Pediatric Residency Training Program

16

Rheumatology

Jerome K. Wang M.D.

Lee Todd Miller M.D.

Frank T. Saulsbury M.D.

  1. Henoch-Schönlein Purpura
  2. Definition

A systemic IgA-mediated vasculitis involving the skin, joints, gastrointestinal (GI) tract, and kidneys.

  1. Epidemiology
  2. Henoch-Schönlein purpura is a disease of young children; 75% of cases occur in children younger than 10 years of age. The median age of onset is 5 years.
  3. Malesare more likely to be affected (male-to-female ratio is 2:1).
  4. Clinical Features
  5. Aviral syndrome or upper respiratory infection precedes Henoch-Schönlein purpura in most patients. Twenty percent of patients have concomitant or prior group A β-hemolytic streptococcal infection.
  6. Distinctive skin, GI, and joint manifestationsfollow the prodrome.
  7. Skin manifestations
  8. Classically, urticarial or erythematous maculopapular lesions progress to petechiae and palpable purpuric lesions concentrated on the buttocks and lower extremities.
  9. Children may also present with edemaof hands, feet, scrotum, and scalp. (Infants may also present with a facial rash in addition to edema.)
  10. GI and joint symptoms may precede the diagnostic rash by days or weeks in 30% of patients.
  11. Joint manifestationsoccur in 80% of patients and manifest as arthralgia or arthritis. The knees and ankles are most commonly involved.
  12. GI manifestations occur in 67% of patients.
  13. Colicky abdominal painthat may be severe
  14. GI bleeding(either occult blood or grossly bloody stool)
  15. Increased risk of intussusception

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  1. Renal manifestations(see Chapter 11, section IV.F.3)
  2. 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).
  3. Renal manifestations may not become clinically apparent for up to 3 months after initial presentation in 25% of patients who develop nephritis.
  4. Diagnosis
  5. History and characteristic physical examinationestablish a clinical diagnosis.
  6. Routine laboratory tests are neither specific nor diagnostic.
  7. Increased serum IgAlevels are present in 50% of patients.
  8. Circulating IgA immune complexes in serum and IgA deposition in skin and glomeruli are suggestive of the diagnosis.
  9. Platelet counts are normaldespite the presence of petechiae and purpura (i.e., the skin rash is a nonthrombocytopenic purpura).
  10. Management

Treatment is based on relief of symptoms, including pain control and hydration. Steroids may be effective for relief of abdominal pain and arthritis.

  1. Prognosis
  2. Most patients recover within 4 weeks.
  3. Henoch-Schönlein purpura recurs at least once in 50% of patients.
  4. Long-term morbidity is dependent on the severity of nephritis.
  5. Kawasaki Disease (Mucocutaneous Lymph Node Syndrome)
  6. Definition

An acute febrile vasculitis of childhood, of unknown origin, involving multiple organ systems, including the heart, skin, mucous membranes, GI tract, central nervous system (CNS), joints, and peripheral vascular bed.

  1. Epidemiology
  2. Kawasaki disease is the most common cause of acquired heart diseasein children in the United States.
  3. Malesare slightly more commonly affected than females (male-to-female ratio is 3:2).
  4. Most common in children of Asian ethnicity
  5. The mean ageat presentation is 18–24 months (80% of cases occur in children younger than 5 years of age).
  6. Diagnostic Criteria (Table 16-1)
  7. Fever 102°F (38.9°C) lasting ≥5 days
  8. The patient must also have four of the following five clinical manifestations:
  9. Bilateral conjunctivitis:bulbar injection with limbic sparing and without exudate

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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 may not be explainable by any other disease process (i.e., exclusion of known infectious etiologic factors, drug reactions, and other rheumatologic conditions, such as juvenile rheumatoid arthritis)

  1. Oropharyngeal changes:pharyngitis, strawberry tongue, or, most commonly, red, cracked, swollen lips
  2. Cervical adenopathy:a unilateral nonsuppurative cervical lymph node ≥ 1.5 cm in diameter
  3. Rash:primarily on the trunk. The rash may assume many forms (polymorphous), including erythematous maculopapular, morbilliform, or scarlatiniform.
  4. Changes in distal extremities
  5. Early(first 7–10 days of illness): brawny edema and induration of the hands and feet with erythematous palms and soles
  6. Later(7–10 days after the start of fever): peeling around the nail beds or of the distal extremities
  7. It is important that the illness must not be explainable by any other disease process.Known infectious causes (including bacterial, viral, and rickettsial infections), rheumatologic conditions (including juvenile rheumatoid arthritis), and drug reactions must be excluded to make the diagnosis of Kawasaki disease.
  8. Other Clinical Features

