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6,301 | However, some experts suggest this treatment option for ado lescents who also have dysmenorrhea, acne, or contraceptive needs. Premenstrual dysphoric disorder (PMDD) is distinguished from other depressive disorders by its timing; mood symptoms are precipitated by ovulation, recur in the luteal phase, and disappear at the end of menstruation. It is distinguished from PMS by the severity and consequences of the affective symptoms. PMDD causes significant distress and functional impairment and may be accom panied by physical and behavioral symptoms (Table 159.8). It is a distinct, treatment responsive depressive disorder. PMDD occurs in 26 of menstruating females worldwide. Accurate diagnosis requires use of a menstrual calendar to prospectively document cyclic symptoms. Other mental health conditions such as depres sion and anxiety disorders may be exacerbated before or during menses, but symptoms will occur throughout the cycle. Selective serotonin reuptake inhibitors (SSRIs) are first line therapy for PMDD and severe PMS. In contrast to the treatment of depression, SSRIs can be rapidly effective for premenstrual symp toms and thus can be prescribed either continuously or intermit tently, beginning at ovulation (or whenever in the luteal phase symptoms begin) and ending when symptoms resolve. Adolescents can be prescribed the standard regimens used for adults, such as fluoxetine 20 mg PO daily. For adolescents who also need contra ception, the drospirenone 3 mg and ethinyl estradiol 0.02 mg com bination pill delivered for 24 days followed by 4 inactive days has been approved by the Food and Drug Administration for PMDD. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. Table 159.8 Criteria for Premenstrual Dysphoric Disorder A. In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve with a few days after the onset of menses, and become minimal or absent in the week post menses. B. One (or more) of the following symptoms must be present: 1. Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection). 2. Marked irritability or anger or increased interpersonal conflicts. 3. Marked depressed mood, feelings of hopelessness, or self deprecating thoughts. 4. Marked anxiety, tension, andor feelings of being keyed up or on edge. C. One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from criterion B. 1. Decreased interest in usual activities (e.g., work, school, friends, and hobbies). 2. Subjective difficulty in concentration. 3. Lethargy, easy fatigability, or marked lack of energy. 4. Marked change in appetite, overeating, or specific food cravings. 5. Hypersomnia or insomnia. 6. A sense of being overwhelmed or out of control. 7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of bloating, or weight gain. Note: The symptoms in criteria A C must have been met for most menstrual cycles that occurred in the preceding year. D. The symptoms are associated with clinically significant distress or interference with work, school, usual |
6,302 | social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home). E. The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (dysthymia), or a personality disorder (although it may co occur with any of these disorders). F. Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation.) G. The symptoms are not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism). From the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., pp. 171172. Copyright 2013. American Psychiatric Association. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 160 u Contraception 1217 The consequences of sexual activity, including unintended pregnancy (see Chapter 161) and sexually transmitted infections (STIs; Chapter 163), occur in adolescents at higher rates than in adults. Significant barriers, including access to confidential care, may delay an adoles cents ability to access reproductive healthcare until after initiation of sexual activity, and many may become pregnant andor acquire an STI during this interval. Early and appropriate counseling and education with adolescents, including direct discussion of the risks of unintended pregnancy and STI prevention, can help to mitigate these risks; adoles cents who plan sexual initiation are 75 more likely to use contracep tion at sexual debut. Therefore appropriate patient centered counseling and provision of contraception as warranted are an essential compo nent of comprehensive healthcare for adolescents. Female refers to cis female but theoretically would include all those with a uterus engaging in sexual behaviors that put them at risk for pregnancy. CONTRACEPTIVE EFFECTIVENESS To decrease rates of unintended pregnancy, the American Academy of Pediatrics (AAP) and American College of Obstetricians and Gyne cologists (ACOG) recommend that healthcare providers counsel about and ensure access to all contraceptive methods for their adolescent patients. Comparing typical effectiveness of contraceptive methods, Figure 160.1 illustrates a tiered system of contraceptive methods rang ing from more effective to least effective. These tiers are categorized by typical use failure rates, which reflect the effectiveness of a method for the average person who may not always use the method consistently or correctly (Table 160.1). For example, for oral contraceptive pills, the typical use failure rate is 7, whereas the perfect use failure rate is 1. Tier 1 methods, the most effective, include those with failure rates of 1 pregnancy per 100 women in a year of typical use, and reversible Tier 1 methods include intrauterine devices (IUDs) and implants. Tier 2 methods have failure rates of 4 7 pregnancies per 100 women in a year of typical use and include injectable contraception, oral contraceptive pills, contraceptive patches, |
6,303 | and the vaginal ring. Tier 3 methods have failure rates of 13 pregnancies per 100 women per year of typical use and include the male and female condom, the diaphragm, withdrawal, the sponge, fertility awarenessbased methods, and spermicides. 160.1 Contraceptive Use Mary E. Romano and Elizabeth M. Alderman SEXUAL ACTIVITY According to the 2021 Youth Risk Behavior Surveillance System, 30 of U.S. high school students had ever had sexual intercourse and approxi mately 22 reported being currently sexually active. These numbers have been decreasing since 2015. However, significant decreases noted from 2019 to 2021 may be attributable to the effect of the COVID pan demic on behaviors. Chapter 160 Contraception Mary E. Romano and Elizabeth M. Alderman Injectable: Get repeat injections on time After procedure follow healthcare providers instructions on when to resume sexual activity with no concerns or risk of pregnancy. IUDImplant: May depend on timing of insertion andor contraceptive use prior to insertion. Vasectomy: Please note that it would be highly unlikely for an adolescent to undergo vasectomy or tubal ligationocclusion, as these are mostly permanent methods of preventing pregnancy that require informed consent from the individual. Condoms, sponge, withdrawal, spermicides, diaphragm: Use correctly every time you have sex Fertility awarenessbased methods: Abstain or use condoms on fertile days. May utilize FDAapproved app (Natural Cycles) to better track ovulation. Pills: Take a pill each day Patch, ring: Keep in place, change on time Implant Vasectomy Tubal occlusion ligation IUD Injectable Pill Patch Ring Male Condom Fertility Awareness Based Methods Diaphragm Sponge Withdrawal Female Condom Spermicides Less effective More than 13 pregnancies per 100 women in 1 year TIER 3 47 pregnancies per 100 women in 1 year TIER 2 Less than 1 pregnancy per 100 women in 1 year TIER 1 More effective How to make your method most effective Fig. 160.1 Effectiveness of contraceptive methods. (Modified from Trussell J, Aiken ARA, Micks E, Guthrie K. Contraceptive efficacy, safety, and personal considerations. In: Hatcher RA, Nelson AL, Trussell J, et al., eds. Contraceptive Technology, 21st ed. New York: Ayer Company Publishers; 2018:102.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1218 Part XI u Adolescent Medicine Table 160.1 Efficacy of Contraceptives METHOD FAILURE RATE () SOME ADVANTAGES SOME ADVERSE EFFECTS AND DISADVANTAGESTYPICAL USE PERFECT USE Implant Convenience; long term contraception; efficacy not dependent on patient adherence; rapid return of fertility after removal Irregular bleeding; amenorrhea, insertion andor removal complicationsNexplanon 0.1 0.1 Intrauterine Devices (IUDs) Convenience; long term contraception; efficacy not dependent on patient adherence; rapid return of fertility after removal Rare uterine perforation; risk of infection with insertion ParaGard T380A 0.8 0.6 Effective for 10 yr; nonhormonal Irregularheavy bleeding and dysmenorrhea Mirena 0.1 0.1 Effective for 8 yr; decreased menstrual bleeding and improved symptoms of dysmenorrhea Irregular bleeding in first 3 6 mo, followed by amenorrhea; unpredictable suppression of ovulation and potential |
6,304 | ovulatory SE (ovarian cysts, PMS, dysmenorrhea) Liletta 0.1 0.1 Decreased menstrual bleeding and improved symptoms of dysmenorrhea Irregular bleeding in first 3 6 mo; unpredictable suppression of ovulation and potential ovulatory SE (ovarian cysts, PMS, dysmenorrhea) Kyleena 0.2 0.2 Smaller T frame and narrower insertion tube Irregular bleeding in first 3 6 mo; unpredictable suppression of ovulation and potential ovulatory SE (ovarian cysts, PMS, dysmenorrhea), unpredictable bleeding pattern for the duration of use Skyla 0.4 0.3 Smaller T frame and narrower insertion tube Irregular bleeding in first 3 6 mo; unpredictable suppression of ovulation and potential ovulatory SE (ovarian cysts, PMS, dysmenorrhea), unpredictable bleeding pattern for the duration of use Injectable Convenience of q3mo injections; same as progestin only oral contraceptives Delayed return to fertility, irregular bleeding, and amenorrhea; weight gain; decreased bone mineral density while receiving injections Depo Provera 4 0.2 Combination Oral Contraceptives 7 0.3 Protection against ovarian and endometrial cancer; suppresses ovulation, which can improve symptoms of PMS, PMDD, and dysmenorrhea; quick return to fertility upon discontinuation Increased rate of thromboembolism, which increases with age and in those with underlying risks for blood clots, nausea; headache; contraindicated with breastfeeding Progestin Only Oral Contraceptives 7 0.3 Safe in breastfeeding women and those with underlying risk of blood clots Irregular, unpredictable bleeding; must take at same time every day, unpredictable suppression of ovulation Transdermal Patch 7 0.3 Convenience of once weekly application; same benefits as combination oral contraceptives Application site reactions; detachment; increased estrogen exposure as compared with oral contraceptives Vaginal Ring 7 0.3 Convenience of once monthly application, benefits similar to combination oral contraceptive pills Discomfort of ring or with insertion; vaginal discharge Diaphragm with Spermicide 17 16 Low cost High failure rate; cervical irritation; there can be increased risk of urinary tract infection and toxic shock syndrome with improper and prolonged use; some require fitting by healthcare professional; may be difficult to obtain; available only by prescription Condoms Only Female 21 5 Protection against STIs; covers external genitalia; OTC High failure rate; difficult to insert; may be less appealing because of need to stop during sexual activity Male 13 2 Protection against STIs, OTC, male participation High failure rate; allergic reactions; may be less appealing because of need to stop during sexual activity; breakage possible Cervical Cap 1632 926 Effective for 48 hr; can be used for 2 yr High failure rate, cervical irritation, risk of toxic shock, limited sizes, requires prescription Withdrawal 20 4 No drugs or devices High failure rate Sponge 1427 920 OTC; low cost; no fitting required; provides 24 hr of protection High failure rate; contraindicated during menses; increased risk of toxic shock syndrome with improper and prolonged use Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 160 u Contraception 1219 Although U.S. teens and European teens have similar levels of sex ual activity and |
6,305 | ages of sexual debut, U.S. teens are less likely to use contraception and less likely to use the most effective methods. Teen pregnancy rates have been declining worldwidea result of delayed initiation of sexual activity and increased contraceptive use. Despite this decline, the United States still had the highest teen birthrate in the Western industrialized world as of 2020, with 16.7 live births per 1,000 females age 15 19 years (Fig. 160.2). This is 8 times higher than the teen birthrate in Switzerland, which has the lowest rate in Western Europe. As of 2020 the teenage pregnancy rate in the United States is 31 preg nancies per 1,000 women, with a rate of 13.61,000 in those 15 17 years and 56.91,000 in those 18 19 years. The majority of these pregnancies are unintended, and one in five births are a repeat birth, indicating an unmet need for reliable, effective contraception that teens will correctly and consistently use. USE OF CONTRACEPTION AMONG TEENS According to the 20172019 National Survey of Family Growth, 78 of females and 89 of males who had their first sexual intercourse before age 20 years used a contraceptive method at first intercourse. The method most used by teenage females is the condom, followed by withdrawal (both least effective methods) and then the pill (a moder ately effective method). IUDs and implants, the most effective revers ible methods, are used by 20 of females 15 19 years, with the implant being more commonly used (15). Use of contraception at first sex has greatly increased over the last 50 years. Factors associated with contra ceptive use at first sex include increasing age among teens up to age 17 years, time spent in college, and planning their sexual debut. More than half of sexually experienced female teens are currently using the most effective reversible contraceptives or moderately effec tive contraceptive methods. U.S. teens use of hormonal methods at last intercourse is less frequent compared with teens in other developed countries. A higher likelihood of female current contraceptive use is associated with older age at sexual initiation, aspirations for higher academic achievement, acceptance of ones own sexual activity, and a positive attitude toward contraception. Despite the importance of dual method use to protect against both unwanted pregnancy and STIs, only 33 of sexually active female U.S. teens report using a barrier method (condoms) plus another method of contraception at last sexual activity. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.2 Contraceptive Counseling Mary E. Romano and Elizabeth M. Alderman The adolescent preventive health visit offers opportunities for confi dential discussions with all adolescents and the opportunity to identify and discuss sexual practices that may be putting the adolescent at risk for STIs or unintended pregnancy. It is also a time to discuss safe sexual behaviors, including abstinence (see Chapter 151). It is important to ask specifically about adolescents sexual behaviors to make sure your counseling is appropriate for their sexual activity. Adolescents with medical conditions, either chronic or acute, are particularly |
6,306 | vulner able to having sexual and reproductive health omitted from their visits, although they have similar sexual health and contraceptive needs (see Chapter 756). Their comorbidities or concurrent medication use may make STIs and unintended pregnancy an increased health risk and may affect contraceptive counselingoptions. The U.S. Medical Eligi bility Criteria for Contraceptive Use (MEC) outlines medical con ditions associated with increased risk for adverse health events with pregnancy and provides recommendations for who can safely use spe cific contraceptive methods. The goals of adolescent contraceptive counseling are to (1) under stand adolescent experiences, preferences, perceptions, and mispercep tions about pregnancy and use of contraceptives; (2) help adolescents understand the risks of unprotected sexual intercourse, including STIs and unintended pregnancy; (3) educate adolescents about the vari ous contraceptive methods available using information that is medi cally accurate, balanced, and provided in a nonjudgmental manner; and (4) engage in patient centered counseling so the adolescent feels empowered to choose a safe and effective method that can either be Table 160.1 Efficacy of Contraceptivescontd METHOD FAILURE RATE () SOME ADVANTAGES SOME ADVERSE EFFECTS AND DISADVANTAGESTYPICAL USE PERFECT USE Fertility Awareness Based Methods 15 Low cost; no drugs or devices High failure rate; can be difficult to use properly if periodsovulation are not well establishedregular, requires periods of abstinence Spermicide Available OTC High failure rate; local irritation; must be reapplied with repeat intercourse; unknown effect on HIV transmission, cost Nonoxynol 9 21 16 Phexxi 14 5 Microbicidal effect, increased viscosity as compared to other spermicides Requires a prescription, local irritation; must be reapplied with repeat intercourse; cannot be used with vaginal ring, costinsurance coverage No Method 85 85 Risk of unintended pregnancy during first year of use; data from Trussel J et al: In: Hatcher RA, Nelson AL, Trussell J, et al., eds. Contraceptive Technology, 21st ed. New York: Ayer Company Publishers; 2018. STIs, Sexually transmitted infections; OTC, over the counter; N 9, Nonoxynol 9. Adapted from Choice of contraceptives. Med Lett 2018;60(1557):161. Switzerland Netherlands Denmark Finland Germany Greece Canada Australia United States 0 5 10 15 Fig. 160.2 Teen birthrates in high income countries, 2020. Live births per 1,000 females age 15 19 yr. (Data from The World Bank Group. United Nations Population Division, World Population Prospects. https: data.worldbank.orgindicatorSP.ADO.TFRT.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1220 Part XI u Adolescent Medicine provided on site or be easily obtained through prescription or by refer ral. If adolescents are comfortable and willing to include their parents in this discussion, it is also always helpful to engage parents in the decision making process and address any parental questions and con cerns. Providers should be aware of state laws affecting confidentiality and an adolescents ability to access confidential contraceptive services (see Chapter 151). Most states allow adolescents confidential access to contraceptive services, but given that many adolescents are |
6,307 | under their parents insurance plan, confidentiality may be unintentionally breached through billing and explanation of benefit statements, as well as through the open notes mandate. This should be discussed with adolescents, especially those who are very concerned about disclosing sexual health information to their parents or guardians. Counseling should include a review of all contraceptive methods available that the adolescent can use safely (see U.S. MEC). Long acting reversible contraception (LARCIUDs and implants) is a safe and effective option for many adolescents, including those who have not been pregnant or given birth. The adolescent should be counseled about method effectiveness using typical use failure rates. Although it is important to highlight the methods most effective at preventing pregnancy, it is also imperative to provide contraceptive counseling within the framework of reproductive justice and to avoid any coercion due to provider preference or bias. The focus of contraceptive counsel ing should be on the priorities of the adolescent, and the adolescent should be allowed to explore all options and determine which method is most appropriate for their contraceptive needs and priorities. It is important to ask about use of withdrawal and discuss its risks given that 60 of female teens have used it for contraception and it has a typical use failure rate of 20. Abstinence should also be discussed as an option even if teens have engaged in sexual intercourse in the past. Abstinence may be the best option if adolescents do not have another method available at a particular time. Necessary concepts to address while discussing individual meth ods include how effective the method is, how long the method works, what behaviors are required for correct and consistent use, what side effects may be seen, any noncontraceptive benefits of the method (e.g., reduced menstrual bleeding, protection from STIs), and what signs or symptoms of complications should prompt a return visit. Review ing common side effects allows teens to anticipate and cope with any changes with reassurance and may avoid method discontinuation. Weighing the possibility of certain side effects with the possibility of an unintended pregnancy may also help with the conversation. It is also important to address any specific misperceptions teens may have for certain contraceptives regarding side effects, effectiveness, or effect on future fertility. Once an adolescent chooses a method, the provider and adolescent should discuss clear plans on correct and consistent use of the chosen method and strategies for appropriate follow up (see Table 160.1). Pro viders should help the adolescent consider potential barriers to cor rect and consistent use (e.g., forgetting to take a pill daily) and develop strategies to deal with each barrier (e.g., use of reminder systems such as daily text messages or phone alarms). The provider should assess whether the teen understood the information discussed and may con firm by asking the teen to repeat back key concepts. The U.S. Selected Practice Recommendations for Contraceptive Use provides guidance for providers regarding when to start contraception, how to be certain the woman is not |
6,308 | pregnant at contraception initia tion, and what examinations and tests are recommended before initiat ing contraception. Generally, women may start a contraceptive method other than an IUD at any time, and an IUD may be placed when a provider is reasonably certain that a woman is not pregnant. The Cen ters for Disease Control and Prevention (CDC) defines this as a patient who has no symptoms or signs of pregnancy, is 7 days after the start of normal menses, has not had sexual intercourse since the start of last normal menses, and has been correctly and consistently using a reliable method of contraception Most women do not require any special exam or additional screen ing for STIs before initiating contraception if they have been recently screened according to the CDCs STI treatment guidelines. A blood pressure reading is advisable. A pelvic examination is only required for placement of an IUD, unless otherwise indicated. STI screening is appropriate at andor before IUD placement, even if a patient does not report sexual activity, as some patients may choose to not disclose this information to their provider. Gonorrhea and chlamydia screen ing using a self or provider collected vaginal swab or urine sample is recommended unless symptoms require a pelvic exam. IUD placement should not be delayed to receive screening results. Cervical cancer screening is not recommended until age 21. Providers should offer confidential services to adolescents and observe all relevant state laws and legal obligations (e.g., notification or reporting of sexual abuse). Chapter 151 discusses confidentiality and consent issues related to contraceptive management. Providers should also encourage adolescents to involve parents or guardians in their healthcare decisions, while giving parents clear information on their teens right to confidentiality, privacy, and informed consent. All services should be provided in a youth friendly manner, meaning that they are accessible, equitable, acceptable, appropriate, comprehensive, effective, and efficient. Resources are available that describe ways to ensure a teen friendly reproductive health visit. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.3 Long Acting Reversible Contraception Mary E. Romano and Elizabeth M. Alderman Long acting reversible contraception (LARC) includes four levonorg estrel (LNG) IUDs, the copper (Cu) IUD, and the etonogestrel sub dermal implant. LARC methods are the only Tier 1 methods that are reversible (see Fig. 160.1). Their efficacy is the result of the fact that LARC does not require frequent office or pharmacy visits and does not depend on user adherence for effectiveness. In the Contraceptive CHOICE Project in St. Louis, Missouri, 9,000 women were given the contraceptive method of their choice at no cost and were followed for 2 3 years. The failure rates among women of all ages, including ado lescents who used oral contraceptive pills, transdermal patch, or vagi nal ring, were 20 times higher than the failure rates for those using a LARC method. Acceptance, continuation, and satisfaction in this proj ect were also higher among adolescents using LARC compared with adolescents using non LARC methods. ACOG and AAP support the use |
6,309 | of LARC methods for adolescents. The U.S. MEC supports safe use of both IUDs and implants for adolescents and nulliparous women. Implants are considered Category 1 for all ages, and IUDs are consid ered Category 2 for women 20 years old and for nulliparous women (Table 160.2). INTRAUTERINE DEVICES IUDs are small, flexible, plastic objects introduced into the uterine cav ity through the cervix. They differ in size, shape, presence or absence of hormone, and dose of hormone delivered daily. In the United States, five IUDs are currently approved by the Food and Drug Administra tion (FDA): the CuT380A (Paragard) and four LNG IUDs (Liletta, Kyleena, Mirena, and Skyla). The LNG IUDs also have various actions, from thickening of cervical mucus and inhibiting sperm survival to suppressing the endometrium. LNG IUDs are effective and approved for use from 3 to 8 years. The Cu IUD releases copper ions into the uterine cavity, which induces an inflammatory response within the endometrium. Copper also impairs sperm motilitymigration, inhibits the acrosomal reaction, and impairs implantation. As with the other IUDs, the Cu IUD is reversible, safe for use in nulliparous women, and effective for at least 10 years. All IUDs have typical use failure rates of 1 (see Fig. 160.1). All LARC meth ods are appropriate and safe to use in the postpartum period. Mirena is FDA approved for the treatment of heavy menstrual bleeding, and studies in adults have demonstrated an 80 reduction in menstrual blood loss in Mirena users, with 50 of users report ing amenorrhea after 2 years of use. Among the other LNG IUDs, Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 160 u Contraception 1221 amenorrhea at 2 years is reported at 26 for Liletta users, and Kyleena and Skyla report prolonged and irregular bleeding at 1 year in 520 of users. Heavier bleeding patterns and increased dysmenorrhea are reported in users of the Cu IUD. Patients should be counseled on bleeding patterns and expected changes to their menstrual bleeding after IUD insertion (Table 160.3). Common misconceptions of IUDs among healthcare providers are that IUDs can cause or increase the risks of infections, cause infertility, and generally are not safe or tolerated by teens or nulliparous women; these misconceptions can be a barrier for teens desiring an IUD to access these highly effective and safe methods. IUDs do not increase risk of infertility and may be inserted safely in teenagers regardless of parity (Category 2; see Table 160.2). Although early studies suggested an increased risk for upper genital tract infection, because of the passing of a foreign body through the cervix, new studies have refuted these concerns. Therefore clinicians are encouraged to consider the use of IUDs in adolescents despite rela tively high prevalence rates of STIs in this population. Teens should be screened for gonorrhea and chlamydia at andor before |
6,310 | IUD place ment, although placement should not be delayed if results have not returned and there are no signs of current infection (e.g., purulent dis charge, erythematous cervix). If STI testing is positive with an IUD in place, the patient may be treated without removing the IUD if she wants to continue the method. There has been evidence that rates of IUD expulsion are higher in adolescents as compared to older women. The data are limited, but the risk seems to be higher with Cu IUD vs hormonal IUD, previous IUD expulsion, and concomitant use of the menstrual cup. A paracervical block with lidocaine may reduce patient discomfort during placement and, along with other medications (e.g., NSAIDs, anxiolytics), may be considered on an individual patient basis, but these are not routinely recommended. IMPLANTS One contraceptive implant is available in the United States. The single rod that releases 60 gday of etonogestrel has been updated to a radi opaque rod with a new inserter. This progestin only method keeps etonogestrel at steady serum levels for at least 3 years and primar ily works to inhibit ovulation. Similar to the levonorgestrel IUD, the progestin acts on the uterus to cause an atrophic endometrium and thicken cervical mucus to block sperm penetration; its typical use fail ure rate is also 1 (see Fig. 160.1). Unlike the IUD, no pelvic exam is required for insertion. A trained provider can quickly place or remove the implant in the upper arm under local anesthesia. The most com mon side effect of the contraceptive implant is irregular and unsched uledunpredictable bleeding. This can include irregular or infrequent bleeding, amenorrhea, and less often, prolonged or frequent bleeding. Although the continuation rates are favorable and comparable to the IUD, the most common reason for discontinuation is dissatisfaction with bleeding patterns. It is important that adolescents be appropriately counseled on the potential for changes to their bleeding pattern before insertion of the implant. Adolescents who present with troublesome bleeding should be evaluated for any underlying gynecologic abnor malities, bleeding or blotting disorders, and the presence of an STI. If these are not present and adolescents desire treatment, they can be treated with a short course of NSAIDs (5 7 days) or low dose com bined oral contraceptives (COCs) if no contraindications to estrogen exist (10 20 days). Any and all adolescents desiring implant removal because of side effects should be offered prompt removal as indicated. One potential unique complication of this method relates to local ized infection and other side effects after implantation, such as bleed ing, hematoma, or scarring, and if inserted too deeply into the muscle, neural damage or migration; however, these events are rare, occurring in 1 of patients. Minor side effects, such as bruising or skin irrita tion, are more common but most often resolve without treatment. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.4 Other Progestin Only Methods Mary E. Romano and Elizabeth M. Alderman Several progestin only contraceptive methods are available and include the |
6,311 | LNG IUDs and implant (see Chapter 160.3), as well as an injectable and progestin only pills. These methods do not contain estrogen and may be useful for teens with contraindications to estrogen use or in Table 160.2 Categories of Medical Eligibility Criteria for Contraceptive Use Category 1: A condition for which there is no restriction for the use of the contraceptive method Category 2: A condition for which the advantages of using the method generally outweigh the theoretical or proven risks Category 3: A condition for which the theoretical or proven risks usually outweigh the advantages of using the method Category 4: A condition that represents an unacceptable health risk if the contraceptive method is used Table 160.3 Conditions Classified as Category 3 and 4 for Combined Hormonal Contraceptive Use Category 4 (a condition that represents an unacceptable health risk if the contraceptive method is used) Complicated valvular heart disease Current breast cancer Severe decompensated cirrhosis Deep venous thrombosispulmonary embolism (acute; history, not on anticoagulation or on established therapy for at least 3 mo with higher risk recurrence; major surgery with prolonged immobilization) Complicated diabetes with nephropathy, retinopathy, neuropathy, or other vascular disease or duration of diabetes 20 yr Migraine with aura Poorly controlled hypertension (blood pressure 160100 mm Hg) or hypertension with vascular disease Ischemic heart disease (history of or current) Hepatocellular adenoma Malignant liver tumor Peripartum cardiomyopathy (diagnosed 6 mo before or with moderately or severely impaired cardiac function) Postpartum 21 days History of cerebrovascular accident Systemic lupus erythematosus with positive antiphospholipid antibodies Thrombogenic pathogenic variants Viral hepatitis (acute or flare) Category 3 (a condition for which the theoretical or proven risks usually outweigh the advantages of using the method) Past breast cancer with no evidence of disease for 5 yr Breastfeeding and 1 mo postpartum Deep venous thrombosispulmonary embolism (history of DVTPE with lower risk recurrence) Gallbladder disease (current, medically treated) History of malabsorptive bariatric surgery History of cholestasis and past combined oral contraceptiverelated Hypertension (adequately controlled or blood pressure 160100 mm Hg) Peripartum cardiomyopathy with mild impairment or 6 mo Postpartum 21 42 days with other risk factors for venous thromboembolism Drug interactions (ritonavir boosted protease inhibitors; certain anticonvulsants; rifampin or rifabutin) First degree family member with a history of a blood clotclotting disorderthromboembolic event From Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. medical eligibility criteria for contraceptive use, 2016, MMWR Recomm Rep 2016;65(RR 3):1104. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1222 Part XI u Adolescent Medicine patients who prefer a method without estrogen such as gender diverse adolescents and young adults (Table 160.4). They are considered safe for use in teens (Category 1 or 2; see Table 160.2). Progestins thicken cervical mucus to block sperm entry into the uterine cavity and induce an atrophic endometrium leading to either amenorrhea or less men strual blood loss; |
6,312 | the implant and injectable also suppress ovulation, whereas the progestin only pills and LNG IUDs may affect the fre quency of ovulation but do not suppress it completely. Teens should be provided anticipatory counseling regarding bleeding irregularities that may normally occur in the first 3 6 months of any hormonal con traception use. DEPO PROVERA An injectable progestin, depot medroxyprogesterone acetate (DMPA, Depo Provera) is a Tier 2 contraceptive method available as a deep intramuscular (IM) injection (150 mg) or as a subcutaneous (SC) injection (104 mg) with typical use failure rates of 4 (see Table 160.1). Both preparations must be readministered every 3 months (13 weeks). When appropriate, DMPA can be given up to 3 weeks before or 7 days after the 13 weeks scheduled interval without any effect on contracep tive efficacy. DMPA works by inhibiting ovulation and thickening cer vical mucus. DMPA may be preferred by patients or parents who are caring for a child with intellectual disabilities. Common concerns with DMPA include bleeding changes, bone effects, and weight gain. After 1 year of use, 50 of DMPA users develop amenorrhea, which may be an added advantage for teens with heavy menstrual bleeding, dysmen orrhea, anemias, or blood dyscrasias. It may also be advantageous for those desiring menstrual suppression because of physical or develop mental disabilities that make hygiene difficult or those in whom men struation causes gender dysphoria. Studies have demonstrated bone mineral density (BMD) loss in adolescents with DMPA use, but this has not been shown to directly increase fracture risk. It is unclear how this decrease in BMD affects the risk for osteoporosis later in life. Other studies have found that BMD is recovered after discontinuation of this method, and it is thus considered safe for use in this population with appropriate counseling and consideration of other risk factors for bone health. Healthcare providers should speak at length with teens and par ents, when appropriate, who are already at high risk for low BMD, such as those receiving chronic corticosteroid therapy or those with eating disorders (see Chapter 749). They should discuss and decide together if DMPA is an appropriate contraceptive choice. Patients and provid ers need to balance the potential bone effects of DMPA with the bone effects that can occur with a teenage pregnancy. Although the FDA issued a black box warning in 2004 because of Depos BMD effects, the AAP and ACOG do not recommend limiting duration of DMPA use and do not recommend routine BMD screening for females using it. Early weight gain may be predictive of progressive gain over time; thus those teens gaining weight in the first 3 6 months after the initiation of DMPA should be monitored and continue to engage in discussions about healthy eating and exercise habits. PROGESTIN ONLY PILLS Progestin only oral contraceptive pills (POPs) are available and safe for use in adolescents. POPs (mini pills) are quickly effective after 2 days of initiation in thickening cervical mucus, but do not reliably inhibit ovulation. |
6,313 | Prior to 2019, the only progestin pill available in the United States contained 0.35 mg of norethindrone. Norethindrone has a short half life, and it is important that this pill is taken at the same time every day, which can make adherence difficult. If a pill is 3 hours late from normal time, an unintended pregnancy may occur. POPs have a typical use failure rate of 7 (see Table 160.1). Noreth indrone POPs are taken continuously, and as a result, the bleeding pattern is variableranging from amenorrhea to irregular and unpre dictable breakthrough bleeding. Acceptance by adolescents is limited by the necessity of taking the pill at the same time daily, and bleeding irregularities In 2019 the FDA approved a new POPSlyndwhich contains 4 mg of drospirenone. This is higher than the dose found in COCs. Dro spirenone is an analog of spironolactone with a longer half life of 25 30 hours, which allows for more flexibility with timing of pills. It also has some antimineralocorticoid activity and therefore should be used with caution in those who may take other medications or have medical comorbidities that can put them at risk for hyperkalemia. Slynd comes in a 28 day pill pack with four inactive pills intended to cause a sched uled withdrawal bleed. Slynd primarily suppresses ovulation. Studies have demonstrated its safety and efficacy along with high rates of sat isfaction among users (85). There may still be unscheduled bleed ing, but it seems to be more favorable than what is experienced with norethindrone use. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.5 Combined Hormonal Contraceptives Mary E. Romano and Elizabeth M. Alderman Combined hormonal contraceptives (CHCs) are methods that include an estrogen in combination with a progestin that has progestational, estrogenic, and androgenic properties. Methods available in the United States include several formulations of COCs, a transdermal patch, and a vaginal ring. The major mechanism of action of the estrogen progestin combination is to prevent the surge of luteinizing hormone and thereby inhibit ovulation. Additional effects to the reproductive tract include thickening of the cervical mucus, which prevents sperm penetration, and thinning of the endometrial lining, which may decrease menstrual blood loss. Typical use failure rates for all CHCs are the same at 7. The COCs, patch, and vaginal ring are classified together as CHCs in the U.S. MEC for Contraceptive Use, and recommendations mostly consider estrogen exposure for a given condition or characteristic (see Tables 160.3 and 160.4). Thromboembolic events such as venous thromboembolism (VTE), pulmonary embolism, or stroke are some of the more serious potential complications of exogenous estrogen use. These serious adverse events are exceedingly rare in adolescents who do not have other risk factors for thromboembolic events. Although the risk of blood clots is increased in those who smoke cigarettes, the likelihood of its occurrence is very small in adolescents, and thus clini cally insignificant, compared to the risk of morbidity and mortality from other pregnancy related complications, including blood clots Table 160.4 Hormonal Intrauterine |
