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Pediatrics_Nelson. Diagnosis can be made by scraping the conjunctiva and culturing the material. Giemsa staining of the conjunctival scrapings revealing the presence of blue-stained intracytoplasmic inclusions within the epithelial cells is diagnostic. PCR is also available. Infants with conjunctivitis and pneumonia are treated with oral erythromycin for 14 days. Topical treatment of conjunctivitis is ineffective and unnecessary. The recommended topical prophylaxis with silver nitrate, erythromycin, or tetracycline for all newborns for the prevention of gonococcal ophthalmia does not prevent neonatal chlamydial conjunctivitis. Engle WE: Infants born late preterm: definition, physiologic and metabolic immaturity, and outcomes, NeoReviews 10:e280, 2009 Frankovich J, Sandborg C, Barnes P, et al: Neonatal lupus and related auto immune disorders of infants, NeoReviews 9:e207–217, 2008 HAPO Study Cooperative Research Group: Hyperglycemia and adverse pregnancy outcomes, N Engl J Med 358(19):1991–2002, 2008


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Pediatrics_Nelson. HAPO Study Cooperative Research Group: Hyperglycemia and adverse pregnancy outcomes, N Engl J Med 358(19):1991–2002, 2008 Jesse N, Neu J: Necrotizing enterocolitis: relationship to innate immunity, clinical features and strategies for prevention, NeoReviews 7:e143, 2006 Kates EH, Kates JS: Anemia and polycythemia in the newborn, Pediatr Rev 28:33–34, 2007 Kattwinkel J, Perlman J: The neonatal resuscitation program: the evidence evaluation process and anticipating edition 6, NeoReviews 11:e673, Shankaran S: Neonatal encephalopathy: treatment with hypothermia, NeoReviews 11:e85, 2010 Silva RA, Moshfeghi DM: Interventions in retinopathy of prematurity, NeoReviews 13:e476, 2012 Steinhorn RH, Farrow KN: Pulmonary hypertension in the neonate, NeoReviews 8:e14–e21, 2007 Wong RJ, Stevenson DK, Ahlfors CE, et al: Neonatal jaundice: bilirubin physiology and clinical chemistry, NeoReviews 8:e58–e67, Kim Blake and Lisa M. Allen 12


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Pediatrics_Nelson. NeoReviews 8:e14–e21, 2007 Wong RJ, Stevenson DK, Ahlfors CE, et al: Neonatal jaundice: bilirubin physiology and clinical chemistry, NeoReviews 8:e58–e67, Kim Blake and Lisa M. Allen 12 The leading causes of mortality (Table 67-1) and morbidity (Table 67-2) in adolescents in the United States are behaviorallymediated. Motor vehicle injuries and other injuries account formore than 75% of all deaths. Unhealthy dietary behaviors andinadequate physical activity result in adolescent obesity withassociated health complications (e.g., diabetes, hypertension). It is the physician’s responsibility to use every opportunity to inquire about risk-taking behaviors (Fig. 67-1), regardless of the presenting issue. Physical symptoms in adolescents are often related to psychosocial problems.


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Pediatrics_Nelson. The adolescent interview shifts from information gathering from the parent to the adolescent. Interviewing an adolescent alone and discussing confidentiality are the cornerstones of obtaining information regarding risk-taking behaviors, anticipatory guidance, and protective factors (see Chapters 7 and 9). The interview should take into account the developmental age of the adolescent (Table 67-3). Conversations about sports, friends, movies, and activities outside of school can be useful for all ages and help build rapport (Fig. 67-2). Confidentiality is a key element when interviewing an adolescent (Table 67-4). The vital, open discussion about risk-taking behavior is more likely to happen when the adolescent is RANK CAUSE RATE (PER 100,000) 1 Unintentional injuries 30.3 2 Assault (homicide) 10.4 3 Suicide 6.9 4 Malignant neoplasms (cancer) 3.2 5 Diseases of the heart 1.6


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Pediatrics_Nelson. RANK CAUSE RATE (PER 100,000) 1 Unintentional injuries 30.3 2 Assault (homicide) 10.4 3 Suicide 6.9 4 Malignant neoplasms (cancer) 3.2 5 Diseases of the heart 1.6 From Centers for Disease Control and Prevention, National Center for Health Statistics: National Vital Statistics 2007. alone (Table 67-5). Some issues cannot be kept confidential, such as suicidal intent and disclosure of sexual or physical abuse. If there is an ambiguous situation, it is wise to obtain legal, ethical, or social work consultation. When caring for a young adolescent, the health care provider should encourage open discussions with a parent, guardian, or other adult.


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Pediatrics_Nelson. The law confers certain rights on adolescents, depending on their health condition and personal characteristics, allowing them to receive health services without parental permission (Table 67-6). Usually adolescents can seek health care without parental consent for reproductive, mental, and emergency health services. Emancipated adolescents and mature minors may be treated without parental consent; such status should be documented in the record. The key characteristics of mature minors are their competence and capacity to understand, not their chronologic age. There must be a reasonable judgment that the health intervention is in the best interests of the minor. Auditory-visual defects 2%–3% Traumatic paralysis 2:1000 Scoliosis 3% males, 5% females Migraine 6%–27% (↑ with increasing age) Diabetes mellitus 1.8:1000 Obesity 25%–30% Anorexia nervosa 0.5%–1% Bulimia 1% (young adolescence),


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Pediatrics_Nelson. Diabetes mellitus 1.8:1000 Obesity 25%–30% Anorexia nervosa 0.5%–1% Bulimia 1% (young adolescence), Figure 67-1 The Structured Communication Adolescent Guide (SCAG). The SCAG is an interviewing tool developed for learners to use with real or standardized adolescent patients. It incorporates the four major interview components: confidentiality, separation of the adolescent from the adult, psychosocial data gathering (using the HEADDSS mnemonic), and a nonjudgmental approach. The SCAG is at a grade 5 reading level and has demonstrated reliability and validity. A printable version is available through MedEdPORTAL. Figure 67-1, cont’d “Get the story”


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Pediatrics_Nelson. Figure 67-1, cont’d “Get the story” Setting Topics Confidentiality Separation HEADDSS See Table 67-5 Relationships Functioning Attitudes Behaviors Be nonjudgmental Avoid lecturing Never give up even if you feel uncomfortable Plan and contract Focus on your adolescent patient’s issues (acne, sore throats, belly pain, mom) and one of your concerns (safe sex, driving safety, depression) Choices – congratulate your adolescent on good choices Behaviors – emphasize the positive; focus on patient accomplishments Contract – with adolescent around 1 or 2 risk-taking issues Interview with empathy, interest, and understanding Figure 67-2 STEP guide for adolescent interviewing. Prepare the preadolescent and parent for confidentiality and being interviewed alone. Discuss confidentiality at the start of the interview. Conversations with parents/guardians/adolescent are confidential (with exceptions*). Reaffirm confidentiality when alone with your adolescent patient.


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Pediatrics_Nelson. Reaffirm confidentiality when alone with your adolescent patient. *Exceptions to confidentiality include major or impending harm to any person (i.e., abuse, suicide, homicide). *The acronym HEADDSS can represent other terms, that is, A = Activities, D = Depression. Also see Figure 67-1. Age of majority (≥18 years of age in most states) Exceptions in which health care services can be provided to a minor*: Emergency care (e.g., life-threatening condition or condition in which a delay in treatment would increase significantly the likelihood of morbidity) Diagnosis and treatment of sexuality-related health care Diagnosis and treatment of drug-related health care Emancipated minors (physically and financially independent of family; Armed Forces; married; childbirth) Mature minors (able to comprehend the risks and benefits of evaluation and treatment) All exceptions should be documented clearly in the patient’s health record. *Determined by individual state laws.


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Pediatrics_Nelson. *Determined by individual state laws. During the physical examination, a choice between the parent and a chaperone being present needs to be offered. Breast budding under the areola (thelarche) and fine straight pubic hair over the mons pubis (adrenarche or pubarche)are early pubertal changes occurring around 11 years of age (range, 8 to 13 years) (see Chapter 174). These changes mark the sexual maturity rating, or Tanner stage, II of pubertal development (Figs. 67-3 and 67-4). Completion of the Tanner stages should take 4 to 5 years. The peak growth spurt usually Stage 1 The breasts are preadolescent. There is elevation of the papilla only.


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Pediatrics_Nelson. Stage 1 The breasts are preadolescent. There is elevation of the papilla only. Figure 67-3 Typical progression of female pubertal development, stages 1 to 5. A, Pubertal development in the size of female breasts. B, Pubertal development of female pubic hair. Note that in stage 1 (not shown) there is no pubic hair. (Courtesy of J.M. Tanner, MD, Institute of Child Health, Department of Growth and Development, University of London, London, England.) occurs approximately 1 year after thelarche at sexual maturity rating stage III to IV breast development and before the onset of menstruation (menarche). Menarche is a relatively late pubertal event. Females grow only 2 to 5 cm in height before menarche (see Chapter 174).


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Pediatrics_Nelson. The mean ages of thelarche and adrenarche are approximately 9 and 10 years for African American and white girls, respectively. The mean ages of menarche are 12.2 and 12.9 years for African American and white girls, respectively. The interval from the initiation of thelarche to the onset of menses (menarche) is 2.3 ± 1 years. Pubertal changes before 6 years of Stage 2 Breast bud stage. A small mound is formed by the elevation of the breast and papilla. The areolar diameter enlarges. Stage 3 There is further enlargement of breast and areola with no separation of their contours. Stage 4 There is a projection of the areola and papilla to form a secondary mound above the level of the breast. Stage 5 The breasts resemble those of a mature female as the areola has recessed to the general contour of the breast. Stage 2 There is sparse growth of long, slightly pigmented, downy hair, straight or only slightly curled, primarily along the labia.


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Pediatrics_Nelson. Stage 2 There is sparse growth of long, slightly pigmented, downy hair, straight or only slightly curled, primarily along the labia. Stage 3 The hair is considerably darker, coarser, and more curled. The hair spreads sparsely over the junction of the pubes. Stage 4 The hair, now adult in type, covers a smaller area than in the adult and does not extend onto the thighs. Stage 5 The hair is adult in quantity and type, with extension onto the thighs. age in African American and 7 years of age in white girls are considered precocious. Testicular enlargement (≥2.5 cm) corresponds to sexual maturity rating, or Tanner, stages I to II (Figs. 67-5 and 67-6). Testicular enlargement is followed by pubic hair development at the base of the penis (adrenarche) and then axillary hair within the year. The growth spurt is a relatively late event; it can occur from 10½ years of age to 16 years of age. Deepening of the


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Pediatrics_Nelson. Figure 67-4 Sequence of pubertal events in the average American female. More recent studies suggest that onset of breast development may be 9 years of age for African American girls and 10 years of age for white girls. (From Brookman RR, Rauh JL, Morrison JA, et al: The Princeton maturation study, 1976, unpublished data for adolescents in Cincinnati, Ohio. Reprinted from Assessment of Pubertal Development, Columbus, Ohio, 1986, Ross Laboratories.) Figure 67-6 Sequence of pubertal events in the average American male. Testicular volume less than 4 mL using an orchidometer (Prader Beads) represents prepubertal stage. (From Brookman RR, Rauh JL, Morrison JA, et al: The Princeton maturation study, 1976, unpublished data for adolescents in Cincinnati, Ohio. Reprinted from Assessment of Pubertal Development, Columbus, Ohio, 1986, Ross Laboratories.) Stage 2 There is sparse growth of long, slightly pigmented, downy hair, straight or only slightly curled, primarily at the base of the penis.


