dermatol1991;24:738\u201343. bytranscriptomeprofiling.BrJCancer2014;110:520\u20139. 4 Vatve M, Ortonne JP, Birch-Machin MA etal. Management of 26 Werner RN, Sammain A, Erdmann R etal. The natural history of field change in actinic keratosis. Br J Dermatol 2007; 157(Suppl. actinic keratosis: a systematic review. Br J Dermatol 2013; 2):21\u20134. 169:502\u201318. 5 Freeman RG. Carcinogenic effects of solar radiation and preven27 Janda M. Teledermatology: its use in the detection and managetionmeasures.Cancer1968;21:1114\u201320. mentofactinickeratosis.CurrProblDermatol2015;46:101\u20137. 6 Ziegler A, Jonason AS, Leffell DJ etal. Sunburn and p53 in the 28 Huerta-Brogeras M, Olmos O, Borbujo J etal. Validation of deronsetofskincancer.Nature1994;372:773\u20136. moscopyasareal-timenoninvasivediagnosticimagingtechnique 7 BarrBB,BentonEC,McLarenKetal.Papillomavirusinfectionand foractinickeratosis.ArchDermatol2012;148:1159\u201364. skincancerinrenalallograftrecipients.Lancet1989;2:224\u20135. 29 Scottish Intercollegiate Guidelines Network. Management of dia8 Baudouin C, Charveron M, Tarroux R etal. Environmental pollubetes:anationalclinicalguideline.Availableat:www.sign.ac.uk/ tantsandskincancer.CellBiolToxicol2002;18:341\u20138. pdf/sign116.pdf(lastaccessed16September2016). 9 Wong ST, Chan HL, Teo SK. The spectrum of cutaneous and 30 Shigaki C, Kruse RL, Mehr D etal. Motivation and diabetes selfinternal malignancies in chronic arsenic toxicity. Singapore Med J management.ChronicIlln2010;6:202\u201314. 1998;39:171\u20133. 31 Stockfleth E. The paradigm shift in treating actinic keratosis: a 10 Norris JF. Sunscreens, suntans, and skin cancer. Local councils comprehensivestrategy.JDrugsDermatol2012;11:1462\u20137. should remove sunbeds from leisure centres. BMJ 1996; 32 Gupta AK, Paquet M, Villanueva E etal. Interventions for actinic 313:941\u20132. keratoses.CochraneDatabaseSystRev2012;12:CD004415. 11 BajdikCD,GallagherRP,AstrakianakisGetal.Non-solarultravio33 Esmann S, Vinding GR, Christensen KB etal. Assessing the influlet radiationand the risk of basaland squamous cell skincancer. ence of actinic keratosis on patients\u2019 quality of life: the AKQoL BrJCancer1996;73:1612\u20134. questionnaire.BrJDermatol2013;168:277\u201383. 12 RoestMA,KeaneFM,AgnewKetal.Multiplesquamousskincar34 EsmannS.Patients\u2019perspectivesonactinickeratosis.CurrProblDercinomas following excess sunbed use. J R Soc Med 2001; 94:636\u2013 matol2015;46:8\u201313. 7. 35 PomerantzH,HoganD,EilersDetal.Long-termefficacyoftopi13 AtkinsD,BangRH,SternbergMRetal.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 19}, {"text": "skincancer. ence of actinic keratosis on patients\u2019 quality of life: the AKQoL BrJCancer1996;73:1612\u20134. questionnaire.BrJDermatol2013;168:277\u201383. 12 RoestMA,KeaneFM,AgnewKetal.Multiplesquamousskincar34 EsmannS.Patients\u2019perspectivesonactinickeratosis.CurrProblDercinomas following excess sunbed use. J R Soc Med 2001; 94:636\u2013 matol2015;46:8\u201313. 7. 35 PomerantzH,HoganD,EilersDetal.Long-termefficacyoftopi13 AtkinsD,BangRH,SternbergMRetal.Reliablemethodstoevalcal fluorouracil cream, 5%, for treating actinic keratosis: a ranuate the burden of actinic keratoses. J Invest Dermatol 2006; domizedclinicaltrial.JAMADermatol2015;151:952\u201360. 126:591\u20134. 36 Witheiler DD, Lawrence N, Cox SE etal. Long-term efficacy and 14 O\u2019Beirn SFO, Judge P, Maccon CF etal. Skin cancer in County safety of Jessner\u2019s solution and 35% trichloroacetic acid versus Galway, Ireland. In: Proceedings of the Sixth National Cancer Conference, 5% fluorouracilin the treatmentofwidespreadfacial actinickersponsoredbytheAmericanCancerSocietyInc.andtheNationalCancerInstitute, atoses.DermatolSurg1997;23:191\u20136. September1968.Philadelphia:Lippincott,1970;489\u2013500. 37 KaminakaC,YamamotoY,YoneiNetal.Phenolpeelsasanovelther15 Harvey I, Frankel S, Marks R etal. Non-melanoma skin cancer apeuticapproachforactinickeratosisandBowendisease:prospective and solar keratoses. I. Methods and descriptive results of the pilottrialwithassessmentofclinical,histologic,andimmunohistoSouthWalesSkinCancerStudy.BrJCancer1996;74:1302\u20137. chemicalcorrelations.JAmAcadDermatol2009;60:615\u201325. 16 Memon AA, Tomenson JA, Bothwell J etal. Prevalence of solar 38 Ditre CM. Treatment of actinic keratosis and photodamaged skin damageandactinickeratosisinaMerseysidepopulation.BrJDerwith 5-fluorouracil 5% cream and glycolic acid peels. Cosmet Dermatol2000;142:1154\u20139. matol2004;17:25\u20137. 17 Eder J, Prillinger K, Korn A etal. Prevalence of actinic keratosis 39 Swinehart JM. Salicylic acid ointment peeling of the hands and among dermatology outpatients in Austria. Br J Dermatol 2014; forearms.Effectivenonsurgicalremovalofpigmentedlesionsand 171:1415\u201321. actinicdamage.JDermatolSurgOncol1992;18:495\u20138. 18 Flohil SC, van der Leest RJ, Dowlatshahi EA etal. Prevalence of 40 Werner RN, Stockfleth E, Connolly SM etal. Evidenceand conactinickeratosisanditsriskfactorsinthegeneralpopulation:the sensus-based(S3)GuidelinesfortheTreatmentofActinicKeratoRotterdamStudy.JInvestDermatol2013;133:1971\u20138. sis \u2013 International League of Dermatological Societies in 19 Marks R, Foley P, Goodman G etal. Spontaneous remission of cooperation with the European Dermatology Forum \u2013 short versolarkeratoses:thecaseforconservativemanagement.BrJDermasion.JEurAcadDermatolVenereol2015;29:2069\u201379. tol1986;115:649\u201355. 