How is Kawasaki disease diagnosed in a child under five years old presenting with fever for at least five days and possible clinical features?

Diagnosing Kawasaki Disease in Children

Primary Diagnostic Approach

Kawasaki disease is diagnosed clinically when a child presents with fever lasting at least 5 days plus 4 out of 5 principal clinical 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), and cervical lymphadenopathy (≥1.5 cm). 1, 2

Key Diagnostic Criteria

• Fever requirement: Temperature exceeding 39-40°C (102.2-104°F) for at least 5 days, with a remittent pattern that persists despite antibiotics and antipyretics 1, 3
• Principal clinical features (need 4 of 5):
  • Bilateral bulbar conjunctival injection without exudate or photophobia 1, 3
  • Oral changes: erythematous cracked lips, strawberry tongue, diffuse oral/pharyngeal erythema (no ulcers or exudates) 1, 3
  • Polymorphous rash: typically maculopapular, truncal with groin accentuation, or erythroderma (never vesicular or bullous) 1, 3
  • Extremity changes: sharp demarcation of erythema/edema at wrists/ankles acutely; periungual desquamation appears 2-3 weeks later 1, 3
  • Cervical lymphadenopathy: unilateral, ≥1.5 cm, anterior cervical triangle (least common feature) 1, 3

Early Diagnosis Exception

• Experienced clinicians can diagnose Kawasaki disease with only 3-4 days of fever when ≥4 principal features are clearly present, particularly with hand/foot swelling. 1, 3

Incomplete (Atypical) Kawasaki Disease

Consider incomplete Kawasaki disease in any child with fever ≥5 days and only 2-3 principal features, or in infants with fever ≥7 days without alternative explanation. 2, 3

Evaluation Algorithm for Incomplete Disease

When fever ≥5 days with only 2-3 features present:

1. Immediately measure ESR and CRP 1, 2
2. If ESR or CRP elevated, obtain:
   • Complete blood count (looking for leukocytosis >15,000/µL, anemia, thrombocytosis >450,000/µL after day 7) 2
   • Serum albumin (hypoalbuminemia ≤3.0 g/dL supports diagnosis) 2
   • Serum transaminases (elevated ALT indicates hepatic involvement) 2
   • Urinalysis (sterile pyuria >10 WBC/hpf is characteristic) 1, 2
3. Obtain echocardiogram to assess for coronary artery abnormalities 1, 2

Echocardiographic Diagnosis

• Classic Kawasaki disease can be diagnosed with only 3 clinical features if coronary artery abnormalities are present on echocardiography (z-score ≥2.5 for LAD or RCA, aneurysm, or ≥3 suggestive features like perivascular brightness, lack of tapering, coronary ectasia) 1, 2

High-Risk Populations Requiring Heightened Suspicion

Infants ≤6 Months

• This age group has the highest risk of coronary abnormalities yet frequently presents with incomplete features—only prolonged fever and irritability may be present. 2, 3
• In infants ≤6 months with fever ≥7 days and no alternative explanation, perform laboratory testing and echocardiography even if classic criteria are absent. 2
• Infants ≤3 months show principal features at lower frequencies: oral changes 84%, conjunctival injection 80%, rash 68%, lymphadenopathy 28%, extremity changes only 24% 4
• 80% of infants ≤3 months develop coronary artery involvement despite incomplete presentations 4

Children of Asian Descent

• Japanese children have incidence rates of 150 per 100,000 versus 10-15 per 100,000 in the United States, requiring lower threshold for diagnosis 5

Critical Diagnostic Pitfalls to Avoid

• Clinical features are typically NOT all present simultaneously—carefully review the history for sequential appearance of signs over the preceding days 1, 3
• Sterile pyuria should never be dismissed as a partially treated urinary tract infection; it is a characteristic finding of Kawasaki disease 2
• Cervical lymphadenopathy as the predominant initial finding mimics bacterial lymphadenitis, causing significant diagnostic delay—maintain suspicion when fever persists despite antibiotics 1, 3
• Rash or strawberry tongue appearing after antibiotic treatment for presumed bacterial infection represents Kawasaki disease, not drug reaction 2, 5
• Children with only 2-3 clinical features but laboratory evidence of inflammation require full evaluation including echocardiography 2

Supportive Laboratory Findings (Not Required for Diagnosis)

• Elevated ESR and CRP (document ongoing inflammation) 2, 3
• Leukocytosis >15,000/µL with neutrophil predominance 2, 3
• Thrombocytosis >450,000/µL (typically after day 7; may be normal early) 2, 3
• Hypoalbuminemia ≤3.0 g/dL 2, 3
• Elevated ALT 2, 3
• Sterile pyuria >10 WBC/hpf 1, 2
• Age-appropriate anemia 2

Differential Diagnosis Requiring Exclusion

• Viral infections: measles, adenovirus (distinguished by clinical pattern and testing) 2
• Bacterial infections: scarlet fever (positive strep test), staphylococcal scalded skin syndrome 2
• Multisystem Inflammatory Syndrome in Children (MIS-C): requires SARS-CoV-2 testing 5

Urgency of Diagnosis and Treatment

Early treatment with IVIG (2 g/kg single infusion) and aspirin within 10 days of fever onset reduces coronary artery abnormality risk from 25% to approximately 5%. 1, 5, 3

• High clinical suspicion permits initiation of IVIG and aspirin before completing full echocardiographic evaluation 2
• Kawasaki disease is the leading cause of acquired heart disease in children in developed countries, making timely recognition critical 5, 6
• Incomplete Kawasaki disease carries at least equal risk of coronary complications as classic disease 5