(not diagnostic criteria)

  1. Cardiovascular manifestations
  2. Coronary artery aneurysmsoccur in 20% of untreated patients, usually around days 7–14 (most commonly in the subacute phase of the disease).
  3. Low-grade myocarditis is common.
  4. Congestive heart failure
  5. Arrhythmias
  6. Aneurysms of the brachial arteries
  7. Urethritis (sterile pyuria)
  8. Aseptic meningitis
  9. Hydrops of the gallbladder, which may occur in 10% of patients and should be considered in patients with acute right upper quadrant abdominal pain
  10. Arthritis (sterile) or arthralgias
  11. Anterior uveitis

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  1. 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 Kawasaki disease. Laboratory findings are not specific but include the following (see Table 16-2):

  1. Acute phase:) erythrocyte sedimentation rate (ESR),) C-reactive protein (CRP)
  2. Subacute phase:) platelet count and a decreasing ESR and CRP
  3. Convalescent phase: Laboratory findings usually normalize within 6–8 weeks.
  4. 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 (ASA), initiated within 10 days of onset of fever substantially decreases the prevalence of coronary artery dilation and aneurysms detected 2 and 7 weeks later.
  2. ASA
  3. Acute phase: high-dose ASAfor its anti-inflammatory effect
  4. Subacute phase: low-dose ASAfor its antiplatelet effect
  5. Steroids.The use of these agents is controversial. Steroids have been contraindicated in the treatment of Kawasaki disease because of a finding of increased morbidity associated with their use. However, steroids may be useful in some patients who are unresponsive to IVIG.

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

 

Phase I Acute Phase

Phase II Subacute Phase

Phase III Convalescent Phase

Time Course

1–2 Weeks

Weeks to Months

Weeks to Years

Clinical manifestations

Fever
Conjunctivitis
Oropharyngeal changes
Cervical adenopathy
Rash
Swollen hands

Defervescence of inflammation
Peeling from nailbeds or distal extremities
Coronary artery aneurysms

Gradual resolution of aneurysms

Laboratory findings

)ESR
)CRP

(ESR and (CRP
)Platelet count

Normalization of all laboratory findings

Treatment

High-dose IVIG
High-doseaspirin

Low-dose aspirin

Continue low-dose aspirin only if aneurysms remain

ESR = erythrocyte sedimentation rate;CRP= C-reactive protein; IVIG = intravenous immune globulin.

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  1. Prognosis
  2. If coronary artery disease is absent, nolong-term sequelae occur.
  3. Even if coronary artery disease is present, mortality is <1%, and aneurysms, even large ones, commonly regress.
  4. Long-term prognosis is unclear. Increased risk of atherosclerotic heart disease in adulthood is possible.

III. Juvenile Rheumatoid Arthritis (JRA)

  1. Definition

JRA is a disorder characterized by chronic joint inflammation in children, with or without extra-articular involvement.

  1. Epidemiology
  2. JRA is the most common pediatric rheumatic disease with arthritisas the distinguishing manifestation.
  3. The mean age of onset is 1–3 years; presentation before 6 months of age is unusual.
  4. JRA most commonly occurs in females, with two exceptions. Males are equally likely to have systemic-onset JRA, and they are much more likely to have late-onset pauciarticular JRA (male-to-female ratio is 10:1).
  5. Classification

The classification of JRA is determined on the basis of the clinical features present during the first 6 months of disease (Table 16-3). There are three categories of JRA: pauciarticular, polyarticular, and systemic. Regardless of type, all patients have arthritis during their clinical course.

  1. Clinical Features
  2. Pauciarticular JRA (≤four joints involved) accounts for approximately 40% of cases.
  3. Subtypes.Two subtypes of pauciarticular JRA are recognized on the basis of the age of onset.
  4. Early-onset pauciarticular JRAis female predominant. Patients usually present at 1–5 years of age. Seventy-five percent of patients have a positive antinuclear antibody (ANA). These patients are at high risk for developing chronic uveitis (50%), which is defined as inflammation of the iris and ciliary body. Uveitis must be monitored by regular slit-lamp evaluations.
  5. Late-onset pauciarticular JRA, unlike all other JRA types and subtypes, is malepredominant. Patients almost always present when older than 8 years of age. As in ankylosing spondylitis, the typical patient with late-onset pauciarticular JRA is male and is HLA-B27 positive, with involvement of the hips and sacroiliac joints. Uveitis is less common.

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  1. Articular involvementmay present with swelling of one or two joints, not necessarily symmetric. The most common joints involved are the knees and hips.

