2002 Self-Assessment Exercise XXI.

. Collagen vascular and other multisystem disorders [Return to Category List] Questions Question 17. Answer.

A 2-year-old girl presents with a swollen, tender, erythematous knee. Two weeks ago she had fever and bloody diarrhea that lasted 4 days. Of the following, the MOST likely organism to be associated with arthritis in this patient is: A. B. C. D. E. Escherichia coli Giardia lamblia Norwalk virus rotavirus Shigella flexneri Answer.

Question 64.

A 12-year-old girl who has systemic lupus erythematosus was exposed to varicella 24 hours ago. She has been receiving prednisone 40 mg bid for 9 weeks because of an exacerbation of nephropathy. She has not had varicella or received varicella immunization.

Of the following, the MOST appropriate next step is to: A. B. C. D. E. administer varicella vaccine administer varicella-zoster immune globulin begin prophylactic doses of acyclovir discontinue the prednisone provide stress doses of prednisone

Question 117. Answer. A previously healthy 10-year-old African-American boy from the southeastern United States has had a cough for more than 4 months. He has had no fever and has stopped playing soccer with his club team because he feels too tired. Findings on physical examination are normal. A skin test with purified protein derivative of tuberculin is negative. Plain radiographs of the chest reveal bilateral peribronchial infiltrates. Of the following, this clinical presentation is MOST consistent with:

A. B. C. D. E.

cough variant asthma Hodgkin disease pulmonary aspergillosis sarcoidosis tuberculosis

Question 167. Answer. A 15-year-old boy complains of intermittent unilateral knee pain occurring at night and unassociated with exercise. He has occasional morning stiffness that is relieved by exercise. Physical examination reveals decreased range of motion of the left knee, no erythema, and minimal swelling. There is also decreased range of motion of the lumbar spine in anterior flexion and loss of lumbar lordosis. Of the following, the MOST likely result of laboratory studies would be: A. B. C. D. E. elevated antistreptolysin O antibody titer elevated leukocytes positive antinuclear antibody positive HLA-B27 antigen positive rheumatoid factor

Question 193. Answer. A 16-year-old boy comes to you complaining of dysuria. His last episode of unprotected sex was 3 weeks ago. On physical examination, you note conjunctival injection and erythema and swelling of the foreskin. Urinalysis reveals 3+ leukocytes. Other clinical manifestations commonly associated with this patient's diagnosis include: A. B. C. D. E. arthritis lymphadenitis nephritis pancreatitis pneumonitis

Question 210. Answer. A 28-year-old woman who has systemic lupus erythematosus is pregnant.

Of the following, the complication MOST likely to cause the infant's death in the neonatal period is: A. B. C. D. E. cholestasis complete heart block glomerulonephritis intracerebral hemorrhage thrombocytopenia

Question 248. Answer. A 14-year-old girl presents with joint pains, fever, chronic fatigue, and weight loss of 2 months' duration. Blood pressure is 160/100 mm Hg, and serum electrolyte levels are normal. Urinalysis reveals: specific gravity, 1.015; pH, 6.0; negative protein; moderate blood; 15 to 20 red blood cells; and 5 to 10 white blood cells. Laboratory tests reveal elevated antinuclear antibody (ANA) and anti-DNA levels and low serum complement levels (C3, C4). Therapy with oral steroids results in clinical improvement. Of the following, the laboratory test result that would BEST indicate response to therapy is: A. B. C. D. E. normalization of blood pressure normalization of C3 and C4 levels reduction of ANA levels reduction of red blood cells in urine reduction of white blood cells in urine

Answers Critique 17. Preferred Response: E

[View Question] Postinfectious or reactive arthritis often occurs several weeks or months after an acute infection. Reactive arthritis frequently follows enteric infections with Shigella, Salmonella, Yersinia, and Campylobacter sp. As described in the vignette, affected children initially develop bloody diarrhea, followed by the onset of arthritis, typically 1 to 2 weeks after the triggering infection. Reactive arthritides are usually acute and self-limited, resolving within weeks or months. There is no specific treatment for reactive arthritis. The patient may need analgesics for pain relief. Of the choices listed, Shigella would be the most likely organism to cause bloody diarrhea and arthritis. Other important examples of reactive arthritis include postvenereal reactive arthritis (especially with Chlamydia trachomatis) and virus-related arthritis. A variety of viruses have

been associated with reactive arthritis, including rubella, hepatitis B, mumps, parvoviruses, and herpesviruses. Poststreptococcal reactive arthritis and acute rheumatic fever (ARF) are two other examples of reactive arthritis. Children who have poststreptococcal reactive arthritis experience prolonged, persistent, and symmetric arthropathy that does not respond as well to aspirin as does typical ARF. In ARF, several joints are affected in quick succession, but each only briefly, producing a migratory polyarthritis. Reactive arthritis does not typically follow infections with Escherichia coli, Giardia lamblia, Norwalk virus, or rotavirus. References: DeCunto CL, Giannini EH, Fink CW, Brewer EJ, Person DA. Prognosis of children with poststreptococcal reactive arthritis. Pediatr Infect Dis J. 1988;7:683-686 Fink CW. Reactive arthritis. Pediatr Infect Dis J. 1988;7:58-65 Miller ML, Cassidy JT. Postinfectious arthritis and related conditions. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:712-713 Petty RE, Tingel AJ. Arthritis and viral infection. J Pediatr. 1988; 113:948-949 Critique 64. Preferred Response: B

[View Question] Varicella-zoster immune globulin (VZIG) can ameliorate or prevent varicella in immunocompromised children if administered within 96 hours of exposure. The decision to administer VZIG is based on whether the exposed child is susceptible to varicella, the childs risk of developing severe varicella, and whether the childs exposure was sufficient to result in infection. The determination of susceptibility to varicella may be complex. In healthy individuals, serologic testing accurately reflects immune status. However, in immunocompromised patients, results of serologic testing may not be reliable. Children receiving immunosuppressive therapy who have no history of varicella and low but measurable concentrations of serum antibody have contracted the disease. Accordingly, obtaining a careful history of varicella is the primary consideration in determining susceptibility. Children receiving immunosuppressive therapy constitute an important group of immunocompromised patients at risk for severe and even fatal varicella. They often have a greater quantity and larger lesions, which can become hemorrhagic. New lesions appear for longer periods, and complications such as pneumonitis are more common. Occasional patients have acute, rapidly evolving varicella that is associated with disseminated intravascular coagulation. These children can die even before antiviral therapy can be initiated. Therefore, VZIG should be used in susceptible, immunocompromised patients to prevent or ameliorate varicella. Candidates for VZIG include those who have T-lymphocyte immunodeficiency, including congenital disorders; those receiving chemotherapy or high-

dose systemic corticosteroids; and those who have human immunodeficiency virus infection. Accordingly, the girl described in the vignette is a candidate for VZIG. It is critical to determine whether the patients exposure was sufficient to result in infection and, therefore, necessitates administration of VZIG. The contagious state lasts from 1 to 2 days before lesions appear and until all the lesions have crusted. Adequate exposure to a contagious individual includes anyone residing in the same household; nontransient face-to-face play (which has been defined as from as little as 5 minutes to as long as 1 hour by different experts); sharing a 2- or 4-bed room or adjacent beds in a larger ward in the hospital; and face-to-face contact with an infectious staff member, patient, or visitor (as defined previously). Infectious exposure to zoster requires intimate physical contact such as touching or hugging. The decision to continue or withhold immunosuppressive therapy after exposure and until the incubation period has ended is complex. It is further complicated by the potential of VZIG to prolong the incubation period by up to 7 days, lengthening its duration to 28 days. The decision about immunosuppressive therapy should be based on the nature of the exposure, the patients clinical condition, and the intensity of the regimen. Corticosteroid therapy is not discontinued at the time of exposure unless the steroid dose is small. If varicella does develop in patients receiving corticosteroids, the need for adequate doses of corticosteroids to tolerate the stress of a potentially severe infection must be considered. Patients receiving prolonged courses of corticosteroids may not be able to respond with adequate endogenous corticosteroid production during the stress of varicella infection. If such stress is encountered, the corticosteroid dose should be equivalent to a minimum of three to five times the physiologic dose. Such stress doses may be necessary when varicella develops, but not at the time of exposure and treatment with VZIG. Varicella vaccine is not recommended for patients who are receiving high doses of systemic corticosteroids, defined as more than 2 mg/kg per day or a total dose of 20 mg/d of prednisone or its equivalent. Acyclovir is used to treat patients who actually develop varicella, but it is not given as prophylactic therapy after exposure to varicella. References: American Academy of Pediatrics. Varicella-zoster infections. In: Pickering LK, ed. 2000 Red Book: Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2000:624-638 Gershon AA. Varicella-zoster virus. In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. 4th ed. Philadelphia, Pa: WB Saunders Co; 1998: 1769-1775 Rosenberg M. Passive immunization with varicella zoster immune globulin. Pediatr Rev. 1994;15:254 Critique 117. Preferred Response: D