41 National Institute for Health and Care Excellence. Improving 20 Criscione VD, Weinstock MA, Naylor MF etal. Actinic keratoses: outcomes for people with skin tumours including melanoma. naturalhistoryandriskofmalignanttransformationintheVeterAvailable at: https://www.nice.org.uk/guidance/csg8 (last ansAffairsTopicalTretinoinChemopreventionTrial.Cancer2009; accessed16September2016). 115:2523\u201330. 42 Chetty P, Choi F, Mitchell T. Primary care review of actinic ker21 Marks R, Rennie G, Selwood TS. Malignant transformation of atosis and its therapeutic options: a global perspective. Dermatol solarkeratosestosquamouscellcarcinoma.Lancet1988;1:795\u20137. Ther(Heidelb)2015;5:19\u201335. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 19}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 39 43 Englert C, Hughes B. A review of actinic keratosis for the nurse 62 Eaglstein WH, Weinstein GD, Frost P. Fluorouracil: mechanism practitioner: diagnosis, treatment, and clinical pearls. J Am Acad of action in human skin and actinic keratoses. I. Effect on DNA NursePract2012;24:290\u20136. synthesisinvivo.ArchDermatol1970;101:132\u20139. 44 Primary Care Dermatology Society. Actinic (solar) keratosis: pri63 Ingenol mebutate (Picato) for actinic keratosis. Med Lett Drugs Ther mary care treatment pathway. Available at: http://www.pcds.or2012;54:35\u20136. g.uk/ee/images/uploads/general/Actinic_%28Solar%29_Kerato64 StockflethE, KerlH, ZwingersT etal. Low-dose5-fluorouracilin sis_Primary_Care_Treatment_Pathway.pdf (last accessed 16 combination with salicylic acid as a new lesion-directed option September2016). to treat topically actinic keratoses: histological and clinical study 45 Primary Care Dermatology Society. Actinic keratosis (syn. solar results.BrJDermatol2011;165:1101\u20138. keratosis). Available at: http://www.pcds.org.uk/clinical-gui65 GuptaAK,PaquetM.Networkmeta-analysisoftheoutcome\u2018pardance/actinic-keratosis-syn.-solar-keratosis (last accessed 16 ticipant complete clearance\u2019 in non-immunosuppressed particiSeptember2016). pantsofeightinterventionsforactinickeratosis:afollow-upona 46 ThompsonSC,JolleyD,MarksR.Reductionofsolarkeratosesby Cochranereview.BrJDermatol2013;169:250\u20139. regularsunscreenuse.NEnglJMed1993;329:1147\u201351. 66 Kurwa HA, Yong-Gee SA, Seed PT etal. A randomized paired 47 Naylor MF, Boyd A, Smith DW etal. High sun protection factor comparison of photodynamic therapy and topical 5-fluorouracil sunscreens in the suppression of actinic neoplasia. Arch Dermatol in the treatment of actinic keratoses. J Am Acad Dermatol 1999; 1995;131:170\u20135. 41:414\u20138. 48 Green A, Williams G, Neale R etal. Daily sunscreen application 67 Robinson TA, Kligman AM. Treatment of solar keratoses of the and betacarotene supplementation in preventionof basal-celland extremities with retinoic acid and 5-fluorouracil. Br J Dermatol squamous-cell carcinomas of the skin: a randomised controlled 1975;92:703\u20136. trial.Lancet1999;354:723\u20139. 68 Pearlman DL. Weekly pulse dosing: effective and comfortable 49 Ulrich C, Jurgensen JS, Degen A etal. Prevention of non-melatopical 5-fluorouracil treatment of multiple facial actinic kernomaskincancerinorgantransplantpatientsbyregularuseofa atoses.JAmAcadDermatol1991;25:665\u20137. sunscreen:a24months,prospective,case\u2013controlstudy.BrJDer69 Epstein E. Does intermittent \u2018pulse\u2019 topical 5-fluorouracil therapy matol2009;161(Suppl.3):78\u201384. allow destruction of actinic keratoses without significant inflam50 Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transmation?JAmAcadDermatol1998;38:77\u201380. plantation.NEnglJMed2003;348:1681\u201391. 70 Jury CS, Ramraka-Jones VS, Gudi V etal. A randomized trial of 51 deGraafYG,KennedyC,WolterbeekRetal.Photodynamicthertopical5%5-fluorouracil(Efudixcream)inthetreatmentofactiapy does not prevent cutaneous squamous-cell carcinoma in nickeratosescomparingdailywithweeklytreatment.BrJDermatol organ-transplant recipients: results of a randomized-controlled 2005;153:808\u201310. trial.JInvestDermatol2006;126:569\u201374. 71 Schlaak M, Simon JC. Topical treatment of actinic keratoses with 52 HarwoodCA,MesherD,McGregorJMetal.Asurveillancemodel low-dose5-fluorouracilincombinationwithsalicylicacid\u2013pilot forskin cancer in organ transplant recipients: a 22-yearprospecstudy.JDtschDermatolGes2010;8:174\u20138. tive study in an ethnically diverse population. Am J Transplant 72 Stockfleth E, Zwingers T, Willers C. Recurrence rates and patient 2013;13:119\u201329. assessedoutcomesof0.5%5-fluorouracilincombinationwithsali53 Dragieva G, Hafner J, Dummer R etal. Topical photodynamic cylicacidtreatingactinickeratoses.EurJDermatol2012;22:370\u20134.