Table 16-3. Distinguishing Features of Juvenile Rheumatoid Arthritis Subtypes

Feature

Pauciarticular (≤ 4 joints)

Polyarticular (> 4 joints)

Systemic

Percentage of cases

40%

40%

20%

Systemic inflammation

Absent

Mild or absent

Severe

Subtypes

Early onset

Late onset

RF-

RF+

None

Sex predominance

Female

Male

Female

Female

Male = female

Serologic markers

ANA+

HLA-B27

RF-

RF+

-

Uveitis

Common

Uncommon

Rare

 

Rare

Joints

Hips and sacroiliac joints spared

Hips and sacroiliac joints involved

Multiple large and small joints

 

Multiple large and small joints

Prognosis

Risk of blindness if uveitis is untreated

Risk of spondylo-arthropathy

Children may suffer from deforming arthritis

 

50% recover completely 50% develop chronic destructive arthritis

RF = rheumatoid factor.

  1. Polyarticular JRA (>four joints involved) accounts for approximately 40% of cases, with systemic involvement and extra-articular features generally mild or absent.
  2. Subtypes.As in pauciarticular disease, polyarticular JRA 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 rheumatoid factor–negative (RF-) and rheumatoid factor–positive (RF+) polyarticular JRA affect females more frequently than males.
  3. RF-negative diseasepresents both early and late in childhood.
  4. RF-positive diseasepresents in children older than 8 years of age and is generally more severe than RF-negative disease, with higher risk of severe arthritis and rheumatoid nodules.
  5. Articular involvementis characterized by a symmetric polyarthritis that typically involves both small joints (hands and feet) and large joints (knees, ankles, and hips).
  6. Systemic-onset JRA (Still's disease) accounts for approximately 20% of cases. At presentation, severe systemic symptoms may overshadow joint symptoms.
  7. High spiking fevers(temperatures > 39°C [102.2°F]) occur most commonly in the late afternoon or evening and subsequently return quickly to baseline or subnormal levels.Still's disease is therefore typically included in the differential diagnosis of “fever of unknown origin.”
  8. Transient salmon-colored rashis 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.

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  1. Hepatosplenomegaly
  2. Lymphadenopathy
  3. Other features:
  4. Fatigue, anorexia, weight loss, and failure to thriveare common.
  5. Serositis, including pericarditis and pleuritis, is also common.
  6. CNS involvement, including meningitis and encephalopathy, may occasionally be present.
  7. Myositis and tenosynovitiscan also be seen in addition to the arthritis.
  8. Diagnosis

is generally on the basis of history and clinical features.Diagnostic criteria are listed in Table 16-4.

  1. aboratory findings

Laboratory results are nonspecific; if present, they reflect the existence or extent of inflammation.

  1. Anemiais usuallymicrocytic and hypochromic, consistent with anemia of chronic disease.
  2. Acute-phase reactantsare elevated, including ESR, CRP, and platelet count.
  3. Rheumatoid markers
  4. RFis negative in the majority of patients with JRA.
  5. ANAis present in 75% of patients with early-onset pauciarticular JRA and in 50% of patients with polyarticular JRA. ANA is not present in children with systemic-onset JRA and late-onset pauciarticular disease.
  6. Management

The goal of treatment is to decrease joint inflammation and preserve function.

  1. Control of inflammation
  2. Nonsteroidal anti-inflammatory drugs (NSAIDs) ease pain and inflammation.
  3. Immunomodulatory medications (e.g., glucocorticoids, methotrexate, sulfasalazine, hydroxychloroquine) are commonly used for more severe symptoms.
  4. Mechanical and physical measuresinclude physical and occupational therapy, as well as selective splinting to minimize joint contractures.

Table 16-4. Diagnostic Criteria for Juvenile Rheumatoid Arthritis

Age of onset ≤ 16 years of age
Arthritis in ≥ 1 joint defined as:
   Swelling or effusion OR
   Limitation of motion, tenderness, increased warmth
Duration of disease > 6 weeks
Exclusion of other causes of arthritis

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  1. Surgeryis generally reserved for patients who have recalcitrant joint contractures or destruction.
  2. Psychosocial support
  3. Prognosis

The outlook is generally good with current therapy. However, the incidence of complications depends on the type and subtype of JRA (see Table 16-3).

  1. Systemic Lupus Erythematosus (SLE)
  2. Definition

This multisystem autoimmune disorder is characterized by widespread inflammation of the connective tissues and immune complex–mediated vasculitis.

