Is IVIG (Intravenous Immunoglobulin) still a viable treatment option for a pediatric patient with Kawasaki disease presenting 10 days after initial symptoms?

Treatment of Kawasaki Disease After 10 Days of Presentation

Yes, IVIG should still be administered to children presenting after 10 days of fever onset if they have ongoing systemic inflammation (elevated ESR or CRP >3.0 mg/dL) with either persistent fever without other explanation or coronary artery aneurysms. 1

Treatment Criteria for Late Presenters

Children presenting after day 10 of illness are candidates for IVIG treatment if they meet specific criteria:

• Persistent fever without alternative explanation plus elevated inflammatory markers (ESR or CRP) 1
• Coronary artery aneurysms (luminal dimension Z score >2.5) with ongoing systemic inflammation 1
• Elevated CRP >3.0 mg/dL together with either persistent fever or coronary abnormalities 1

Patients who do NOT require IVIG after day 10:

• Fever has resolved AND laboratory values have normalized AND echocardiogram is normal 1

Standard Treatment Protocol

The recommended regimen remains unchanged regardless of timing:

• IVIG 2 g/kg as a single infusion over 10-12 hours 1, 2
• High-dose aspirin 80-100 mg/kg/day divided into four doses until afebrile for 48-72 hours 1, 2
• Transition to low-dose aspirin 3-5 mg/kg/day as a single daily dose after fever resolution, continuing for 6-8 weeks if no coronary abnormalities 1, 2, 3

Evidence Supporting Late Treatment

The rationale for treating late presenters is based on preventing coronary complications:

• Without treatment, coronary artery abnormalities develop in 15-25% of patients; with IVIG this decreases to approximately 5% for any abnormality and 1% for giant aneurysms 1
• While optimal treatment is within the first 10 days (ideally days 5-10), late treatment still provides benefit when inflammation persists 1, 4
• Research shows that 95.6% of children achieve resolution of coronary abnormalities within 6 months regardless of treatment timing 5

Critical Assessment Requirements

Before treating late presenters, evaluate for:

• Inflammatory markers: ESR and CRP levels to document ongoing inflammation 1
• Echocardiography: Assess for coronary artery abnormalities (Z score >2.5 indicates aneurysm) 1
• Fever pattern: Persistent or recurrent fever without alternative infectious etiology 1

Management of IVIG-Resistant Disease

Approximately 10-20% of patients fail initial IVIG therapy (persistent/recurrent fever ≥36 hours post-infusion):

• First-line for resistance: Second dose of IVIG 2 g/kg as single infusion 2, 3, 6
• Second-line options: Methylprednisolone 20-30 mg/kg IV for 3 days OR infliximab 5 mg/kg IV over 2 hours 2, 3
• IVIG-resistant patients have significantly higher risk for coronary artery aneurysms (OR 10.38) and giant aneurysms (OR 54.06) 7

Important Caveats and Pitfalls

Common pitfalls when managing late presenters:

• Do not withhold treatment solely based on timing if inflammation persists—the goal is preventing coronary damage, not adhering rigidly to day 10 cutoff 1
• Incomplete Kawasaki disease is more common in infants <1 year who paradoxically have higher rates of coronary aneurysms if untreated 1, 3
• Age <1 year and ESR >40 mm/hour predict delayed resolution of coronary lesions even with treatment 5

Essential post-treatment considerations:

• Defer measles and varicella immunizations for 11 months after high-dose IVIG administration 1, 2, 3
• Annual influenza vaccination is mandatory for children on long-term aspirin therapy due to Reye's syndrome risk 1, 2, 3
• Avoid ibuprofen in children taking aspirin as it antagonizes antiplatelet effects 1, 2, 3

Long-Term Anticoagulation Based on Coronary Status

For patients with coronary abnormalities detected at late presentation:

• No abnormalities: Low-dose aspirin until 6-8 weeks after onset 2, 3
• Small aneurysms: Low-dose aspirin indefinitely 1, 3
• Moderate aneurysms (4-6 mm): Low-dose aspirin plus clopidogrel 1 mg/kg/day (max 75 mg/day) 2, 3
• Giant aneurysms (≥8 mm): Low-dose aspirin plus warfarin (target INR 2.0-2.5) or therapeutic low-molecular-weight heparin 2, 3, 6

Monitoring Protocol

Intensive surveillance is required for late presenters:

• Frequent echocardiography and ECG during first 3 months, especially with giant aneurysms 2, 3, 6
• Highest thrombosis risk occurs within first 3 months, peaking at days 15-45 2, 3, 6