Kawasaki Disease
Kawasaki disease is an acute systemic medium-sized vessel vasculitis that usually affects young children, with characteristic coronary artery involvement.
Epidemiology
Kawasaki disease is the 2nd most common systemic vasculitis in children
Usually seen in children from 6 months to 5 years of age, and is more common in
- Males
- East Asian populations (“Kawasaki” is a Japanese name)
- Winter and spring
Causes
No clear cause has been identified.
It is thought to be an exaggerated immune-mediated vasculitis triggered by an as-yet unidentified infectious exposure in genetically susceptible children
Clinical Features and Diagnosis
Kawasaki disease is primarily a clinical diagnosis.
Consider the possibility of Kawasaki disease in ALL children with fever lasting ≥ 5 days.
There is no single investigation or imaging test that can confirm Kawasaki disease.
Echocardiography is important for assessing cardiac complications, particularly coronary artery aneurysms, but it is not used to diagnose Kawasaki disease, and a normal echocardiogram does NOT exclude Kawasaki disease.
Classic diagnostic criteria:
- Fever for at least 5 days, PLUS
- At least 4 out of 5 of the classic clinical features of Kawasaki disease
| Clinical feature | Description / notes |
|---|---|
| Fever for at least 5 days |
|
| The 5 classic clinical features (to fulfil the 2nd part of the diagnostic criteria) | |
| Conjunctival injection |
|
| Oral changes |
|
| Cervical lymphadenopathy |
|
| Rash | The rash is typically widespread:
|
| Extremity changes (hands and feet) |
|
CRASH is a commonly used acronym used to remember the 5 classic clinical features:
- Conjunctival injection
- Rash
- Adenopathy (cervical
- Strawberry tongue and other oral changes
- Hands and feet erythema and swelling
Complications
Cardiac complications of Kawasaki disease are most serious and important, including:
- Coronary artery aneurysm – most common
- Aneurysm rupture is highly fatal
- Thrombosis / stenosis can lead to myocardial ischaemia or infarction
- Myocarditis / pericarditis
- Aortic root dilatation
- Arrhythmias
Macrophage activation syndrome is a rare but serious complication, suggested by:
- Persistent higher fever and CRP
- Low ESR and fibrinogen
- High or rising ferritin level (>1,000)
- Cytopaenia (at least 2 cell lineages) or falling cell counts
- High triglycerides and LFTs
Investigations
Investigations During Acute Illness
As mentioned above, no single investigation or imaging test can confirm Kawasaki disease. Characteristic laboratory findings may help support the diagnosis (esp. in atypical cases) and help exclude differential diagnoses.
| Investigation / laboratory test | Findings in Kwasaki disease / purpose |
|---|---|
| Hb |
|
| Platelet count |
|
| WCC and inflammatory markers |
|
| LFTs and U&Es |
|
| Blood cultures |
|
| Throat swab, ASOT, anti-DNase B |
|
| Urine dipstick and microscopy |
|
Cardiac Monitoring
ALL patients diagnosed with Kawasaki disease should be referred to paediatric cardiology
- ECG and echocardiography for at least 2 occasions are necessary (at 2-3 weeks, and 6-8 weeks after diagnosis)
- Subsequent follow-up depends on the echo findings
- Purpose: to check for a coronary artery aneurysm (most frequent location: proximal left anterior descending artery)
- Echo findings may range from dilated coronary artery, small aneurysm, medium aneurysm, and giant aneurysm
If the patient were found to have a giant coronary artery aneurysm, long-term warfarin should be started to prevent thrombosis (INR target: 2.0-2.5)
Role of echocardiography in the acute / diagnostic phase:
- Do NOT delay initiation of IV immunoglobulin to perform echocardiography
- An urgent echo is useful in those with strongly suspected Kawasaki disease who do NOT fulfil all the clinical criteria for diagnosis
- The presence of a coronary artery abnormality is diagnostic of incomplete Kawasaki disease
- However, a normal echo does NOT exclude Kawasaki disease
Management
Standard 1st line management:
- IV immunoglobulin (IVIG) single dose of 2g/kg over 12 hours (reduces risk of complications), and
- Aspirin (provides cardiovascular protection)
- Initially, high-dose aspirin (7.5-12.5 mg/kg QDS) should be given
- Once fever has subsided for 24 hours and inflammatory markers are down-trending, change to low-dose aspirin (2-5 mg/kg OD)
- Low-dose aspirin should be continued for at least 6-8 weeks
IVIG is the most important treatment for Kawasaki disease
- It rapidly reduces inflammation and lowers the risk of coronary artery aneurysm development
- For full benefits, it should be given within 10 days of fever onset
IVIG and MMR/varicella vaccination:
- Administration of IVIG can interfere with the immune response to parenteral live vaccines if given concomitantly with or shortly before or after the vaccine
- The Greenbook recommends:
- Defer MMR and varicella vaccination for 3 months post-IVIG (but likely better if deferred for 9 months)
- If the vaccine was given 14 days or more prior to IVIG, no repeat dose of vaccination is necessary
Although aspirin is generally contraindicated in children because of the risk of Reye’s syndrome, Kawasaki disease is an important exception.
In Kawasaki disease, aspirin is used because the risk of serious cardiac complications, particularly coronary artery aneurysms and thrombosis, outweighs the rare risk of Reye’s syndrome.
80-90% of patients respond to the above-mentioned treatment within 36 hours.
If symptoms persist at 48 hours or recur within 2 weeks of initial treatment:
- Consider an alternative diagnosis
- Discuss with a specialist
- Consider 2nd line treatment (if an alternative diagnosis is unlikely): 2nd dose of IVIG with adjuvant steroids
Refractory cases may involve other immunomodulators like anti-TNF alpha, ciclosporin, anakinra, cyclophosphamide)