6,314 | Devices MIRENA KYLEENA LILETTA SKYLA Duration of use FDA approved 8 yr FDA approved 5 yr FDA approved 8 yr FDA approved 3 yr Daily hormone delivery over time 20 mcg LNGday 9 mcg day (52 mcg total) 17.5 mcg LNGday 7.4 mcgday (19.5 mcg total) 19.5 mcg LNGday 9.8 mcgday (52 mcg total) 14 mcg LNGday 5 mcg day (13.5 mcg total) Device size 32 mm 32 mm 28 mm 30 mm 32 mm 32 mm 28 mm 30 mm Diameter of insertion rod 4.4 mm 3.8 mm diameter 4.4 mm diameter 3.8 mm diameter FDA, Food and Drug Administration; LNG, levonorgestrel. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 160 u Contraception 1223 associated with the high estrogen levels that occur during pregnancy and in the postpartum period. COMBINED ORAL CONTRACEPTIVES Oral contraceptive pills (OCs) can be either COCs or POPs and are commonly referred to as the pill. The pill is one of the most common contraceptive methods used among women of all ages. To decrease risk of pregnancy and increase continuation, providers are encouraged to provide OCs at the time of patient presentation to start immediately rather than waiting for next menses, as long as the provider is reason ably sure that the patient is not pregnant. Providers are also encour aged to provide up to 13 pill packs at a time, based on evidence that more pill packs provided is associated with higher continuation rates. However, it is important to see an adolescent in follow up once starting contraception to discuss adherence and satisfaction with the method selected. Advanced provision of emergency contraceptive pills is also recommended should patients miss pills and have unprotected sex. The effectiveness of COCs depends on adherence, and it can be difficult for any patient to remember to take a pill each day. Figures 160.3 and 160.4 list the rules for missed pills or after vomiting or diarrhea. COCs contain between 50 g and 10 g of an estrogenic substance, typically ethinyl estradiol, and as many as 10 progestins are available in the United States for combined pills. Multiple preparations are avail able to help select the formulation that satisfies an individual patient, with minimal side effects. Studies looking at the effects of estrogen dos ing on bone health have found lower rates of bone accrual in those taking COCs containing 20 mcg as compared with nonusers. It is rec ommended that adolescents start on a COC containing 30 35 g of an estrogenic substance. COCs can be packaged as 28 day monophasic pills, which contain the same dose of active pills for 21 or 24 days, followed by 7 or 4 days of placebo pills, respectively. Monophasic formulations are also available for extended cycles of 91 days or 1 year so that withdrawal bleeding does not occur each month, but at the |
6,315 | end of each extended cycle. Extended cycling of monophasic COCs for adolescents has some anticipated benefits associated with increased ovarian activity suppression and may decrease failure rates. Other advantages include menstrual suppression in those patients in whom that is a priority and diminished frequency of hormonal withdrawal (premenstrual) effects, including headaches and migraines, mood changes, and heavy monthly bleeding. The most common side effect of extended cycle OCs is intermenstrual bleeding andor spotting, with the total days of bleeding over the first year of treatment being similar for extended cycle users and users following a 28 day cycle regimen. The unscheduled bleeding pattern diminishes over time. Multiphasic pill packs contain various levels of estrogen and progestin for 21 active pills and contain 7 placebo pills. Multiphasic formulations are not available for extended cycle use. Providers can refer to the U.S. Selected Practice Recommendations for Contraceptive Use to counsel patients on how to manage late or missed COCs. The short term adverse effects of COCs, such as nausea and weight gain, often interfere with compliance in adolescent patients. These effects are usually transient and may be overlooked by the ben eficial effects of a shortened menses and the relief of dysmenorrhea. The inhibition of ovulation or the suppressant effect of estrogens on prostaglandin production by the endometrium makes COCs effec tive in preventing dysmenorrhea (see Chapter 159). Acne is typically improved by COCs, as estrogen can reduce the effects of circulating androgens. There is no evidence that one particular COC is superior to Fig. 160.3 Algorithm showing recommended actions after late or missed combined oral contraceptives. (From Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep 2016;65RR 4:166, Fig. 2, p. 28.) If one hormonal pill is late: (?24 hours since a pill should have been taken). Take the late or missed pill as soon as possible. Continue taking the remaining pills at the usual time (even if it means taking two pills on the same day). No additional contraceptive protection is needed. Emergency contraception is not usually needed but can be considered if hormonal pills were missed earlier in the cycle or in the last week of the previous cycle. Take the most recent missed pill as soon as possible. (Any other missed pills should be discarded.) Continue taking the remaining pills at the usual time (even if it means taking two pills on the same day). Use backup contraception (e.g., condoms) or avoid sexual intercourse until hormonal pills have been taken for 7 consecutive days. If pills were missed in the last week of hormonal pills (e.g., days 1521 for 28day pill packs): Omit the hormonefree interval by finishing the hormonal pills in the current pack and starting a new pack the next day. If unable to start a new pack immediately, use backup contraception (e.g., condoms) or avoid sexual intercourse until hormonal pills from a new pack have been taken for 7 consecutive days. Emergency contraception should be |
6,316 | considered if hormonal pills were missed during the first week and unprotected sexual intercourse occurred in the previous 5 days. Emergency contraception may also be considered at other times as appropriate. If one hormonal pill has been missed: (24 to ?48 hours since a pill should have been taken). If two or more consecutive hormonal pills have been missed: (?48 hours since a pill should have been taken). Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1224 Part XI u Adolescent Medicine another in targeting acne, but theoretically it would be better to use a pill with nonandrogenic progestins (see Chapter 710). Drospirenone, a progestin with antimineralocorticoid activity, has been shown to reduce premenstrual symptomatology, but the potential for hyperka lemia as a side effect eliminates patients with renal, liver, or adrenal diseases and patients taking certain medications. The FDA has concluded that drospirenone containing OCs may be associated with a higher risk of VTE than other progestin containing pills. Although no studies have provided consistent estimates of the comparative risk of VTE between OCs that contain drospirenone and those that do not, or accounted for patient characteristics that may affect VTE risk, there has been a threefold increased risk of VTE reported for drospirenone containing pills as compared with products containing levonorgestrel or other progestins. As a result, the FDA requires that labeling be revised for the OCs marketed under the Beyaz, Safyral, Yas min, and Yaz brands. This clot risk has not been established for Slynd, which contains 4 mg of drospirenone and no estrogenic component. Despite the risk of VTE with all OCs, the absolute risk remains lower than the risk of developing VTE during pregnancy or the postpartum period. TRANSDERMAL PATCH The transdermal patch releases a combination of ethinyl estradiol and a progestin daily. It is applied to the lower abdomen, buttocks, or upper body, excluding the breasts. It is worn continuously for 1 week and changed weekly for a total of 3 weeks, then no patch is worn for the fourth week, at which time bleeding occurs (see Table 160.1). Limited studies in adolescents suggest higher rates of partial or full detach ment compared with adults, with high patient satisfaction and 5083 continuation rates from 3 to 18 months of use (Fig. 160.5). As with other combined hormonal methods, the patch is a Tier 2 contraceptive. Providers can refer to the U.S. Selected Practice Recommendations to counsel patients on how to manage delayed application or detachment of the patch. The first patch available was Ortho Evra, now available only in a generic version called Xulane. It releases 35 g ethinyl estradiol and 150 g norelgestromin daily. Compared with the pharmacokinetics of COCs, the area under the curve for the patch is about 55 higher for patch users. This caused concerns about increased risk of clots with higher estrogen exposure, |
6,317 | although there have been no data to confirm this risk. Studies to date have had conflicting data on the risk of VTE in patients using nonoral combined hormonal contraception. There is also concern for efficacy of the patch in those whose weight was 90 kg, and this should be discussed with patients in consideration of use. The Xulane patch can be used to extend cycles similar to COC extended cycle pills. Patients may choose to wear patches consecutively without any patch free week but should be aware that this can carry a risk of breakthrough bleeding, as occurs with extended cycle COC use. In 2020 Twirla was developed to address the need for a lower dose product to reduce the cumulative estrogen exposure from patch use. Twirla releases 30 g ethinyl estradiol (EE) and 120 g levonorgestrel (LNG) daily, and the maximum steady state concentrations were 60 (EE) and 18 (LNG) as compared with Xulane. Initial studies did not demonstrate a significantly decreased clot risk as compared to other methods of combined hormonal contraception, but as with Xulane, efficacy seemed to be affected by body mass index (BMI), in particular in those who were categorized by BMI as obese. Twirla was not studied for extended use. VAGINAL RING The vaginal contraceptive ring is a flexible, transparent, colorless vagi nal ring that is inserted into the vagina by the patient. It releases a daily dose of ethinyl estradiol and a progestin. It remains in place for 3 weeks, during which time these hormones are absorbed. It is then typically Fig. 160.4 Algorithm showing recommended steps after vomiting or diarrhea while using combined oral contraceptives. (From Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep 2016;65RR 4:166, Fig. 5, p. 30.) Vomiting or diarrhea (for any reason, for any duration) that occurs within 24 hours after taking a hormonal pill. Taking another hormonal pill (redose) is unnecessary. Continue taking pills daily at the usual time (if possible, despite discomfort). No additional contraceptive protection is needed. Emergency contraception is not usually needed but can be considered as appropriate. Continue taking pills daily at the usual time (if possible, despite discomfort). Use backup contraception (e.g., condoms) or avoid sexual intercourse until hormonal pills have been taken for 7 consecutive days after vomiting or diarrhea has resolved. If vomiting or diarrhea occurred in the last week of hormonal pills (e.g., days 1521 for 28day pill packs): Omit the hormonefree interval by finishing the hormonal pills in the current pack and starting a new pack the next day. If unable to start a new pack immediately, use backup contraception (e.g., condoms) or avoid sexual intercourse until hormonal pills from a new pack have been taken for 7 consecutive days. Emergency contraception should be considered if vomiting or diarrhea occurred within the first week of a new pill pack and unprotected sexual intercourse occurred in the previous 5 days. Emergency contraception may also be considered at other |
6,318 | times as appropriate. Vomiting or diarrhea, for any reason, continuing for 24 to ?48 hours after taking any hormonal pill. Vomiting or diarrhea, for any reason, continuing for ?48 hours after taking any hormonal pill. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 160 u Contraception 1225 removed for 7 days during which time a withdrawal bleed should occur. If the ring is accidentally expelled or removed for intercourse, it should be reinserted; however, if it is out of place 48 hours or the ring is not replaced within 7 days after removal, a backup method of contraception should be used (Fig. 160.6). The vaginal ring is a Tier 2 contraceptive. Providers can refer to the U.S. Selected Practice Recom mendations to counsel patients on how to manage delayed insertion or reinsertion with the vaginal ring. The first contraceptive ring available was NuvaRing, which measures about 2.1 inches in diameter and releases 1 g ethinyl estradiol and 120 g etonogestrel daily. Users use one ring per 4 week cycle with 3 weeks in and 1 week out and a scheduled withdrawal bleed. It should be noted that although it is labeled for 28 days of use, it contains enough hormones to be used for up to 35 days and can be replaced once every calendar month. The ring can be used to extend cycles similar to COC extended cycle pills. Patients may choose to use the Nuva Ring consec utively without any ring free week but should be aware that this can carry a risk of breakthrough bleeding, as occurs with extended cycle COC use. Annovera is FDA approved and offers a single ring, which can be reused for 13 consecutive cycles and does not require refrigera tion when not in use. Annovera has a diameter of about 2.2 inches and releases 13 g of EE and 150 g of segesterone acetate daily. It has not been studied for extended use, and initial studies did not include those with a BMI 29 kgm2. CONTRAINDICATIONS Contraceptive counseling should include a discussion and assessment for any absolute or relative contraindications to estrogen use. Contra indications to the use of estrogen containing methods include those conditions for which CHCs pose an unacceptable health risk (Category 4) in the U.S. MEC for Contraceptive Use (see Table 160.3); current breast cancer; severe cirrhosis, acute deep venous thrombosispulmo nary embolism (DVTPE) or history of DVTPE with higher risk for recurrence, major surgery with prolonged immobilization, diabetes with nephropathy, retinopathy, or neuropathy, migraines with focal neurologic aura, stage II hypertension, vascular disease, ischemic heart disease, hepatocellular adenoma or malignant liver tumors, multiple risk factors for cardiovascular disease, peripartum cardiomyopathy, postpartum 21 day, complicated solid organ transplantation, history of cerebrovascular accident, systemic lupus erythematosus with posi tive antiphospholipid antibodies, thrombogenic pathogenic variants, and complicated valvular heart disease. The initial history taken |
6,319 | before prescribing CHCs should specifically address these risks. The U.S. MEC provides contraceptive safety guidance with 1,800 recommendations for 120 medical conditions or characteristics. According to the MEC, obesity is not a contraindication to estrogen or contraceptive use, and these adolescents would be considered at high risk for pregnancy com plications. Therefore adolescents with obesity should be counseled on and offered contraception when indicated and if desired by the patient. Other things to discuss and consider when evaluating an adolescent for COC use are a family history of blood clots or clotting disorders and any medications that might interact with COCs. If a patient has a first degree relative with history of VTE, evaluation for a familial thrombophilia is advisable. There are few medication interactions for progestin only methods, but there are medications that may be affected by or affect levels of COCs. This includes certain anticonvulsants and psychotropic medications as well as herbal supplements, which may affect COC levels. The CDC has a resource for antiretrovirals and their potential for interactions with hormonal contraception. Lexicomp and UpToDate provide additional information on interactions with COCs. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.6 Emergency Contraception Mary E. Romano and Elizabeth M. Alderman Unprotected intercourse at mid cycle carries a pregnancy risk of 2030. At other times during the cycle, the risk is 24. Emergency Fig. 160.5 Algorithm showing recommended actions after delayed application or detachment with combined hormonal patch. (From Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep 2016;65RR 4:166, Fig. 3, p. 28.) Apply a new patch as soon as possible. Keep the same patch change day. Use backup contraception (e.g., condoms) or avoid sexual intercourse until a patch has been worn for 7 consecutive days. If the delayed application or detachment occurred in the third patch week: Omit the hormonefree week by finishing the third week of patch use (keeping the same patch change day) and starting a new patch immediately. If unable to start a new patch immediately, use backup contraception (e.g., condoms) or avoid sexual intercourse until a new patch has been worn for 7 consecutive days. Emergency contraception should be considered if the delayed application or detachment occurred within the first week of patch use and unprotected sexual intercourse occurred in the previous 5 days. Emergency contraception may also be considered at other times as appropriate. Delayed application or detachment for ?48 hours since a patch should have been applied or reattached. Apply a new patch as soon as possible. (If detachment occurred ?24 hours since the patch was applied, try to reapply the patch or replace with a new patch.) Keep the same patch change day. No additional contraceptive protection is needed. Emergency contraception is not usually needed but can be considered if delayed application or detachment occurred earlier in the cycle or in the last week of the previous cycle. Delayed application or detachment for ?48 hours since a patch should have |
6,320 | been applied or reattached. If detachment takes place but the woman is unsure when the detachment occurred, consider the patch to have been detached for ?48 hours since a patch should have been applied or reattached. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1226 Part XI u Adolescent Medicine contraception (EC) refers to methods of contraception that are used after sexual intercourse to reduce the risk of pregnancy but do not interrupt an existing pregnancy. EC may be used up to 120 hours after unprotected intercourse or contraceptive failure. Table 160.5 lists the indications for use of EC. EC methods include the Cu IUD, LNG 52 mg IUD, and emergency contraceptive pills, which include ulipris tal acetate, LNG, and COCs following the Yuzpe method. Although the mechanism of action of the IUD as EC is unclear, all emergency contraceptive pills work to delay ovulation and are effective only for intercourse that occurs before administration. Initiation of a regular contraceptive method is necessary to prevent pregnancy for any inter course that occurs for the remainder of the cycle and for future cycles. If pregnancy has already occurred, emergency contraceptive pills will not terminate an existing pregnancy or have teratogenic effects on the fetus. Teens can access EC information through a hotline at 888 NOT 2 LATE to obtain EC pills over the counter (OTC). The Guttmacher Institute maintains an up to date listing on EC. The ACOG and AAP recommend advance provision of EC pills for at risk adolescents to remove barriers to access and increase awareness of the utility of EC. No examination or testing is required before use of EC, but a follow up appointment is recommended to determine the effec tiveness of treatment and to diagnose a possible early pregnancy. The visit also provides an opportunity to counsel the adolescent, explore the situation leading up to the unprotected intercourse or contracep tive failure, test for STIs, offer HIV testing, and engage in a discussion about contraception when appropriate. It is also important to engage adolescent males in discussions about the availability and use of EC if they have engaged in unprotected intercourse, especially when and how to access Plan B, which is available OTC. COPPER IUD The CuT380A (Paragard) is not FDA approved for EC, but it has been shown to be 99 effective if used within 5 days (120 hours) after unprotected sex. The additional benefit of using the Cu IUD for EC is that it also provides long term reversible contraception. Efficacy of the Cu IUD is not affected by BMI. LNG 52 mg IUD The Mirena IUD is not FDA approved for EC, but studies have shown it is as effectivenoninferior to the Cu IUD for EC if used within 5 days (120 hours) after unprotected sex. Similar to the Cu IUD, it also provides long term reversible |
6,321 | contraception and efficacy is not affected by BMI. Fig. 160.6 Algorithm showing recommended actions after delayed insertion or reinsertion with combined vaginal ring. (From Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. selected practice recommendations for contraceptive use, 2016. MMWR Recomm Rep 2016;65RR 4:166, Fig. 4, p. 29.) Insert ring as soon as possible. Keep the ring in until the scheduled ring removal day. Use backup contraception (e.g., condoms) or avoid sexual intercourse until a ring has been worn for 7 consecutive days. If the ring removal occurred in the third week of ring use: Omit the hormonefree week by finishing the third week of ring use and starting a new ring immediately. If unable to start a new ring immediately, use backup contraception (e.g., condoms) or avoid sexual intercourse until a new ring has been worn for 7 consecutive days. Emergency contraception should be considered if the delayed insertion or reinsertion occurred within the first week of ring use and unprotected sexual intercourse occurred in the previous 5 days. Emergency contraception may also be considered at other times as appropriate. Delayed insertion of a new ring or delayed reinsertion for ?48 hours since a ring should have been inserted. Insert ring as soon as possible. Keep the ring in until the scheduled ring removal day. No additional contraceptive protection is needed. Emergency contraception is not usually needed but can be considered if delayed insertion or reinsertion occurred earlier in the cycle or in the last week of the previous cycle. Delayed insertion of a new ring or delayed reinsertion of a current ring for ?48 hours since a ring should have been inserted. If removal takes place but the woman is unsure of how long the ring has been removed, consider the ring to have been removed for ?48 hours since a ring should have been inserted or reinserted. Table 160.5 Possible Indications for Emergency Contraception SEXUAL ASSAULT HIGH RISK SEXUAL ACTIVITY No contraception during intercourse Intoxication (alcohol, drugs) Coitus interruptus CONTRACEPTION FAILURES Condom breaking, spillage, leaks, intentional removal Dislodgement andor breaking of diaphragm, female condom, cervical cap Expulsion of IUD Spermicide failure to melt before coitus DELAYED OR MISSED CONTRACEPTION 2 consecutive missed days of combined oral contraceptive 1 missed day of progestin only oral contraceptives 2 wk late injection of depot medroxyprogesterone 2 days late start of vaginal ring or patch cycle Incorrect timing of spermicidegel before sexual activity OTHER Exposure to teratogens in the absence of contraception IUD, Intrauterine device. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 160 u Contraception 1227 ULIPRISTAL ACETATE Ulipristal acetate (UPA) is available for EC and is FDA approved for use up to 120 hours after unprotected sex. UPA is available only by prescription regardless of age. A few studies have shown it to be more effective than LNG at and beyond |
6,322 | 72 hours. If starting OC pills after taking UPA, it is recommended to start or resume pills no sooner than 5 days after taking UPA to avoid decreased efficacy of contraceptive pills as a result of its antiestrogenic effect. Studies have shown an increased risk of ovulation if COC pills are started immediately after UPA use. Studies have not looked at UPA efficacy when Depo or a progestin containing LARC is initiated immediately after UPA use. If starting a method requires an extra visit (e.g., IUDs, implant, Depo Provera), starting the method at the time of ulipristal use may be considered, weighing the risk of decreasing the effectiveness of ulipristal with the risk of not starting a contraceptive method. Patients should be encour aged to take a pregnancy test within 3 weeks after UPA use either in the office or on their own. Studies have suggested UPA is less effective in overweight and obese women (BMI 25). This should be discussed with patients, and all attempts should be made to provide UPA as soon as possible after unprotected sexual activity. LEVONORGESTREL In 2013 the FDA approved the emergency contraceptive drug Plan B One Step as an OTC option for all persons of childbearing potential. Experience with adolescents has demonstrated more effective use of EC with advance provision, and this is not associated with more fre quent unprotected intercourse or less condom andor pill use. Nau sea and vomiting are uncommon side effects, and LNG has been shown to be more effective at preventing pregnancy than the Yuzpe method. However, LNG has been shown to be less effective than UPA when taken 72 hours and in women who are obese and overweight (BMI 25). This should be discussed with women in deciding with EC method is most appropriate for use. Patients should be encouraged to take a pregnancy test within 3 weeks after EC use either in the office or on their own. Yuzpe Method The Yuzpe method has been replaced by the more effective methods of EC, but may be useful for women who do not have access to other meth ods andor already have COCs at home and desire EC. It is most effective when taken up to 72 hours after unprotected intercourse. For EC, COC pills with 200 g ethinyl estradiol and 2 mg norgestrel or 1 mg levonorg estrel should be taken in two doses, 12 hours apart. This method is effec tive in reducing the risk of pregnancy by 75. The most common side effects are nausea (50) and vomiting (20), prompting some clinicians to prescribe or recommend antiemetics along with the COCs. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.7 Condoms Mary E. Romano and Elizabeth M. Alderman The use of condoms is the only contraceptive method that protects against pregnancy and STIs, including HIV. Condoms, also referred to as barrier contraception, prevent sperm from being deposited in the vagina. The use of condoms in conjunction with hormonal contracep tion (or Cu IUD) is always |
6,323 | recommended to reduce the risk of preg nancy and protect against STIs. This is sometimes referred to as dual protection. Although correct and consistent condom use with every act of sexual intercourse theoretically protects against pregnancy and STIs, providers should encourage adolescents to use condoms for STIHIV protection along with a more effective method for pregnancy protection. No major medical side effects are associated with condom use, and condoms are available for use by males and females. Nonlatex condoms are available for those with a latex allergy, and these include lambskin and synthetic polyurethane condoms. Lambskin condoms do not pro tect against HIV and other viral infections, although they do work to prevent pregnancy. Although condom use at last sexual intercourse had steadily increased from the early 1990s to the mid 2000s, the percentage of students reporting condom use at last intercourse has remained stable, with 54 of adolescents reporting condom use at last intercourse. Earlier increases in condom use were thought to be the result of increased awareness of HIV risks. Only 9 of high school students reported using dual methods of contraception (condom plus something else) at last intercourse. The main advantages of condoms are their low price, availability without prescription, male involvement in the responsibility for contraception, and effectiveness in prevent ing transmission of STIs, including HIV and human papillomavirus (HPV). The typical use failure rate for male condoms is 18 for all users and is thought to be higher in adolescents. For the most effective dual protection, male latex condoms are recommended as protection against STIs and should be used in conjunction with another method of contraception. According to the National Survey of Family Growth, only 21.3 of females used another contraceptive method along with a condom at last sex during the past 12 months. There is only one female condom available in the United States. It is available OTC or can be ordered online. It is nonlatex. It can be harder to use properly and has a higher typical use failure rate (21) than the male condoms. There are no human studies demonstrating its effectiveness against STIs. Adolescents intending to use this method should be provided education on proper use and hands on practice to ensure effective use. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 160.8 Other Barrier Methods Mary E. Romano and Elizabeth M. Alderman Although these methods are not widely available or used, they are important to know about for patients who wish to use nonhormonal contraception at the time of intercourse. DIAPHRAGM, CERVICAL CAP, AND SPONGE These methods have few side effects but are much less likely to be used by teenagers. Typical use failure rates exceed 14. The sponge has limited OTC availability in the United States, and the cervical cap and diaphragm require a visit with a healthcare provider for fitting. The cervical cap and sponge have lower failure rates in nulliparous women, whereas the diaphragm has similar rates among nulliparous and parous women. The sponge is used with water, |
6,324 | whereas the cervi cal cap and diaphragm are used with spermicide before being placed over the cervix. Adolescents may feel less comfortable and be less likely to use these methods because of the messiness of the jelly or the need for insertion and removal interrupting the spontaneity of sex (to be inserted before sex and left in for several hours afterward). Spermicide must be reapplied before every act of intercourse. Adolescents may also be less comfortable touching their genitals. 160.9 Other Contraceptive Methods Mary E. Romano and Elizabeth M. Alderman The only OTC spermicide available in the United States is Nonoxynol 9 (N 9). It is available as a foam, film, gel, cream, suppository, and tablet. It must be placed in the vagina no more than 1 hour before intercourse and again before each act of intercourseejaculation. Side effects, although rare, include local irritation or contact vaginitis. There have been concerns about the vaginal and cervical mucosal damage observed with N 9 and its impact on HIV transmission. Results thus far have been inconclusive. There were some studies that suggested that N 9 is gonococcicidal and spirocheticidal, but this has not been substantiated in randomized clinical trials. Spermicides should be used in combination with barrier methods because their typical use failure rate alone is 21 Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1228 Part XI u Adolescent Medicine Phexxi is a prescription vaginal gel that is FDA approved. It is non hormonal and user controlled. It can be used alone or in conjunction with other methods, although it is not recommended for use with the intravaginal ring. It is prepackaged in a single dose applicator and must be inserted intravaginally up to 1 hour before vaginal intercourse. It works to maintain vaginal pH in an acidic range (3.5 to 4.5) despite the presence of alkaline semensperm, which limits motility and inca pacitates sperm. When compared with other OTC spermicidal gels, Phexxi has a higher viscosity, which minimizes vaginal leakage of the product and is thought to further affect sperm motility and provide an additional barrier to cervical penetration. Data also suggest Phexxi may have microbicidal effects in that by maintaining an acidic vagi nal pH, Phexxi may enhance the vaginas natural microbicidal mecha nisms. This effect seems more consistent and reliable than what has been found with the use of N 9. As with N 9, the most commonly reported side effect was vaginal discomfort and irritation. There has been no evidence that it affects HIV transmission. It should not be used in women with recurrent urinary tract infections (UTIs) or any urinary tract abnormalities. WITHDRAWAL The pregnancy risk with use of withdrawal as a contraceptive method is probably underestimated in adolescents, and a high typical use fail ure rate of 20 should be specifically addressed with all adolescents, given that up to |
6,325 | 60 of teens have reported using withdrawal for contraception. FERTILITY AWARENESSBASED METHODS Fertility awareness methods require that one be aware of the fertile days of their menstrual cycle and either avoid intercourse during that time or use barrier contraception. Methods typically involve calculat ing the length of ones menstrual cycle, observing changes in body tem perature andor cervical secretions. Fertility awareness methods are based on regular ovulatory cycles, which are less common in teens, and therefore fertility awareness methods may be difficult for a teenager to use effectively. Methods include the Standard Days method, basal body temperature method, Billings method, and lactational amenorrhea. Be aware that the lactational amenorrhea method may be a highly effec tive, temporary contraceptive method if the following criteria are met: (1) no return of menses, (2) the infant is 6 months old, and (3) the woman is exclusively breastfeeding. There is an FDA approved mobile applicationNatural Cyclesthat may be used to best predict fertility days to plan for abstinence or barrier contraceptive use. Other apps do exist, but they are not FDA approved. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. EPIDEMIOLOGY There has been a trend of decreasing teen births and pregnancies since 1991 (Fig. 161.1). Teen birthrates in the United States are at a historic low secondary to increased use of contraception at first intercourse, use of dual methods of condoms and hormonal contraception among sexually active teenagers, and access to abortion (see Chapter 161.1). Despite these data, the United States continues to lead other indus trialized countries in having high rates of adolescent pregnancy, with 700,000 pregnancies per year. Nonetheless, the National Survey of Family Growth (NSFG) 20062010 revealed that less than one third of Chapter 161 Adolescent Pregnancy Cora Collette Breuner 15 to 19 year old females consistently used contraceptive methods at last intercourse. The improvement in U.S. female teen birthrates is attributed to three factors: more teens are delaying the onset of sexual intercourse, are using some form of contraception when they begin to have sexual intercourse, and are using long lasting contraceptive agents such as injections, implants, and intrauterine devices (IUDs). Most pregnancies among U.S. adolescents are unintended (unwanted or mistimed); 88 of births to teenagers 15 17 years old were the result of unintended pregnancies. Birthrate statistics underestimate actual adolescent pregnancy rates because the birthrate numerator includes the number of actual births per 1,000 individuals in that age group, but the pregnancy rate includes actual births, abortions, and best estimates of fetal loss per 1,000 adolescents in that age group. The reported abortion rate among adolescents in 2019 for those 15 years of age was 0.4 per 1,000 females (of the same age group), and for those 15 19 years, it was 6.0 per 1,000; this compares to the most com mon age for having an abortion (20 29) of 18 19 per 1,000 females. It is unknown how many abortions go unreported (see Chapter 161.1). ETIOLOGY In industrialized countries with policies supporting access to protec tion against pregnancy |
6,326 | and sexually transmitted infections (STIs), older adolescents are more likely to use hormonal contraceptives and condoms, resulting in a lowered risk of unplanned pregnancy. Younger teenagers are likely to be less deliberate and logical about their sexual decisions, and their sexual activity is likely to be sporadic or even coer cive, contributing to inconsistent contraceptive use and a greater risk of unplanned pregnancy. Better personal hopes for employment and higher educational goals are associated with lowered probability of childbearing in most groups. In nonindustrialized countries, laws per mitting marriage of young and mid teens, poverty, and limited female education are associated with increased adolescent pregnancy rates. CLINICAL MANIFESTATIONS Adolescents may experience the traditional symptoms of pregnancy: morning sickness (vomiting, nausea that may also occur any time of the day), swollen tender breasts, weight gain, and amenorrhea. Often the presentation is less classic; headache, fatigue, abdominal pain, dizziness, and scanty or irregular menses are common presenting complaints. In the pediatric office, some teens are reluctant to divulge concerns of pregnancy. Denial of sexual activity and menstrual irregularity should not preclude the diagnosis in face of other clinical or histori cal information. An unanticipated request for a complete checkup or a visit for contraception may uncover a suspected pregnancy. Pregnancy is still the most common diagnosis when adolescents present with second ary amenorrhea. DIAGNOSIS Table 161.1 provides classic symptoms, laboratory tests, and physical changes in the diagnosis of pregnancy. On physical examination, the findings of an enlarged uterus, cervical cyanosis (Chadwick sign), a soft uterus (Hegar sign), or a soft cervix (Goodell sign) are highly suggestive of an intrauterine pregnancy. A confirmatory pregnancy test is always recommended, either qualita tive or quantitative. Modern qualitative urinary detection methods are efficient at detecting pregnancy, whether performed at home or in the office. These tests are based on detection of the beta subunit of human chorionic gonadotropin (hCG). Although claims for nonprescription home pregnancy tests may indicate 98 detection on the day of the first missed menstrual period, sensitivity and accuracy vary consider ably. Office or point of care tests have increased standardization and generally have increased sensitivity, with the possibility of detecting a pregnancy within 3 4 days after implantation. However, in any men strual cycle, ovulation may be delayed, and in any pregnancy, the day of implantation may vary considerably, as may rate of production of hCG. This variability, along with variation of urinary concentration, may affect test sensitivity. Consequently, each negative test should be Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 161 u Adolescent Pregnancy 1229 1991 1995 2000 2005 2010 2015 2020 2021 0 20 40 60 80 100 1519 years 1517 years 1819 years R at e pe r 1, 00 0 fe m al es Fig. 161.1 Birth rates for teenagers by age of mother: United States, final 19912020 and provisional |