  1. Epidemiology
  2. There is a femalepredominance (female-to-male ratio is 8:1).
  3. Age of onsetis rare before 10 years of age and peaks in adolescence.
  4. Etiology

The cause of SLE is unknown, but the disease may be triggered by drug reactions, excessive sun exposure, infections, or hormonal changes (menarche, menopause, pregnancy).

  1. Clinical features

Signs and symptoms are variable and may involve multiple organ systems.

  1. Constitutional symptomssuch as fever, weight loss, and malaise are common.
  2. CNSinvolvement includes headache, encephalopathy, seizures, psychosis, and transverse myelitis.
  3. Skin findingsmay include amalar rash (“butterfly distribution” covering the nasal bridge and upper cheeks) and photosensitivity, both common at presentation or during an illness flare. Other common skin findings include alopecia and Raynaud's phenomenon.
  4. Arthralgias and arthritisare typically migratory and transient. SLE, unlike rheumatoid arthritis, rarely causes joint deformity or erosion. Myositis may also occur.
  5. GI involvementmay manifest as hepatosplenomegaly, splenic infarction, mesenteric thrombosis (secondary to vasculitis), and sterile peritonitis.
  6. Cardiovascular involvementis variable, withpericarditis 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 involvementmay include pleuritis, pulmonary hemorrhage, and interstitial fibrosis.
  8. Renal involvementis nearly universal, although lupus nephritis may be subclinical. Glomerulonephritis, nephrotic syndrome, hypertension, and subsequent renal failure are common.

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  1. Hematologicmanifestations typically include low white blood cell counts. In addition to leukopenia, anemia of chronic disease, thrombocytopenia, and Coombs-positive hemolytic anemia are also common findings.
  2. Diagnostic Criteria for SLE

(Table 16-5)

  1. Laboratory Findings
  2. Elevated ESR and CRP
  3. Anemia of chronic disease or anemia secondary to hemolysis
  4. Leukopenia
  5. Thrombocytopenia
  6. Urinalysis may show proteinuria depending on the extent of renal disease.
  7. Rheumatologic markers
  8. ANAis almost universally elevated (> 95%) in SLE. However, ANA isnonspecific for SLE and is found in many other diseases.
  9. RFis often elevated in SLE, but like ANA, is nonspecific.
  10. Anti–double-stranded DNA (anti-dsDNA) antibodiesare much more specific (found only in SLE), and their levels can be used as markers for active disease, especially nephritis.
  11. Anti-Smith (anti-Sm) antibodiesare 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.
  12. Others
  13. Antiphospholipid antibodies(e.g., positive lupus anticoagulant or anticardiolipin antibodies) present in patients with SLE reflect an increased risk of thrombotic events.
  14. Decreased complement (C3 and C4) is seen especially with active disease, and represents immune complex–mediated complement activation.

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)
Neurologic symptoms (encephalopathy, seizures, or psychosis)
Malar rash (butterfly rash)
Discoid lupus

* Four of eleven criteria provide a sensitivity and specificity of 96%.RPR = rapid plasma reagin; VDRL = Venereal Disease Research Laboratories; ANA = antinuclear antibody.

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  1. Management

Therapy is based on a multidisciplinary, team approach that attempts (1) to minimize and prevent inflammation and end-organ dysfunction and (2) to treat complications.

  1. Control of inflammation
  2. NSAIDsare useful only in the treatment of minor inflammatory symptoms, such as myalgias and arthralgias.
  3. Immunosuppressive medications
  4. Glucocorticoidsare 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.
  5. Cyclophosphamide, intravenously pulsed, is useful for children with severe lupus nephritis. Adverse effects of this cytotoxic agent include infertility and gonadal failure, secondary malignancies, and hemorrhagic cystitis.
  6. Other agentsinclude azathioprine, methotrexate, and cyclosporine.
  7. Treatment of complications
  8. Patients withthrombosisand antiphospholipid antibodies should be anticoagulated with low-molecular weight heparin or warfarin.
  9. Patients withrenal failuremay require dialysis, fluid and electrolyte management, and ultimately renal transplant.
  10. Psychosocial and family support
  11. 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 90% at 5–10 years after initial diagnosis. The major causes of mortality are infection (because of immunosuppression), renal failure or nephritis, and CNS complications.

  1. Dermatomyositis
  2. Definition

This inflammatory condition of muscle results in progressive muscle weakness with characteristic skin findings.

