Role of Steroids in Kawasaki Disease
Primary Treatment in High-Risk Patients
For high-risk patients predicted to be IVIG-resistant (using validated Japanese scoring systems), adding corticosteroids to initial IVIG and aspirin therapy significantly reduces coronary artery aneurysms and should be strongly considered, though risk stratification tools perform poorly in non-Japanese populations. 1
Evidence for Primary Adjunctive Steroid Therapy
The landmark RAISE study demonstrated that adding prednisolone (2 mg/kg/day IV for 5 days followed by oral taper) to standard IVIG (2 g/kg) and aspirin in high-risk Japanese patients reduced coronary artery abnormalities from 23% to 3% (p<0.0001) 2
A subsequent prospective cohort study (Post-RAISE) confirmed these findings, showing coronary artery abnormalities in only 5.9% of 676 high-risk patients treated with primary IVIG plus prednisolone 3
Multiple Japanese trials using different steroid regimens (pulse methylprednisolone 30 mg/kg or prednisolone 2 mg/kg/day with oral taper) consistently showed lower rates of coronary abnormalities and treatment resistance in high-risk patients 1
Critical Limitation for Non-Japanese Populations
The major caveat is that Japanese risk-stratification scores (Kobayashi, Egami, Sano) have low sensitivity in North American and European populations, making it difficult to identify which patients would benefit from primary steroid therapy 1
A U.S. Pediatric Heart Network trial using single-dose pulse methylprednisolone (30 mg/kg) added to IVIG showed no overall benefit, though post-hoc analysis suggested possible benefit in highest-risk patients 1, 4
The ongoing European KD-CAAP trial is testing whether adjunctive prednisolone benefits unselected (not risk-stratified) European KD patients, addressing the high coronary complication rates observed across Europe 5
Treatment of IVIG-Resistant Disease
Corticosteroids should be used for patients who remain febrile after two doses of IVIG have failed to control fever and inflammation. 1
Recommended Approach for IVIG Resistance
First-line retreatment for IVIG resistance (persistent/recrudescent fever ≥36 hours after completing initial IVIG) is a second dose of IVIG 2 g/kg 6, 7, 8
For patients failing two IVIG infusions, the American Heart Association recommends corticosteroid therapy, most commonly IV pulse methylprednisolone 30 mg/kg for 2-3 hours daily for 1-3 days 1
Alternative steroid regimens include methylprednisolone 20-30 mg/kg IV for 3 days, or longer tapering courses of prednisolone (2 mg/kg/day tapered over 2-3 weeks) for persistent inflammation 7, 8
Infliximab (5 mg/kg IV) is an equally effective alternative to steroids for IVIG-resistant disease, with similar efficacy 1, 6, 8
Rationale for Delayed Steroid Use
The recommendation to restrict steroids until after two IVIG failures stems from older concerns about potential detrimental effects, though subsequent studies have shown either no ill effects or possible benefit 1
Corticosteroids consistently reduce fever duration and inflammatory markers (ESR, CRP) in IVIG-resistant patients 1, 9
Special Considerations for Cardiac Involvement
Patients with significant cardiac involvement (such as left atrial dilation) warrant escalation to steroids even after a single IVIG failure, as this indicates severe ongoing inflammation requiring aggressive treatment. 7
Approximately 10-20% of patients develop IVIG resistance, and those with cardiac involvement are at particularly high risk for progressive coronary damage 7, 8
Frequent echocardiography is essential to monitor progression, as the highest thrombosis risk occurs within the first 3 months, peaking at days 15-45 6, 8
Practical Steroid Regimens
For Primary Treatment (High-Risk Patients)
- RAISE protocol: Prednisolone 2 mg/kg/day IV for 5 days, then oral taper over weeks, combined with IVIG 2 g/kg and aspirin 30 mg/kg/day 1, 2, 3
- Pulse methylprednisolone: 30 mg/kg IV daily for single dose or 1-3 days 1
For IVIG-Resistant Disease
- Standard regimen: Methylprednisolone 30 mg/kg IV over 2-3 hours daily for 1-3 days 1
- Alternative: Methylprednisolone 20-30 mg/kg IV for 3 days 7, 8
- Extended course: Prednisolone 2 mg/kg/day with taper over 2-3 weeks for refractory cases 7
Important Caveats and Safety
Serious adverse events with short-term steroid use are uncommon; the RAISE study reported hypertension and bacteremia in 2 of 724 patients, likely steroid-related 3
The American Heart Association emphasizes not withholding treatment based solely on timing if inflammation persists—the goal is preventing coronary damage 6
Steroids reduce fever and inflammation reliably, but their effect on coronary outcomes remains most convincing in high-risk Japanese populations using validated risk scores 1
For patients on long-term aspirin after steroid treatment, annual influenza vaccination is mandatory due to Reye's syndrome risk 6, 8