What is the treatment for Kawasaki disease?

Treatment of Kawasaki Disease

Initial Treatment: IVIG Plus Aspirin

Administer intravenous immunoglobulin (IVIG) 2 g/kg as a single infusion combined with high-dose aspirin (80-100 mg/kg/day divided into four doses) as early as possible within the first 10 days of fever onset to significantly reduce coronary artery abnormalities. 1, 2

Timing and Dosing Details

• IVIG should be given promptly after diagnosis, ideally within the first 10 days of fever, as this significantly reduces the risk of coronary artery abnormalities 1, 2
• Early treatment (by day 5 or earlier) results in less coronary ectasia at 1 year compared to treatment on days 6-9, without increasing treatment failures 3
• High-dose aspirin (80-100 mg/kg/day divided into four doses) should be continued until the patient is afebrile for at least 48 hours 1, 2
• After fever resolution, transition to low-dose aspirin (3-5 mg/kg/day as a single daily dose) and continue until 6-8 weeks after disease onset if no coronary abnormalities are present 1, 2

Important Caveat on Aspirin Dosing

While high-dose aspirin is traditionally recommended, research suggests no significant benefit of high-dose versus low-dose aspirin in reducing fever duration or preventing coronary abnormalities when combined with IVIG 4. However, current American Heart Association guidelines still recommend the high-dose regimen initially 2.

Incomplete Kawasaki Disease

Treat incomplete Kawasaki disease (fever plus fewer than 4 classic criteria) if there is evidence of coronary artery abnormalities or elevated inflammatory markers (CRP, ESR) 1, 2. This is particularly critical in children under 1 year, who paradoxically have higher rates of coronary aneurysms if untreated 2.

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Management of IVIG-Resistant Disease

Approximately 10-20% of patients develop persistent or recrudescent fever at least 36 hours after completing the initial IVIG infusion 2.

First-Line Treatment for IVIG Resistance

Administer a second dose of IVIG (2 g/kg as a single infusion) as the first-line treatment for IVIG resistance 1, 2

Alternative Therapies for Persistent Fever

If fever persists after two doses of IVIG, consider:

• High-dose pulse methylprednisolone (20-30 mg/kg intravenously for 3 days) as an alternative to a second IVIG infusion 1
• Infliximab (5 mg/kg) as an alternative to second IVIG or corticosteroids 1, 2
• The RAISE protocol (intravenous prednisolone 2 mg/kg/day for 5 days followed by oral taper) has shown efficacy in high-risk patients 2

Important Note on Moderate-Dose IVIG

A moderate dose of 1 g/kg IVIG has lower efficacy in preventing coronary artery abnormalities compared to the standard 2 g/kg regimen, with a 27% overall rate of coronary abnormalities versus the expected lower rate with high-dose therapy 5. Always use 2 g/kg as the standard dose.

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Long-Term Antiplatelet and Anticoagulation Management

Patients Without Coronary Abnormalities

• Continue low-dose aspirin (3-5 mg/kg/day) until 6-8 weeks after disease onset 1, 2

Patients With Small Coronary Aneurysms

• Continue low-dose aspirin indefinitely 2

Patients With Moderate-Sized Aneurysms (4-6 mm)

• Low-dose aspirin plus a second antiplatelet agent 2

Patients With Giant Aneurysms (≥8 mm)

• Low-dose aspirin plus warfarin (target INR 2.0-3.0) OR
• Aspirin plus therapeutic doses of low-molecular-weight heparin (particularly for infants or children where warfarin is difficult to regulate) 1, 2

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Monitoring Protocol

• Perform frequent echocardiography and ECG evaluation during the first 3 months after diagnosis, especially for patients with giant coronary aneurysms 1, 2
• The highest risk for coronary artery thrombosis occurs within the first 3 months, with peak incidence in the first 15-45 days 1, 2

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Critical Pitfalls and Special Considerations

Vaccination Timing

• Defer measles, mumps, rubella, and varicella immunizations for 11 months after high-dose IVIG administration due to interference with vaccine efficacy 1, 2
• Administer annual influenza vaccination for all children on long-term aspirin therapy to reduce the risk of Reye syndrome 1, 2

Drug Interactions

• Avoid ibuprofen in children taking aspirin for antiplatelet effects, as it antagonizes the irreversible platelet inhibition induced by aspirin 2

Delayed Treatment Risk

• Delaying treatment beyond 10 days increases the risk of coronary artery abnormalities 2

High-Risk Populations

• Incomplete Kawasaki disease is more common in children under 1 year, who have higher rates of coronary aneurysms if not treated 2