  1. Epidemiology
  2. Affected individuals are usually 5–14 yearsof age. The mean age of onset is 6 years of age.
  3. Femalesare more likely to be affected (female-to-male ratio is 2:1).
  4. Clinical Features
  5. Constitutional symptomsare common and include fatigue, anorexia, malaise, low-grade fevers, and weight loss.
  6. Characteristic cutaneous findings, particularly over sun-exposed areas, include:
  7. Periorbital violaceous heliotrope rash, which may also cross the nasal bridge
  8. Gottron's papules, in which the skin over the metacarpal and proximal interphalangeal joints (knuckles) may become erythematous and hypertrophic

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  1. Proximal muscle weakness(mostly of the hip girdle and legs) is insidious in onset and occurs weeks to months after the eruption of skin findings. It is characterized by a positiveGowers' sign, which is difficulty standing from the sitting position and having to “climb” up the thighs for support.
  2. Other manifestations include:
  3. Neck flexor muscle weakness
  4. Calcinosis(calcium deposition in muscle, fascia, and subcutaneous tissue), which may occur in approximately 40% of children
  5. Nail bed telangiectasias
  6. Constipationfrom GI smooth muscle dysfunction
  7. Dysphagia
  8. Cardiac involvementwith conduction abnormalities and dilated cardiomyopathy
  9. Diagnosis
  10. Classic clinical presentationof proximal muscle weakness with associated characteristic rashes
  11. Abnormal electromyographyfindings
  12. Abnormal muscle biopsyfindings
  13. Increased muscle enzymes(creatine phosphokinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and aldolase)
  14. Management
  15. Corticosteroidsare the mainstay of therapy.
  16. Other immunosuppressive agents, including methotrexate, cyclophosphamide, and cyclosporine, may be required for severe muscle disease.
  17. Vitamin D and calcium supplementationmay be necessary to help repair osteopenia and decrease frequency of fractures.
  18. Complications
  19. Aspiration pneumoniais a frequent complication as a result of a diminished gag reflex.
  20. Intestinal perforationmay result from GI vasculitis.
  21. Osteopeniasecondary to steroid therapy and muscle weakness may result in frequent fractures.
  22. Prognosis
  23. Prognosis is better in childrenthan in adults.
  24. There is no association with malignancy in pediatric dermatomyositis.(In adult disease, malignancy develops in 25% of patients.)
  25. Mortality rate is approximately 3%.

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  1. Rheumatic Fever
  2. Definition

Rheumatic fever is a delayed, nonsuppurative, autoimmune complication of upper respiratory infection with group A β-hemolytic streptococcus (Streptococcus pyogenes) that is characterized by inflammation of the connective tissues. Rheumatic fever predominantly affects the heart, blood vessels, joints, CNS, and skin.

  1. Epidemiology
  2. Rheumatic fever is now rare in the United Statesand Western Europe but was a worldwide problem during the 1960s. It is currently still common in developing nations.
  3. It is most common in children 5–15 years of age, reflecting the age group most susceptible to streptococcal throat infections.
  4. It has no gender predilection.
  5. The major risk factor is pharyngitiscaused by certain strains of group A β-hemolytic streptococcus (GABHS). The streptococcal strains that cause streptococcal skin infection (i.e., impetigo) do not cause rheumatic fever.
  6. Etiology

The cause of rheumatic fever is unknown, but the disease appears to be autoimmune in nature.

  1. Clinical Features
  2. Major features
  3. Cardiac involvementis found in50% of patients. It is thehallmark and most important complication of rheumatic fever. The inflammatory process may involve all layers of the heart, including the endocardium, myocardium, and pericardium.
  4. Endocarditisis the most common cardiac finding and typically causes insufficiency of the left-sided valves (mitral and aortic). It rarely affects the pulmonic or tricuspid valves.
  5. Myocarditisis usually manifested by tachycardia out of proportion to the extent of the fever. Other severe manifestations include cardiac dilatation and heart failure.
  6. Pericarditisand pericardial effusions are less common.
  7. Polyarthritisis classically migratory, asymmetric, and exquisitely painful. It occurs in 70% of patients and most commonly involves the elbows, knees, ankles, and wrists.It does not result in chronic joint disease.
  8. Sydenham's choreaoccurs 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.
  9. Skin involvement
  10. Erythema marginatumis a nonpruritic rash that starts as pink to red macules, which may coalesce and spread centripetally with central clearing over the trunk and proximal limbs.

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  1. 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 featuresinclude fever, arthralgias, leukocytosis, increased ESR, and prolonged PR interval on electrocardiogram.
  3. 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.

