Kawasaki Disease
Kawasaki disease is an acute vasculitis of childhood primarily affecting medium-sized arteries, particularly the coronary arteries. Treatment with IVIG within 10 days of fever onset reduces coronary aneurysm risk from 25% to <5%.
Key Facts
Kawasaki disease: Most common acquired heart disease in children in developed countries Peak age: 6 months to 5 years; boys > girls (1.5:1); higher incidence in East Asian populations Diagnostic criteria: Fever ≥5 days + ≥4 of 5 clinical features (CRASH: Conjunctivitis, Rash, Adenopathy, Strawberry tongue/lip changes, Hand/foot changes) IVIG 2g/kg single infusion within 10 days of fever onset — reduces coronary aneurysm risk from ~25% to <5% High-dose aspirin (30-50mg/kg/day in divided doses) during acute phase; reduce to low-dose (3-5mg/kg/day) after defervescence for 6-8 weeks Coronary artery aneurysms develop in ~25% without treatment; ~5% with treatment Incomplete Kawasaki: Fever ≥5 days with <4 clinical features — still diagnose and treat if supporting laboratory/echo findings Echocardiography: At diagnosis, 2 weeks, 6-8 weeks — assess coronary arteries
Overview
Key Facts
Kawasaki disease is the leading cause of acquired heart disease in children in developed countries. It is a clinical diagnosis with no confirmatory test. Early treatment with IVIG has dramatically reduced the risk of coronary artery complications.
Epidemiology
Incidence in the UK: approximately 8-9 per 100,000 children <5 years. Much higher in Japan (~300 per 100,000 <5 years). Peak age: 6 months to 5 years. Male:female ratio 1.5:1. Slight seasonal variation (winter/spring).
Aetiology
- Unknown: Likely an abnormal immune response to one or more infectious triggers in genetically susceptible children
- NOT directly infectious but has seasonal and geographic clustering
- Genetic susceptibility factors identified (ITPKC, CASP3 polymorphisms — particularly in Japanese populations)
Pathophysiology
Kawasaki disease is a systemic vasculitis predominantly affecting medium-sized arteries (especially coronary arteries). The acute phase involves neutrophilic infiltration of arterial walls, endothelial damage, and disruption of the internal elastic lamina. This leads to aneurysm formation, particularly at bifurcation points of the coronary arteries. The coronary artery inflammation can cause stenosis, thrombosis, and myocardial infarction.
Clinical Presentation
Diagnostic Criteria (Fever + 4/5 Features)
CRASH mnemonic:
- Conjunctivitis: Bilateral, non-purulent, limbal sparing
- Rash: Polymorphous (maculopapular, erythema multiforme-like, diffuse erythema); NOT vesicular
- Adenopathy: Cervical lymphadenopathy >1.5cm (often unilateral — least common feature)
- Strawberry tongue + lip changes: Red, cracked lips; strawberry tongue; oropharyngeal erythema
- Hand/foot changes: Erythema and oedema acutely; periungual desquamation (peeling) in convalescent phase (weeks 2-3)
Other Features
- Extreme irritability (very characteristic)
- Perianal erythema/desquamation
- BCG site inflammation
- Arthritis, aseptic meningitis, hepatitis, hydrops of gallbladder
Red Flags
- Coronary artery dilatation on echo — treat urgently
- Shock/haemodynamic instability — Kawasaki shock syndrome (10%)
- IVIG-resistant (persistent fever >36h post-IVIG) — second dose IVIG or infliximab
- Incomplete Kawasaki — diagnose and treat even with <4 features if supporting evidence
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Kawasaki disease | Fever ≥5d, 4/5 CRASH features, irritability | Clinical, echo, raised ESR/CRP |
| Scarlet fever | Sandpaper rash, strawberry tongue, GAS pharyngitis | Throat swab, ASOT |
| Measles | Coryza, cough, conjunctivitis, Koplik spots, maculopapular rash | Clinical, measles IgM |
| Viral exanthem | Various rashes, usually mild | Clinical |
| Drug reaction | Drug history, timing, mucosal involvement | Clinical, drug history |
| Systemic JIA | Quotidian fever, salmon-pink rash, arthritis | Ferritin, FBC |
Diagnosis / Investigation
Bloods
- FBC: Leucocytosis, thrombocytosis (peaks week 2-3 — very characteristic), anaemia
- CRP and ESR: Markedly elevated (CRP >100, ESR >40 supports diagnosis)
- LFTs: Raised transaminases, hypoalbuminaemia
- U&Es: Sterile pyuria (urine WCC from urethral inflammation)
- Blood cultures: Negative (exclude bacterial infection)
Imaging
- Echocardiography: At diagnosis, 2 weeks, and 6-8 weeks — assess coronary artery dimensions (Z-scores), LV function, pericardial effusion, valve regurgitation
Special Tests
- Urine microscopy: Sterile pyuria
- ECG: Prolonged PR, ST changes, arrhythmia (rare)
- CT/MR coronary angiography: For follow-up of known aneurysms in older children
Management
Pharmacological
- IVIG 2g/kg IV over 10-12 hours — single infusion; give within 10 days of fever onset
- Aspirin high-dose: 30-50mg/kg/day in 4 divided doses during acute febrile phase
- Aspirin low-dose: 3-5mg/kg/day after defervescence; continue for 6-8 weeks (or lifelong if aneurysm)
IVIG-Resistant (Fever >36h Post-IVIG)
- Second dose IVIG 2g/kg
- IV methylprednisolone: 30mg/kg for 3 days
- Infliximab 5mg/kg: Single dose (anti-TNF-α)
Coronary Aneurysm Management
- Small/medium aneurysm: Low-dose aspirin ± clopidogrel; serial echo
- Giant aneurysm (>8mm or Z-score >10): Aspirin + warfarin/LMWH; cardiology follow-up; may need coronary intervention
Non-pharmacological
- Rest: During acute phase
- Avoid live vaccines: For 11 months after IVIG (immunoglobulin interferes with vaccine response)
Referral Criteria
- All suspected Kawasaki — paediatric assessment and echo within 24h
- Coronary artery abnormalities — paediatric cardiology
- IVIG-resistant — discuss with tertiary centre
Prognosis
- Without treatment: ~25% develop coronary artery aneurysms
- With IVIG within 10 days: <5% develop coronary artery aneurysms
- Giant aneurysms: Risk of thrombosis, stenosis, MI; lifelong cardiology follow-up
- Coronary regression: ~50% of small-medium aneurysms regress within 1-2 years
- Mortality: <0.1% in developed countries with treatment
- Long-term: Children with coronary involvement need lifelong cardiovascular follow-up; may develop premature atherosclerosis
Other Relevant Information
Kawasaki Disease Treatment Timeline
| Phase | Treatment |
|---|---|
| Acute (febrile) | IVIG 2g/kg + high-dose aspirin |
| Subacute (weeks 2-6) | Low-dose aspirin; serial echo |
| Convalescent (6-8 weeks) | Echo; stop aspirin if no aneurysm |
| Long-term (if aneurysm) | Aspirin ± anticoagulation; lifelong cardiology |
Coronary Artery Classification (Z-Scores)
| Classification | Criteria |
|---|---|
| No involvement | Z-score <2 |
| Dilation | Z-score 2-2.5 |
| Small aneurysm | Z-score 2.5-5 |
| Medium aneurysm | Z-score 5-10 |
| Giant aneurysm | Z-score ≥10 or absolute >8mm |