What is the treatment for Kawasaki disease?

Treatment of Kawasaki Disease

Initial Treatment: IVIG Plus Aspirin

All patients with Kawasaki disease should receive IVIG 2 g/kg as a single infusion combined with aspirin, administered as early as possible within the first 10 days of fever onset (ideally days 5-10) to reduce coronary artery aneurysm risk from 25% to less than 5%. 1, 2, 3

IVIG Administration

• Administer 2 g/kg as a single infusion over 10-12 hours 1, 3
• Treatment should be given within the first 10 days of illness, preferably within 7 days 1, 2
• For patients presenting after day 10 with persistent fever without other explanation or with aneurysms and ongoing systemic inflammation (elevated ESR or CRP), IVIG should still be administered 1
• Critical caveat: Treatment before day 5 may be associated with increased need for IVIG retreatment, so optimal timing is days 5-7 unless severe disease is present 1

Aspirin Dosing Protocol

Recent high-quality evidence suggests IVIG alone may be sufficient, but current guidelines still recommend aspirin. 4 A 2025 randomized trial of 134 children demonstrated noninferiority of IVIG alone compared to IVIG plus aspirin for CAL reduction 4. However, established guidelines continue to recommend:

• High-dose aspirin: 80-100 mg/kg/day divided into four doses, given concurrently with IVIG 1, 2, 5
• Continue high-dose aspirin until the patient is afebrile for 48-72 hours 1, 2, 5
• Low-dose aspirin: Reduce to 3-5 mg/kg/day as a single daily dose after fever resolution 1, 2, 5
• Continue low-dose aspirin until 6-8 weeks after disease onset if no coronary abnormalities are present 1, 2, 5
• For patients with coronary abnormalities, continue aspirin indefinitely 1, 5

Important caveat: Avoid ibuprofen in children taking aspirin for antiplatelet effects, as it antagonizes irreversible platelet inhibition 1, 3

Management of IVIG-Resistant Disease

Approximately 10-20% of patients develop persistent or recrudescent fever ≥36 hours after completing initial IVIG infusion. 1, 5, 3

Treatment Algorithm for IVIG Resistance

First-line for IVIG resistance: Administer a second dose of IVIG 2 g/kg as a single infusion 1, 2, 5, 3

Second-line options (if fever persists after second IVIG):

• Methylprednisolone: 20-30 mg/kg IV for 3 days, with or without subsequent oral prednisone taper 1, 5, 3
• Infliximab: 5 mg/kg IV over 2 hours (alternative to steroids with similar efficacy) 1, 5, 3

Third-line for highly refractory cases:

• Cyclosporine: 4-6 mg/kg/day orally (monitor for hyperkalemia, which occurs in 32% of patients) 1, 5
• Plasma exchange: Reserved for patients failing all medical therapies due to significant risks 1, 5
• Cytotoxic agents (cyclophosphamide): For exceptional patients with particularly refractory disease 1

Long-Term Antiplatelet and Anticoagulation Management

Treatment is stratified by coronary artery involvement:

No Coronary Abnormalities

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

Small Coronary Aneurysms

• Low-dose aspirin indefinitely 5, 3

Moderate Aneurysms (4-6 mm)

• Low-dose aspirin PLUS clopidogrel 1 mg/kg/day (max 75 mg/day) 5, 3

Giant Aneurysms (≥8 mm)

• Low-dose aspirin PLUS warfarin (target INR 2.0-3.0) 2, 5, 3
• Alternative: Aspirin plus therapeutic doses of low-molecular-weight heparin for infants or when warfarin is difficult to regulate 5, 3

Monitoring Protocol

• Frequent echocardiography and ECG during the first 3 months after diagnosis, especially for patients with giant aneurysms 2, 5, 3
• Highest thrombosis risk: First 3 months, with peak incidence at days 15-45 2, 5, 3

Critical Caveats and Common Pitfalls

Incomplete Kawasaki Disease

• Fever plus fewer than 4 classic criteria should still be treated if coronary artery abnormalities are present on echocardiography or if inflammatory markers are elevated 2, 5
• Incomplete KD is more common in children under 1 year, who paradoxically have higher rates of coronary aneurysms if untreated 5

Vaccination Considerations

• Defer measles and varicella immunizations for 11 months after high-dose IVIG administration 2, 5, 3
• Annual influenza vaccination is mandatory for children on long-term aspirin therapy to reduce Reye syndrome risk 1, 2, 5, 3
• Parents should be instructed to contact their physician promptly if the child develops symptoms of or is exposed to influenza or varicella while on salicylates 1

Reye Syndrome Risk

• Reye syndrome is a risk in children taking salicylates during active varicella or influenza infection 1
• Some physicians substitute another antiplatelet medication for aspirin during the 6-week period after varicella vaccine 1