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 20}, {"text": "recipients: a 22-yearprospecstudy.JDtschDermatolGes2010;8:174\u20138. tive study in an ethnically diverse population. Am J Transplant 72 Stockfleth E, Zwingers T, Willers C. Recurrence rates and patient 2013;13:119\u201329. assessedoutcomesof0.5%5-fluorouracilincombinationwithsali53 Dragieva G, Hafner J, Dummer R etal. Topical photodynamic cylicacidtreatingactinickeratoses.EurJDermatol2012;22:370\u20134. therapyin thetreatmentofactinickeratosesand Bowen\u2019sdisease 73 Szeimies RM, Dirschka T, Prechtl A etal. Efficacy of low-dose 5intransplantrecipients.Transplantation2004;77:115\u201321. fluorouracil/salicylic acid in actinic keratoses in relation to treat54 McNamara IR, Muir J, Galbraith AJ. Acitretin for prophylaxis of mentduration.JDtschDermatolGes2015;13:430\u20138. cutaneous malignancies after cardiac transplantation. J Heart Lung 74 Hadley G, Derry S, Moore RA. Imiquimod for actinic keratosis: Transplant2002;21:1201\u20135. systematic review and meta-analysis. J Invest Dermatol 2006; 55 Jirakulaporn T,EndrizziB, LindgrenBetal. Capecitabineforskin 126:1251\u20135. cancer prevention in solid organ transplant recipients. Clin Trans75 Stockfleth E, Meyer T, Benninghoff B etal. A randomized, douplant2011;25:541\u20138. ble-blind,vehicle-controlledstudytoassess5%imiquimodcream 56 Black HS, Herd JA, Goldberg LH etal. Effect of a low-fat diet on forthetreatmentofmultipleactinickeratoses.ArchDermatol2002; theincidenceofactinickeratosis.NEnglJMed1994;330:1272\u20135. 138:1498\u2013502. 57 RiversJK,ArletteJ,ShearNetal.Topicaltreatmentofactinicker76 Korman N, Moy R, Ling M etal. Dosing with 5% imiquimod atoseswith 3.0%diclofenacin 2.5%hyaluronangel.Br JDermatol cream 3 times per week for the treatment of actinic keratosis: 2002;146:94\u2013100. resultsoftwophase3,randomized,double-blind,parallel-group, 58 Akarsu S, Aktan S, Atahan A etal. Comparison of topical 3% vehicle-controlledtrials.ArchDermatol2005;141:467\u201373. diclofenac sodium gel and 5% imiquimod cream for the treat77 Alomar A, Bichel J, McRae S. Vehicle-controlled, randomized, mentofactinickeratoses.ClinExpDermatol2011;36:479\u201384. double-blindstudytoassesssafetyandefficacyofimiquimod5% 59 Szeimies RM, Gerritsen MJ, Gupta G etal. Imiquimod 5% cream creamappliedoncedaily3daysperweekinoneortwocourses for the treatment of actinic keratosis: results from a phase III, of treatment of actinic keratoses on the head. Br J Dermatol 2007; randomized, double-blind, vehicle-controlled, clinical trial with 157:133\u201341. histology.JAmAcadDermatol2004;51:547\u201355. 78 FoleyP,MerlinK,CummingSetal.Acomparisonofcryotherapy 60 Jorizzo J, Dinehart S, Matheson R etal. Vehicle-controlled, douand imiquimod for treatment of actinic keratoses: lesion clearble-blind, randomized study of imiquimod 5% cream applied ance, safety, and skin quality outcomes. J Drugs Dermatol 2011; 3days per week in one or two courses of treatment for actinic 10:1432\u20138. keratosesonthehead.JAmAcadDermatol2007;57:265\u20138. 79 Pini AM, Koch S, Scharer L etal. Eruptive keratoacanthoma fol61 DarlingtonS,WilliamsG,NealeRetal.Arandomizedcontrolledtrial lowing topical imiquimod for in situ squamous cell carcinoma of toassesssunscreenapplicationandbetacarotenesupplementationin the skin in a renal transplant recipient. J Am Acad Dermatol 2008; thepreventionofsolarkeratoses.ArchDermatol2003;139:451\u20135. 59(5Suppl.):S116\u20137. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 20}, {"text": "Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 20}, {"text": "40 Guidelinesforactinickeratosis2017, D.deBerkeretal. 80 Serra-GuillenC,NagoreE,HuesoLetal.Arandomizedcompara96 Anderson L, Melgaard A, Schmeider G etal. Two-day topical tivestudyoftoleranceandsatisfactioninthetreatmentofactinic treatment with ingenol mebutate gel, 0.05% for actinic keratoses keratosisofthefaceandscalpbetween5%imiquimodcreamand on the trunk and extremities: analysis of data pooled from two photodynamictherapywithmethylaminolaevulinate.BrJDermatol trials.JAmAcadDermatol2012;66:AB159. 2011;164:429\u201333. 97 US Food and Drug Administration. Picato (ingenol mebutate) 81 Krawtchenko N, Roewert-Huber J, Ulrich M etal. A randomised gel: drug safety communication \u2013 FDA warns of severe adverse studyoftopical5%imiquimodvs.topical5-fluorouracilvs.cryoevents,requireslabelchanges.Availableat:http://www.fda.gov/ surgery in immunocompetent patients with actinic keratoses: a Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicomparisonofclinicalandhistologicaloutcomesincluding1-year calProducts/ucm459311.htm(lastaccessed16September2016). follow-up.BrJDermatol2007;157(Suppl.2):34\u201340. 98 KuJ.Clinicalreview.NDA202833.PICATOTM(ingenolmebutate 82 LeePK,HarwellWB,LovenKHetal.Long-termclinicaloutcomes gel, PEP005 gel). Available at: http://www.accessdata.fda.- following treatment of actinic keratosis with imiquimod 5% gov/drugsatfda_docs/nda/2012/202833Orig1s000MedR.pdf cream.DermatolSurg2005;31:659\u201364. (lastaccessed16September2016). 83 HankeCW,BeerKR,StockflethEetal.Imiquimod2.5%and3.75% 99 Erlendsson AM, Karmisholt KE, Haak CS etal. Topical corticosforthetreatmentofactinickeratoses:resultsoftwoplacebo-conteroidhasnoinfluenceon inflammation or efficacyafteringenol trolledstudiesofdailyapplicationtothefaceandbaldingscalpfor mebutatetreatmentofgradeItoIIIactinickeratoses(AK):arantwo3-weekcycles.JAmAcadDermatol2010;62:573\u201381. domizedclinicaltrial.JAmAcadDermatol2016;74:709\u201315. 84 Hanke CW, Swanson N, Bruce S etal. Complete clearance is sus100 IanhezM,FleuryLFJr,MiotHAetal.Retinoidsforpreventionand tained for at least 12months after treatment of actinic keratoses treatmentofactinickeratosis.AnBrasDermatol2013;88:585\u201393. of the face or balding scalp via daily dosing with imiquimod 101 KangS, GoldfarbMT,Weiss JS etal.Assessmentofadapalenegel 3.75%or2.5%cream.JDrugsDermatol2011;10:165\u201370. for the treatment of actinic keratoses and lentigines: a random85 SwansonN,AbramovitsW,BermanBetal.Imiquimod2.5%and izedtrial.JAmAcadDermatol2003;49:83\u201390. 