6,327 | 2021. Source: National Center for Health Statistics, National Vital Statistics System, Natality. (From Ham ilton BE, Martin JA, Osterman JA, Division of Vital Statistics, National Center for Health Statistics. Births: provisional data for 2021. Nat Vital Stats Rapid Release. 2022;20, Fig. 2.) Table 161.1 Diagnosis of Pregnancy Dated from First Day of Last Menstrual Cycle CLASSIC SYMPTOMS Missed menses, breast tenderness, nipple sensitivity, nausea, vomiting, fatigue, abdominal and back pain, weight gain, urinary frequency. Teens may present with unrelated symptoms that enable them to visit the doctor and maintain confidentiality. LABORATORY DIAGNOSIS Tests for human chorionic gonadotropin in urine or blood may be positive 7 10 days after fertilization, depending on sensitivity. Irregular menses make ovulationfertilization difficult to predict. Home pregnancy tests have a high error rate. PHYSICAL CHANGES 2 3 wk after implantation: cervical softening and cyanosis. 8 wk: uterus size of orange. 12 wk: uterus size of grapefruit and palpable suprapubically. 20 wk: uterus at umbilicus. If physical findings are not consistent with dates, ultrasound will confirm. repeated in 1 4 weeks if there is a heightened suspicion of pregnancy. The most sensitive pregnancy detection test is a serum quantitative hCG radioimmunoassay, with reliable results within 7 days after fertiliza tion. This more expensive test is used primarily during evaluations for ectopic pregnancy, to detect retained placenta after pregnancy termi nation, or in the management of a molar pregnancy. It is used when serial measurements are necessary in clinical management. Although not used for primary diagnosis of pregnancy, pelvic or vaginal ultrasound can be helpful in detecting and dating a pregnancy. Pelvic ultrasound will detect a gestational sac at about 5 6 weeks (dated from last menstrual period) and vaginal ultrasound at 4.5 5 weeks. This tool may also be used to distinguish diagnostically between intra uterine and ectopic pregnancies. PREGNANCY COUNSELING AND INITIAL MANAGEMENT Once the diagnosis of pregnancy is made, it is important to begin addressing the psychosocial and the medical aspects of the pregnancy. The patients response to the pregnancy should be assessed and her emotional issues addressed. It should not be assumed that the preg nancy was unintended. Discussion of the patients options should be initiated. These options include (1) releasing the child to an adoptive family, (2) electively terminating the pregnancy, and (3) raising the child herself with the help of family, father of the baby, friends, and or other social resources. Options should be presented in a supportive, informative, nonjudgmental fashion; for some young women, they may need to be discussed over several visits. Physicians who are uncomfort able in presenting options to their young patients should refer their patients to a provider who can provide this service expeditiously. Preg nancy terminations implemented early in the pregnancy are generally less risky and less expensive than those initiated later. These include the prescription use of mifepristone and misoprostol within 10 weeks (the World Health Organization WHO recommends 12 weeks) of the pregnancy (see Chapter 161.1). Other issues that may need discussion are how |
6,328 | to inform and involve the patients parents and the father of the infant; implementing strate gies for ensuring continuation of the young mothers education; dis continuation of tobacco, alcohol, and illicit drug use; discontinuance and avoidance of any medications that may be considered teratogenic; starting folic acid, calcium, and iron supplements; proper nutrition; and testing for STIs. Especially in younger adolescents, the possibility of coercive sex (see Chapter 162) must be considered and appropri ate social worklegal referrals made if abuse has occurred, although most pregnancies are not a result of coercive sex. Patients who elect to continue their pregnancy should be referred as soon as possible to an adolescent friendly obstetric provider. Risk factors for teen pregnancy include growing up in poverty, hav ing parents with low levels of education, growing up in a single parent family, fewer opportunities in their community for positive youth involvement, neighborhood physical disorder, foster care (such teens are more than twice as likely to become pregnant than those not in foster care), and having poor performance in school (see Psychosocial OutcomesRisks for Mother and Child later). The Importance of Prevention Teen pregnancy and childbearing bring substantial social and eco nomic costs through immediate and long term impacts on teen parents and their children. In 2010, teen pregnancy and childbirth accounted for at least 9.4 billion in costs for increased healthcare and foster care, increased incarceration rates among children of teen parents, and lost tax revenue because of lower educational attainment and income among teen mothers. ADOLESCENT FATHERS Those who become fathers as adolescents also have poorer educational achievement than their age matched peers. They are more likely than other peers to have been involved with illegal activities and with the use of illegal substances. Adult men who father the children of teen mothers are poorer and educationally less advanced than their age matched peers and tend to be 2 3 years older than the mother, but any combination of age differences may exist. Younger teen mothers are more likely to have a greater age difference between themselves and the father of their child, raising the issue of coercive sex or statutory rape (see Chapter 162). Male partners have a significant influence on the young womans decisiondesire to become pregnant and to parent her child. Sensitively and appropriately including the male partner in discussions of fam ily planning, contraception, and pregnancy options may be a useful strategy in improving outcomes for all. This can only be successful if the young female patient is willing to have her partner involved in such discussions. MEDICAL COMPLICATIONS OF MOTHERS AND BABIES Although pregnant teens are at higher than average risk for some complications of pregnancy, most teenagers have pregnancies that are without major medical complications, delivering healthy infants. The Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1230 Part XI u |
6,329 | Adolescent Medicine miscarriagestillbirth risk for adolescents is estimated at 1520. In the United States, elective pregnancy termination rates peaked from 1985 to 1988 at 4146, decreasing since then to approximately 30 in 2008. Teen mothers have low rates of age related chronic disease (diabetes or hypertension) that might affect the outcomes of a preg nancy. They also have lower rates of twin pregnancies than older women. They tolerate childbirth well with few operative interventions. However, compared with 20 to 39 year old mothers, teens have higher incidences of low birthweight infants, preterm infants, neonatal deaths, passage of moderate to heavy fetal meconium during parturition, and infant deaths within 1 year after birth. The highest rates of poor out comes occur in the youngest and most economically disadvantaged mothers. Gastroschisis, although rare, has a much higher incidence in infants of teen mothers, for reasons that are unclear. Teen mothers also have higher rates of anemia, pregnancy associated hypertension, and eclampsia, with the youngest teens having rates of pregnancy associated hypertension higher than the rates of women in their 20s and 30s. The youngest teens also have a higher incidence of poor weight gain (16 lb) during their pregnancy. This correlates with a decrease in the birthweights of their infants. Poor maternal weight gain also has correlated strongly with teens late entrance into prenatal care and with inadequate use of prenatal care. Sexually active teens have higher rates of STIs than older sexually active women. Globally, many young women who become pregnant have been exposed to violence or abuse in some form during their lives. There is some evidence that teenage women have the highest rates of violence during pregnancy of any group. Violence has been associated with injuries and death as well as preterm births, low birthweight, bleed ing, substance abuse, and late entrance into prenatal care. An analysis of the Pregnancy Mortality Surveillance System indicates that in the United States 19911999, homicide was the second leading cause of injury related deaths in pregnant and postpartum women. Women age 19 years and younger had the highest pregnancy related homicide rate (see Chapter 156). Ectopic pregnancy occurs in 12 of conceptions and is more com mon in women with a previous history of an ectopic pregnancy, pelvic inflammatory disease, prior appendicitis, infertility, in utero exposure to diethylstilbestrol, and possibly an IUD. Most ectopic pregnancies are in the fallopian tube (tubal pregnancy). Manifestations include vaginal spotting after a missed menstrual period that may progress to more intense vaginal bleeding (suggestive of spontaneous abortion); vaginal bleeding is absent in 1020. Abdominal pain is associated with dis tention of the fallopian tube; tubal rupture results in more intense pain, hemorrhagic shock, and peritonitis. Some women have nonspecific abdominal complaints and are misdiagnosed with gastroenteritis. Cer vical motion and adnexal tenderness (and adnexal mass) may be pres ent. Transvaginal sonography (not transabdominal) is the diagnostic test of choice to detect an ectopic pregnancy and reveals an adnexal mass and no uterine pregnancy. Nonetheless, some women will |
6,330 | have pregnancy of unknown location by transvaginal sonography; approxi mately 20 of these will have an ectopic pregnancy. Measurement of sensitive quantitative serum hCG levels together with transvaginal sonography has value in diagnosing an ectopic pregnancy. If the ini tial hCG is above the discriminatory zone (level at which one expects an intrauterine pregnancy) but on transvaginal sonography there is no intrauterine pregnancy, there may be an ectopic pregnancy or an abnormal uterine pregnancy. In addition, if the hCG is below the discriminatory level (usually 3,000 mIUmL) with no definitive diag nosis by sonography, serial hCG testing should be performed every 48 hours. In a normal uterine pregnancy, hCG levels should increase approximately 50 every 48 hours; declining levels may suggest a mis carriage or an ectopic pregnancy. Some would perform a dilation and curettage and check for products of conception or follow serial hCG levels. If there are no products of conception or if hCG levels plateau or increase, an ectopic pregnancy is present. Treatment of unstable or advanced patients is usually by laparoscopic surgery or by laparotomy. Because of early detection, many patients remain stable (unruptured). Stable patients with an unruptured ectopic pregnancy may be treated with single dose, or more often, multidose methotrexate to induce abortion. Contraindications to methotrexate in a stable patient include size of the ectopic mass (3.5 cm) and embryonic cardiac motion. Prematurity and low birthweight increase the perinatal morbid ity and mortality for infants of teen mothers. These infants also have higher than average rates of sudden infant death syndrome (see Chap ter 423), possibly because of less use of the supine sleep position or cosleeping, and are at higher risk of both intentional and unintentional injury (see Chapter 17). One study showed that the risk of homicide is 9 10 times higher if a child born to a teen mother is not the mothers firstborn compared with the risk to a firstborn of a woman age 25 years or older. The perpetrator is often the father, stepfather, or boyfriend of the mother. After childbirth, depressive symptoms may occur in as many as 50 of teen mothers. Depression seems to be greater with additional social stressors and with decreased social supports. Support from the infants father and the teens mother seems to be especially important in pre venting depression. Pediatricians who care for parenting teens should be sensitive to the possibility of depression, as well as to inflicted injury to mother or child; appropriate diagnosis, treatment, and referral to mental health or social agencies should be offered and facilitated. PSYCHOSOCIAL OUTCOMESRISKS FOR MOTHER AND CHILD Educational Issues Pregnancy and birth are significant contributors to high school drop out rates among girls. Only about 50 of teen mothers receive a high school diploma by age 22, whereas approximately 90 of women who do not give birth during adolescence graduate from high school. Moth ers who have given birth as teens generally remain 2 years behind their age matched peers in formal educational attainment at |
6,331 | least through their third decade. Maternal lack of education limits the income of many of these young families (see Chapter 1). The children of teenage mothers are more likely to have lower school achievement and to drop out of high school, have more health prob lems, and face unemployment as a young adult. Substance Use See also Chapter 157. Teenagers who abuse drugs, alcohol, and tobacco have higher preg nancy rates than their peers. Most substance abusing mothers appear to decrease or stop their substance use while pregnant. Use begins to increase again about 6 months postpartum, complicating the parenting process and the mothers return to school. Repeat Pregnancy In the United States, approximately 20 of all births to adolescent mothers (age 15 19) are second order or higher. Prenatal care is begun even later with a second pregnancy, and the second infant is at higher risk of poor outcome than the first birth. Mothers at risk of early repeat pregnancy (2 years) include those who do not initiate long acting contraceptives after the index birth, those who do not return to school within 6 months of the index birth, those with mood disorders, those receiving major childcare assistance from the adolescents mother, those who are married or living with the infants father, those hav ing peers who were adolescent parents, and those who are no longer involved with the babys father and who meet a new boyfriend who wants to have a child. To reduce repeat pregnancy rates in these teens, programs must be tailored for this population, preferably offering comprehensive healthcare for both the young mother and her child. Healthcare providers should remember to provide positive reinforce ment for teen parenting successes (i.e., compliment teen parents when they are doing a good job). Children Born to Teen Mothers Many children born to teen mothers have behavioral problems that may be seen as early as the preschool period. Many drop out of school early (33), become adolescent parents (25), or, if male, are incar cerated (16). Explanations for these poor outcomes include poverty, parental learning difficulties, negative parenting styles of teen parents, Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 161 u Adolescent Pregnancy 1231 maternal depression, parental immaturity, poor parental modeling, social stress, exposure to surrounding violence, and conflicts with grandparents, especially grandmothers. Continued positive paternal involvement throughout the childs life may be somewhat protective against negative outcomes. Many of these poor outcomes appear to be attributable to the socioeconomicdemographic situation in which the teen pregnancy has occurred, not solely to maternal age. Even when socioeconomic status and demographics are controlled, infants of teen mothers have lower achievement scores, lower high school graduation rates, increased risk of teen births themselves, and, at least in Illinois (where records include age of birth mother), a higher probability of abuse and neglect. Comprehensive programs |
6,332 | focused on supporting adolescent moth ers and infants using life skills training, medical care, and psychosocial support demonstrate higher employment rates, higher income, and less welfare dependency in participating adolescents. PREVENTION OF TEEN PREGNANCIES Adolescent pregnancy is a multifaceted problem that requires mul tifactorial solutions. The provision of contraception and education about fertility risk from the primary care physician is important but insufficient to address the problem fully. Family and community involvement are essential elements for teen pregnancy prevention. Strategies for primary prevention (preventing first birth) are differ ent from the strategies needed for secondary prevention (prevent ing second or more births). Over the past 30 years, many models of teen pregnancy prevention programs have been implemented and evaluated. Table 161.2 lists the common components of successful evidence based programs. Abstinence only sexual education aims to teach adolescents to wait until marriage to initiate sexual activity but, unfortunately, does not mention contraception. Abstinence education is sometimes coupled with virginity pledges in which teenagers pledge to remain abstinent until they marry. Other educational programs emphasize HIV and STI prevention and in the process prevent pregnancy, whereas others include both abstinence and contraception in their curricula. Sex edu cation and teaching about contraception do not lead to an increase in sexual activity. Teenagers who participate in programs with compre hensive sex education components generally have lower rates of preg nancy than those exposed solely to abstinence only programs or no sex education at all. In many U.S. communities, programs that engage youth in commu nity service and that combine sex education and youth development are also successful in deterring pregnancy. Programs vary in their sites of service from schools to social agencies, health clinics, youth organi zations, and churches. Programs must be tailored to the cultural back ground, ethnicity, age group, and gender of the group being targeted for the prevention services. Secondary prevention programs are fewer in number. In the United States, some communities have tried to pay young mothers not to become pregnant again, but these efforts have not always been fruitful. Home visiting by nurses has been successful in some areas, and many communities have developed Teen Tot clinics that provide a one stop shopping model for healthcare for both the teen mother and the baby in the same site at the same time. Both programs have reported some successes. In the practice setting, the identification of the sexually active ado lescent through a confidential clinical interview is a first step in preg nancy prevention. The primary care physician should provide the teenager with factual information in a nonjudgmental manner and then guide the teenager in the decision making process of choosing a contraceptive (see Chapter 160). The practice setting is an ideal set ting to support the teenager who chooses to remain abstinent. When a teenager does become pregnant and requires prenatal care services, healthcare providers should remember that the pregnant teenager is an adolescent who has become pregnant, not a pregnant woman who happens to be an |
6,333 | adolescent. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 161.1 Abortion Alison S. Kliegman and Robert M. Kliegman Abortion is a safe, common, and essential reproductive healthcare evidencebased intervention. Worldwide 30 of all pregnancies and 60 of all unintended pregnancies are voluntarily terminated. In the past by age 45 25 of U.S. pregnant persons had an abor tion. The WHO defines abortion as the termination of pregnancy before 20 weeks gestation. Abortions can be voluntary or sponta neous (miscarriages). Access to reproductive care, including abor tion care, is considered by all health organizations as a basic human right. The American Academy of Pediatrics supports a young per sons right of access to comprehensive, evidence based reproduc tive healthcare services, including abortion. Abortion should be available to any person requesting it without a specific indication. The most common indication is unintended (unplanned) preg nancy, which includes not being able to afford a child, poorly timed pregnancy, and not having a suitable partner; additional indications include being subjected to coercive sexual encounters, as well as medical conditions that place the pregnant person at risk and cer tain fatal fetal conditions. EPIDEMIOLOGY Most abortions occur in patients between 20 and 30 years of age (Table 161.3). In addition, the majority of abortions occur in the first trimes ter (Fig. 161.2). The highest ratio of abortion (number of abortions per 1,000 live births) is noted in persons 15 years (Fig. 161.3). Among 15 to 19 year olds, the United States has one of the highest rates of adolescent pregnancy but among one of the lowest rates of adolescent pregnancies ending in abortion when compared to other developed countries (Fig. 161.4). Seventy five percent of adolescent pregnancies in the United States are unplanned, while 30 end with an abortion (among those 15 17 years). Abortion Care The WHO 2022 report recommends that: Abortions must be decriminalized Be made available at request Be made available by telemedicine Be made available for self management, not just in clinic Have a wide range of eligible providers Provide an enabling environment (Fig. 161.5) The National Academies of Sciences, Engineering and Medicine provides an outline for continuum of abortion care; preabortion, preg nancy termination, and post abortion care (Fig. 161.6). Table 161.2 Common Components of Most Successful Evidence Based Programs to Prevent Teen Pregnancy Information is provided about the benefits of abstinence. Information is provided about contraception for those who are already sexually active. Information is provided about the signs and symptoms of STIs and how to prevent STIs. Interactive sessions on peer pressure are presented. Teenagers are taught communication skills. Programs are tailored to meet the needs of specific groups of young people (e.g., young men or young women, cultural groups, younger or older teens). STI, Sexually transmitted infection. Adapted from Suellentrop K. What Works 20112012: Curriculum Based Programs That Help Prevent Teen Pregnancy. Washington, DC: National Campaign to Prevent Teen and Unplanned Pregnancy, http:www.c hubonline.orgsitesdefaultfilesresourcesm ainWhatWorks0.pdf. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by |
6,334 | Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1232 Part XI u Adolescent Medicine Methods Abortion methods vary depending on gestational age, location (in clinic vs self managed), and procedure (medical vs surgical). Medi cally managed abortion (abortion pill) is FDA approved up to 10 weeks, although the WHO suggests up to 12 weeks and has also been used off label at later gestational ages. It consists of mifepristone (a potent progesterone antagonist) 200 mg PO one dose, followed within 24 48 hours by misoprostol 800 g (a prostaglandin to induce uterine contractions) by buccal, sublingual, or vaginal routes. Medi cal abortion represents 50 of abortions in the United States (Fig. 161.7). This treatment is available in clinic but also via tele health, where a prescriber then mails the medication to be taken at home (self managed medical abortion). This latter mail order avail ability is FDA approved. Self managed medical abortion is safe and 96 effective; complications are rare (1) and include hemor rhage or infection; no deaths have been reported from self managed medical abortion. Contraindications include porphyria, a bleeding disorder, taking anticoagulants, adrenal insufficiency, long term systemic steroid use, ectopic pregnancy, and the presence of an IUD. Acute side effects during a self managed abortion are to be expected and include nausea and vomiting, headaches, diarrhea, and flulike symptoms and, once the abortion starts, cramping and bleeding. Excessive bleeding (two or more pads per hour for 2 hours), fever (100F), or severe abdominal pain requires medical attention. After Table 161.3 Characteristics of Persons Who Had an Abortion in an Outpatient Setting in 2014, by Percent CHARACTERISTIC PERCENT Age 15 17 3.6 18 19 8.2 20 24 33.6 25 29 26.3 30 34 16.0 35 12.2 Prior Pregnancies No prior pregnancies 29.2 Prior birth only 26.0 Prior abortion only 11.7 Prior birth and abortion 33.1 Education Not a high school graduate 12.2 High school graduate or GED 29.0 Some college or associates degree 39.2 College graduate 19.7 Family Income as a Percentage of Federal Poverty Level 100 49.3 100 199 25.7 200 25.0 Note: Percentages may not sum to 100 because of rounding. Sources: Jones RK, Jerman J. Characteristics and circumstances of U.S. women who obtain very early and second trimester abortions. PLoS One. 2017b;12:e0169969 (n 8,098); Jerman J, Jones RK, Onda T. Characteristics of U.S. abortion patients in 2014 and changes since 2008. 2016. October 17, 2016. https:www .guttmacher .orgsitesdefault filesreportpdfcharacteristics us abortion patients 2014 .pdf (n 8,380). Modified from National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Population Health and Public Health Practice; Committee on Reproductive Health Services. Assessing the Safety and Quality of Abortion Care in the U.S. Washington, DC: National Academies Press; 2018: Table 1 2. 10 14 4 4 18 50 18 32 10 74 14 65 5 87 7 82 3 93 4 90 1 96 2 95 3 |
6,335 | 100 1 97 0 4 5 6 7 8 9 10 Number of weeks gestation at time of abortion 11 12 13 14 15 16 17 abortions Cumulative abortions80 90 60 70 40 50 20 10 30 100 Fig. 161.2 Percentage and cumulative percentage of outpatient abortions by weeks gestation, 20142015. (From Jones RK, Jerman J. Characteristics and circumstances of US women who obtain very early and second trimester abortions. PLoS One 2017; 12(1):e0169969.) 1000 0 200 1 5 1 5 19 20 2 4 25 2 9 Age group (yrs) 30 3 4 35 3 9 4 0 400 600 800 Fig. 161.3 Abortion ratio by age group of persons who obtained a le gal abortion in selected states of the United States in 2001. Abortion ra tio refers to number of abortions per 1,000 live births. (From Strauss LT, Herndon J, Chang J, et al. Abortion surveillanceUnited States, 2001. MMWR Surveill Summ. 2004;53:132.) 70 10 20 0 Pregnancies per 1,000 females 1519 years old P er ce nt o f t ee n pr eg na nc ie s en di ng in a bo rt io n 70605040 SVK USA BEL ISR POR SCO NZ HUN ENG EST SPAICE SIN NET SVN NOR FIN FRA SWI DEN SWE 302010 40 30 50 60 Fig. 161.4 Percentage of teen pregnancies ending in abortion is in versely correlated with teen pregnancy rate. BEL, Belgium; DEN, Den mark; ENG, England and Wales; EST, Estonia; FIN, Finland; FRA, France; HUN, Hungary; ICE, Iceland; ISR, Israel; NET, The Netherlands; NOR, Norway; NZ, New Zealand; POR, Portugal; SCO, Scotland; SIN, Singa pore; SPA, Spain; SVK, Slovakia; SVN, Slovenia; SWE, Sweden; SWI, Switzerland; USA, United States. (From Sedgh G, Finer LB, Bankole A, et al. Adolescent pregnancy, birth, and abortion rates across countries: levels and recent trends. J Adolesc Med. 2010;56:223230, Fig. 1.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 161 u Adolescent Pregnancy 1233 the abortion, do not use tampons for 5 days and get a pregnancy test 3 weeks later to ensure a complete abortion. After that, a contracep tive should be started in sexually active individuals (may not be indi cated in cases of rape or incest). Medical abortion has an exceptional safety record; long term studies demonstrate no adverse effect on fer tility, premature birth, breast cancer, or mental health issues. The medications can be available by online consultation from Aid Access (aidaccess.org); pills will be mailed directly from Aid Access to persons in all states permitting self managed abortion. Shield laws pro tect telemedicine providers serving patients in states where abortion is illegal. Surgical methods for abortion require in clinic presence and a skilled provider. These include suction curettage (aspiration method) used between 6 and 16 weeks gestation, dilation, and evacuation (12 24 weeks); induction of labor; and, if necessary, rarely |
6,336 | a hysterotomy (C section) at 24 weeks. Anesthesia (local or general) is needed for these procedures. Restricting access to or banning legal abortions will not reduce the total number of abortions but increases the risk of criminalization and potentially the number of unsafe procedures. On a global basis, unsafe abortions represent 45 of all abortions. Unsafe abortion increases the risk of incomplete abortion (retained products of con ception), hemorrhage, infection, uterine perforation, other organ injury, and infertility. Restricting access to abortion with resultant pregnancy will have adverse economic and educational conse quences for the pregnant adolescent (see Chapter 161). In addition, the United States has one of the highest maternal mortality rates (23.8 deaths per 100,000 live births in 2020) of developed countries. The risk of death from pregnancy is much higher than from any form of legal abortion. Challenges and Barriers There are multiple logistic and legal challenges to obtaining an abor tion. Some are generalizable to all ages, whereas others are specific to adolescent patients. Some states have a complete ban against abortions, necessitating travel to another state or country. In other states, there is a limit to gestational age (usually first trimester). Many are limiting abortion to 6 weeks or when fetal heart beats are detected. The majority of states require a physician to perform an abortion. Some states restrict the use of public funding, and others restrict private insurance use for abortions. In one study, 45 of fees were paid by the pregnant person; in states that ban Medicaid fund ing for abortion, the patient pays the full cost. States vary in the require ment for preabortion counseling and a waiting period. If counseling is needed, it should be from an abortion provider, not a state mandated program, which may be biased against abortion. The criminalization of abortion (the pregnant person, the provider, others involved) has created a climate of enhanced surveillance and added barriers. Laws have been proposed to require abortion pro viders to register all patients requesting an abortion. These report ing mandates will compromise patient provider confidentiality and possibly violate Health Insurance Portability and Accountability Act (HIPAA) regulations. Nonetheless HIPAA may not be applicable if legal action is filed against a patient andor provider. Other laws will C o n te xt s pe ci fic s er vi ce d el iv er y ap pro aches Integration within health systems Commodities Finances Links to other servicesH om e Ph ar m ac y Community outreach centres Primary care facility Higherlevel facilityS el f Fa cil ity based health workers Other health w orkers In form ation, counselling (where desired) P ri m in g, P ai n m an ag em en t, A nt ib io tic s Medical and surgical methods Contraception, Managing com plication sP re a bo rt io n Abortion Postabortion HOW WHERE WHO WHAT Values Preferences Respect for human rights Supportive framework of law and policy Availability and accessibility of information Supportive health systems Enabling |
6,337 | environment Fig. 161.5 Conceptual framework of the WHO abortion care guidelines. (From World Health Organization. Abortion Care Guideline. Geneva: World Health Organization; 2022. License: CC BY NC SA 3.0 IGO. Fig.1 https:www.who.intpublicationsiitem9789240039483.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1234 Part XI u Adolescent Medicine permit private citizens to sue pregnant persons having an abortion or those who help (even those transporting the pregnant person to another state). With these legal obstacles in place, patients seeking an abortion must be vigilant in keeping abortion seeking behaviors private and unavailable to litigious prosecution. This should include internet browsing and searches, text messages, period tracking apps, payments, and travel plans, all of which may be used as evidence. Although a self managed medically induced abortion is clinically indistinguishable from a spontaneous miscarriage, a prosecutor may use electronic information as evidence to identify an induced abortion. The concept of fetal personhood and laws defining this as starting at conception add another legal concern. Fetal personhood proponents suggest that the unborn fetus has rights similar to a child after birth and that any action thought to harm the fetus will be considered ille gal. Pregnant persons can thus be detained or arrested for actions per ceived as harmful to the fetus (beginning in the first trimester). Most of the cases have been related to a pregnant persons use of drugs; such patients have been accused of child abuse or even distributing drugs to a minor. In addition to the effects that the concept of fetal personhood will have on abortions, it may have implications for persons with an IUD, those using emergency contraception, embryos created for IVF, and those experiencing an ectopic pregnancy. In addition to challenges experienced by all persons seeking an abor tion, adolescents who are minors have age specific barriers. Minors may not be able to travel to locations providing abortion (finances, drivers license, purchase airline ticket) and in most states, they are required to have some form of parental (grandparent or other adult relative in some states) involvement by notification or actual consent (PNA). PNA can be avoided by using a judicial bypass after appealing to a judge. In this case, the judge will determine if the adolescent requesting an abor tion is mature and informed. States with legal access to abortion may eliminate PNA altogether (e.g., Illinois). Various organizations have facilitated access to self managed abor tions or to provide referrals to the nearest abortion provider. Aid Access (http:www.aidaccess.org) is an online international abortion consult service that will make mifepristonemisoprostol available by mail (including minors). Another site (http:www.ineedana.com) helps locate the nearest abortion provider, and http:www.elevatedaccess.org helps arrange flights to legal abortion sites. Other resources include Women on Web http:www. womenonweb.orgen and Planned Parenthood as a patient navigator or provider of abortions. To get help with funding: National Network of Abortion Funds |
6,338 | https:abortionfunds.org or https:prochoice.org Locating Plan C pills: https:www.plancpills.org?gclidCjwKCAjw b6WBhAQEiwAp4HyIKGkcL2gncj28MXzfN1eONGC4a3pI9FLRx f4Iv8NZ5HqDD04JwxoC6LQQAvDBwE Help with a self managed abortion: https:www.mahotline.org Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. Telehealth Physical examlaboratory tests Informed consent Patient counseling Contraceptive counseling Preabortion PostabortionPregnancy termination Medication Aspiration Dilation and evacuation Induction Followup care Contraceptive services (referral or provision) Fig. 161.6 Continuum of abortion care. (Modified from National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Population Health and Public Health Practice; Committee on Reproductive Health Services. Assessing the Safety and Quality of Abortion Care in the U.S. Washington, DC: National Academies Press; 2018: Fig.1 1.) 2000 2001 2005 2008 2011 2014 2017 2020 0 20 0 6 14 17 24 31 39 54 40 60 Medication abortion Fig. 161.7 As of 2020, medication abortions account for the majority of all U.S. abortions. Based on preliminary data. (From Guttmacher Institute. Medication abortion now accounts for more than half of all US abortions, 2022. https:www.guttmacher.orgprintarticle202202me dication abortion now accounts more half all us abortions.) Rape is an act of violence, not an act of sex. Rape is historically defined as coercive sexual intercourse involving physical force or psychologic manipulation of a female or a male. Recognizing that sexual inter course is not a requirement for the definition, the U.S. Department of Justice (DOJ) defines rape as the penetration, no matter how slight, of the vagina or anus with any body part or object, or oral penetration by a sex organ of another person, without the consent of the victim. Though definitions may vary by state, sexual assault is a more inclusive term that according to the U.S. DOJ means any nonconsensual sexual act proscribed by Federal, tribal, or State law, including when the vic tim lacks capacity to consent. EPIDEMIOLOGY Exact figures on the incidence of rape are unavailable because sexual assault is underreported. In the 2019 National Crime Victimization Survey, only 0.56 per 1,000 persons over 12 years of age reported sex ual assault to police. According to the National Intimate Partner and Sexual Violence Survey of 2015 (NISVS 2015), over 43 women and nearly 25 of men experienced some form of sexual violence in their lifetime. Females exceed males as reported rape victims, but male rape may be more underreported than female rape. Adolescence is a high risk age group for sexual assault, with 43.2 of females and 51.3 of males experiencing their first sexual assault before the age of 18 years, and 81.3 of females and 70.8 males experi encing their first sexual assault before the age of 25 years (NISVS 2015). Between 1995 and 2013 the rate of rape and sexual assault was highest for adolescent females between ages 18 and 24 years. The National Sur vey of Childrens Exposure to Violence (NatSCEV 2014) revealed that 12.9 of 14 to 17 year olds experienced any sexual victimization in the past year, 21.7 had experienced any sexual victimization in their lifetime, 4.2 experienced sexual assault in the past |
6,339 | year, and 10.2 in their lifetime. This survey also demonstrated how other experiences with violence compound the risk for sexual victimization. Youth with a history of maltreatment by a caregiver were four times more likely to experience sexual victimization and more than four times more likely to experience sexual victimization if they were a witness to violence. Among older adolescents age 18 24 years, the rate of rape and sexual Chapter 162 Adolescent Sexual Assault Allison M. Jackson, Adrianne R. Artis, and Norrell K. Atkinson Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1234 Part XI u Adolescent Medicine permit private citizens to sue pregnant persons having an abortion or those who help (even those transporting the pregnant person to another state). With these legal obstacles in place, patients seeking an abortion must be vigilant in keeping abortion seeking behaviors private and unavailable to litigious prosecution. This should include internet browsing and searches, text messages, period tracking apps, payments, and travel plans, all of which may be used as evidence. Although a self managed medically induced abortion is clinically indistinguishable from a spontaneous miscarriage, a prosecutor may use electronic information as evidence to identify an induced abortion. The concept of fetal personhood and laws defining this as starting at conception add another legal concern. Fetal personhood proponents suggest that the unborn fetus has rights similar to a child after birth and that any action thought to harm the fetus will be considered ille gal. Pregnant persons can thus be detained or arrested for actions per ceived as harmful to the fetus (beginning in the first trimester). Most of the cases have been related to a pregnant persons use of drugs; such patients have been accused of child abuse or even distributing drugs to a minor. In addition to the effects that the concept of fetal personhood will have on abortions, it may have implications for persons with an IUD, those using emergency contraception, embryos created for IVF, and those experiencing an ectopic pregnancy. In addition to challenges experienced by all persons seeking an abor tion, adolescents who are minors have age specific barriers. Minors may not be able to travel to locations providing abortion (finances, drivers license, purchase airline ticket) and in most states, they are required to have some form of parental (grandparent or other adult relative in some states) involvement by notification or actual consent (PNA). PNA can be avoided by using a judicial bypass after appealing to a judge. In this case, the judge will determine if the adolescent requesting an abor tion is mature and informed. States with legal access to abortion may eliminate PNA altogether (e.g., Illinois). Various organizations have facilitated access to self managed abor tions or to provide referrals to the nearest abortion provider. Aid Access (http:www.aidaccess.org) is an online international abortion consult service that will make |
