Persistent Fever After IVIG in an Infant With Coronary Dilation
A 4-month-old girl is admitted on day 7 of fever. She has had 6 days of fever to 39°C, non-exudative bulbar conjunctivitis, a polymorphous truncal rash, reddening at the BCG scar, and marked irritability; her lips are dry but not cracked and the extremities are not yet changed. CRP is 14 mg/dL, ESR 70 mm/h, platelets 610,000/µL, albumin 2.9 g/dL, ALT 78 U/L, hemoglobin 9.2 g/dL, and urinalysis shows sterile pyuria. Echocardiography on admission shows a left anterior descending artery z-score of +3.0, right coronary artery +1.8, no aneurysm, and normal systolic function. She received IVIG 2 g/kg and high-dose aspirin at hour 0; 40 hours later she is still febrile to 39.4°C with unchanged irritability and a rising CRP.
1. Is this IVIG resistance, recrudescence, or an alternative diagnosis? What is your next treatment step and why?
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Interpretation Persistent fever beyond 36 hours after the end of a 2 g/kg infusion meets the usual definition of IVIG resistance. Before escalating, briefly re-screen for mimics: adenovirus, enterovirus, scarlet fever, staphylococcal scalded skin, and MIS-C (consider exposure history and inflammatory markers). The clinical picture, age, and BCG-site erythema still favor Kawasaki disease, which in infants under 6 months is frequently incomplete and frequently diagnosed late - the main reason for coronary involvement.
Next step
- Escalate adjunctive anti-inflammatory therapy rather than simply repeating IVIG, since a second dose has weak supporting evidence. Reasonable options are infliximab 5 mg/kg as a single dose (non-inferior to a second IVIG dose in the RAISE trial), pulsed intravenous methylprednisolone 30 mg/kg daily for 3 days, or anakinra in refractory cases.
- Continue low-dose aspirin (3-5 mg/kg/day) rather than high-dose once the diagnosis is secure and coronary changes are present.
- Reassess fever, CRP, and echocardiography within 24-48 hours; if still refractory, switch mechanism rather than repeating the same agent.
2. How do you classify the coronary findings and what monitoring and antithrombotic plan follows?
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Classification (AHA 2017 framework)
- Dilation only: z-score 2 to <2.5.
- Small aneurysm: z 2.5 to <5.
- Medium: z 5 to <10, or absolute diameter <8 mm.
- Large/giant: z ≥10 or absolute ≥8 mm.
Her LAD at z 3.0 is a small aneurysm and the RCA is dilated.
Monitoring
- Echocardiography at 1-2 weeks, 4-6 weeks, and then at 6-12 months if changes persist; consider cardiac CT or MRI if aneurysms are medium or larger, or if the distal vessels cannot be seen.
- Teach parents to recognize fever and to seek immediate review, since recurrent fever after day 10 raises concern for recrudescence.
Antithrombotic therapy
- Low-dose aspirin until the z-score normalizes; if the aneurysm enlarges to medium or large, add a second antiplatelet agent or anticoagulation after discussing bleeding risk.
- Activity restriction is not needed for small aneurysms but applies to medium/large aneurysms and to those with thrombosis.
3. The parents ask about vaccines, aspirin duration, and long-term outlook. What do you tell them?
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Vaccines High-dose IVIG (2 g/kg) blunts the response to live viral vaccines, so measles-mumps-rubella and varicella should be deferred for about 11 months after the infusion; inactivated vaccines, including influenza, can be given on schedule and are recommended for household contacts. If she requires prolonged corticosteroids or biologics, live vaccines must wait until immunosuppression is reduced.
Aspirin Low-dose aspirin continues until the echocardiogram normalizes, usually 6-8 weeks if there is no persistent involvement; parents should be warned about bleeding and about Reye syndrome if varicella or influenza-like illness occurs while on aspirin.
Outlook, stated honestly
- Small aneurysms often regress; her risk of myocardial ischemia now is low but not zero.
- Lifelong cardiology follow-up is needed if any dilation persists, with periodic imaging and counseling about atherosclerosis risk factors.
- Emphasize the infant's age: this illness was diagnosed late and she needs a defined follow-up schedule and a family plan for fever, chest pain, or breathlessness.