BRS – Pediatrics: Rheumatology

Source: BRS Pediatrics, 2019

I. Henoch–Schönlein Purpura (HSP)

A. Definition. A systemic IgA-mediated vasculitis that primarily involves the skin, joints, gastrointestinal (GI) tract, and kidneys.
B. Epidemiology

1. HSP is primarily a disease of children (ages 3–15 years); the peak incidence is at 4– 6 years.
2. HSP is the most common form of vasculitis of childhood.
3. Males are more likely to be affected.
4. HSP occurs primarily in the fall, winter, and spring.

C. Clinical features

1. A viral syndrome or upper respiratory infection precedes HSP in about half of patients, particularly in patients who have had a prior group A β-hemolytic streptococcal infection.
2. Distinctive skin, GI, and joint manifestations follow the prodrome.
a. Skin manifestations

1. Classically, urticarial or erythematous maculopapular lesions progress to petechiae and palpable purpuric lesions, concentrated on gravity-dependent areas (the buttocks and lower extremities).
2. Children may also present with edema of hands, feet, scrotum, and scalp. Infants may present with a facial rash in addition to edema.
3. GI and joint symptoms may precede the diagnostic rash by days or weeks in 25% of patients.

b. Joint manifestations occur in 80% of patients as arthralgia or arthritis. The knees and ankles are most commonly involved.

1. Primarily involves large joints in the lower extremities and can be very painful.
2. Swelling is periarticular but lacks effusions or increased warmth and does not cause chronic damage.

c. GI manifestations occur in about 50% of patients.

1. Colicky abdominal pain that may be severe
2. GI bleeding (either occult blood or grossly bloody stool)
3. Increased risk of intussusception (most common GI complication of HSP)

3. Renal manifestations (see Chapter 11, section V.F.3)
a. Presentations range widely, from mild hematuria and trace proteinuria to gross hematuria, nephrotic syndrome, chronic renal insufficiency, and end-stage renal disease (1% of cases).
b. Onset of renal manifestations occurs within four weeks in most patients but can occur up to 6 months later.

D. Diagnosis
1. History and characteristic physical examination establish a clinical diagnosis.
2. Routine laboratory tests are neither specific nor diagnostic.
3. Skin biopsies show leukocytoclastic vasculitis with IgA deposition.
4. Increased serum IgA levels are present in 50% of patients.
5. Circulating IgA immune complexes in serum and IgA deposition in skin and glomeruli are suggestive of the diagnosis.
6. Platelet counts are normal despite the presence of petechiae and purpura (i.e., the skin rash is a nonthrombocytopenic purpura).

E. Management. Treatment is based on relief of symptoms, including use of analgesics and hydration, and monitoring for complications.
1. Steroids may be effective for relief of abdominal pain and arthritis but do not impact the clinical course.
2. Patients should be followed up with urinalysis and blood pressure monitoring every 2 weeks for 1–2 months after presentation, then monthly for at least 6 months. Hematuria, proteinuria, or hypertension should prompt referral to a nephrologist.

F. Prognosis
1. Most patients recover within 4 weeks.
2. HSP recurs at least once in one-third of patients, usually within 3–4 months of presentation.
3. Long-term morbidity is dependent on the severity of renal disease.

II. Kawasaki Disease (KD)

A. Definition. An acute febrile vasculitis of childhood; this disease involves multiple organ systems, including the heart, skin, mucous membranes, GI tract, central nervous system (CNS), joints, and peripheral vascular bed.
B. Epidemiology
1. KD is the most common cause of acquired heart disease in children in the United States.
2. Males are slightly more commonly affected than females.
3. Most common in children of Asian ethnicity but can occur in any ethnicity.
4. The mean age at presentation is 18–24 months (80–90% of cases occur in children younger than 5 years). It is uncommon in children younger than 6 months.
C. Diagnostic criteria (Table 16-1)
1. Temperature > 38.9°C (102°F) lasting ≥5 days—most consistent manifestation of KD
2. The patient must also have four of the following five clinical manifestations:
a. Bilateral conjunctivitis: bulbar injection with limbic sparing and without exudate
b. Mucous membrane changes: pharyngitis; strawberry tongue; or most commonly,
red, cracked, swollen lips
c. Cervical adenopathy: a unilateral nonsuppurative cervical lymph node ≥1.5 cm in diameter. This is the least consistent feature of KD.
d. Rash: primarily on the trunk. The rash may assume many forms (“polymorphous”), including erythematous, maculopapular, morbilliform, or scarlatiniform. It often begins as perineal erythema and desquamation.
e. Changes in distal extremities
1. Early (first 7–10 days of illness): swelling and induration of the hands and feet with erythematous palms and soles
2. Later (7–10 days after the start of fever): peeling around the nail beds of the distal extremities
f. It is important that the illness must not be explainable by any other disease process. Known infectious conditions (including bacterial, viral, and rickettsial infections), rheumatologic conditions (including systemic juvenile idiopathic arthritis), and drug reactions must be excluded to make the diagnosis of KD.
D. Other clinical features (not diagnostic criteria)
1. Cardiovascular manifestations
a. Coronary artery aneurysms occur in 20% of untreated patients, usually around days 7–14 (most commonly in the subacute phase of the disease).
b. Low-grade myocarditis is common.
c. Congestive heart failure
d. Arrhythmias
e. Aneurysms of the brachial arteries
2. Urethritis (sterile pyuria), which can be missed by catheterization that bypasses the urethra to obtain urine directly from the bladder
3. Aseptic meningitis
4. Hydrops of the gallbladder may occur in 10% of patients and should be considered in patients with acute right upper quadrant abdominal pain.
5. Arthritis (sterile) or arthralgias
6. Anterior uveitis
E. Time course of disease. The clinical course is triphasic (see Table 16-2).
1. Phase I: Acute phase (1–2 weeks)
2. Phase II: Subacute phase (weeks to months)

