What is Kawasaki disease, its typical presentation, treatment, and prevention in children under 5 years old?

Kawasaki Disease Overview

Kawasaki disease is an acute systemic vasculitis of unknown etiology that predominantly affects children under 5 years of age (80% of cases) and represents the leading cause of acquired heart disease in children in developed countries. 1

Epidemiology and Risk Factors

• Incidence varies significantly by ethnicity: highest in Asian/Pacific Islander children (32.5/100,000), intermediate in African Americans (16.9/100,000) and Hispanics (11.1/100,000), and lowest in whites (9.1/100,000) 1
• Male predominance: boys outnumber girls by 1.5:1 to 1.7:1 1
• Peak age: median age is 2 years, with 76% of cases occurring in children under 5 years 1
• Seasonal pattern: more common during winter and early spring months 1
• Mortality: case fatality rate is 0.08-0.17%, with virtually all deaths resulting from cardiac complications 1

Clinical Presentation

Classic Diagnostic Criteria

The American Heart Association defines classic Kawasaki disease as fever lasting at least 5 days PLUS at least 4 of the following 5 principal features: 1, 2, 3

1. Oral mucosal changes: erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa 1, 3

2. Bilateral bulbar conjunctival injection: nonexudative, painless, with limbal sparing 1, 3

3. Polymorphous rash: most commonly diffuse maculopapular eruption, erythroderma, or erythema multiforme-like 1, 3

4. Extremity changes:

   • Acute phase: erythema and edema of hands and feet 1, 3
   • Convalescent phase: membranous periungual desquamation of fingertips 1, 3

5. Cervical lymphadenopathy: usually unilateral, ≥1.5 cm diameter (least common principal feature) 1, 3

Fever Characteristics

• High-spiking fever typically exceeding 39-40°C (102.2-104°F) with remittent pattern 1, 2, 3
• Without treatment, fever persists 1-3 weeks (mean 11 days) 1, 3
• Day of fever onset counts as day 1 2, 3

Modified Diagnostic Timing

• Diagnosis can be made with only 4 days of fever when ≥4 principal features are present, particularly with hand/foot swelling 2, 3
• Experienced clinicians may diagnose with 3 days of fever in rare classic presentations 2, 3
• Diagnosis can be made with only 3 clinical features if coronary artery abnormalities are detected on echocardiography 1

Incomplete (Atypical) Kawasaki Disease

Consider incomplete Kawasaki disease in children with fever ≥5 days AND only 2-3 principal features, or infants with fever ≥7 days without other explanation. 2, 4

High-Risk Populations Requiring Heightened Suspicion

• Infants <6 months may present with only prolonged fever and irritability, yet have the highest risk of coronary abnormalities 2, 3, 4
• Older children and adolescents often have delayed diagnosis and higher prevalence of coronary artery abnormalities 2, 4

Evaluation Algorithm for Incomplete Disease

When incomplete Kawasaki disease is suspected: 2, 4

• Check inflammatory markers (ESR and CRP) 2, 4
• If ESR ≥40 mm/hr and/or CRP elevated, assess supplemental laboratory criteria 2, 4
• Obtain echocardiogram to evaluate for coronary artery abnormalities 4

Supportive Laboratory and Clinical Findings

Laboratory Abnormalities

• Elevated ESR and CRP (acute phase reactants) 1, 2, 3
• Leukocytosis with left shift and neutrophil predominance 1, 3
• Thrombocytosis (common in second week after fever onset) 1, 2, 3
• Hypoalbuminemia and hyponatremia 1, 3
• Elevated serum transaminases 1, 3
• Sterile pyuria 1, 3

Additional Clinical Features

• Cardiovascular: gallop rhythm, distant heart sounds, ECG changes (arrhythmias, prolonged PR/QT intervals, ST-T wave changes), pericardial effusion 1
• Gastrointestinal: diarrhea, vomiting, abdominal pain, hydrops of gallbladder, mild jaundice 1, 3
• Musculoskeletal: arthritis and arthralgia in approximately one-third of patients in acute phase 2, 3

Critical Diagnostic Pitfalls

• Clinical features are typically not all present simultaneously—watchful waiting and careful review of prior signs/symptoms may be necessary 3
• Cervical lymphadenopathy as predominant initial finding can mimic bacterial lymphadenitis, significantly delaying diagnosis 3
• No specific diagnostic test exists for Kawasaki disease; diagnosis is entirely clinical 1, 4

Treatment

Acute Phase Management

First-line treatment is intravenous immunoglobulin (IVIG) 2 g/kg as a single infusion PLUS high-dose aspirin (80-100 mg/kg/day divided into 4 doses). 1

• Early treatment with IVIG and aspirin within 10 days of fever onset significantly reduces coronary artery abnormality risk from approximately 20% to 3-5% 1, 2, 3
• Fever typically resolves within 36 hours after IVIG completion; persistence indicates IVIG resistance requiring further therapy 2, 3

IVIG-Refractory Cases

Approximately 10-20% of patients do not respond to initial IVIG 1, 5

Treatment options for refractory cases include: 1, 5

• Second dose of IVIG
• Corticosteroids (methylprednisolone pulse therapy)
• Infliximab (TNF-alpha blockade)
• Other immunomodulatory agents in severe cases

Long-term Management

• Aspirin dose reduced to antiplatelet dose (3-5 mg/kg/day) once fever resolves and continued for 6-8 weeks if no coronary abnormalities 1
• Patients with coronary aneurysms require lifelong cardiology follow-up and uninterrupted thromboprophylaxis 1
• Risk stratification based on maximal coronary artery luminal dimensions, normalized as Z scores 1

Etiology and Pathogenesis

• Etiology remains unknown, though clinical and epidemiological features strongly suggest an infectious trigger in genetically susceptible individuals 1
• Hypothesis: ubiquitous infectious agent produces clinically apparent disease only in genetically predisposed children, particularly Asians 1
• Pathogenesis involves endothelial cell activation, CD68 monocyte/macrophages, CD8 lymphocytes, and oligoclonal IgA plasma cells 1
• Prominence of IgA plasma cells suggests respiratory portal of entry 1

Prevention

No preventive measures exist as the etiology is unknown and there is no vaccine. Early recognition and prompt treatment remain the only strategies to prevent cardiac complications. 1