Kawasaki Disease: Diagnosis and Treatment
Diagnosis of Kawasaki Disease
Diagnose classic Kawasaki disease when a child presents with fever lasting at least 5 days plus at least 4 of the 5 principal clinical features: bilateral conjunctival injection, oral mucosal changes, polymorphous rash, extremity changes, and cervical lymphadenopathy. 1
Principal Clinical Features
The five cardinal features required for diagnosis are:
- Bilateral conjunctival injection: Non-purulent, primarily affecting the bulbar conjunctiva with limbal sparing, notably without photophobia or eye pain 1, 2
- Oral mucosal changes: Erythema and cracking of lips, strawberry tongue, and diffuse injection of oral and pharyngeal mucosa 1, 2
- Polymorphous rash: Most commonly diffuse maculopapular eruption, erythroderma, or erythema multiforme-like pattern, typically truncal with groin accentuation 1, 3
- Extremity changes: Acute phase shows erythema and edema of hands and feet with sharp demarcation at wrists/ankles; convalescent phase (2-3 weeks later) shows periungual desquamation 1, 2
- Cervical lymphadenopathy: Usually unilateral, ≥1.5 cm diameter, confined to anterior cervical triangle (least common principal feature) 1, 3
Fever Characteristics
The fever in Kawasaki disease has specific patterns that aid diagnosis:
- Temperature typically exceeds 39-40°C (102.2-104°F) with a remittent pattern 2, 3
- Persists despite antibiotic and antipyretic treatment 4, 5
- Without treatment, lasts an average of 11 days (range 1-3 weeks) 3, 4
- Day of fever onset counts as day 1 2, 3
Modified Diagnostic Timing
Experienced clinicians can make the diagnosis with only 4 days of fever when ≥4 principal features are present, particularly when hand and foot swelling are evident. 2, 3 In rare cases with classic presentations, diagnosis may be established with only 3 days of fever, though this requires significant clinical experience 2, 3.
Incomplete (Atypical) Kawasaki Disease
Consider incomplete Kawasaki disease in children with fever ≥5 days AND only 2-3 principal features, or in infants with fever ≥7 days without other explanation. 3, 4
When incomplete Kawasaki disease is suspected, follow this algorithm:
Patients with fever and fewer than 4 principal symptoms can be diagnosed with Kawasaki disease when coronary artery disease is detected by 2-dimensional echocardiography or coronary angiography. 1
Supportive Laboratory Findings
While not diagnostic, these findings support the diagnosis:
- Elevated ESR and CRP (acute phase reactants) 2, 4
- Leukocytosis with neutrophil predominance 2, 4
- Thrombocytosis (common in second week after fever onset) 2, 3
- Low serum sodium and albumin 2, 4
- Elevated serum liver enzymes 2, 4
- Sterile pyuria 2, 6
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, 4 This age group often has incomplete presentations, making diagnosis particularly challenging and delaying treatment 6. Children of Asian descent have significantly higher incidence rates, with Japanese children having rates of 150 per 100,000 versus 10-15 per 100,000 in the United States 4, 5.
Critical Diagnostic Pitfalls
Clinical features are typically not all present simultaneously—careful review of prior signs and symptoms over the preceding days is essential to establish diagnosis. 2, 4 Cervical lymphadenopathy as the predominant initial finding can mimic bacterial lymphadenitis, significantly delaying diagnosis; fever persists and other typical features follow 2, 4. Do not attribute strawberry tongue and rash solely to antibiotic reaction 4.
Treatment of Kawasaki Disease
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 four doses). 1
Timing of Treatment
Initiate IVIG as early as possible within the first 10 days of illness onset (day of fever onset), as soon as the diagnosis can be established. 1 Early treatment with IVIG and aspirin within 10 days of fever onset significantly reduces coronary artery abnormality risk from approximately 25% to 4-5% 1, 4.
Treatment for Delayed Diagnosis
IVIG should also be administered to children presenting after the tenth day of illness if they have ongoing systemic inflammation manifested by elevation of ESR or CRP (CRP >3.0 mg/dL) together with either persistent fever without other explanation or coronary artery aneurysms (luminal dimension Z score >2.5). 1 Those in whom fever has resolved, laboratory values have normalized, and echocardiograms are normal do not require IVIG treatment 1.
IVIG Administration Details
- Dose: 2 g/kg as a single infusion 1
- Infusion time: Usually given over 10-12 hours 1
- Expected response: Fever typically resolves within 36 hours after IVIG completion 2, 3
The efficacy of this regimen is well-established through meta-analyses demonstrating a dose-response effect, with higher doses given in a single infusion having the greatest efficacy 1.
Aspirin Regimen
High-dose aspirin (80-100 mg/kg/day divided into four doses) should be given with IVIG during the acute phase. 1 After fever resolution and clinical improvement, aspirin is typically continued at lower anti-platelet doses for thromboprophylaxis 1.
IVIG-Resistant Kawasaki Disease
Approximately 10-20% of patients do not respond to initial IVIG, defined as persistent or recurrent fever after initial IVIG infusion. 1
For IVIG-resistant patients, treatment options include:
- Second dose of IVIG (2 g/kg) with or without corticosteroids 1, 7
- Intravenous pulsed methylprednisolone 5, 8
- Infliximab (TNF-α antagonist) 1, 5
- Combinations of these approaches 5, 8
The 2017 American Heart Association guidelines provide detailed recommendations for additional therapies in IVIG-refractory patients 1.
Echocardiographic Monitoring
Perform baseline echocardiography at diagnosis to assess for coronary artery dilatation or aneurysm formation. 1, 5 Echocardiography is the diagnostic imaging modality of choice to screen for coronary aneurysms 7. Careful initial management of evolving coronary artery abnormalities is essential, necessitating increased frequency of assessments and escalation of thromboprophylaxis 1.
Recurrent Kawasaki Disease
Patients with recurrent Kawasaki disease, defined as a repeat episode after complete resolution of the previous episode, should receive standard therapy with IVIG and aspirin. 1
Long-Term Management
Risk stratification for long-term management is based primarily on maximal coronary artery luminal dimensions, normalized as Z scores, and is calibrated to both past and current involvement. 1 Patients with aneurysms require life-long and uninterrupted cardiology follow-up 1. The long-term prognosis is determined by the initial and current level of coronary artery involvement 1.