3. Phase III: Convalescent phase (weeks to years)
F. Laboratory findings. No laboratory tests are pathognomonic for KD. Laboratory findings are not specific but include the following (see Table 16-2):
1. Acute phase: (↑) erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Other common laboratory findings include elevations in white blood cell (WBC) count, transaminases (AST/ALT), sterile pyuria, and cerebrospinal fluid (CSF) pleocytosis. A normocytic, normochromic anemia is frequently observed, as is low serum albumin.
2. Subacute phase: (↑) platelet count and a decreasing ESR and CRP
3. Convalescent phase: Laboratory findings usually normalize within 6–8 weeks.
G. Management. Treatment includes anti-inflammatory therapy and assessment for coronary artery disease with serial echocardiography.
1. Intravenous immune globulin (IVIG). High-dose (2 g/kg) IVIG, in combination with aspirin (acetylsalicylic acid [ASA]). Initiation within 10 days after the onset of fever substantially decreases the prevalence of coronary artery dilation and aneurysms detected 2 and 7 weeks later. A second dose of IVIG is typically given if fever returns 24– 36 hours after initial treatment.
2. ASA
a. Acute phase: high-dose ASA for its anti-inflammatory effect
b. Subacute phase: low-dose ASA for its antiplatelet effect
3. Steroids are not the preferred first-line agent for the treatment of KD. Steroids may be useful, however, in some patients who are unresponsive to IVIG.
4. Tumor necrosis factor (TNF) inhibitors are also not indicated as primary treatment for KD, but may have a role for patients who are unresponsive to IVIG.
H. Incomplete or atypical KD
1. A subset of patients suspected of having KD may not fulfill all of the clinical diagnostic criteria. These patients have “incomplete” or “atypical” KD.
2. Patients must still have at least 5 days of fever but otherwise have only have 2–3 clinical features from Table 16-1 and no alternative explanation for symptoms.
3. Laboratory and echocardiographic studies are used to make the diagnosis in these children.
4. Treatment is the same as for typical KD.
I. Prognosis
1. If coronary artery disease is absent, mortality is rare. Recurrence is also rare.
2. Even if coronary artery disease is present, the mortality is <1%, and aneurysms, especially those <8 mm, commonly regress over time.
3. Long-term prognosis is unclear. It’s possible that there may be an increased risk of atherosclerotic heart disease in adulthood.

Table 16-1
Diagnostic Criteria of Kawasaki Disease

I. Fever for at least 5 days
AND
II. Four of the following features:

Conjunctivitis Oropharyngeal changes Cervical adenopathy Rash
Changes in distal extremities AND
III. The illness cannot be explainable by any other disease process (i.e., exclusion of known infectious etiologic factors, drug
reactions, and other rheumatologic conditions, such as juvenile idiopathic arthritis)

Table 16-2
Clinical Manifestations, Laboratory Findings, and Treatment of Kawasaki Disease

Phase I Phase II Phase III
Acute Phase Subacute Phase Convalescent Phase
Time Course 1–2 Weeks Weeks to Months Weeks to Years
Clinical
manifestations Fever Defervescence and decreased inflammation Gradual resolution of aneurysms
Conjunctivitis
Oropharyngeal
changes Peeling from nail beds or distal extremities
Cervical
adenopathy
Rash Coronary artery aneurysms
Swollen hands
Laboratory
findings (↑) ESR and CRP ESR and CRP decreasing from acute phase(↑)
Platelet count Normalization of all laboratory findings
(↑) WBC count
(↓) Hemoglobin
(↑) AST/ALT
(↓) Albumin
Sterile CSF
pleocytosis
Sterile pyuria
Treatment High-dose IVIG Low-dose aspirin Continue low-dose aspirin only if
aneurysms remain
High-dose
aspirin
ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; WBC = White blood cell count; AST = aspartate aminotransferase; ALT = alanine aminotransferase; IVIG = intravenous immune globulin; CSF = cerebrospinal fluid.

III. Juvenile Idiopathic Arthritis (JIA)
A. Definition. JIA is a disorder characterized by chronic joint inflammation in children, with or without extraarticular involvement.
B. Epidemiology
1. JIA is the most common pediatric rheumatic disease with arthritis as the distinguishing manifestation.
2. The mean age of onset is 1–3 years; presentation before 6 months of age is unusual.
3. JIA most commonly occurs in females, with two exceptions. Males are equally likely to have systemic-onset JIA, and they are much more likely to have late-onset human leukocyte antigen B27(HLA-B27)–related diseases.
C. Diagnosis of JIA is based on history and clinical features. Diagnostic criteria are listed in
Table 16-3.
D. Classification. The classification of JIA is determined on the basis of the number and types of joints involved, along with extraarticular manifestations (Table 16-4). The categories of JIA include oligoarthritis, polyarthritis, systemic arthritis, enthesitis-related arthritis, and psoriatic arthritis. Regardless of type, all patients have arthritis during their clinical course.
E. Clinical features (see Table 16-4)
1. Oligoarticular JIA (≤ four joints involved) accounts for 50% of cases. Patients usually present at 1–5 years of age with a female predominance. A good majority (65–85%) of patients have a positive antinuclear antibody (ANA). These patients are at high risk for developing chronic uveitis, which is defined as inflammation of the iris and ciliary body. Uveitis must be monitored by regular slit-lamp evaluations.
a. Subtypes. Subtypes of oligoarticular JIA are recognized on the basis of the presence and timing of joint involvement.
1. Persistent oligoarthritis describes patients with one to four joints involved in the first 6 months of disease who do not develop arthritis in additional joints.
2. Extended oligoarthritis describes patients with one to four joints involved during the first 6 months of disease who then develop arthritis in greater than four joints.
b. Articular involvement may present with swelling of one or two joints, not necessarily symmetric. The most common joints involved are the knees and hips.
2. Polyarticular JIA (five or more joints involved) accounts for approximately 30–40% of cases, with systemic involvement and extraarticular features generally mild or absent.
a. Subtypes. As in oligoarticular disease, polyarticular JIA can also be divided into two subtypes. Subtypes are based on the absence or presence of serum rheumatoid factor (RF), which is an IgM molecule directed against IgG. Both RF-negative (RF−) and RF-positive (RF+) polyarticular JIA affect females more frequently than males.
1. RF− disease presents both early and late in childhood.
2. RF+ disease presents in children older than 8 years and is generally more severe than RF− disease, with higher risk of severe arthritis and rheumatoid nodules.
b. Articular involvement is characterized by a symmetric polyarthritis that typically involves both small joints (hands and feet) and large joints (knees, ankles, and hips).
3. Systemic-onset JIA accounts for 10–15% of cases. At presentation, severe systemic symptoms may overshadow symptoms of arthritis.
a. High spiking fevers (temperature > 39°C [102.2°F]) occur most commonly in the late afternoon or evening and subsequently return quickly to baseline or subnormal

levels (Quotidian fever pattern). Systemic JIA is typically included in the differential diagnosis of “fever of unknown origin.”
b. Transient salmon-pink macular rash is most commonly found on the trunk and proximal extremities, especially during febrile episodes. The rash is evanescent (occurs with fever spikes and then fades) and nonpruritic.
c. Hepatosplenomegaly
d. Lymphadenopathy
e. Other features include the following:
1. Fatigue, anorexia, weight loss, and failure to thrive are common.
2. Serositis, including pericarditis and pleuritis, is also common.
3. CNS involvement, including meningitis and encephalopathy, may occasionally be present.
4. Myositis and tenosynovitis can also be seen in addition to the arthritis.
F. Laboratory findings. Laboratory results are nonspecific; if present, they reflect the existence or extent of inflammation and are useful to evaluate for other disease processes.
1. Anemia is usually microcytic and hypochromic, consistent with anemia of chronic disease.
2. Acute-phase reactants are elevated, including ESR, CRP, and platelet count.
3. Rheumatoid markers
a. RF is negative in most patients with JIA. RF positivity is not diagnostic but can help determine prognosis for patients with polyarticular disease.
b. ANA is present in 65–85% of patients with oligoarticular JIA and in 50% of patients with polyarticular JIA. An ANA is not a diagnostic test for JIA but can help determine the risk of uveitis. ANA is rare in children with systemic-onset JIA.
G. Management. The goal of treatment is to decrease joint inflammation and preserve function.
1. Control of inflammation
a. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce pain and inflammation.
b. Immunomodulatory medications (e.g., glucocorticoids, methotrexate, sulfasalazine, TNF inhibitors) are commonly used for more severe symptoms.
2. Mechanical and physical measures include physical and occupational therapy.
3. Surgery (e.g., joint replacement, synovectomy) is generally reserved for patients who have recalcitrant joint contractures or destruction. Owing to advances in pharmacotherapy, surgery is becoming much less common.
4. Psychosocial support
H. Prognosis. The outlook is excellent with appropriate early diagnosis and treatment. However, the incidence of complications depends on the type and subtype of JIA.