6,340 | mifepristonemisoprostol available by mail (including minors). Another site (http:www.ineedana.com) helps locate the nearest abortion provider, and http:www.elevatedaccess.org helps arrange flights to legal abortion sites. Other resources include Women on Web http:www. womenonweb.orgen and Planned Parenthood as a patient navigator or provider of abortions. To get help with funding: National Network of Abortion Funds https:abortionfunds.org or https:prochoice.org Locating Plan C pills: https:www.plancpills.org?gclidCjwKCAjw b6WBhAQEiwAp4HyIKGkcL2gncj28MXzfN1eONGC4a3pI9FLRx f4Iv8NZ5HqDD04JwxoC6LQQAvDBwE Help with a self managed abortion: https:www.mahotline.org Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. Telehealth Physical examlaboratory tests Informed consent Patient counseling Contraceptive counseling Preabortion PostabortionPregnancy termination Medication Aspiration Dilation and evacuation Induction Followup care Contraceptive services (referral or provision) Fig. 161.6 Continuum of abortion care. (Modified from National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division; Board on Health Care Services; Board on Population Health and Public Health Practice; Committee on Reproductive Health Services. Assessing the Safety and Quality of Abortion Care in the U.S. Washington, DC: National Academies Press; 2018: Fig.1 1.) 2000 2001 2005 2008 2011 2014 2017 2020 0 20 0 6 14 17 24 31 39 54 40 60 Medication abortion Fig. 161.7 As of 2020, medication abortions account for the majority of all U.S. abortions. Based on preliminary data. (From Guttmacher Institute. Medication abortion now accounts for more than half of all US abortions, 2022. https:www.guttmacher.orgprintarticle202202me dication abortion now accounts more half all us abortions.) Rape is an act of violence, not an act of sex. Rape is historically defined as coercive sexual intercourse involving physical force or psychologic manipulation of a female or a male. Recognizing that sexual inter course is not a requirement for the definition, the U.S. Department of Justice (DOJ) defines rape as the penetration, no matter how slight, of the vagina or anus with any body part or object, or oral penetration by a sex organ of another person, without the consent of the victim. Though definitions may vary by state, sexual assault is a more inclusive term that according to the U.S. DOJ means any nonconsensual sexual act proscribed by Federal, tribal, or State law, including when the vic tim lacks capacity to consent. EPIDEMIOLOGY Exact figures on the incidence of rape are unavailable because sexual assault is underreported. In the 2019 National Crime Victimization Survey, only 0.56 per 1,000 persons over 12 years of age reported sex ual assault to police. According to the National Intimate Partner and Sexual Violence Survey of 2015 (NISVS 2015), over 43 women and nearly 25 of men experienced some form of sexual violence in their lifetime. Females exceed males as reported rape victims, but male rape may be more underreported than female rape. Adolescence is a high risk age group for sexual assault, with 43.2 of females and 51.3 of males experiencing their first sexual assault before the age of 18 years, and 81.3 of females and 70.8 males experi encing their first sexual assault before the age of 25 years (NISVS 2015). Between 1995 and 2013 the rate of rape and sexual assault was highest |
6,341 | for adolescent females between ages 18 and 24 years. The National Sur vey of Childrens Exposure to Violence (NatSCEV 2014) revealed that 12.9 of 14 to 17 year olds experienced any sexual victimization in the past year, 21.7 had experienced any sexual victimization in their lifetime, 4.2 experienced sexual assault in the past year, and 10.2 in their lifetime. This survey also demonstrated how other experiences with violence compound the risk for sexual victimization. Youth with a history of maltreatment by a caregiver were four times more likely to experience sexual victimization and more than four times more likely to experience sexual victimization if they were a witness to violence. Among older adolescents age 18 24 years, the rate of rape and sexual Chapter 162 Adolescent Sexual Assault Allison M. Jackson, Adrianne R. Artis, and Norrell K. Atkinson Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 162 u Adolescent Sexual Assault 1235 Table 162.1 Adolescents at High Risk of Rape Victimization MALE, FEMALE, NONBINARY ADOLESCENTS Drug and alcohol users Runaways Those with intellectual disability or developmental delay Street youths Transgender youth Youths with a history of sexual abuse PRIMARILY FEMALES Survivors of prior sexual assault Newcomers to a town or college PRIMARILY MALES Those in institutionalized settings (detention centers, prison) Gay males assault was 1.2 times higher for those not enrolled in college than those in college. Further, several studies of youth in the juvenile justice sys tem demonstrate a particularly high prevalence of prior sexual victim ization of young females in that setting. Rape occurs worldwide and is especially prevalent in war and armed conflicts. The World Health Organization estimates that rape and domestic violence are respon sible for 516 of healthy years of life lost by females of reproductive age. Female adolescents and young adults have the highest rates of rape compared to any other age group. The normal developmental growth tasks of adolescence may contribute to this vulnerability in the follow ing ways: (1) the emergence of independence from parents and the establishment of relationships outside the family may expose adoles cents to environments with which they are unfamiliar and situations that they are unprepared to handle; (2) dating and becoming comfort able with ones sexuality may result in activities that are unwanted, but the adolescent is too inexperienced to avoid the unwanted actions; and (3) young adolescents may be nave and more trusting than they should be (see Chapter 150). Many teens are technologically compe tent, which gives sexual perpetrators access to unsuspecting vulner able populations who were previously beyond their reach. Social media and online dating sites represent a major risk for adolescents, as they facilitate correspondence with individuals unknown to them or protec tive family members, while simultaneously providing a false sense of security because of remote electronic communications. A determined perpetrator can obtain specific information to |
6,342 | identify the adolescent and arrange for a meeting that is primed for sexual victimization. Some adolescents are at higher risk of being victims of rape than others (Table 162.1). TERMINOLOGY Sexual violence is a term that broadly encompasses criminal acts including sexual assault, rape and sexual abuse, and which dispro portionately affects adolescents and young adults. Because of the prev alence of sexual violence in the adolescent population, it is important for healthcare providers to have a general understanding of the types of sexual violence that may affect children and adolescents. Providers should also be aware that every state carries their own legal definition of these crimes. These definitions dictate if or how a crime is prose cuted, which could affect survivors who have disclosed sexual violence. Delayed disclosures of sexual violence are common. The circum stances and relationship of the assailant to the survivor can often affect if, when, and how a child or youth discloses an assault. Sexual violence is typically perpetrated by someone who knows their victim; less fre quently the assailant is a stranger. The gender of the survivor may also affect the disclosure process. Males are less likely to disclose sexual vio lence compared with females. Individuals who are transgender, gender nonconforming, nonbinary, or other noncisgender identities are less likely to disclose sexual assault than those who identify as cisgender. In any scenario where rape is facilitated by threats, coercion, physical force, or illicit andor legal substances, the disclosure process for a sur vivor of sexual assault can be impacted. TYPES OF SEXUAL VIOLENCE Sexual assault is defined as sexual contact or behavior that occurs without explicit consent of the victim. It can include things such as attempted rape, rape, fondling, or forcing a person to perform sexual acts. It is important to remember that force is not always physical, but it can also be intimidation or coercive control of the person. Force may also include threatening to hurt the person or those close to them. Rape is a form of sexual assault involving penetration. Not all sex ual assaults are rape. Rape can further be defined as stranger rape vs acquaintance rape. Intimate partner sexual violence is a form of acquaintance rape. An intimate partner is defined as a person with which the survivor has had a close personal or sexual relationship; thus this form of sexual violence can be prevalent among adolescents. Inti mate partner sexual violence can often start with controlling or emo tionally abusive behaviors, which then escalate to assault. Rape can frequently involve illicit andor legal substances to facili tate the assault. Drug facilitated rape involves perpetrators adminis tering substances such as hydroxybutyric acid (GHB), flunitrazepam (Rohypnol), and ketamine hydrochloride to their victim. More com monly, substances such as alcohol, tetrahydrocannabinoids (THC), benzodiazepines, stimulants, barbiturates, opioids, or other drugs are used during the course of an assault. Detection of these drugs requires a high index of suspicion, and a medical evaluation within 8 12 hours is necessary for prompt detection |
6,343 | of these substances, Specific testing is used that is more sensitive than routine toxicology screens, which are often insufficient. Sexual abuse is a type of child abuse (see Chapter 17). The Ameri can Academy of Pediatrics defines child sexual abuse as a child or ado lescent who engages in sexual activities that they cannot comprehend, for which they are developmentally unprepared and unable to give informed consent, andor when there is a violation of the legal or social taboos of society. It includes many things ranging from oral, genital, or anal contact and fondling by or of the child, to noncontact abuses, such as exhibitionism, voyeurism, or various forms of child exploita tions such as pornography. The commercial sexual exploitation of children (CSEC), also known as sex trafficking, is a more complex form of sexual violence and is considered a form of child abuse (see Chapter 16). Sex traffick ing is federally defined as the recruiting, harboring, transporting, pro viding, obtaining, patronizing, or soliciting of an individual through the means of force, fraud, or coercion for commercial sex. Although a pimp often personally recruits victims, they may use others to recruit. These youth may experience physical and sexual assault by the pimp as well as the johns. Many of these youth have a history of child mal treatment, increasing their vulnerability to this form of abuse. Fear of the consequences of disclosure and the survival skills acquired often yield a very guarded presentation in the healthcare setting. Survivors of sexual violence often experience long term symptoms related to the trauma they have sustained. Untreated trauma can nega tively affect the physical and emotional health of an adolescent into adulthood. Engagement in trauma focused therapy, combined with a supportive environment for the adolescent to grow, can help to miti gate the effects of the trauma that they have sustained. Providers should be knowledgeable of trauma focused therapists in their community where adolescent survivors of sexual violence can receive care. CLINICAL MANIFESTATIONS The adolescents acute presentation after a rape may vary considerably, from histrionics to near mute withdrawal. Even if they do not appear afraid, most victims are extremely fearful and very anxious about the incident, the rape report, the examination, and the entire process, including potential repercussions. Because adolescents are between the developmental lines of childhood and adulthood, their responses to rape may have elements of both child and adult behaviors. Many teens, Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1236 Part XI u Adolescent Medicine particularly young adolescents, may experience some level of cognitive disorganization. Adolescents may be reluctant to report rape for a variety of reasons, including self blame, fear, embarrassment, or in the cir cumstances of drug facilitated rape, uncertainty of event details. Adolescent victims, unlike child victims who elicit sympathy and support, often face intense scrutiny regarding their credibility and |
6,344 | inappropriately misplaced societal blame for the assault. This view is baseless and should not be used during an evaluation of any teen age victim of sexual violence. When adolescents do not report a rape, they may present at a future date with concerns for pregnancy; symptoms of or concerns for a sexually transmitted infection (STI); and symptoms of posttraumatic stress disorder (see Chapter 38), such as sleep disturbances, nightmares, mood swings, and flash backs. Other teens may present with psychosomatic complaints or difficulties with schoolwork. All adolescents should be screened for possible sexual victimization at health examination visits. INTERVIEW AND PHYSICAL EXAMINATION The purpose of the adolescent medical evaluation after a sexual assault is to provide medical care for the teen and to collect and document evidence of the assault when applicable. Although many teens delay seeking medical care, others present to a medical facil ity within 72 hours (or up to 96 hours depending on the protocol used) of the rape, at which time forensic evidence collection should be offered to the patient. Whether presenting acutely or more remotely, a comprehensive physical exam is recommended to the extent that the patient allows. Experienced clinicians with training and knowledge of forensic evidence collection and medical legal procedures should complete the rape evaluation or supervise the evaluation when possible. The clinicians responsibilities are to provide support, obtain the history in a nonjudgmental and noncoercive manner, conduct a complete examination without retraumatizing the victim, and collect forensic evidence. The clinician must complete laboratory testing, administer prophylaxis treatment for STIs and emergency contraception, arrange for counseling services, and file a report to appropriate authorities in accordance with the law. In some juris dictions, healthcare professionals are required to report all sexual assaults of minors regardless of the relationship of the victim to the perpetrator. Although healthcare professionals are legally mandated to report sexual abuse, when the perpetrator is an acquaintance or stranger, some jurisdictions leave the decision of reporting up to the victim, requiring the victim to report the sexual assault. It is not the clinicians responsibility to decide whether a sexual assault has occurred; the legal system will make that determination. Further more, absence of injury does not exclude the possibility that sexual assault occurred. Ideally, a clinician trained in forensic interviewing should obtain the history. In all cases, the history should be obtained by asking only open ended questions to obtain information about (1) what happened, (2) where it happened, (3) when it happened, and (4) who did it. After obtaining a concise history, including details of the type of physical contact that occurred between the victim and the assailant, the clinician should conduct a thorough and com plete physical examination and document all injuries (nongenital and genital). Clinicians should provide sensitive, nonjudgmental support during the entire evaluation, as the adolescent victim has experienced a major trauma and is susceptible to retraumatization during this process. Each component of the evaluation should be explained in detail to the victim, allowing the adolescent |
6,345 | as much control as possible, including refusal to complete any part or all of the forensic evidence collection process. For sensitive examina tions like these, a chaperone should be offered. Additionally, it is often useful to permit a trusted supportive person, such as a family member, friend, or rape crisis advocate, to be present during the evaluation if that is the adolescents wish. The examining clinician should be familiar with forensic evidence collection and the physical evidence recovery kit (PERK) before ini tiating the examination. In the United States, each states PERK is dif ferent, but most include some or all of the following components: swabs of suspected semen deposits, swabs of bite mark impressions to collect genetic markers (DNA, ABO group); swabs of any penetrated orifice or body surface where saliva may be present; and documen tation of acute cutaneous injuries using body diagram charts and photographs with visible standard measurements. Areas of restraint should be carefully inspected for injuries; these areas include the extremities and neck. Inspection of the skin may also reveal suction injuries or bite impressions. Inspection of the mouth, with particular attention to the oral frenula and palate, may reveal mucosal injury. Although use of alternative light sources, such as the Wood lamp or blue light, enhance detection of semen and saliva, other common substances such as urine and lotion also fluoresce with alternative light sources. Swabs of sites that fluoresce under such light should be obtained for further forensic analysis. The genital examination of a female rape victim should be undertaken with the patient in the lithotomy position. The prone knee chest position may be used as an exam clarifying technique, specifically to evaluate the posterior rim of the hymen and perianal area. The genital exam of a male rape victim should be undertaken with the patient in the supine position. The clinicians exam should include careful inspection of the entire pelvic, genital, and peri anal areas. The clinician should document any acute injuries such as edema, erythema, petechiae, bruising, hemorrhage, or tearing. Aqueous solution of toluidine blue (1), which adheres to nucle ated cells, may be used during the acute examination to improve visualization of microtrauma in the perianal area. Any disruption to the superficial epidermis will allow for dye uptake and thus cannot differentiate between disruption of the skin from trauma, irritation, or infection. Additionally, a colposcope may be used to provide magnification and photo documentation of injuries. LABORATORY DATA When adolescents present for medical care within 72 120 hours of a sexual assault, a forensic evidence collection kit should be offered to the patient. The time frames of eligibility for forensic evidence collection vary according to jurisdiction, so it is important to know the criteria of the jurisdiction investigating the assault. Regardless of an adolescents decision to have evidence collection completed, medical care, including physical examination, laboratory testing (Table 162.2), and prophylactic therapies, should be offered to the patient. Follow up evaluations should be scheduled to repeat these laboratory studies. TREATMENT |
6,346 | Treatment includes prophylactic antimicrobials for STIs (see Chapter 163) and emergency contraception (see Chapter 160.6). The Centers for Disease Control and Prevention (CDC) reports that trichomoniasis, bacterial vaginosis, gonorrhea, and chlamydia are the most frequently diagnosed infections among women who have been sexually assaulted. Antimicrobial prophylaxis is recom mended for adolescent rape victims because of the risk of acquiring an STI and the risk of pelvic inflammatory disease (Table 162.3). HIV postexposure prophylaxis (PEP) must be considered and an infectious disease specialist consulted if higher transmission risk factors are identified (e.g., knowing that the perpetrator is HIV positive, significant mucosal injury of the victim) to prescribe a triple antiretroviral regimen (Fig. 162.1). Hepatitis B infection can be prevented with immunoglobulin andor vaccination depending on the victims immunization status and the perpetrators status; thus similar considerations should be made for possible exposure Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 162 u Adolescent Sexual Assault 1237 to the hepatitis B virus in vaccinatedunvaccinated individuals. Human papilloma virus (HPV) vaccination is also recommended because persons who have been sexually assaulted are also at risk for infection, and the efficacy of the HPV vaccine is high. Clini cians should review the importance for the patients compliance with medical treatment, psychologic treatment, and follow up care. Counseling should be provided about the symptoms of STIs and the need for urgent follow up if symptoms develop. Abstinence from sexual intercourse should be recommended until the completion of the STI prophylactic course. At the time of presentation, the clinician should address the need for follow up care, including psychologic counseling. Adoles cent victims are at increased risk of posttraumatic stress disorder, depression, self abusive behaviors, suicidal ideation, delinquency, substance abuse, eating disorders, and sexual revictimization. It is important for the adolescent victim and parents to understand the value of timely counseling services to decrease these potential long term sequelae. Counseling services should be arranged during the initial evaluation, with follow up arranged with the primary care physician to improve compliance. FOLLOW UP Follow up evaluation should be arranged within 1 week of the initial evaluation with a child abuse pediatrician or a Child Advocacy Center to provide an opportunity for prompt review of STI test results, to monitor for medication adherence and possible side effects, to ensure healing and documentation of injuries, and to evaluate for the resolution of symptoms initially present, the development of new physical symptoms, or emerg ing mental health concerns. If no STI prophylaxis was given, follow up testing for gonorrhea, chlamydia, and trichomonas can be repeated in 1 2 weeks after the assault. If prophylaxis was provided, follow up test ing is not needed unless symptoms develop. If infection in the assailant cannot be ruled out, serologic testing for syphilis can be repeated in 4 6 weeks and 3 months, and for HIV in |
6,347 | 6 weeks and 3 months. PREVENTION Primary prevention may be accomplished through education of pre adolescents and adolescents on the issues of consent, rape, healthy Table 162.2 Laboratory Evaluation of Sexual Assault Within 8 12 hr (if Indicated by History) Urine and blood for date rape drugs (GHB, Rohypnol, and ketamine) Within 24 hr (if Indicated by History) Blood for comprehensive toxicology screen (for other classes of drugs) Within 72 hr (or up to 96 hr Depending on Protocol Used) Forensic evidence kit Pregnancy test Hepatitis B screen (hepatitis B surface antigen, surface antibody, and core antibody) Syphilis (rapid plasma reagin RPR or Venereal Disease Research Laboratory VDRL) HIV (HIV 12 AgAb immunoassay, point of care testing can be useful in persons unlikely to follow up with a provider) Bacterial vaginosis (BV) and candidiasis: point of care testing and or wet mount of vaginal secretions with measurement of pH and KOH application for whiff test Trichomonas vaginalis: nucleic acid amplification tests (NAATs) by urine or vaginal specimen or point of care testing (i.e., DNA probes) from vaginal specimen Chlamydia and Neisseria gonorrhoeae: NAATs at sites of penetration or attempted penetration: N. gonorrhoeae: oropharynx (), rectum (), urine () Chlamydia: rectum (), urine () Men who have sex with men (MSM) should be offered screening of gonorrhea and chlamydia if they report receptive oral or anal sex during the preceding year even if there was not contact at these sites during the assault. NAAT can be obtained on a dirty urine sample as an alternative to a genital swab. From Centers for Disease Control and Prevention. Sexually transmitted diseases: treatment guidelines 2015, MMWR Recomm Rep. 2015;64(RR 3):1140; and Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIVUnited States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:458. Table 162.3 Postexposure Prophylaxis (PEP) for Acute Sexual Assault Victims ROUTINE Recommended regimen for STI prophylaxis Ceftriaxone 500 mg IM once in a single dose PLUS Doxycycline 100 mg orally twice a day for 7 days (azithromycin 1 g orally in a single dose should be considered in persons at high risk for noncompliance) PLUS (for females) Metronidazole 500 mg orally twice a day for 7 days (2 g orally in a single dose should be considered in persons at high risk for noncompliance) Pregnancy prophylaxis Levonorgestrel (Plan B) 1.5 mg orally in a single dose Ulipristal acetate (Ella) 30 mg is effective for up to 120 hr HPV Assess HPV vaccination history; vaccine should be provided at initial evaluation if unimmunized or partially immunized If unimmunized and 15 yr at the time of the initial exam, give first dose and, two follow up doses at 1 2 mo and 6 mo If 15 yr, a single follow up dose at 6 12 mo If partially immunized, a follow up dose if 5 mo since the first dose or 12 wk since the second dose AS INDICATED HIV Preferred regimen Tenofovir 300 mg and fixed dose combination emtricitabine |
6,348 | 200 mg (Truvada) once daily PLUS Raltegravir 400 mg orally twice a day OR Dolutegravir 50 mg orally once a day All persons with a potential exposure within 72 hours should be offered PEP, which includes a 28 day course of a three drug antiretroviral regimen. Hepatitis B Alternative regimens available. Specific indications for vaccine, immunoglobulin, andor booster depend on assailants status If 150 kg, give 1 g of ceftriaxone IM once. Provided for patients with negative urine pregnancy screen. In addition, an antiemetic (Compazine, Zofran) can be prescribed for patients receiving emergency contraception. HIV PEP is provided for patients with penetration and when the assailant is known to be HIV positive or at high risk because of a history of incarceration, intravenous drug use, or multiple sexual partners. If provided, laboratory studies must be drawn before administration of medication (HIV, CBC, LFTs, BUNCr, amylase, lipase), and follow up must be arranged. Data from Workowski, KA, Bachmann, LH, Chan, PA Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021;70:128 135. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1238 Part XI u Adolescent Medicine Substantial exposure risk 72 hours since exposure 72 hours since exposure Source patient known to be HIVpositive PEP recommended Substantial risk for HIV acquisition Exposure of vagina, rectum, eye, mouth, or other mucous membrane, nonintact skin, or percutaneous contact With blood, semen, vaginal secretions, rectal secretions, breast milk, or any body fluid that is visibly contaminated with blood When the source is known to be HIVpositive Negligible risk for HIV acquisition Exposure of vagina, rectum, eye, mouth, or other mucous membrane, intact or nonintact skin, or percutaneous contact With urine, nasal secretions, saliva, sweat, or tears if not visibly contaminated with blood Regardless of the known or suspected HIV status of the source PEP not recommended Casebycase determination Source patient of unknown HIV status Negligible exposure risk Fig. 162.1 Algorithm to evaluate the need for nonoccupational HIV postexposure prophylaxis among adult and adolescent survivors of sex ual assault. (From Workowski, KA, Bachmann, LH, Chan, PA. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70:128135; adapted from Announcement: updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIVUnited States, 2016. MMWR Morb Mortal Wkly Rep. 2016;65:458.) relationships, internet dangers, and drug and alcohol facilitated rape. Prevention messages should be targeted at males, females, and nonbinary youth at high schools and colleges. Particular emphasis on prevention efforts during college orientation is highly recommended. High risk situations that may increase the likelihood of a sexual assault should be discouraged, such as the use of drugs or alcohol, drinking from a container that has been left unattended, and accept ing drinks from strangers. Secondary prevention includes informing adolescents of the benefits of timely medical evaluations when rape has occurred. Individual clinicians should ask adolescents about |
6,349 | past experiences of forced and unwanted sexual behaviors and offer help in dealing with those experiences. The importance of prevention can not be overstated because adolescents are disproportionately affected by sexual assault, and they are particularly vulnerable to long term consequences. Counseling services for family members of the victim may improve their ability to provide appropriate support to the adolescent victim. Caution parents not to use the assault as a validation of their parental guidance, as it will only serve to place blame inappropriately on the adolescent victim. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 163 u Sexually Transmitted Infections 1239 Age specific rates of many sexually transmitted infections (STIs) are highest among sexually experienced adolescents and young adults, after controlling for sexual activity. Although some STI pathogens present as STI syndromes with a specific constellation of symptoms, most are asymptomatic and only detected by a laboratory test. The approach to prevention and control of these infections lies in educa tion, screening, and early diagnosis and treatment. ETIOLOGY Any adolescent who has had oral, vaginal, or anal sexual intercourse is behaviorally vulnerable to acquiring an STI. Not all adolescents are at equal risk; physical, behavioral, and social factors contribute to an ado lescents risk. Adolescents who initiate sex at a younger age; youth resid ing in detention facilities; youth attending STI clinics; youth involved in commercial sex exploitation or survival sex and exchange sex for drugs, money, food, or housing; young males having sex with males (YMSM); adolescent women and young adult women having sex with older men; transgender youth; youth with disabilities; and youth who are injection drug users are at higher risk for STIs. Risky behaviors, such as sex with multiple concurrent partners or multiple sequential partners of limited duration, failure to use barrier protection consis tently and correctly, and increased biologic susceptibility to infection also contribute to risk (Table 163.1). Although all 50 states and the District of Columbia explicitly allow minors to consent for their own sexual health services (at varying ages), many adolescents encounter multiple obstacles to accessing this care, including poverty, insurance coverage, and fears of lack of confidentiality (see Table 163.1). Adoles cents who are survivors of sexual assault need reassurance, protection, and appropriate intervention when these circumstances are uncovered (see Chapter 162). EPIDEMIOLOGY STI prevalence varies by age, gender, race, and ethnicity. In the United States, although adolescents and young adults ages 15 24 represent 25 of the sexually experienced population, this age group accounts for almost 50 of all incident STIs each year. Chlamydia is the most frequently reported infectious disease in the United States and is the second most common STI in U.S. adolescents and young adults after human papillomavirus (HPV). In 2019, young adult females ages 20 24 (3,797.8 cases per 100,000 females) followed |
6,350 | by females ages 15 19 (2,697.0 cases per 100,000 females) had the highest rates of chlamydia in the United States (Fig. 163.1). Notably age specific rates of reported cases of chlamydia among males, although substantially lower than rates among females, were still highest in young adult males 20 24 years (1,680.0 cases per 100,000 males). Chlamydia remains com mon among all races and ethnic groups. In 2021, a total of 1,644,416 cases of Chlamydia trachomatis infection were reported to the CDC, making it the most common notifiable sexually transmitted infection in the United States for that year. This case count corresponds to a rate of 495.5 cases per 100,000 population, an increase of 3.9 compared with the rate in 2020. During 2020 to 2021, rates of reported chlamydia increased among both males and females, in all regions of the United States, among most age groups, and among all raceHispanic ethnicity groups. Rates of reported chlamydia are highest among adolescents and young adults. In 2021, almost twothirds (58) of all reported chlamydia cases were among persons aged 1524 years. Reported rates of other bacterial STIs are also high among adoles cents and young adults. In 2021, gonorrhea rates among adolescents were 360.1100,000 for males ages 15 19 compared to 587.8100,000 for young women ages 15 19. Gonorrhea rates for young adult males ages 20 24 years old (844.2100,000) were significantly higher than rates for males at any other agesex group and slightly lower than for young women ages 20 24 (873.2100,000). Pelvic inflammatory disease (PID) is a clinical syndrome that results from the ascension of microorganisms from the cervix and vagina to the upper genital tract. PID is a serious complication of chla mydia and gonorrhea, two of the most common reportable infectious diseases and STIs in the United States. PID rates are highest among females ages 15 24 compared with older women. Syphilis rates have increased at an alarming rate, especially among males, since 2000. In 2021, young adult males age 2024 had the third highest rate of primary and secondary syphilis at 51.2 per 100,000. Rates among adolescent males ages 1519 were lower at 12.0 per 100,000. Chapter 163 Sexually Transmitted Infections Tamera Coyne Beasley, Nefertiti H. Durant, and Samantha V. Hill Table 163.1 Circumstances Contributing to Adolescents Susceptibility to Sexually Transmitted Infections PHYSICAL Younger age at puberty Cervical ectopy Smaller introitus leading to traumatic sex Asymptomatic nature of sexually transmitted infection Uncircumcised penis BEHAVIOR INFLUENCED BY DEVELOPMENTAL STAGES Early adolescence: Lack ability to think abstractly Middle adolescence: Believe in uniqueness and lack of vulnerability SOCIAL FACTORS Poverty Limited access to adolescent friendly healthcare services Adolescent health seeking behaviors (forgoing care because of confidentiality concerns or denial of health problem) Sexual abuse, trafficking, and violence Lower levels of condom use Mental health issues and substance useabuse Decreased access to confidential medical care leading complexity in seeking care Homelessness Young adolescent females with older partners Young men having sex with men Data from Wangu, G Burstein. Adolescent sexuality: updates to |
6,351 | the Sexually Transmitted Infection Guidelines. Ped Clin North Am. 2017;64:389341; and Spear LP. Adolescent neurodevelopment. J Adolesc Health. 2013;52:S7S13. 823.0 1,680.0 1,087.4 658.0 385.2 231.7 114.9 46.9 7.9 357.4 11.7 3,900 0 Male rate Female rate Age group (Years) 2,697.0 3,797.5 1,672.1 767.9 388.7 167.2 73.7 20.1 2.5 628.8 83.1 3,9000 1014 1519 2024 2529 3034 3539 4044 4554 5564 65 Total Fig. 163.1 Chlamydia: Rates of reported cases by age group and sex, United States, 2021. (Data from the Centers for Disease Control and Prevention: www.cdc.govstdstatistics2021data.zip.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1240 Part XI u Adolescent Medicine Rates of female primary and secondary syphilis are much lower than male rates (7.5100,000 among 1519 year olds; 19.5100,000 among 2024 year olds). Adolescents also carry a large burden of viral STIs. U.S. youth are at persistent risk for HIV infection. However, according to the 2021 Youth Risk Behavior Survey, only 6 of high school students have ever been tested for HIV. Adolescents (persons aged 1319 years) and young adults (persons aged 2024 years) accounted for 21 of the 36,801 diagnoses of HIV infection in 2019 in the United States and 6 depen dent areas. They are the least likely of any age group to be aware of their HIV infection, retained in care, or have a suppressed viral load. From 2015 through 2019 in the United States and 6 dependent areas, the number of diagnoses of HIV infection among adolescents and young adults for males, females, and transgender MTF decreased. In 2019, diagnoses of HIV infection among adolescent and young adult males (85) and females (12) accounted for approximately 97 of HIV diagnoses. Transgender MTF adolescents and young adults accounted for 3 of annual diagnoses. From 2015 through 2019 in the United States, the rate of diagnosis of HIV infection for Asian, BlackAfrican American, and multiracial adolescents decreased. The rates of diagnosis of HIV infection for HispanicLatino and White adolescents remained stable. In 2019, the highest rate was 23.5 for BlackAfrican American adolescents, followed by 6.3 for Hispanic Latino, and 4.2 for multiracial adolescents. Racial and ethnic dispari ties persist. Human papillomavirus (HPV) is the most frequently acquired STI in the United States. According to the National Health and Nutrition Examination Survey (NHANES), prevalence of HPV vac cine types 6, 11, 16, and 18 (4vHPV) declined between the pre vaccine (20032006) and vaccine (20092012) eras: from 11.5 to 4.3 among females ages 14 19 and from 18.5 to 12.1 among females ages 20 24. Within 6 years of introduction of the HPV vac cine, there was a 64 decrease in 4vHPV type prevalence among female youth ages 14 19 and a 34 decrease among young adult women ages 20 24. Efforts are ongoing to improve vaccination among all youth. Herpes simplex virus type 2 (HSV 2) is the most prevalent viral STI |
6,352 | (see Chapter 299). According to NHANES data, prevalence of both HSV 1 and HSV 2 decreased from 19992000 to 20152016 (from 59.4 to 48.1 and from 18.0 to 12.1, respectively). According to Centers for Disease Control and Prevention (CDC) data, seroprevalence for HSV 2 for adolescents ages 14 19 was low, at 0.8. It is important to note that among young adults ages 20 29, HSV 2 prevalence is higher, at 7.6. Prevalence of HSV 1 among 14 to 19 year olds was 27 compared to 41 among those ages 20 29. There are notable ethnic, racial, and gender disparities in HSV prevalence. Prevalence of HSV 1 was highest among Mexican American persons and lowest among non Hispanic White persons. HSV 2 prevalence was highest among Hispanic Black persons and lowest among non Hispanic Asian persons. Both HSV 1 and HSV 2 were higher among females than males. PATHOGENESIS During puberty, increasing levels of estrogen cause the vaginal epithelium to thicken and cornify and the cellular glycogen content to rise, with the latter causing the vaginal pH to fall. These changes increase the resistance of the vaginal epithelium to penetration by certain organisms (including Neisseria gonorrhoeae) and increase the susceptibility to others (Candida albicans and Trichomonas; see Chapter 330). The transformation of the vaginal cells leaves columnar cells on the ectocervix, forming a border of the two cell types on the ectocervix known as the squamocolumnar junc tion. The appearance is referred to as ectopy (Fig. 163.3). With maturation, this tissue involutes. Before involution, it represents a unique vulnerability to infection for adolescent females. The association of early sexual debut and younger gynecologic age with increased risk of STIs supports this explanation of the pathogenesis of infection in young adolescents. SCREENING Early detection and treatment are primary STI control strategies. Some of the most common STIs in adolescents, including HPV, HSV, chlamydia, and gonorrhea, are usually asymptomatic and, if undetected, can be spread inadvertently by the infected host. Screening initiatives for chlamydial infections have demonstrated reductions in PID cases by up to 40. Fed eral and professional medical organizations recommend annual chlamydia and gonorrhea screening for sexually active females 25 years old (Table 163.2). The lack of a dialog about STIs or the provision of STI services at annual preventive service visits to sexually experienced adolescents is a missed opportunity for screening and education. Comprehensive, con fidential, reproductive health services, including STI screening, should be offered to all sexually experienced adolescents (see Table 163.2). COMMON INFECTIONS AND CLINICAL MANIFESTATIONS STI syndromes are generally characterized by the location of the manifestation (vaginitis, enteritis) or the type of lesion (genital ulcer). Certain constellations of presenting symptoms suggest the inclusion of a possible STI in the differential diagnosis. Urethritis Urethritis is an STI syndrome characterized by inflammation of the urethra, usually caused by an infectious etiology. Urethritis may pres ent with urethral discharge, dysuria, urethral irritation, or meatal pruritus. Urgency, frequency of urination, erythema of the urethral meatus, and urethral pain or burning |