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Pediatrics_Nelson. Stage 2 There is sparse growth of long, slightly pigmented, downy hair, straight or only slightly curled, primarily at the base of the penis. Stage 3 The hair is considerably darker, coarser, and more curled. The hair spreads sparsely over the junction of the pubes. Stage 4 The hair, now adult in type, covers a smaller area than in the adult and does not extend onto the thighs. Stage 5 The hair is adult in quantity and type, with extension onto the thighs. Figure 67-5 Typical progression of male pubertal development. A, Pubertal development in the size of male genitalia. B, Pubertal development of male pubic hair. Note that in stage 1 there is no pubic hair. (Courtesy of J.M. Tanner, MD, Institute of Child Health, Department of Growth and Development, University of London, London, England.) voice, facial hair, and acne indicate the early stages of puberty. See Chapter 174 for discussion of disorders of puberty. Changes Associated with Physical Maturation


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Pediatrics_Nelson. Changes Associated with Physical Maturation Tanner stages mark biologic maturation that can be related to specific laboratory value changes and certain physical conditions. The higher hematocrit values in adolescent boys than in adolescent girls are the result of greater androgenic stimulation of the bone marrow and not loss through menstruation. Alkaline phosphatase levels in boys and girls increase during puberty because of rapid bone turnover, especially during the growth spurt. Worsening of mild scoliosis is common in adolescents during their growth spurt. SEE TABLE 67-3 AND CHAPTERS 7 AND 9.


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Pediatrics_Nelson. SEE TABLE 67-3 AND CHAPTERS 7 AND 9. When interviewing an adolescent, use a nonjudgmental approach and find some common ground to get the adolescent talking about himself or herself. The HEADDSS (home, education, alcohol, drugs, diet, sex, suicide/depression) mnemonic addresses important risk-taking elements of the history (see Table 67-5). Adolescents who experiment in one area of risk-taking often have contemplated or tried multiple other risk-taking behaviors. When all of the risk-taking information has been gathered, the physician should choose one or two health care issues to discuss, making it clear that the information is confidential and that he or she is there to help the adolescent in a partnership way. Although the focus in adolescent care is on psychosocial issues, a general examination also needs to be performed (Table 68-1). Pediatric issues, such as immunization (see Chapter 94) and health screening, should be included (see Table 9-5).


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Pediatrics_Nelson. Rapid changes in physical appearance and behavior are the major characteristics of early adolescence, leading to a great dealof self-consciousness and need for privacy. The history focuseson the early adolescent’s physical and psychosocial health. Autonomy and a global sense of identity are the major characteristics of middle adolescence. The history focuses on Explain to your patient what you are going to do. Explain how you are going to do it. Ask whether your adolescent wants his or her parent in the room.* Be sensitive to the adolescent’s needs. Always use a sheet or blanket to provide privacy. Let the adolescent remain dressed and work around the clothing. Ask some questions as you go through the physical to keep the adolescent at ease. Give reassurance that elements of the physical are normal for this age. Examination can be used to offer reassurance about normalcy.† Assess the following: Skeletal: scoliosis, Osgood-Schlatter disease, slipped capital


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Pediatrics_Nelson. Examination can be used to offer reassurance about normalcy.† Assess the following: Skeletal: scoliosis, Osgood-Schlatter disease, slipped capital Signs of substance abuse, risk-taking behaviors, and trauma *If not, you will need a chaperone. †For example, 70% of boys can have breast enlargement (gynecomastia), and girls often have one breast larger than the other. the middle adolescent’s interactions with family, school, and peers. High-risk behaviors as a result of experimentation are common. Individuality and planning for the future are the major characteristics of late adolescence. Greater emphasis is placed on the late adolescent’s responsibility for his or her health.


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Pediatrics_Nelson. Individuality and planning for the future are the major characteristics of late adolescence. Greater emphasis is placed on the late adolescent’s responsibility for his or her health. A full pelvic examination is rarely required in a virginal adolescent girl. A bimanual rectal-abdominal examination (all midline internal genitalia are immediately anterior to the rectal wall) is as efficient as a vaginal-abdominal examination. In some girls, anesthesia may be required for a full pelvic examination. Before a pelvic examination, the patient should be informedabout the importance of the assessment and what maneuverswill take place; she should be encouraged to ask questionsbefore, during, or after the examination. A chaperone shouldbe offered when a family caregiver is not present. Assuringthe patient that she has complete control over the examination and allowing participating by using a mirror or guidingthe examiner is important. The examiner should maintain


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Pediatrics_Nelson. Classic or juvenile fibroadenoma (70%) Fibrocystic disease Breast cyst Abscess/mastitis Intraductal papilloma Fat necrosis/lipoma Cystosarcoma phyllodes (low-grade malignancy) Adenomatous hyperplasia Hemangioma, lymphangioma, lymphoma (rare) Carcinoma (<1%) eye contact during the examination. Before all maneuvers,the patient must be informed of what to expect and the sensations. A padded examination table with the patient in a frog-leg position maximizes comfort of a pelvic examination. Stirrups can be used but are less comfortable. The examination room, lubricants, and instruments should be warm. The examination should be unhurried but efficient.


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Pediatrics_Nelson. Inspection of the genitalia includes evaluation of thepubic hair, labia majora and minora, clitoris, urethra, andhymenal ring. When a speculum examination is required,it must be performed before bimanual palpation of internalgenitalia because lubricants interfere with the evaluationof microscopic and microbiologic samples. The speculumallows visualization of the vaginal walls and cervical os forcollection of appropriate specimens, such as cultures orPapanicolaou (Pap) smears. A Pap smear is not needed untilthe adolescent is sexually active, unless there is a history ofsexual abuse or vulvar infection with human papillomavirus. In the rare circumstance that a vaginal examination isnecessary in a virginal girl, a Huffman (0.5 in. × 4.5 in.) orPederson (0.9 in. × 4.5 in.) speculum should be used. A non-virginal introitus frequently admits a small to medium-sizedadult speculum.


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Pediatrics_Nelson. It is not unusual for one breast to begin growth before (or to grow more rapidly than) the other, with resulting asymmetry. Reassurance that after full maturation the asymmetry will be less obvious and that all women have some degree of asymmetry is needed by some. The breast bud is a pea-sized mass below the nipple that is often tender. Occasionally young women present with a breast mass; usually these are benign fibroadenomas or cysts (Table 68-2). Breast cancer is extremely rare in this age group. An ultrasound evaluation is better for the evaluation of young, dense breasts and avoids the radiation exposure of mammography. Peripubertal girls (sexual maturity rating stage III) often complain of vaginal discharge. If the discharge is clear without Drugs Antiandrogens Antibiotics (isoniazid, ketoconazole, metronidazole) Antacids (H2 blockers) Cancer chemotherapy (especially alkylating agents) Cardiovascular drugs Drugs of abuse Alcohol Amphetamines Heroin Marijuana


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Pediatrics_Nelson. Drugs of abuse Alcohol Amphetamines Heroin Marijuana Psychoactive agents (e.g., diazepam, phenothiazines, tricyclics) symptoms of pruritus or odor, it is most likely physiologic leukorrhea, due to ovarian estrogen stimulation of the uterus and vagina. A physical examination should reveal evidence of an estrogenized vulva and hymen without erythema or excoriation. The physician should always be alert for signs of abuse. If there are symptoms, cultures should be obtained. In these circumstances, vaginal cultures can be obtained without a speculum because sexually transmitted infections are vaginal until menarche, when cervical infections are the rule. Inspection of physiologic leukorrhea shows few white blood cells, estrogen maturation of vaginal epithelial cells, and no pathogens on a culture.


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Pediatrics_Nelson. Menarche typically occurs approximately 2 years afterthelarche, at the average age of 12.6 years. The initial menses are anovulatory and tend to be irregular in duration. Thisirregularity may persist for 2 to 5 years, so reassurance may berequired. During this phase, estrogen feedback on the hypothalamus decreases gonadotropin secretion, which reducesestrogen production and induces an estrogen withdrawalbleed that can be prolonged and heavy. Anovulatory bleedingis usually painless. As the hypothalamic-pituitary-gonadalaxis matures, the cycle becomes ovulatory, and menses aresecondary to progesterone withdrawal. When ovulation isestablished, the average cycle length is 21 to 45 days. Someadolescents ovulate with their first cycle, as indicated by pregnancy before menarche. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com Breast enlargement in boys is usually a benign, self-limited condition. Gynecomastia is noted in 50% to 60% of boys during early adolescence. It is often idiopathic, but it may be noted in various conditions (Table 68-3). Typical findings include the appearance of a 1to 3-cm, round, freely mobile, often tender, and firm mass immediately beneath the areola during sexual maturity rating stage III. Large, hard, or fixed enlargements and masses associated with any nipple discharge warrant further investigation. Reassurance is usually the only treatment required. If the condition worsens and is associated with psychological morbidity, it may be treated with bromocriptine. Surgical treatment with reduction mammoplasty can be helpful with massive hypertrophy. Irregular menses is the most common complaint of early adolescent girls. As regular, ovulatory cycles become established, pain with menstruation (dysmenorrhea) is a frequent complaint.


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Pediatrics_Nelson. Irregular menses is the most common complaint of early adolescent girls. As regular, ovulatory cycles become established, pain with menstruation (dysmenorrhea) is a frequent complaint. Available @ StudentConsult.com Primary amenorrhea is the complete absence of menstruation by 16 years of age in the presence of breast development or by 14 years of age in the absence of breast development. However 98% of adolescents have onset of menarche by age 15; therefore, investigations should begin at that age in young women without menses. Secondary amenorrhea refers to the cessation of menses for more than 3 consecutive months, any time after menarche.


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Pediatrics_Nelson. Primary amenorrhea may be a result of functional or anatomic abnormalities of the hypothalamus, pituitary gland, ovaries, uterus, or vagina. Physiologic immaturity, stress, excessive exercise, and abnormal dietary patterns (anorexia/bulimia) are the most common causes of amenorrhea. Pregnancy should be considered in all cases of secondary amenorrhea, even if the patient denies sexual activity.