Table 16-3
Diagnostic Criteria for Juvenile Idiopathic Arthritis

Age of onset ≤16 years of age
Arthritis in ≥one joint defined as follows:

Swelling or effusion OR

Limitation of motion, tenderness, increased warmth
Duration of disease ≥ 6 weeks
Exclusion of other causes of arthritis
Table 16-4
Distinguishing Features of the Subtypes of Juvenile Idiopathic Arthritis

Subtype Definition (% of JIA) Age of Onset Sex Ratio
Oligoarticular There are 2 subtypes of oligoarticular JIA:

Persistent oligoarticular arthritis: Never affects more than four joints
Extended oliogoarticular arthritis: Affects more than four joints after the first 6 months of disease 50% Early childhood; peak at 2–4 years Female > male
Polyarticular There are 2 subtypes of polyarticular JIA:

RF–negative RF–positive 30–40%
for both subtypes
RF-
negative: Biphasic distribution; early peak 2–4 years and later peak at 6–
12 years
RF-positive: Late childhood or adolescence Female > male
Systemic onset Arthritis in one or more joints with or preceded by fever of at least 2 weeks’ duration that is documented as daily (“Quotidian”) for at least 3 days and accompanied by one or more of the following: (1) rash (evanescent), (2) lymphadenopathy, (3) hepatomegaly or splenomegaly, and
(4) serositis 10–15% Throughout childhood Female = male
Psoriatic Arthritis and psoriasis, or arthritis and at least two of the following: (1) dactylitis, (2) nail pitting, and (3) psoriasis in first-degree relative 2–11% Biphasic distribution; early peak at 2–4 years and later peak at
9–11 years Female > male
Enthesitis related Arthritis or enthesitis with two or more of the following: (1) sacroiliac tenderness or lumbosacral pain, (2) presence of HLA-B27, (3) onset of arthritis in male >6 years of age, (4) acute anterior uveitis, and (5) family history in a first-degree
relative of HLA-B27 associated disease 3–11% Late childhood or adolescence Male > female
RF = rheumatoid factor; Enthesitis = inflammation of tendinous insertions on bone; HLA-B27 = human leukocyte antigen B27.

IV. Systemic Lupus Erythematosus (SLE)
A. Definition. This multisystem autoimmune disorder is characterized by widespread chronic inflammation and immune complex–mediated vasculitis.
B. Epidemiology
1. There is a female predominance (female-to-male ratio is 8:1).
2. Age of onset is rarely younger than 10 years and peaks in adolescence.
3. SLE occurs most often in patients of Asian, African, or Latino ethnicity.
C. Etiology. The cause of SLE is unknown, but the disease may be triggered by drug reactions, excessive sun exposure, infections, or hormonal changes (e.g., menarche, menopause, pregnancy).
D. Clinical features. Signs and symptoms are variable and may involve multiple organ systems.
1. Constitutional symptoms such as fever, weight loss, and fatigue are common.
2. CNS involvement includes headache, encephalopathy, seizures, psychosis, and transverse myelitis.
3. Skin findings may include a malar rash (“butterfly distribution” covering the nasal bridge and upper cheeks sparing the nasolabial folds) and photosensitivity, both common at presentation or during an illness flare. Other common skin findings include alopecia and Raynaud phenomenon.
4. Arthralgias and arthritis are typically migratory and transient. SLE, unlike JIA, rarely causes joint deformity or erosion. Myositis may also occur.
5. GI involvement may manifest as hepatosplenomegaly, splenic infarction, mesenteric thrombosis (secondary to vasculitis), and sterile peritonitis.
6. Cardiovascular involvement is variable, with pericarditis as the most frequent manifestation. Congestive heart failure, arrhythmias, and sterile valvular vegetations (Libman–Sacks endocarditis) may also occur. Neonates born to mothers with SLE may have congenital heart block secondary to transplacental passage of maternal antibodies.
7. Pulmonary involvement may include pleuritis, pulmonary hemorrhage, and interstitial fibrosis.
8. Renal involvement is nearly universal, although lupus nephritis may be subclinical. Glomerulonephritis, nephrotic syndrome, hypertension, and subsequent renal failure are common.
9. Hematologic manifestations typically include low WBC counts. In addition to leukopenia, anemia of chronic disease, immune-mediated thrombocytopenia, and Coombs-positive hemolytic anemia are also common findings.
E. Diagnostic criteria for SLE (Table 16-5)
F. Laboratory findings
1. Elevated ESR
2. Anemia (anemia of chronic disease or hemolytic anemia)
3. Leukopenia
4. Thrombocytopenia
5. Urinalysis may show proteinuria depending on the extent of renal disease.
6. Rheumatologic markers
a. ANA is almost universally elevated (>99%) in SLE and is an excellent screening test. However, ANA is nonspecific for SLE and is found in many other diseases.
b. RF is often elevated in SLE, but like ANA, is nonspecific.
c. Anti–double-stranded DNA (anti-dsDNA) antibodies are much more specific (found only in SLE), and their levels can be used as markers for active disease, especially nephritis.