  1. Laboratory Findings
  2. Nonspecific inflammatory markers
  3. Elevated ESR and C-reactive protein
  4. Elevated white blood cell (WBC) count
  5. Serologic markers
  6. Antistreptolysin-Otiters are abnormally elevated in 70–80% of patients with rheumatic fever and are evidence of a recent GABHS infection.
  7. Anti-DNaseand anti-hyaluronidase antibodies may also be used to document GABHS infection.
  8. Echocardiography typically shows evidence of carditis, such as decreased ventricular function, valvular insufficiency, or pericardial effusion.
  9. Management
  10. Eradication of GABHS infection
  11. Benzathine penicillinintramuscular injection (one dose) or
  12. Penicillin orally for 10 days
  13. Control of inflammation
  14. NSAIDsare 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.

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

Major criteria:
   Migratory polyarthritis
   Carditis
   Sydenham's chorea
   Erythema marginatum
   Subcutaneous nodules
Minor criteria:
   Fever
   Arthralgia
   Previous rheumatic fever
   Leukocytosis
   Elevated erythrocyte sedimentation rate
   Elevated C-reactive protein
   Prolonged PR interval on electrocardiogram

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

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  2. Corticosteroidsare often used in patients with severe cardiac involvement, such as congestive heart failure and severe valvular dysfunction.
  3. Supportive therapy
  4. Congestive heart failureis treated with diuretics, dietary salt restriction, digoxin, and bed rest.
  5. Sydenham's chorea, if severe, may be treated with haloperidol.
  6. Long-term managementincludes continuous antimicrobial prophylaxis to prevent recurrent episodes of rheumatic fever.
  7. Prognosis
  8. There are no chronic sequelae of the joint, skin, and CNS manifestations of rheumatic fever.
  9. 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.

VII. Lyme Disease

  1. Definition

This reactive inflammatory disorder of the skin, heart, CNS, and connective tissues is caused by spirochetal infection with Borrelia burgdorferi and transmitted via a tick bite.

  1. 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.

  1. Etiology
  2. Vector.In the United States, most human infections occur during feeding by an infected deer tickIxodes scapularis. Transmission from Ixodes pacificus, which is the tick most prevalent in the Western United States, is less common.
  3. Organism.B. burgdorferi is passed into the bloodstream of the human host while the tick engorges itself with blood. Theinfected tick must be attached for more than 36–48 hours before the risk of B. burgdorferi transmission becomes substantial.
  4. 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 intotwo stages, early and late disease.

  1. Early disease(1–4 months after transmission)

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  1. Early localized diseaseis the first stage of Lyme disease and results from local cutaneous invasion and subsequent inflammation.
  2. Erythema migransis 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.
  3. Constitutional symptomsmay begin to occur during this stage and include fever, headache, myalgias, fatigue, arthralgias, and lymphadenopathy.
  4. Early disseminated diseaseis the second stage of Lyme disease and typically occurs within 1–4 months after the tick bite. In addition to cutaneous findings, it is characterized by involvement of other organ systems.
  5. Skin.Up to 25% of children may develop multiple secondary erythema migrans lesions, which tend to be smaller than the initial lesion.
  6. Constitutional symptoms(see section VII.D.1.a.(2)) may initially appear during and continue through this stage.
  7. Neurologic
  8. Aseptic meningitismay occur at this stage, but is rare (1%).
  9. Facial nerve palsyis 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.
  10. Encephalitis
  11. Carditis is rarebut usually presents asheart block or myocarditis.
  12. Late disease(5–12 months after transmission) occurs in approximately 7% of children, and its hallmark is arthritis, with other manifestations occurring less frequently.
  13. Diagnosis
  14. The diagnosisis strongly suggested in the presence of epidemiologic risk factors and a classic erythema migrans rash.
  15. Laboratory diagnosisis important in establishing a definitive diagnosis because erythema migrans is not always present and the clinical features and routine laboratory test results for Lyme disease may be nonspecific.
  16. Serologic testinginvolves the measurement of antibodies to B. burgdorferi in the patient's serum and is the recommended laboratory approach. The Centers for Disease Control and Prevention currently recommends a two-step procedure:
  17. Enzyme-linked immunosorbent assay (ELISA), which has a relatively high sensitivity
  18. Western blot, if the ELISA is positive or equivocal to confirm the diagnosis.
  19. Other laboratory tests(e.g., polymerase chain reaction, cultures from body fluids or tissue) are occasionally used but currently offer no advantage over the recommended serologic method.

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  1. Management. Treatment

is aimed at eradicating B. burgdorferi, with the caveat that symptoms caused by immune-mediated inflammation may not resolve immediately.