6,353 | are less common clinical pre sentations. Approximately 3050 of males are asymptomatic but may have signs of discharge on diagnosis. On examination, the classic finding is mucoid or purulent discharge from the urethral meatus (Fig. 163.4). If no discharge is evident on exam, providers may attempt to 12.0 51.2 68.1 67.7 51.3 37.1 24.8 14.8 3.1 25.2 0.0 70 0 Male rate Female rate Age group (Years) 7.5 19.5 22.3 18.9 16.7 12.2 5.8 1.7 0.2 7.3 0.2 700 1014 1519 2024 2529 3034 3539 4044 4554 5564 65 Total Fig. 163.2 Primary and secondary syphilisRates of reported cases by age group and sex, United States, 2021. (Data from the Centers for Disease and Control and Prevention: www.cdc.govstdstatistics2021data.zip.) Fig. 163.3 Cervical ectopy. (From Seattle STDHIV Prevention Train ing Center, University of Washington, Claire E. Stevens.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 163 u Sexually Transmitted Infections 1241 express discharge by applying gentle pressure to the urethra from the base distally to the meatus 3 4 times. Chlamydia trachomatis and N. gonorrhoeae are the most commonly identified pathogens. Mycoplasma genitalium has been associated with urethritis, but data supporting Ureaplasma urealyticum have been inconsistent. Trichomonas vagi nalis can cause nongonococcal urethritis (NGU), but the prevalence varies. HSV 1, HSV 2, and Epstein Barr virus (EBV) are also potential urethritis pathogens in some cases. Sensitive diagnostic C. trachomatis and N. gonorrhoeae tests are available for the evaluation of urethritis. However, other pathogens can be considered when NGU is not respon sive to treatment. Noninfectious causes of urethritis include urethral trauma or foreign body. Unlike in females, urinary tract infections (UTIs) are rare in males who have no genitourinary medical history. In the typical sexually active adolescent male, dysuria and urethral dis charge suggest the presence of an STI unless proven otherwise. Epididymitis The inflammation of the epididymis in adolescent males is most often associated with an STI, most frequently C. trachomatis or N. gonor rhoeae. The presentation of unilateral scrotal swelling and tenderness, often accompanied by a hydrocele and palpable swelling of the epidid ymis, associated with the history of urethral discharge constitute the presumptive diagnosis of epididymitis. Males who practice insertive anal intercourse are also vulnerable to Escherichia coli infection. Tes ticular torsion, a surgical emergency usually presenting with sudden onset of severe testicular pain, should be considered in the differential Table 163.2 Routine Laboratory Screening Recommendations for Sexually Transmitted Infections in Sexually Active Adolescents and Young Adults CHLAMYDIA TRACHOMATIS AND NEISSERIA GONORRHOEAE Routine screening for C. trachomatis and N. gonorrhoeae of all sexually active females age 25 yr is recommended annually. Extragenital chlamydia and gonorrhea screening (pharyngeal or rectal) can be considered on the basis of reported sexual behaviors and exposure, through shared clinical decision making between the patient and the provider. Routinely screen sexually active adolescent and young adult MSM at |
6,354 | sites of contact for chlamydia (urethra, rectum) and gonorrhea (urethra, rectum, pharynx) at least annually regardless of condom use. NAAT is preferred for provider or self collected specimens. More frequent screening (i.e., at 3 to 6 mo intervals) is indicated for MSM, including those taking PrEP and those with HIV infection, if risk behaviors persist or if they or their sex partners have multiple partners or anonymous partners or have sex with illicit drug use. Consider screening for C. trachomatis of sexually active adolescent and young adult males annually who have a history of multiple partners in clinical settings with high prevalence rates, such as jails or juvenile correction facilities, national job training programs, STD clinics, high school clinics, or adolescent clinics. HUMAN IMMUNODEFICIENCY VIRUS (HIV) The following recommendations apply to testing for HIV: HIV testing is recommended for all adolescents and young adults seeking STI evaluation andor treatment who are not already known to have HIV infection. Testing should be routine at the time of the STI evaluation, regardless of whether the patient reports any specific behavioral risks for HIV. The CDC and USPSTF recommend HIV screening at least once for all persons age 13 64 yr or 1565, respectively. Persons at higher risk for HIV acquisition, including sexually active gay, bisexual, and other MSM, should be screened for HIV at least annually. Providers can consider the benefits of offering more frequent screening (e.g., every 3 6 months) among MSM at increased behavioral risk for acquiring HIV. All pregnant adolescents should be tested for HIV during the first prenatal visit. A second test during the third trimester, preferably at 36 weeks gestation, should be considered and is recommended for adolescents and young adults who are at high risk for acquiring infection. HIV screening should be voluntary and free from coercion. Patients should not be tested without their knowledge. Providers should use a laboratory based antigenantibody (Ag Ab) combination assay as the first test for HIV, unless persons are unlikely to follow up with a provider to receive their HIV test results; in those cases screening with a rapid POC test can be useful. Providers should test for HIV RNA if initial testing according to the HIV testing algorithm recommended by the CDC is negative or indeterminate when concerned about acute HIV infection (https: stacks.cdc.govviewcdc50872). HIV screening should be discussed and offered to all adolescents at least once by age 16 18 yr and throughout young adulthood in healthcare settings. HIV risk should be assessed annually for 13 yr and offered if HIV risk factors are identified. Routinely screen sexually active adolescent and young adult MSM at least annually regardless of condom use. More frequent screening (i.e., at 3 to 6 mo intervals) is indicated for MSM who have multiple or anonymous partners or who have sex with illicit drug use. SYPHILIS Syphilis screening should be offered to sexually active adolescents reporting risk factors, including MSM. Routinely screen sexually active adolescent and young adult MSM at least annually regardless of |
6,355 | condom use. More frequent screening (i.e., at 3 to 6 mo intervals) is indicated for MSM who have multiple or anonymous partners or who have sex with illicit drug use. Screen women at 1st prenatal visit, at 28 weeks, at delivery if at greater behavioral risk. Screen asymptomatic women who may have increased behavioral vulnerability (history of incarceration, transactional sex, higher rate in community). Providers should consult with their local health department regarding local syphilis prevalence and associated risk factors that are associated with syphilis acquisition. HEPATITIS B VIRUS All MSM should be screened with HBsAg, HBV core antibody, and HBV surface antibody. Vaccination against both HAV and HBV is recommended for all MSM when a previous infection or vaccination cannot be documented. HEPATITIS C VIRUS AND UNIVERSAL HEPATITIS C SCREENING The CDC recommends hepatitis C screening at least once in a lifetime for all adults age 18 yr and older, except in settings where the prevalence of HCV infection (HCV RNA positivity) is 0.1. Hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection (HCV RNA positivity) is less than 0.1. Screening adolescents younger than 18 yr old for HCV who report risk factors, that is, injection drug use, receipt of an unregulated tattoo, received blood products or organ donation before 1992, received clotting factor concentrates before 1987, or long term hemodialysis. Given the high HCV prevalence among young injection drug users, screening should be strongly considered. All people living with HIV should be screened during the initial HIV evaluations and at least annually thereafter. Screening should be performed using HCV antibody assays followed by HCV RNA testing for those with a positive antibody test. Routine screening of adolescents and young adults who are asymptomatic for certain STIs (i.e., syphilis, trichomoniasis, BBV, HSV, HAV, and HB) is not typically recommended. From Centers for Disease Control and Prevention: https:www.cdc.govstdtreatment guidelinesscreening recommendations.htm and https:www.cdc.govhepatitishcvguideline sc.htm. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1242 Part XI u Adolescent Medicine diagnosis (see Chapter 582). The evaluation for epididymitis should include obtaining evidence of urethral inflammation by physical exam, Gram stain of urethral secretions, urine leukocyte esterase test, or urine microscopy. A C. trachomatis and N. gonorrhoeae nucleic acid amplification test (NAAT) should be performed. Vaginitis Vaginitis is a superficial infection of the vaginal mucosa frequently presenting as vaginal discharge, with or without vulvar involvement (see Chapter 586). Bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis are the predominant infections associated with vaginal discharge. Bacterial vaginosis is caused by replacement of the normal hydrogen peroxide (H2O2)producing Lactobacillus spe cies vaginal flora by an overgrowth of anaerobic microorganisms, as well as Gardnerella vaginalis, Ureaplasma, and Mycoplasma. It is diagnosed based on an individual having at least three out of four of Amsels criteria: (1) thin, gray, homogenous discharge, (2) vagi nal |
6,356 | pH 4.5, (3) fishy odor after the addition of potassium hydroxide (KOH) to discharge, and (4) at least 20 clue cells present on wet prep. It is important to note that research has shown there to be sig nificant variability in providers abilities to read wet preps; thus stan dardization of wet prep analysis via laboratories is recommended. BV NAATs are also available but should be used only by symptomatic women because accuracy has not been determined for asymptom atic women. Researchers do not know the cause of bacterial vaginosis or how some women acquire it. We do know the condition typically occurs in sexually active women. We also know that sexual activity is associated with increased frequency of bacterial vaginosis. Addition ally, history of a diagnosis of bacterial vaginosis increases the risk of acquisition of other STIs. Vulvovaginal candidiasis, usually caused by C. albicans, can trigger vulvar pruritus, pain, swelling, redness, and dysuria. Findings on vaginal examination include vulvar edema, fis sures, excoriations, or thick curdy vaginal discharge. Trichomoniasis is caused by the protozoan T. vaginalis. Infected females may pres ent with symptoms characterized by a diffuse, malodorous, yellow green vaginal discharge with vulvar irritation or may be diagnosed by screening an asymptomatic patient. Cervicitis can sometimes cause a vaginal discharge. Laboratory confirmation is recommended because clinical presentations may vary and patients may be infected with more than one pathogen. Cervicitis The inflammatory process in cervicitis involves the deeper structures in the mucous membrane of the cervix uteri. Vaginal discharge can be a manifestation, but cervicitis is frequently asymptomatic. Patients also present with complaints of irregular or postcoital bleeding. Two major diagnostic signs characterize cervicitis: (1) a purulent or mucopurulent endocervical exudate visible in the endocervical canal or on an endo cervical swab specimen (e.g., swab sign; Fig. 163.5), called mucopu rulent cervicitis or cervicitis, and (2) sustained endocervical bleeding easily induced by gentle passage of a cotton swab through the cervi cal os, signifying friability. Cervical changes associated with cervicitis must be distinguished from cervical ectopy in the younger adolescent to avoid the overdiagnosis of inflammation (Fig. 163.6 and see Fig. 163.3). The pathogens identified most frequently with cervicitis are C. trachomatis and N. gonorrhoeae, although no pathogen is identified in most cases. HSV is a less common pathogen associated with ulcerative and necrotic lesions on the cervix. Pelvic Inflammatory Disease PID encompasses a spectrum of inflammatory disorders of the female upper genital tract, including endometritis, salpingitis, tuboovarian abscess, and pelvic peritonitis, usually in combination rather than as separate entities. N. gonorrhoeae and C. trachomatis predominate as the involved pathogenic organisms in younger adolescents (see Chapters 238 and 271), although PID should be approached as having Fig. 163.4 Gonococcal urethral discharge. (From Seattle STDHIV Prevention Training Center, University of Washington, Connie Celum and Walter Stamm.) Fig. 163.5 Mucopurulent cervical discharge positive swab test. (From Seattle STDHIV Prevention Training Center, University of Washington, Claire E. Stevens and Ronald E. Roddy. http:www2a.cdc.govstdtraini ngready to usepid.htm.) Fig. 163.6 Inflamed cervix caused |
6,357 | by gonococcal cervicitis. (From Centers for Disease Control and Prevention: STD clinical slides. http: www.cdc.govstdtrainingclinicalslidesslides dl.htm.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 163 u Sexually Transmitted Infections 1243 a multiorganism etiology, including pathogens such as anaerobes, G. vaginalis, Haemophilus influenzae, enteric gram negative rods, and Streptococcus agalactiae. In addition, cytomegalovirus, Mycoplasma hominis, U. urealyticum, and M. genitalium may be associated with PID. PID (tuboovarian abscess) has rarely been reported in virgins and is usually caused by E. coli and associated in some patients with obesity and possible pooling of urine in the vagina. PID is difficult to diagnose because of the wide variation in symp toms and signs. Many females with PID have subtle or mild symptoms, resulting in many unrecognized cases. Healthcare providers should consider the possibility of PID in young, sexually active females pre senting with vaginal discharge or abdominal pain. The clinical diagnosis of PID is based on the presence of at least one of the minimal criteria, either cervical motion tenderness, uterine ten derness, or adnexal tenderness, to increase the diagnostic sensitivity and reduce the likelihood of missed or delayed diagnosis. Providers should also consider that adolescents are the population in whom PID is typically diagnosed and thus should have a low threshold for ini tiating empirical treatment. In addition, the majority of females with PID have either mucopurulent cervical discharge or evidence of white blood cells (WBCs) on a microscopic evaluation of a vaginal fluid saline preparation. If the cervical discharge appears normal and no WBCs are observed on the wet prep of vaginal fluid, the diagnosis of PID is unlikely, and alternative causes of pain should be investigated. Specific, but not always practical, criteria for PID include evidence of endometritis on biopsy, transvaginal sonography or MRI evidence of thickened, fluid filled tubes, or Doppler evidence of tubal hyperemia or laparoscopic evidence of PID. Enteritis Among men who have sex with men (MSM), both Chlamydia and the gonococcus can cause enteric (colitis, proctitis) symptoms. In addition, infections with enteric pathogens (Shigella, Campylobacter, Ameba) have been noted. Sepsis Although there are rare urogenital tract cases of meningococcal infec tions with heterosexual intercourse (similar to gonococcus), men who have sex (particularly oral sex) with men are at increased risk for invasive meningococcal infections, which often occur as an out break. Meningococcus may colonize the pharyngeal, anal, or urethral mucosa. Meningococcemia must be distinguished from disseminated gonococcal infection (DGI), which will manifest with a gram negative diplococci positive blood culture along with tenosynovitis, septic arthritis, petechialpustular rash, and less often, endocarditis. Genital Ulcer Syndromes An ulcerative lesion in a mucosal area exposed to sexual contact is the unifying characteristic of infections associated with genital ulcer syn dromes. Genital ulcer lesions are most frequently seen on the penis and vulva, but also occur on oral and rectal mucosa, depending on |
6,358 | the ado lescents sexual practices. HSV and Treponema pallidum (syphilis) are the most common organisms associated with genital ulcer syndromes. Table 163.3 presents the clinical characteristics differentiating the lesions of the most common infections associated with genital ulcers, along with the required laboratory diagnosis to identify the causative agent accurately. Genital herpes, the most common ulcerative STI among adoles cents, is a chronic, lifelong viral infection. Two sexually transmitted HSV types have been identified: HSV 1 and HSV 2. The majority of cases of recurrent genital herpes are caused by HSV 2. However, among young women and MSM, an increasing proportion of anogeni tal herpes has been HSV 1. Most HSV 2infected persons are unaware of their diagnosis because they experience mild or unrecognized infec tions but continue to shed virus intermittently in the genital tract. Therefore most genital herpes infections are transmitted by asymptom atic persons who are unaware of their infection. Although the initial herpetic lesion is a vesicle, by the time the patient presents clinically, the vesicle often has ruptured spontaneously, leaving a shallow, painful ulcer (Fig. 163.7A). Recurrences are gener ally less intense and painful (see Fig. 163.7B). Up to 50 of first genital herpes episodes are caused by HSV 1. However, recurrences and sub clinical shedding are much more frequent for genital HSV 2 infection. Syphilis is a less common cause of genital ulcers in adolescents than in adults. Syphilis is caused by T. pallidum. Primary syphilis presents as a single painless ulcer or chancre at the site of infec tion. However, it can also present with multiple atypical or pain ful lesions. Secondary syphilis manifestations include skin rash, Table 163.3 Signs, Symptoms, and Presumptive and Definitive Diagnoses of Genital Ulcers SIGNSSYMPTOMS HERPES SIMPLEX VIRUS SYPHILIS (PRIMARY) CHANCROID Ulcers Vesicles rupture to form shallow ulcers Ulcer with well demarcated, indurated borders and a clean base (chancre) Nonindurated and undermined borders and a purulent base Painful Painful Painless Painful Number of lesions Usually multiple Usually single Multiple Inguinal lymphadenopathy First time infections may cause constitutional symptoms and lymphadenopathy Usually mild and minimally tender Unilateral or bilateral painful adenopathy in 50 Inguinal bubo formation and rupture may occur Clinical suspicion Typical lesions; positive HSV 2 typespecific virologic test from the lesion by NAAT or culture OR Type specific serologic testing A presumptive diagnosis requires two laboratory serologic tests, a nontreponemal test (i.e., VDRL or RPR), and a treponemal test (TP PA assay, various EIAs, chemiluminescence assays CIA, and immunoblots or rapid treponemal assay) If all four criteria are met: 1. 1 Painful genital ulcers 2. Typical ulcers and regional lymphadenopathy 3. No evidence of T. pallidum 4. HSV 1 or HSV 2 NAAT or HSV culture performed on the ulcer exudate or fluid are negative Definitive diagnosis Detection of HSV by culture or PCR from ulcer scraping or aspiration of vesicle fluid Identification of Treponema pallidum from a chancre or lymph node aspirate on dark field microscopy Detection of Haemophilus ducreyi by culture Primary syphilitic ulcers may |
6,359 | be painful if they become coinfected with bacteria or one of the other organisms responsible for genital ulcers. EIA, Enzyme immunoassay; HSV, herpes simplex virus; PCR, polymerase chain reaction; RPR, rapid plasma reagin; VDRL, Venereal Disease Research Laboratories. From https:www.cdc.govstdtreatment guidelinesdefault.htm Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1244 Part XI u Adolescent Medicine mucocutaneous lesions, and lymphadenopathy in addition to other nonspecific symptoms (e.g., sore throat, malaise), gastrointestinal symptoms (e.g., hepatitis), and renal symptoms. Tertiary syphilis presents with cardiac involvement, gummatous lesions, tabes dorsa lis, and general paresis. Latent syphilis lacks clinical manifestations and is detected by serologic testing. Latent syphilis acquired within the preceding year is referred to as early latent syphilis. Latent syphi lis acquired at least 1 year prior is referred to as late latent syphilis. Infections of the central nervous system (CNS) (neurosyphilis), of the visual system (ocular syphilis), or auditory system (otosyphilis) can occur at any stage. Lymphogranuloma venereum caused by C. trachomatis serovars L1 L3 is uncommon, although outbreaks do occur in MSM. In these circumstances, proctitis or proctocolitis is the usual manifestation. HIV is often present in affected men. Unusual infectious causes of geni tal, anal, or perianal ulcers in the United States and other industrialized countries include chancroid and donovanosis. Monkeypox (see Chapter 767) has been reported after sexual con tact, particularly among MSM. The differential diagnosis of genital ulcers also includes Behet dis ease (see Chapter 202), Crohn disease (see Chapter 382.2), aphthous ulceration, and acute genital ulcers caused by cytomegalovirus (see Chapter 302) or EBV (see Chapter 301). Acute genital ulcers often fol low a flu or mononucleosis like illness in an immunocompetent person and are unrelated to sexual activity. The lesions are 0.5 2.5 cm in size, bilateral, symmetric, multiple, painful, and necrotic and are associated with inguinal lymphadenopathy. This primary infection is also associ ated with fever and malaise. The diagnosis may require EBV titers or polymerase chain reaction (PCR) testing. Treatment is supportive care, including pain management. Genital Lesions and Ectoparasites Lesions that present as outgrowths on the surface of the epithelium and other limited epidermal lesions are included under this catego rization of syndromes. HPV can cause genital warts and genital cervical abnormalities that can lead to cancer (see Chapter 313). Genital HPV types are classified according to their association with cancer. Infections with low risk types, such as HPV types 6 and 11, can cause benign or low grade changes in cells of the cervix, geni tal warts, and recurrent respiratory papillomatosis. High risk HPV types can cause cervical, anal, vulvar, vaginal, head, and neck can cers. High risk HPV types 16 and 18 are detected in approximately 70 of cervical cancers. Persistent infection increases the risk of cervical cancer. Molluscum contagiosum and condyloma latum associated with secondary syphilis complete the classification of genital lesion syndromes. As |
6,360 | a result of the close physical contact during sexual contact, com mon ectoparasitic infestations of the pubic area occur as pediculosis pubis or the papular lesions of scabies (see Chapter 709.2). HIV, Hepatitis B, and Hepatitis C HIV and hepatitis B virus (HBV) present as asymptomatic, unex pected occurrences in most infected adolescents. High vaccina tion coverage rates among infants and adolescents have resulted in substantial declines in acute HBV incidence among U.S. born adolescents. Risk factors identified in the history or routine screen ing during prenatal care are much more likely to result in suspicion of infection, leading to the appropriate laboratory screening, than are clinical manifestations in this age group (see Chapters 322 and 406). HIV incidence among adolescents has also declined, though disparities based on race, ethnicity, gender, and region persist. Young adults continue to be affected by HIV as well. The US Pre ventive Services Task Force (USPSTF) recommends all individuals between ages 15 and 65 be tested for HIV at least once in their life, and the CDC recommends HIV testing once between 13 and 64 and once a year based on behaviors. Hepatitis C virus (HCV) incidence continues to be on the rise not only among individuals known to be part of the baby boomer generation but also among young adults. Because of the rise in injection opioid use and HCV, the American Association for the Study of Liver Disease and Infectious Disease Society of America (AASLDIDSA), and CDC recommend HCV screening among all individuals 18 years old and older. They also recommend screening based on risk behaviors among individuals younger than age 18 (see Table 163.2). DIAGNOSIS Most often, adolescents infected with bacterial and viral STI patho gens do not report symptoms suggestive of infection. With the use of very sensitive, noninvasive chlamydia and gonorrhea NAAT, pro viders are finding that most genital infections in females and many males are asymptomatic. A thorough sexual history is key to identi fying adolescents who should be screened for STIs and for identify ing those who require a laboratory diagnostic evaluation for an STI syndrome. Fig. 163.7 A, Initial herpes infection showing multiple erosions with polycyclic outlines surrounded by an erythematous halo and associated with intense pain. B, Erosions surrounded by an erythematous halo. Clinical signs and symptoms of recurrences are usually less intense than those of initial infection. (From Martn JM, Villaln G, Jord E. Update on treatment of genital herpes. Actas Dermosifiliogr. 2009;100:2232, Figs. 1 and 2.) A B Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 163 u Sexually Transmitted Infections 1245 When eliciting a sexual health history, discussions should be appro priate for the patients developmental level. In addition to questions regarding vaginal or urethral discharge, genital lesions, and lower abdominal pain among females, one should ask about prior treatment of any STI symptoms, including |
6,361 | self treatment using nonprescription medications. Dyspareunia is a consistent symptom in adolescents with PID. Providers must ask about oral or anal sexual activity to determine sites for specimen collection. Urethritis should be objectively documented by evidence of inflam mation or infectious etiology. Patient complaint without objective clinical or laboratory evidence does not fulfill diagnostic criteria. Inflammation can be documented by (1) observing urethral mucopu rulent discharge, (2) 2 WBCs per high power field on microscopic examination of Gram stain urethral secretions, (3) urine microscopic findings of 10 WBCs per high power field of first void urine speci men, or (4) a positive urine leukocyte esterase test of a first void specimen. Laboratory evaluation is essential to identify the involved pathogens to determine treatment, partner notification, and disease control. C. trachomatis and N. gonorrhoeae NAATs of a urine specimen are recommended. The presence of gram negative intracellular diplo cocci on microscopy obtained from a male urethral specimen confirms the diagnosis of gonococcal urethritis. An essential component of the diagnostic evaluation of vaginal, cervical, or urethral discharge is a chlamydia and gonorrhea NAAT. NAATs are the most sensitive tests available in such cases and are licensed for use with urine, urethral, vaginal, and cervical specimens. Many of the chlamydia NAATs are approved by the U.S. Food and Drug Administration (FDA) to test patient collected vaginal swabs in the clinical setting and liquid cytology specimens. Female vaginal swab specimens and male first void urine are considered the optimal specimen types. Female urine remains an acceptable chlamydia and gonorrhea NAAT specimen, but it may have slightly reduced perfor mance when compared with cervical or vaginal swab specimens. Urine is the recommended specimen for male urethral infection. Gonor rhea and chlamydia NAATs perform well on rectal and oropharyngeal specimens and can be performed by clinical laboratories that have completed the appropriate verification studies to obtain Clinical Labo ratory Improvement Amendments (CLIA) approval. Evaluation of adolescent females with vaginitis includes laboratory data. Traditionally, the cause of vaginal symptoms was determined by pH and microscopic examination of the discharge. However, CLIA waived point of care vaginitis tests are available. Using pH paper, an elevated pH (i.e., 4.5) is common with bacterial vaginosis and trichomoniasis. Because pH testing is not highly specific, discharge should be further examined. For microscopic exam, a slide can be made with the discharge diluted in 1 2 drops of 0.9 normal saline solution and another slide with discharge diluted in 10 KOH solu tion. Examining the saline specimen slide under a microscope may reveal motile or dead T. vaginalis or clue cells (epithelial cells with borders obscured by small bacteria), which are characteristic of bac terial vaginosis. WBCs without evidence of trichomonads or yeast are usually suggestive of cervicitis. This evaluation has been consis tently shown to be highly subjective, which is why there are more NAAT tests available for diagnosis. The yeast or pseudohyphae of Candida species are more easily identified in the KOH specimen (Fig. 163.8). The sensitivity of microscopy is |
6,362 | approximately 50 and requires immediate evaluation of the slide for optimal results. Therefore lack of findings does not eliminate the possibility of infec tion. More sensitive point of care vaginitis tests include the OSOM Trichomonas Rapid Test (Sekisui Diagnostics, Lexington, MA), an immunochromatographic capillary flow dipstick technology with reported 83 sensitivity. The OSOM BVBLUE Test (Sekisui) detects Saline: 40X objective RBCs RBCs Trichomonas Trichomonas Trichomonas Yeast buds Yeast buds Squamous epithelial cell Squamous epithelial cell Folded squamous epithelial cells NOT a clue cell NOT a clue cell Clue cell PMN PMN PMN PMNs Sperm Artifact Saline: 40X objective Saline: 40X objectiveSaline: 40X objective Yeast buds Yeast buds PMNs NOT a clue cell Yeast pseudohyphaeYeast pseudohyphae Lactobacilli Lactobacilli Lactobacilli Artifact Lysed squamous epithelial cells Masses of yeast pseudohyphae Lysed squamous epithelial cells Squamous epithelial cells Saline: 40X objective Saline: 40X objective 10 KOH: 10X objective 10 KOH: 40X objective Fig. 163.8 Common normal and abnormal microscopic findings during examination of vaginal fluid. KOH, Potassium hydroxide solution; PMN, polymorphonuclear leukocyte; RBCs, red blood cells. (From Adolescent Medicine: State of the Art Reviews, vol. 14, no. 2. Philadelphia: Hanley Belfus; 2003:350351.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1246 Part XI u Adolescent Medicine elevated vaginal fluid sialidase activity, an enzyme produced by bac terial pathogens associated with bacterial vaginosis, including Gard nerella, Bacteroides, Prevotella, and Mobiluncus, and has a reported 90 sensitivity. Both tests are CLIA waived, with results available in 10 minutes. Clinical laboratorybased vaginitis tests are also available. The Affirm VPIII (Becton Dickenson) is a moderate complexity nucleic acid probe test that evaluates for T. vaginalis, G. vaginalis, and C. albi cans and has a sensitivity of 63 and specificity of 99.9, with results available in 45 minutes. Some gonorrhea and chlamydia NAATs also offer an assay for T. vaginalis testing of female specimens tested for N. gonorrhoeae and C. trachomatis, considered the gold standard for Trichomonas testing. Objective signs of vulvar inflammation in the absence of vaginal pathogens, along with a minimal amount of vaginal discharge, suggest the possibility of mechanical, chemical, allergic, or other noninfectious irritation of the vulva (Table 163.4). The definitive diagnosis of PID is difficult based on clinical findings alone. Clinical diagnosis is imprecise, and no single historical, physical, or laboratory finding is both sensitive and specific for the diagnosis of acute PID. Clinical criteria have a positive predictive value of only 6590 compared with laparoscopy. Although healthcare providers should maintain a low threshold for the diagnosis of PID, additional criteria to enhance the specificity of diagnosis, such as transvaginal ultrasonography, can be considered (Table 163.5). Cell culture and PCR are the preferred HSV tests. Viral culture sensitivity is low, and intermittent viral shedding causes false negative results. NAATs, including PCR assays for HSV DNA, are more sensitive and increasingly available for diagnosing genital HSV. The Tzanck test |
6,363 | is insensitive and nonspecific and should not be con sidered reliable. Accurate type specific HSV serologic assays are based on the HSV specific glycoproteins G2 (HSV 2) and G1 (HSV 1). Both laboratory based point of care tests are available. Because almost all HSV 2 infections are sexually acquired, the presence of type specific HSV 2 antibody implies anogenital infection. The presence of HSV 1 antibody alone is more difficult to interpret because of the frequency of oral HSV infection acquired during childhood. Type specific HSV serologic assays might be useful in the following scenarios: (1) recurrent geni tal symptoms or atypical symptoms with negative HSV cultures; (2) a clinical diagnosis of genital herpes without laboratory confirmation; and (3) a patient with a partner with genital herpes, especially if con sidering suppressive antiviral therapy to prevent transmission. For syphilis testing, nontreponemal tests, such as the rapid plasma reagin (RPR) or Venereal Disease Research Laboratories (VDRL), and treponemal testing, such as fluorescent treponemal antibody absorbed tests, the T. pallidum passive particle agglutination (TP PA) assay, and various enzyme and chemiluminescence immunoassays (EIACIA), are recommended. However, many clinical laboratories have adopted a reverse sequence of screening in which a treponemal EIACIA is per formed first, followed by testing of reactive sera with a nontreponemal test (e.g., RPR). Treponemal tests often remain positive for life, with only 1525 becoming serologically nonreactive, if treated early in primary syphilis. A positive treponemal EIA or CIA test can identify both previously treated and untreated or incompletely treated syphilis. False positive results can occur, particularly among populations with low syphilis prevalence. Persons with a positive treponemal screen ing test should have a standard nontreponemal test with titer (RPR or VDRL) to guide patient management decisions. If EIACIA and RPR VDRL results are discordant, the laboratory should perform a different treponemal test to confirm the results of the initial test. Patients with discordant serologic results by EIACIA and RPRVDRL testing whose sera are reactive by TP PA testing are considered to have past or present syphilis; if sera is TP PA nonreactive, syphilis is unlikely (Fig. 163.9). Rapid HIV testing with third and fourth generation test results available in 10 20 minutes can be useful when the likelihood of adoles cents returning for their results is low. Point of care CLIA waived tests for whole blood finger stick (fourth generation) and oral fluid speci men (third generation) testing are available. Clinical studies have dem onstrated that the rapid HIV test performance is comparable to those of EIAs. Because some reactive test results may be false positive, every reactive rapid test must be confirmed. Table 163.4 Pathologic Vaginal Discharge INFECTIVE DISCHARGE OTHER REASONS FOR DISCHARGE COMMON CAUSES COMMON CAUSES Organisms Retained tampon or condom Chemical irritation Allergic responses Ectropion Endocervical polyp Intrauterine device Atrophic changes Candida albicans Trichomonas vaginalis Chlamydia trachomatis Neisseria gonorrhoeae Mycoplasma genitalium Conditions Bacterial vaginosis Acute pelvic inflammatory disease Postoperative pelvic infection Postabortal sepsis Puerperal sepsis LESS COMMON CAUSES Physical trauma Vault granulation tissue Vesicovaginal fistula |
6,364 | Rectovaginal fistula Neoplasia CervicitisLESS COMMON CAUSES Ureaplasma urealyticum Syphilis Escherichia coli From Mitchell H. Vaginal dischargecauses, diagnosis, and treatment. BMJ. 2004;328:13061308; and Sexually Transmitted Infections Treatment Guidelines, 2021: Vulvovaginal Itching, Burning, Irritation, Odor or Discharge: https:www.cdc.govstdtr eatment guidelinesvaginal discharge.htm. Table 163.5 Evaluation for Pelvic Inflammatory Disease (PID) 2021 CDC DIAGNOSTIC CRITERIA Minimal Criteria Cervical motion tenderness or Uterine tenderness or Adnexal tenderness Additional Criteria to Enhance Specificity of the Minimal Criteria Oral temperature 38.3C (101F) Abnormal cervical or vaginal mucopurulent discharge Presence of abundant numbers of WBCs on saline microscopy of vaginal secretions Elevated ESR or C reactive protein Laboratory documentation of cervical Neisseria gonorrhoeae or Chlamydia trachomatis infection Most Specific Criteria to Enhance the Specificity of the Minimal Criteria Transvaginal sonography or MRI techniques showing thickened, fluid filled tubes, with or without free pelvic fluid or tuboovarian complex, or Doppler studies suggesting pelvic infection (e.g., tubal hyperemia) Endometrial biopsy with histopathologic evidence of endometritis Laparoscopic abnormalities consistent with PID Differential Diagnosis (Partial List) Gastrointestinal: appendicitis, constipation, diverticulitis, gastroenteritis, inflammatory bowel disease, irritable bowel syndrome Gynecologic: ovarian cyst (intact, ruptured, or torsed), endometriosis, dysmenorrhea, ectopic pregnancy, mittelschmerz, ruptured follicle, septic or threatened abortion, tuboovarian abscess Urinary tract: cystitis, pyelonephritis, urethritis, nephrolithiasis ESR, Erythrocyte sedimentation rate; WBCs, white blood cells If the cervical discharge appears normal and no WBCs are observed on the wet prep of vaginal fluid, the diagnosis of PID is unlikely and alternative causes of pain should be investigated. Adapted from Centers for Disease Control and Prevention (CDC): https:www.cdc.gov stdtreatment guidelinespid.htm. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 163 u Sexually Transmitted Infections 1247 Reactive Nontreponemal Nonreactive Step 1 Step 2 Step 3 Lab interpretation Reactive Nonreactive Reactive Consistent with current or past syphilis infection No laboratory evidence of syphilis infection Inconclusive for syphilis infection; potentially early infection or false positive Consistent with past or potential early syphilis infection Nonreactive Treponemal (Immunoassay) Supplemental treponemal Fig. 163.9 Centers for Disease Control and Prevention (CDC)recommended algorithm for reverse sequence syphilis screening: Treponemal test screen ing followed by nontreponemal test confirmation. The supplemental treponemal test should use a unique platform andor antigen different from the first treponemal test. (From Association of Public Health Laboratories. Suggested Reporting Language for Syphilis Serological Testing. Association of Public Health Laboratories August 2020 https:www.aphl.orgprogramsinfectiousdiseasestdDocumentsID2020AugSyphilisReportingLanguage.pdf.) Table 163.6 Management Guidelines for Uncomplicated Bacterial STIs in Adolescents and Adults PATHOGEN RECOMMENDED REGIMENS ALTERNATIVE REGIMENS AND SPECIAL CONSIDERATIONS Chlamydia trachomatis Doxycycline 100 mg orally 2day for 7 days For pregnancy: Azithromycin 1 g orally in a single dose Azithromycin 1 g orally in a single dose OR Levofloxacin 500 mg orally 1day for 7 days For pregnancy: Amoxicillin 500 mg orally 3day for 7 days Neisseria gonorrhoeae (cervix, urethra, and rectum) Ceftriaxone 500 mg IM in a single dose for persons weighing 150 kg If chlamydial infection has not been excluded, treat |
