When to Suspect Kawasaki Disease
Suspect Kawasaki disease in any child—particularly those under 5 years old—who presents with fever lasting ≥5 days (typically >39°C/102.2°F) that fails to respond to antibiotics or antipyretics, especially when accompanied by any combination of bilateral non-purulent conjunctival injection, oral mucosal changes (cracked lips, strawberry tongue), polymorphous rash, extremity changes, or cervical lymphadenopathy. 1, 2
Classic Diagnostic Criteria
The diagnosis requires fever for at least 5 days PLUS 4 out of 5 principal clinical features 3, 1:
- Bilateral conjunctival injection: Non-purulent, primarily bulbar with limbal sparing; notably absent photophobia or eye pain 3, 2
- Oral mucosal changes: Erythema and cracking of lips, strawberry tongue, diffuse erythema of oral/pharyngeal mucosa 1, 2
- Polymorphous rash: Most commonly diffuse maculopapular eruption, erythroderma, or erythema multiforme-like pattern 1, 2
- Extremity changes: Erythema and edema of hands/feet with sharp demarcation at wrists/ankles (acute phase); periungual desquamation starting 2-3 weeks later (subacute phase) 3, 2
- Cervical lymphadenopathy: Usually unilateral, ≥1.5 cm diameter, confined to anterior cervical triangle—this is the least common principal feature 1, 2
Critical Timing Modifications
You can diagnose with only 4 days of fever when ≥4 principal features are present, particularly when hand and foot swelling are evident 1, 2. Experienced clinicians may even diagnose with 3 days of fever in rare classic presentations, though this requires significant clinical judgment 1, 2.
High-Risk Populations Requiring Heightened Suspicion
Infants <6 Months
Maintain extremely high suspicion in infants under 6 months, as they may present with only prolonged fever and irritability yet have the highest risk of coronary abnormalities 1, 2. Consider incomplete Kawasaki disease in any infant with fever ≥7 days without other explanation 1, 2.
Older Children and Adolescents
Older children and adolescents often have delayed diagnosis and higher prevalence of coronary artery abnormalities due to atypical presentations 1.
Asian Descent
Children of Asian descent have significantly higher incidence rates (up to 20 times higher than Caucasians), with Japanese children having rates of 150 per 100,000 versus 10-15 per 100,000 in the United States 3, 4.
Incomplete (Atypical) Kawasaki Disease
Suspect incomplete Kawasaki disease when:
- Children with fever ≥5 days AND only 2-3 principal features 1, 2
- Infants with fever ≥7 days without other explanation 1, 2
This is critically important because coronary artery complications occur at least as frequently in incomplete cases as in classic cases 3, with up to 25% developing coronary aneurysms if untreated 5.
Evaluation Algorithm for Incomplete Disease
When fever ≥5 days with only 2-3 features present 1, 5:
Key Fever Characteristics
- Temperature typically exceeds 39-40°C (102.2-104°F) with remittent pattern 3, 1, 2
- Persists despite antibiotic and antipyretic treatment 4
- Untreated, lasts average 11 days (range 1-3 weeks) 3, 2
- Day of fever onset counts as day 1 2
Supportive Laboratory Findings
While not diagnostic, these findings increase suspicion 2:
- Elevated ESR and CRP (acute phase reactants) 3, 2
- Leukocytosis with neutrophil predominance 2, 6
- Thrombocytosis (common in second week after fever onset) 1, 2
- Low serum sodium and albumin 2
- Elevated liver enzymes 2, 6
- Sterile pyuria 2
Critical Diagnostic Pitfalls to Avoid
Sequential Appearance of Features
Clinical features are typically NOT all present simultaneously—careful review of prior signs and symptoms over the preceding days is essential 2. Taking a meticulous history is necessary in children who lack clear explanation for fever 3.
Mimicry of Bacterial Lymphadenitis
When cervical lymphadenopathy is the predominant initial finding, it can mimic bacterial lymphadenitis and significantly delay diagnosis—fever persists despite antibiotics and other typical features follow 2.
Antibiotic Reaction Misattribution
Do not attribute strawberry tongue and rash solely to antibiotic reaction if the patient was initially treated for presumed bacterial infection—this is a classic missed diagnosis scenario 5.
Absence of Conjunctivitis
Do not dismiss Kawasaki disease because conjunctivitis is absent—incomplete disease is more common in infants <1 year and can present with fewer than 4 principal features 5.
Additional Clinical Features That Should Raise Suspicion
- Extreme irritability (particularly in infants) 1
- Musculoskeletal features: Arthritis and arthralgia occur in approximately one-third of patients in acute phase 1, 2
- Gastrointestinal features: Diarrhea, vomiting, abdominal pain, hepatitis, gallbladder hydrops 2
- Perineal desquamation (early finding) 5
Differential Diagnosis Considerations
The American Heart Association emphasizes that many clinical features of Kawasaki disease may be present in other illnesses, requiring exclusion of alternative diagnoses 3:
- Scarlet fever: High fever, strawberry tongue, sandpaper-like rash (most common ages 5-15 years) 5
- Multisystem Inflammatory Syndrome in Children (MIS-C): Overlapping features but typically more prominent GI symptoms, lower platelet counts, higher CRP levels; requires SARS-CoV-2 testing 5
Urgency of Recognition
Early treatment with IVIG (2 g/kg) and aspirin within 10 days of fever onset significantly reduces coronary artery abnormality risk from 25% to approximately 5% 1, 2, 5. This makes timely recognition critical for preventing the most feared complication: coronary artery aneurysms that can lead to myocardial infarction, sudden death, or ischemic heart disease 3, 7.
Kawasaki disease has replaced acute rheumatic fever as the leading cause of acquired heart disease among children in developed countries 3, making it imperative to maintain high clinical suspicion in any child with prolonged unexplained fever.