Kawasaki Disease

Epidemiology

• Predominantly affects children under 5 years, with peak incidence at 6-24 months
• More common in boys than girls
• Highest incidence in Asian children - approximately 1 in 80 Japanese children develops KD by age 5 (incidence: 20-100 per 100,000 children under 5 in Asia)
• Occurs in all racial groups; found worldwide
• Seasonal variation: peaks in winter and spring
• No confirmed infectious agent has been identified, though epidemiologic patterns (seasonality, community outbreaks) strongly support an infectious trigger
• Fitzpatrick's Dermatology, Ch. 142
• Rosen's Emergency Medicine, p. 2417

Pathogenesis

1. Neutrophil necrotizing arteritis - occurs in the first 2 weeks; damages vessel wall structural integrity
2. Subacute/chronic vasculitis - begins in the first 2 weeks, can persist months to years; comprised of CD8 T lymphocytes, IgA plasma cells, eosinophils, and macrophages
3. Luminal myofibroblastic proliferation - closely linked to chronic vasculitis; leads to progressive arterial stenosis months to years later

• Fitzpatrick's Dermatology, Ch. 142

Clinical Features

Phase I: Acute Febrile Phase (~12 days)

• Prolonged high fever (often >39-40°C) lasting >5 days - the cardinal feature
• Bilateral non-exudative conjunctival injection with limbal sparing (~90% of cases)
• Oral mucosal changes: red, dry, cracked, bleeding lips; "strawberry" tongue; diffuse oropharyngeal erythema (no ulcers)
• Polymorphous rash - begins on palms/soles, spreads to extremities and trunk within 2 days
• Erythema and painful edema of the hands and feet
• Cervical lymphadenopathy - at least one node >1.5 cm; usually unilateral and nonfluctuant (least common feature, ~75%)
• Arthritis of small interphalangeal joints can occur
• Myocarditis present in >50% of patients during this phase, manifested as tachycardia disproportionate to fever

Phase II: Subacute Phase (up to ~30 days)

• Fever resolves
• Periungual desquamation beginning at fingertips/toes, progressing to the entire soles and palms
• Thrombocytosis (platelet count often >450,000/mm³ after day 7)
• Arthritis, arthralgias
• High risk of sudden death if untreated (coronary aneurysm most vulnerable)

Phase III: Convalescent Phase (~6-8 weeks)

• Most signs resolve
• ESR normalizes
• Coronary aneurysms, if present, are diagnosed here (echocardiography or coronary angiography)

Typical facial features: conjunctival injection and red, dry lips - Fitzpatrick's Dermatology, Ch. 142

Periungual desquamation of the feet in the subacute phase - Fitzpatrick's Dermatology, Ch. 142

Diagnostic Criteria (CDC/AHA)

• Textbook of Family Medicine, 9e, p. 915

Laboratory Findings

• Leukocytosis (WBC ≥15,000/mm³ with neutrophil predominance)
• Elevated ESR and CRP (ESR >40 mm/h; elevated CRP) - elevated in acute/subacute phases
• Thrombocytosis (platelets ≥450,000/mm³ after day 7 of illness)
• Elevated ALT (liver involvement)
• Hypoalbuminemia (albumin ≤3.0 g/dL)
• Normocytic anemia
• Sterile pyuria (≥10 WBC/HPF on urinalysis)
• ECG: PR and QT prolongation, ST/T wave changes
• Aseptic meningitis may be found on lumbar puncture

Complications

• Coronary artery dilation and aneurysms in ~25% of untreated cases
• Myocardial infarction - from aneurysm thrombosis (most common in first few months) or from coronary stenosis (months to years later)
• Aneurysm rupture - less common, usually within the first month
• Pericardial effusion - present in the acute phase, usually resolves spontaneously
• Aneurysms of other medium-sized arteries (iliac, femoral, axillary) in severe cases
• Valvulitis (rare)

Long-term consequences are confined to the heart and vascular tree. There are no known long-term non-cardiovascular sequelae.

• Fitzpatrick's Dermatology, Ch. 142

Management

Acute Treatment (within first 10 days of fever):

• IVIG 2 g/kg as a single infusion - the cornerstone of treatment. IVIG given within the first 10 days reduces coronary artery aneurysm prevalence from 25% down to ~5% (a fivefold reduction)
• High-dose aspirin (80-100 mg/kg/day in 4 divided doses) during the acute febrile phase - anti-inflammatory
• After fever resolves, aspirin is reduced to low-dose (3-5 mg/kg/day) for antiplatelet effect, continued until echocardiography confirms no coronary abnormalities (typically 6-8 weeks)

What NOT to use:

• Antibiotics - not useful unless a concomitant bacterial infection is present
• Corticosteroids - may actually increase the incidence of aneurysms and should be avoided if possible in routine cases (though used as adjunct therapy for IVIG-resistant cases per recent data)

Monitoring:

• Serial echocardiograms - at diagnosis, 2-3 weeks into illness, and 1 month later
• Early cardiology evaluation is essential
• Textbook of Family Medicine, 9e; Rosen's Emergency Medicine; Fitzpatrick's Dermatology, Ch. 142

Differential Diagnosis

• Scarlet fever (streptococcal)
• Viral exanthems (measles, adenovirus, EBV)
• Stevens-Johnson syndrome / toxic epidermal necrolysis
• Juvenile idiopathic arthritis (systemic form)
• Toxic shock syndrome
• Drug hypersensitivity reactions
• Staphylococcal scalded skin syndrome

2024 AHA Update

• New criteria defining North American patients at high risk for coronary artery aneurysms who may benefit from more intensive initial treatment
• Advances in cardiovascular imaging (CT angiography, MRI) improving detection of coronary stenosis
• Updated safety and dosing data for several anti-inflammatory adjunct therapies
• New anticoagulation strategies and MI management protocols for patients with established aneurysms

Key Summary Points