What is Kawasaki disease?

Kawasaki Disease

Kawasaki disease is an acute systemic vasculitis of childhood that predominantly affects the coronary arteries, representing the leading cause of acquired heart disease among children in developed countries. 1, 2

Clinical Features and Diagnosis

Kawasaki disease primarily affects children under 5 years of age, with a higher incidence in children of Asian descent, particularly Japanese. The male-to-female ratio is approximately 1.5:1 1.

Diagnostic Criteria

Diagnosis is based on clinical criteria, as no specific diagnostic test exists:

Classic (Typical) Kawasaki Disease:

• Fever persisting at least 5 days
• Plus at least 4 of the following 5 principal features:
  1. Changes in extremities:
     • Acute: Erythema and edema of hands and feet
     • Convalescent: Membranous desquamation of fingertips
  2. Polymorphous exanthema/rash (primarily truncal, often with accentuation in the groin)
  3. Bilateral, painless bulbar conjunctival injection without exudate
  4. Changes in lips and oral cavity: Erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
  5. Cervical lymphadenopathy (≥1.5 cm in diameter), usually unilateral 1

Important note: The diagnosis can still be made by experienced physicians if classic features are present before day 5 of fever 1. Additionally, Kawasaki disease can be diagnosed with only 3 clinical features if coronary artery abnormalities are detected on echocardiography 1.

Incomplete (Atypical) Kawasaki Disease

This refers to patients with fever lasting at least 5 days who have fewer than 4 of the principal clinical features. Diagnosis is particularly challenging in these cases, but important because:

• More common in children younger than 1 year
• These children paradoxically have a higher risk of coronary artery aneurysms if not treated 1

Laboratory Findings

While not specific, these findings support the diagnosis:

• Elevated ESR (often >40 mm/hour) and CRP (≥3 mg/dL)
• Leukocytosis with left shift
• Hypoalbuminemia
• Mild anemia
• Thrombocytosis (typically in the second week)
• Elevated liver enzymes
• Sterile pyuria 1, 2

Cardiovascular Manifestations

Cardiac findings may include:

• Gallop rhythm or distant heart sounds
• ECG changes (arrhythmias, abnormal Q waves, prolonged PR/QT intervals)
• Cardiomegaly on chest X-ray
• Echocardiographic changes:
  • Coronary artery abnormalities (lack of tapering, perivascular brightness, ectasia, aneurysms)
  • Decreased ventricular function
  • Mild valvular regurgitation
  • Pericardial effusion 1, 2

Treatment

Early treatment is crucial to reduce the risk of coronary artery abnormalities from 20-25% to less than 5% 2, 3.

Standard Initial Therapy

• IVIG: 2 g/kg as a single infusion, ideally within the first 10 days of illness
• Aspirin: High-dose (80-100 mg/kg/day divided into four doses) during the acute phase until the patient is afebrile for 48-72 hours, then reduced to low-dose (3-5 mg/kg/day) for antiplatelet effect 2, 3

Management of IVIG Resistance

Approximately 10-20% of patients develop recrudescent or persistent fever at least 36 hours after IVIG infusion. Options include:

• Second dose of IVIG (2 g/kg)
• Corticosteroids for those who fail to respond to a second IVIG dose
• Infliximab (5 mg/kg IV) may be considered after failure of a second IVIG dose
• Other alternatives for refractory cases include cyclosporine, anakinra, cyclophosphamide, or methotrexate 2, 3, 4

Follow-up and Monitoring

• Echocardiography should be performed at diagnosis, within 1-2 weeks, and 4-6 weeks after treatment for uncomplicated cases
• For patients with coronary abnormalities, more frequent imaging (at least twice weekly) until dimensions stabilize
• Long-term aspirin therapy is recommended for patients who develop coronary artery abnormalities 2

Important Considerations

• Medication interactions: Avoid ibuprofen in children taking aspirin as it may antagonize aspirin's antiplatelet effect
• Immunizations: Defer measles and varicella immunizations for 11 months after high-dose IVIG administration
• Annual influenza vaccination is recommended for children on long-term aspirin therapy to reduce the risk of Reye syndrome 2

Long-term Implications

• Sclerotic vascular changes may occur in post-Kawasaki disease patients, even in those without coronary lesions during the acute phase
• Endothelial dysfunction and risk factors for atherosclerosis have been observed in the late phase of Kawasaki disease
• Long-term follow-up is essential, especially for those who developed coronary abnormalities 4

Differential Diagnosis

Common conditions that may mimic Kawasaki disease include adenovirus infection, scarlet fever, and drug reactions. Features that would help exclude the diagnosis include exudative conjunctivitis or pharyngitis, discrete intraoral lesions, bullous or vesicular rash, and generalized lymphadenopathy 1.