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Pediatrics_Nelson. The history and physical examination should guide theinvestigation. An outflow tract obstruction should be ruled outin adolescents with primary amenorrhea, abdominal pain, andsecondary sexual characteristics. An abdominal mass resulting from accumulated blood may be present. Low outflowtract obstructions, such as an imperforate hymen, are visibleon examination. An endocrine evaluation is indicated for girlswith primary amenorrhea without secondary sexual characteristics and an unremarkable history and physical examination.Elevated follicle-stimulating hormone (FSH) and luteinizinghormone (LH) indicate primary ovarian insufficiency, whichmay reflect ovarian dysgenesis or ovarian agenesis and warrantsa karyotype. Turner syndrome is a common cause, but other chromosomal anomalies, fragile X premutation carriers, andautoimmune etiologies should be ruled out. Low levels of FSHand LH suggest hypothalamic dysfunction, which may be dueto physiologic immaturity (often familial), isolated


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Pediatrics_Nelson. X premutation carriers, andautoimmune etiologies should be ruled out. Low levels of FSHand LH suggest hypothalamic dysfunction, which may be dueto physiologic immaturity (often familial), isolated gonadotropin deficiency, or hypogonadotropic hypogonadism (chronicillness, low body weight, stressful life events). Additional hormone evaluation includes thyroid-stimulating hormone andprolactin. Hypothyroidism is a common cause of menstrualdysfunction. A prolactinoma, although rare, must be ruled out.


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Pediatrics_Nelson. Girls with secondary amenorrhea have secondary sexual characteristics. The most common causes are pregnancy, anorexia/stress (low LH, FSH, and estradiol), and polycystic ovary syndrome (PCOS). In PCOS there may be symptoms of androgen excess, such as acne and hirsutism, and weight gain and, with insulin resistance, acanthosis. If hirsutism or virilization is present, free and total testosterone, androstenedione, and dihydroepiandrosterone sulfate should be measured to rule out ovarian or adrenal tumors. A normal 17-hydroxyprogesterone level rules out late-onset congenital adrenal hyperplasia. PCOS is diagnosed with two of the following: infrequent menstrual bleeding or secondary amenorrhea, clinical or biochemical hyperandrogenism, and polycystic morphology of ovaries on ultrasound. Estradiol may be normal or low; and androgens, including dihydroepiandrosterone sulfate, may be elevated, although not to the extent that a tumor produces. Patients may have impaired glucose tolerance or


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Pediatrics_Nelson. may be normal or low; and androgens, including dihydroepiandrosterone sulfate, may be elevated, although not to the extent that a tumor produces. Patients may have impaired glucose tolerance or hypercholesterolemia.


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Pediatrics_Nelson. In a patient with amenorrhea (primary or secondary), normalsecondary sex characteristics, negative pregnancy test, normalprolactin and thyroid-stimulating hormone, and no evidence of outflow tract obstruction, the total effect of estrogen on theuterus (rather than a single point estradiol level) can be determined by a progesterone withdrawal test. To achieve this, 5 to 10 mg of medroxyprogesterone (depending on body weight)is given daily for 5 days. If the uterus is normal and primed byestrogen (an intact hypothalamic-pituitary-gonadal axis) withno outflow tract obstruction, there should be bleeding within 1week after the last progesterone tablet. If there is bleeding, theamenorrhea is secondary to anovulation. If there is no progesterone withdrawal bleeding, the uterus has been insufficientlyexposed to estrogen, and there is systemic estrogen deficiency.


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Pediatrics_Nelson. Therapy for the amenorrhea should be directed at the cause. Anovulation can be managed with either cyclic progesterone withdrawal or combined hormonal contraceptives (CHCs). In hypothalamic amenorrhea and ovarian failure, there is an associated hypoestrogenism; therapy is directed at replacing estrogen and progesterone, usually with a CHC. PCOS usually can be treated effectively with weight loss, exercise, progesterone withdrawal, or CHC. If there is evidence of androgen excess, CHCs reduce androgen production from the ovaries and increases sex hormone–binding globulin to reduce the amount of available androgen. Spironolactone helps treat hirsutism, and when there is evidence of insulin insensitivity, metformin can restore ovulatory cycles. Contraception should be prescribed, if applicable. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com Normal, ovulatory menses can occur 21 to 45 days apart, measuring from the first day of menstruation to the first day ofthe next menstruation. The average duration of flow is 3 to 7days, with more than 7 days considered prolonged. More than8 well-soaked pads or 12 tampons per day may be consideredexcessive, although classically blood loss is difficult to estimate. Table 69-1 defines menstrual disorders according to thenew International Federation of Gynecology and Obstetricsnomenclature and classification of abnormal uterine bleeding (AUB). If the menstrual problem is unclear and nonacute,observation and charting on a menstrual calendar are warranted. Excessively heavy, prolonged, or infrequent bleedingin the first year after menarche is often physiologic but shouldbe investigated, especially if there is associated iron deficiencyanemia.


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Pediatrics_Nelson. Approximately 20% of adolescents with heavy or prolonged menses, especially those presenting in early menarche, have a coagulation disorder and 10% have other pathology. If an underlying pathology is discovered, treatment should be directed at the primary disorder and the secondary menstrual dysfunction. Duration Prolonged menstrual >8 days of flow bleeding Shortened menstrual <2 days of flow bleeding


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Pediatrics_Nelson. Duration Prolonged menstrual >8 days of flow bleeding Shortened menstrual <2 days of flow bleeding The differential diagnosis of AUB is found in Table 69-2. Anovulation is the most common etiology of AUB in adolescents. Without progesterone from the corpus luteum, unopposed estrogen causes endometrial hyperplasia and irregularendometrial shedding, which can be prolonged and heavy,sometimes life threatening. Progesterone induces a secretoryendometrium. When progesterone is withdrawn, the endometrium sheds in a synchronous fashion with myometrial and vascular contractions (causing dysmenorrhea but limiting bloodloss). For the first 1 to 2 years post-menarche, the majority ofadolescent cycles are anovulatory. After 1 year of regular cycles,irregular bleeding usually indicates an organic abnormality.


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Pediatrics_Nelson. A thorough history with a menstrual calendar indicating the amount of flow and associated symptoms is followed by physical examination, including a pelvic examination in a nonvirginal adolescent or an ultrasound in a virginal adolescent. Physical examination should also assess for signs of anemia, bruising or petechia, signs of hyperandrogenism or thyroid disease. A complete blood count, pregnancy test, thyroid function tests, and coagulation screen should be performed. In sexually active adolescents, sexually transmitted infections (STIs) should be ruled out.


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Pediatrics_Nelson. Unpredictable, heavy, and prolonged menses may impair school attendance and social functioning; iron deficiency anemia is associated with lower academic scores. Treatment is indicated for heavy menses. Chronic and acute bleeding can be managed with CHCs; multiple daily doses may be required until blood loss is controlled. Occasionally uncontrollable bleeding requires hospitalization for intravenous fluids and high-dose estrogen. Uterine curettage is rarely indicated in adolescents. Iron therapy is also important. Use of CHCs to regulate menstruation and allow the hypothalamic-pituitary-gonadal axis to mature is appropriate; only 6 to 12 months of therapy may be required. CHCs are paramount in the management of heavy menstrual bleeding in individuals with bleeding disorders (von Willebrand disease), although adjuvant therapy with tranexamic acid may be needed for management of any scheduled withdrawal bleeds. Parents are often concerned that CHC use will cause their daughter to become


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Pediatrics_Nelson. disease), although adjuvant therapy with tranexamic acid may be needed for management of any scheduled withdrawal bleeds. Parents are often concerned that CHC use will cause their daughter to become sexually active, but literature and experience do not support this.


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Pediatrics_Nelson. Pregnancy, including ectopic pregnancy Infection—usually sexually transmitted Endocrine disorder—thyroid disorder, PCOS, pituitary disorder Blood dyscrasia Systemic disease Trauma Medications Contraception Vaginal, cervical, or uterine disorders Ovarian tumor/cyst Foreign body PCOS, Polycystic ovary syndrome. *When all excluded, the diagnosis of dysfunctional uterine bleeding can be made. Available @ StudentConsult.com


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Pediatrics_Nelson. PCOS, Polycystic ovary syndrome. *When all excluded, the diagnosis of dysfunctional uterine bleeding can be made. Available @ StudentConsult.com The most common gynecologic complaint of young women is painful menstruation, or dysmenorrhea, during the first 1 to 3 days of bleeding. Primary dysmenorrhea is defined as pelvic pain during menstruation in the absence of pelvic pathology and is a feature of ovulation, typically developing 1 to 3 years after menarche, with an increasing incidence to the age of 24, as ovulatory cycles are established. The release of prostaglandins and leukotrienes from the degenerating endometrium after progesterone levels decline causes increased uterine tone and increased frequency and dysrhythmia of uterine contractions. This creates excessive uterine pressures and ischemia that heightens the sensitivity of pain fibers to bradykinin and other physical stimuli.


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Pediatrics_Nelson. Secondary dysmenorrhea is menstrual pain associated with pelvic pathology and is caused most frequently by endometriosis or pelvic inflammatory disease. Adolescents with endometriosis usually have mild to moderate disease, but girls with obstructed outflow tracts tend to have severe endometriosis soon after menarche. The types of dysmenorrhea usually can be distinguished by history and physical examination. Ultrasound is preferred as the initial screen for obstructing genital tract lesions. Magnetic resonance imaging may be useful in complex reproductive tract anomalies. Laparoscopy is required to diagnose endometriosis and pelvic inflammatory disease with certainty, although it usually is reserved for patients who fail medical therapy.


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Pediatrics_Nelson. Treatment of primary dysmenorrhea should be considered with symptoms causing significant distress. First-line therapy is nonsteroidal anti-inflammatory drugs (NSAIDs) (Table 69-3). To maximize pain relief, NSAIDs should be taken before or as soon as menstruation begins, and the dosing schedule should be followed closely. Typically NSAIDs are needed for 2 to 3 days. If NSAIDs fail to provide adequate relief, CHCs or long-acting reversible contraceptives (LARCs) may be added. Prescription Ibuprofen 400 mg PO qid Naproxen 500 mg PO stat then 250 PO to 500 mg PO bid Mefenamic acid 500 mg PO stat then 250 mg qid or 500 mg LNG, Levonorgestrel; NSAIDs, nonsteroidal anti-inflammatory drugs. These contraceptives may be first-line therapy, depending on need for pregnancy prevention.


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Pediatrics_Nelson. LNG, Levonorgestrel; NSAIDs, nonsteroidal anti-inflammatory drugs. These contraceptives may be first-line therapy, depending on need for pregnancy prevention. If dysmenorrhea persists despite an adequate trial of CHCs (>4 months), an alternative diagnosis, such as endometriosis, should be considered. When CHCs fail, a laparoscopy may be performed before advancing therapy to confirm the diagnosis and excise endometriotic lesions. Extended CHC therapy (84 days of active CHC followed by a 5to 7-day hormone-free interval) may control symptoms. Alternatives are depot medroxyprogesterone acetate (150 mg) every 2 months until symptoms are controlled, then every 3 months of levonorgestrel-releasing intrauterine system. Endometriosis may be treated with gonadotropin-releasing hormone agonists (nafarelin or leuprolide) and hormonal therapy, in older adolescents (>16 years of age) when symptom relief is required.