6,365 | for chlamydia with doxycycline 100 mg orally 2day for 7 days For person weighing 150 kg, ceftriaxone 1g should be administered If cephalosporin allergy or unavailable: Gentamicin 240 mg IM in a single dose PLUS Azithromycin 2 g orally in a single dose OR Cefixime 800 mg orally in a single dose Neisseria gonorrhoeae (pharynx) Ceftriaxone 500 mg IM in a single dose for person weighing 150 kg Ceftriaxone 1g IM for a person weighing 150 kg Treponema pallidum (primary and secondary syphilis or early latent syphilis, i.e., infection 12 mo) Benzathine penicillin G 2.4 million units IM in a single dose Penicillin allergy: Doxycycline 100 mg orally twice daily for 14 days or tetracycline 500 mg orally 4 times daily for 14 days; limited data suggest ceftriaxone 1 2 g daily either IM or IV for 10 14 days OR Azithromycin 2 g orally in a single dose has been effective, but treatment failures have been documented Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1248 Part XI u Adolescent Medicine TREATMENT See Part XV for chapters on the treatment of specific microorganisms and Tables 163.6 163.8. Treatment regimens using nonprescription products for candidal vaginitis and pediculosis reduce financial and access barriers to rapid treatment for adolescents, but potential risks for inappropriate self treatment and complications from untreated, more serious infections must be considered before using this approach. Minimizing noncompliance with treatment, notifying and treating the sexual partners, addressing prevention and contraceptive issues, offering available vaccines to prevent STIs, and making every effort to preserve fertility are additional physician responsibilities. Chlamydia and gonorrhea infected males and females should be retested approximately 3 months after treatment, regardless of whether they believe that their sex partners were treated, or whenever persons next present for medical care in the 12 months after initial treatment. Adolescents who are pregnant with chlamydia and gonorrhea infec tions should be retested in approximately 1 month after treatment. Ado lescents with oral gonorrhea should be retested in 714 days. Once an infection is diagnosed, partner evaluation, testing, and treatment are rec ommended for sexual contacts within 60 days of symptoms or diagnosis, or the most recent partner if sexual contact was 60 days, even if the partner is asymptomatic. Abstinence is recommended for at least 7 days Table 163.7 Management Guidelines for Uncomplicated Miscellaneous Sexually Transmitted Infections in Adolescents and Adults PATHOGEN RECOMMENDED REGIMENS ALTERNATIVE REGIMENS AND SPECIAL CONSIDERATIONS Trichomoniasis Women: Metronidazole 500 mg orally 2day for 7 days Men: Metronidazole 2 g orally in a single dose For women and men: Tinidazole 2 g orally in a single dose Phthirus pubis (pediculosis pubis, e.g., pubic lice) Permethrin 1 cream rinse applied to affected areas and washed off after 10 min OR Pyrethrins with piperonyl butoxide applied to affected areas and washed off after 10 min Launder clothing and bedding |
6,366 | Malathion 0.5 lotion applied for 8 12 hr and washed off OR Ivermectin 250 gkg orally, repeat in 7 14 days Sarcoptes scabiei (scabies) Permethrin 5 cream applied to all areas of the body (from neck down), wash after 8 14 hr OR Ivermectin 200 gkg body weight orally, repeated in 14 days Launder clothing and bedding Lindane (1) 1 oz of lotion or 30 g of cream in thin layer to all areas of body from neck down; wash off after 8 hr Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases: treatment guidelines. MMWR. 2021;64(RR 3); https:www.cdc.govstdtreatment guidelinesSTI Guidelines 2021.pdf. PATHOGEN RECOMMENDED REGIMENS ALTERNATIVE REGIMENS AND SPECIAL CONSIDERATIONS Treponema pallidum (late latent syphilis or syphilis of unknown duration) Benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM each at 1 wk intervals Penicillin allergy: Doxycycline 100 mg orally twice daily for 28 days or tetracycline 500 mg orally 4 times daily for 28 days, with close serologic and clinical follow up Treponema pallidum (neurosyphilis, ocular syphilis, and otosyphilis) Aqueous crystalline penicillin G 18 24 million units per day, administered as 3 4 million units by IV every 4 hr or continuous infusion, for 10 14 days Procaine penicillin G 2.4 million units IM 1day for 10 14 days PLUS Probenecid 500 mg orally 4day for 10 14 days Haemophilus ducreyi (chancroid: genital ulcers, lymphadenopathy) Azithromycin 1 g orally in a single dose OR Ceftriaxone 250 mg IM in a single dose OR Ciprofloxacin 500 mg orally 2 daily for 3 days OR Erythromycin base 500 mg orally 3 daily for 7 days Chlamydia trachomatis serovars L1, L2, or L3 (lymphogranuloma venereum) Doxycycline 100 mg orally 2 daily for 21 days Alternative: Erythromycin base 500 mg orally 4 daily for 21 days OR Azithromycin 1 g orally once weekly for 3 wk IM, Intramuscularly; IV, intravenously; NAAT, nucleic acid amplification test. Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases: treatment guidelines, 2021. MMWR Recomm Rep. 2021;70:1187, https:www.cdc.govstd treatment guidelinesdefault.htm. Table 163.6 Management Guidelines for Uncomplicated Bacterial STIs in Adolescents and Adultscontd Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 163 u Sexually Transmitted Infections 1249 Table 163.8 Management Guidelines for Uncomplicated Genital Warts and Genital Herpes in Adolescents and Adults PATHOGEN RECOMMENDED REGIMENS ALTERNATIVE REGIMENS AND SPECIAL CONSIDERATIONS HUMAN PAPILLOMAVIRUS (HPV) External anogenital warts (penis, groin, scrotum, vulva, perineum, external anus, and perianus) Patient applied: Imiquimod 3.755 cream self applied to warts at bedtime nightly for up to 16 wk; wash off after 6 10 hr OR Podofilox 0.5 solution or gel self applied to warts twice daily for 3 consecutive days each wk followed by 4 days of no therapy. May be repeated for up to four cycles. OR Sinecatechins 15 ointment self applied 3 times daily for up |
6,367 | to 16 wk. Do not wash off after use, and avoid genital, anal, and oral sexual contact while ointment is on skin. Provider administered: Cryotherapy with liquid nitrogen or cryoprobe. Repeat applications every 1 2 wk. OR Surgical removal either by tangential scissor excision, electrocautery, tangential shave excision, curettage, laser or electrosurgery. OR Trichloroacetic acid (TCA) or bichloracetic acid (BCA) 8090; small amount applied only to warts and allowed to dry, when white frosting develops; can be repeated weekly. Provider administered: Podophyllin resin 1025 in a compound tincture of benzoin applied to each wart and then allowed to air dry; thoroughly wash off after 1 4 hr; can be repeated weekly. Systemic toxicity has been reported when podophyllin resin was applied to large areas of friable tissue and was not washed off within 4 hr. Many persons with external anal warts also have intraanal warts and might benefit from inspection of anal canal by digital examination, standard anoscopy, or high resolution anoscopy. Cervical warts Cryotherapy with liquid nitrogen OR Surgical removal OR TCA or BCA 8090 solution Management should include consultation with a specialist. Vaginal warts Cryotherapy with liquid nitrogen; avoid cryoprobe use because of risk for vaginal perforation and fistula formation. OR Surgical removal OR TCA or BCA 8090; small amount applied only to warts and allowed to dry, when white frosting develops; can be repeated weekly. Urethral meatal warts Cryotherapy with liquid nitrogen OR Surgical removal Intraanal warts Cryotherapy with liquid nitrogen OR Surgical removal OR TCA or BCA 8090 applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. Can be repeated weekly. Management of intraanal warts should include consultation with a specialist. HERPES SIMPLEX VIRUS (HSV; GENITAL HERPES) First clinical episode Treat for 7 10 days with one of the following: Acyclovir 400 mg orally 3 daily Valacyclovir 1 g orally 2 daily Famciclovir 250 mg orally 3 daily Consider extending treatment if healing is incomplete after 10 days of therapy. Episodic therapy for recurrences Treat with one of the following: Acyclovir 800 mg orally 2 daily for 5 days Acyclovir 800 mg orally 3 daily for 2 days Valacyclovir 500 mg orally 2 daily for 3 days Valacyclovir 1,000 mg orally once daily for 5 days Famciclovir 1,000 mg orally 2 daily for 1 day Famciclovir 500 mg orally once, then 250 mg 2 daily for 2 days Famciclovir 125 mg orally twice daily for 5 days Effective episodic treatment of recurrences requires initiation of therapy within 1 day of lesion onset or during the prodrome that precedes some outbreaks. The patient should be provided with a supply or a prescription for the medication with instructions to initiate treatment immediately when symptoms begin. Suppressive therapy to reduce frequency of recurrences Treat with one of the following: Acyclovir 400 mg orally 2 daily Valacyclovir 500 mg orally once daily or 1 g orally once daily Famciclovir 250 mg orally 2 daily All patients |
6,368 | should be counseled regarding suppressive therapy availability, regardless of number of outbreaks per year. Because the frequency of recurrent outbreaks diminishes over time in many patients, providers should periodically discuss the need to continue therapy. Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1250 Part XI u Adolescent Medicine after both patient and partner have completed treatment. A test for preg nancy should be performed for all females with suspected PID because the test outcome will affect management. Repeat testing 3 months after treatment is also recommended for Trichomonas infection. Diagnosis and therapy are often carried out within the context of a confidential relationship between the physician and the patient. There fore the need to report certain STIs to health department authorities should be clarified at the outset. Health departments are Health Insur ance Portability and Affordability Act (HIPAA) exempt and will not violate confidentiality. The health departments role is to ensure that treatment and case finding have been accomplished and that sexual partners have been notified of their STI exposure. Expedited partner therapy (EPT), the clinical practice of treating sex partners of patients diagnosed with chlamydia or gonorrhea by providing prescriptions or medications to the patient to take to the partner without the health care provider first examining the partner, is a strategy to reduce further transmission of infection. In randomized trials, EPT has reduced the rates of persistent or recurrent gonorrhea and chlamydia infection. Serious adverse reactions are rare with recommended chlamydia and gonorrhea treatment regimens, such as doxycycline, azithromycin, and ceftriaxone. Transient gastrointestinal side effects are more common but rarely result in severe morbidity. Most states expressly permit EPT or may allow its practice. Resources for information regarding EPT and state laws are available at the CDC website. PREVENTION Healthcare providers should integrate comprehensive sexuality education into clinical practice with children from early childhood through adolescence. Providers should counsel adolescents regarding sexual behaviors associated with risk of STI acquisition and should educate using evidence based prevention strategies, which include a discussion of abstinence and other risk reduction strategies, such as consistent and correct condom use, and distribution of educa tional materials for reinforcement. The USPSTF recommends high intensity behavioral counseling to prevent STIs for all sexually active adolescents. The following recommendations for the primary prevention of STIs through vaccination are based on published guidelines from the Advi sory Committee on Immunization Practices: HPV vaccination is recommended through age 26 years for males and females not vaccinated previously at the routine age of 11 or 12 years. Vaccination can be started at age 9. Two doses of HPV vaccine are recommended for most persons starting the se ries before their 15th birthday; three doses are recommended at 15 years. The HBV vaccination series is recommended for all adolescents and young adults who have not previously received the universal HBV vaccine series |
6,369 | during childhood. Mpox vaccination is recommended for gay, bisexual, transgender persons and if the patient has had sexual or intimate contact with someone who may have mpox. Mpox vaccination is a twodose schedule separated by 4 weeks. Preexposure prophylaxis (PrEP) offers another strategy to specifi cally prevent HIV infection (Table 163.9). The CDC and USPSTF recommend offering HIV PrEP to adoles cents weighing 35 kg and young adults who are HIV negative and Table 163.8 Management Guidelines for Uncomplicated Genital Warts and Genital Herpes in Adolescents and Adultscontd PATHOGEN RECOMMENDED REGIMENS ALTERNATIVE REGIMENS AND SPECIAL CONSIDERATIONS Daily suppressive therapy in persons with HIV infection Acyclovir 400 800 mg orally 2 3 daily OR Famciclovir 500 mg orally 2 daily OR Valacyclovir 500 mg orally 2 daily If lesions persist or recur in a patient receiving antiviral treatment, acyclovir resistance should be suspected and a viral culture obtained for phenotypic sensitivity testing. Consultation with an infectious disease specialist is recommended. Episodic infection in persons with HIV Acyclovir 400 mg orally 3 daily for 7 10 days OR Famciclovir 250 mg orally 3day for 7 10 days OR Valacyclovir 1g orally 2 for 7 10 days If lesions persist or recur in a patient receiving antiviral treatment, acyclovir resistance should be suspected and a viral culture obtained for phenotypic sensitivity testing. Consultation with an infectious disease specialist is recommended. Daily suppressive therapy of recurrent genital herpes in pregnant women Treatment is recommended to start at 36 wk gestation: Acyclovir 400 mg orally 3 daily OR Valacyclovir 500 mg orally 2 per day Valacyclovir 500 mg once daily might be less effective than other valacyclovir or acyclovir dosing regimens in patients who have very frequent recurrences (i.e., 10 episodes per yr). Adapted from Centers for Disease Control and Prevention. Sexually transmitted diseases: treatment guidelines, MMWR 2021;64(RR 3): https:www.cdc.govstdtreatment guidelinesSTI Guidelines 2021.pdf. Table 163.9 Option for PreExposure Prophylaxis (PrEP) for HIV Prevention GENERIC DOSE FREQUENCY POPULATION Tenofovir disproxil fumarate emtricitabine (FTDF) 200 mg300 mg Daily pill Any person weighing at least 35 kg Tenofovir alafenamide emtricitabine (FTAF) 200 mg25 mg Daily pill Individuals engaging in anal sex who are cis male, transwomen weighing at least 35 kg Cabotegravir 200 mgmL Every 2 month injection Any person weighing at least 35 kg FTDF is also available by brand name and generic depending on insurance. It can also be used as intermittent dosing for cismen and transwomen engaging in anal sex. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. PART XII Immunology Immunology 1252 Section 1 Evaluation of the Immune System Primary immune deficiency diseases (PIDDs) comprise more than 450 disorders that impair the development or function of the immune system. Most these disorders result from a single gene pathogenic vari ant, although more complex inheritance patterns can also occur. The initial diagnosis and subsequent treatment of PIDDs are often |
6,370 | delayed due to a low index of suspicion, a rare individual disease inci dence, protein manifestations including infection, autoimmunity, cuta neous lesions, and failure to thrive all in the background of a higher frequency of more common childhood illnesses (nonspecific viral ill ness, allergy). This diagnostic delay can lead to irreversible end organ damage or death. Newborn screening for severe combined immune deficiency (SCID) has helped the early detection of SCID and other immune deficien cies associated with very low T cells. However, the vast majority of immune deficiencies will not be detected by this method. Physicians must be aware of concerning manifestations or events that suggest an underlying PIDD. The varied presentations and complex phenotypes, some of which have minimal or no infectious manifestations, make the initial diagnosis of PIDDs difficult (Table 164.1). Manifestations of PIDD include recurrent andor sentinel infections, fever without a focus, periodontitis, poor formation of pus at a site of infection, and unusual inflammatory (including autoimmune) diseases. PIDDs may involve defects in one or more host defense mechanism, or they may be an independent isolated disorder or part of a recognizable syndrome (Table 164.2). The immune system is primarily responsible for protecting the body against invading infectious pathogens. Recurrent (often in mul tiple sites), severe, or unusual infections are typical presentations of PIDDs. Viral, bacterial, fungal, and mycobacterial infections each require distinct arms of the immune system for eradication; identifi cation of the microbe causing an infection is helpful in directing the evaluation of a patient with suspected PIDD (see Table 164.1; Table 164.3). Children who exceed the normal frequency of infections or who have very prolonged symptoms suggesting failure of pathogen clear ance may also warrant evaluation. The typical preschool child can have 6 10 viral respiratory infections per year, making this assessment less than straightforward. Patients with PIDD are significantly more likely to have severe infections requiring hospitalization and prolonged or unsuccessful treatment with IV antibiotics. Infections with unusual pathogens (opportunistic organisms) or infections resulting from live attenuated virus vaccines (rotavirus, varicella, MMR) are important warning signs. Neutropenia or lymphocytopenia may be present. In addition to pathogen defense, the immune system must demon strate tolerance to the host and prevent excessive inflammation that can result in tissue damage. In addition to infections, patients can present with autoimmune disease andor autoinflammatory conditions. The presence of a family history of PIDD or consanguinity should increase suspicion for these conditions. The patients clinical presentation can help guide the initial labora tory evaluation (Fig. 164.1). INFECTION RED FLAGS Infections are one of the more common reasons to initiate an immu nologic evaluation. The pattern and etiology of the infections dictate the appropriate diagnostic evaluation. A high burden of infections in a child is the most common reason for referral to an immunology Chapter 164 Orientation to the Consideration of Inborn Errors of Immunity Soma Jyonouchi and Kathleen E. Sullivan Table 164.1 Patterns of Infections and Other Conditions in Primary Immunodeficiency DISORDER ILLNESSES TYPE OF INFECTION OTHER CONDITIONS |
6,371 | Antibody defects Sinopulmonary infections (Streptococcus pneumoniae, Haemophilus influenzae, or Mycoplasma sp.) Gastrointestinal (enteroviruses, Salmonella, Campylobacter, Giardia, norovirus) Autoimmune disease (thrombocytopenia, hemolytic anemia, neutropenia) Inflammatory bowel disease Lymphadenopathy, splenomegaly Otitis, mastoiditis Cell mediated immunity defects Pneumonia (Pneumocystis jirovecii), Mycobacterium avium intracellulare Severe Epstein Barr infection Gastrointestinal disease (viruses, cytomegalovirus) Fungi of the skin, nails, mucous membranes Failure to thrive Splenomegaly, lymphadenopathy Defects of phagocytosis Skin, liver, lymph nodes, abscesses (Staphylococcus, gram negative bacteria, fungi) Inflammatory bowel disease Granulomatous infiltrations Defects of complement Sepsis and other blood borne encapsulated bacteria; meningitis, (Streptococcus, Pneumococcus, Neisseria) Autoimmune disease (systemic lupus erythematosus, ANA, glomerulonephritis) ANA, Antinuclear antibodies. From Leung DYM, Akdis CA, Bacharier LB, et al., eds. Pediatric Allergy Principles and Practice. 4th ed. Philadelphia: Elsevier; 2021. Table 4.1, p. 32. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 164 u Orientation to the Consideration of Inborn Errors of Immunity 1253 center; there are certain patterns that can collectively be thought of as red flags, mandating an immunologic evaluation. Recurrent Sinopulmonary Infections Recurrent bacterial sinopulmonary infections (ear, sinus, pneumonia) with encapsulated organisms are a common presentation for PIDDs. It can be challenging to define a number of infections that represent a threshold to begin an immunologic evaluation. Typically, most patients with a PIDD will have a diversity of sites impacted by infection; the frequency will be higher or the severity more severe than the clinician would expect. Recurrent sinopulmonary infections are highly sugges tive of patients with antibody deficiencies, such as common variable immunodeficiency (CVID; see Chapter 165) or X linked agammaglob ulinemia (XLA; see Chapter 166). Patients often require longer courses Table 164.2 Types of Primary Immune Defects IMMUNODEFICIENCIES AFFECTING CELLULAR AND HUMORAL IMMUNITY T B NK SCID Common gamma chain (IL2RG, X linked), JAK3 T B NK SCID IL7 , T cell receptor defects, CD45, PNP deficiency T B SCID RAG1, RAG2 defects, adenosine deaminase deficiency COMBINED IMMUNODEFICIENCIES, GENERALLY LESS SEVERE MHC class I and II defects; T cell receptor defects; DOCK8, IL21, and IL21R, and others COMBINED IMMUNODEFICIENCIES WITH SYNDROMIC OR OTHER FEATURES With thrombocytopenia Wiskott Aldrich syndrome DNA repair defects Ataxia telangiectasia, Nijmegen breakage syndrome; Bloom syndrome, dyskeratosis congenital, LIG 4 Hyper IgE syndromes STAT3 loss of function, and others Immuno osseous dysplasias Cartilage hair hypoplasia Schimke immuno osseous dysplasia Ectodermal dysplasia IKBKG deficiency (NEMO) THYMIC DEFECTS WITH ADDITIONAL CONGENITAL ANOMALIES DiGeorge, velocardiofacial syndrome CHARGE syndrome ANTIBODY DEFECTS Agammaglobulinemias X linked and autosomal forms of agammaglobulinemia Hyper IgM syndromes X linked and autosomal forms IgG or IgA deficiency IgG subclass and IgA deficiency IgG, and IgA and or IgM deficiency Common variable immunodeficiency DISEASES OF IMMUNE DYSREGULATION Familial hemophagocytic lymphohistiocytosis Perforin deficiency; UNC13D. With hypopigmentation Chdiak Higashi, Griscelli, Hermansky Pudlak syndromes With autoimmunity Autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy, autoimmune lymphoproliferative syndrome With defects of regulatory T cells X linked immune dysregulation, polyendocrinopathy |
6,372 | enteropathy (IPEX), defects of CTLA4, STAT3 Leading to severe Epstein Barr virus X linked autoimmune lymphoproliferative syndrome, XIAP deficiency, magnesium transporter 1 (MAGT1) With colitis IL 10 defects CONGENITAL DEFECTS OF PHAGOCYTE NUMBER OR FUNCTION Neutropenia Elastase deficiency, HAX1 deficiency, and others Defects of motility Leukocyte adhesion deficiency Defects of respiratory burst Chronic granulomatous disease Other nonlymphoid defects GATA2 deficiency DEFECTS IN INTRINSIC AND INNATE IMMUNITY Mycobacterial disease IL 12, IL 23, INF , STAT1 defects, and others Warts Epidermodysplasia verruciformis (EVER), hypogammaglobulinemia, infections, myelokathexis syndrome (WHIM) Viral infections STAT1, STAT2, IRF7, and others Herpes simplex encephalitis TLR3, UNC93B1 Fungal diseases CARD9, IL17 defects, STAT1 Bacterial susceptibility IRAK4, MYD88, IRAK1, and others COMPLEMENT DEFICIENCY Classical pathway C1q C9 defects Alternative pathway Factors B, D, I, H, properdin, and others Regulatory and membrane controls Co factor proteins CHARGE defect, Disorder with coloboma, heart defects, atresia choanae (also known as choanal atresia), growth retardation, genital abnormalities, and ear abnormalities; Ig, immunoglobulin; MHC, major histocompatibility complex; NK, natural killer; PNP, purine nucleoside phosphorylase; SCID, severe combined immunodeficiency. From Leung DYM, Akdis CA, Bacharier LB, et al., eds. Pediatric Allergy Principles and Practice. 4th ed. Philadelphia: Elsevier; 2021. Table 4.2, p. 33 34. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1254 Part XII u Immunology of antibiotics to clear infections and may not have improvement with standard interventions such as bilateral myringotomy tubes or sinus surgery. Recurrent Invasive Pneumococcal Infections Invasive pneumococcal infections (sepsis, septic arthritis, meningitis) may occur in patients with antibody deficiency (Table 164.4). A single episode need not imply a PIDD. Recurrent invasive pneumococcal infections should elicit an evaluation. Pneumococcus has a polysac charide capsule that permits it to evade the immune system. Antibod ies bind to these bacteria (opsonization), which facilitates phagocytosis and bacterial killing. The early complement fragment C3b also opso nizes bacteria, labeling it for destruction. Patients with early classi cal complement component deficiencies (see Chapter 173) have an increased risk of invasive infections with encapsulated bacteria such as pneumococcus. The spleen plays a key role in the phagocytosis and clearance of nonopsonized bacteria. Thus primary or secondary asplenia is associated with an increased risk of disseminated infections with pneumococcus (and meningococcus) requiring patients to take antibiotic prophylaxis. Patients with toll like receptor (TLR) defects (IRAK4, MyD88, and NEMO deficiency) develop invasive pneumo coccal and Staphylococcus aureus infections. These patients uniquely fail to (or minimally) manifest signs of inflammation (fevers, elevated CRP, ESR) despite having invasive infections; this is the result of a block in the pathway that produces inflammatory cytokines such as interleu kin (IL) 6 and tumor necrosis factor (TNF) , critical for recruitment of neutrophils and fever generation. Severe Papillomavirus A number of PIDDs are characterized by recurrent, severe human papillomavirus (HPV) infections (see Table 164.3). Warts are common in the general population but high numbers should suggest |
6,373 | a PIDD. Patients with WHIM syndrome (warts, hypogammaglobulinemia, immunodeficiency, myelokathexis) have a unique susceptibility to HPV induced warts in addition to bacterial sinopulmonary infections and cutaneous abscesses (immunity to other viral infections is intact) (see Fig. 708.6). One of the hallmarks of DOCK8 deficiency is severe cutaneous viral infections with HPV, molluscum contagiosum, herpes simplex, and varicella zoster. Patients with epidermodysplasia ver ruciformis have markedly increased susceptibility to cutaneous HPV infections. Patients with GATA2 deficiency can suffer from severe dis seminated HPV, including genital locations, and molluscum contagio sum infections. Treatment is distinct for each condition, but knowing Table 164.3 Sentinel Infections and Related Genes INFECTIONS RECOGNIZED GENE DEFECTS AND WELL CHARACTERIZED SYNDROMES VIRUSES Herpes simplex encephalitis TBK1, TLR3, TRAF3, TRIF, UNC93B Cutaneous herpes simplex Severe T cell defects, DOCK8, GATA2, WAS EBVchronic CD21, CD27, CORO1A, ITK, MAGT1, PRKCD, CXCR4 EBVHLH AP3B1, LYST1, PRF1, RAB27A, SH2D1A, STX11, UNC13D, XIAP CMV Severe T cell defects, Good syndrome, DOCK8, GATA2, STIM1, WAS Papilloma virus Idiopathic CD4 lymphopenia, ATM, CD40L, EVER1, EVER2, DOCK8, GATA2, IKBKG, MST1, RORH, STK4, CXCR4 FUNGI Candida AIRE, CARD9, IL17F, IL17RA, STAT1 Aspergillus Idiopathic CD4 lymphopenia, CYBA, CYBB, DOCK8, GATA2, ITGB2, NCF1, NCF2, NCF4, STAT3 BACTERIA Pseudomonas Congenital neutropenia, IRAK4, ITGB2, MYD88, BTK (neutropenia), CD40LG (neutropenia) Salmonella CYBB, IFNGR1, IFNGR2, IL12B, IL12RB1 Serratia CYBA, CYBB, NCF1, NCF2, NCF4 Neisseria C5, C6, C7, C8A, C8B, C8G, C9, CFD, CFH, CFI, CFP Streptococcus pneumoniae C1QA, C1QB, C1QC, C4A C4B, C2, C3, IRAK4, MYD88 MYCOBACTERIA Mycobacteria CYBA, CYBB, GATA2, IFNGR1, IFNGR2, IKBKG, IL12, IL12RB1, IRF8, NCF1, NCF2, NCF4, STAT1, TYK2 CMV, Cytomegalovirus; EBV, Epstein Barr virus; HLH, hemophagocytic lymphohistiocytosis. From Sullivan KE, Stiehm ER, eds. Stiehms Immune Deficiencies. 2nd ed. London: Elsevier; 2020. Table 1.2. Neisseria Earlyonset lupus Encapsulated bacterial infections Abscesses Adenitis Severe bacterial infections Poor wound healing Periodontal disease Failure to thrive Severe viral infections Pneumocystis Candida Low TRECs Recurrent sinopulmonary infections Enteroviral meningoencephalitis Bronchiectasis Recurrent gastroenteritis B cell Phagocyte T cell Complement IgG, IgA, IgM, IgE Vaccine titers Lymphocyte flow cytometry Lymphocyte count Lymphocyte flow cytometry T cell proliferation Neutrophil count Oxidative burst (DHR) CH50 AH50 Fig. 164.1 When infections are the major manifestation of the inborn error of immunity, several types of laboratory tests can yield a diagnosis. The specific type of infection suggests the effector arm of the immune system that may be dysfunctional, and the testing can be applied in a targeted fashion. Laboratory evaluation is noted in the light blue boxes. DHR, dihydrorhodamine, Ig, immunoglobulin; TRECs, T cell receptor excision circles. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 164 u Orientation to the Consideration of Inborn Errors of Immunity 1255 the immune etiology is critical because of the substantial morbidity associated with continually spreading warts. Herpes Simplex Virus Encephalitis Several innate PIDDs uniquely present with recurrent herpes sim plex virus (HSV) encephalitis (without mucosal HSV infections) due |
6,374 | to disruption of the signaling pathways regulating antiviral cytokines interferon (IFN) and , which are critical for control of HSV infec tions (see Table 164.3). Examples of these PIDDs include TLR3 defi ciency, UNC93b deficiency, and interferon regulatory factor 3 (IRF3) deficiency. The importance of recognition relates to the likelihood of recurrence, with the attendant central nervous system (CNS) dysfunc tion that can result. Epstein Barr Virus Severe life threatening infections with fulminant Epstein Barr virus (EBV) are a hallmark of certain PIDDs, whereas typical outpatient infectious mononucleosis infections are not concerning (see Chapter 301) (see Table 164.3). Patients with familial hemophagocytic lym phohistiocytosis (HLH) have a block in the cytotoxic lymphocyte (NK and CD8 T cell) pathway necessary to control EBV infections (see Chapter 556). Patients develop uncontrolled immune hyperac tivation (cytokine storm) from unchecked EBV infections resulting in life threatening HLH. Clinical symptoms include fever, hepato splenomegaly, pancytopenia, and multi system organ failure. There may be evidence of hemophagocytosis activated by macrophages in a bone marrow biopsy. Patients with X linked lymphoproliferative syndrome (XLP) are predisposed to fatal fulminant EBV with or with out HLH, as well as lymphoma. Patients with XLP who survive acute EBV infections will often go on to develop hypogammaglobulinemia. Multiple PIDD disorders have an increased risk of HLH (Table 164.5). These conditions are more likely to require hematopoietic cell trans plantation (see Chapter 176) than HLH occurring in the non PIDD community. Severe Candida Severe oral thrush from Candida albicans (as well as other opportu nistic infections such a Pneumocystis jiroveci) can be seen in patients with SCID who have very low CD3 T cells (classically 300) and poor T cell function; this mirrors the clinical phenotype of infants with HIV who also have low T cells (see Table 164.3). Intact T cell IL 17 immu nity is essential for control of Candida infections and overall decre ments in the entire T cell population or selective defects in the Th17 population are strongly associated with Candida. Patients with spe cific gene pathogenic variants in IL 17 signaling (IL 17RA, IL 17RC, IL 17F, and ACT1) present with chronic mucocutaneous candidiasis (CMCC; Candida infections of the skin, nails, mucosa). STAT1 gain of function pathogenic variants result in decreased IL 17 production that also predisposes patients to skin and mucosal Candida infections. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. Patients develop CMCC and autoimmune endocrine disorders such as hypoparathyroidism and adrenal insufficiency. Aspergillus Neutrophils are responsible for engulfing and killing fungal organisms. Aspergillus species are a major cause of infections in chronic granu lomatous disease (CGD), a PIDD characterized by defective neutro phil function (see Table 164.3). CGD patients most commonly develop Aspergillus pneumonia or osteomyelitis, although all sites are suscep tible to fungal infection. Aspergillus nidulans infections occur almost exclusively in CGD and result in a much higher rate of osteomyelitis and mortality than A. fumigatus. Exposure to Aspergillus through han |
6,375 | dling of mulch with gardening or exposure to hay can cause fulmi nant pneumonitis in CGD patients. Patients with GATA2 deficiency and STAT1 gain of function pathogenic variants can develop fungal infections such as aspergillus and histoplasmosis as well as atypical mycobacteria. Patients with autosomal dominant hyper IgE syndrome Table 164.4 Recurrent Invasive Pneumococcal Infections CONDITION GENECONDITION SUBSET INHERITANCE OTHER FEATURES Asplenia ATRX XL Developmental delay, low set ears, single palmar crease Asplenia HMOX1 AR Hemolysis, nephritis Asplenia NKX2 5 AD Asplenia RPSA AD Asplenia ZEB2 AD Mowat Wilson syndrome, microcephaly, Hirschsprung disease, defects in corpus callosum Asplenia Gene unknownsyndromic Can occur in heterotaxy syndromes Antibody deficiency BTK XL Antibody deficiency Hypogammaglobulinemia Various Antibody deficiency Specific antibody deficiency Various Antibody deficiency IgG subclass deficiency Various Antibody deficiency CVID Various Innate immune deficiency MYD88 AR Poor fever formation Innate immune deficiency IRAK4 AR Poor fever formation Innate immune deficiency IKBKG XL Peg teeth, ectodermal dysplasia Complement deficiency C2 AR Can have lupus Complement deficiency C1 AR Can have lupus Complement deficiency C4 AR Can have lupus Complement deficiency C3 AR Glomerulonephritis AD, Autosomal dominant; AR, autosomal recessive; CVID, common variable immunodeficiency; XL, X linked. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1256 Part XII u Immunology (STAT3 deficiency) commonly develop lung pneumatoceles (cavities), which can then become superinfected with Aspergillus. Sentinel Bacterial Infections Certain bacterial infections are considered sentinel infections because the pathogen is highly associated with specific PIDDs. The following bacteria are considered highly suspicious for CGD: Burkholderia cepa cia, Nocardia, Serratia marcescens, Chromobacterium violaceum, and Granulibacter bethesdensis. Unlike patients with cystic fibrosis, B. cepa cia in CGD can cause pneumonia but also rapidly fatal sepsis. Terminal complement (C5 C9) and alternative complement defects (proper din or factor D deficiency) have increased susceptibility to recurrent invasive Neisseria species (recurrent meningococcal and disseminated gonococcal infections). Complement deficiencies are also found more frequently in patients with meningitis due to unusual serotypes of Neisseria. Mycobacterial Infections Intact IL 12 and IFN signaling is required to activate phagocytes such as macrophages to clear intracellular pathogens such as mycobac teria (see Table 164.3). Patients who have defects along this pathway such as IL 12 p40, IL 12 receptor, and IFN receptor deficiency pres ent with atypical mycobacterial infections; these infections can spread to bones and visceral organs (rather than isolated uncomplicated cervi cal lymphadenitis, which does not suggest a PIDD). STAT1 deficiency is associated with mycobacterial infections because STAT1 is required for IFN signaling. Patients with NEMO deficiency due to pathogenic variants in IKBKG develop mycobacterial disease due to impaired IL 12 production in response to infection and impaired TLR signaling. Atypical mycobacteria also cause pulmonary disease in patients with CGD. Patients with the PIDDs mentioned previously born outside of the United States who receive the bacilli Calmette Gurin (BCG) attenuated vaccine can present with disseminated BCG strain |
6,376 | myco bacterial infection often complicating subsequent hematopoietic cell transplantation. Severe Cryptosporidia Cryptosporidium is a protozoan parasite that causes diarrheal dis ease in humans. Exposure occurs from contaminated drinking water sources as well as fresh water and public swimming pools. Patients with PIDD can develop infections outside of the GI tract such as the lungs, biliary tract, and pancreas. Intact T cell immunity appears to play a critical role in resolution of Cryptosporidium infection as evidenced by the high incidence of this infection in patients with HIV. PIDDs with impaired T cell immunity are characterized by increased risk for developing Cryptosporidium. In X linked hyper IgM syndrome, major histocompatibility complex (MHC) class II deficiency, DOCK8 defi ciency, IL 21 receptor deficiency, sclerosing cholangitis, and cirrhosis from chronic Cryptosporidium infection can occur. The presence of liver disease from Cryptosporidium appears to increase the risk of mor tality from curative hematopoietic cell transplantation. SCHEMA FOR DIAGNOSIS Clues to the diagnosis of a PIDD may be obtained by the past and cur rent history and the physical exam (Tables 164.6 and 164.7) Laboratory studies typically used in the diagnosis of PIDD are rudi mentary. Typical laboratory studies measure the amount of antibody or count the numbers of a given cell type (T cells as an example). There is a relatively limited ability to test function. Figures 164.1 and 164.2 outline a strategy to approach the diagnostic testing for PIDDs. NONINFECTIOUS PRESENTATIONS SUGGESTING PIDD Autoimmunity and inflammation can be indicators of a possible PIDD. Infections may be falsely attributed to the medications used to control the autoimmunity or inflammation. Often the usual immunologic test ing is normal. Many of the autoimmune or autoinflammatory disor ders associated with PIDD may need to be identified through genetic sequencing. Autoimmunity Autoimmunity can be the presenting manifestation of a PIDD. Rather than having the more familiar infectious phenotype, these patients have defects in tolerance or lymphocyte function that compromise their homeostasis. HLH is a profound form of immune dysregulation (see Chapter 556.2). These conditions are important to recognize because targeted therapies can be beneficial and because they can evolve to complex phenotypes with severe morbidity. The typical laboratory Table 164.5 Primary Immune Deficiency Disease and Risk of Hemophagocytic Lymphohistiocytosis CONDITION GENECONDITION SUBSET INHERITANCE RISK OF HLH OTHER FEATURES CD48 deficiency CD48 AD High Chdiak Higashi syndrome LYST AR High Pigmentary dilution NLRC4 NLRC4 High IBD Perforin deficiency (FHL2) PRF1 AR High Griscelli syndrome, type 2 RAB27A AR High Pigmentary dilution X linked lymphoproliferative disease 1 SH2D1A XL High Syntaxin 11 deficiency (FHL4) STX11 AR High STXBP2Munc18 2 deficiency (FHL5) STXBP2 AR or AD High Hypogammaglobulinemia, IBD UNC13DMunc13 4 deficiency (FHL3) UNC13D AR High X linked lymphoproliferative disease 2 XIAP XL High CD27 deficiency CD27 AR Medium Unable to control EBV Chronic granulomatous disease All genetic types XL, AR Low Infections, granulomas Hermansky Pudlak syndrome, type 2 AP3B1 AR Low Pigmentary dilution Hermansky Pudlak syndrome, type 10 AP3D1 AR Low Pigmentary dilution Lysinuric protein intolerance SLC7A7 deficiency SLC7A7 AR Low |