3.75% for the treatment of actinic keratoses: results of two pla102 WeinstockMA,BinghamSF,LewRAetal.Topicaltretinointhercebo-controlled studies of daily application to the face and baldapyandall-causemortality.ArchDermatol2009;145:18\u201324. ing scalp for two 2-week cycles. J Am Acad Dermatol 2010; 103 Thai KE, Fergin P, Freeman M etal. A prospective study of the 62:582\u201390. useofcryosurgeryforthetreatmentofactinickeratoses.IntJDer86 Jorizzo JL, Markowitz O, Lebwohl MG etal. A randomized, doumatol2004;43:687\u201392. ble-blinded, placebo-controlled, multicenter, efficacy and safety 104 Szeimies RM, Karrer S, Radakovic-Fijan S etal. Photodynamic study of 3.75% imiquimod cream following cryosurgery for the therapy using topical methyl 5-aminolevulinate compared with treatmentofactinickeratoses.JDrugsDermatol2010;9:1101\u20138. cryotherapy for actinic keratosis: a prospective, randomized 87 Goldenberg G, Linkner RV, Singer G etal. An investigatorstudy.JAmAcadDermatol2002;47:258\u201362. initiated study to assess the safety and efficacy of imiquimod 105 FreemanM,VinciulloC,FrancisDetal.Acomparisonofphotody3.75% cream when used after cryotherapy in the treatment of namictherapyusingtopicalmethylaminolevulinate(Metvix)with hypertrophic actinic keratoses on dorsal hands and forearms. J single cycle cryotherapy in patients with actinic keratosis: a ClinAesthetDermatol2013;6:36\u201343. prospective,randomizedstudy.JDermatologTreat2003;14:99\u2013106. 88 Smith SR, Morhenn VB, Piacquadio DJ. Bilateral comparison of 106 KaufmannR,SpelmanL,WeightmanWetal.Multicentreintrainthe efficacyandtolerabilityof3% diclofenacsodiumgeland 5% dividual randomized trial of topical methyl aminolaevulinate5-fluorouracil cream in the treatment of actinic keratoses of the photodynamic therapy vs. cryotherapy for multiple actinic kerfaceandscalp.JDrugsDermatol2006;5:156\u20139. atosesontheextremities.BrJDermatol2008;158:994\u20139. 89 Segatto MM, Dornelles SI, Silveira VB etal.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 21}, {"text": "of topical methyl aminolaevulinate5-fluorouracil cream in the treatment of actinic keratoses of the photodynamic therapy vs. cryotherapy for multiple actinic kerfaceandscalp.JDrugsDermatol2006;5:156\u20139. atosesontheextremities.BrJDermatol2008;158:994\u20139. 89 Segatto MM, Dornelles SI, Silveira VB etal. Comparative study of 107 Morton C, Campbell S, Gupta G etal. Intraindividual, right\u2013left actinickeratosistreatmentwith3%diclofenacsodiumand5%5comparison of topical methyl aminolaevulinate-photodynamic fluorouracil.AnBrasDermatol2013;88:732\u20138. therapyandcryotherapyinsubjectswithactinickeratoses:amul90 Wolf JE, Taylor JR, Tschen E etal. Topical 3.0% diclofenac in ticentre, randomized controlled study. Br J Dermatol 2006; 2.5% hyaluronan gel in the treatment of actinic keratoses. Int J 155:1029\u201336. Dermatol2001;40:709\u201313. 108 Chiarello SE. Cryopeeling (extensive cryosurgery) for treatment 91 Pflugfelder A, Welter AK, Leiter U etal. Open label randomized of actinic keratoses: an update and comparison. Dermatol Surg studycomparing3monthsvs.6monthstreatmentofactinicker2000;26:728\u201332. atoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of 109 AbadirDM.Combinationoftopical5-fluorouracilwithcryothertheGermanDermatologicCooperativeOncologyGroup.JEurAcad apy for treatment of actinic keratoses. J Dermatol Surg Oncol 1983; DermatolVenereol2012;26:48\u201353. 9:403\u20134. 92 Anderson L, Schmieder GJ, Werschler WP etal. Randomized, 110 JorizzoJ,WeissJ,FurstKetal.Effectofa1-weektreatmentwith double-blind,double-dummy,vehicle-controlledstudyofingenol 0.5% topical fluorouracil on occurrence of actinic keratosis after mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad cryosurgery: a randomized, vehicle-controlled clinical trial. Arch Dermatol2009;60:934\u201343. Dermatol2004;140:813\u20136. 93 Lebwohl M,SwansonN, AndersonLL etal. Ingenol mebutategel 111 MotleyR,KerseyP,LawrenceCetal.Multiprofessionalguidelines foractinickeratosis.NEnglJMed2012;366:1010\u20139. forthemanagementofthepatientwithprimarycutaneoussqua94 Lebwohl M, Shumack S, Stein Gold L etal. Long-term follow-up mouscellcarcinoma.BrJDermatol2002;146:18\u201325. study of ingenol mebutate gel for the treatment of actinic ker112 MoriartyM,DunnJ,DarraghAetal.Etretinateintreatmentofactiatoses.JAMADermatol2013;149:666\u201370. nickeratosis.Adouble-blindcrossoverstudy.Lancet1982;1:364\u20135. 