What is the treatment for Kawasaki disease?

Treatment of Kawasaki Disease

The definitive treatment for Kawasaki disease is intravenous immunoglobulin (IVIG) at a dose of 2 g/kg as a single infusion, combined with high-dose aspirin (80-100 mg/kg/day divided into four doses), administered as early as possible within the first 10 days of fever onset. 1

Initial Treatment Protocol

• IVIG should be administered promptly after diagnosis to significantly reduce the risk of coronary artery abnormalities 1
• 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 at least 48 hours 1
• After fever resolution, aspirin should be reduced to low-dose (3-5 mg/kg/day as a single daily dose) and continued until 6-8 weeks after disease onset if no coronary abnormalities are present 1
• For children who develop coronary abnormalities, aspirin may be continued indefinitely 1
• Delaying treatment beyond 10 days increases the risk of coronary artery abnormalities 1, 2
• Early treatment (≤5 days of fever) has been associated with less coronary ectasia at 1 year after disease onset 2

Management of IVIG-Resistant Disease

Approximately 10-20% of patients fail to respond to initial IVIG therapy, defined as persistent or recrudescent fever 36 hours after completion of the initial IVIG infusion. Treatment options include:

1. Second dose of IVIG (2 g/kg as a single infusion) - first-line treatment for IVIG resistance 3, 1
2. High-dose pulse steroids (methylprednisolone 20-30 mg/kg intravenously for 3 days) - alternative to second IVIG infusion 3
3. Longer tapering course of prednisolone/prednisone (2-3 weeks) with IVIG and aspirin 3
4. Infliximab (5 mg/kg) - alternative to second IVIG or corticosteroids 3, 1
5. Cyclosporine - for patients who fail to respond to second IVIG, infliximab, or steroids 3
6. Other options for highly refractory cases:
   • Anakinra (IL-1 receptor antagonist) 3
   • Plasma exchange - reserved for patients where all reasonable medical therapies have failed 3
   • Cytotoxic agents like cyclophosphamide with oral steroids 3
   • Methotrexate has been reported in case studies 4

Long-term Antiplatelet/Anticoagulation Management

• For patients without coronary abnormalities: low-dose aspirin (3-5 mg/kg/day) until 6-8 weeks after disease onset 1
• For patients with small coronary aneurysms: indefinite low-dose aspirin 1
• For patients with moderate-sized aneurysms (4-6 mm): aspirin plus a second antiplatelet agent 1
• For 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 for infants or children where warfarin is difficult to regulate 1

Monitoring

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

Special Considerations and Caveats

• Incomplete Kawasaki disease (fever plus fewer than 4 classic criteria) should still be treated if there is evidence of coronary artery abnormalities or elevated inflammatory markers 1
• Incomplete Kawasaki disease is more common in children under 1 year, who paradoxically have higher rates of coronary aneurysms if not treated 1
• Measles and varicella immunizations should be deferred for 11 months after high-dose IVIG administration 1
• Annual influenza vaccination is recommended for children on long-term aspirin therapy 1
• Ibuprofen should be avoided in children taking aspirin for its antiplatelet effects as it antagonizes the irreversible platelet inhibition induced by aspirin 1
• Adult cases of Kawasaki disease have been reported (91 cases in literature), with 21 cases in HIV-infected patients 5
• Low-dose IVIG regimens (1 g/kg) have shown lower efficacy in preventing coronary artery abnormalities compared to the standard 2 g/kg dose 6

The evidence strongly supports early intervention with IVIG plus aspirin as the cornerstone of treatment for Kawasaki disease, with a structured approach to managing IVIG-resistant cases to minimize the risk of coronary artery complications.