6,377 | Lung disease, feeding intolerance Other primary immune deficiency diseases, including most T cell deficiencies have been associated with HLH in rare patients. AD, Autosomal dominant; AR, autosomal recessive; HLH, Hemophagocytic lymphohistiocytosis; IBD, inflammatory bowel disease. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 164 u Orientation to the Consideration of Inborn Errors of Immunity 1257 evaluations used in the diagnosis of the PIDD are often unrevealing or minimally abnormal, leading to delay in diagnosis and implementation of appropriate therapy. The prognosis may be poor; hematopoietic cell transplantation is recommended. Early Onset Systemic Lupus Erythematosus Prepubertal systemic lupus erythematosus (SLE) is uncommon and onset of SLE before 5 years of age is exceptionally unusual (Table 164.8); onset before 5 years of age suggests a monogenic condition such as early complement component deficiencies (see Chapter 173). Comple ment deficiencies also have an infection phenotype. SLE is the domi nant phenotype for C1 and C4 deficiencies. The mechanism by which these complement deficiencies lead to susceptibility to SLE is through impaired clearance of apoptotic material and compromised tolerance. SLE may present in infancy in C1 and C4 deficiencies and it is typi cally severe. C2 deficiency, in contrast, is associated with a milder sus ceptibility to SLE and proportionally higher susceptibility to infection. Other gene defects associated with early onset SLE include lymphocyte defects such as PRKCD, FAS, and FASL. Manifestations of the inter feronopathies such as Aicardi Goutires can resemble SLE and may have a high rate of antinuclear antibodies (ANA). CNS involvement and a cutaneous vasculopathy are hallmarks of interferonopathies (see Chapter 205). Early Onset Enteropathy Small bowel enteropathy in these conditions is defined as nongluten sensitive and associated with villous blunting or atrophy (Table 164.9). A key component of the differential diagnosis is the congenital diar rheas associated with either solute carrier defects or altered epithelial function (see Chapter 385). However, many of the solute carrier defects do not have villous blunting or atrophy. The early onset enteropathy conditions are most often related to T cell defects in intolerance and are classically associated with dysfunctional regulatory T cells such as in IPEX (immune dysregulation enteropathy X linked). Identical but milder enteropathy is also seen in patients with STAT5B deficiency and IL2RA deficiency. Both of these molecules are required for critical signal transduction in regulatory T cells. Although enteropathy is often the presenting manifestation in these regulatory T cell deficiency states, many of these patients will develop additional autoimmune features. The progression of autoimmune involvement of different organ systems can only be altered through hematopoietic cell transplantation. Enter opathy can also be seen in older individuals with one of the immune dysregulation conditions associated with CVID. In these conditions, the enteropathy may appear in early childhood or as late as middle age. The key to suspecting a monogenic immune dysregulation condition is the finding |
6,378 | of villous atrophy that is not gluten restriction responsive. Expanded populations of intraepithelial lymphocytes are also common. Pleomorphic Autoimmunity Autoimmunity in children usually does not imply an inherited mono genic condition (Table 164.10). In a setting where there is a strong fam ily history and a suspected autosomal dominant condition, the first onset of autoimmunity may prompt a genetic evaluation; a single organ autoimmune disease does not strongly suggest that there is a mono genic condition underlying that autoimmune disease. Pleomorphic autoimmunity refers to autoimmune disease affecting multiple organs in a pattern that is not typical for either age of onset or evolution. SLE can affect a number of organs as can mixed connec tive tissue disease, but it would be unusual for those conditions to also be associated with diabetes mellitus or autoimmune hepatitis. When autoimmunity does not fall cleanly into a particular diagnosis, it is sug gestive of pleomorphic autoimmunity. There is a broad range of defects in T and B cell tolerance and con ditions associated with impaired regulation of T cell behavior that can lead to an array of autoimmune conditions. The organs affected by autoimmunity typically accrue over time and in a pattern that is not standard for the known sporadic systemic autoimmune conditions. In some cases, these conditions may also have peculiar pathologic fea tures that represent a clue that the underlying diagnosis is something other than a standard autoimmune disease of childhood. Table 164.10 attempts to categorize conditions according to the pathway implicated. There is wide heterogeneity in the timing of the autoimmune disease, the penetrance of the disease, and the end organs affected. This com bination makes this particular subset of PIDD extraordinarily difficult to conceptualize. Only a high index of suspicion and the use of genetic evaluations can identify these patients who will often benefit from tar geted therapeutics. Table 164.6 Clinical Aids to the Diagnosis of Immunodeficiency SUGGESTIVE OF B CELL DEFECT (HUMORAL IMMUNODEFICIENCY) Recurrent bacterial infections of the upper and lower respiratory tracts Recurrent skin infections, meningitis, osteomyelitis secondary to encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Neisseria meningitidis) Severe Giardia lamblia infections Paralysis after vaccination with live attenuated poliovirus Reduced levels of immunoglobulins SUGGESTIVE OF T CELL DEFECT (COMBINED IMMUNODEFICIENCY) Systemic illness after vaccination with any live virus or BCG Unusual life threatening complication after infection with benign viruses (giant cell pneumonia with measles; varicella pneumonia) Chronic oral candidiasis after 6 mo of age Chronic mucocutaneous candidiasis Graft versus host disease after blood transfusion Reduced lymphocyte counts for age Low level of immunoglobulins Absence of lymph nodes and tonsils Small thymus Chronic diarrhea Failure to thrive Recurrent infections with opportunistic organisms Generalized, recurrent, recalcitrant warts SUGGESTIVE OF MACROPHAGE DYSFUNCTION Disseminated atypical mycobacterial infection, recurrent Salmonella infection Fatal infection after BCG vaccination CONGENITAL SYNDROMES WITH IMMUNODEFICIENCY Ataxia telangiectasia: ataxia, telangiectasia Autoimmune polyglandular syndrome: hypofunction of one or more endocrine organs, chronic mucocutaneous candidiasis Cartilage hair hypoplasia: short limbed dwarfism, sparse hair, neutropenia Wiskott Aldrich syndrome: thrombocytopenia, male gender, |
6,379 | eczema Chdiak Higashi syndrome: oculocutaneous albinism, nystagmus, recurrent bacterial infections, peripheral neuropathies DiGeorge syndrome (22q deletion syndrome): unusual facies, heart defect, hypocalcemia CHARGE syndrome: coloboma, heart defects, atresia choanae, retarded growth, genital hypoplasia, ear anomaliesdeafness Short limb skeletal dysplasia with combined immune deficiency: metaphyseal dysplasia, ADA deficiency, or Omenn syndrome X linked agammaglobulinemia with growth hormone deficiency: hypogammaglobulinemia, growth hormone deficiency Kabuki syndrome: long palpebral fissures, prominent eyelashes, congenital heart disease Timothy syndrome: prolonged QT, congenital heart disease, developmental delay PTEN tumor hamartoma syndrome: multiple hamartomas, cancer SUGGESTIVE OF ASPLENIA Heterotaxia, complex congenital heart disease, Howell Jolly bodies on blood smear, sickle cell anemia ADA, Adenosine deaminase; BCG, bacille Calmette Gurin. From Verbsky JW, Routes JM. Recurrent fever, immune deficiency, and autoinflammatory disorders. In: Kliegman RM, Toth H, Bordini BJ, Basel D, eds. Nelson Pediatric Symptom Based Diagnosis. 2nd ed. Philadelphia: Elsevier; 2023.Table 54.7, p. 1028. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1258 Part XII u Immunology Inflammatory Diseases Many of the recognized inflammatory diseases are the periodic fever (autoinflammatory) syndromes (see Chapter 204). Distinguishing fevers related to infection and those fevers that are driven by endog enous immune dysfunction is often initially difficult. The first contact with the healthcare system may be by a subspecialist who may only recognize the initial presenting manifestation. The inflammatory dis eases are typically managed according to the pathway that is defective; therefore the distinction between these conditions and the autoim mune conditions is critically important. Very Early Onset Inflammatory Bowel Disease A key setting where a monogenic inflammatory condition should be considered is infantile onset inflammatory bowel disease or early onset inflammatory bowel disease with additional autoimmune features (see Chapter 382.1). Overall, approximately 20 of children who develop inflammatory bowel disease prior to 6 years of age will have a mono genic immune based condition. The frequency increases with infantile onset or with panenteric disease. The diagnosis is most often estab lished through genetic sequencing because the implicated genes are numerous and diverse (see Chapters 174 and 382.3). These conditions are managed with targeted biologic or small molecule agents with a few select patient subsets requiring hematopoietic cell transplantation. Fever Syndromes The central feature of the inherited fever syndromes is fever arising in the absence of infectious trigger (see Chapter 204). Infants and toddlers may have infections with a frequency of one per month and take as long as 2 weeks to recover. Nevertheless, the parents will often remark that the fevers came out of the blue or no one else in the household was ill at the time and express surprise at the frequency with which their child has been diagnosed with a viral infection with no viral symptoms. Some of the fever syndromes have fever that is typi cally isolated with no additional end organ effects, whereas others have fever as a component |
6,380 | of a much larger systemic inflammatory picture. The most familiar inherited fever syndromes are those associ ated with inflammasome activation and typically treated with IL 1 inhibitors. A key consideration in the differential diagnosis for these conditions is the nongenetic condition called periodic fever aphthous stomatitis pharyngitis adenitis (PFAPA; see Chapter 204). Table 164.7 Special Physical Features Associated with Immunodeficiency Disorders CLINICAL FEATURES DISORDERS DERMATOLOGIC Eczema Wiskott Aldrich syndrome, IPEX, hyper IgE syndromes, hypereosinophilia syndromes, IgA deficiency Sparse andor hypopigmented hair Cartilage hair hypoplasia, Chdiak Higashi syndrome, Griscelli syndrome Ocular telangiectasia Ataxia telangiectasia Oculocutaneous albinism Chdiak Higashi syndrome Severe dermatitis Omenn syndrome Erythroderma Omenn syndrome, SCID, graft versus host disease, Coml Netherton syndrome Recurrent abscesses with pulmonary pneumatoceles Hyper IgE syndromes Recurrent organ granulomas or abscesses, lung, liver, and rectum especially CGD Recurrent abscesses or cellulitis CGD, hyper IgE syndrome, leukocyte adhesion defect Cutaneous granulomas Ataxia telangiectasia, SCID, CVID, RAG deficiency Oral ulcers CGD, SCID, congenital neutropenia Periodontitis, gingivitis, stomatitis Neutrophil defects Oral or nail candidiasis T cell immune defects, combined defects (SCIDs); mucocutaneous candidiasis; hyper IgE syndromes; IL 12, IL 17, and IL 23 deficiencies; CARD9 deficiency; STAT1 deficiency Vitiligo B cell defects, mucocutaneous candidiasis Alopecia B cell defects, mucocutaneous candidiasis Chronic conjunctivitis B cell defects EXTREMITIES Clubbing of nails Chronic lung disease caused by antibody defects Arthritis Antibody defects, Wiskott Aldrich syndrome, hyper IgM syndrome ENDOCRINOLOGIC Hypoparathyroidism DiGeorge syndrome, mucocutaneous candidiasis Endocrinopathies (autoimmune) Mucocutaneous candidiasis Diabetes, hypothyroid IPEX and IPEX like syndromes Growth hormone deficiency X linked agammaglobulinemia Gonadal dysgenesis Mucocutaneous candidiasis HEMATOLOGIC Hemolytic anemia B and T cell immune defects, ALPS Thrombocytopenia, small platelets Wiskott Aldrich syndrome Neutropenia Hyper IgM syndrome, Wiskott Aldrich variant, CGD Immune thrombocytopenia B cell immune defects, ALPS SKELETAL Short limb dwarfism Short limb dwarfism with T cell andor B cell immune defects Bony dysplasia ADA deficiency, cartilage hair hypoplasia ADA, Adenosine deaminase; ALPS, autoimmune lymphoproliferative syndrome; CGD, chronic granulomatous disease; CVID, common variable immunodeficiency; IPEX, X linked immune dysfunction enteropathy polyendocrinopathy; SCID, severe combined immunodeficiency. From Goldman L, Ausiello D, ed. Cecil Textbook of Medicine. 22nd ed. Philadelphia: Saunders; 2004. p 1599. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 164 u Orientation to the Consideration of Inborn Errors of Immunity 1259 Fig. 164.2 Initial work up and follow up studies of patients with suspected immune deficiency. Consultation with a clinical immunologist is rec ommended to guide advanced testing and interpret results. CGD, Chronic granulomatous disease; Ig, immunoglobulin; LAD, leukocyte adhesion defect; NK, natural killer; IL, interleukin; IFN, interferon. (From Verbsky JW, Routes JM. Recurrent fever, immune deficiency, and autoinflammatory disorders. In Kliegman RM, Toth H, Bordini BJ, Basel D, eds. Nelson Pediatric Symptom Based Diagnosis. 2nd ed. Philadelphia: Elsevier; 2023. Fig. 54.9, p. 1029.) If normal, consult with clinical immunologist, consider the following History and physical exam CBC with differential counts CulturesImaging IgG, IgA, |
6,381 | IgM, IgE levels Diphtheria, tetanus titers Pneumococcus, Haemophilus titers CH50, AH50 Suspect phagocyte defect Suspect humoral defect Suspect combined defect Dihydrorhodamine for CGD Flow cytometry for T cells (CD4, CD8), B cells, NK cells Flow cytometry for T cells (CD4, CD8), B cells, NK cells Flow cytometry for LAD1 (CD11CD18) or LAD2 (CD15) Enumerate percentage of nave, memory, and switched memory B cells Enumerate percentage of memory vs nave T cells (CD45 isoform expression) Consider neutrophil chemotaxis assays Functional B cell studies T cell mitogen studies IL12 receptorIFN receptor expression and function Table 164.8 Early Onset Monogenic Systemic Lupus Erythematosus PATHWAY GENE INHERITANCE SLE FREQUENCY OTHER FEATURES Complement C1QA AR High Infections Complement C1QB AR High Infections Complement C1QC AR High Infections Complement C1R AR High Infections Complement C1S AR High Infections Complement C2 AR Low Infections Complement C3 AR Low Infections, GN Complement C4 AR High Infections Type I Interferon AGS ADAR AR or AD (DN) Low AGS, CNS Type I Interferon AGS IFIH1 AD (GOF) Low AGS, arthropathy, CNS Type I Interferon AGS RNASEH2ABC AR Low AGS Type I Interferon AGS SAMHD1 AR Low AGS, FCL, CNS Type I Interferon AGS TREX1 AR or AD (DN) Low AGS, FCL Type I Interferon ACP5 AR High Bone, CNS Type I Interferon DNASE1 AR High Type I Interferon DNASE2 AR High GN Type I Interferon DNASE1L3 AR High HUVS Type I Interferon OTUD1 AD Medium Arthritis, IBD Type I Interferon STING AD (GOF) Medium Vasculopathy, arthritis, ILD Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1260 Part XII u Immunology PATHWAY GENE INHERITANCE SLE FREQUENCY OTHER FEATURES RASMAPK KRAS AD Low Short stature RASMAPK PTPN1 AD Low Short stature RASMAPK SHOC2 AD Low Noonan like syndrome Proteasome PSMA3 AD Low Dermatosis, lipodystrophy Proteasome PSMB4 AD Low Dermatosis, lipodystrophy Proteasome PSMB8 AD Low Dermatosis, lipodystrophy Proteasome PSMB9 AD Low Dermatosis, lipodystrophy Apoptosis FASLG AD Medium ALPS Apoptosis TNFRSF6 AD Medium ALPS Tolerance PRKCD AR High Infections Tolerance RAG12 AR Medium Infections, granulomas Oxidase CYBB XL Low Males, CGD; females, discoid SLE AKT PTEN AD Medium Malignancy risk Collagen PEPD AR Low Leg ulcers Amino acids SLC7A7 AR Low Lysinuric protein intolerance Carbohydrate MAN2B1 AR Low Mannosidase NFKappaB TNFAIP3 AD Medium Vasculitis, ALPS Adenosine ADA2 AR Low Vasculitis, CNS, ALPS Transcription factor IKZF1 AD Low Leukemia, infections AD, Autosomal dominant; AGS, Aicardi Goutires syndrome; ALPS, autoimmune lymphoproliferative syndrome; AR, autosomal recessive; CNS, central nervous system; DN, domi nant negative; FCL, familial chilblains lupus; GOF, gain of function; GN, glomerulonephritis; HUVS, hypocomplementemic urticarial vasculitis; IBD, inflammatory bowel disease; ILD: interstitial lung disease; SLE, systemic lupus erythematosus; XL, X linked. Table 164.8 Early Onset Monogenic Systemic Lupus Erythematosuscontd Table 164.9 Early Onset Enteropathy (Not Gluten Sensitive) CONDITION GENE INHERITANCE ENTEROPATHY FREQUENCY OTHER FEATURES Microvillous inclusion disease MYO5B AR Always Neonatal onset Microvillous inclusion disease STX3 AR Always |
6,382 | Neonatal onset Tufting enteropathy EPCAM AR Always Neonatal onset Tufting enteropathy SPINT2 AR Always Keratitis, analchoanal atresia Trichohepatoenteric syndrome SKIV2L AR Always Trichorrhexis nodosa, IUGR Trichohepatoenteric syndrome TTC37 AR Always Trichorrhexis nodosa, IUGR Multiple intestinal atresia TTC7A AR High Lymphopenia, IA Immune dysregulation CARD11 AD Low CVID, alopecia, atopy Immune dysregulation CTLA4 AD Medium (broad age of onset) LP, CVID, infections Immune dysregulation DEF6 AR Medium Cardiomyopathy, infections Immune dysregulation FOXP3 XL Always Diabetes Immune dysregulation ICOS AR Medium (broad age of onset) LP, CVID, infections Immune dysregulation IL2RA AR Low Lymphopenia, infections, LP Immune dysregulation LRBA AR Medium (broad age of onset) LP, CVID, infections Immune dysregulation MALT1 AR High Infections, LP, eczema Immune dysregulation RLTPR AR Medium Infections, EBV Immune dysregulation STAT1 AD (GOF) High Candida, diabetes Immune dysregulation STAT3 AD (GOF) High Short, LP Immune dysregulation XIAP XL High EBV, HLH MHC class II deficiency RFXANK AR Low Infection, cytopenias MHC class II deficiency CIITA AR Low Infection, cytopenias MHC class II deficiency RFX5 AR Low Infection, cytopenias MHC class II deficiency RFXAP AR Low Infection, cytopenias AD, Autosomal dominant; AR, autosomal recessive; CVID, Common variable immune deficiency; EBV, Epstein Barr virus; GOF, gain of function; HLH, hemophagocytic lymphohistiocytosis; IA, intestinal atresia and fibrosis; IUGR, intrauterine growth retardation; LP, lymphocytic infiltrates in multiple organs; MHC, major histocompatibility complex; XL, X linked. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 164 u Orientation to the Consideration of Inborn Errors of Immunity 1261 Although genetic fever syndromes may have a cutaneous compo nent, abdominal pain, or nausea, fever is by far the dominant mani festation. There may be a family history or there may be an ethnic background that suggests the diagnosis (e.g., familial Mediterra nean fever). Other fever syndromes are related to proteasome dysfunction. These often have a very strong cutaneous component that can be a neutrophilic dermatosis or more of a vasculopathic picture with chilblains affecting the ears, fingers, and toes. Over time, these conditions may develop lipodystrophy. Fever is often seen in these conditions before 5 years of age. Treatment often includes a Jak inhibitor. In their most severe form, interferonopathies present with the infantile onset leukoencephalopathy called Aicardi Goutires syn drome. There are milder variants leading to interferon production that can be associated with later onset and a picture more typical for SLE. The earlier the onset the more likely there is to be significant brain involvement. These conditions are treated with Jak inhibitors. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. Table 164.10 Pleomorphic Autoimmunity (Autoimmunity Not Limited to a Single Organ) PATHWAY GENE INHERITANCE MAIN ORGANS INVOLVED NONIMMUNE FEATURES INFECTIONS B cell tolerance AID AR Lymphoid hyperplasia, cytopenias, GI High IgM, frequent infections T cell tolerance AIRE ARAD Endocrine organs, lung, skin Nail dystrophy Candida T cell tolerance ARPC1B AR Cytopenias, GI Thrombocytopenia Frequent infections T cell |
6,383 | tolerance CTLA4 AD GI, lung, CNS Frequent infections T cell tolerance COPA AD Lung, joint, renal T cell tolerance FOXP3 XL GI, endocrine, skin T cell tolerance HAVCR2 AR HLH, panniculitis, SLE like, joint Lymphoma T cell tolerance IL2RA AR Skin, GI, endocrine Viral T cell tolerance IL2RB AR GI, skin Viral T cell tolerance ITCH AR Joints, lung, enteropathy Developmental delay T cell tolerance JAK1 AD (GOF) Skin, renal, GI T cell tolerance LRBA AR GI, lung, CNS T cell tolerance ORAI1 AR Cytopenias, vasculitis Myopathy, poor dental enamel Frequent infections T cell tolerance PRKCD AR SLE like Frequent infections T cell tolerance PTEN AD Cytopenias, GI, endocrine Malignancy, macrocephaly, developmental delay T cell tolerance STAT1 AD (GOF) GI, endocrine Candida T cell tolerance STAT3 AD (GOF) GI, lung, endocrine Short stature T cell tolerance STIM1 AR Cytopenias, Sjgren syndrome Myopathy, poor dental enamel Frequent infections T cell tolerance TPP2 AR Hematopoietic CNS Viral T cell tolerance WAS XL Cytopenias, GI Thrombocytopenia Frequent infections T cell tolerance WIP AR Cytopenias, GI Thrombocytopenia Frequent infections Inflammatory pathway RBCK1 AR Joints, skin, GI Amylopectin deposits in muscle Frequent infections Inflammatory pathway RIPK1 AD GI, joint HSM episodic Fevers Inflammatory pathway RNF31 AR Joints, skin Amylopectin deposits in muscle Frequent infections, CVID like Inflammatory pathway TNFAIP3 AD Mucosal ulcers, GI, arthritis, skin Fevers Lysinuric protein intolerance SLC7A7 AR HLH, SLE, PAP HSM, poor growth, osteoporosis, renal Infections trigger metabolic decompensation AD, Autosomal dominant; AR, autosomal recessive; CNS, central nervous system; CVID, common variable immune deficiency; GI, gastrointestinal, GOF, gain of function; HLH, hemophagocytic lymphohistiocytosis; HSM, hepatosplenomegaly; PAP, pulmonary alveolar proteinosis; SLE, systemic lupus erythematosus; XL, X linked. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1262 Part XII u Immunology T CELL AND COMBINED DEFICIENCIES T lymphocytes (T cells) play a central role in the orchestration and regula tion of the adaptive immune response. CD4 T cells help B cells synthesize specific IgG, IgA, and IgE antibodies and develop into memory B cells, help macrophages kill intracellular pathogens, and regulate the immune response. CD8 T cells kill virus infected or malignant cells. Immune deficiency diseases that disrupt T cell development or function are usu ally severe, affecting multiple aspects of adaptive immunity, and are thus combined immune deficiency diseases. A hallmark of the adaptive immune response is specific recognition of pathogen proteins via antigen receptors, the T cell receptor (TCR) in T cells and immunoglobulin in B cells. Antigen receptors have a variable region that is formed by random rearrangement of two to three gene segments, V(D)J, allowing a large variety of antigen recognition. TCRs recognize a fragment of a protein that is presented by the major histocompatibility complex (MHC) molecules; therefore the randomly generated variable region of the TCR needs to be able to inter act with the individuals MHC molecules. During T cell development |
6,384 | in the thymus, only thymocytes with TCRs that recognize the individuals MHC molecules are selected to survive (positive selection) and all other thymocytes die (by neglect). Among the thymocytes that survive, those with self reactive TCRs are eliminated (negative selection) or develop into regulatory T cells to prevent autoimmune disease (Fig. 165.1). There is a symbiotic relationship between the thymus and developing thymocytes, where the absence of a thymus affects T cell development and the absence of thymocytes leads to disruption of the thymic architecture. Pathogenic gene variants affecting any of the signaling pathways, DNA recombination, and repair enzymes as well as the thymic environment can lead to T cell and combined immune deficiency diseases. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography 165.1 Severe Combined Immunodeficiencies Ramsay L. Fuleihan Severe combined immunodeficiency (SCID) is caused by diverse patho genic gene variants that lead to absence of T and B cell function. Patients with this group of disorders have the most severe immunodeficiency. GENETICS AND PATHOGENESIS SCID is caused by pathogenic variants in genes crucial for lymphoid cell development or function (Table 165.1 and Fig. 165.2). All patients with SCID have very small thymuses that contain no thymocytes and lack corticomedullary distinction and lack Hassalls corpuscles. The thymic epithelium appears histologically normal. Both the follicular and the paracortical areas of the spleen are depleted of lymphocytes. Lymph nodes, tonsils, adenoids, and Peyer patches are absent or extremely underdeveloped. Section 2 The T, B, and NKCell Systems Chapter 165 TCell and Combined Deficiencies Ramsay L. Fuleihan Fig. 165.1 Schematic representation of T cell development in the thymus. Thymocyte precursors leave the bone marrow and enter the thymus with no expression of CD3, CD4, or CD8 (double negative T cells). Later the thymo cytes express CD3 and both CD4 and CD8. If the newly formed T cell receptor (TCR) recog nizes major histocompatibility complex (MHC) class I or class II molecules, the thymocytes re ceive a positive selection signal and develop into CD8 or CD4 single positive thymocytes, respectively. Single positive thymocytes with TCR that recognize self proteins will be killed by apoptosis or develop into regulatory T cells (Treg) to prevent autoimmune disease. Single positive thymocytes that are nonself reactive leave the thymus as nave single positive T cells ready to engage in the immune response when needed. Thymus Bone marrow thymic precursors Double positive thymocyte Positive selectionMHC class II recognition MHC class I recognition Selfrecognition Apoptosis No selfrecognition CD3 CD4 CD3 CD8 Selfrecognition Negative selection Nave single positive T cells Recent thymic emigrants CD3 CD4 CD8 CD3 CD4 CD8 CD3 CD4 CD3 CD8 CD3 CD4 FoxP3 ApoptosisTreg CD3 CD4 CD3 CD8 Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 165 u TCell and Combined Deficiencies 1263 The 4 most common types of SCID are the X linked forms caused by pathogenic variants in CD132, |
6,385 | autosomal recessive RAG1 and RAG2 defi ciencies, and adenosine deaminase (ADA) deficiency. Additional forms are listed in Table 165.1. For X linked SCID and ADA deficiency, gene therapy exists, but genetic counseling is the most compelling reason for genetic sequencing to identify the pathogenic gene variant. Several spe cific pathogenic gene variants are associated with increased sensitivity to radiation and chemotherapy, and their early identification can lead to a better transplant experience by avoiding or reducing dosages of condition ing agents. CLINICAL MANIFESTATIONS SCID is included in the newborn screening program in all states in the United States and in several countries around the world. Thus infants can be identified and treated prior to development of symptoms, which has dramatically improved the survival of infants with SCID. A few genetic types of SCID are not detected by newborn screening, and there are many countries where newborn screening for SCID is not yet performed. Therefore an awareness of the clinical presentation of SCID remains important in the early diagnosis and treatment of patients. When infants with SCID are not detected through newborn screen ing, they most often present with infection during infancy. Diarrhea, pneumonia, otitis media, sepsis, and cutaneous infections are common presentations. Infections with a variety of opportunistic organisms, either through direct exposure or immunization, can lead to death. Potential infectious threats include Candida albicans, Pneumocystis jiroveci (PJP), parainfluenza 3 virus, adenovirus, respiratory syncy tial virus (RSV), cytomegalovirus (CMV), Epstein Barr virus (EBV), varicella zoster virus, measles virus, and attenuated organisms from the MMRV (measles, mumps, rubella, varicella), rotavirus, oral polio, nasal influenza, yellow fever, or bacille Calmette Gurin (BCG) vac cines. Disseminated BCG infection may be the presenting feature of SCID in countries where the vaccine is given at birth. Infants with SCID also lack the ability to reject foreign tissue and are therefore at risk for severe or fatal graft versus host disease (GVHD) from T lymphocytes in nonirradiated blood products or maternal immunocompetent T cells Table 165.1 Genetic Basis of Severe Combined Immunodeficiency and SCID Variants DISEASE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT T B SCID Reticular dysgenesis AR Impaired mitochondrial energy metabolism and leukocyte differentiation Severe neutropenia, deafness Pathogenic variants in adenylate kinase 2 GCSF, HSCT Reticular dysgenesis AD Impaired hematopoiesis Severe neutropenia but no deafness, gain of function variant in RAC2 HSCT Adenosine deaminase deficiency AR Accumulation of toxic purine nucleosides Neurologic, hepatic, renal, lung, skeletal, bone marrow abnormalities HSCT, PEG ADA, gene therapy RAG1 and RAG2 deficiency AR Defective V(D)J recombination None HSCT Artemis deficiency AR Defective V(D)J recombination, radiation sensitivity DCLERE1C pathogenic gene variants HSCT DNA PK deficiency AR Defective V(D)J recombination None HSCT DNA ligase IV deficiency AR Defective V(D)J recombination, radiation sensitivity Growth delay, microcephaly, bone marrow abnormalities, lymphoid malignancies HSCT Cernunnos XLF AR Defective V(D)J recombination, radiation sensitivity Growth delay, microcephaly, birdlike facies, bone defects HSCT T B SCID c (CD132) deficiency XL Abnormal signaling via c ILRs (IL 2, 4, 7, 9, 15, 21) None HSCT, gene therapy Jak3 deficiency |
6,386 | AR Abnormal signaling downstream of c None HSCT IL 7R deficiency AR Abnormal IL 7R signaling Thymus absent HSCT CD45 deficiency AR None HSCT CD3 deficiency AR Arrest of thymocytes differentiation at CD4CD8 stage Thymus size may be normal HSCT CD3 deficiency AR Arrest of thymocytes differentiation at CD4CD8 stage T cells absent HSCT CD3 deficiency AR Abnormal signaling None HSCT Coronin 1A deficiency AR Abnormal T cell egress from thymus and lymph nodes Normal thymus size Attention deficit disorder HSCT LAT deficiency AR Defective T cell development in the thymus Autoimmune disease HSCT SLP76 AR Abnormal signaling Neutrophil defect, skin abscesses, rash, autoimmunity HSCT attempted c, Common gamma chain; AD, Autosomal dominant; AR, Autosomal recessive; GCSF, granulocyte colony stimulating factor; HSCT, hematopoietic stem cell transplantation; IL, interleukin; Jak3, Janus kinase 3; PEG ADA, polyethylene glycol modified adenosine deaminase; R, receptor; RAG1, RAG2, recombinase activating genes 1 and 2; SCID, severe combined immune deficiency; V(D)J, variable, diversity, joining domains; XL, X linked. Adapted from Roifman CM, Grunebaum E. Primary T cell immunodeficiencies. In: Rich RR, Fleisher TA, Shearer WT, et al., eds. Clinical Immunology. 4th ed. Philadelphia: Saunders; 2013. pp. 440 441. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1264 Part XII u Immunology that crossed the placenta during pregnancy. The latter is usually not fatal but can be severe. This devastating presentation is characterized by expansion of the allogeneic cells, rash, hepatosplenomegaly, and diar rhea. A third presentation is often called Omenn syndrome, caused by hypomorphic pathogenic variants in SCID causing genes, which allow few T cells to be generated in the infant that then expand, unregulated, and cause a clinical picture similar to GVHD (Fig. 165.3) with a severe dermatitis, lymphadenopathy, and diarrhea. The difference in this case is that the cells are the infants own cells. Dermatitis, especially if it is difficult to treat, failure to thrive, and infection in the first 6 months of life, particularly severe infections from commonly mild pathogens or opportunistic organisms, should raise the suspicion of SCID. All genetic types of SCID are associated with profound immuno deficiency. A small number have other associated features or atypical features that are important to recognize. ADA deficiency can be associ ated with pulmonary alveolar proteinosis and chondroosseous dyspla sia. Adenylate kinase 2 (AK2) deficiency causes a picture referred to as reticular dysgenesis where neutrophils, myeloid cells, and lympho cytes are all low. This condition is also often associated with deafness. DIAGNOSIS A high index of suspicion is very important in the diagnosis of SCID. A key feature of SCID is that almost all patients will have a low lympho cyte count. Some patients may have a normal lymphocyte count from proliferation of B cells andor natural killer (NK) cells. A combination of infection and a persistently low lymphocyte count is an indication to test for SCID. The |
6,387 | diagnostic strategy both for symptomatic infants and those detected by newborn screening or with a family history of SCID is to perform flow cytometry to quantitate the T, B, and NK cells in the infant (Fig. 165.4). The CD45RA (nave T cell) and CD45RO (mem ory T cell) markers can be helpful to identify patients with maternal engraftment or Omenn syndrome with predominantly memory T cells. Identification of a limited TCR repertoire is also helpful in the diagno sis of Omenn syndrome. T cell function is often assessed by measuring proliferative responses to stimulation with mitogens. Gene sequencing is often done by requesting a SCID gene panel or a more extensive primary immunodeficiency (PID) gene panel. There are certain laboratory features that predict specific gene defects. When both T and B cells are low with normal numbers of NK cells, often a gene encoding a protein involved in V(D)J recombination is the cause such as RAG1 and 2. Similarly, certain cytokine receptor defects are associated with specific SCID lymphocyte phenotypes, such as absent T cells and NK cells, but normal or elevated numbers of B cells in X SCID caused by pathogenic variants in the common gamma chain (CD132) of cytokine receptors. Pathogenic variants in Janus kinase (JAK)3, which signal downstream of CD132, cause an autosomal reces sive form of SCID affecting both females and males, with an identical lymphocyte phenotype as X SCID. The diagnosis of SCID can be established by the presence of a known pathogenic gene variant, low T cell counts with proliferative response to the mitogen phytohemagglutinin (PHA) less than 10 of a normal control, or the identification of maternal T cells in the child. In male infants, this can be determined by fluorescence in situ hybridization (FISH) for the X and Y chromosomes. Newborn Screening Newborn screening for SCID has allowed the early diagnosis and treat ment of SCID, improving the outcome of therapy and changing the natural history of the disease. Newborn screening is based on quan titative polymerase chain reaction (PCR) of T cell receptor excision circles (TRECs), which are formed during V(D)J rearrangement of the variable region of the TCR chains. These TRECs do not replicate during cell division; they are thus present in most or all recent thy mic emigrants but get diluted out as T cells divide in the periphery. The TREC assay identifies low numbers of recent thymic emigrants, which is not diagnostic of SCID, but raises suspicion to proceed with an evaluation of lymphocyte subsets and function followed by confir mation with genetic testing. Other diseases with low T cell counts may also be identified by newborn screening and include 22Q11.2 deletion syndrome, Rac2 deficiency, trisomy 21, and idiopathic lymphopenia, which was not well appreciated until newborn screening was imple mented. In many countries, kappa excision circles (KRECs), generated during B cell development, are assayed simultaneously with TRECs allowing a larger number of types of SCID to be identified as well as allowing identification of infants with agammaglobulinemia. |
6,388 | TREATMENT SCID is a true pediatric immunologic emergency. Unless immunologic reconstitution is achieved through hematopoietic stem cell transplan tation (HSCT) or gene therapy, death usually occurs during the first year of life and almost invariably before 2 years of age. HSCT in the first 100 days of life or in an infant prior to infection is associated with a 95 survival rate. In patients with SCID, 92 have survived after T celldepleted parental marrow is given soon after birth when the infant is healthy, without pretransplant chemotherapy or posttrans plant GVHD prophylaxis, although T cell reconstitution is improved with pretransplant conditioning including reduced intensity protocols. 216 SCIDs: Genetic types 10 RAG 4.6 99 c Def 45.8 13 Jak3 Def 6 34 ADA Def 15.7 1 CD3 Def 0.5 26 IL7R Def 12 2 CD3 Def 0.9 1 CD3 Def 0.5 1 CD45 Def 0.5 13 AutoRec 6 9 Unknown 4.2 7 Artemis 3.2 Fig. 165.2 Relative frequencies of the different genetic types of se vere combined immunodeficiency (SCID) among 216 patients seen consecutively. (From Buckley RH, Orange JS. Primary immunodeficien cy diseases. In: Burks AW, Holgate ST, OHehir RE, et al., eds. Mid dletons Allergy: Principles and Practice. 9th ed. Philadelphia: Elsevier; 2020. Fig. 69.2, p. 1126.) Fig. 165.3 Typical clinical features in an infant with Omenn syndrome. Note generalized erythroderma with scaly skin, alopecia, and edema. (From Notarangelo LD. T cell immunodeficiencies. In: Leung DYM, Ak dis CA, Bacharier LB, et al., eds. Pediatric Allergy Principles and Prac tice. 4th ed. Philadelphia: Elsevier; 2021. Fig 6.1.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 165 u TCell and Combined Deficiencies 1265 Bone marrow transplantation remains the most important and effec tive therapy for SCID. In ADA deficient and X linked SCID, there has been success in correcting the immune defects with ex vivo gene transfer to autologous hematopoietic stem cells. Initial protocols of gene therapy for X linked SCID resulted in insertional mutagenesis with the development of leukemic like clonal T cells or lymphoma in some patients. Modification of the gene therapy protocol has greatly reduced the risk of insertional mutagenesis. ADA deficient SCID can also be treated with enzyme replacement by repeated injections of polyethylene glycol ADA (PEG ADA), although the immune reconsti tution achieved is not as effective as with HSCT or gene therapy. Until definitive therapy can be achieved, SCID patients should be treated with supportive care for prevention and treatment of infections with immunoglobulin replacement and microbial prophylaxis starting at 4 6 weeks of age including PJP prophylaxis as well as viral and fungal prophylaxis. Breastfeeding should be avoided if the mother is CMV or EBV positive as infection can be transmitted via breast milk. Visit Elsevier eBooks at eBooks.Health.Elsevier.com for Bibliography. 165.2 Combined Immunodeficiencies Ramsay L. Fuleihan Combined immunodeficiency (CID) is distinguished from SCID by the presence |