d. Anti-Smith (anti-Sm) antibodies are less prevalent in patients with SLE but, when present, are very specific. Unlike anti-dsDNA, anti-Sm antibody levels cannot be used as a measure of disease activity.
7. Other findings
a. Antiphospholipid antibodies (e.g., positive lupus anticoagulant or anticardiolipin antibodies) present in patients with SLE reflect an increased risk of thrombotic events.
b. Decreased complement (C3 and C4) is seen especially with active disease and represents immune complex–mediated complement activation.
c. Ro (SSA) and La (SSB) antibodies are less strongly associated with SLE (more specific for Sjögren syndrome). Babies born to mothers with these antibodies are at risk for neonatal lupus.
G. Management. Therapy is based on a multidisciplinary, team approach that attempts (1) to prevent or minimize inflammation and end-organ dysfunction, (2) to treat complications, and
(3) to provide psychosocial and family support, as follows:
1. Control of inflammation
a. NSAIDs are useful in the treatment of minor inflammatory symptoms, such as myalgias and arthralgias. Use should be carefully monitored owing to the risk of renal disease in SLE.
b. Immunosuppressive medications
1. Glucocorticoids are the mainstay of therapy for children with SLE. Depending on disease severity and extent, treatment ranges from low-dose oral to high-dose intravenously pulsed steroids.
2. Cyclophosphamide, intravenously pulsed, is useful for children with severe clinical manifestations, including renal and CNS disease. Adverse effects of this cytotoxic agent include infertility and gonadal failure, secondary malignancies, and hemorrhagic cystitis.
3. Hydroxychloroquine is useful for patients with mild disease and is often used as a maintenance therapy. Numerous studies have shown a beneficial effect on long-term disease activity and survival. Patients require ophthalmologic screening owing to the side-effect of potential vision damage with its use.
4. Other agents include mycophenolate, rituximab, azathioprine, methotrexate, and cyclosporine. Mycophenolate, in particular, is being used more often as an alternative to cyclophosphamide to treat lupus nephritis.
2. Treatment of complications
a. Patients with thrombosis and antiphospholipid antibodies should be anticoagulated with low–molecular weight heparin or warfarin.
b. Patients with renal failure may require dialysis, fluid and electrolyte management, and ultimately renal transplant.
3. Psychosocial and family support
H. Prognosis. Before the advent of effective therapy, the outlook for patients with SLE was historically poor and uniformly fatal. However, with current treatment, the survival rate is now 85–100% at 5–10 years after initial diagnosis. The major causes of mortality are infection (because of immunosuppression), renal failure, and CNS complications.

TABLE 16-5
Diagnostic Criteria for Systemic Lupus Erythematosus*

Mnemonic “SOAP BRAIN MD”
Serositis (pleuritis or pericardial inflammation)
Oral or nasal mucocutaneous ulcerations

Arthritis, nonerosive
Photosensitivity
Blood cytopenias (leukopenia, hemolytic anemia, or thrombocytopenia)
Renal disease (hematuria, proteinuria, hypertension)
ANA-positive
Immunoserology abnormalities (antibodies to double-stranded DNA, Smith antigen, false-positive RPR or VDRL assays, or
antiphospholipid antibodies)
Neurologic symptoms (encephalopathy, seizures, or psychosis)
Malar rash (butterfly rash)
Discoid lupus (red raised patches with scaling, can cause scarring)
*Four of eleven criteria provide a sensitivity and specificity of 96%.
RPR = rapid plasma reagin; VDRL = Venereal Disease Research Laboratories; ANA = antinuclear antibody.

V. Juvenile Dermatomyositis (JDM)
A. Definition. This inflammatory condition of children results in myopathy, progressive muscle weakness, and characteristic skin findings.
B. Epidemiology
1. JDM is the most common idiopathic inflammatory myopathy of childhood (85% of all myopathies).
2. Individuals are usually 5–10 years of age. The mean age of onset is 6 years.
3. Females are more likely to be affected.
C. Clinical features
1. Constitutional symptoms are common and include fatigue, anorexia, malaise, low-grade fevers, and weight loss.
2. Characteristic cutaneous findings, particularly over sun-exposed areas, include the following:
a. Periorbital violaceous heliotrope rash, which may also cross the nasal bridge
b. Gottron papules, in which the skin over the metacarpal and proximal interphalangeal joints (knuckles) may become erythematous and hypertrophic
3. Proximal muscle weakness (mostly of the hip girdle and legs) is insidious in onset, is symmetric, and occurs weeks to months after the eruption of skin findings. It is the primary manifestation of JDM. Gowers sign may be positive (i.e., difficulty standing from the seated position, such that one has to use his or her arms to “climb” up the thighs for support).
4. Other manifestations include
a. Neck flexor muscle weakness
b. Calcinosis (calcium deposition in muscle, fascia, and subcutaneous tissue), which occurs in approximately 40% of children
c. Nail bed capillary changes
d. Constipation from GI smooth muscle dysfunction
e. Dysphagia
f. Cardiac involvement with conduction abnormalities and dilated cardiomyopathy
D. Diagnosis
1. Classic clinical presentation of proximal muscle weakness with associated characteristic rashes
2. Increased muscle enzymes (creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase)
3. Magnetic resonance imaging (MRI) shows diffuse muscle edema in proximal muscle groups and can be used to avoid more painful procedures, such as electromyography (EMG) and muscle biopsy.
4. Abnormal EMG (used only when diagnosis is not certain)
5. Abnormal muscle biopsy (used only when diagnosis is not certain)
E. Complications
1. Aspiration pneumonia is a frequent complication resulting from a diminished gag reflex.
2. Intestinal perforation may result from GI vasculitis.
3. Frequent fractures may result from muscle weakness and osteopenia secondary to steroid therapy.
F. Management
1. Corticosteroids are the initial drugs of choice.
2. Other immunosuppressive agents, including methotrexate, IVIG, hydroxychloroquine,

cyclophosphamide, and cyclosporine are often used in combination with steroids to minimize adverse effects of long-term high dose corticosteroid use.
3. Vitamin D and calcium supplementation may be necessary to help treat osteopenia and decrease frequency of fractures.
G. Prognosis
1. Prognosis is better in children than in adults.
2. There is no association with malignancy in pediatric dermatomyositis (in contrast to adult disease, in which malignancy develops in 25% of patients).
3. Long-term survival is >95%. Morbidity is related to functional disability and calcinosis.