[View Question] Sarcoidosis is a chronic multisystem disease of unknown etiology characterized by noncaseating granulomatous lesions. In the United States, sarcoidosis occurs more frequently in African-Americans, who are affected more severely than Caucasians. Most cases present during adulthood, although pediatric cases do occur. Granulomas may develop in any organ system, creating a variety of clinical manifestations. Involvement of the lung occurs in almost all patients, followed by the skin, eyes, lymphatics, and liver. The most common presenting symptoms are fatigue, anorexia, weight loss, fever, and cough, two of which are reported for the boy in the vignette. The finding of noncaseating granulomas in a biopsy specimen supports but is not diagnostic of sarcoidosis. A thorough evaluation for other known causes is necessary, including tests for histoplasmosis and mycobacteria. Sarcoidosis remains a diagnosis of exclusion. Unfortunately, measurements of serum angiotensin-converting enzyme activity and gallium 67 scanning, once thought to be specific diagnostic tests, are not helpful because of their poor specificity. The typical findings on chest radiography are bilateral peribronchial infiltrates. Although sarcoidosis is often a chronic respiratory disease, there are asymptomatic patients whose lung involvement is discovered on chest radiography. The clinical course is variable and often uncertain. Spontaneous recovery is common, but some patients have progressive disease, and others may develop late relapses. Pulmonary fibrosis and cardiac complications are leading causes of death. The granulomas of sarcoidosis contain macrophages that produce and secrete the active form of vitamin D that causes hypercalcemia and hypercalciuria. All patients should be monitored for renal damage due to hypercalciuria. Patients need regular examinations for asymptomatic ophthalmologic lesions that may progress to blindness. Eye disease and renal damage from hypercalciuria may be suppressed by treatment with adrenal corticosteroids. A patient who has cough variant asthma is unlikely to have bilateral peribronchial infiltrates on chest radiography. The most common presenting sign of Hodgkin disease is cervical or supraclavicular adenopathy. At the time of initial diagnosis, an anterior mediastinal mass frequently is found on chest radiography. Pulmonary aspergillosis usually presents as an acute cough, often with hemoptysis, in an immunosuppressed or chronically ill child. A diagnosis of tuberculosis is supported by a history of fever and positive skin test. Results of a Mantoux test are positive in 90% of immunocompetent children who have pulmonary tuberculosis 4 to 8 weeks after inhalation of the pathogenic mycobacteria. References: Leigh MW. Sarcoidosis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:2143-2144 Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med. 1997;336: 1224-1234 Critique 167. Preferred Response: D

[View Question] Intermittent oligoarthritis, especially in the lower extremities, night pain, and morning stiffness that is relieved by exercise, as experienced by the adolescent in the vignette, is characteristic of ankylosing spondylitis (AS). The findings on examination of his lumbar spine (flattening or loss of lumbar lordosis) also are classic for AS. Other associated signs of AS include hip and ankle arthritis and, occasionally, inflammation of the small joints of the feet. Localized tenderness also may be demonstrated at the insertion of the Achilles tendon or the plantar fascia. Although a history of low back or buttock pain should be sought, evidence of arthritis of the sacroiliac joints and spine may not be apparent for 5 to 10 years after onset. Extra-articular manifestations of AS are uncommon but include unilateral acute iritis, aortic valve insufficiency, and atlantoaxial subluxation. Confirmation of the diagnosis of AS by laboratory studies is difficult because many results are variable and nonspecific. The primary goal is to exclude other conditions that can mimic arthritis, such as sepsis, malignancy, and trauma. In a pediatric patient suspected of having AS, an erythrocyte sedimentation rate may be normal or elevated. The platelet count also may be elevated. Rheumatoid factor and antinuclear antibodies are universally absent. Results of human leukocyte antigen (HLA) studies are probably the most diagnostic because HLA-B27 is present in up to 90% of the AS population. Antistreptolysin O antibody titers are not elevated in patients who have AS. This test may be useful in the diagnosis of rheumatic fever. References: Cabral DA, Malleson PN, Petty RE. Spondyloarthropathies of childhood. Pediatr Clin North Am. 1995;42:1051-1070 Schaller JG. Juvenile rheumatoid arthritis. Pediatr Rev. 1997;18:337-349 Critique 193. Preferred Response: A

[View Question] The finding of 3+ leukocytes on urinalysis suggests a diagnosis of urethritis for the sexually active adolescent boy described in the vignette. Urethritis (Figure 193A) usually is categorized as gonococcal or nongonococcal. Pathogens causing nongonococcal urethritis include Chlamydia trachomatis, Ureaplasma urealyticum, and Trichomonas vaginalis. Mycoplasma genitalium and herpes simplex virus (HSV) also have been associated with urethral infections, but lesions such as ulcers or blisters frequently accompany HSV infections. In approximately 20% of cases of urethritis, the organism is unknown. Signs and symptoms of urethritis include dysuria, urinary frequency, and urethral discharge. Inflammation is confirmed by the presence of at least five polymorphonuclear leukocytes (PMNs) per high-power field on a Gram stain of a urethral smear or greater than

10 PMNs per high-power field in the centrifuged sediment of a first void urine. More specific tests may be undertaken to detect Neisseria gonorrhoeae and C trachomatis, although the presence of gram-negative intracellular diplococci in the urethral discharge supports the presumptive diagnosis of gonococcal urethritis. The absence of gram-negative intracellular diplococci with at least five PMNs per high-power field is indicative of nongonococcal urethritis. It is important to remember that in at least 50% of gonococcal infections, there is simultaneous infection with another sexually transmitted disease (STD) such as C trachomatis. The teenage boy described in the vignette displays some of the physical findings typical of Reiter syndrome, which is characterized by conjunctivitis, arthritis, nonbacterial urethritis or cervicitis, and mucocutaneous lesions. The mucocutaneous lesions include balanitis; painless ulcerations on the tongue, palate, pharynx, and buccal mucosa; onycholysis; and skin vesicles or papules that can mimic psoriasis (keratoderma blennorrhagicum). Although the exact etiology is unknown, Reiter syndrome is believed to occur as a result of an autoimmune response to an STD, most commonly C trachomatis or an enteric bacterial infection. Individuals who have human leukocyte antigen (HLA) B-27 are at increased risk of developing Reiter syndrome. Lymphadenitis, nephritis, pancreatitis, and pneumonitis are not present in patients who have Reiter syndrome, but may be associated with other arthritides. References: Lappa S, Moscicki AB. The pediatrician and the sexually active adolescent: a primer for sexually transmitted diseases. Pediatr Clin North Am. 1997;44:1405-1445 Neinstein LS. Reiters syndrome. In: Adolescent Health Care: A Practical Guide. 3rd ed. Baltimore, Md: Williams & Wilkins; 1996:606-609 Critique 210. Preferred Response: B

[View Question] Neonatal lupus erythematosus (NLE) is a rare disease caused by placental transfer of maternal immunoglobulin G autoantibodies. As many as 80% of mothers of infants who have NLE are asymptomatic; the remainder have been diagnosed as having systemic lupus erythematosus or another rheumatic disease. Maternal autoantibodies in infants who have NLE cause tissue damage that may affect the newborns heart, skin (Figure 210A), and liver. The major cause of morbidity and mortality is complete (third-degree) congenital heart block (CHB). CHB in NLE results from immune damage to the fetal cardiac conduction system and is associated with transplacental passage of maternal anti-Ro (SSA) and, occasionally, anti-LA (SSB) antibodies. CHB occurs in approximately 50% of infants who have NLE and, unlike other manifestations that resolve as maternal antibodies disappear, usually is permanent and complete. It may be asymptomatic or cause fetal bradycardia, intrauterine congestive heart failure, hydrops fetalis, or neonatal death. The infant who has CHB may require

pacemaker insertion, although death rates as high as 15% have been reported despite this intervention. Approximately 15% of infants who have NLE have hepatic involvement either alone or in association with cardiac, skin, or hematologic abnormalities. Typically, affected infants exhibit hepatomegaly, biochemical evidence of cholestasis, and possibly elevation of transaminases. Despite this, there do not appear to be long-term consequences of neonatal liver disease. Thrombocytopenia, occasionally accompanied by anemia or neutropenia, occurs in as many as 10% of affected infants. Platelet numbers generally normalize over the first few weeks of life, and treatment with high-dose corticosteroids only occasionally is required. An unusual complication caused by thrombocytopenia is intracerebral hemorrhage. Glomerulonephritis only rarely has been associated with NLE and is transient. References: McCauliffe DP. Neonatal lupus erythematosus. In: Harper J, Oranje A, Prose N, eds. Textbook of Pediatric Dermatology. Malden, Mass: Blackwell Science, Ltd; 2000:111-116 Rennebohm RM. Inflammatory noninfectious cardiovascular diseases. In: Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP, eds. Moss and Adams Heart Disease in Infants, Children, and Adolescents: Including the Fetus and Young Adult. 5th ed. Baltimore, Md: Williams & Wilkins; 1995:1441-1453 Silverman ED, Laxer RM. Neonatal lupus erythematosus. Rheum Dis Clin North Am. 1997;23:599-618 Critique 248. Preferred Response: B

