What is Kawasaki disease in children under 5 years old?

What is Kawasaki Disease

Kawasaki disease is an acute, self-limited systemic vasculitis that predominantly affects children under 5 years of age and represents the leading cause of acquired heart disease in developed countries, with the most serious consequence being coronary artery aneurysms that develop in 25% of untreated patients. 1, 2

Disease Characteristics

Etiology and Pathogenesis:

• The cause remains unknown, though clinical and epidemiological features strongly suggest an infectious trigger in genetically susceptible individuals 1
• The disease manifests as fever, rash, conjunctival injection, oral mucosal changes, and cervical adenopathy—a pattern consistent with infectious etiology 1
• Epidemiological patterns include winter-spring seasonality, community outbreaks with wave-like geographic spread, and apparent epidemic cycles 1
• The rarity in very young infants and adults suggests an infectious agent to which adults are immune and from which infants are protected by maternal antibodies 1

Pathophysiology:

• Coronary arteritis begins 6-8 days after disease onset, causing inflammation of all arterial layers with complete circumferential spread 3
• The inflammation is characterized by granulomatous changes with severe monocyte/macrophage accumulation, leading to structural arterial damage and dilation 3
• Peak mortality occurs 15-45 days after fever onset when established coronary vasculitis coincides with marked platelet elevation and hypercoagulability 1

Epidemiology

Incidence Patterns:

• In the United States, approximately 4,248 hospitalizations occur annually with a median patient age of 2 years 1
• Race-specific incidence (per 100,000 children <5 years): Asian/Pacific Islander descent (32.5), African American (16.9), Hispanic (11.1), and white (9.1) 1
• Boys outnumber girls by 1.5 to 1.7:1 1
• 76% of affected children are under 5 years old 1

Mortality:

• Case fatality rate is 0.08% in Japan and 0.17% in-hospital mortality in the United States 1
• Virtually all deaths result from cardiac sequelae, including sudden death from myocardial infarction that may occur years later in patients with coronary aneurysms and stenoses 1

Clinical Diagnosis

Classic Diagnostic Criteria:

• Fever lasting at least 5 days PLUS at least 4 of 5 principal clinical features 4, 5, 6:
  • Bilateral bulbar conjunctival injection (nonexudative, primarily affecting bulbar conjunctiva) 4, 6
  • Oral mucosal changes (erythema and cracking of lips, strawberry tongue, erythema of oral/pharyngeal mucosa) 4, 6
  • Polymorphous rash (most commonly maculopapular, diffuse erythroderma, or erythema multiforme-like) 4, 6
  • Extremity changes (erythema and edema of hands/feet in acute phase; periungual desquamation in subacute phase starting 2-3 weeks later) 4, 6
  • Cervical lymphadenopathy (usually unilateral, ≥1.5 cm diameter, confined to anterior cervical triangle—this is the least common feature) 4, 6

Fever Characteristics:

• High-spiking fever typically exceeding 39-40°C (102.2-104°F) with remittent pattern 4, 5
• Without treatment, fever persists 1-3 weeks with a mean of 11 days 4, 6
• Day of fever onset counts as day 1 4

Diagnostic Timing Modifications:

• Diagnosis can be made with only 4 days of fever when ≥4 principal features are present, particularly with hand and foot swelling 4, 5
• Experienced clinicians may establish diagnosis with only 3 days of fever in rare cases with classic presentations 4, 5

Incomplete (Atypical) Kawasaki Disease

When to Consider:

• Children with fever ≥5 days AND only 2-3 principal features 4, 5, 6
• Infants with fever ≥7 days without other explanation 4, 5
• This presentation is more common in children younger than one year, who paradoxically have higher rates of coronary artery aneurysms if untreated 1

Evaluation Algorithm:

• When fever ≥5 days with only 2-3 features present, immediately measure ESR and CRP 6
• Consider complete blood count, comprehensive metabolic panel, urinalysis, and echocardiography 6
• Coronary artery complications occur at least as frequently in incomplete cases as in classic cases 6

High-Risk Populations Requiring Heightened Suspicion

Infants Under 6 Months:

• May present with only prolonged fever and irritability 4, 5
• Have the highest risk of coronary abnormalities despite minimal clinical features 4, 5, 6

Older Children and Adolescents:

• Often have delayed diagnosis and higher prevalence of coronary artery abnormalities 5

Supportive Laboratory Findings

• Elevated ESR (often >40 mm/hour, commonly ≥100 mm/hour) and CRP (typically ≥3 mg/dL) 1, 4, 6
• Normal or elevated white blood cell count with neutrophil predominance 4, 6
• Thrombocytosis (common in second week after fever onset) 4, 5
• Low serum sodium and albumin levels 4, 6
• Elevated serum liver enzymes 4, 6
• Sterile pyuria 4, 6

Critical Diagnostic Pitfalls

Temporal Evolution:

• Clinical features are typically not all present simultaneously—watchful waiting and careful review of prior signs and symptoms may be necessary 4, 6
• Features evolve over days, requiring serial examinations 6

Mimicking Conditions:

• Cervical lymphadenopathy as the predominant initial finding can mimic bacterial lymphadenitis, significantly delaying diagnosis 4, 6
• Exudative conjunctivitis or pharyngitis, discrete intraoral lesions, bullous or vesicular rash, and generalized lymphadenopathy would help exclude the diagnosis 1
• Scarlet fever and Multisystem Inflammatory Syndrome in Children (MIS-C) should be considered in differential diagnosis 6

Treatment and Prognosis

Acute Management:

• Early treatment with IVIG (2 g/kg single dose) and high-dose aspirin (80-100 mg/kg/day divided into four doses) within 10 days of fever onset significantly reduces coronary artery abnormality risk from 25% to approximately 5% 1, 4, 6, 2
• Fever typically resolves within 36 hours after IVIG completion; persistence indicates IVIG resistance requiring further therapy 4, 5
• High-dose aspirin is reduced to low-dose (3-5 mg/kg/day) for antiplatelet effect, continued until 6-8 weeks after disease onset if no coronary abnormalities are present 1

Long-term Implications:

• Kawasaki disease is the leading cause of acquired heart disease among children in developed countries 6, 2
• Giant coronary artery aneurysms develop in approximately 1% of treated patients 1
• Many cases of fatal and nonfatal myocardial infarction in young adults have been attributed to "missed" Kawasaki disease in childhood 1