What are the symptoms and treatment of Kawasaki disease?

Kawasaki Disease: Clinical Presentation and Management

Kawasaki disease is diagnosed by fever lasting at least 5 days plus at least 4 of 5 principal clinical features: bilateral nonexudative conjunctivitis, oral mucosal changes (erythema and cracking of lips, strawberry tongue), polymorphous rash, extremity changes (erythema/edema of hands and feet or periungual desquamation), and cervical lymphadenopathy (≥1.5 cm, usually unilateral). 1, 2

Diagnostic Criteria

Classic Kawasaki Disease

The diagnosis requires:

• Fever for ≥5 days (first calendar day of fever = illness day 1) 1, 2
• Plus ≥4 of the 5 principal clinical features listed above 1, 2

Important exception: Diagnosis can be made with only 4 days of fever when ≥4 principal features are present, particularly when hand/foot swelling is evident. 1, 2 Experienced clinicians may rarely diagnose with only 3 days of fever in classic presentations. 1, 2

Key Clinical Features in Detail

Fever characteristics:

• Typically high-spiking, reaching 39-40°C (102.2-104°F) or higher 1, 2
• Remittent pattern with peaks and valleys 1
• Without treatment, persists 1-3 weeks on average 2

Conjunctivitis:

• Bilateral bulbar injection without exudate 1, 2
• Characteristically spares the limbus (avascular zone around iris) 1
• Anterior uveitis often detected on slit-lamp examination 1

Oral mucosal changes:

• Erythema and cracking of lips 1, 2
• Strawberry tongue appearance 1, 2
• Diffuse erythema of oral and pharyngeal mucosa 1, 2

Rash:

• Most commonly diffuse maculopapular eruption 1, 2
• May also present as scarlatiniform erythroderma or erythema multiforme-like patterns 1
• Typically extensive on trunk and extremities 1
• Accentuation in groin with early desquamation is characteristic 1
• Critical caveat: Bullous, vesicular, or petechial rashes are NOT consistent with Kawasaki disease and should prompt alternative diagnosis 1

Extremity changes:

• Acute phase: erythema and edema of hands and feet 1, 2
• Subacute phase (weeks 2-3): periungual desquamation 1, 2

Cervical lymphadenopathy:

• Least common of the principal features 1, 2
• Usually unilateral, ≥1.5 cm diameter 1, 2
• Confined to anterior cervical triangle 1
• Important pitfall: May be the most prominent initial finding, mimicking bacterial lymphadenitis and delaying diagnosis 1

Incomplete (Atypical) Kawasaki Disease

Consider this diagnosis in:

• Children with fever ≥5 days AND only 2-3 principal features 2
• Infants with fever ≥7 days without other explanation 2

Critical to recognize: Incomplete disease has at least as high a risk of coronary complications as classic disease. 1 This is particularly important in:

• Infants <6 months: May present with only prolonged fever and irritability, yet have the highest risk of coronary abnormalities 2
• Older children and adolescents: Often have delayed diagnosis and higher prevalence of coronary artery abnormalities 2

Evaluation algorithm for incomplete disease:

• Check inflammatory markers (ESR, CRP) 2
• Assess supplemental laboratory criteria 2
• Perform echocardiography to evaluate for coronary abnormalities 1, 2

Treatment Protocol

Initial Therapy

Standard treatment consists of:

• IVIG 2 g/kg as a single infusion 1, 3, 4
• High-dose aspirin 80-100 mg/kg/day divided into 4 doses 3, 4
• Timing is critical: Administer as early as possible within first 10 days of fever onset to significantly reduce coronary artery abnormality risk 2, 3, 4

Aspirin management:

• Continue high-dose until afebrile for at least 48 hours 3, 4
• Then reduce to low-dose 3-5 mg/kg/day as single daily dose 3, 4
• Continue low-dose until 6-8 weeks after disease onset if no coronary abnormalities present 3, 4
• For patients with coronary abnormalities, may continue indefinitely 3

Expected response: Fever typically resolves within 36 hours after IVIG completion; persistence indicates IVIG resistance requiring further therapy. 2, 3

IVIG-Resistant Disease (10-20% of patients)

First-line for resistance:

• Second dose of IVIG 2 g/kg as single infusion 3, 4

Second-line options if fever persists after second IVIG:

• Methylprednisolone 20-30 mg/kg IV for 3 days 3, 4
• Infliximab 5 mg/kg IV over 2 hours 3, 4

Third-line for highly refractory cases:

• Cyclosporine 4-6 mg/kg/day orally (monitor for hyperkalemia) 3
• Plasma exchange reserved for patients failing all medical therapies 3

Long-term Antiplatelet/Anticoagulation

Risk-stratified approach:

No coronary abnormalities:

• Low-dose aspirin until 6-8 weeks after disease onset 3, 4

Small coronary aneurysms:

• Low-dose aspirin indefinitely 3

Moderate aneurysms (4-6 mm):

• Low-dose aspirin PLUS second antiplatelet agent (e.g., clopidogrel 1 mg/kg/day, max 75 mg/day) 3

Giant aneurysms (≥8 mm):

• Low-dose aspirin PLUS warfarin (target INR 2.0-3.0) 3, 4
• Alternative: aspirin plus therapeutic low-molecular-weight heparin for infants or when warfarin difficult to regulate 3, 4

Critical Monitoring

Highest thrombosis risk: First 3 months, with peak incidence days 15-45 3, 4

Surveillance requirements:

• Frequent echocardiography and ECG during first 3 months, especially for giant aneurysms 3, 4

Essential Caveats and Pitfalls

Vaccination considerations:

• Defer measles and varicella immunizations for 11 months after high-dose IVIG 3, 4
• Annual influenza vaccination recommended for children on long-term aspirin therapy 3, 4

Drug interactions:

• Avoid ibuprofen in children taking aspirin for antiplatelet effects—it antagonizes irreversible platelet inhibition 3

Delayed diagnosis risks:

• Treatment beyond 10 days increases coronary artery abnormality risk 3
• Incomplete disease more common in infants <1 year, who paradoxically have higher aneurysm rates if untreated 3

Clinical features may not all be present simultaneously—careful history may reveal features that resolved before presentation. 1 Spontaneous fever resolution after 7 days should NOT exclude Kawasaki disease diagnosis. 1

Prognosis Without Treatment

Coronary artery aneurysms or ectasia develop in 15-25% of untreated children, potentially leading to myocardial infarction, sudden death, or ischemic heart disease. 1 This makes Kawasaki disease the leading cause of acquired heart disease in children in developed countries. 1