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Pediatrics_Nelson. The median age of first intercourse in the United States is 17years for girls and 16 years for boys; this is similar to otherdeveloped countries. Although the age of coital initiation is similar among different socioeconomic groups, the prevalence ofadolescent childbearing is greatest in the lower socioeconomic strata. Risk factors for adolescent pregnancy include lower socioeconomic status, lower education, low self-esteem, lack of access to contraception, alcohol and drug use, and adverse earlylife experiences in the adolescent home. Approximately 900,000


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Pediatrics_Nelson. U.S. females 12 to 19 years of age become pregnant each year. Inwomen younger than 20 years of age, there are 97 pregnancies,54 births, and 29 abortions per 1000. Increased use of contraceptives has reduced adolescent pregnancy by up to 35% since thepeak year of 1990. Adolescents who continue their pregnancyhave an increased incidence of preterm and very preterm births,low birth weight infants, infant neonatal admission, postneonatal mortality, child abuse, subsequent maternal unemployment, and poor maternal educational achievement. These risksare influenced by behavior and socioeconomic status, as well asinherent biologic risks within adolescents. Good prenatal care,nutrition, and social support improve pregnancy outcomes.


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Pediatrics_Nelson. Pregnancy should be considered and ruled out in any adolescent presenting with secondary amenorrhea. Frequently pregnant adolescents delay seeking a diagnosis until several periods have been missed and initially may deny having intercourse. Early adolescents often present with other symptoms, such as vomiting, vague pains, or deteriorating behavior and may report normal periods. Because of the varied presentations of adolescent pregnancy, a thorough menstrual history should be obtained in all menstruating adolescents. Urine pregnancy tests are sensitive approximately 7 to 10 days after conception. Rape or incest should be ruled out in all cases of adolescent pregnancy.


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Pediatrics_Nelson. When pregnancy is confirmed, immediate gestational dating is important to assist in planning. Options are to continue or terminate the pregnancy (if not beyond 20 to 24 weeks’ gestation). With the former, the adolescent may choose to parent the child or have the child adopted. Pregnant adolescents should be encouraged to involve their families to assist with decision making; parents may be more understanding than the adolescent expects. Continuation of the Pregnancy Adolescents who continue the pregnancy need early, consistent, and comprehensive prenatal care by a team of health care providers. Their socioeconomic situation should be evaluated in an effort to optimize the infant’s health and development. Although fewer than 5% of adolescents have their infants adopted, this option should be discussed. Pregnancy is the most common cause for females to drop out of school, so special attention should be given to keeping the adolescent in school during and after pregnancy.


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Pediatrics_Nelson. If a pregnant adolescent chooses to terminate her pregnancy, she should be referred immediately to a nonjudgmental abortion service. The options for pregnancy termination depend on the gestational age. Surgical procedures include manual vacuum aspiration (<8 weeks’ gestational age), suction curettage (<12 to 14 weeks’ gestational age, depending on the provider), and dilation and evacuation (14 to 20 weeks’ gestational age). Early pregnancy (<8 weeks’ gestational age) can be terminated medically with oral mifepristone (RU-486) in combination with misoprostol, methotrexate with misoprostol, or misoprostol alone. Adolescents rarely present early enough to explore this option. In the second trimester (>12 weeks’ gestational age), labor induction and delivery can be effected by vaginal misoprostol or the intra-amniotic instillation of prostaglandins or hypertonic saline. Psychosocial support and subsequent contraceptive counseling and implementation should be available for adolescents who


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Pediatrics_Nelson. or the intra-amniotic instillation of prostaglandins or hypertonic saline. Psychosocial support and subsequent contraceptive counseling and implementation should be available for adolescents who choose abortion.


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Pediatrics_Nelson. Adolescents often begin intercourse without adequate birth control. Because unintended pregnancy can be associated with significant psychosocial morbidity for the mother, father, and child, prevention should be a primary goal. All methods of contraception significantly reduce the risk of pregnancy when used in a consistent and correct fashion. The best form of contraception is the one an individual will use. Contraceptives can be divided into user-based methods and LARCs. It is important to remind young women that steroidal contraception or LARCs do not provide any protection from STIs, and condoms should be used to reduce the risk of infection.


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Pediatrics_Nelson. Abstaining from sexual intercourse is the most commonly used and most effective form of adolescent birth control. A degree of self-control, self-assuredness, and self-esteem is necessary. Adolescents who choose to be sexually active should be offered birth control, because there is a 70% chance of pregnancy in 1 year of regular, unprotected intercourse.


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Pediatrics_Nelson. Combined oral contraceptives (COCs) contain a synthetic estrogen and progesterone that suppress gonadotropin secretion and ovarian follicle development and ovulation. COCs also produce an atrophic endometrium (inhospitable for blastocyst implantation) and thicken cervical mucus to inhibit sperm penetration. COCs are 99% effective if taken regularly and have numerous noncontraceptive benefits (decreased acne, less dysmenorrhea, and lighter menstrual flow). After a history and physical examination, COCs can be started on the first day of the next menstrual period or as a Quick Start. The Quick Start method refers to starting on any day of the cycle, usually on the day of the visit to the health care provider, as long as pregnancy has been ruled out. Contraindications and relative contraindications to COCs are listed in Tables 69-4 and 69-5. Blood pressure measurement to rule out preexisting hypertension should be obtained before prescribing a COC. Initially the adolescent should be seen


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Pediatrics_Nelson. to COCs are listed in Tables 69-4 and 69-5. Blood pressure measurement to rule out preexisting hypertension should be obtained before prescribing a COC. Initially the adolescent should be seen monthly to reinforce good contraceptive use and safer sex. Unless adolescents show the ability to take a pill daily, contraception with COCs should be avoided. When COCs are prescribed, 28-day packets are recommended because they encourage a daily routine. One novel contraceptive regimen has packaged 84 active tablets to be taken sequentially followed by a 7-day hormone-free interval and the next package. Any COC can be used in such a fashion to induce long intervals between withdrawal bleeding.


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Pediatrics_Nelson. Initial side effects, such as nausea (pills should be takenat night to reduce this), breast tenderness, and breakthroughbleeding (especially if pills are missed), are common andusually transient. COCs do not generally cause weight gain.Usually 3 to 4 months on one COC are needed to determineacceptability. If there is breakthrough bleeding, the physician


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Pediatrics_Nelson. Smoking and age >35 yr Hypertension (systolic ≥160 mm Hg or diastolic ≥100 mm Hg) Current or history of venous thromboembolism Ischemic heart disease History of cerebrovascular accident Complicated valvular heart disease (pulmonary hypertension, atrial fibrillation, history of subacute bacterial endocarditis) Migraine with focal neurologic symptoms Breast cancer (current) Diabetes with retinopathy/nephropathy/neuropathy Severe cirrhosis Liver tumor (adenoma or hepatoma) <1 month postpartum and breastfeeding or <21 days postpartum not breastfeeding Adequately controlled hypertension Hypertension (systolic 140–159 mm Hg, diastolic 90–99 mm Hg) Migraine and age >35 yr Currently symptomatic gallbladder disease Mild cirrhosis History of combined oral contraceptive-related cholestasis History of malabsorptive bariatric surgery procedure 1 Active pill delayed Take 1 active pill as soon as possible. for <24 hours in any Continue taking 1 pill OD until end of week pack.


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Pediatrics_Nelson. 1 or more active pills Take 1 active pill as soon as possible. missed (Week 1) Continue taking 1 pill OD until end of pack. Back up contraception for 7 days. Consider emergency contraception. <3 pills missed (Week Take 1 active pill as soon as possible. 2 or 3) Continue taking 1 pill OD until end of pack. Discard any placebo pills. Start new cycle of COC without an HFI. 3 or more missed pills Take 1 active pill as soon as possible. (Week 2 or 3) Continue taking 1 pill OD until end of pack. Discard any placebo pills and start new cycle without an HFI. Back up contraception for 7 days. Consider emergency contraception. COC, Combined oral contraceptive; HFI, hormone-free interval; OD, once daily. should determine how often pills are forgotten before changingpills. Adolescents should be taught the appropriate responseto missed doses (Table 69-6). Health care providers usuallysuggest the use of additional contraception in the first month.


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Pediatrics_Nelson. Although not as widely used as COCs, the progestogen-only (or progestin-only) pill, norethindrone (Micronor), is a safe and effective form of contraception when used consistently. It is supplied in packages of 28 tablets, each containing norethindrone with no hormone-free interval. It prevents pregnancy through reduced volume, increased viscosity, and altered molecular structure of cervical mucus, resulting in little or no sperm penetration. In addition, endometrial changes reduce the potential for implantation, and ovulation is partially or completely suppressed. Approximately 40% of women using progestogen-only contraceptives continue to ovulate. Pro-gestogen-only contraception is indicated for women who have a contraindication to estrogen-based contraceptives (see Table 69-4) or have estrogen-related side effects.


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Pediatrics_Nelson. The contraceptive vaginal ring (NuvaRing) is a flexible, Silas-tic ring. The ring releases a constant rate of 15 mg of ethinyl estradiol and 0.120 mg of etonogestrel per day. Each ring is used continuously for 3 weeks and then removed. A new ring is inserted 7 days later. The contraindications and side effects are the same as with COCs. The contraceptive patch (norelgestromin [Evra]) is a 25-cm2 pink patch that is applied, usually on the buttocks, for 1 week followed by removal and application of a new patch for a total of 3 weeks of patch use, then a patch-free week for a withdrawal bleed. The 4-week cycle is repeated. The daily dose is equivalent to a 35-mg ethinyl estradiol COC. In women weighing 90 kg or more, the contraceptive patch is less efficacious. Contraindications and side effects are the same as those in COCs.


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Pediatrics_Nelson. Contraindications and side effects are the same as those in COCs. Intramuscular injection of 150 mg of medroxyprogesteroneacetate (Depo-Provera) every 12 to 14 weeks is an effectiveform of birth control. Progestogen-only contraception is associated with menstrual irregularities (70% amenorrhea and 30%frequent menstrual bleeding). Medroxyprogesterone acetate(Depo-SubQ Provera 104) is designed for subcutaneous useevery 12 to 14 weeks and may be self-administered with minimal training. An implant containing the progestin etonogestrel(Implanon) is now available on the U.S. market. This single rodimplant is inserted subcutaneously and is effective for 3 years.These forms of contraception are userand coital-independentand reduce failure secondary to missed doses.


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Pediatrics_Nelson. Intrauterine devices (IUDs) are inserted into the uterus wherethey release either copper (ParaGard) that is spermicidal or levonorgestrel (Mirena) that prevents implantation by inducingan atrophic endometrium. The copper IUD, which lasts up to10 years, may increase the amount and duration of bleeding aswell as dysmenorrhea. The levonorgestrel-releasing intrauterine system is highly effective for up to 5 years while decreasing bleeding and dysmenorrhea, even causing amenorrhea.Although a small increased risk of pelvic inflammatory diseaseexists for 21 days after insertion of an IUD, the risk followingthat transient period lowers and continues at a low rate for theremainder of time that the young woman uses an IUD. Adolescents should be screened for STIs at the time of IUD insertion, with treatment provided as soon as possible for positive resultsor if there is a concern of compliance at the time of IUD insertion. Insertion in nulliparous women can be aided by the use of a paracervical


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Pediatrics_Nelson. provided as soon as possible for positive resultsor if there is a concern of compliance at the time of IUD insertion. Insertion in nulliparous women can be aided by the use of a paracervical block. IUDs require no active involvement bythe user, thus eliminating error and can be considered as oneof the first line options for adolescent contraception. Condomsshould be encouraged to reduce the risk of STI.