[View Question] Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology that ultimately may result in multisystem organ dysfunction. Although SLE is more prevalent in adults, children may be affected. Females are affected more often than males. A diagnosis of SLE is based on the presence of at least four criteria, as defined by the American College of Rheumatology. SLE may begin insidiously or acutely. Typical clinical manifestations include fever, malaise, arthritis or arthralgia, and rash. As a vasculitic condition, SLE may affect any organ system. Although the symptoms resemble those of various autoimmune and infectious diseases, the diagnosis is clear when there are high serum levels of antinuclear antibody (ANA) and double-stranded DNA (dsDNA or antiDNA), as described for the girl in the vignette. Low serum C3 and C4 levels and elevated Smith antigen confirm the diagnosis. Any organ system may become inflamed in the patient who has SLE. For example, carditis, pleuritis, colitis, and nephritis are commonly observed in many affected patients. Studies show that two thirds of patients who have SLE will develop nephritis. The symptoms of SLE nephritis are similar to those observed in any nephritis and include hematuria, hypertension, edema, and possibly proteinuria. Urinalysis should be obtained for any child who has SLE on every visit to the physician. If red blood cells (RBCs) are detected, renal function should be evaluated completely, including lupus serologies and serum electrolytes.

If protein is detected in addition to RBCs, referral to a pediatric nephrologist is warranted because a child who has SLE and RBCs or protein in the urine requires a renal biopsy to stage the disease in the kidney. The World Health Organization has developed a classification of renal disease in patients who have SLE. Specifically, types III (focal proliferative glomerulonephritis) and IV (diffuse proliferative glomerulonephritis) indicate advanced renal disease and require aggressive therapy. The prognosis for patients who have SLE nephritis, even types III or IV, has improved remarkably with the advent of aggressive therapy with steroids and cytotoxic (cyclophosphamide) medications. Type II (mesangial SLE nephritis) and type V (membranous SLE nephritis) are more mild renal diseases but may, like types III and IV, eventually progress to end-stage renal disease. Children who have SLE must be followed closely by a team of physicians that includes a general pediatrician, pediatric rheumatologist, and if necessary, pediatric nephrologist. During visits, close attention should be paid to any symptoms indicating a lupus flare, including fever, malaise, arthritis, or rash. Regardless of the presence or absence of symptoms, frequent laboratory analysis of serum ANA, antiDNA, C3, and C4 are essential. A rise in ANA and antiDNA titer and fall in C3 and C4 levels are indicative of active and uncontrolled SLE. Conversely, normalization of C3 and C4 levels best indicates a good response to therapy. The prognosis for patients who have SLE has improved substantially with greater awareness of the symptoms and more aggressive treatment. Because SLE is a systemic vasculitis, many patients exhibit hypertension, which may be exacerbated by the use of steroids to treat SLE. Accordingly, normalization of blood pressure is not a good indicator of response to therapy. The hypertension may be recalcitrant to aggressive antihypertensive therapy, requiring multiple medications for adequate control. Severe hypertension may be an indication of either uncontrolled SLE or poor compliance. All patients who have SLE nephritis will exhibit RBCs and white blood cells in the urine. The quantity of RBCs in the urine has been shown to correlate with the severity of SLE nephritis, but neither a reduction in RBCs nor white blood cells indicates a treatment response. Serum ANA levels generally do decrease with clinical improvement, but because they are antibody tests, ANA levels can be falsely elevated in some other conditions (eg, syphilis). References: Cameron JS. Lupus nephritis in childhood and adolescence. Pediatr Nephrol. 1994;8:230-249 Garin EH, Donnelly WH, Fennell RS III, Richard GA. Nephritis in systemic lupus erythematosus in children. J Pediatr. 1976;89:366-371 Lehman TJ, Mouradian JA. Systemic lupus erythematosus. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology. 4th ed. Baltimore, Md: Lippincott, Williams & Wilkins; 1999:793-810 2001 Self-Assessment Exercise

XXI. Collagen vascular and other multisystem disorders [Return to Category List] Questions [Print Directions] Question 17. Answer.

A 3-year-old girl has a 2-week history of high, spiking fevers. Physical examination reveals bilateral conjunctivitis, cervical adenopathy, and superficial desquamation of her hands and feet. You suspect Kawasaki syndrome. Of the following, the laboratory finding that would be MOST likely in this girl is A. B. C. D. E. circulating anticoagulant microcytic anemia neutropenia positive antinuclear antibody thrombocytosis Answer.

Question 83.

A 4-year-old boy has a 1-month history of fevers to 39C (102.2F) twice a day accompanied by a rash. He feels well during his afebrile periods. Physical examination reveals generalized lymphadenopathy. Of the following, the MOST common other manifestation of this boy's illness would be A. B. C. D. E. iridocyclitis joint pain marked leukocytosis presence of antinuclear antibodies presence of rheumatoid factor

Question 164. Answer. A 7-year-old girl has a 2-month history of generalized weakness and a rash. Findings on physical examination include a violaceous discoloration of the malar regions, erythematous papules located over the interphalangeal joints, and nail fold telangiectasias. Proximal muscle strength is 3/5. Of the following, the MOST appropriate initial step in evaluating this patient's symptoms is to obtain a(n) A. antinuclear antibody titer

B. C. D. E.

creatine kinase concentration electromyogram magnetic resonance image of muscle muscle biopsy

Question 241. Answer. A preterm infant delivered at 32 weeks' gestation has thin, soft skin that is hyperextensible; hypermobile joints; and a cardiac murmur. Echocardiography reveals a floppy mitral valve. Of the following, the MOST likely etiology of these findings is A. B. C. D. E. cutis laxa Ehlers-Danlos syndrome homocystinuria Marfan syndrome osteogenesis imperfecta

Answers Critique 17. Preferred Response: E

[View Question] Thrombocytosis is one of the most common laboratory features of Kawasaki disease, but the platelet count usually is normal initially. By the fifth day of illness, 50% of patients have thrombocytosis, and by day 10, almost all have platelet counts reaching a peak of 650 to 2,000 x 109/L (650,000 to 2,000,000/mm3). The white blood cell count tends to be elevated, peaking at 7 to 12 days of the illness, with a predominance of segmented neutrophils and immature neutrophils. Mild-to-moderate normocytic anemia is common, but it does not differ from the anemia often seen during acute illnesses in children. Acute-phase reactants, including erythrocyte sedimentation rate, alpha-1antitrypsin, and C-reactive proteins, almost always are elevated early in the illness and may remain elevated for 4 to 6 weeks. However, antinuclear antibody, circulating anticoagulant, and rheumatoid factor are not present. Hepatic abnormalities are noted in 40% of patients; 10% of patients have a serum bilirubin greater than 34.2 mcmol/L (2 mg/dL) and an elevated direct fraction. Transaminases are moderately elevated to more than twice the normal limit in the first week of illness in 40% of patients. Hydrops of the gallbladder may be noted. Cerebrospinal fluid pleocytosis is found in approximately 25% of patients, with a typical mononuclear cell count of 50 to 150 x 106/L (50 to 150/mm3). Protein levels usually are normal to slightly elevated, while glucose levels are normal.

