How is Kawasaki disease diagnosed and managed in a child under five years old?

Kawasaki Disease: Diagnosis and Management in Children Under Five

Diagnostic Approach

Diagnose Kawasaki disease clinically when a child presents with fever lasting ≥5 days plus at least 4 of 5 principal features: bilateral non-purulent conjunctival injection, oral mucosal changes (cracked lips, strawberry tongue, diffuse oral erythema), polymorphous rash, extremity changes (erythema/edema of hands and feet with sharp demarcation at wrists/ankles), and cervical lymphadenopathy (≥1.5 cm, usually unilateral). 1, 2

Classic (Complete) Kawasaki Disease

The diagnosis requires:

• Fever ≥5 days (typically >39-40°C, remittent pattern, unresponsive to antibiotics/antipyretics) 1, 2
• Plus ≥4 of the following 5 principal features: 1, 3, 2
  • Bilateral conjunctival injection (bulbar, non-purulent, limbal sparing, no photophobia) 1, 2
  • Oral changes (erythematous cracked lips, strawberry tongue, diffuse oral/pharyngeal erythema) 2
  • Polymorphous rash (maculopapular, diffuse erythroderma, or erythema multiforme-like; often with perineal accentuation) 4, 2
  • Extremity changes (erythema and edema of hands/feet with sharp demarcation at wrists/ankles; periungual desquamation occurs 2-3 weeks later) 4, 2
  • Cervical lymphadenopathy (≥1.5 cm, usually unilateral, anterior cervical triangle) 2

Critical diagnostic caveat: Clinical features are typically not all present simultaneously—carefully review the entire illness course for sequential appearance of criteria. 2

Incomplete (Atypical) Kawasaki Disease

Suspect incomplete Kawasaki disease in children with fever ≥5 days and only 2-3 principal features, or in infants ≤6 months with fever ≥7 days without alternative explanation. 1, 3, 2

Incomplete disease carries at least as high a risk of coronary complications as classic disease, making recognition critical. 1, 2

Evaluation Algorithm for Suspected Incomplete Disease:

1. Measure inflammatory markers: ESR and CRP 1, 3

2. If ESR/CRP elevated, obtain supplemental laboratory criteria: 1, 3

   • CBC (leukocytosis >15,000/mm³, anemia for age, platelets >450,000/µL after day 7) 3
   • Comprehensive metabolic panel (albumin ≤3.0 g/dL, elevated ALT) 3
   • Urinalysis (sterile pyuria >10 WBC/hpf) 3

3. Obtain echocardiogram if: 1, 3

   • ≥3 supplemental laboratory criteria are positive, OR
   • Infant ≤6 months with fever ≥7 days regardless of laboratory findings 3

4. Echocardiogram is positive if any of: 1, 3

   • Coronary artery z-score ≥2.5 (LAD or RCA) 3
   • Aneurysm by Japanese Ministry of Health criteria 1
   • ≥3 suggestive features (perivascular brightness, lack of tapering, decreased LV function, mitral regurgitation, pericardial effusion, or z-scores 2-2.5) 1, 3

If echocardiogram is positive OR clinical suspicion remains high with ongoing inflammation (elevated ESR/CRP), treat immediately. 1, 3

High-Risk Populations Requiring Heightened Vigilance

• Infants <6 months: Highest risk for coronary abnormalities; may present with only prolonged fever and irritability 3, 2
• Infants ≤6 months with fever ≥7 days: Perform laboratory testing and echocardiography even without classic clinical criteria 1, 3
• Asian descent children: Significantly higher incidence (150/100,000 in Japanese children vs. 10-15/100,000 in US) 1, 2
• Older children/adolescents: Often have delayed diagnosis and higher prevalence of coronary abnormalities 1

Management

Treat with intravenous immunoglobulin (IVIG) plus aspirin within 10 days of fever onset to reduce coronary artery abnormality risk from 25% to approximately 5%. 2, 5

Acute Phase Treatment:

• IVIG: Single infusion (dosing per protocol) 5, 6
• Aspirin: High-dose anti-inflammatory therapy initially 5, 7
• Treatment can be initiated before completing echocardiographic evaluation if clinical suspicion is high 3

IVIG-Refractory Disease:

Approximately 10% of children remain febrile within 36 hours after IVIG completion, which is associated with higher risk of coronary lesions. 8, 7

For IVIG resistance: 7, 6

• Second dose of IVIG with or without corticosteroids 5, 6
• Consider methylprednisolone pulse therapy or infliximab (TNF-α blockade) 7, 6

Long-Term Monitoring:

• All patients require echocardiography at diagnosis 3, 5
• Follow-up intensity determined by presence and severity of coronary abnormalities 5, 7
• Pediatric cardiology supervision is mandatory initially 7

Critical Diagnostic Pitfalls to Avoid

• Sterile pyuria should not be dismissed as partially treated UTI—it is a characteristic feature of Kawasaki disease 3
• Cervical lymphadenopathy can mimic bacterial lymphadenitis; consider Kawasaki disease if rash and other features develop after antibiotic treatment 2
• Strawberry tongue and rash after antibiotics should not be attributed solely to drug reaction 2
• Infants <6 months may present atypically with only fever and irritability yet have the highest coronary risk 3, 2
• Clinical features appear sequentially, not simultaneously—review the entire illness timeline 2

Differential Diagnosis Considerations

Exclude these mimics before diagnosing Kawasaki disease: 2, 8

• Viral infections: Measles, adenovirus (differentiate by clinical presentation and testing) 3
• Bacterial infections: Scarlet fever, staphylococcal scalded skin syndrome 3
• Multisystem Inflammatory Syndrome in Children (MIS-C): Consider SARS-CoV-2 testing 2

Why Early Recognition Matters

Kawasaki disease is the leading cause of acquired heart disease in children in developed countries. 1, 2 Mortality results almost exclusively from cardiac sequelae, with peak risk 15-45 days after fever onset when coronary vasculitis coincides with thrombocytosis and hypercoagulability. 1 Untreated, 15-25% develop coronary aneurysms that can lead to myocardial infarction, sudden death, or chronic ischemic heart disease. 1, 8