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Pediatrics_Nelson. Emergency postcoital contraception should be discussed at every visit. A prescription should be given in advance of need when no over-the-counter access is available. Emergency contraception reduces the risk of pregnancy after unprotected intercourse if used within 5 days, although efficacy is greatest when used as early as possible. Other indications and contraindications to emergency postcoital contraception are listed in Table 69-7. There are two forms of emergency contraception: (a) Plan B (0.75 mg of levonorgestrel), one pill taken twice, 12 hours apart, or two tablets given once and (b) using a CHC pill the equivalent of 50 mg of ethinyl estradiol and 250 μg of norgestrel, each repeated in 12 hours. Plan B is also associated with significantly less nausea and vomiting than the CHC regimen. Mifepristone is also an effective postcoital contraceptive; however it is not approved for this use in the United States. A copper IUD can be inserted 7 days from the act of unprotected


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Pediatrics_Nelson. CHC regimen. Mifepristone is also an effective postcoital contraceptive; however it is not approved for this use in the United States. A copper IUD can be inserted 7 days from the act of unprotected intercourse and has an efficacy of greater than 99%. This method is not generally recommended for adolescents.


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Pediatrics_Nelson. No method of contraception being used Condom breaks Diaphragm dislodged/removed <6 h Missed birth control pills >1 wk late for Depo-Provera Ejaculation on external genitalia Sexual assault Known pregnancy If strong contraindications to estrogens, use progestin. When condoms and spermicide (foam, gel, film, sponge) are used together in a correct fashion (film must be placed 10 minutes before intercourse), they are almost as effective as COCs in the prevention of pregnancy, especially in individuals who have infrequent intercourse. This method is available over-the-counter (latex and polyurethane condoms) without the need for a physician visit or prescription and reduces the risk of STIs, including human immunodeficiency virus (HIV). The female condom (Reality) is an additional barrier method made of polyurethane that affords females more control, but adolescents usually do not consider it aesthetically pleasing. Sponge, Caps, and Diaphragm


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Pediatrics_Nelson. Sponge, Caps, and Diaphragm The vaginal sponge (Protectaid) is a spermicide-impregnated synthetic sponge that is effective for 24 hours of intercourse. The FemCap is a silicone cap fitted by a health care provider and then placed on the cervix by the user before intercourse. This method is technically difficult, especially for an adolescent. The diaphragm is fitted by a health care provider but is technically simpler to use than the cap because the edges go into the vaginal fornices. To be effective, the diaphragm should be used with spermicide applied to the cervical side and along the rim. The diaphragm needs additional spermicide with each act of intercourse. The Lea’s Shield is a silicone device, similar to a diaphragm, that covers the cervix and adheres to the vaginal vault by a mild vacuum generated by its design. All of these methods need to be left in place for 6 hours after the last act of intercourse for optimal efficacy.


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Pediatrics_Nelson. Withdrawal is a common method of birth control used by sexually active adolescents, but it is ineffective because sperm are released into the vagina before ejaculation, and withdrawal may occur after ejaculation has begun. The rhythm method is the practice of periodic abstinence justbefore, during, and just after ovulation. This method requires the user to have an accurate knowledge of her cycle, awareness of clues indicating ovulation, and discipline. Adolescents tend to have unpredictable cycles and consequently lesspredictable ovulation, so it is difficult to determine with anyaccuracy a time of the month that can be considered completely safe.


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Pediatrics_Nelson. Some adolescents engage in oral or anal sex because they believe that it eliminates the need for contraception. Many do not consider this activity to mean “having sex.” Condoms generally are not used during oral or anal sex, but the risk of acquiring an STI is still present. Adolescents should be asked specifically about nonvaginal forms of sexual activity, and adolescents who engage in oral and anal sex require STI and HIV counseling and screening.


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Pediatrics_Nelson. Rape is a legal term for nonconsensual intercourse. Almost half of rape victims are adolescents, and the perpetrator is known in 50% of cases. Although gathering historical and physical evidence for a criminal investigation is important, the physician’s primary responsibility is to perform these functions in a supportive, nonjudgmental manner. The history should include details of the sexual assault, time from the assault until presentation, whether the victim cleaned herself, date of last menstrual period, and previous sexual activity, if any.


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Pediatrics_Nelson. For optimal results, forensic material should be collected within 72 hours of the assault. Clothes, especially undergarments, need to be placed in a paper bag for drying (plastic holds humidity, which allows organisms to grow, destroying forensic evidence). The patient should be inspected for bruising, bites, and oral, genital, and anal trauma. Photographs are the best record to document injuries. Specimens should be obtained from the fingernails, mouth, vagina, pubic hair, and anus. The sexual assault kit provides materials to obtain DNA from semen, saliva, blood, fingernail scrapings, and pubic hair. A wet mount of vaginal fluids shows the presence or absence of sperm under the microscope. Cultures for STIs should be taken but are often negative (unless previously infected), because 72 hours are needed for the bacterial load to be sufficient for a culture. Blood should be drawn for baseline HIV and syphilis (Venereal Disease Research Laboratories test). All materials must be


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Pediatrics_Nelson. 72 hours are needed for the bacterial load to be sufficient for a culture. Blood should be drawn for baseline HIV and syphilis (Venereal Disease Research Laboratories test). All materials must be maintained in a “chain of evidence” that cannot be called into question in court.


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Pediatrics_Nelson. Therapy after a rape includes prophylaxis for emergency contraception and STI and, if indicated, hepatitis immune globulin and hepatitis vaccine. A single oral dose of cefixime, 400 mg, and azithromycin, 1 g, treats Chlamydia, gonorrhea,and syphilis. An alternative regimen is a single intramuscular dose of ceftriaxone, 125 mg, with a single oral dose of azithromycin, 1 g. For prophylaxis against bacterial vaginosis and Trichomonas, a single oral dose of metronidazole, 2 g, is recommended. Repeat cultures, wet mounts, and a pregnancy test should be performed 3 weeks after the assault, followed by serology for syphilis, hepatitis, and HIV at 12 weeks. Longterm sequelae are common; patients should be offered immediate and ongoing psychological support, such as that offered by local rape crisis services.


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Pediatrics_Nelson. Eating disorders are common chronic diseases in adolescents, especially in females. The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), classifies these as psychiatric illnesses. The diagnosis in young adolescents (pregrowth spurt, premenstrual) may not follow the typical diagnostic criteria (Table 70-1). The prevalence of anorexia nervosa is 1.5% in teenage girls. The female-to-male ratio is approximately 20:1, and the condition shows a familial pattern. The cause of anorexia nervosa is unknown, but it involves a complex interaction between social, environmental, psychological, and biologic events (Fig. 70-1), with risk factors having been identified (Fig. 70-2).


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Pediatrics_Nelson. Screening for eating disorders is important and is best done as a part of the larger psychosocial screen for risk-taking factors (see Fig. 67-1). Although it is recommended that the adolescent be interviewed alone, he or she may minimize the problem; thus interviewing the parent(s) alone is also important. The first event usually described by an affected patient is a behavioral change in eating or exercise (i.e., food obsession, food-related ruminations, mood changes). The patient has an unrealistic body image and feels too fat, despite appearing excessively thin. Parents’ response to this situation can be anger, self-blame, focusing attention on the child, ignoring the disorder, or approving of the behavior.


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Pediatrics_Nelson. The physician should be nonjudgmental, collect information, and assess the differential diagnosis. The differential diagnosis of weight loss includes gastroesophageal reflux, peptic ulcer, malignancy, chronic diarrhea, malabsorption, inflammatory bowel disease, increased energy demands, hypothalamic lesions, hyperthyroidism, diabetes mellitus, and Addison disease. Psychiatric disorders also need to be considered (e.g., drug abuse, depression, obsessive-compulsive disorders). The clinical features of anorexia include wearing oversized layered clothing to hide appearance, fine hair on the face and trunk (lanugo-like hair), rough and scaly skin, bradycardia, hypothermia, decreased body mass index, erosion of enamel of teeth (acid from emesis), and acrocyanosis of hands and feet. Signs of hyperthyroidism should not be present (see Chapter 175). The diagnostic criteria for anorexia nervosa are listed in Table 70-2.


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Pediatrics_Nelson. Treatment requires a multidisciplinary approach, including a feeding program as well as individual and family therapy. Feeding is accomplished through voluntary intake of regular foods, nutritional formula orally or by nasogastric tube. When vital signs are stable, discussion and negotiation of a detailed treatment contract with the patient and the parents Early adolescence— Fear of growing up increased body awareness Middle adolescence— Rebelliousness increased self-awareness Late adolescence— Anxiety and worry for the future identity Anxious Sad Angry Down Feeling: “I’m fat” “I hate...” Rebellious Thoughts: Restrictions Binging Purging Eating disorder behaviors Figure 70-1 The eating disorder cycle.


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Pediatrics_Nelson. Anxious Sad Angry Down Feeling: “I’m fat” “I hate...” Rebellious Thoughts: Restrictions Binging Purging Eating disorder behaviors Figure 70-1 The eating disorder cycle. are essential. The first step is to restore body weight. Hospitalization may be necessary (Table 70-3). When 80% of normal weight is achieved, the patient is given freedom to gain weight at a personal pace. The prognosis includes a 3% to 5% mortality (suicide, malnutrition) rate, the development of bulimic symptoms (30% of individuals), and persistent anorexia nervosa syndrome (20% of individuals). Available @ StudentConsult.com Table 70-4 presents the diagnostic criteria for bulimia nervosa. The prevalence of bulimia nervosa is 5% in female college students. The female-to-male ratio is 10:1. Binge-eating episodes consist of large quantities of often forbidden foods or leftovers or both, consumed rapidly, followed by vomiting. Metabolic abnormalities result from the excessive vomiting or laxative


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Pediatrics_Nelson. Risk Factors Familial Personality types Previous overweight Affective disorders (family history) Impulsive/negative (bulimia nervosa) Psychiatric disease Clinical features -Wearing oversized clothing Fine hair on the face and trunk (lanugo-like hair) Bradycardia, hypothermia Decreased body mass index Erosion of enamel of teeth (acid from emesis) Acrocyanosis of hands and feet. Susceptible individual Feeling that something is not right: With self With control (environment) Behavioral change Exercise or Eating Eating disorder cycle Figure 70-2 The slippery slope to eating disorders. Refusal to maintain body weight at or above a minimally normal weight for age and height (e.g., weight loss leading to body weight <85% of ideal)* Intense fear of gaining weight or becoming fat, even though underweight


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Pediatrics_Nelson. Intense fear of gaining weight or becoming fat, even though underweight Denial of the seriousness of the low body weight—a disturbance in the way in which one’s body weight or shape is experienced *The diagnostic criteria may be difficult to meet in a young adolescent. Allow for a wide spectrum of clinical features. Weight loss >25% ideal body weight* Risk of suicide Bradycardia, hypothermia Dehydration, hypokalemia, dysrhythmias Outpatient treatment fails *Less weight loss accepted in young adolescent. Recurrent episodes of binge eating, at least twice a week for 3 months, characterized by the following: Eating in a discrete period an amount of food that is definitely larger than most people would eat during a similar period A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating)


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Pediatrics_Nelson. A sense of lack of control over eating during the episode (e.g., a feeling that one cannot stop eating or control what or how much one is eating) Compensatory behavior to prevent weight gain (i.e., self-induced vomiting, misuse of laxatives or diuretics, excessive exercise) Disturbance does not occur exclusively during episodes of anorexia nervosa. and diuretic intake. Binge-eating episodes and the loss of control over eating often occur in young women who are slightly overweight with a history of dieting.