Sterile pyuria is found in approximately 60% of patients. Some red blood cells may be present in the urine, but protein is not. Arthritis also can develop in patients who have Kawasaki disease, with synovial fluid white blood cell counts frequently greater than 100 x 106/L (100,000/mm3), low glucose concentrations, and increased protein levels. However, arthritis has become much less common with the use of intravenous gamma globulin therapy. All of these laboratory studies are employed simply to provide support for a clinical diagnosis. There is no specific diagnostic laboratory test for Kawasaki disease. The single critical study for suspected Kawasaki disease is two-dimensional echocardiography, which is required to monitor the development of coronary artery abnormalities. This should be performed at the time of diagnosis, at 2 to 3 weeks, and at 6 to 8 weeks after the onset of the illness. If abnormalities are not detected by this time, additional follow-up studies are optional. Some centers obtain routine follow-up echocardiograms 1 year later, but their usefulness has not been proven. If abnormalities are detected, more frequent studies and monitoring in consultation with a pediatric cardiologist are recommended. References: Melish ME. Kawasaki syndrome. Pediatr Rev. 1996;17:153-162 Rowley AH, Shulman ST. Kawasaki disease. In: Behrman RE, Kliegman RM, Nelson WE, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:725-726 Critique 83. Preferred Response: C

[View Question] The patient described in the vignette has the early symptoms of systemic juvenile rheumatoid arthritis (JRA). Leukocytosis is common in children who have systemic JRA, and strikingly high counts (30 to 50 x 109/L [30,000 to 50,000/mm3]) may occur. Systemic symptoms can begin concurrently with arthritis or may precede joint involvement by several months. Joint symptoms (Figure 83A) commonly are overlooked because of the severity of systemic symptoms. High fevers often occur several times a day in an ill-appearing child and can reach or exceed 39C (102.2F). They are followed by a rapid return to normal temperatures. Patients usually experience one or two high-fever spikes per day. The fevers are more frequent in the evening, but can occur in the morning. Concurrent symptoms include shaking chills and a rash. The rash usually is apparent when the patient has a fever, but it can appear after defervescence. It consists of small, pale red macules that often have central clearing and may coalesce. This evanescent rash can occur anywhere on the body but is found most frequently on the trunk and proximal extremities. Although it appears most commonly during the febrile periods, heat, pressure, and emotions also can trigger it.

Patients who have systemic JRA also frequently present with lymphadenopathy and hepatosplenomegaly. The hepatosplenomegaly may be associated with mild hepatic dysfunction. Such findings can confuse the diagnosis with malignancies such as lymphoma. Other common characteristics of systemic JRA include severe anemia, abdominal pain, pleuritis, or pericarditis. Iridocyclitis is not a common finding in systemic JRA, and affected patients have no evidence of rheumatoid factor or antinuclear antibodies. These findings are seen more commonly in young girls presenting at a later age with pauciarticular arthritis. A few patients who have systemic JRA do not develop arthritis until months or years after the onset of systemic symptoms. Usually systemic symptoms are self-limited, but occasionally there may be recurrences. Such recurrences are rare after the patient reaches adulthood, but the chronic arthritis may persist. The significant morbidity suffered by these patients is due to chronic joint symptoms. References: Miller ML, Cassidy JT. Juvenile rheumatoid arthritis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:704-709 Schaller JG. Juvenile rheumatoid arthritis. Pediatr Rev. 1997;18:337-349 Critique 164. Preferred Response: B

[View Question] Characteristic cutaneous abnormalities (eg, heliotrope [Figure 164A], Gottron papules [Figure 164B], nail fold telangiectasias) and proximal muscle weakness described for the girl in the vignette are suggestive of dermatomyositis. In addition to skin lesions and muscle weakness, other diagnostic criteria are elevation of serum muscle enzyme concentrations, electromyographic (EMG) findings consistent with a myopathy, and typical findings on muscle biopsy. Diagnosis is considered definite when four criteria are present, probable in the presence of three, and possible when two criteria exist. Characteristic skin changes always must be present for diagnosis. The most appropriate initial step in the evaluation of a child suspected of having dermatomyositis is to measure levels of enzymes that are released as a result of muscle injury. The most sensitive indicator of disease activity is creatine kinase, but because muscle enzyme levels may be variably elevated, it also is useful to measure aldolase, aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase. Low-titer serum antinuclear antibody levels are common in dermatomyositis, but this is a nonspecific finding. Although an EMG study will reveal membrane instability and random fiber destruction in a child who has dermatomyositis, it is a painful procedure and rarely performed in children. Magnetic resonance imaging is an alternative study that can be used to confirm the diagnosis and to select appropriate sites for muscle biopsy, but it is not an appropriate initial diagnostic examination. During disease activity, the signal intensity on T1-weighted images of involved muscles is increased because of accumulated extracellular

fluid. The signals return to normal with suppression of disease activity. Muscle biopsy is useful if skin changes are not typical and muscle enzymes are not clearly elevated. Characteristic findings include evidence of vasculitis, inflammatory cell infiltrates, focal necrosis and phagocytosis of muscle fibers, and regeneration. References: Kovacs SO, Kovacs SC. Dermatomyositis. J Am Acad Dermatol. 1998;39:899-922 Pachman LM. Juvenile dermatomyositis. Pathophysiology and disease expression. Pediatr Clin North Am. 1995;42:1071-1098 Sills EM, Barnett NK, Provost TT. Connective tissue diseases and arthritides. In: Schachner LA, Hansen RC, eds. Pediatric Dermatology. 2nd ed. New York, NY: Churchill Livingstone; 1995:1119-1124 Critique 241. Preferred Response: B

[View Question] Infants who have Ehlers-Danlos syndrome type I, an autosomal dominant (AD) disorder, exhibit velvety, hyperextensible skin (Figure 241A); joint hypermobility that can lead to dislocation of the shoulder, hip, elbow, knee, or clavicle; easy bruisability; and cardiac abnormalities (eg, mitral valve prolapse). Delayed wound healing and prolonged bleeding due to blood vessel friability are also common. The pregnancy is often complicated by premature rupture of the membranes. Affected women are predisposed to postpartum hemorrhage, and all affected patients must be aware of the increased risk for prolonged bleeding after trauma or any surgical procedure. There is wide variability in the expression of the disease, with mildly and severely affected patients appearing in the same family. In addition to type I disease, nine other forms of Ehlers-Danlos syndrome have been delineated (Table). Neonatal Marfan syndrome is more severe than cases observed in older children and usually presents with congenital contractures and severe cardiac disease, including valval regurgitation and aortic root dilation. Clinical features include high palate, chest deformities, and dislocated lenses. Cutis laxa is a rare disorder in which the skin appears to be too large and tends to sag. However, the skin is not hyperextensible, and joint laxity is not a feature. Homocystinuria is an inborn error of metabolism that results from decreased cystathionine synthetase activity. Untreated neonates may develop seizures, developmental delay, or thromboembolus later in infancy or in childhood. Osteogenesis imperfecta is a connective tissue disorder that occurs in several forms. The infantile presentation of the disease includes congenital fractures, but there are no skin changes. References: Byers PH. Disorders of collagen biosynthesis and structure. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw Information Services Co; 1995:4029-4078

Robinson LK. Marfan syndrome. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: WB Saunders Co; 2000:2131-2132 Yeowell HN, Pinnell SR. The Ehlers-Danlos syndromes. Semin Dermatol. 1993;12:229-240 2000 Self-Assessment Exercise XXI. Collagen vascular and other multisystem disorders [Return to Category List] Questions [Print Directions] Question 47. Answer.

A 16-year-old girl who has systemic lupus erythematosus develops pain and swelling in the left lower leg followed within 24 hours by tachypnea. Findings on physical examination are normal except for a malar butterfly rash, swelling of the left calf, and pain on dorsiflexion of the left foot that has been present for several months. Of the following, the MOST likely etiology of these symptoms is A. B. C. D. E. disseminated intravascular coagulation immune thrombocytopenic purpura myositis thromboembolic disease vasculitis

Question 126. Answer. A 16-year-old girl presents with fatigue, myalgia, and joint swelling. Laboratory evaluation reveals: hemoglobin, 8 g/dL; creatinine, 1.5 mg/dL; C3 complement, 25 mg/dL (normal, >80 mg/dL); antinuclear antibody titer, 1:3,200; anti-DNA titer (double-strand), 1:320; antineutrophil cytoplasmic antibodies, negative; and urinalysis, red blood cells, >100/highpower field and urine protein, 300 mg/dL. Of the following, the MOST likely explanation for these findings is A. B. C. D. E. giant cell (Takayasu) arteritis Henoch-Schnlein purpura polyarteritis nodosa systemic lupus erythematosus Wegener granulomatosis

Question 206. Answer.

