What is the treatment for Kawasaki disease?

Treatment of Kawasaki Disease

All patients with acute Kawasaki disease should receive IVIG 2 g/kg as a single infusion combined with aspirin, administered within the first 10 days of fever onset to prevent coronary artery abnormalities. 1, 2

Initial Treatment Protocol

IVIG Administration

• Administer IVIG 2 g/kg as a single infusion over 10-12 hours as soon as the diagnosis is made, ideally within the first 7-10 days of illness 3, 1, 2
• Treatment should not be delayed beyond day 10 if the diagnosis was missed earlier, particularly if persistent fever or ongoing systemic inflammation (elevated ESR or CRP) is present 3, 1
• Treatment before day 5 of illness may increase the need for IVIG retreatment without additional benefit in preventing cardiac sequelae, so treatment on days 5-7 is optimal 3
• The 10-12 hour infusion time is recommended based on the established efficacy data and may reduce coronary aneurysm risk compared to faster infusions 4

Aspirin Dosing Strategy

High-dose aspirin (80-100 mg/kg/day divided into four doses) should be given concurrently with IVIG and continued until the patient is afebrile for 48-72 hours. 1, 2

However, recent high-quality evidence challenges this traditional approach:

• A 2025 randomized controlled trial demonstrated that IVIG alone was noninferior to IVIG plus high-dose aspirin for preventing coronary artery lesions (CAL occurrence: 1.5% vs 2.9% at 6 weeks, p=0.65) 5
• Despite this recent evidence, current American Heart Association guidelines still recommend the combination therapy, and this remains the standard of care in most centers 1, 2
• One retrospective study found that low-dose aspirin from diagnosis was associated with 3-times higher odds of IVIG resistance compared to initial high-dose aspirin (23% vs 8.7%, p=0.003) 6

After fever resolution for 48-72 hours, 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. 3, 1, 2

Important Aspirin Considerations

• For children who develop coronary abnormalities, continue aspirin indefinitely 3, 1
• Avoid ibuprofen in children taking aspirin for antiplatelet effects, as it antagonizes irreversible platelet inhibition 3, 1
• Children on long-term aspirin therapy require annual influenza vaccination to reduce Reye syndrome risk 3, 1, 2
• Defer measles and varicella immunizations for 11 months after high-dose IVIG administration 1, 2

Management of IVIG-Resistant Disease

IVIG resistance is defined as persistent or recrudescent fever at least 36 hours after completion of the initial IVIG infusion, occurring in approximately 10-20% of patients. 1, 2

Treatment Algorithm for IVIG Resistance

1. First-line: Administer a second dose of IVIG 2 g/kg as a single infusion 1, 2
2. Second-line options if fever persists after two IVIG doses:
   • High-dose pulse methylprednisolone (20-30 mg/kg IV for 3 days) 2
   • Infliximab 5 mg/kg as a single infusion 1, 2
   • Longer course of corticosteroids (e.g., RAISE protocol: IV prednisolone 2 mg/kg/day for 5 days followed by oral taper) 1

Long-term Antiplatelet and Anticoagulation Management

The intensity of antithrombotic therapy is stratified by coronary artery aneurysm size:

No Coronary Abnormalities

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

Small Coronary Aneurysms

• Continue low-dose aspirin indefinitely 1

Moderate-Sized Aneurysms (4-6 mm)

• Low-dose aspirin plus a second antiplatelet agent 1

Giant Aneurysms (≥8 mm)

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

Monitoring and Follow-up

• Perform echocardiography at diagnosis, at 2 weeks, and at 6-8 weeks after disease onset 7
• The highest risk for coronary artery thrombosis occurs within the first 3 months, with peak incidence at 15-45 days, requiring more frequent monitoring for patients with coronary abnormalities 1, 2

Critical Pitfalls to Avoid

• Incomplete Kawasaki disease (fever ≥5 days with only 2-3 classic features) should still be treated if coronary abnormalities or elevated inflammatory markers are present, as these patients remain at risk for coronary complications 1, 2, 7
• Infants ≤6 months old are at particularly high risk and may present with incomplete disease, requiring a lower threshold for laboratory testing and echocardiography 7
• Delaying treatment beyond 10 days increases the risk of coronary artery abnormalities, though treatment should not be withheld if active inflammation persists 1, 7