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Pediatrics_Nelson. and diuretic intake. Binge-eating episodes and the loss of control over eating often occur in young women who are slightly overweight with a history of dieting. Nutritional, educational, and self-monitoring techniques are used to increase awareness of the maladaptive behavior, following which efforts are made to change the eating behavior. Patients with bulimia nervosa may respond to antidepressant therapy because they often have personality disturbances, impulse control difficulties, and family histories of affective disorders. Patients feel embarrassed, guilty, and ashamed of their actions. Attempted suicide and completed suicide (5%) are an important concern.


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Pediatrics_Nelson. The age at which street drugs are first used is decreasing (<12 years), and females are overtaking males in terms of substance use. Ninety percent of adult smokers begin their habit during their adolescent years. Marijuana and stimulant drug use is increasing. Inhalant use (glue solvents, aerosol products) is prevalent in younger adolescents and in Native Americans. The use of club drugs by adolescents from upper income groups at rave parties (3,4-methylenedioxymethamphetamine [Ecstasy]) and so-called date-rape drugs (gamma-hydroxybutyrate or flunitrazepam [Rohypnol]) has risen sharply. Anabolic steroid use has increased in adolescent boys seeking enhanced athletic performance.


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Pediatrics_Nelson. A history of drug use should be taken in a nonjudgmentaland supportive manner and include the types of substances,frequency, timing, circumstances, and outcomes of substance use. Table 71-1 is a helpful screening tool. There are few physicalfindings even with chronic adolescent substance use. An adolescent may present in an overdose or intoxicated state, or ina psychosis triggered by a hallucinogen, such as phencyclidine(“angel dust”). Club drugs have direct (coma and seizures) andindirect (sexual assault and dehydration) adverse effects. Anabolic steroids also have direct (gynecomastia and testicular atrophy) and indirect (mood swings and violence) adverse effects. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com Many drugs (most commonly alcohol, amphetamines, opiates, and cocaine) can result in a toxicologic emergency, often with first time use (Table 71-2). Initial management should be directed at appropriate supportive medical treatment, with follow-up counseling after the toxic effects have diminished. Alcohol (Meths) Disinhibition, ataxia, slurred Ingested (depends on amount Urine and blood speech, respiratory and CNS and tolerance) depression Nicotine Relaxation, CNS dependence, Inhaled (minutes) ↑ blood pressure, ↑ heart rate, ↓ Snuffed, dipped, chewed temperature Marijuana Euphoria, relaxation, ↑ appetite, ↓ Inhaled (minutes) Urine up to 1 mo (Cannabis, hashish, joints) reaction time Tablets (30 min +) Stimulants Alertness, euphoria Inhaled and snorted Urine up to 48 h Cocaine (crack) Insomnia, ↓ appetite (Quick high) Tablets (longer effect) Hallucinogens Hallucination, anxiety Oral


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Pediatrics_Nelson. Stimulants Alertness, euphoria Inhaled and snorted Urine up to 48 h Cocaine (crack) Insomnia, ↓ appetite (Quick high) Tablets (longer effect) Hallucinogens Hallucination, anxiety Oral Mescaline Psychosis, dilated pupils Injected, sniffed, ingested Immunoassay LSD “Artistic high” 2–12 h “trip” “Lucy in the sky with diamonds” Phencyclidine (PCP, angel dust) Microdots in many colors Ecstasy not detected by urine combinations, i.e., Ecstasy (club drugs: screen of hallucinogens and amphetamines) Opiates Euphoria, ataxia, miosis, slurred Oral, IV, smoked, snorted, and speech sniffed OxyContin (cotton, hillbilly)—new Sedatives (barbiturates, “downers”) Inhalants (solvents, gasoline) Like alcohol Inhaled Common side effects (treatment) of substance abuse drugs are paranoia (haloperidol), seizures (diazepam), hyperthermia (slow cooling), hypertension (β-blockers), and opiate overdose (naloxone).


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Pediatrics_Nelson. Common side effects (treatment) of substance abuse drugs are paranoia (haloperidol), seizures (diazepam), hyperthermia (slow cooling), hypertension (β-blockers), and opiate overdose (naloxone). From Office of the Surgeon General: Reducing tobacco use: a report of the Surgeon General, August 9, 2000 (website). http://www.surgeongeneral.gov/library/ reports/tobacco_use/index.html . Accessed October 31, 2013. CNS, central nervous system; EDMA, 3,4-ethylenedioxy-N-methylamphetamine; LSD, lysergic acid diethylamide; PCP, phencyclidine.


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Pediatrics_Nelson. CNS, central nervous system; EDMA, 3,4-ethylenedioxy-N-methylamphetamine; LSD, lysergic acid diethylamide; PCP, phencyclidine. Heavy alcohol use can cause acute gastritis and acute pancreatitis. Intravenous drug use can result in hepatitis B, bacterial endocarditis, osteomyelitis, septic pulmonary embolism, infection, or acquired immunodeficiency syndrome (commonly known as AIDS). Chronic marijuana or tobacco use is associated with bronchoconstriction and bronchitis. Compulsive drug or alcohol use results in an adolescent being unable to help himself or herself out of the psychosocial sequelae that attend such habituation (e.g., stealing, prostitution, drug dealing, unemployment, school failure, social isolation). Specific management of substance use by adolescents depends on many individual patient factors. Because of the highly addictive (physical and psychological) nature of most substances, residential drug treatment facilities are suggested, especially for younger adolescents.


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Pediatrics_Nelson. Black A, Fleming N, Rome E: Pregnancy in adolescents, Adolesc Med State Art Rev Apr 23(1):123–138, 2012 Blake K, Mann K, Kutcher M: The structured communication adolescent guide (SCAG), MedEdPORTAL, 2008. https:// www.mededportal.org/publication/798 . Accessed October 31, 2013. The Emergency Contraception Website, Office of Population Research: Princeton, NJ. http://ec.princeton.edu/ . Updated June 2012. Hartman L, Monasterio E, Hwang L: Adolescent contraception: review and guidance for pediatric clinicians, Curr Probl Pediatr Adolesc Health Care 24:221–263, 2012 Keel PK, Brown TA: Update on course and outcome in eating disorders, Int J Eat Disord 43(3):195–204, 2010 Williams C, Creighton S: Menstrual disorders in adolescents: review of current practice, Horm Res Paediatr 78(30):135–143, 2012 James W. Verbsky 13


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Pediatrics_Nelson. Williams C, Creighton S: Menstrual disorders in adolescents: review of current practice, Horm Res Paediatr 78(30):135–143, 2012 James W. Verbsky 13 The major components of host defense include anatomic barriers and the innate and adaptive immune systems. Integrity of the anatomic and mucociliary barrier (i.e., skin and mucous membranes) is essential for protection against infection, and defects in this barrier function can lead to infections (Table 72-1). The innate immune system acts as the first line of defense against pathogens, responding rapidly but nonspecifically before the development of the more versatile adaptive immune system. The innate immune system includes soluble factors, including acute-phase proteins, cytokines, chemokines,and complement, as well as cellular components, including neutrophils, monocytes/macrophages, and natural killer (NK) cells. The adaptive immune system is made up of T and B lymphocytes and their effector molecules (Table 72-2).


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Pediatrics_Nelson. Recognition of pathogens by the innate immune system is facilitated by receptors on macrophages, NK cells, and neutrophils that recognize conserved pathogen motifs called pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide of gram-negative bacteria, lipoteichoic acid of gram-positive bacteria, mannans of yeast, and specific nucleotide sequences of bacterial and viral DNA. Recognition of PAMPs by the innate immune system leads to the production of cytokines and chemokines that initiate inflammation and recruit inflammatory cells, induce an acute phase response (e.g., C-reactive protein, mannose binding lectin, complement), and activate the adaptive immune system. Complement proteins kill pathogens by facilitating uptake by phagocytic cells or by lysis of pathogens. Polymorphonuclear neutrophils ingest pyogenic bacteria and some fungi. Macrophages are effective in killing facultative intracellular organisms such as Mycobacterium, Toxoplasma, and Legionella. In


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Pediatrics_Nelson. Polymorphonuclear neutrophils ingest pyogenic bacteria and some fungi. Macrophages are effective in killing facultative intracellular organisms such as Mycobacterium, Toxoplasma, and Legionella. In addition NK lymphocytes mediate cytotoxic activity against virus-infected cells and cancer cells.


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Pediatrics_Nelson. The key features of the adaptive immune system are antigen specificity and the development of immunologic memory, produced by expansion and maturation of antigen-specific T cells and B cells. Antibodies (immunoglobulin) produced by B cells neutralize toxins released by pathogens, opsonize pathogens to facilitate uptake by phagocytic cells, activate complement causing cytolysis of the pathogen, and direct NK cells to kill infected cells through antibody-mediated cytotoxicity. T cells kill virus-infected cells and cancer cells, activate macrophage to kill intracellular pathogens, and deliver the necessary signals for B-cell antibody synthesis and memory B-cell formation. Immunodeficiency can result from defects in one or more components of innate or adaptive immunity, leading Aspiration syndromes (gastroesophageal reflux, ineffective cough, foreign body) Cleft palate, eustachian tube dysfunction Adenoidal hypertrophy


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Pediatrics_Nelson. Aspiration syndromes (gastroesophageal reflux, ineffective cough, foreign body) Cleft palate, eustachian tube dysfunction Adenoidal hypertrophy Nasal polyps Obstruction of paranasal sinus drainage (osteomeatal complex disease), encephaloceles Tracheoesophageal fistula, bronchobiliary fistula Pulmonary sequestration, bronchogenic cysts Vascular ring Tumor, foreign body, or enlarged lymph nodes Primary ciliary dyskinesia syndromes, Young syndrome Cystic fibrosis Bronchopulmonary dysplasia Bronchiectasis Allergic disease (allergic rhinitis, asthma) Burns Chronic atopic dermatitis Ureteral obstruction, vesicoureteral reflux IV drug use Central venous line, artificial heart value, CSF shunt, peritoneal dialysis catheter, urinary catheter Dermal sinus tract CSF, Cerebrospinal fluid.