A healthy 14-year-old girl is worried about an area of skin thickening, tightness, and discoloration that developed about 3 months ago. There is no history of trauma to the area, and there are no associated symptoms. Physical examination reveals a shiny, hypopigmented patch with a brown border. The affected skin is immobile, firm, and has a bound-down feeling. Of the following, the MOST likely explanation for these findings is A. B. C. D. E. lichen sclerosus et atrophicus linear scleroderma postinflammatory hypopigmentation progressive systemic sclerosis vitiligo

Answers Critique 47 Preferred Response: D

[View Question] Systemic lupus erythematosus (SLE) is associated with many hematologic complications, including an increased risk of thromboembolic disease. The so-called lupus anticoagulant complicates the course of 10% to 20% of affected patients. This phenomenon is described more accurately as a circulating, antiphospholipid antibody that inhibits the effectiveness of phospholipid-protein complexes, which play an important cofactor role in coagulation. It should be noted that many disorders other than SLE are associated with these anticoagulants, and in children they probably are associated most often with viral illnesses. These antiphospholipid antibodies prolong the activated partial thromboplastin time (PTT) and inhibit the ability of normal plasma to correct the prolonged PTT in the laboratory. In spite of what would appear to be a hemorrhagic effect, patients who have these antibodies are at increased risk for venous or arterial thromboses. Affected patients do not demonstrate excessive bleeding unless there is associated thrombocytopenia or acquired factor II (prothrombin) deficiency. Antiphospholipid antibodies are detected best using a series of specifically designed clotting tests and by identifying the anticardiolipin antibodies usually found in these patients. Antibody cross-reactivity is responsible for the false-positive serology test for syphilis (VDRL) in patients who have SLE. Children who have SLE and demonstrate persistence of a lupus anticoagulant have a 16- to 25-fold greater risk of thromboembolic events compared with those lacking the anticoagulant. The differential diagnosis of thromboembolus in patients who have SLE includes vasculitis and myositis, which are less localized and not associated with a palpably thrombosed vein. Venous Doppler studies will distinguish between these conditions.

Immune thrombocytopenia is common among patients who have SLE, but it usually does not cause deep hematomas that would result in pain and swelling. However, patients who have chronic immune thrombocytopenic purpura without lupus also have an increased incidence of antiphospholipid antibodies. Disseminated intravascular coagulation rarely occurs in patients who have SLE and usually is associated with cutaneous and mucous membrane bleeding rather than a hematoma. The most common hematologic manifestation of SLE is anemia, which is seen in 50% of children. It usually is due to the chronic inflammatory disease, but autoimmune hemolytic anemia may be present in approximately 10% of patients. Other hematologic manifestations include leukopenia, immune thrombocytopenia, and a variety of inhibitors to specific coagulation factors, which occasionally can result in bleeding. References: Andrew M, Montgomery RR. Acquired disorders of hemostasis. In: Nathan DG, Orkin SH, eds. Nathan and Oski's Hematology of Infancy and Childhood. 5th ed. Philadelphia, Pa: WB Saunders Co; 1998:1696-1697 Lang BA, Silverman ED. A clinical overview of systemic lupus erythematosus in childhood. Pediatr Rev. 1993;14:194-201 Lascari AD. Cardiac diseases. Hematologic Manifestations of Childhood Diseases. New York, NY: Thieme-Stratton, Inc; 1984:106-109 Critique 126 Preferred Response: D

[View Question] Systemic lupus erythematosus (SLE) is an immunologic form of vasculitis that predominantly affects females in a ratio of 3:1 among children and 9:1 among adults. The annual incidence of SLE in childhood is estimated to be 0.6 per 100,000 population. In Caucasians, there is a higher association with the histocompatibility grouping A1B8DRw3. There also is a higher frequency of the disease among Hispanics, Asians, and African-Americans. Several inherited defects of the immune system have been reported to predispose to SLE, including defects in complement production and immunoglobulin A deficiency. However, the hallmark of active SLE is increased activity of the immune system. The etiology of this hyperactivity is unknown. A child who has SLE may present with symptoms related to any organ system. Hematuria, proteinuria, and hypertension are the most common renal manifestations. Approximately two thirds of affected patients have renal involvement, which ranges from minimal pathologic findings to severe diffuse proliferation with crescents. Other symptoms include a butterfly malar rash; arthralgia and arthritis; pallor; hemorrhage; neurologic symptoms (eg, paresthesias); cardiac symptoms due to valvulitis (Libman-Sacks valvulitis), pericarditis, and myocarditis; pleurisy and pleural effusions; hepatomegaly and splenomegaly; and photosensitivity.

The laboratory manifestations of SLE are as varied as its clinical presentations. Hypocomplementemia, with low concentrations of both C3 and C4, is common, particularly during episodes of disease activity. A positive antinuclear antibody titer supports the diagnosis of SLE and is present in more than 90% of cases. However, elevated titers of antinuclear antibody also can be present in patients who have juvenile rheumatoid arthritis and Lyme disease. Antibodies directed to the double-strand DNA, as described for the girl in the vignette, commonly are considered specific for active SLE. A definitive diagnosis of SLE in a child or adolescent requires fulfilling four of the 11 revised criteria of the American Rheumatism Association. These criteria are summarized by a mnemonic SOAP BRAIN MD (Table). In patients who have active SLE, aggressive treatment with steroids is indicated. Some children require the administration of intravenous alkylating agents, cyclosporine, and other cytotoxic medications. Plasmapheresis is reserved for children who have severe neurologic involvement. Giant cell (Takayasu) arteritis is caused by segmental inflammation of the arteries that results in aneurysms and stenosis of large muscular arteries, especially the aorta and its major branches. It is relatively uncommon in North America and Europe, although it is the third most common form of vasculitis (after Henoch-Schnlein purpura and Kawasaki disease) worldwide. Manifestations include fever, night sweats, anorexia, weight loss, and arthritis. Hypertension or congestive heart failure associated with pulse deficits may be noted. Laboratory evaluation reveals increased sedimentation rate, weakly positive antinuclear antibody titer, and antiaorta antibodies. Magnetic resonance angiography or standard angiography is needed to demonstrate the defects. Treatment includes the administration of steroids and other cytotoxic medications, antiplatelet agents, and in some cases, reconstructive surgery when the disease is inactive. Henoch-Schnlein purpura (HSP), the most common form of vasculitis in childhood, involves the small blood vessels. It occurs more commonly in children during the first decade of life. The salient features are purpura in the absence of thrombocytopenia, arthritis or arthralgia, and abdominal pain. The purpura is most prominent on the shins, back of the thighs, and the buttocks. Toddlers may have swelling of the dorsum of the feet and hands as well as the scalp; the rash may involve the face in this age group. More than 50% of affected children have glomerulonephritis, and 10% may have serious renal complications, including nephrotic syndrome, hypertension, crescentic glomerulonephritis, and renal failure. In children who have HSP, negative antinuclear antibody and anti-DNA (double-strand) titers and normal complement levels are typical. The concentration of immunoglobulin A is elevated in 40% to 50% of affected patients. Treatment with corticosteroids is reserved for those patients who have complicated HSP nephritis or severe gastrointestinal involvement. Polyarteritis nodosa (PAN) is a vasculitis that may affect medium-sized (macroscopic PAN) or small-sized (microscopic PAN) arteries. In patients who have macroscopic PAN, the primary clinical findings at the time of presentation include malaise, fever, rash, abdominal pain, and arthropathy. Myalgia, ischemic heart pain, testicular pain, neurologic symptoms, hematuria, hypertension, and organic psychosis also have been reported. In the microscopic form of the disease, hypertension is the prominent feature, and this usually is associated

with hematuria and proteinuria. Involvement of the eyes, skin, gut, nervous system, and lungs has been reported. The diagnosis of PAN depends on demonstrating the small-vessel vasculitis in the kidney or any other organ, which can be accomplished by angiography. Patients have an elevated sedimentation rate, increased levels of C-reactive protein, anemia, leukocytosis, thrombocytosis, and abnormal urinary findings. Antineutrophil cytoplasmic antibodies (ANCA) with peripheral staining (p-ANCA) are positive and directed against neutrophil granule myeloperoxidase. Central staining ANCA (c-ANCA) titers usually are negative. Complement levels are normal, and antinuclear antibody titers generally are not detectable. Treatment of PAN involves the administration of corticosteroids and cytotoxic agents. Wegener granulomatosis is a necrotizing granulomatous vasculitis of the upper and lower respiratory tract that is associated with glomerulonephritis and systemic small-vessel vasculitis. The presence of a triad of symptoms, including sinusitis, pulmonary involvement (eg, hemoptysis), and glomerulonephritis (eg, hematuria, proteinuria), suggests the diagnosis. Biopsy of involved tissue, particularly the kidney, usually confirms the diagnosis. In addition, most patients have high c-ANCA titers. Treatment involves aggressive use of corticosteroids and cyclophosphamide. References: Cameron JS. Lupus nephritis in childhood and adolescence. Pediatr Nephrol. 1994;8:230-249 Dillon MJ. Vasculitis. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology. 4th ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:779-792 Lang BA, Silverman ED. A clinical overview of systemic lupus erythematosus in childhood. Pediatr Rev. 1993; 14:194-201 Yang LY, Chen WP, Lin CY. Lupus nephritis in children-a review of 167 patients. Pediatrics. 1994;94: 335-340 Critique 206 Preferred Response: B