VI. Rheumatic Fever
A. Definition. Rheumatic fever is a delayed, nonsuppurative, autoimmune complication occurring 2– 4 weeks after an upper respiratory infection with group A β-hemolytic streptococcus (GABHS) (Streptococcus pyogenes). It is characterized by inflammation of the heart, blood vessels, joints, CNS, and skin.
B. Epidemiology
1. Rheumatic fever is now rare in the United States and Western Europe but was a worldwide problem during the 1960s. It remains a primary cause of cardiac death in the developing world in patients younger than 50 years.
2. It is most common in children 5–15 years of age, reflecting the age group most susceptible to streptococcal throat infections.
3. There is no gender predilection.
4. The major risk factor is pharyngitis caused by certain strains of GABHS. The streptococcal strains that cause streptococcal skin infection (i.e., impetigo) do not cause rheumatic fever.
C. Etiology. The cause of rheumatic fever is unknown, but the disease appears to be autoimmune in nature and may represent “molecular mimicry,” in which streptococcal antigens resemble autoantigens and trigger an autoimmune response.
D. Clinical features. These may be classified as “major” and “minor” features (Jones criteria).
1. Major features
a. Cardiac involvement is the hallmark and most important complication of rheumatic fever. The inflammatory process may involve all layers of the heart (pancarditis), including the epicardium, endocardium, myocardium, and pericardium.
1. Valvulitis is frequent and typically causes insufficiency of the left-sided valves (mitral and aortic). Mitral regurgitation is the most common early valvular manifestation. It rarely affects the pulmonic or tricuspid valves.
2. Myocarditis is usually manifested by tachycardia out of proportion to the extent of the fever. Other severe manifestations include cardiac dilatation and heart failure.
3. Pericarditis and pericardial effusions are less common.
b. Arthritis is classically migratory, asymmetric, and exquisitely painful and often the earliest manifestation of acute rheumatic fever. It occurs in 70% of patients and most commonly involves the elbows, knees, ankles, and wrists. It does not result in chronic joint disease and responds quickly to NSAIDs and aspirin.
c. Sydenham chorea occurs later than the other rheumatic fever manifestations, often beginning subtly, months after GABHS pharyngitis. It reflects involvement of the basal ganglia and caudate nuclei. Chorea may start as hand clumsiness and progress to choreoathetoid movements with emotional lability.
d. Skin involvement
1. Erythema marginatum is an evanescent, nonpruritic rash that starts as pink to red macules, which may coalesce and spread centrifugally with central clearing over the trunk and proximal limbs.
2. Subcutaneous nodules, although rarely seen, are associated with severe cardiac involvement. These small, mobile, and painless nodules occur on the bony prominences of the extensor surfaces of the extremities.
2. Minor features include fever, arthralgias, leukocytosis, increased ESR, and prolonged PR interval on electrocardiogram.
E. Diagnosis. The Jones criteria for rheumatic fever are shown in Table 16-6. Diagnosis requires

evidence of recent streptococcal infection and either two major criteria or one major plus two minor criteria.
F. Laboratory findings
1. Nonspecific inflammatory markers
a. Elevated ESR and CRP
b. Elevated WBC count
2. Serologic markers
a. Antistreptolysin-O titers are abnormally elevated in 70–80% of patients with rheumatic fever and are evidence of a recent GABHS infection.
b. Anti-DNase antibodies may also be used to document GABHS infection.
3. Echocardiography typically shows evidence of carditis, such as decreased ventricular function, valvular insufficiency, or pericardial effusion.
G. Management
1. Eradication of GABHS infection
a. Benzathine penicillin intramuscular injection (one dose) or
b. Penicillin orally for 10 days
2. Control of inflammation
a. NSAIDs are useful for control of joint pain and swelling, but if given before definitive diagnosis, they may obscure the diagnosis by halting the development of migratory arthritis. Therefore, their use is recommended only after the diagnosis of rheumatic fever is certain.
b. Corticosteroids are often used in patients with severe cardiac involvement, such as congestive heart failure and severe valvular dysfunction.
3. Supportive therapy
a. Congestive heart failure is treated with diuretics, dietary salt restriction, digoxin, and bed rest.
b. Sydenham chorea, if severe, may be treated with haloperidol.
4. Long-term management includes continuous antimicrobial prophylaxis to prevent recurrent episodes of rheumatic fever. Duration of prophylaxis depends on severity of heart disease.
H. Prognosis
1. There are no chronic sequelae of the joint, skin, and CNS manifestations of rheumatic fever.
2. Cardiac inflammation often leads to severe valvular dysfunction, which may require intervention immediately or many years after the event. Valvular insufficiency or stenosis is usually delayed (usually more than 3 years after rheumatic fever) and, if severe, may require valve replacement or valvuloplasty.

TABLE 16-6
The Jones Criteria for Diagnosis of Rheumatic Fever*

Major criteria
Migratory polyarthritis
Carditis
Sydenham chorea
Erythema marginatum
Subcutaneous nodules
Minor criteria
Fever
Arthralgia
Previous rheumatic fever
Leukocytosis
Elevated erythrocyte sedimentation rate

Elevated C-reactive protein

*The diagnosis requires evidence of previous streptococcal infection and either (1) two major criteria or (2) one major plus two minor criteria.

VII. Lyme Disease
A. Definition. This reactive inflammatory disorder of the skin, heart, CNS, and connective tissues is caused by spirochetal infection with Borrelia burgdorferi (in the United States) and transmitted via a tick bite.
B. Epidemiology. High-risk areas reflect the natural habitat of ticks of the Ixodes species, which are the vectors for Lyme disease transmission. These ticks are especially prevalent in woodlands and fields in the New England states and parts of the Pacific coast and Midwestern United States. Disease onset typically occurs during the summer months.
C. Etiology
1. Vector. In the United States, most human infections occur during feeding by an infected deer tick, Ixodes scapularis. Transmission from Ixodes pacificus, which is the tick most prevalent in the Western United States, is less common.
2. Organism. B. burgdorferi is passed into the bloodstream of the human host while the tick engorges itself with blood. The infected tick must be attached for more than 36–
48 hours before the risk of B. burgdorferi transmission becomes substantial.
D. Clinical features. Clinical features are initially caused by the invasion of B. burgdorferi into local and distant tissues, and in later stages by a systemic inflammatory response against the spirochete. The untreated clinical course of Lyme disease is, therefore, divided into two stages, early and late disease. Early disease is further broken down into early localized and early disseminated disease.
1. Early disease (<4 months after transmission)
a. Early localized disease can occur within days of transmission, resulting from local cutaneous invasion and subsequent inflammation.
1. Erythema migrans is the classic rash of Lyme disease and is typically the first manifestation. It occurs in two-thirds of patients and is described as annular and “targetlike” with variable degrees of central clearing. Erythema migrans may be asymptomatic, pruritic, or painful and, if untreated, may expand (thus the term migrans) to more than 12 inches in diameter. It is the only manifestation that permits diagnosis without laboratory confirmation.
2. Constitutional symptoms may begin to occur during this stage and include fever, headache, neck pain, myalgias, fatigue, arthralgias, and lymphadenopathy.
b. Early disseminated disease typically occurs within 1–4 months after the tick bite. In addition to cutaneous findings, it is characterized by involvement of other organ systems.
1. Skin. Up to 25% of children may develop multiple secondary erythema migrans lesions, which tend to be smaller than the initial lesion.
2. Constitutional symptoms [see section VII.D.1.a.(2)] may initially appear and continue through this stage.
3. Neurologic
a. Aseptic meningitis may occur at this stage but is rare (1%).
b. Facial nerve palsy is seen in approximately 3% of children. Lyme disease must therefore be considered in a child with unilateral or bilateral palsy of the seventh cranial nerve.
c. Encephalitis
4. Carditis is rare but usually presents as heart block or myocarditis.
2. Late disease (months after transmission) is the second stage and presents with arthritis as the most common manifestation. Arthritis typically is mono or oligoarticular and