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Pediatrics_Nelson. CSF, Cerebrospinal fluid. to recurrent, opportunistic, or life-threatening infections. Primary immunodeficiency diseases are relatively rare individually, but together they cause significant chronic disease, morbidity, and mortality (Table 72-3).


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Pediatrics_Nelson. The frequency, severity, and location of the infection and thepathogens involved can help differentiate infections in a normalhost from infections in an immunodeficient patient (see Table 72-3). Although otitis media and sinopulmonary infectionsare common in children, recurrent infections, invasive or deepseeded infections, infections that require multiple rounds of oralantibiotics or need intravenous antibiotics, or infections with opportunistic infections suggest a primary immunodeficiency.Recurrent sinopulmonary infections with encapsulated bacteria suggest a defect in antibody-mediated immunity becausethese pathogens evade phagocytosis. Failure to thrive, diarrhea,malabsorption, and infections with opportunistic infections (i.e., fungi, Candida sp, Pneumocystis jiroveci [carinii]) suggest T-cell immunodeficiency. Recurrent viral infections can resultfrom T-cell or NK-cell deficiency. Deep-seated abscesses and infections with Staphylococcus aureus, Serratia marcescens, and


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Pediatrics_Nelson. suggest T-cell immunodeficiency. Recurrent viral infections can resultfrom T-cell or NK-cell deficiency. Deep-seated abscesses and infections with Staphylococcus aureus, Serratia marcescens, and Aspergillus suggest a disorder of neutrophil function, such as chronic granulomatous disease (CGD). Delayed separation ofthe umbilical cord, especially in the presence of omphalitis andlater onset periodontal disease, in addition to poorly formedabscesses, indicates leukocyte adhesion deficiency.


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Pediatrics_Nelson. Age of onset of symptoms can be helpful in defining animmune deficiency, although significant variability does occur. Neutrophil defects (e.g., congenital neutropenia, leukocyte adhesion deficiency) typically present in the first severalmonths of life. Antibody defects (e.g., agammaglobulinemia)and T-cell defects (e.g., severe combined immunodeficiency[SCID]) typically present after 3 months of life after maternal antibody levels have waned. Presentation with symptomsof an antibody deficiency in adolescence or young adulthoodsuggests common variable immunodeficiency (CVID) ratherthan agammaglobulinemia, although milder phenotypes ofprimary immunodeficiency disease may not present until later


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Pediatrics_Nelson. Table 72-2 Cytokines and Chemotactic Cytokines and Their Functions FACTOR SOURCE FUNCTION IL-1 Macrophages Co-stimulatory effect on T cells, enhances antigen presentation, acute phase response, fever IL-2 T cells Primary T-cell growth factor; B-cell and NK-cell growth factors; required for T regulatory cell function and survival T cells, macrophages, Enhances immunoglobulin synthesis, antiviral activity, induces acute phase response, fever, fibroblasts, endothelium hematopoietic effects IL-7 Stromal cells Enhances growth of pre-T cells T cells, macrophages, Neutrophil-activating protein; T lymphocyte and neutrophil chemotactic factor epithelium IL-9 T cells Acts in synergy with IL-4 to induce IgE production, mast cell growth T cells, including regulatory Cytokine synthesis inhibitory factor; suppresses macrophage function; enhances B-cell T cells, macrophages growth; inhibits IL-12 production; suppresses inflammation at mucosal surfaces


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Pediatrics_Nelson. Macrophages, neutrophils NK cell stimulatory factor; cytotoxic lymphocyte maturation factor; enhances IFN-γ synthesis; inhibits IL-4 synthesis IL-17 T cells Induces IL-1β and IL-6 synthesis, important in fungal infections TGF-β T cells, including regulatory Inhibits T-cell and B-cell proliferation and activation, induces T regulatory cells T cells, many other cells RANTES T cells, endothelium Chemokine for monocytes, T cells, eosinophils MIP-1α Mononuclear cells, Chemokine for T cells; enhances differentiation of CD4+ T cells endothelium IP-10 Monocytes, macrophages, Chemokine for activated T cells, monocytes, and NK cells endothelium IFN, Interferon; NK, natural killer; RANTES, regulated on activation, normal T expressed and secreted; Th2, T helper 2. Recurrent pyogenic infections with extracellular encapsulated organisms, such as Streptococcus pneumoniae, Haemophilus influenzae type b, and group A streptococcus


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Pediatrics_Nelson. Recurrent pyogenic infections with extracellular encapsulated organisms, such as Streptococcus pneumoniae, Haemophilus influenzae type b, and group A streptococcus Otitis, sinusitis, recurrent pneumonia, bronchiectasis, and conjunctivitis Few problems with fungal or viral infections (except enterovirus and poliomyelitis) Diarrhea common, especially secondary to infection with Giardia lamblia Compatible with survival to adulthood or for several years after onset unless complications occur Recurrent bacterial infections with extracellular encapsulated organisms, such as S. pneumoniae and H. influenzae Susceptibility to recurrent infections with Neisseria meningitides Increased incidence of autoimmune disease Severe or recurrent skin and respiratory tract infection Recurrent infections with less virulent or opportunistic organisms, such as fungi, Candida sp mycobacteria, viruses, and protozoa as well as bacteria


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Pediatrics_Nelson. Recurrent infections with less virulent or opportunistic organisms, such as fungi, Candida sp mycobacteria, viruses, and protozoa as well as bacteria Growth retardation, malabsorption, diarrhea, and failure to thrive common Anergy Susceptible to graft-versus-host disease from nonirradiated blood or from maternal engraftment Fatal reactions may occur from live virus or bacille Calmette-Guérin vaccination. High incidence of malignancy Poor survival beyond infancy or early childhood Recurrent dermatologic infections with bacteria such as Staphylococcus, Pseudomonas, and Escherichia coli, and fungi such as Aspergillus Subcutaneous, lymph node, lung, and liver abscesses Pulmonary infections common, including abscess and pneumatocele formation, contributing to chronic disease Delayed separation of umbilical cord


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Pediatrics_Nelson. Subcutaneous, lymph node, lung, and liver abscesses Pulmonary infections common, including abscess and pneumatocele formation, contributing to chronic disease Delayed separation of umbilical cord Absence of pus at site(s) of infection Poor wound healing in life. The presence of associated problems, such as congenital heart disease and hypocalcemia (DiGeorge syndrome),abnormal gait and telangiectasia (Ataxia-telangiectasia),atopic dermatitis (hyper-IgE syndrome, Omenn syndrome),and easy bruising or a bleeding disorder (Wiskott-Aldrichsyndrome) can be informative in guiding an immune workup.Finally a family history of a primary immune deficiency or death of a young child due to infections should prompt an immune evaluation, particularly in the setting of recurrentinfections.


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Pediatrics_Nelson. Immunosuppressive agents (e.g., corticosteroids, radiation, and antimetabolites) Malignancy (leukemia, Hodgkin disease, nonlymphoid cancer) Acquired asplenia Acquired neutropenia (autoimmune, viral, or drug-induced) Stem cell transplantation/graft-versus-host disease Systemic lupus erythematosus and other autoimmune diseases Sarcoidosis


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Pediatrics_Nelson. Recurrent infection in immunologically deficient children is associated with pathology at sites of infection resulting in substantial morbidity, such as scarring tympanic membranes leading to hearing loss or chronic lung disease due to recurrent pneumonia. Height and weight percentiles, nutritional status, and presence of subcutaneous fat should be assessed. Oral thrush, purulent nasal or otic discharge, and chronic rales may be evidence of repeated or persistent infections. Absence of lymphoid tissue (e.g., tonsils) suggests agammaglobulinemia or SCID, whereas increased size of lymphoid tissue suggests CVID, CGD, or human immunodeficiency virus (HIV) infection. Cerebellar ataxia and telangiectasia indicate ataxia-telangiectasia. Severe eczema and inflammatory bowel disease are seen in some disorders of immune regulation with polyendocrinopathy and enteropathy that is X-linked (IPEX), whereas eczema and petechiae or bruises suggest Wiskott-Aldrich syndrome.


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Pediatrics_Nelson. There are many secondary causes of immunodeficiency that should be considered, particularly if the immunologic testing is nonrevealing (Table 72-4). In patients with primary immunodeficiencies, infections develop at multiple sites (e.g., ears, sinuses, lungs, skin), whereas in individuals with anatomic problems (e.g., sequestered pulmonary lobe, ureteral reflux), infections are confined to a single anatomic site. Asplenia is associated with recurrent and severe infections, even in the presence of protective antibody titers. Infection with HIV should be considered in any patient presenting with a history suggesting a T-cell immunodeficiency. The diagnosis of patients with primary immunodeficiency diseases depends on early recognition of signs and symptoms, followed by laboratory tests to evaluate immune function. Recognizing the patient who may have an immunodeficiency disease prompts an evaluation and referral to an immunologist (see Table 72-3).


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Pediatrics_Nelson. A diagnosis of primary immunodeficiency disease cannot be established without the use of laboratory tests based on the clinical history (Table 72-5). A complete blood count with differential should always be obtained to identify patients with neutropenia or lymphopenia (SCID) as well as the presence of eosinophils (allergic disease) and anemia (chronic disease). Serum immunoglobulin levels are essential to the workup of suspected primary immunodeficiency. Antibody levels vary with age, with normal adult values of IgG at full-term birth from transplacental transfer of maternal IgG, a physiologic nadir occurring between 3 and 6 months of age, and a gradual increase to adult values over several years. IgA and IgM are low at birth, and levels increase gradually over several years, with IgA taking the longest to reach normal adult values. Low albumin levels with low immunoglobulin levels suggest low synthetic rates for all proteins or increased loss of proteins, as in protein-losing


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Pediatrics_Nelson. IgA taking the longest to reach normal adult values. Low albumin levels with low immunoglobulin levels suggest low synthetic rates for all proteins or increased loss of proteins, as in protein-losing enteropathy. High immunoglobulin levels suggest intact B-cell immunity and can be found in diseases with recurrent infections, such as CGD, immotile cilia syndrome, cystic fibrosis, HIV infection, and autoimmune diseases. Elevated IgE levels can be found in a number of immune deficiencies such as hyper-IgE syndrome, as well as in atopic dermatitis.


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Pediatrics_Nelson. Specific antibody titers after childhood vaccination (tetanus, diphtheria, Haemophilus influenzae type b, or Streptococcus pneumoniae vaccines) reflect the capacity of the immune system to synthesize specific antibodies and to develop memory B cells. If titers are low, immunization with a specific vaccine and titers obtained 4 to 6 weeks later confirm response to the immunization. Poor response to bacterial polysaccharide antigens is normal before 24 months of age but is also associated with IgG subclass deficiency or specific antibody deficiency. The development of protein-conjugate polysaccharide vaccines has prevented infections with these organisms in early childhood. Antibody responses to the S. pneumoniaeserotypes found in the 23-valent polysaccharide vaccine, but not in the conjugate vaccine, can be used to test antibody responses to polysaccharide antigens.