[View Question] Scleroderma is a rare connective tissue disorder that is believed to have an autoimmune etiology. It may be separated into localized and systemic forms. Localized scleroderma is more common than the systemic type. Lesions of localized scleroderma begin as areas of indurated skin surrounded by a violaceous halo. Over time, the violaceous color is lost and the skin takes on a waxy, ivory appearance. As the disease remits, the skin becomes atrophic and hypo- or hyperpigmented. Localized scleroderma may occur in three clinical patterns: linear scleroderma, morphea, and generalized morphea. In linear scleroderma, as exhibited by the patient described in the vignette, lesions develop in a band-like distribution, typically are unilateral, and usually involve the extremities, although the face and trunk may be affected. Lesions may span joints, resulting in diminished range of motion or deformity, and may extend to soft tissue, muscle, or bone. In morphea, one or two lesions are present,

often located on the trunk. Generalized morphea is characterized by the presence of widespread or coalescent lesions. In most instances, localized scleroderma is self-limited, with disease activity lasting an average of 3 to 5 years. Although the disease eventually remits, there may be considerable morbidity, particularly when the face is involved or joint function is compromised. Fortunately, it is very rare for localized scleroderma to progress to a systemic form. The treatment of localized scleroderma is unsatisfactory; no therapy is curative. Topical or intralesional corticosteroids or topical calcipotriene may halt the progression of expanding lesions that are characterized by an erythematous border. Emollients are helpful in relieving dryness or pruritus of affected areas. When sclerotic skin overlies joints, physical therapy is indicated to preserve mobility and prevent contractures. Severe, widespread, or progressive disease may require a more aggressive therapeutic approach. Agents that have been employed with variable success include penicillamine, hydroxychloroquine, chloroquine, systemic corticosteroids, methotrexate, and phenytoin. A number of dermatologic disorders are characterized by hypopigmentation, but do not present with the thickening or sclerosis seen in scleroderma. Lichen sclerosus et atrophicus produces hypopigmented areas that are atrophic, not sclerotic. In children, the lesions often are located on the genitalia where they may become eroded and cause pruritus or dysuria. Disorders characterized by inflammation, such as atopic dermatitis, can cause hypopigmentation. Affected areas are flat, exhibit reduced pigment, and have indistinct borders. In contrast, the lesions of vitiligo lack any pigment and, therefore, are completely white and sharply demarcated. Systemic sclerosis is very rare in children. Most affected individuals experience tightening of the skin overlying the digits or Raynaud phenomenon, not the focal cutaneous involvement characteristic of localized scleroderma. In addition, there may be involvement of multiple organ systems (eg, gastrointestinal, musculoskeletal, cardiac, pulmonary, and renal). References: Black CM. Scleroderma and fasciitis in children. Curr Opin Rheumatol. 1995;7:442-448 Cunningham BB, Landells ID, Langman C, Sailer DE, Paller AS. Topical calcipotriene for morphea/linear scleroderma. J Am Acad Dermatol. 1998;39:211-215 Haber PL. Clinical manifestations of scleroderma. Pediatr Rev. 1995;16:49 Nelson AM. Localized scleroderma including morphea, linear scleroderma, and eosinophilic fasciitis. Curr Probl Pediatr. 1996;26:318-324 Uziel Y, Miller ML, Laxer RM. Scleroderma in children. Pediatr Clin North Am. 1995;42:11711203 1999 Self-Assessment Exercise

XXI. Collagen vascular and other multisystem disorders [Return to Category List] Questions [Print Directions] Question 24. Answer.

A 14-year-old girl who has juvenile rheumatoid arthritis complains of substernal chest discomfort and light-headedness with standing. Recently her prednisone dosing was tapered from daily to every other day. Findings include: visible jugular pulsations while sitting, decrease in brachial pulse intensity with each inspiration, and distant heart sounds, but no murmurs or rubs. Radiography shows a greatly enlarged cardiac silhouette. The most appropriate INITIAL step is to A. B. C. D. E. administer high-dose corticosteroids intravenously administer methotrexate intravenously obtain computed tomography of the chest obtain electrocardiography perform pericardiocentesis Answer.

Question 83.

An 18-month-old boy treated 6 days ago with amoxicillin for otitis media returns today with a persistent daily fever of at least 39.8C (103.6F). Physical examination reveals a listless child who has a maculopapular rash over the trunk, injected sclera, and dry and fissured lips. The palms of his hands and fingertips are indurated and erythematous. Of the following, the MOST likely diagnosis is A. B. C. D. E. drug reaction juvenile rheumatoid arthritis Kawasaki syndrome measles scarlet fever

Question 141. Answer. A 14-year-old boy is referred for evaluation of a heart murmur noted on a sports preparticipation physical. Physical examination reveals a very tall and thin boy who has a pectus excavatum deformity of the chest, hyperextensible joints, and an apical pansystolic cardiac murmur with mid-diastolic rumble.

The MOST helpful diagnostic evaluation to determine the etiology of these findings is A. B. C. D. E. electromyography studies magnetic resonance imaging of the spine and sternum measurement of plasma amino acid concentrations skeletal survey slitlamp ophthalmologic examination

Question 204. Answer. A female infant was delivered at 34 weeks gestation because of progressive hydrops to a 34-year-old woman who has had two previous miscarriages. A persistent fetal bradyarrhythmia had been noted at 28 weeks gestation. Of the following, the laboratory test that would be MOST useful in confirming a diagnosis of neonatal lupus is A. B. C. D. E. antinuclear antibody test anti-Ro/SS-A and anti-La/SS-B antibodies human lymphocyte antigens quantitative immunoglobulins serum complement level

Question 240. Answer. A 9-year-old girl is noted to have a linear fibrotic hyperpigmented plaque extending down the posterior aspect of her left leg from her thigh to her knee. The lesion has been stable for 6 months. A skin biopsy confirms your clinical diagnosis of linear morphea, a linear variant of localized scleroderma. Of the following, the MOST appropriate management is to A. B. C. D. E. administer a tapering course of oral corticosteroids to soften the cutaneous lesion initiate oral penicillamine therapy to prevent progression to systemic disease observe the lesion and consider photo-chemotherapy if it progresses refer the girl to physical therapy to prevent contracture formation refer the girl to plastic surgery for repair of the cutaneous defect

Answers Critique 24 Preferred Response: E

[View Question] Pericarditis with sterile pericardial effusion is a welldescribed complication of juvenile rheumatoid arthritis (JRA). Patients who have JRA are likely to complain of pericarditic chest pains as the only symptom of pericarditis. The chest pains of pericarditis are different from benign chest pains of childhood and adolescence. Pericarditis pain often is nagging and present for most of the day over a period of days. It may worsen in the supine position. In contrast, benign chest pains usually last seconds to minutes, are intermittent, and often appear at infrequent intervals for weeks or months. The development of cardiac tamponade from a large pericardial effusion is rare in patients who have JRA. It is more commonly a presenting problem in children or adolescents who have systemic lupus erythematosus. The findings of jugular venous pulse distension and marked decrease in the strength of the brachial arterial pulse during each inspiration (pulsus paradoxus) in the girl described in the vignette are diagnostic of tamponade. Its presence necessitates immediate pericardiocentesis. Echocardiographic guidance of pericardiocentesis is useful, but there is no need for a strictly diagnostic echocardiographic study because the diagnosis of cardiac tamponade already is obvious. Similarly, computed tomography of the chest would be diagnostic, but could delay appropriate therapy. Typical electrocardiographic findings of diffuse S-T elevation are not present in all patients who have pericarditis. In patients who have JRA, pericarditis may develop more frequently when their dosage of antiinflammatory medications is tapered or stopped, such as the girl described in the vignette. A small or moderate effusion that is diagnosed by echocardiography obtained in response to chest pain or pericardial rub on examination may resolve with treatment with antiinflammatory drugs (eg, corticosteroids, methotrexate). However, such pharmacologic therapy would not provide immediate relief of such symptoms of tamponade as described in the vignette. Reference: Rennebohm RM. Inflammatory "noninfectious" cardiovascular diseases. In: Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP, eds. Moss and Adams Heart Disease in Infants, Children, and Adolescents. 5th ed. Baltimore, Md: Williams & Wilkins; 1995:14411452 Critique 83 Preferred Response: C