  1. Early localized disease, or late disease with arthritis only, is typically treated with either doxycycline (for children $ 9 years of age) or amoxicillin.
  2. Carditisand meningitis require intravenous ceftriaxone or penicillin.
  3. 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 (*).

  1. Seronegative spondyloarthropathies

This group of disorders involves the joints or axial skeleton and is characterized by the absence of RF, ANA, or other disease-specific serologic markers.

  1. Reactive arthritis.Inflammation of the joints is triggered by a microorganism, typically an enteric or sexually transmitted pathogen. An example is Reiter's disease, with its triad of arthritis, urethritis, and conjunctivitis, which is classically triggered by Chlamydia trachomatis.
  2. Psoriatic arthritis.This arthritis of the small and large joints is seen in patients with psoriatic skin disease. It is associated with the psoriatic findings of scaly skin plaques, nail pitting, and onycholysis (separation of the nail from the nailbed).
  3. Ankylosing spondylitis.This male-predominant, HLA-B27–related syndrome of arthritis affects the joints of the lower extremities and axial skeleton. It is characterized by enthesitis, which is inflammation of the tendinous insertions on the bone. Males with late-onset pauciarticular JRA are at high risk for developing this syndrome as adults.
  4. Arthritis of inflammatory bowel disease (IBD).This arthritis is associated with ulcerative colitis or Crohn's disease. Some patients with IBD and joint symptoms may be HLA-B27positive and have involvement of the axial skeleton in a pattern indistinguishable from ankylosing spondylitis.
  5. Other vasculitides

Like previously described vasculitic diseases (e.g., Kawasaki disease, SLE, Henoch-Schönlein purpura), these disorders are characterized by constitutional symptoms and inflammation of blood vessels.

  1. Takayasu's arteritis. This disease is a large-vessel vasculitis. The classic patient is an Asian female adolescent or young adult, 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).

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  1. *Wegener's 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.
  2. *Sjögren's syndrome

This syndrome is defined by a classic triad of findings, including sicca syndrome (dry mouth and eyes), high titers of autoantibodies (usually ANA or RF), and connective tissue disease.

  1. *Scleroderma
  2. 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.
  3. CREST syndromerefers to a form of scleroderma with less extensive involvement, manifesting with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerosis of the skin, and telangiectasias.

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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.

  1. A 4-year-old boy presents to the emergency department for evaluation after 1 day of diffuse abdominal pain and multiple petechial bruises on his bilateral thighs. He has no known history of prior bleeding or easy bruisability 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. However, 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/°mL. Hospital admission for which of the following treatments would be the most appropriate course of management 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) Observation and possible steroid therapy for a presumed diagnosis of Henoch-Schönlein purpura

(E) Parenteral antibiotic therapy for a presumed diagnosis of meningococcemia pending blood culture results

  1. A 3-year-old boy presents to the emergency department for evaluation of acute right upper quadrant abdominal pain. Further history reveals a 1-week history of spiking 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 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

  1. 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 to 103°F (39°C), 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 fever of 102.6°F (39.2°C) and a pink-red 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.

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  1. 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.

  1. 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.

  1. A 12-year-old boy presents with severe arthritis of the hips and sacroiliac joints. Laboratory studies reveal that the patient is HLA-B27 positive. Which of the following is the most likely diagnosis?

(A) Early-onset pauciarticular juvenile rheumatoid arthritis (JRA)

(B) Late-onset pauciarticular JRA

(C) Rheumatoid factor–negative polyarticular JRA

(D) Rheumatoid factor–positive polyarticular JRA

(E) Systemic-onset JRA

  1. 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/°mL

(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 set.

For each patient, select the most likely diagnosis.

  1. An HLA-B27–positive 14-year-old girl with abdominal pain and chronic diarrhea.

(A) Henoch-Schönlein purpura

(B) Psoriatic arthritis

(C) Still's disease

(D) Reiter's disease

(E) Arthritis of inflammatory bowel disease

(F) Systemic lupus erythematosus

(G) Kawasaki disease

(H) Dermatomyositis

(I) Pauciarticular juvenile rheumatoid arthritis

(J) Rheumatic fever

(K) Lyme disease

  1. A 6-year-old boy with erythematous and hypertrophic papules over the metacarpal and proximal interphalangeal joints and “dark rings” around the eyes.