involves the knee in >90% of cases.
E. Diagnosis
1. The diagnosis is strongly suggested in the presence of epidemiologic risk factors and a classic erythema migrans rash.
2. Laboratory diagnosis is important in establishing a definitive diagnosis because erythema migrans is not always present, and the clinical features and routine laboratory test results may be nonspecific. Testing should only be performed on patients with appropriate risk factors and symptoms.
a. Serologic testing involves the measurement of antibodies to B. burgdorferi in the patient’s serum and is the recommended laboratory approach. The US Centers for Disease Control and Prevention currently recommends a two-step procedure:
1. Enzyme-linked immunosorbent assay (ELISA), which has a relatively high sensitivity. If negative, no further testing is indicated.
2. Western blot, if the ELISA is positive or equivocal, to confirm the diagnosis. Patients require either five positive IgG bands or two positive IgM bands.
b. Other laboratory tests (e.g., polymerase chain reaction, cultures from body fluids or tissue) are occasionally used, but their clinical utility is limited, offering no advantage over the recommended serologic method.
F. Management is aimed at eradicating B. burgdorferi, with the caveat that symptoms caused by systemic inflammation may not resolve immediately.
1. Early localized disease, or late disease with arthritis only, is typically treated with doxycycline (for children ≥9 years of age), amoxicillin, or cefuroxime.
2. Carditis and meningitis require intravenous ceftriaxone.
G. Prognosis. Children who are treated, even with arthritis or neurologic manifestations, have an excellent prognosis. Recurrent symptoms or chronic sequelae are rare.

VIII. Other Rheumatologic Conditions of Childhood
Disorders that are rare in children and adolescents are marked with an asterisk (*).

A. Seronegative spondyloarthropathies. This group of disorders involves inflammation of entheses (tendinous insertions into bones), joints, or axial skeleton and are characterized by the absence of RF, ANA, or other disease-specific serologic markers.
1. Reactive arthritis. Inflammation of the joints triggered by an infection, typically an enteric or sexually transmitted pathogen. An example is the triad of arthritis, urethritis, and conjunctivitis (Reiter syndrome), which is most commonly triggered by Chlamydia trachomatis. The most common enteric pathogens which are associated with reactive arthritis include Salmonella, Shigella, Yersinia, Campylobacter, and Clostridium difficile.
2. Psoriatic arthritis (see also Table 16-4). This arthritis of the small and large joints is seen in patients with or without psoriatic skin disease. It is also associated with dactylitis (digital swelling), nail pitting, and onycholysis. Diagnosis is based on the presence of arthritis and psoriasis. If psoriasis is absent, the diagnosis can also be established if there is a first- degree relative with psoriasis.
3. Ankylosing spondylitis. This male-predominant, HLA-B27–related syndrome of arthritis affects the joints of the hips and sacroiliac joint. It is characterized by enthesitis.
4. Inflammatory bowel disease (IBD)–associated arthritis. This arthritis is associated with ulcerative colitis or Crohn disease. It typically involves the large joints of the lower extremity and can wax and wane based on GI disease activity. Some patients with IBD and joint symptoms may be HLA-B27 positive and have involvement of the axial skeleton in a pattern indistinguishable from ankylosing spondylitis.
B. Other vasculitides. Like the previously described vasculitic diseases (e.g., KD, SLE, HSP), these disorders are characterized by constitutional symptoms and inflammation of blood vessels.
1. Takayasu arteritis. This disease is a large-vessel vasculitis. The classic patient is an Asian adolescent or young adult female, with constitutional symptoms and aneurysmal dilation or thrombosis of the aorta, carotid, or subclavian arteries.
2. *Polyarteritis nodosa. This vasculitis is characterized by aneurysms and thrombosis of the small- and medium-sized vessels (e.g., brachial, femoral, or mesenteric arteries).
3. *Granulomatosis with polyangiitis (formerly known as Wegener granulomatosis). This vasculitis is characterized by necrotizing granulomas in multiple organs, most commonly the respiratory tract and kidneys. Classic clinical features include constitutional symptoms, severe sinusitis, hemoptysis, and glomerulonephritis. It is associated with PR3 antineutrophil cytoplasmic antibody, also known as the C-ANCA.
C. *Sjögren syndrome. This syndrome is defined by a classic triad of findings, including sicca syndrome (dry mouth and eyes), high titers of autoantibodies (usually ANA, RF, SSA, SSB), and connective tissue disease.
D. *Scleroderma
1. Systemic scleroderma. This disorder is better termed systemic sclerosis because it is characterized by excessive fibrosis and subsequent dysfunction of multiple organ systems. This process affects the skin and vessels of the heart, kidneys, lungs, and GI tract. The cutaneous hallmark is skin thickening with loss of dermal ridges, resembling “tightened” skin.
2. CREST syndrome refers to a form of scleroderma with less extensive involvement, manifesting with calcinosis, Raynaud phenomenon, esophageal involvement, sclerosis of the skin, and telangiectasias.

Review Test
1. A 10-year-old girl presents for evaluation of fatigue, diminished appetite, and weakness. On physical examination, a periorbital violaceous heliotrope rash is evident. Which of the following statements is most accurate regarding the probable diagnosis?
A. Children with this diagnosis typically present with distal muscle weakness with an ascending pattern.
B. This patient has a 25% likelihood of developing a subsequent malignancy.
C. Steroids are contraindicated.
D. The clinical course may be complicated by calcium deposition in the muscle, fascia, and subcutaneous tissue.
E. This patient’s disease is more common in males than in females.
2. A 4-year-old boy presents to the emergency department for evaluation after 1 day of abdominal pain and a petechial rash on his bilateral thighs. He has no known history of prior bleeding or easy bruising but does have a 4-day history of upper respiratory tract infection (URI) symptoms and low-grade fevers. Physical examination is remarkable for a nontoxic, alert, and afebrile child. There is a petechial eruption on the lateral thighs, along with some edema of the hands and bilateral ankles. The abdomen is not distended, and bowel sounds are present. On examination, the abdomen is mildly tender to palpation in the periumbilical region without rebound tenderness. Laboratory studies reveal a white blood cell count of 14,000 cells/mm3, hemoglobin of 11.8 g/dL, and platelet count of 260,000 platelets/µL. Which of the following treatments would be the most appropriate at this time?
A. Intravenous immune globulin therapy for a presumed diagnosis of Kawasaki disease
B. Intravenous immune globulin therapy for a presumed diagnosis of immune thrombocytopenic purpura
C. Further evaluation by Child Protective Services for possible nonaccidental injury
D. Conservative management for a presumed diagnosis of Henoch–Schönlein purpura
E. Parenteral antibiotic therapy for a presumed diagnosis of meningococcemia pending blood culture results
3. A 3-year-old boy presents to the emergency department for evaluation of acute right upper quadrant abdominal pain. Further history reveals a 7-day history of fevers and sore throat. Physical examination reveals an irritable but consolable child with a temperature of 39.9°C (103.8°F). Other pertinent findings include bilateral nonpurulent conjunctivitis; red, cracked lips; swollen indurated fingers with erythematous palms; and an erythematous macular rash on the trunk. Which of the following is the most likely cause of the acute abdominal pain?
A. Henoch–Schönlein purpura
B. Hydrops of the gallbladder
C. Intussusception
D. Referred pain from arthritis involving the spine
E. Constipation from gastrointestinal smooth muscle dysfunction
4. A 3-year-old girl is brought to your office by her parents, who report that she has had
2 months of intermittent high-spiking fevers with temperature up to 39°C (103°F), which occur nightly and return quickly to normal. The parents report that their daughter’s activity and appetite are diminished. She is often reluctant to walk because of swelling of her ankles and knees. Six months ago her weight was at the 50th percentile, and now her weight is at the 25th percentile for age. On examination, you note a temperature of 39.2°C (102.6°F) and a salmon- colored maculopapular rash on the trunk. Diffuse lymphadenopathy is present, and the liver is palpable 4 cm below the right costal margin. Which of the following statements regarding this patient’s likely diagnosis is most accurate?

