What is the recommended post‑intravenous immunoglobulin (IVIG) management for a child who has just completed the initial 2 g/kg IVIG infusion for Kawasaki disease?

Post-IVIG Management in Kawasaki Disease

Immediate Aspirin Management

Continue high-dose aspirin at 80–100 mg/kg/day divided into four doses until the child has been afebrile for 48–72 hours, then transition to low-dose aspirin 3–5 mg/kg/day once daily. 1, 2

• Maintain low-dose aspirin until 6–8 weeks after disease onset if echocardiograms show no coronary abnormalities 1, 2
• For patients who develop coronary abnormalities, continue aspirin indefinitely 2

Monitoring for IVIG Resistance

IVIG resistance is defined as persistent or recrudescent fever ≥36 hours after completion of the initial 2 g/kg IVIG infusion. 1, 2, 3

• This occurs in approximately 10–20% of patients and represents a significant risk factor for coronary artery abnormalities 2, 4
• Monitor temperature closely during the 36–48 hour window post-IVIG completion 1
• Use C-reactive protein (CRP) rather than ESR to assess ongoing inflammation, as IVIG artificially elevates ESR 2

Treatment Algorithm for IVIG-Resistant Disease

If fever persists or recurs ≥36 hours after the first IVIG dose, administer a second dose of IVIG 2 g/kg as a single infusion. 1, 2

• This is the first-line rescue therapy with Class IIa, Level B evidence 1
• Approximately 58% of febrile patients receive retreatment in clinical practice 4

Second-Line Options for Persistent Fever After Two IVIG Doses

If fever continues after the second IVIG infusion, consider: 1, 2

• Methylprednisolone 20–30 mg/kg IV daily for 3 days (with or without oral prednisone taper) 1, 2
• Infliximab 5 mg/kg IV as a single infusion over 2 hours 1, 2

Third-Line Options for Highly Refractory Disease

For patients who fail second IVIG, steroids, and infliximab: 1

• Cyclosporine may be considered (Class IIb, Level C evidence) 1
• Plasma exchange is reserved for exceptional cases where all reasonable medical therapies have failed 1

Echocardiographic Surveillance

Perform echocardiography at diagnosis, 2 weeks, and 6–8 weeks after treatment initiation. 2

• Patients with giant aneurysms require frequent echocardiography and ECG during the first 3 months, as thrombosis risk peaks at days 15–45 5, 2
• Color flow Doppler with low Nyquist limit should demonstrate flow in proximal coronary arteries 1

Long-Term Antiplatelet Strategy Based on Coronary Findings

No Coronary Abnormalities

• Discontinue low-dose aspirin at 6–8 weeks if serial echocardiograms remain normal 5, 2

Small Coronary Aneurysms

• Continue low-dose aspirin 3–5 mg/kg/day indefinitely 5, 2

Moderate Aneurysms (4–6 mm)

• Low-dose aspirin 3–5 mg/kg/day plus clopidogrel 1 mg/kg/day (maximum 75 mg/day) 1, 2

Giant Aneurysms (≥8 mm)

• Low-dose aspirin 3–5 mg/kg/day plus warfarin (target INR 2.0–3.0) or therapeutic low-molecular-weight heparin 1, 2

Critical Immunization Timing

Defer measles, mumps, rubella, and varicella vaccinations for 11 months after high-dose IVIG administration. 5, 2

• High-dose IVIG interferes with live vaccine efficacy 5, 2
• Children at high risk for measles exposure may receive an early dose, followed by re-immunization 11 months after IVIG if serologic testing shows inadequate response 2

Essential Safety Precautions for Children on Aspirin

Administer annual influenza vaccination to all children receiving long-term aspirin therapy to reduce Reye syndrome risk. 5, 2

• Never co-administer ibuprofen with aspirin, as it antagonizes aspirin's irreversible platelet inhibition 5, 2
• Instruct parents to contact the physician immediately if the child develops influenza or varicella symptoms while on aspirin 2
• Some clinicians substitute an alternative antiplatelet agent during the 6-week period following varicella vaccination to further reduce Reye syndrome risk 2

Common Pitfalls to Avoid

Do not use the 36-hour fever criterion rigidly for late presenters (>10 days of illness). 5

• Children presenting after day 10 should still receive IVIG if they have ongoing systemic inflammation (CRP >3.0 mg/dL) with either persistent fever or coronary artery aneurysms 1, 5
• Infants <1 year are at highest risk for incomplete presentations and paradoxically have the highest rates of coronary aneurysms if untreated 5, 2

A new rash appearing post-IVIG without fever does not indicate IVIG resistance. 2

• Escalation of therapy is reserved for fever criteria, not rash alone 2
• Post-IVIG rash without fever is most likely a benign hypersensitivity reaction to the IVIG product 2