95 Garbe C, Basset-Seguin N, Poulin Y etal. Efficacy and safety of 113 Watson AB. Preventative effect of etretinate therapy on multiple follow-upfieldtreatmentofactinickeratosiswithingenolmebuactinickeratoses.CancerDetectPrev1986;9:161\u20135. tate 0.015% gel: a randomized, controlled 12-month study. Br J 114 Smit JV, de Sevaux RG, Blokx WA etal. Acitretin treatment in Dermatol2016;174:505\u201313. (pre)malignant skin disorders of renal transplant recipients: BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 21}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 41 histologic and immunohistochemical effects. J Am Acad Dermatol 130 Scola N, Terras S, Georgas D etal. A randomized, half-side com2004;50:189\u201396. parativestudyofaminolaevulinatephotodynamictherapyvs.CO 2 115 EBPGExpertGrouponRenalTransplantation.Europeanbestpraclaserablationinimmunocompetentpatientswithmultipleactinic tice guidelines for renal transplantation. Section IV: long-term keratoses.BrJDermatol2012;167:1366\u201373. management of the transplant recipient. IV.6.2. Cancer risk after 131 Patel G, Armstrong AW, Eisen DB. Efficacy of photodynamic renal transplantation. Skin cancers: prevention and treatment. therapy versus other interventions in randomized clinical trials NephrolDialTransplant2002;17:S31\u20136. for the treatment of actinic keratoses: a systematic review and 116 Kovach BT, Murphy G, Otley CC etal. Oral retinoids for chemometa-analysis.JAMADermatol2014;150:1281\u20138. prevention of skin cancers in organ transplant recipients: results 132 Serra-Guillen C, Nagore E, Hueso L etal. A randomized pilot ofasurvey.TransplantProc2006;38:1366\u20138. comparative study of topical methyl aminolevulinate photody117 Elmets CA, Viner JL, Pentland AP etal. Chemoprevention of nonnamic therapy versus imiquimod 5% versus sequential applicamelanomaskincancerwithcelecoxib:arandomized,double-blind, tionofboththerapiesinimmunocompetentpatientswithactinic placebo-controlledtrial.JNatlCancerInst2010;102:1835\u201344. keratosis: clinical and histologic outcomes. J Am Acad Dermatol 118 LiebmanTN,SteinJA,PolskyD.Cyclo-oxygenase-2inhibitorsfor 2012;66:e131\u20137. chemoprevention of nonmelanoma skin cancer: is there a role 133 Hadley J, Tristani-Firouzi P, Hull C etal. Results of an investigafortheseagents?JAmAcadDermatol2013;68:173\u20136. tor-initiated single-blind split-face comparison of photodynamic 119 Dirschka T, Radny P, Dominicus R etal. Photodynamic therapy therapy and 5% imiquimod cream for the treatment of actinic withBF-200ALAforthetreatmentofactinickeratosis:resultsof keratoses.DermatolSurg2012;38:722\u20137. a multicentre, randomized, observer-blind phase III study in 134 Sotiriou E, Apalla Z, Maliamani F etal. Intraindividual, right-left comparison with a registered methyl-5-aminolaevulinate cream comparison of topical 5-aminolevulinic acid photodynamic therandplacebo.BrJDermatol2012;166:137\u201346. apy vs. 5% imiquimod cream for actinic keratoses on the upper 120 Szeimies RM, Radny P, Sebastian M etal. Photodynamic therapy extremities.JEurAcadDermatolVenereol2009;23:1061\u20135. withBF-200ALAforthetreatmentofactinickeratosis:resultsof 135 HauschildA,StockflethE,PoppGetal.Optimizationofphotodya prospective, randomized, double-blind, placebo-controlled namic therapy with a novel self-adhesive 5-aminolaevulinic acid phaseIIIstudy.BrJDermatol2010;163:386\u201394. patch:resultsoftworandomizedcontrolledphaseIIIstudies.BrJ 121 Morton CA, Szeimies RM, Sidoroff A etal. European guidelines Dermatol2009;160:1066\u201374. for topical photodynamic therapy part 1: treatment delivery and 136 Szeimies RM, Stockfleth E, Popp G etal. Long-term follow-up of currentindications\u2013actinickeratoses,Bowen\u2019sdisease,basalcell photodynamic therapy with a self-adhesive 5-aminolaevulinic carcinoma.JEurAcadDermatolVenereol2013;27:536\u201344. acidpatch:12monthsdata.BrJDermatol2010;162:410\u20134. 122 Klein A, Karrer S, Horner C etal. Comparing cold-air analgesia, 137 Wiegell SR, Haedersdal M, Philipsen PA etal. Continuous activasystemically administered analgesia and scalp nerve blocks for tion of PpIX by daylight is as effective as and less painful than pain management during photodynamic therapy for actinic kerconventional photodynamic therapy for actinic keratoses; a ranatosisofthescalppresentingasfieldcancerization:arandomized domized, controlled, single-blinded study.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 22}, {"text": "for tion of PpIX by daylight is as effective as and less painful than pain management during photodynamic therapy for actinic kerconventional photodynamic therapy for actinic keratoses; a ranatosisofthescalppresentingasfieldcancerization:arandomized domized, controlled, single-blinded study. Br J Dermatol 2008; controlledtrial.BrJDermatol2015;173:192\u2013200. 158:740\u20136. 123 Petersen B, Wiegell SR, Wulf HC. Light protection of the skin 138 Wiegell SR, Haedersdal M, Eriksen P etal. Photodynamic therapy after photodynamic therapy reduces inflammation: an unblinded of actinic keratoses with 8% and 16% methyl aminolaevulinate randomizedcontrolledstudy.BrJDermatol2014;171:175\u20138. andhome-baseddaylightexposure:adouble-blindedrandomized 124 Tarstedt M, Rosdahl I, Berne B etal. A randomized multicenter clinicaltrial.BrJDermatol2009;160:1308\u201314. study to compare two treatment regimens of topical methyl 139 Wiegell SR, Fabricius S, Stender IM etal. A randomized, multiaminolevulinate (Metvix(cid:1))-PDT in actinic keratosis of the face centre studyof directeddaylight exposure timesof 1\u00bd vs.2\u00bd h andscalp.ActaDermVenereol2005;85:424\u20138. in daylight-mediated photodynamic therapy with methyl amino125 Piacquadio DJ, Chen DM, Farber HF etal. Photodynamic therapy laevulinate in patients with multiple thin actinic keratoses of the withaminolevulinicacidtopicalsolutionandvisiblebluelightin faceandscalp.BrJDermatol2011;164:1083\u201390. the treatment of multiple actinic keratoses of the face and scalp: 140 Rubel DM, Spelman L, Murrell DF etal. Daylight photodynamic investigator-blinded, phase 3, multicenter trials. Arch Dermatol