Treatment of Kawasaki Disease
All patients with acute Kawasaki disease should receive IVIG 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, 2
Initial Treatment Protocol
IVIG should be administered promptly after diagnosis at 2 g/kg as a single infusion, typically over 10-12 hours, to significantly reduce the risk of coronary artery abnormalities. 1, 2
High-dose aspirin (80-100 mg/kg/day divided into four doses) must be given concurrently with IVIG and 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 for 6-8 weeks after disease onset if no coronary abnormalities are present. 1, 2
For children who develop coronary abnormalities, aspirin should be continued indefinitely. 1
Important Caveat About Aspirin
While guidelines recommend high-dose aspirin, the evidence for its benefit is limited. Research shows aspirin has never been proven to prevent coronary aneurysms, and studies comparing high-dose versus low-dose aspirin found no significant difference in fever duration or coronary outcomes. 3, 4 However, current American Heart Association guidelines still recommend the high-dose regimen for its anti-inflammatory and antipyretic effects. 5, 1
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. 1, 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
Second-Line Options for Persistent Fever
If fever persists after two doses of IVIG, consider the following alternatives:
High-dose pulse methylprednisolone (20-30 mg/kg intravenously for 3 days, with or without subsequent oral prednisone taper) may be considered. 5, 2
A longer tapering course of prednisolone or prednisone (2-3 weeks), together with IVIG 2 g/kg and aspirin, may be considered for retreatment. 5
Infliximab (5 mg/kg) may be considered as an alternative to a second IVIG infusion or corticosteroids. 5, 2
Third-Line Options for Highly Refractory Disease
Cyclosporine may be considered in patients with refractory disease in whom second IVIG, infliximab, or steroids have failed. 5
For highly refractory patients, consider immunomodulatory monoclonal antibody therapy (such as anakinra for IL-1 blockade), cytotoxic agents like cyclophosphamide with oral steroids, or rarely plasma exchange. 5
Long-Term Antiplatelet and Anticoagulation Management
The antithrombotic strategy is tailored to the size of coronary aneurysms:
For patients without coronary abnormalities: Continue low-dose aspirin (3-5 mg/kg/day) for 6-8 weeks after disease onset, then discontinue. 2, 4
For patients with small coronary aneurysms: Continue low-dose aspirin indefinitely. 1
For patients with moderate-sized aneurysms (4-6 mm): Use aspirin plus a second antiplatelet agent (such as clopidogrel). 1
For patients with giant aneurysms (≥8 mm): Use 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, 2
Monitoring and Follow-Up
Frequent echocardiography and ECG evaluation during the first 3 months after diagnosis are essential, 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
Critical Pitfalls and Special Considerations
Timing of Treatment
- Delaying treatment beyond 10 days of fever onset significantly increases the risk of coronary artery abnormalities. 1
Incomplete Kawasaki Disease
Incomplete Kawasaki disease (fever plus fewer than 4 classic criteria) should still be treated aggressively if there is evidence of coronary artery abnormalities or elevated inflammatory markers (CRP, ESR). 1, 2
Children under 1 year are more likely to present with incomplete disease and paradoxically have higher rates of coronary aneurysms if not treated promptly. 1
Vaccination Considerations
Measles and varicella immunizations must be deferred for 11 months after high-dose IVIG administration due to interference with vaccine efficacy. 1, 2
Annual influenza vaccination is recommended for all children on long-term aspirin therapy to prevent Reye syndrome. 1, 2
Drug Interactions
- Ibuprofen should be avoided in children taking aspirin for antiplatelet effects, as it antagonizes the irreversible platelet inhibition induced by aspirin. 1
Kawasaki Disease Shock Syndrome (KDSS)
Approximately 7% of patients develop KDSS, characterized by hypotension requiring volume expanders or vasopressor agents. 5
KDSS is associated with more severe inflammation, higher risk of coronary arterial dilation, and increased likelihood of IVIG resistance requiring additional anti-inflammatory treatment. 5