After a child with Kawasaki disease receives the standard 2 g/kg intravenous immunoglobulin (IVIG), when should the rash resolve, and what should be done if it persists beyond 48‑72 hours?

When Does the Rash Improve After IVIG in Kawasaki Disease?

The rash in Kawasaki disease typically resolves within the first few days after IVIG administration as part of the overall clinical response, but the rash alone should never be used to determine treatment success—only fever resolution matters for defining IVIG response. 1

Primary Response Criteria Post-IVIG

The American Heart Association defines treatment response based exclusively on fever, not rash:

• IVIG resistance is defined as persistent or recrudescent fever lasting ≥36 hours after completion of the initial 2 g/kg IVIG infusion. 1
• The presence or persistence of rash without fever does NOT constitute treatment failure and should not trigger additional IVIG doses. 1
• High-dose aspirin (80–100 mg/kg/day divided into four doses) should be continued until the patient has been afebrile for 48–72 hours, regardless of rash status. 2, 1

Expected Timeline for Rash Resolution

Based on the American Heart Association guidelines:

• The rash typically appears within the first 5 days of illness and is truncal with groin accentuation. 2, 3
• After successful IVIG treatment, the rash generally fades within days as inflammation subsides, though no specific timeline is mandated in the diagnostic criteria. 2
• The rash may persist briefly even after fever resolution without indicating treatment failure. 1

Critical Management Algorithm Post-IVIG

If Patient Becomes Afebrile Within 36 Hours:

• Continue high-dose aspirin until afebrile for 48–72 hours. 2, 1
• Transition to low-dose aspirin (3–5 mg/kg/day) and continue for 6–8 weeks if no coronary abnormalities. 1, 4
• Do not escalate therapy based on persistent rash alone. 1

If Fever Persists or Recurs ≥36 Hours After IVIG:

• Administer a second dose of IVIG 2 g/kg as a single infusion. 1, 4
• Consider methylprednisolone (20–30 mg/kg IV for 3 days) or infliximab (5 mg/kg IV) if fever persists after two IVIG doses. 1, 4

Common Pitfalls to Avoid

• Do not confuse a post-IVIG hypersensitivity rash with IVIG resistance—resistance requires documented fever ≥36 hours, not rash persistence. 1
• Do not stop aspirin due to rash alone; aspirin should continue at high dose until fever resolves for 48–72 hours. 1
• Do not use the rash as a marker for incomplete Kawasaki disease once the diagnosis is established and treatment initiated. 1

Monitoring Inflammation Post-IVIG

• Use C-reactive protein (CRP) rather than erythrocyte sedimentation rate (ESR) to monitor inflammation after IVIG, because IVIG artificially elevates ESR. 2, 1
• Resolution of CRP confirms adequate treatment response. 1

Long-Term Considerations

• Perform echocardiography at diagnosis, 2 weeks, and 6–8 weeks after treatment to assess for coronary artery abnormalities. 1
• Defer measles, mumps, rubella, and varicella vaccinations for 11 months after high-dose IVIG administration. 1, 4
• Administer annual influenza vaccination to all children on long-term aspirin therapy to reduce Reye syndrome risk. 1, 4