[View Question] The toddler described in the vignette not only has failed to respond to the amoxicillin, but his condition has worsened, with the additional signs and symptoms of a truncal rash, conjunctivitis, and red, indurated palms. These findings suggest that his illness is more than otitis unresponsive to current therapy. Rather, these symptoms and signs are consistent with Kawasaki syndrome (KS). No etiologic agent has been identified for this disease, so the diagnosis is made clinically by finding at least five of six established criteria:

Fever (>40C [>104F]) for 5 days or longer Bilateral nonexudative conjunctivitis Acute cervical lymphadenopathy Fissured, dry, and swollen lips

Erythema and induration of the palms and soles, later developing into a desquamation extending from the fingertips to proximal surfaces of hands Polymorphic, erythematous, maculopapular eruption on the trunk

The child described in the vignette exhibits five of these criteria. In addition to the physical findings listed, children who have KS may exhibit an intensely red perineal rash that also desquamates. Other findings include pneumonia, diarrhea, photophobia, aseptic meningitis, and carditis. Drug reactions to the penicillin class of drugs can result in maculopapular rashes over the trunk and extremities and swollen joints. However, neither fevers in the range of 39.8C (103.6F) nor indurated red palms are typical of the hypersensitivity reaction to amoxicillin. Juvenile rheumatoid arthritis (JRA), particularly the systemic type, should be considered in a toddler who presents with high fever and rash, but the pattern of symptoms described in the vignette is more acute than what usually develops in these patients. The fevers in JRA usually occur over several weeks, with an evanescent, reticular rash appearing when the fever is at its peak. Other findings associated with JRA include arthritis, hepatosplenomegaly, lymphadenopathy, pleural effusions, and cardiomegaly. Nonexudative conjunctivitis, fissured lips, and induration of the palms are not associated with this disease. Measles is an infrequent diagnosis in the United States today, but it is not unusual in individuals from countries where the vaccine is not administered routinely. It has been estimated that more than 1 million deaths occur annually in developing countries from measles and its complications. Initially, the patient exhibits fever, coryza, and exudative conjunctivitis. A macular rash develops approximately 4 days later. It begins along the hairline, extends down the neck, and spreads over the extremities and trunk in the next 24 hours. In contrast, the rash described in the vignette is distributed over the trunk only without evidence of this progression. The rash of scarlet fever is fine and sandpaper-like, and it is caused by a group A beta-hemolytic streptococcal infection. The rash is distributed diffusely over the body, although it may be more prominent in the flexural areas, such as the antecubital fossa and groin. The nonexudative conjunctivitis and induration of the extremities in the child described in the vignette are not typical of scarlet fever. References: Harville TO. Kawasaki disease. In: Rudolph AM, ed. Rudolph's Pediatrics. 20th ed. Stamford, Conn: Appleton & Lange; 1996:495-497

Melish ME. Kawasaki syndrome. Pediatrics in Review. 1996;17:153-162 Pichichero ME. Group A beta-hemolytic streptococcal infections. Pediatrics in Review. 1998;19:291-302 Schaller JG. Juvenile rheumatoid arthritis. Pediatrics in Review. 1997;18:337-349 Critique 141 Preferred Response: E

[View Question] Marfan syndrome is an autosomal dominant disorder that results from mutations in the fibrillin gene and is characterized by the development of skeletal, cardiac, and ocular symptoms. The musculoskeletal abnormalities include tall stature, pectus deformity of the chest, scoliosis, a high arched palate and dental crowding, hyperextensible joints, pes planus, and arachnodactyly. Cardiac findings can include murmurs associated with aortic regurgitation, mitral valve prolapse, and mitral regurgitation; prolapse and regurgitation of the mitral valve also may occur concomitantly. Affected patients are at risk for dilatation of the ascending aorta and aortic rupture beginning in childhood. The diagnosis of Marfan syndrome requires the presence of a major feature in at least two organ systems and involvement of a third organ system. The patient described in the vignette has both skeletal and cardiac features evident on physical examination that warrant further assessment by careful cardiac evaluation, including echocardiography and electrocardiography. In addition, an ophthalmologic examination should be undertaken to search for ectopia lentis (displacement of the lens of the eye). The latter is a major feature of the disorder that is present in up to 60% of affected individuals. When the diagnosis of Marfan syndrome is confirmed, both parents should be examined to determine if they are affected. Marked inter- and intrafamily variation in clinical severity of the syndrome has been noted. Approximately 15% of patients who have Marfan syndrome represent a new mutation; many of these new mutations occur in offspring of older men, a phenomenon that has been observed in other autosomal dominant disorders. For some families, prenatal and presymptomatic molecular diagnosis can be made either by the direct detection of mutations in the fibrillin of the gene or by linkage analysis (when the mutation is unknown). Individuals who have Marfan syndrome require careful ongoing monitoring and symptomatic care to minimize morbidity and mortality. Scoliosis of greater than 10 degrees should be treated aggressively, and all patients require careful monitoring of their cardiac status. Beta-adrenergic blockers are recommended to prevent severe aortic complications; in some cases, surgical correction of the proximal aorta and aortic valve may be required. For women, an additional concern is the increased risk of aortic dissection during pregnancy, presumably due to increased blood volume and cardiac output. Results of electromyography studies usually are normal in affected patients, but they would be helpful in those suspected of having myotonic dystrophy. Although patients who have this disorder occasionally have a marfanoid habitus and myopathic facies, they should exhibit the neurologic findings of myotonia. Magnetic resonance imaging of the spine

and sternum is not essential for making the diagnosis of Marfan syndrome, although in some patients who report back pain, it may reveal dural ectasia (outpouching of the dura mater). Similarly, a skeletal survey is not necessary to confirm the diagnosis, although in some instances hand radiography may be useful to document arachnodactyly. Measurement of plasma amino acid concentrations would be useful in differentiating Marfan syndrome from homocystinuria, a disorder that has similar skeletal and ocular features, but not the cardiac findings, found in Marfan syndrome. References: Beighton P. McKusick's Heritable Disorders of Connective Tissue. 5th ed. St Louis, Mo: Mosby-Year Book, Inc; 1993 Jones KL. Marfan syndrome. In: Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, Pa: WB Saunders Co; 1997:472-473 Critique 204 Preferred Response: B

[View Question] Nonimmune hydrops fetalis is a rare disease of multiple causes, which include fetal cardiac arrhythmia. Congenital heart block is recognized increasingly in the offspring of mothers who have systemic lupus erythematosus (SLE) and may result in congestive cardiac failure and hydrops in the affected fetus. The infant described in the vignette has been delivered prematurely at 34 weeks' gestation because of progressive hydrops. The history of persistent fetal bradyarrhythmia noted at 28 weeks' gestation suggests the possibility of congenital heart block as a cause of hydrops. The history of two previous miscarriages in the 34-year-old mother is consistent with a diagnosis of maternal SLE. SLE is an autoimmune disease that has a wide spectrum of clinical manifestations in children and adolescents. The primary problem is persistent nonspecific activation of polyclonal B cells that results in widespread tissue deposition of immune complexes. The nature of the immune complexes and the location of their deposition are determined by genetic factors and previous environmental exposures. Thus, no two patients have an identical pattern of immune complexes or clinical expression of disease. Primary SLE in the newborn is extremely rare. Transient SLE has been reported in infants of mothers who have SLE, and this is caused by the transplacental passage of maternal antinuclear antibodies. In adulthood, there is a marked female predominance of SLE, with a female-to-male ratio of 9:1, compared with a 2:1 ratio in neonates. Transient neonatal SLE is characterized by a scaly, erythematous rash involving the face, particularly the periorbital area, the trunk, and the upper extremities. The rash commonly resolves by 6 months of age, but may leave residual skin atrophy and telangiectasis. Hematologic abnormalities (eg, hemolytic anemia, leukopenia, thrombocytopenia) are seen in 10% of cases. Hepatosplenomegaly and pericarditis are less frequent manifestations of transient neonatal SLE.

