In a child under five years with Kawasaki disease who has just completed the standard 2 g/kg intravenous immunoglobulin (IVIG) infusion and develops a new rash, what is the most likely etiology and appropriate management?

Kawasaki Rash Post-IVIG

Most Likely Etiology

A new rash developing after IVIG infusion in a child with Kawasaki disease is most commonly a hypersensitivity reaction to the IVIG itself, not a sign of treatment failure or disease progression. 1

The key distinction is timing and clinical context:

• Hypersensitivity/allergic reaction to IVIG typically occurs during or within hours after infusion, presenting as urticaria, pruritic rash, or generalized erythema 1
• IVIG-resistant disease is defined as persistent or recrudescent fever ≥36 hours after completing IVIG, not the appearance of new rash alone 2, 3
• The presence of new rash without fever does not meet criteria for IVIG resistance 2

Immediate Management Algorithm

Step 1: Assess for Severe Hypersensitivity

• Stop the infusion immediately if still ongoing and evaluate for anaphylaxis (respiratory distress, hypotension, angioedema) 1
• Have epinephrine available and administer if signs of anaphylaxis develop 1
• Most hypersensitivity reactions resolve promptly when infusion is slowed or stopped 1

Step 2: Check Temperature and Clinical Status

• If afebrile >36 hours post-IVIG: The rash is likely a benign hypersensitivity reaction, not treatment failure 2, 3
• If fever persists or recurs ≥36 hours post-IVIG: This indicates IVIG resistance, and the rash may represent ongoing disease activity 2, 3

Step 3: Symptomatic Management for Hypersensitivity Rash

• Antihistamines (diphenhydramine or cetirizine) for pruritic rash 1
• Continue monitoring vital signs 1
• The rash typically resolves within 24-48 hours without specific intervention 1

When to Escalate Treatment

Do NOT administer additional IVIG or escalate therapy based on rash alone. 2, 3

Escalation is indicated only if:

• Persistent fever ≥36 hours after completing initial IVIG → Administer second dose of IVIG 2 g/kg 2, 3
• Recrudescent fever ≥36 hours after initial IVIG → Administer second dose of IVIG 2 g/kg 2, 3
• After two IVIG doses fail → Consider methylprednisolone 20-30 mg/kg IV for 3 days or infliximab 5 mg/kg IV 3, 4

Critical Monitoring Parameters

• Continue high-dose aspirin 80-100 mg/kg/day until afebrile for 48-72 hours, regardless of rash 3, 4
• Monitor for hemolysis (rare but serious IVIG complication): check hemoglobin, reticulocyte count, and direct antiglobulin test if pallor or jaundice develops 5
• Perform echocardiography at 2 weeks and 6-8 weeks post-treatment to assess for coronary artery abnormalities 3, 4

Common Pitfalls to Avoid

• Do not confuse post-IVIG rash with IVIG resistance – resistance requires persistent/recrudescent fever, not just rash 2, 3
• Do not mistake the rash for a drug reaction to aspirin and discontinue aspirin prematurely – aspirin must continue until fever resolves 3, 4
• Do not administer ibuprofen for fever or discomfort, as it antagonizes aspirin's antiplatelet effects 3, 4
• Do not assume the rash represents incomplete Kawasaki disease requiring additional diagnostic criteria – the child already has confirmed KD and received treatment 2, 3

Special Considerations

• IgA-deficient patients with anti-IgA antibodies have greater risk of severe hypersensitivity reactions to IVIG (which contains trace IgA at ~46 micrograms/mL) 1
• If severe hypersensitivity occurs, document the reaction and consider alternative preparations or premedication with antihistamines/corticosteroids for future IVIG doses if needed 1
• Hemolytic anemia from passive transfer of anti-A/anti-B antibodies in IVIG can occur, particularly in non-O blood types receiving high cumulative doses; monitor hemoglobin if clinical signs of anemia develop 5