therapywithmethylaminolevulinatecreamasaconvenient,sim2004;140:41\u20136. ilarly effective, nearly painless alternative to conventional photo126 Taub AF, Garretson CB. A randomized, blinded, bilateral intraindynamic therapy in actinic keratosis treatment: a randomized dividual, vehicle-controlled trial of the use of photodynamic controlledtrial.BrJDermatol2014;171:1164\u201371. therapy with 5-aminolevulinic acid and blue light for the treat141 Lacour JP, Ulrich C, Gilaberte Y etal. Daylight photodynamic mentofactinickeratosesoftheupperextremities.JDrugsDermatol therapy with methyl aminolevulinate cream is effective and 2011;10:1049\u201356. nearly painless in treating actinic keratoses: a randomised, inves127 Tschen EH, Wong DS, Pariser DM etal. Photodynamic therapy tigator-blinded, controlled, phase III study throughout Europe. J using aminolaevulinic acid for patients with nonhyperkeratotic EurAcadDermatolVenereol2015;29:2342\u20138. actinic keratoses of the face and scalp: phase IV multicentre 142 Morton CA, Wulf HC, Szeimies RM etal. Practical approach to clinical trial with 12-month follow up. Br J Dermatol 2006; the use of daylight photodynamic therapy with topical methyl 155:1262\u20139. aminolevulinate for actinic keratosis: a European consensus. J Eur 128 SotiriouE,ApallaZ,ChovardaEetal.Singlevs.fractionatedphoAcadDermatolVenereol2015;29:1718\u201323. todynamictherapyforfaceandscalpactinickeratoses:arandom143 SeeJA,ShumackS,MurrellDFetal.Consensusrecommendations ized,intraindividualcomparisontrialwith12-monthfollow-up.J on the use of daylight photodynamic therapy with methyl EurAcadDermatolVenereol2012;26:36\u201340. aminolevulinatecreamforactinickeratosesin Australia.AustralasJ 129 Togsverd-Bo K, Haak CS, Thaysen-Petersen D etal. Intensified Dermatol2016;57:167\u201374. photodynamic therapy of actinic keratoses with fractional CO 144 Wiegell SR, Wulf HC, Szeimies RM etal.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 22}, {"text": "of daylight photodynamic therapy with methyl EurAcadDermatolVenereol2012;26:36\u201340. aminolevulinatecreamforactinickeratosesin Australia.AustralasJ 129 Togsverd-Bo K, Haak CS, Thaysen-Petersen D etal. Intensified Dermatol2016;57:167\u201374. photodynamic therapy of actinic keratoses with fractional CO 144 Wiegell SR, Wulf HC, Szeimies RM etal. Daylight photodynamic 2 laser:arandomizedclinicaltrial.BrJDermatol2012;166:1262\u20139. therapy for actinic keratosis: an international consensus: \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 2, "page": 22}, {"text": "42 Guidelinesforactinickeratosis2017, D.deBerkeretal. International Society for Photodynamic Therapy in Dermatology. 164 Cannon PS, O\u2019Donnell B, Huilgol SC etal. The ophthalmic sideJEurAcadDermatolVenereol2012;26:673\u20139. effects of imiquimod therapy in the management of periocular 145 Genovese G, Fai D, Fai C etal. Daylight methyl-aminolevulinate skinlesions.BrJOphthalmol2011;95:1682\u20135. photodynamictherapyversusingenolmebutateforthetreatment 165 Tallon B, Turnbull N. 5% Fluorouracil chemowraps in the manof actinic keratoses: an intraindividual comparative analysis. Deragement of widespread lower leg solar keratoses and squamous matolTher2016;29:191\u20136. cellcarcinoma.AustralasJDermatol2013;54:313\u20136. 146 de Vries K, Prens EP. Laser treatment and its implications for 166 Wallingford SC, Russell SA, Vail A etal. Actinic keratoses, actinic photodamagedskinand actinickeratosis.CurrProblDermatol2015; field change and associations with squamous cell carcinoma in 46:129\u201335. renal transplant recipients in Manchester, U.K. Acta Derm Venereol 147 Ostertag JU, Quaedvlieg PJ, van der Geer S etal. A clinical com2015;95:830\u20134. parison and long-term follow-up of topical 5-fluorouracil versus 167 InghamAI,WeightmanW.Theefficacyandsafetyoftopical5% laserresurfacinginthetreatmentofwidespreadactinickeratoses. 5-fluorouracil in renal transplant recipients for the treatment of LasersSurgMed2006;38:731\u20139. actinickeratoses.AustralasJDermatol2014;55:204\u20138. 148 Hantash BM, Stewart DB, Cooper ZA etal. Facial resurfacing for 168 Annemans L, Caekelbergh K, Roelandts R etal. Real-life practice nonmelanoma skin cancer prophylaxis. Arch Dermatol 2006; study of the clinical outcome and cost-effectiveness of photody142:976\u201382. namic therapy using methyl aminolevulinate (MAL-PDT) in the 149 SherrySD,MilesBA,FinnRA.Long-termefficacyofcarbondioxmanagement of actinic keratosis and basal cell carcinoma. Eur J idelaserresurfacingforfacialactinickeratosis.JOralMaxillofacSurg Dermatol2008;18:539\u201346. 2007;65:1135\u20139. 169 CaekelberghK,AnnemansL,LambertJetal.Economicevaluation 150 IyerS,FriedliA,BowesLetal.Fullfacelaserresurfacing:therapy of methyl aminolaevulinate-based photodynamic therapy in the and prophylaxis for actinic keratoses and non-melanoma skin management of actinic keratosis and basal cell carcinoma. Br J cancer.LasersSurgMed2004;34:114\u20139. Dermatol2006;155:784\u201390. 151 Ostertag JU, Quaedvlieg PJF, Neumann MHAM, Krekels GA. 170 Colombo GL, Chimenti S, Di Matteo S etal. Cost-effectiveness Recurrence rates and long-term follow-up after laser resurfacing analysis of topical treatments for actinic keratosis in the perspecasatreatmentforwidespreadactinickeratosesinthefaceandon tive of the Italian health care system. G Ital Dermatol Venereol 2010; thescalp.DermatolSurg2006;32:261\u20137. 