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Pediatrics_Nelson. Delayed-type hypersensitivity skin tests to protein antigens such as tetanus, diphtheria, Candida, or mumps demonstrate the presence of antigen-specific T cells and functional antigen-presenting cells. If delayed-type hypersensitivity skin test results are negative, patients should receive a booster vaccination and be retested 4 weeks later. Complete blood count, including hemoglobin, differential white blood cell count and morphology, and platelet count Radiographs to document infection in chest, sinus, mastoids, and long bones, if indicated by clinical history Cultures, if appropriate Quantitative immunoglobulin levels: IgG, IgA, IgM, IgE, Isohemagglutinin titers (anti-A, anti-B, measures IgM function) Specific antibody levels: Protein antigens: diphtheria, tetanus Protein-conjugated antigens: Haemophilus influenzae, Streptococcus pneumoniae (conjugate vaccine) Polysaccharide antigens: S. pneumoniae (unconjugated vaccine) B-cell numbers and subsets by flow cytometry


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Pediatrics_Nelson. Polysaccharide antigens: S. pneumoniae (unconjugated vaccine) B-cell numbers and subsets by flow cytometry Delayed hypersensitivity skin tests (Candida, tetanus toxoid, mumps): measure T-cell and macrophage function T-cell and NK cell numbers and subsets by flow cytometry T-lymphocyte functional analyses (mitogen responses, cytokines) NK cell cytotoxicity assays Nitroblue tetrazolium dye test/dihydrorhodamine 123 using flow cytometry Staphylococcal killing, chemotaxis assay Myeloperoxidase stain Total hemolytic complement CH50: measures classical and common pathway activity AH50: measures alternative and common pathway activity Levels of individual complement components NK, Natural killer.


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Pediatrics_Nelson. Lymphocyte phenotyping by flow cytometry enumerates the percentage and absolute numbers of T-cell, B-cell, and NK-cell subsets. Flow cytometry can also test for the presence of surface proteins that are necessary for normal immunity, such as major histocompatibility complex molecules or adhesion molecules, as well as intracellular analysis of signaling proteins and cytokines. T-cell proliferation assays to mitogens (phytohemagglutinin, concanavalin A, or pokeweed mitogen) or antigens (tetanus toxoid or Candida) are in vitro assays that confirm the capacity of T cells to proliferate in response to a nonspecific stimulus (mitogens) or the presence of antigen-specific memory T cells (antigens). Such presence requires prior vaccination (tetanus) or exposure (Candida)to the antigen. Tests for cytokine synthesis or expression of activation markers by T cells may be performed in specialized research laboratories and can help identify defects in T-cell function when, despite present T cells,


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Pediatrics_Nelson. cytokine synthesis or expression of activation markers by T cells may be performed in specialized research laboratories and can help identify defects in T-cell function when, despite present T cells, the clinical history suggests a T-cell disorder.


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Pediatrics_Nelson. Complement assays include the CH50 test, which measures the presence of proteins in the classical pathway of complement(C1, C2, C3, C4), and the AH50 test, which tests the proteins of the alternative pathway of complement (C3, factor B, proper-din). If both the CH50 and AH50 levels are abnormal, a defect in the common pathway is likely (C5−C9). Specialized laboratories can measure the presence or function of specific complement proteins. Tests for C1-inhibitor antigen and function areused to diagnose hereditary or acquired angioneurotic edema.


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Pediatrics_Nelson. Tests for neutrophil function include the nitroblue tetrazolium (NBT) or dihydrorhodamine 123 (DHR) test for CGD,in which oxygen radicals generated by activated neutrophilsoxidize NBT to an insoluble blue dye and DHR to a fluorescentmolecule. Patients with CGD have no blue-staining neutrophilswith NBT and little fluorescence when DHR is used. In vitro tests for evaluation of neutrophil phagocytosis, chemotaxis,bacterial killing, and for the presence of myeloperoxidase activity are available in some laboratories. Tests for the expression ofadhesion molecules such as CD18 (leukocyte function–associated antigen type 1, LFA-1) can be performed by flow cytometry.


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Pediatrics_Nelson. Genetic testing to confirm the diagnosis of a primary immunodeficiency disease can be performed in specialized laboratories and may be helpful for deciding on a course of treatment, determining the natural history and prognosis of the disease, genetic counseling, and prenatal diagnosis. In patients in whom DiGeorge syndrome is suspected, fluorescent in situ hybridization studies for deletions of chromosome 22 can be helpful. In patients in whom ataxia-telangiectasia is suspected, chromosomal studies for breakage in chromosomes 7 and 14 are useful. The absence of a thymus on chest x-ray suggests DiGeorge syndrome or other defects in T-cell development. Abnormalities in the cerebellum are found in patients with ataxia-telangiectasia. Otherwise the use of diagnostic imaging in the evaluation of immunodeficiency diseases is essentially limited to the diagnosis of infectious diseases.


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Pediatrics_Nelson. Disorders that affect lymphocyte development or function result in significant immunodeficiency because lymphocytes provide antigen specificity and memory responses. Hematopoietic stem cells give rise to lymphoid precursors that develop into T lymphocytes in the thymus or B lymphocytes in the bone marrow (Fig. 73-1). Isolated B-cell disorders result in antibody deficiency diseases, whereas T-cell disorders usually cause combined immunodeficiency because they are necessary for cell-mediated immunity to clear intracellular pathogens and for antibody synthesis by B cells. NK cells are an important component of the innate immune response, develop from lymphoid precursors, and can kill virus-infected cells and tumor cells. Antibodies can enhance NK cell function by antibody-mediated cellular cytotoxicity. Available @ StudentConsult.com Disorders of B cells result in an increased susceptibility to infections by encapsulated bacteria.


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Pediatrics_Nelson. Available @ StudentConsult.com Disorders of B cells result in an increased susceptibility to infections by encapsulated bacteria. Agammaglobulinemia results from the absence or defective function of B cells with subsequent severe decrease in immunoglobulin levels and a total absence of specific antibody. X-linked agammaglobulinemia affects males and is characterized by a profound deficiency of B cells, severe hypogammaglobulinemia, and absence of lymphoid tissue (Table 73-1; see Fig. 73-1). The defect is caused by mutations in a gene encoding the tyrosine kinase Btk on chromosome Xq22 that is involved in a signaling of the pre-B-cell receptor and the B-cell antigen receptor. Autosomal recessive agammaglobulinemiaresults from a variety of defects in the pre-B-cell and B-cell antigen receptor complexes and includes mutations in the μ heavy chain gene, λ5, Igα, Igβ, and BLNK. X-linked agammaglobulinemia is more common than the autosomal recessive forms.


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Pediatrics_Nelson. Patients with agammaglobulinemia usually present during the first 6 to 12 months of life as maternally derived antibodies wane, although patients can present years later. These patients develop infections with Streptococcus pneumoniae, Haemophilus influenzae type b, Staphylococcus aureus, and Pseudomonas, organisms for which antibody is an important opsonin. They also have increased susceptibility to giardiasis and enteroviral infections, leading to chronic enteroviral meningoencephalitis and vaccine-associated poliomyelitis (if immunized with oral live, attenuated poliovirus vaccine).


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Pediatrics_Nelson. Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by hypogammaglobulinemia developing after an initial period of normal immune function, most commonly in the second and third decades of life (see Table 73-1). Serum IgG levels are less than 500 mg/dL (usually <300 mg/dL) with IgA levels less than 10 mg/dL and/or low IgM levels. Antibody titers to protein antigens, suchas tetanus and diphtheria, and to polysaccharide antigens,such as pneumococcus, are low or absent. T-cell numbersand function are highly variable, and B-cell numbers can be normal or low. Patients exhibit normal-sized or enlargedtonsils and lymph nodes and may have splenomegaly. Theyare susceptible to frequent respiratory tract infections due to Streptococcus pneumoniae, Haemophilus influenzae type b, and Mycoplasma. Gastrointestinal infections with Giardia, Campylobacter, Salmonella, Helicobacter, and enteroviruses are common. Autoimmune hemolytic anemia and thrombocytopenia occur


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Pediatrics_Nelson. type b, and Mycoplasma. Gastrointestinal infections with Giardia, Campylobacter, Salmonella, Helicobacter, and enteroviruses are common. Autoimmune hemolytic anemia and thrombocytopenia occur frequently, and granulomatous diseaseaffecting the gastrointestinal tract, liver, and lungs leadsto significant morbidity. Cancer, especially lymphoma, is amajor cause of mortality.


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Pediatrics_Nelson. Common variable immunodeficiency Defects in T cell & B cell development T− B− SCID Defects in T cell activation and function Differentiation Pre–B cell Mature B cellB LYMPHOCYTE LINEAGEIsotype Switching/ Somatic Hypermutation IgA Stem cell T LYMPHOCYTE LINEAGEThymus Mature T cell Effector helper, functions Effector cytotoxic, functions DiGeorge syndrome /MHC deficiency Agammaglobulinemia Defects in T cell development T− B+ SCID PROLIFERATION PROLIFERATION CD8+ CD4+ CD34+ Plasma cells IgG Bone marrow X-linked hyper IgM Hyper IgMSelective Ig isotype deficiencies Memory cell Figure 73-1 Sites of cellular abnormalities in congenital immunodeficiencies. In primary immunodeficiency diseases, the maturation or activation of B or T lymphocytes may be blocked at different stages. , Inhibition; B, B lymphocyte; T, T lymphocyte. (Adapted from Abbas AK, Lichtman AH, Pober JS: Cellular and Molecular Immunology, ed 3, Philadelphia, 1997, Saunders.)


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Pediatrics_Nelson. The gene defects leading to the majority of cases of CVID decreased while total IgG levels are normal. Normal indiare unknown. Some patients have a defect in the gene encod-viduals can express low levels of one or more subclasses, so ing for inducible co-stimulator (ICOS) on activated T cells, a history of recurrent infections is important. An inability to transmembrane activator and calcium-modulating cyclophi-synthesize specific antibody titers to protein or polysaccharide lin ligand interactor (TACI), CD19, CD21, CD81, or BAFF-R. antigens is the best marker of IgG subclass deficiency associ-It is important to exclude X-linked agammaglobulinemia, ated with recurrent infections and requiring therapy. X-linked lymphoproliferative disease, or hyper-IgM syndrome Transient hypogammaglobulinemia of infancy is a temas well as other causes of hypogammaglobulinemia, such as porary condition characterized by delayed immunoglobulin hypogammaglobulinemia associated with thymoma,


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Pediatrics_Nelson. of infancy is a temas well as other causes of hypogammaglobulinemia, such as porary condition characterized by delayed immunoglobulin hypogammaglobulinemia associated with thymoma, second-production. The pathogenesis of this disorder is unknown ary to protein losing enteropathy, or secondary to medica-but is thought to result from a prolongation of the physiologic tions, before making the diagnosis of CVID. hypogammaglobulinemia of infancy. The immunoglobulin