A. Measuring the erythrocyte sedimentation rate will confirm the diagnosis.
B. Admission to the hospital and immediate treatment with intravenous immune globulin are necessary.
C. Antinuclear antibodies are likely to be positive.
D. The rash on the trunk is nonpruritic and is likely evanescent.
E. The patient has a 10% chance of developing severe chronic arthritis.
5. A 10-year-old boy develops a headache, fever, and rash approximately 2 weeks after camping with his family. The rash is annular and “targetlike” with central clearing. Which of the following is most accurate regarding the most likely diagnosis?
A. This patient has a high likelihood of developing carditis.
B. An infected tick must be attached to the skin for at least 36–48 hours before there is a significant risk of developing this condition.
C. The prognosis for a child with this disease is poor, even with treatment.
D. Treatment should be immediately initiated with an intravenous first-generation cephalosporin.
E. Serologic testing for this condition is unreliable, and the diagnosis must be confirmed by culture of body fluids or tissue.
6. A 7-year-old boy with complaints of shortness of breath, nonpruritic rash, and very painful migratory arthritis presents to your clinic for evaluation. Two weeks ago, he had a sore throat and fever. On physical examination, a truncal macular rash is evident, and a grade 3/6 loud holosystolic murmur is audible at the apex and axilla. Which of the following statements is most accurate regarding this patient’s likely diagnosis?
A. Management may include corticosteroid therapy.
B. Antistreptolysin-O titers would be expected to be abnormally high in 25% of patients with this condition.
C. Laboratory evaluation is likely to demonstrate an elevated erythrocyte sedimentation rate and leukopenia.
D. Chorea is also likely to be found on examination of this patient.
E. Development of chronic and debilitating arthritis is likely.
7. A 12-year-old boy presents with severe arthritis of the hips and sacroiliac joints. Laboratory studies reveal that the patient is human leukocyte antigen B27 (HLA-B27) positive. Which of the following is the most likely diagnosis?
A. Early-onset oligoarticular juvenile idiopathic arthritis (JIA)
B. Juvenile ankylosing spondylitis
C. Rheumatoid factor–negative polyarticular JIA
D. Rheumatoid factor–positive polyarticular JIA
E. Systemic-onset JIA
8. A 3-year-old girl is referred to you for evaluation of fever. Her fever has lasted 6 days, and her parents have noticed eye redness, a truncal rash, and swollen lips. Your physical examination confirms these findings, along with an enlarged left cervical lymph node measuring 3 cm in diameter. On the basis of your findings, you suspect Kawasaki disease. Which of the following findings on physical examination or laboratory analysis would best correlate at this time with the finding of coronary artery aneurysms on echocardiogram?
A. Her current signs of fever, truncal rash, and swollen lips
B. Elevated erythrocyte sedimentation rate
C. Elevated platelet count of 840,000 platelets/µL
D. Cervical adenopathy
E. Laboratory evidence of aseptic meningitis

The response options for statements 9–14 are the same. You will be required to select one answer

for each statement in the following set.

A. Henoch–Schönlein purpura
B. Psoriatic arthritis
C. Systemic-onset juvenile idiopathic arthritis
D. Reactive arthritis
E. Inflammatory bowel disease-associated arthritis
F. Systemic lupus erythematosus
G. Kawasaki disease
H. Dermatomyositis
I. Oligoarticular juvenile idiopathic arthritis
J. Rheumatic fever
K. Lyme disease

For each patient, select the most likely diagnosis.

1. An human leukocyte antigen B27 (HLA-B27)–positive 14-year-old boy with abdominal pain and chronic diarrhea.
2. A 6-year-old boy with erythematous and hypertrophic papules over the metacarpal and proximal interphalangeal joints and “dark rings” around the eyes.
3. A sexually active 16-year-old boy with arthritis and conjunctivitis.
4. A 3-year-old boy with fever, bilateral knee swelling, and a “salmon-colored” rash on the trunk and proximal extremities.
5. A 14-year-old girl with arthritis, alopecia, leukopenia, and “a bad sunburn” on her face.
6. A 5-year-old girl with arthritis, abdominal pain, and a petechial eruption on her buttocks.

Answers and Explanations
1. The answer is D [V.C]. The constellation of clinical signs and symptoms that include fatigue, muscle weakness, and a heliotrope rash in a girl between 5 and 10 years of age is suggestive of dermatomyositis. Calcinosis, or calcium deposition, in muscle, fascia, and subcutaneous tissue occurs in up to 40% of children with this disorder. Dermatomyositis typically presents with proximal muscle weakness, characterized by a positive Gowers sign (difficulty standing from the sitting position and, as a result, having to “climb” up the thighs for support). Females are twice as likely as males to develop dermatomyositis. In childhood dermatomyositis, unlike in adult dermatomyositis, there is no association with malignancy. Steroids are the mainstay of therapy.
2. The answer is D [I.A, I.C.1–2, and I.E] Henoch–Schönlein purpura is an IgA-mediated vasculitis that involves the skin, joints, gastrointestinal tract, and kidneys. Despite the presence of petechiae, the platelet count is normal (i.e., a nonthrombocytopenic purpura). Steroids are indicated for patients who present with severe abdominal pain, poorly controlled joint pain, or nephritis. The diagnosis of Kawasaki disease is unlikely given the absence of fever for a minimum of 5 days and the absence of at least four of the five diagnostic criteria. The patient’s normal platelet count is inconsistent with the diagnosis of immune thrombocytopenic purpura. Although nonaccidental trauma must always be considered, there is no other bruising of concern on examination, and the clinical presentation is most consistent with the diagnosis of Henoch–Schönlein purpura. The diagnosis of meningococcemia is also unlikely because this patient is nontoxic, alert, and afebrile.
3. The answer is B [II.C and II.D.4]. This patient meets the diagnostic criteria for Kawasaki disease based on the duration of fever and the presence of four of the five diagnostic criteria, including conjunctivitis, oropharyngeal changes, a truncal rash, and swelling of the distal extremities. Approximately 10% of patients with Kawasaki disease may develop hydrops of the gallbladder, which presents with acute right upper quadrant pain. Sore throat, conjunctivitis, and red cracked lips are not associated with constipation, arthritis, or intussusception. Dermatomyositis may present with constipation from smooth muscle dysfunction and constitutional symptoms, but abdominal pain is not a feature of the disorder. Although edema of the hands and abdominal pain can be seen in Henoch–Schönlein purpura, fevers and mucous membrane findings are not usually present.
4. The answer is D [III.E.3]. This patient has features consistent with systemic-onset juvenile idiopathic arthritis (JIA). Intermittent high-spiking fevers, joint pain and swelling, lymphadenopathy, and hepatosplenomegaly are common features. The classic rash of systemic-onset JIA is described as salmon-colored and maculopapular, located on the trunk and proximal extremities. It is nonpruritic and evanescent (comes and goes) and tends to be more prominent during febrile episodes. Diagnosis is on the basis of characteristic clinical features and does not rely on specific laboratory tests. Although the erythrocyte sedimentation rate is often elevated, it is nonspecific because it is also elevated in many other inflammatory conditions, such as infectious disorders, some malignancies, and other rheumatologic conditions. Moderate to severe symptoms can be treated with anti-inflammatory (e.g., aspirin) or immunomodulatory (e.g., glucocorticoids) medications, but intravenous immune globulin is not recommended for use in JIA. Children with systemic-onset JIA have a 50% chance of having a severe, erosive arthritis. Antinuclear antibodies (ANA) in patients with systemic- onset JIA are negative, in contrast to most patients with early-onset oligoarticular JIA and 50% of patients with polyarticular JIA in whom ANA is positive.
5. The answer is B [VII.C.2, VII.D.1–2, and VII.F.1]. The scenario of constitutional symptoms in the face of a classic rash suggestive of erythema migrans, shortly after a camping trip,