Antibodies directed against the nuclear antigens Ro (SSA) and La (SSB) have been associated with transient neonatal SLE, particularly in infants who have congenital heart block. The cause of the heart block is thought to be damage caused by deposition of immune complexes in the connective tissue of the conduction system. Antinuclear antibody (ANA) testing is a useful screening test for patients who are suspected of having SLE. However, although this test has a high sensitivity (ie, the vast majority of children who have SLE are ANA-positive), it has poor specificity (ie, the vast majority of ANA-positive children do not have SLE). Human lymphocyte antigens and quantitative immunoglobulins are nonspecific markers of autoimmune disease. Decreased levels of serum complement may be seen in patients who have active SLE, but most children, including neonates, who have mild or transient SLE do not exhibit decreased levels of serum complement. References: Lehman TJ. A practical guide to systemic lupus erythematosus. Pediatr Clin North Am. 1995;42:1223-1238 Sher MR. Neonatal systemic lupus erythematosus (NSLE). In: Taeusch HW, Ballard RA, Avery ME, eds. Schaffer & Avery's Diseases of the Newborn. 6th ed. Philadelphia, Pa: WB Saunders Co; 1991:829-830 Critique 240 Preferred Response: C

[View Question] The child described in the vignette has linear morphea, a linear variant of localized scleroderma that is the most common form of this connective tissue disorder in children. In morphea, lesions are restricted to the skin and subcutaneous tissue, with only occasional involvement of underlying bony structures. Morphea typically begins insidiously as a linear hyperpigmented patch that becomes progressively fibrotic. Children complain of skin tightness, and contractures may form when the lesion crosses joints, resulting in a decreased range of motion. Fortunately, most cases of linear morphea are self-limiting, but pigmentary changes, fibrosis, and atrophy may persist indefinitely. No treatment has been shown in controlled studies to shorten the course of the disease or decrease the risk of complications. Accordingly, management usually is limited to careful observation and administration of topical lubricants to address associated dryness and itching. In some patients, pigmentary changes and fibrosis may improve with photochemotherapy (PUVA). Surgical intervention usually is not necessary, and some reports even have suggested that surgery can reactivate disease. Those who do have contractures respond well to splinting and physical therapy. The girl in described the vignette, however, does not have any contractures. Rarely, children who have morphea may develop extensive, progressive, disfiguring plaques on the face, trunk, or extremities. Complications can include visual impairment,

cranial nerve palsies, and seizures. Anecdotal reports have suggested that the administration of such drugs as corticosteroids, methotrexate, cyclophosphamide, and penicillamine may help with such plaques. However, these should be used only as a last resort because of their serious side effects. References: Christianson HB, Dorsey CS, O'Leary PA, Kierland RR. Localized scleroderma; a clinical study of 235 cases. AMA Arch Dermat. 1956;74:629-639 Haber PL. Clinical manifestations of scleroderma. Pediatrics in Review. 1995;16:49 Lehman TJ. Systemic and localized scleroderma in children. Curr Opin Rheumatol. 1996;8:576-579 Nelson AM. Localized forms of scleroderma, including morphea, linear scleroderma, and eosinophilic fasciitis. Curr Opin Rheumatol. 1996;8:473-476 1998 Self-Assessment Exercise XXI. Collagen vascular and other multisystem disorders [Return to Category List] Questions [Print Directions] Question 73. Answer.

A 12-year-old girl who has a 4-year history of chronic immune thrombocytopenic purpura was otherwise well until 3 weeks ago. At that time she developed intermittent fever; malaise; and tender, painful swelling of the knees and wrists. Laboratory findings include: hemoglobin, 12.6 g/dL; platelet count, 35,000/mm; and 15 to 20 white blood cells and 10 to 30 red blood cells per high power field on urinalysis. The MOST likely explanation for these findings is A. B. C. D. E. Henoch-Schnlein purpura human immunodeficiency virus infection juvenile rheumatoid arthritis Lyme disease systemic lupus erythematosus

Question 181. Answer. A 14-year-old girl who has systemic lupus erythematosus has developed diffuse proliferative glomerulonephritis.

Among the following, the MOST appropriate dose of oral prednisone, in mg/kg per day, for this patient is A. B. C. D. E. 0.1 0.2 0.5 1.0 2.0

Answers Critique 73 Preferred Response: E

[View Question] Most children who develop immune purpura (ITP) have an acute, self-limited disease. However, 10% to 20% of children fail to recover within 6 months, and they are considered to have chronic ITP. Chronic disease is more common among females and older children, particularly those older than 10 years of age. Most children who have chronic ITP have no other underlying disease process, but other diseases should be excluded when ITP is not acute and self-limited. Collagen vascular disorders, human immunodeficiency virus (HIV) infection, humoral immunodeficiency (particularly immunoglobulin A [IgA] deficiency), common variable hypogammaglobulinemia, and Hodgkin disease all are associated with an increased risk of chronic ITP. Approximately 1% of children who have chronic ITP develop autoimmune hemolytic anemia before, during, or after the development of thrombocytopenia. Systemic lupus erythematosus (SLE) develops in as many as 5% of adolescent females presenting with ITP. Thrombocytopenia may precede the development of other clinical manifestations of lupus (eg, facial rash) by months or years. Although serologic testing for SLE often is performed, the majority of patients who have ITP and positive antinuclear antibody studies do not develop SLE, which suggests a limited value to routine antinuclear antibody studies in these patients. However, the development of fever, arthritis, and renal abnormalities, such as seen in the patient in the vignette, is an indication for such testing; typically, such findings herald the development of clinical SLE. Circulating anticoagulants often occur in these patients and may be associated paradoxically with thrombotic complications. Therapy of SLE-associated ITP is similar to that of "idiopathic" chronic ITP, although it may be more resistant to treatment. HIV infection is an increasingly frequent cause of chronic ITP in children. The diagnosis usually is evident from maternal history or findings on the initial clinical examination. Many of these children have recurrent infections, failure to thrive, persistent candidiasis, axillary adenopathy, hepatosplenomegaly, or anemia or an abnormal white blood cell count or differential. However, isolated thrombocytopenia may be the initial

manifestation, and this diagnosis must be considered in the child who has chronic thrombocytopenia of undefined etiology. However, the findings of arthritis, pyuria, and hematuria, as seen in the girl in the vignette, are not characteristic of HIV infection. Similarly, these clinical findings with associated thrombocytopenia are unlikely manifestations of Lyme disease or juvenile rheumatoid arthritis. Henoch-Schnlein purpura is a vasculitis that is not associated with thrombocytopenia. References: Beardsley DS. Platelet abnormalities in infancy and childhood. In: Nathan DG, Oski FA, eds. Hematology of Infancy and Childhood. 4th ed. Philadelphia, Pa: WB Saunders Co: 1993:15761580 Bussel J, Cines D. Immunothrombocytopenic purpura, neonatal alloimmune thrombocytopenia and post-transfusion purpura. In: Hoffman R, Benz EJ, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 2nd ed. New York, NY: Churchill Livingstone; 1995:1854-1855 Critique 181 Preferred Response: E

[View Question] Treatment plans for any child who has systemic lupus erythematosus (SLE) is directed by the extent and severity of the disease. Major organ disease (eg, diffuse proliferative glomerulonephritis) necessitates the use of high-dose corticosteroids. The initial dose of oral prednisone is 2 mg/kg per day (maximum, 60 to 80 mg) in divided doses for a minimum of 3 to 4 weeks followed by consolidation, then a gradual tapering of the dosage. The use of a high-dose pulse regimen of intravenous methylprednisolone (30 mg/kg per day, maximum 1 g, for 3 consecutive days) also has been advocated. The undesirable side effects of steroid therapy, including cushingoid appearance, suppression of linear growth, weight gain, osteoporosis, hypertension, central nervous system effects, and suppression of the hypothalamic-pituitary-adrenal axis, should be expected if large doses are required for a significant period of time. There now is general agreement that intravenous cyclophosphamide therapy is indicated for the child who has active SLE complicated by diffuse proliferative glomerulonephritis. The most striking observation following initiation of systemic intravenous cyclophosphamide therapy for these children has been the dramatic improvement in their overall well-being. A substantial reduction has occurred in the frequency of intercurrent infections, arthritis, and other manifestations of active disease. Complications of intravenous cyclophosphamide include nausea, hair loss, and leukopenia, but these are generally reversible. References: Lang BA, Silverman ED. A clinical overview of systemic lupus erythematosus in childhood.01716 Pediatrics in Review. 1993;14:194-201

Lehman TJ. A practical guide to systemic lupus erythematosus. Pediatr Clin North Am. 1995;42:1223-1238 Schaller JG. Systemic lupus erythematosus. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, Pa: WB Saunders Co; 1996:673-676