145:573\u201381. 152 GanSD,HsuSH,ChuangGetal.Ablativefractionallasertherapy 171 GoldMH. Pharmacoeconomicanalysisofthe treatmentofmultiforthetreatmentofactinickeratosis:asplit-facestudy.JAmAcad pleactinickeratoses.JDrugsDermatol2008;7:23\u20135. Dermatol2016;74:387\u20139. 172 Wilson EC. Cost effectiveness of imiquimod 5% cream compared 153 Prens SP, de Vries K, Neumann HA etal. Non-ablative fractional with methyl aminolevulinate-based photodynamic therapy in the resurfacingincombinationwithtopicaltretinoincreamasafield treatment of non-hyperkeratotic, non-hypertrophic actinic (solar) treatment modality for multiple actinic keratosis: a pilot study keratoses: a decision tree model. Pharmacoeconomics 2010; 28:1055\u2013 and areview of other fieldtreatmentmodalities.J DermatologTreat 64. 2013;24:227\u201331. 173 MustonD,DownsA,RivesV.Aneconomicevaluationoftopical 154 ColemanWP,YarboroughJM,MandySH.Dermabrasionforprotreatments for actinic keratosis.", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 23}, {"text": "keratosis: a pilot study keratoses: a decision tree model. Pharmacoeconomics 2010; 28:1055\u2013 and areview of other fieldtreatmentmodalities.J DermatologTreat 64. 2013;24:227\u201331. 173 MustonD,DownsA,RivesV.Aneconomicevaluationoftopical 154 ColemanWP,YarboroughJM,MandySH.Dermabrasionforprotreatments for actinic keratosis. J Dermatolog Treat 2009; 20:266\u2013 phylaxis and treatment of actinic keratoses. Dermatol Surg 1996; 75. 22:17\u201321. 174 GibbsS,DavisT.Usageandpatientexperienceof5%fluorouracil 155 WintonGB,SalascheSJ.Dermabrasionofthescalpasatreatment cream.ClinExpDermatol2015;40:88. foractinicdamage.JAmAcadDermatol1986;14:661\u20138. 175 PereraE,McGuiganS,SinclairR.Costforthetreatmentofactinic 156 MastrolonardoM.Topicaldiclofenac3%gelpluscryotherapyfor keratosisontheriseinAustralia.F1000Res2014;3:184. treatmentofmultipleandrecurrentactinickeratoses.ClinExpDer176 Pariser DM, Lowe NJ, Stewart DM etal. Photodynamic therapy matol2009;34:33\u20135. with topical methyl aminolevulinate for actinic keratosis: results 157 BerlinJM,RigelDS.Diclofenacsodium3%gelinthetreatmentof of a prospective randomized multicenter trial. J Am Acad Dermatol actinickeratosespostcryosurgery.JDrugsDermatol2008;7:669\u201373. 2003;48:227\u201332. 158 VanderGeerS,KrekelsGA.Treatmentofactinickeratosesonthe 177 Colechin E, Sims A, Reay C etal. Ambulight photodynamic therdorsum of the hands: ALA-PDT versus diclofenac 3% gel folapy.Availableat:http://www.nice.org.uk/guidance/mtg6/doculowed by ALA-PDT. A placebo-controlled, double-blind, pilot ments/ambulight-photodynamic-therapy-for-the-treatment-ofstudy.JDermatologTreat2009;20:259\u201365. nonmelanoma-skin-cancer-external-assessment-centre-report2 159 Gilbert DJ. Treatmentof actinic keratoseswith sequential combi- (lastaccessed16September2016). nationof5-fluorouracilandphotodynamictherapy.JDrugsDerma178 Gov.uk. National tariff payment system 2014/15. Available at: tol2005;4:161\u20133. https://www.gov.uk/government/publications/national-tariff-pay160 ShaffelburgM.Treatmentofactinickeratoseswithsequentialuse ment-system-2014-to-2015.(lastaccessed16September2016). ofphotodynamictherapy;and imiquimod5% cream.JDrugs Der179 Personal Social Services Research Unit. Unit costs of health and matol2009;8:35\u20139. social care 2015. Available at: http://www.pssru.ac.uk/project161 HooverWD3rd,JorizzoJL,ClarkARetal.Efficacyofcryosurgery pages/unit-costs/2015(lastaccessed16September2016). and5-fluorouracilcream0.5%combinationtherapyforthetreatmentofactinickeratosis.Cutis2014;94:255\u20139. Supporting information 162 Tuppurainen K. Cryotherapy for eyelid and periocular basal cell carcinomas: outcome in 166 cases over an 8-year period. Graefes AdditionalSupportingInformationmaybefoundintheonline ArchClinExpOphthalmol1995;233:205\u20138. version ofthis articleat thepublisher\u2019s website: 163 Couch SM, Custer PL. Topical 5-fluorouracil for the treatment of periocular actinic keratosis and low-grade squamous malignancy. Appendix S1.Search strategy. OphthalPlastReconstrSurg2012;28:181\u20133. BritishJournalofDermatology(2017)176,pp20\u201343 \u00a92017BritishAssociationofDermatologists Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 23}, {"text": "Guidelinesforactinickeratosis2017, D.deBerkeretal. 43 Appendix 1 Levelsofevidence Levelofevidence Typeofevidence 1++ High-qualitymeta-analyses,systematicreviewsofRCTs,orRCTswithaverylowriskofbias 1+ Well-conductedmeta-analyses,systematicreviewsofRCTs,orRCTswithalowriskofbias 1(cid:3) Meta-analyses,systematicreviewsofRCTs,orRCTswithahighriskofbiasa 2++ High-qualitysystematicreviewsofcase\u2013controlorcohortstudies.High-qualitycase\u2013controlorcohortstudieswitha verylowriskofconfounding,biasorchanceandahighprobabilitythattherelationshipiscausal 2+ Well-conductedcase\u2013controlorcohortstudieswithalowriskofconfounding,biasorchance,andamoderateprobability thattherelationshipiscausal 2(cid:3) Case\u2013controlorcohortstudieswithahighriskofconfounding,biasorchanceandasignificantriskthattherelationship isnotcausala 3 Nonanalyticalstudies(forexamplecasereports,caseseries) 4 Expertopinion,formalconsensus RCT,randomizedcontrolledtrial.aStudieswithalevelofevidence\u2018(cid:3)\u2019shouldnotbeusedasabasisformakingarecommendation. Appendix 2 Strengthsofrecommendation Class Evidence A