(A) Henoch-Schönlein purpura

(B) Psoriatic arthritis

(C) Still's disease

(D) Reiter's disease

(E) Arthritis of inflammatory bowel disease

(F) Systemic lupus erythematosus

(G) Kawasaki disease

(H) Dermatomyositis

(I) Pauciarticular juvenile rheumatoid arthritis

(J) Rheumatic fever

(K) Lyme disease

  1. A sexually active 16-year-old girl with arthritis and conjunctivitis.

(A) Henoch-Schönlein purpura

(B) Psoriatic arthritis

(C) Still's disease

(D) Reiter's disease

(E) Arthritis of inflammatory bowel disease

(F) Systemic lupus erythematosus

(G) Kawasaki disease

(H) Dermatomyositis

(I) Pauciarticular juvenile rheumatoid arthritis

(J) Rheumatic fever

(K) Lyme disease

  1. A 3-year-old boy with fever, bilateral knee swelling, and a “salmon-colored” rash on the trunk and proximal extremities.

(A) Henoch-Schönlein purpura

(B) Psoriatic arthritis

(C) Still's disease

(D) Reiter's disease

(E) Arthritis of inflammatory bowel disease

(F) Systemic lupus erythematosus

(G) Kawasaki disease

(H) Dermatomyositis

(I) Pauciarticular juvenile rheumatoid arthritis

(J) Rheumatic fever

(K) Lyme disease

  1. A 14-year-old girl with arthritis, alopecia, leukopenia, and a “bad sunburn” on her face.

(A) Henoch-Schönlein purpura

(B) Psoriatic arthritis

(C) Still's disease

(D) Reiter's disease

(E) Arthritis of inflammatory bowel disease

(F) Systemic lupus erythematosus

(G) Kawasaki disease

(H) Dermatomyositis

(I) Pauciarticular juvenile rheumatoid arthritis

(J) Rheumatic fever

(K) Lyme disease

  1. A 5-year-old girl with arthritis, abdominal pain, and a petechial eruption on her buttocks.

(A) Henoch-Schönlein purpura

(B) Psoriatic arthritis

(C) Still's disease

(D) Reiter's disease

(E) Arthritis of inflammatory bowel disease

(F) Systemic lupus erythematosus

(G) Kawasaki disease

(H) Dermatomyositis

(I) Pauciarticular juvenile rheumatoid arthritis

(J) Rheumatic fever

(K) Lyme disease

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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 14 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, 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 or with arthritis. 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 compatible 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, II.D.4]. This patient meets the diagnostic criteria for Kawasaki disease based on the duration of fever and the presence of four of 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.D.3]. This patient has features consistent with systemic-onset juvenile rheumatoid arthritis (JRA). Intermittent high-spiking fevers, joint pain and swelling, lymphadenopathy, and hepatosplenomegaly are common features. The classic rash of systemic-onset JRA 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 medications (e.g., glucocorticoids), but intravenous immune globulin is not recommended for use in JRA. Children with systemic-onset JRA have a 50% chance of having a severe, erosive arthritis. Antinuclear antibodies (ANA) in patients with systemic-onset JRA are negative, in contrast to most patients with early-onset pauciarticular JRA and 50% of patients with polyarticular JRA in whom ANA is positive.
  5. The answer is B[VII.C.2, VII.D.1, 2, 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 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 $ 9 years of age 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 5–12 months after the initial clinical presentation. It occurs in approximately 7% of children with Lyme disease. Serologic testing (enzyme-linked immunosorbent assay and Western blot analysis) is recommended for confirmation of disease.

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  1. The answer is A[VI.A, VI.B.4, VI.D, VI.E, VI.G, 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's 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.
  2. The answer is B[III.D and Table 16-3]. Unlike all other types and subtypes of JRA, late-onset pauciarticular JRA is male predominant and almost always presents in children older than 8 years of age. Typically, patients with late-onset pauciarticular JRA, similar to patients with ankylosing spondylitis, are HLA-B27–positive and have involvement of the hips and sacroiliac joints. In contrast, patients with early-onset pauciarticular JRA 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 JRA (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 JRA may be either male or female and also have involvement of large and small joints, with sacroiliac joints less commonly affected. Other presenting features of systemic-onset JRA include fever, a characteristic transient skin rash (salmon-colored), hepatosplenomegaly, and lymphadenopathy.
  3. 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, brawny 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.

9–14. The answers are E, H, D, C, F, and A, respectively [VIII.A.4, V.C.2, VIII.A.1, III.D.3, IV.C, D, 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's disease. Some patients with inflammatory bowel disease are also HLA-B27 positive and have involvement of the axial skeleton that 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's papules). Reiter's disease is an example of a reactive arthritis triggered by an enteric or sexually transmitted pathogen (classically, Chlamydia trachomatis). Reiter's disease presents with arthritis, conjunctivitis, and urethritis. The diagnosis of systemic-onset juvenile rheumatoid arthritis (Still's disease) 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's 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.