supports the diagnosis of Lyme disease. To transmit Lyme disease, an infected tick must be attached to the skin for at least 36-48 hours. Early in the disease, patients may present with fever, headache, myalgias, arthralgias, and lymphadenopathy, along with an annular, or “targetlike,” skin eruption with central clearing. Treatment of early disease includes oral doxycycline for children ≥8 years of age, oral cefuroxime or oral amoxicillin. Subsequent neurologic complications are not common but may include aseptic meningitis, facial cranial nerve palsy, and encephalitis. Cardiac complications are quite rare and may include heart block and myocarditis. The prognosis for a child with any stage of Lyme disease, if treated, is excellent. Arthritis, the hallmark of late disease, occurs months after the initial clinical presentation. Serologic testing (enzyme-linked immunosorbent assay and Western blot analysis) is recommended for confirmation of disease.
6. The answer is A [VI.A, VI.B.4, VI.D, VI.E, VI.G, and Table 16-6]. This patient’s clinical presentation should raise suspicion for acute rheumatic fever. The diagnosis of acute rheumatic fever requires evidence of previous group A β-hemolytic streptococcal infection, in addition to either two major Jones criteria or one major and one minor Jones criteria. The major Jones criteria include erythema marginatum, carditis, migratory polyarthritis, subcutaneous nodules, and Sydenham chorea. Unlike the other major criteria, the onset of chorea is usually several months after the other manifestations. Minor Jones criteria include fever, arthralgias, elevated erythrocyte sedimentation rate, and leukocytosis (not leukopenia). The great majority of patients (70–80%) with acute rheumatic fever have elevated antistreptolysin-O titers. Acute management includes eradication of streptococcal infection with penicillin and control of inflammation with nonsteroidal anti-inflammatory agents or corticosteroids. This patient’s shortness of breath may be caused by congestive heart failure or a pericardial effusion. There are usually no chronic joint sequelae from acute rheumatic fever.
7. The answer is B [III.D and Table 16-4]. Unlike all other types and subtypes of juvenile idiopathic arthritis (JIA), juvenile ankylosing spondyloarthritis is male predominant and almost always presents in children older than 8 years. Typically, patients with ankylosing spondylitis are human leukocyte antigen B27 (HLA-B27) positive and have involvement of the hips and sacroiliac joints. In contrast, patients with early-onset oligoarticular JIA are usually female, present between 1 and 5 years of age, have a high risk of developing chronic uveitis, and do not have involvement of the sacroiliac joints. Patients with polyarticular JIA (whether rheumatoid factor–positive or –negative) are also usually female and have involvement of multiple large and small joints but not typically the sacroiliac joints. Patients with systemic- onset JIA may be either male or female. Other presenting features of systemic-onset JIA include fever, a characteristic transient skin rash (salmon-colored), hepatosplenomegaly, and lymphadenopathy.
8. The answer is C [II.C–F]. Coronary artery aneurysms in Kawasaki disease are more likely to occur during the subacute phase of the disease, which begins 1–2 weeks after the onset of fever. The subacute phase is also characterized by decreasing erythrocyte sedimentation rate (ESR) and by marked thrombocytosis. High-spiking fevers, rash, swollen lips, cervical adenopathy, edema of the distal extremities, and elevations of the ESR and C-reactive protein are all characteristic of the acute phase of Kawasaki disease. Aseptic meningitis is a well- described complication of Kawasaki disease, but there is no known increased incidence of aneurysm formation in patients with aseptic meningitis.
9. The answers are E, H, D, C, F, and A, respectively [VIII.A.4, V.C.2, VIII.A.1, III.E.3, IV.C–E, Table 16-5, and I.C]. Abdominal pain and chronic diarrhea may be caused by inflammatory bowel disease. Arthritis may be associated with either ulcerative colitis or Crohn disease. Some patients with inflammatory bowel disease are also human leukocyte antigen B27 (HLA- B27) positive and have involvement of the axial skeleton, which is clinically indistinguishable from ankylosing spondylitis. The diagnosis of dermatomyositis should be suspected in a child

with proximal muscle weakness, a violaceous heliotrope rash around the eyes, and erythematous, hypertrophic papules over the knuckles (Gottron papules). Reactive arthritis is triggered by an enteric or sexually transmitted pathogen (classically, Chlamydia trachomatis). Reactive arthritis can present with arthritis, conjunctivitis, and urethritis. The diagnosis of systemic-onset juvenile idiopathic arthritis should be considered in a child presenting with fever of unknown origin, an evanescent salmon-colored rash, arthritis, organomegaly, and polyserositis. Systemic lupus erythematosus may be diagnosed when four of eleven diagnostic criteria are fulfilled, including photosensitivity and a malar rash. Adolescent females might also present with alopecia or Raynaud phenomenon when their disease is active. Henoch– Schönlein purpura is a systemic IgA-mediated vasculitis that involves the skin, joints, gastrointestinal tract, and kidneys. It commonly presents with a nonthrombocytopenic purpuric or petechial eruption on the buttocks or thighs with abdominal pain, arthritis, and glomerulonephritis.