Atleastonemeta-analysis,systematicrevieworRCTratedas1++,anddirectlyapplicabletothetargetpopulation,or AsystematicreviewofRCTsorabodyofevidenceconsistingprincipallyofstudiesratedas1+,directlyapplicabletothetarget populationanddemonstratingoverallconsistencyofresults,or EvidencedrawnfromaNICEtechnologyappraisal B Abodyofevidenceincludingstudiesratedas2++,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistency ofresults,or Extrapolatedevidencefromstudiesratedas1++or1+ C Abodyofevidenceincludingstudiesratedas2+,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistency ofresults,or Extrapolatedevidencefromstudiesratedas2++ D Evidencelevel3or4,or Extrapolatedevidencefromstudiesratedas2+,or Formalconsensus D(GPP) Agoodpracticepoint(GPP)isarecommendationforbestpracticebasedontheexperienceoftheGuidelineDevelopmentGroup RCT,randomizedcontrolledtrial;NICE,NationalInstituteforHealthandCareExcellence. \u00a92017BritishAssociationofDermatologists BritishJournalofDermatology(2017)176,pp20\u201343 Downloaded from https://academic.oup.com/bjd/article/176/1/20/6747903 by guest on 05 February 2026", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 24}, {"text": "NO COMPROMISE, JUST CLEARANCE Bimzelx\u00ae (bimekizumab) offers the opportunity for complete, fast, and lasting skin clearance and proven PsA efficacy 1\u20137 51.5% 68.2% 75.9% 76.9% (n=222/431) 50.6% (n=238/349) (n=265/349) (N=52)\u2020 (n=135/267) and of biologic-na\u00efve of patients of patients of patients and TNFi-IR PsA patients with PsO achieved with PsO achieved with PsO achieved achieved ACR 50 at PASI 100 at Week 16 PASI 75 at Week 4 PASI 100 at 5 years3 Week 104/100, respectively\u20211,4\u20136 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 (vs 1.2% placebo [n=1/86], p<0.0001)*,**2 BIMZELX was well tolerated, the most frequently reported adverse reactions were: upper respiratory tract infections and oral candidiasis. Other common reported adverse reactions include tinea infections, ear infections, herpes simplex infections, oropharyngeal candidiasis, gastroenteritis, folliculitis, headache, rash, dermatitis, eczema, acne, injection site reactions, fatigue, and vulvovaginal mycotic infection (including vulvovaginal candidiasis).4 This promotional material has been created and funded by UCB Pharma Ltd and These data are from different clinical trials and cannot be directly compared. is intended for healthcare professionals in the UK. Co-primary endpoints PASI 90 and IGA 0/1 at Week 16 were met.**Secondary endpoints. \u2020N= mNRI, missing data BIMZELX is indicated for the treatment of: moderate to severe plaque PsO in adults were imputed with mNRI (patients with missing data following treatment discontinuation due to lack of efficacy who are candidates for systemic therapy; active PsA, alone or in combination or a TRAE were counted as non-responders; multiple imputation methodology was used for other missing data). with methotrexate, in adults who have had an inadequate response, or who have \u202143.9% (n=189/431), and 43.4% (n=116/267) of biologic-na\u00efve and TNFi-IR PsA patients achieved the primary been intolerant, to one or more DMARDs; active nr-axSpA with objective signs of endpoint of ACR 50 at Week 16 in BE OPTIMAL and BE COMPLETE, respectively (vs 10.0% [n=28/281] and 6.8% inflammation as indicated by elevated CRP and/or MRI, in adults who have responded [n=9/133] placebo, p<0.0001); 54.5% (n=235/431) and 51.7% (n=138/267) maintained it at Week 52 (NRI).", "source": "actinic keratosis guideline.pdf", "chunk_id": 0, "page": 25}, {"text": "in adults who have responded ACR 50, \u226550% response in the American College of Rheumatology criteria; AS, ankylosing spondylitis; CRP, inadequately or are intolerant to conventional therapy; and active moderate to severe C-reactive protein; DMARD, disease-modifying antirheumatic drug; HS, hidradenitis suppurativa; IGA, Investigator\u2019s HS (acne inversa) in adults with an inadequate response to conventional systemic HS Global Assessment; (m)NRI, (modified) non-responder imputation; MRI, magnetic resonance imaging; nrtherapy.4 axSpA, non-radiographic axial spondyloarthritis; NSAID, non-steroidal anti-inflammatory drug; PASI 75/90/100, Prescribing information for United Kingdom click here. \u226575/90/100% improvement from baseline in Psoriasis Area and Severity Index; PsA, psoriatic arthritis; PsD, psoriatic Please refer to the SmPC for further information. disease; PsO, psoriasis; TNFi-IR, tumour necrosis factor-\u03b1 inhibitor \u2013 inadequate responder; TRAE, treatmentrelated adverse event. References: 1. Gordon KB, et al. Lancet. 2021;397(10273):475\u2013486. 2. Blauvelt. 2025. AAD Presentation 62275. 3. Mease PJ, et al. Rheumatol Ther. 2024;11(5):1363\u20131382. 4. BIMZELX SmPC. 5. Ritchlin CT, et al. Ann Rheum Dis. 2023;82(11):1404\u20131414. 6. Coates LC, et al. RMD Open. 2024;10(1):e003855. 7. Strober B, et al. AAD 2024;oral \uf071This medicine is subject to additional monitoring. This will allow quick presentation. identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.mhra.gov.uk for the UK. Adverse events should also be reported to UCB Pharma Ltd at UCBCares.UK@UCB.com or 0800 2793177 for UK. GB-BK-2500315 | July 2025 UCB Biopharma SRL, 2025. All rights reserved.", "source": "actinic keratosis guideline.pdf", "chunk_id": 1, "page": 25}]
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