6,389 | of low but not absent T cell function. CID is a syndrome of diverse genetic causes and, therefore, diverse clinical and laboratory char acteristics. Patients with CID may have recurrent or chronic pulmonary infections, opportunistic infections, failure to thrive, oral or cutaneous candidiasis, chronic diarrhea, recurrent skin infections, gram negative bacterial sepsis, urinary tract infections, or severe varicella in infancy. Although they usually survive longer than infants with SCID, patients with CID fail to thrive and often die before reaching adulthood. Neutropenia and eosinophilia are common. Serum immunoglobulins may be normal or elevated for all classes; selective IgA deficiency, marked elevation of IgE, and elevated IgM levels occur in some cases. Although antibody forming capacity is impaired in most patients, it may not be absent. Studies of cellular immune function may show lymphopenia, defi ciencies of T cells, specific T cell subsets, or switched memory B cells, and extremely low but not absent lymphocyte proliferative responses to mitogens, antigens, or allogeneic cells in vitro. Peripheral lymphoid tis sues may demonstrate paracortical lymphocyte depletion. The thymus is usually small, with a paucity of thymocytes and usually no Hassalls corpuscles. There is a large number and variety of CIDs caused by pathogenic vari ants in many different genes. A list of known causes of CID with some of their characteristic features can be found in Tables 165.2 to 165.7. COMBINED IMMUNODEFICIENCIES THAT ARE GENERALLY LESS PROFOUND THAN SCID Several types of CID are characterized by a severe immunodeficiency but affected patients tend to survive longer than patients with SCID (see Table 165.2). These patients are susceptible to severe viral, oppor tunistic, andor fungal infections. Their laboratory features are variable from normal lymphocyte subsets to a severe deficiency of CD4, CD8, or both cell types. Invariably, T cell function is decreased but prolif erative responses to mitogens and, in some cases, to antigens may be normal, making it difficult to have unifying laboratory characteristics for this group of diseases. The severity of clinical infection andor the presence of a family history of CID should raise suspicion and initiate a laboratory evaluation for these diseases. COMBINED IMMUNODEFICIENCY FROM DEFICIENCY IN CD4 T CELL HELPER FUNCTION CD4 T cells play an important role in orchestrating the immune response. Helper function from CD4 T cells is critical for immuno globulin isotype switching, somatic hypermutation, and B cell memory MHC II deficiency ZAP70 deficiency Low CD8Low CD4 TB NormalLow Absolute lymphocytes TB Omenn syndrome Normal CD4 CD8 Absent Normal PNP activity Absent Normal ADA activity Xlinked IL2RG TBNK TBNKTB TBNK PNP deficiency IL7Ra, CD45, CD3? ADA deficiency RAG1 or RAG2 Fig. 165.4 Using the absolute lymphocytes count as a starting place to suggest the type of severe combined immunodeficiency (SCID) that may be present. ADA, Adenosine deaminase; MHC, major histocompatibility complex; PNP, purine nucleoside phosphorylase. (From Cunningham Rundles C. Approach to the child with recurrent infections and molecular diagnosis. In: Leung DYM, Akdis CA, Bacharier LB, et al., eds. Pediatric Allergy Principles and Practice. 4th ed. Philadelphia: |
6,390 | Elsevier; 2021. Fig. 4.2.) Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1266 Part XII u Immunology Table 165.2 Combined Immunodeficiencies Generally Less Profound Than SCID DISEASE (DEFICIENCY) INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT CD40 Ligand (CD154) XL Defective CD40 ligand:CD40 signaling Opportunistic infections, neutropenia, biliary tract and liver diseasecancer, neuroectodermal cancer HSCT CD40 AR Defective CD40 ligand:CD40 signaling Opportunistic infections, neutropenia, biliary tract and liver disease HSCT ICOS AR Autoimmunity, gastroenteritis, granulomas ICOS Ligand AR Decreased T and B cells Neutropenia CD3 AR Low TCR expression Autoimmunity of variable severity CD8 AR Absent CD8 T cells May be asymptomatic ZAP 70 LOF AR Low CD8 T cells, poor CD4 T cell function May have immune dysregulation, autoimmunity HSCT ZAP 70 LOFGOF AR Low CD8 T cells Severe autoimmunity, bullous pemphigoid, inflammatory colitis HSCT MHC class I (TAP1, TAP2, TAPBP, 2 microglobulin) AR Low CD8 T cells, absent MHC I on lymphocytes and thymic epithelium Vasculitis, pyoderma gangrenosum MHC class II (CIITA, RFX5, RFXANK, RFXAP) AR Low CD4 T cells absent MHC II on lymphocytes and thymic epithelium Failure to thrive, liver biliary tract disease HSCT IKAROS AD No memory T cells or B cells Opportunistic infections, early CID onset DOCK2 AR Low T cells and poor NK cell function Invasive herpesvirus infections, poor interferon responses Polymerase and (POLD1, POLD2) AR Low CD4 T cells Skin infections, warts and molluscum, short stature, intellectual disability RHOH AR Restricted TCR repertoire HPV infection, lung granulomas, molluscum, lymphoma STK4 AR Low CD4 T cells Intermittent neutropenia, viral and Candida infection, lymphoproliferation, autoimmune cytopenias, lymphoma, congenital heart disease TCR AR Absent TCR Immune dysregulation, autoimmunity, diarrhea LCK AR Poor TCR signaling, low CD4 T cells and low regulatory T cells, restricted TCR repertoire Immune dysregulation, autoimmunity ITK AR Decreased T cell activation, progressive decline in CD4 T cells EBV associated B cell lymphoproliferation, immune dysregulation MALT1 AR Poor T cell proliferation CARD11 LOF AR Poor T cell proliferation Opportunistic infections BCL10 AR Poor T cell antigen or anti CD3 proliferation, few memory T cells and Tregs Candidiasis, gastroenteritis IL 21 AR Low T cell function, low memory switched B cells Opportunistic infections, liver disease IL 21R AR Low cytokine production, low T cell antigen proliferation OX40 AR Low Ag specific memory CD4 T cells Impaired immunity to HHV8, Kaposis sarcoma IKBKB AR Impaired TCR activation, absent Treg and T cells Opportunistic infections HSCT NIK AR Poor T cell antigen proliferation, low switched memory B cells Cryptosporidium infection RelB AR Reduced TCR diversity with poor proliferation to mitogens and absent to antigens Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 165 u TCell and Combined Deficiencies 1267 Table 165.2 Combined Immunodeficiencies Generally |
6,391 | Less Profound Than SCIDcontd DISEASE (DEFICIENCY) INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT RelA haploinsufficiency AD Impaired NFB activation with decreased inflammatory cytokines Chronic mucocutaneous ulceration Moesin XL Defective T cell migration and proliferation Varicella infections, neutropenia TFRC AR Poor T cell proliferation, low memory B cells Neutropenia, thrombocytopenia c Rel AR Poor T and B cell proliferation, low memory CD4 and low memory B cells Mycobacteria and Salmonella infections, opportunistic infections, defective innate immunity FCHO1 AR Poor T cell proliferation Mycobacterial infections, lymphoproliferation, failure to thrive Ag, antigen; AD, Autosomal dominant; AR, autosomal recessive; CID, combined immune deficiency; EBV, Epstein Barr virus; HHV8, human herpesvirus 8; HPV, human papillomavirus; HSCT, hematopoietic stem cell transplantation; IL, interleukin; GOF, gain of function; LOF, loss of function; MHC, major histocompatibility complex; NK, natural killer; R, receptor; TCR, T cell receptor; Treg, regulatory T cell; XL, X linked. Adapted from Tangye SG, AlHerz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022;42:14731507. Table 165.3 DNA Repair Defects Other Than Causing SCID DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT Ataxia telangiectasia ATM AR Progressive decrease in T cells, poor T cell proliferation Ataxia, telangiectasia, elevated IgM, lymphoreticular malignancy, increased radiosensitivity, chromosomal instability and translocations Ig replacement, supportive care, avoid ionizing radiation Nijmegen breakage syndrome NBS1 AR Progressive decrease in T cells Microcephaly, dysmorphic features, lymphomas and solid tumors, hyper IgM Ig replacement, supportive care, avoid ionizing radiation Bloom syndrome BLM AR Marrow failure, low Ig Short stature, dysmorphic facies, sun sensitive erythema, leukemia, lymphoma, chromosomal instability Ig replacement, supportive care, avoid ionizing radiation Immunodeficiency with centromeric instability and facial anomalies (ICF types 1, 2, 3, 4) DNMT3B ZBTB24 CDCA7 HELLS AR Decreased T cells, decreased response to PHA, hypogammaglobulinemia with variable antibody deficiency Facial dysmorphism, developmental delay, macroglossia, opportunistic infections, malabsorption, cytopenias, malignancies, multiradial configurations of chromosomes 1, 9, 16 Ig replacement, supportive care, avoid ionizing radiation PMS2 deficiency PMS2 AR Low B cells, abnormal antibody responses Caf au lait spots, hyper IgM, lymphoma, colorectal carcinoma, brain tumors Ig replacement, supportive care, avoid ionizing radiation Radiosensitivity, immune deficiency, dysmorphic features, learning difficulties (RIDDLE) syndrome RNF168 AR Low IgG or IgA Short stature, mild defects of motor control to ataxia, may have learning difficulties Ig replacement, supportive care, avoid ionizing radiation MCM4 deficiency MCM4 AR Low number and function of NK cells Short stature, B cell lymphoma, adrenal failure Supportive care, avoid ionizing radiation Polymerase subunit 1 deficiency (FILS syndrome) POLE1 AR Decreased T cell proliferation Short stature, facial dysmorphism, livedo Ig replacement, supportive care, avoid ionizing radiation Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1268 Part XII u Immunology Table 165.4 Immunoosseous Dysplasias DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT Cartilage hair hypoplasia RMRP AR Normal to severely decreased |
6,392 | T cell counts Decreased T cell proliferation Short limbed dwarfism with metaphyseal dysostosis, sparse hair, bone marrow failure, autoimmunity, susceptibility to lymphoma and other cancers, impaired spermatogenesis, neuronal dysplasia of the intestine HSCT for the immunodeficiency Schimke immuno osseous dysplasia SMARCAL1 AR Decreased T cells Short stature, spondyloepiphyseal dysplasia, intrauterine growth restriction; nephropathy; bacterial, viral, fungal infections; may present as SCID; bone marrow failure HSCT for the immunodeficiency MYSM1 deficiency MYSM1 AR Decreased T cells, nave T cells, and NK cells B cell deficiency with hypogammaglobulinemia Short stature; recurrent infections; congenital bone marrow failure, myelodysplasia; immunodeficiency affecting B cells and granulocytes; skeletal anomalies; cataracts; developmental delay HSCT for the immunodeficiency MOPD1 deficiency (Roifman syndrome) RNU4ATAC AR Decreased NK cell function Decreased total and memory B cells Hypogammaglobulinemia, variably decreased specific antibodies Recurrent bacterial infections; lymphadenopathy; spondyloepiphyseal dysplasia, extreme intrauterine growth restriction; retinal dystrophy; facial dysmorphism; may present with microcephaly; short stature HSCT for the immunodeficiency Immunoskeletal dysplasia with neurodevelopmental abnormalities (EXTL3 deficiency) EXTL3 AR Decreased T cells, decreased to normal Ig levels Short stature; cervical spinal stenosis, neurodevelopmental impairment; eosinophilia; may have early infant mortality HSCT for the immunodeficiency AR, Autosomal recessive; HSCT, hematopoietic stem cell transplantation; Ig, immunoglobulin; NK, natural killer; SCID, severe combined immune deficiency. Adapted from Tangye SG, AlHerz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022;42:14731507. Table 165.3 DNA Repair Defects Other Than Causing SCIDcontd DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT Polymerase subunit 2 deficiency POLE2 AR Lymphopenia, absent T cell proliferation to Ags, hypogammaglobulinemia Disseminated BCG, autoimmunity (type 1 diabetes), hypothyroidism, facial dysmorphism Ig replacement, supportive care, avoid ionizing radiation Ligase 1 deficiency LIG1 AR Lymphopenia, increased T cells, decreased T cell proliferation, hypogammaglobulinemia antibody deficiency Growth restriction, sun sensitivity, radiation sensitivity, macrocytic RBC Ig replacement, supportive care, avoid ionizing radiation NSMCE3 deficiency NSMCE3 AR Decreased T cells and T cell response to mitogens and antigens Thymic hypoplasia, severe lung disease, chromosomal breakage, radiation sensitivity Ig replacement, supportive care, avoid ionizing radiation ERCC6L2 deficiency ERCC6L2 AR Lymphopenia Facial dysmorphism, microcephaly, bone marrow failure Supportive care, avoid ionizing radiation GINS1 deficiency GINS1 AR Low NK cells, high IgA with low IgM and IgG Neutropenia, IUGR Supportive care, avoid ionizing radiation Ag, Antigen; AR, Autosomal recessive; BCG, bacilli Calmette Gurin; FILS, facial dysmorphism, immunodeficiency, livedo, and short stature; ICF, instability, centromeric, facial anoma lies; Ig, immunoglobulin; IUGR, intrauterine growth retardation; NK, natural killer; PHA, phytohemagglutinin; RBC, red blood cell. Adapted from Tangye SG, AlHerz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022;42:14731507. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 165 u TCell and Combined Deficiencies 1269 Table 165.5 |
6,393 | Other Combined Immunodeficiencies DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT PNP deficiency PNP AR Progressive decrease in T cells Autoimmune hemolytic anemia, neurologic impairment HSCT Immunodeficiency with multiple intestinal atresias TTC7A AR Variable T cell counts but may be as low as SCID with low TRECs at NBS Multiple intestinal atresias, intrauterine polyhydramnios, early demise, bacterial (sepsis), viral and fungal infections HSCT for severe T cell deficiency Trichohepatoenteric syndrome (THES) TTC37 SKIV2L AR Impaired IFN production, variably low switched memory B cells, hypogammaglobulinemia, may have low antibody responses Respiratory infections; IUGR; facial dysmorphic features, wooly hair; early onset intractable diarrhea, liver cirrhosis; platelet abnormalities Hepatic venoocclusive disease with immunodeficiency (VODI) SP110 AR Decreased memory T and B cells; low IgG, IgA, and IgM; absent germinal centers and tissue plasma cells Hepatic venoocclusive disease Susceptibility to opportunistic infections: PJP, CMV, Candida Thrombocytopenia, hepatosplenomegaly, cerebrospinal leukodystrophy BCL11B deficiency BCL11B AD Decreased T cell counts with poor proliferation Congenital abnormalities, neonatal teeth, dysmorphic facies; absent corpus callosum, neurocognitive deficits EPG5 deficiency (Vici syndrome) EPG5 AR Very low CD4 T cells, decreased Ig levels especially IgG2, defective B cells Chronic mucocutaneous candidiasis, recurrent infections, agenesis of the corpus callosum, microcephaly, cataracts; cardiomyopathy, skin hypopigmentation, intellectual disability HOIL1 deficiency RBCK1 AR Decreased memory B cells with poor antibody response to polysaccharide antigens Bacterial infections, autoinflammation, amylopectinosis HOIP deficiency RNF31 AR Decreased memory B cells with decreased Ig levels Bacterial infections, autoinflammation, amylopectinosis, lymphangiectasia Hennekam lymphangiectasia lymphedema syndrome CCBE1 FAT4 AR Variably decreased T and B cell counts, decreased Ig levels Facial anomalies and other dysmorphic features, lymphangiectasia and lymphedema Activating de novo mutations in nuclear factor, erythroid 2 like (NFE2L2) NFE2L2 AD Decreased switched memory B cells, hypogammaglobulinemia and decreased antibody responses Recurrent respiratory and skin infections; growth restriction, developmental delay; white matter cerebral lesions; increased level of homocysteine; increased expression of stress response genes STAT5b deficiency STAT5B AR Slightly decreased T cells, decreased Treg number and function, hypogammaglobulinemia with elevated IgE Growth hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstitial pneumonitis, autoimmunity STAT5b deficiency STAT5B AD (dominant negative variants) Increased IgE Growth failure, eczema, lack immune defects of AR STAT5b deficiency Kabuki syndrome (type 1 and 2) KMT2D KDM6A AD XL (females may be affected) Low IgA, occasionally low IgG Typical facial abnormalities, cleft or high arched palate, skeletal abnormalities, short stature; intellectual disability; congenital heart defects; recurrent infections (otitis media, pneumonia); autoimmunity Continued Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1270 Part XII u Immunology Table 165.6 Thymic Disorders DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT DiGeorgeVelocardio facial syndrome chromosome 22Q11.2 deletion syndrome TBX1 deficiency 22Q11.2del including TBX1, TBX1 Unknown AD (Unknown defects are sporadic) Variable T cell counts, may have low TRECs at NBS, may have hypogammaglobulinemia Conotruncal cardiac defects, hypoparathyroidism, abnormal facies, velopalatal insufficiency, intellectual disability, autoimmunity Thymic transplant for severe T cell deficiency |
6,394 | CHARGE syndrome CHD7 SEMA3E Unknown AD AD Variable T cell counts, may have low TRECs at NBS, may have hypogammaglobulinemia Coloboma of eye; heart anomaly; choanal atresia; intellectual disability; genital and ear anomalies (CHARGE), CNS malformation Thymic transplant for severe T cell deficiency Winged helix nude FOXN1 deficiency FOXN1 AR Very low T cells, decreased Ig levels Severe infections, abnormal thymic epithelium, congenital alopecia, nail dystrophy, neural tube defect Thymic transplant attempted FOXN1 haploinsufficiency FOXN1 AD Severe T cell lymphopenia at birth, normal by adulthood Recurrent, viral and bacterial respiratory tract infections; (eczema, dermatitis), nail dystrophy Chromosome 10p13 p14 deletion syndrome (10p13 p14DS) 10p13 p14del AD T cell lymphopenia rarely with decreased proliferation to mitogens and antigens, may have hypoplastic thymus Hypoparathyroidism, renal disease, deafness, growth retardation, facial dysmorphism, cardiac defects may be present, may have recurrent infections Chromosome 11q deletion syndrome (Jacobsen syndrome) 11q23del AD T, B, and NK cell lymphopenia, low switched memory B cells, variable Ig levels and antibody responses Recurrent respiratory infections; multiple warts; facial dysmorphism, growth retardation Ig replacement for antibody deficiency PAX1 PAX1 AR Absent thymus Omenn like syndrome HSCT attempted, thymic transplantation attempted AD, Autosomal dominant; AR, Autosomal recessive; del, deletion; CNS, central nervous system; HSCT, hematopoietic stem cell transplantation; TREC, T cell receptor excision circle; NBS, newborn screening; Ig, immunoglobulin. Adapted from Tangye SG, AlHerz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022;42:14731507. Table 165.5 Other Combined Immunodeficienciescontd DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT KMT2A deficiency (Wiedemann Steiner syndrome) KMT2A AD Decreased memory B cells, hypogammaglobulinemia with decreased antibody responses Respiratory infections; short stature; hypertelorism; hairy elbows; developmental delay, intellectual disability AD, Autosomal dominant; AR, Autosomal recessive; CMV, cytomegalovirus; HSCT, hematopoietic stem cell transplantation; IFN, interferon; Ig, immunoglobulin; IUGR, intrauterine growth retardation; NBS, newborn screening; PJP, Pneumocystis jiroveci; PNP, purine nucleoside phosphorylase; SCID, severe combined immune deficiency; TREC, T cell receptor excision circle; Treg, regulatory T cells; XL, X linked. Adapted from Tangye SG, AlHerz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022;42:14731507. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 165 u TCell and Combined Deficiencies 1271 Table 165.7 Hyper IgE Syndromes DISEASE GENE INHERITANCE PATHOGENESIS ADDITIONAL FEATURES TREATMENT HIE (Job syndrome) STAT3 AD (DN LOF) Decreased response to STAT3 activating cytokines; decreased Th17, T follicular helper, MAIT, NKT cells, reduced memory B cells, elevated IgE Coarse facial features, broad nasal bridge; staphylococcal abscesses, eczema, pneumatoceles, pulmonary Aspergillus, PJP, mucocutaneous candidiasis; hyperextensible joints, osteoporosis and bone fractures, scoliosis, retained primary teeth; coronary and cerebral aneurysms Bacterial and fungal prophylaxis DOCK8 deficiency DOCK8 AR T cell lymphopenia with poor proliferation, few Tregs with poor |
6,395 | function, reduced MAIT and NKT cells, very high IgE Low NK cells with poor function Eosinophilia, recurrent infections, cutaneous viral, fungal and staphylococcal infections, severe atopyallergic disease, cancer diathesis HSCT IL 6 receptor deficiency IL6R AR Decreased switched memory B cells, very high IgE Recurrent pyogenic infections, cold abscesses, elevated IL 6 levels Bacterial prophylaxis IL 6 signal transducer (IL6ST) deficiency IL6ST AR Decreased Th17 cells, reduced memory B cells, high IgE, variable antibody responses Bacterial infections, abscesses, eczema, pulmonary abscesses, pneumatoceles; bone fractures; scoliosis; retention of primary teeth; craniosynostosis Bacterial prophylaxis IL6ST IL6ST AD (DN) Increased Th2, nave T cells, low memory T and B cells, low to normal NK cell counts, elevated IgE with normal or low IgG Similar to AD HIE syndrome: dermatitis eczema, eosinophilia, recurrent skin infections, pneumonia, bronchiectasis, pneumatoceles, pulmonary aspergillosis, connective tissue defects (scoliosis, face, joints, fractures, palate, tooth retention) Bacterial and fungal prophylaxis IL6ST IL6ST AR (LOF) Death in utero or in neonatal period Fatal Stuve Wiedemann like syndrome; skeletal dysplasia, lung dysfunction, renal abnormalities, thrombocytopenia, dermatitis, eczema, defective acute phase response, complete unresponsiveness to IL 6 family cytokines None ZNF341 deficiency ZNF341 AR Decreased Th17 and NK cells, reduced memory B cells, decreased response to STAT3 activating cytokines Similar to AD HIE: mild facial dysmorphism; early onset eczema, mucocutaneous candidiasis, bacterial skin infections, Staphylococcus aureus abscesses, recurrent bacterial respiratory infections, pneumatoceles; hyperextensible joints; bone fractures and retention of primary teeth Bacterial and fungal prophylaxis ERBIN deficiency ERBB2IP AD Increased Treg, moderate increased IgE Susceptibility to S. aureus, eczema, recurrent respiratory infections, hyperextensible joints, scoliosis, arterial dilatation in some patients Bacterial prophylaxis Loeys Dietz syndrome TGFBR1, TGFBR2 AD Elevated IgE Recurrent respiratory infections; eczema, food allergies; hyperextensible joints, scoliosis, retention of primary teeth; aortic aneurysms Bacterial prophylaxis Coml Netherton syndrome SPINK5 AR Low memory B cells, elevated IgE and IgA, variable antibody responses Congenital ichthyosis, bamboo hair, atopic diathesis, bacterial infections, failure to thrive Bacterial prophylaxis; Ig replacement for antibody deficiency PGM3 deficiency PGM3 AR May have low T cells, B cells, memory B cells, normal or elevated IgG, IgA, and high IgE, eosinophilia Severe atopy; autoimmunity; bacterial and viral infections; short stature, brachydactyly, dysmorphic facial features; intellectual disability and cognitive impairment, delayed CNS myelination in some patients CARD11 deficiency CARD11 DN LOF AD Defective T cell activation and proliferation, high IgE, Th2 skewing, poor specific antibody production, impaired activation of the NF B and mTORC1 pathways Variable atopy, eczema, food allergy, eosinophilia; cutaneous viral infections, recurrent respiratory infections; lymphoma; CID Ig replacement for antibody deficiency AD, Autosomal dominant; AR, Autosomal recessive; CID, combined immunodeficiency; CNS, central nervous system; DN, dominant negative; HIE, hyper IgE; Ig, immunoglobulin; IL, interleukin; IL6ST, gp130 common signal transducer of the IL 6 cytokine family; LOF, loss of function; MAIT, mucosal associated invariant T cells; NKT, natural killer T cells; PJP, Pneumocystis jiroveci; Th, T helper; Treg, regulatory T cells. Adapted from Tangye SG, AlHerz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on |
6,396 | the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022;42:14731507. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1272 Part XII u Immunology formation as well as helping macrophages kill intracellular pathogens. In addition, patients with poor or absent CD4 T cell helper function are susceptible to opportunistic infection. The consequences of defects in CD40 ligand and CD40 highlight the role CD4 T celldependent helper function plays in immunity. CD40 LIGAND AND CD40 DEFICIENCY CD40 ligand (CD154) deficiency (X linked) and similarly, CD40 defi ciency (autosomal recessive), cause a severe form of hyper IgM syn drome that is a CID. Genetics and Pathogenesis Pathogenic variants in the CD40 ligand or CD40 genes, disrupt the interaction between CD4 T cells and antigen presenting cells (APCs): dendritic cells, monocytesmacrophages, and B cells. CD40 ligand is expressed on activated CD4 T cells and delivers signals to APC via CD40 to stimulate expression of co stimulatory molecules that help T cell activation and differentiation, immunoglobulin isotype switch ing and somatic hypermutation in B cells as well as memory B cell development, and signals to macrophages to kill intracellular patho gens. Therefore disruption of the CD40 signaling pathway affects sev eral key elements of the adaptive immune response leading to a CID disease characterized by failure of immunoglobulin isotype switch ing, a process important for synthesis of IgG, IgA, and IgE antibodies; failure of somatic hypermutation, a process by which B cells generate antibodies of higher affinity; and absent B cell memory, susceptibil ity to opportunistic infections including PJP, and Cryptosporidium and enhanced susceptibility to some cancers especially of the liver or of neuroectodermal origin. Clinical Manifestations Recurrent and opportunistic infections usually develop in the first year of life. About half the patients present with PJP pneumonia. Recurrent bacterial sinopulmonary infections are also common as well as Cryp tosporidium infection and sclerosing cholangitis. Chronic or recurrent neutropenia is also a feature of this disease, although the pathogenesis of neutropenia is not well known. Patients have a higher susceptibility to cancer of the liver or biliary tree as well as primitive neuroectodermal car cinoma, which usually develop after the first 10 years of life. Few patients survive beyond 30 years of age. Some patients with milder genetic varia tions present in adolescence with parvovirus induced aplastic anemia. Diagnosis Serum immunoglobulin levels show very low or absent IgG, IgA, and IgE, with normal or elevated IgM. Some patients have normal serum IgA levels, likely the result of a nonCD40 dependent isotype switch ing mechanism. The term hyper IgM is a misnomer because most patients are identified before they have elevation of serum IgM levels. Lymphocyte subsets as well as lymphocyte proliferation to mitogens are usually normal. Characteristically, there is an absence or paucity of switched memory B cells. Patients may or may not have neutropenia, which |
6,397 | can be severe. Flow cytometry for expression of CD40 on resting B cells or CD40 ligand on activated T cells can identify patients with these defects. Staining for CD40 ligand expression with soluble CD40 will identify all CD40 ligand variants that prevent binding to CD40. Gene sequencing of CD40 and CD40 ligand can be done separately or within a larger PID gene panel with known pathogenic variants con firming the disease. Treatment Patients should be treated with immunoglobulin replacement therapy and PJP prophylaxis as soon as the diagnosis is suspected. Attention to hygiene and clean drinking water as well as avoiding swimming in lakes will help prevent exposure to opportunistic organisms such as Cryptosporidium. HSCT can be curative and is recommended if the patient has a matched related or unrelated donor. Outcomes after stem cell transplantation have a trend toward improved survival and a reduced risk for cancer and improved quality of life. MHC CLASS II DEFICIENCY AND OTHER CAUSES OF CD4 T CELL DEFICIENCY MHC class I and II molecules play an important role in T cell develop ment and function by presenting a peptide fragment from a pathogen derived protein to the TCR of CD8 or CD4 T cells, respectively. MHC class II molecules are required for processing and presentation of pep tides derived from exogenous antigens to CD4 T cells and for posi tive selection of CD4 T cells in the thymus. Therefore MHC class II deficiency is a severe form of bare lymphocyte syndrome resulting in decreased CD4 T cells and impairment in their function. Clinical Manifestations Patients with low, or occasionally normal, CD4 T cell numbers from MHC class II deficiency are susceptible to bacterial, viral, fungal, and opportunistic infections. Patients usually present in the first year of life with respiratory infections, chronic diarrhea, and failure to thrive. Cryptosporidium infections may be associated with sclerosing cholan gitis and liver failure. Genetics and Pathogenesis MHC class II deficiency results from defects in genes encoding for transcription factors necessary for expression of MHC class II mole cules from the HLA DR, HLA DP, and HLA DQ loci including CIITA, RFXANK, RFX5, and RFXAP, which explains the concomitant loss of expression from all three loci. Diagnosis Immunodeficiencies with MHC class II deficiency can be identified by absent or low CD4 T cells on lymphocyte phenotyping by flow cytom etry and absent MHC class II molecules. In some cases, CD8 T cell numbers are also decreased. Lymphocyte proliferation to mitogens is normal but absent in response to antigens. Treatment The prognosis for MHC class II deficiency is poor with most patients dying in the first decade of life. HSCT has been performed and improves CD4 T cell proliferation but not numbers because it does not correct the expression of MHC class II molecules on thymic epithelial cells. The outcome of HSCT in MHC class II deficiency is not as good as in SCID and other severe immunodeficiency diseases. MHC CLASS I DEFICIENCY AND OTHER CAUSES OF CD8 T CELL |
6,398 | DEFICIENCY MHC class I molecules play an important role in T cell development and function by presenting a peptide fragment from an intracellular patho gen, such as viruses, or cancer derived proteins to the TCR of CD8 T cells. In the thymus, MHC class I molecules provide the positive selec tion signal for thymocytes to develop into CD8 T cells. Therefore the absence of MHC class I molecules in the thymus (and on all nucleated cells) is associated with very low or absent CD8 T cells. There are several other pathogenic gene variants that cause a deficiency in CD8 T cells. Genetics and Pathogenesis MHC class I deficiency results from pathogenic variants in the trans porter associated with antigen processing (TAP) 1 or 2, TAP binding protein, or 2 microglobulin genes. The TAP proteins play an impor tant role in allowing the expression of MHC class I molecules on the surface of all nucleated cells and 2 microglobulin associates with MHC class I molecules on the surface of cells. Clinical Manifestations Patients with low CD8 T cells from MHC class I deficiency may be asymptomatic in some cases but may present with chronic respiratory infections including bronchiectasis and granulomatous skin ulcers. Diagnosis Immunodeficiency patients with MHC class I deficiency can be identi fied by absent or low CD8 T cells on lymphocyte phenotyping by flow Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. Chapter 165 u TCell and Combined Deficiencies 1273 cytometry and absent MHC class I molecules. Lymphocyte prolifera tion is normal. Treatment MHC class I deficiency is treated with supportive therapy and avoid ance of immunosuppression if possible. OTHER FORMS OF CD8 DEFICIENCY CD8 Gene Defects CD8 deficiency also results from pathogenic variants in the CD8 gene. Patients are susceptible to bacterial and viral respiratory infec tions. CD8 T cell numbers are low and there is an increase in CD4 CD8 T cells. Lymphocyte proliferation is normal. CD8 deficiency is also treated with supportive therapy and avoidance of immunosup pression if possible. Defects in the Zeta Associated Protein 70 The zeta associated protein (ZAP 70) is a severe immunodeficiency similar to SCID with absent or very low numbers of CD8 T cells. Although CD4 T cells develop in adequate numbers, they are defec tive in proliferation and function. Patients with ZAP 70 deficiency are susceptible to all types of infection including opportunistic infections, disseminated varicella, and mucocutaneous candidiasis with failure to thrive and diarrhea. The diagnosis of ZAP 70 deficiency can be made by low CD8 T cell counts and deficient T cell proliferation to mitogens that can be rescued by bypassing ZAP 70 signaling with phorbol ester and ionomycin, helping confirm that the defect is in the proximal sig naling pathway in T cells. The diagnosis is confirmed by identification of a homozygous or combined heterozygous pathogenic variant in the ZAP |
6,399 | 70 gene. Treatment of ZAP 70 deficiency requires HSCT. Immu noglobulin replacement and microbial prophylaxis should be initiated until immune reconstitution after HSCT is achieved. COMBINED IMMUNODEFICIENCIES WITH CONGENITAL THROMBOCYTOPENIA Wiskott Aldrich Syndrome Wiskott Aldrich syndrome (WAS) is an X linked recessive disorder characterized by atopic dermatitis, thrombocytopenic purpura with normal appearing megakaryocytes but small defective platelets, and susceptibility to infection. Genetics and Pathogenesis The Wiskott Aldrich syndrome protein (WASP) controls the assembly of actin filaments required for cell migration and cell cell interactions. Specific pathogenic variants in the WASP gene cause X linked throm bocytopenia (XLT) without immunodeficiency and gain of function variants cause X linked severe congenital neutropenia. A similar phe notype to WAS occurs with pathogenic variants in the WASP interac tive Protein (WIP) that is an autosomal recessive disease affecting both females and males. Clinical Manifestations Patients often have prolonged bleeding from the circumcision site or bloody diarrhea during infancy. The thrombocytopenia is not caused initially by antiplatelet antibodies, although autoimmunity may develop later in life. Atopic dermatitis and recurrent infections usually develop during the first year of life. Streptococcus pneumoniae and other bacteria having polysaccharide capsules cause otitis media, pneumonia, meningitis, and sepsis. Later, infections with agents such as P. jiroveci and the herpesviruses become more frequent. Infections, bleeding, and EBV associated malignancies are major causes of death. Diagnosis The predominant immunoglobulin pattern is a low serum level of IgM, elevated IgA and IgE, and a normal or slightly low IgG. Percent ages of T cells are moderately reduced, and lymphocyte responses to mitogens are variably depressed. The presence of low numbers of platelets that are small in size is typical. Immunologically, patients with this defect uniformly have an impaired humoral immune response to polysaccharide antigens, as evidenced by absent or greatly diminished isohemagglutinins, and poor or absent antibody responses after immu nization with polysaccharide vaccines. In addition, antibody responses to protein and conjugate vaccines may also be diminished. Treatment Good supportive care includes appropriate nutrition, immunoglobu lin replacement, use of killed vaccines, and aggressive management of eczema and associated cutaneous infections. Because of their profound antibody deficiency, these patients should be given immunoglobulin replacement regardless of their serum levels of the different immuno globulin isotypes. HSCT is the treatment of choice when a high quality matched donor is available and is usually curative. Gene therapy has resulted in sustained benefits in several patients. As in X SCID, early tri als of gene therapy were associated with the development of malignancy. In addition to WAS and WIP deficiency, there is a third cause of immunodeficiency with thrombocytopenia from pathogenic variants in the ARPC1B gene affecting Arp23 mediated filament branching presenting with mild thrombocytopenia but normal sized platelets and recurrent infections. Patients have high IgA and IgE as in WAS. DNA REPAIR DEFECTS OTHER THAN THOSE CAUSING SCID DNA repair plays an important role during lymphocyte development and differentiation including V(D)J recombination and immunoglob ulin isotype switching. Therefore defects in DNA repair enzyme are frequently associated |
6,400 | with CID and many have other characteristic fea tures to identify them (see Table 165.3). ATAXIA TELANGIECTASIA Ataxia telangiectasia is a complex syndrome with immunologic, neu rologic, endocrinologic, hepatic, and cutaneous abnormalities. Genetics and Pathogenesis The ataxia telangiectasia pathogenic variant (ATM) gene encodes a protein critical for responses to DNA damage. Cells from patients, as well as from heterozygous carriers, have increased sensitivity to ion izing radiation, defective DNA repair, and frequent chromosomal abnormalities. In vitro tests of lymphocyte function have generally shown moder ately depressed proliferative responses to T and B cell mitogens. Per centages of CD3 and CD4 T cells are moderately reduced, with normal or increased percentages of CD8 T cells and elevated numbers of T cells. The thymus is very hypoplastic, exhibits poor organization, and lacks Hassalls corpuscles. Clinical Manifestations The most prominent clinical features are progressive cerebellar ataxia, oculocutaneous telangiectasias, chronic sinopulmonary disease, a high incidence of malignancy, and variable humoral and cellular immuno deficiency. Ataxia typically becomes evident soon after these children begin to walk and progresses until they are confined to a wheelchair, usually by age 10 12 years. The telangiectasias begin to develop at 3 6 years of age, contributing to a delay in diagnosis. Recurrent sinopulmo nary infections occur in approximately 80 of patients. Although com mon viral infections have not usually resulted in untoward sequelae, fatal varicella has occurred. The malignancies associated with ataxia telangiectasia are usually of the lymphoreticular type, but adenocar cinomas also occur. Carriers of pathogenic variants have an increased incidence of malignancy. Diagnosis Patients have elevated serum fetoprotein levels. The most frequent humoral immunologic abnormality is the selective absence of IgA, which occurs in 5080 of these patients. IgG2 or total IgG levels may be decreased, and specific antibody levels may be decreased or nor mal. Some patients have an elevated serum IgM level. Identification of homozygous or compound heterozygous pathogenic variants in the ATM gene confirms the diagnosis. Downloaded for mohamed ahmed (dr.mms2020gmail.com) at University of Southern California from ClinicalKey.com by Elsevier on April 21, 2024. For personal use only. No other uses without permission. Copyright 2024. Elsevier Inc. All rights reserved. 1274 Part XII u Immunology Treatment Therapy in ataxia telangiectasia is supportive but includes immunoglobu lin replacement and avoidance of ionizing radiation unless absolutely nec essary to establish a clinical diagnosis and initiate appropriate treatment. Immunoosseous Dysplasias Immunoosseous dysplasias are a group of combined immune defi ciency diseases affecting bone development as well as T cell develop ment or function. They are characterized by skeletal abnormalities and recurrent infections (see Table 165.4). CARTILAGE HAIR HYPOPLASIA Cartilage hair hypoplasia (CHH) is an unusual form of metaphyseal dysplasia with frequent and severe infections. It occurs with a high frequency among the Amish and Finnish people (Chapter 741). Genetics and Pathogenesis CHH is an autosomal recessive condition. Numerous pathogenic vari ants that cosegregate with the CHH phenotype have been identified in the untranslated RNase MRP (RMRP) gene. The RMRP endoribonu clease consists of an RNA molecule |
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