What's the next step for a child with Kawasaki disease who hasn't improved after receiving Intravenous Immunoglobulin (IVIG) and Intravenous (IV) aspirin?

Management of IVIG-Resistant Kawasaki Disease

Administer a second dose of IVIG at 2 g/kg as a single infusion, which is the recommended first-line treatment for children with Kawasaki disease who have persistent or recurrent fever at least 36 hours after completing the initial IVIG infusion. 1, 2

Defining IVIG Resistance

• IVIG resistance is defined as persistent or recrudescent fever occurring at least 36 hours after completion of the initial IVIG infusion 1
• Approximately 10-20% of Kawasaki disease patients fail to respond to initial IVIG therapy 1, 3
• These IVIG-resistant patients are at significantly increased risk of developing coronary artery abnormalities, making prompt retreatment critical 1

First-Line Retreatment: Second Dose of IVIG

The American Heart Association recommends retreatment with IVIG 2 g/kg as a single infusion for IVIG-resistant cases. 1, 2

• This approach is based on the dose-response effect of IVIG, where higher serum immunoglobulin G levels correlate with better outcomes 1
• The second IVIG dose should be administered as a single infusion over 10-12 hours 2
• Continue high-dose aspirin (80-100 mg/kg/day divided into four doses) during retreatment until the patient is afebrile for 48-72 hours 1, 2

Second-Line Options If Fever Persists After Second IVIG

If the patient remains febrile after the second IVIG dose, you have two equally acceptable options:

Option 1: Intravenous Methylprednisolone

• Administer IV methylprednisolone 20-30 mg/kg/day for 3 consecutive days 1, 2, 3
• This can be followed by oral prednisolone (2 mg/kg/day) tapered over 2-3 weeks for more refractory cases 1, 2
• Studies show similar efficacy to additional IVIG with potentially shorter fever duration 1

Option 2: Infliximab

• Administer infliximab 5 mg/kg IV as a single infusion over 2 hours 2, 3, 4
• Infliximab is a monoclonal antibody against TNF-α that has shown effectiveness in IVIG-resistant cases 1
• This may be particularly useful if you want to avoid prolonged steroid exposure 1

Important Considerations During Retreatment

Aspirin Management

• Continue high-dose aspirin (80-100 mg/kg/day) until the patient is afebrile for 48-72 hours, then transition to low-dose aspirin (3-5 mg/kg/day) 1, 2, 3
• Low-dose aspirin should continue until 6-8 weeks after disease onset if no coronary abnormalities develop, or indefinitely if abnormalities are present 1, 2, 3

Cardiac Monitoring

• Perform echocardiography to assess for coronary artery abnormalities, as IVIG-resistant patients have higher risk of developing aneurysms 1, 3, 4
• The highest risk for coronary artery thrombosis occurs within the first 3 months, with peak incidence at days 15-45 2, 3

Third-Line Options for Highly Refractory Cases

If the patient fails both second IVIG and corticosteroids/infliximab:

• Cyclosporine 4-6 mg/kg/day orally can be considered, though monitor for hyperkalemia which occurs in approximately 32% of patients 2, 4
• Plasma exchange is reserved for patients failing all medical therapies due to significant risks 2, 4

Common Pitfalls to Avoid

• Do not wait beyond 36 hours after IVIG completion to initiate retreatment if fever persists, as delays increase coronary artery complication risk 1
• Avoid ibuprofen in these patients as it antagonizes the antiplatelet effect of aspirin 1, 2, 3
• Do not withhold steroids after two failed IVIG courses based on outdated concerns about coronary outcomes—modern evidence supports their use 1
• Remember to defer measles and varicella immunizations for 11 months after high-dose IVIG administration 1, 2, 3
• Ensure annual influenza vaccination for children on long-term aspirin therapy to reduce Reye's syndrome risk 1, 2, 3

Evidence Quality Note

While the 2017 American Heart Association guidelines acknowledge that "there are no robust data from clinical trials to guide the clinician in the choice of therapeutic agents for the child with IVIG resistance," 1 the consensus recommendation strongly favors second-dose IVIG as first-line retreatment, with corticosteroids or infliximab reserved for cases failing two IVIG doses. This stepwise approach balances efficacy with the known safety profile of each intervention.