Kawasaki Disease Treatment: What the Evidence Shows

Why Kawasaki Disease Treatment Matters

Kawasaki disease is the leading cause of acquired heart disease in children in developed countries. In the United States, the incidence is estimated at 18–25 per 100,000 children under five years of age, while in Japan it exceeds 370 per 100,000—meaning roughly 1 in 100 Japanese children develop the condition by age ten. Without treatment, approximately one in four children develops coronary artery dilation or aneurysm, which carries long-term risk of thrombosis, stenosis, myocardial infarction, and sudden cardiac death.

Because the disease disproportionately affects young children—80% of patients are under five—and because coronary artery damage can lead to cardiac events decades later, optimising acute treatment is a high priority. The 2024 AHA scientific statement emphasised that identifying high-risk patients early and intensifying therapy may prevent coronary artery aneurysm formation. This review synthesises the evidence supporting current therapeutic strategies.

Key Findings in Kawasaki Disease Treatment

IVIG Remains the Cornerstone of Acute Treatment

The 2023 Cochrane review by Broderick and colleagues, encompassing 31 RCTs with 4,609 participants, provides the most robust evidence to date that high-dose IVIG (2 g/kg as a single infusion) reduces coronary artery abnormalities compared with aspirin alone or lower-dose IVIG regimens. Earlier Cochrane data had already established that IVIG within the first 10 days of illness onset reduces the incidence of coronary abnormalities from approximately 25% in untreated patients to 3–5%. The 2023 update confirms this finding and adds that single high-dose infusion is likely superior to the older 400 mg/kg/day for five days regimen, with a relative risk for coronary abnormalities of 4.47 (95% CI 1.55–12.86) favouring the single high-dose approach.

Across all included comparisons, no clinically significant increase in adverse events was observed with high-dose IVIG, reinforcing its favourable safety profile. The 2024 AHA statement reaffirms that treatment should be initiated as soon as the diagnosis is made—even at day four if all clinical criteria are met—and that echocardiography should not delay IVIG administration.

Adjunctive Corticosteroids Benefit High-Risk Patients

Whether corticosteroids should be added to initial IVIG therapy has been one of the most debated questions in Kawasaki disease management. The evidence now points toward benefit for patients at high risk of coronary complications, though the picture is nuanced. The RAISE study (Kobayashi et al. 2012) demonstrated that adding prednisolone to IVIG in Japanese patients identified as high-risk by the Kobayashi score reduced the incidence of coronary artery abnormalities. Chen and colleagues’ 2016 meta-analysis of 16 studies (n=2,746) found that adjunctive corticosteroids reduced coronary abnormalities compared with IVIG alone (OR 0.424, 95% CI 0.270–0.665), with the benefit driven by the subgroup receiving corticosteroids as initial therapy rather than rescue therapy.

However, the Newburger et al. 2007 NEJM trial found that a single pulse of intravenous methylprednisolone did not reduce coronary outcomes in an unselected North American population. This apparent contradiction is largely explained by patient selection: the benefit appears concentrated in high-risk patients, and Japanese risk-scoring systems have poor predictive accuracy in ethnically diverse populations. The 2022 Cochrane review by Green and colleagues concluded that corticosteroids reduce the risk of coronary abnormalities without increasing adverse events, while also shortening fever duration and hospital stay. Longer courses of corticosteroids, tapered over two to three weeks, appear to outperform single pulse-dose approaches.

A 2024 North American retrospective study by Wang and colleagues found that a modified RAISE corticosteroid regimen in high-risk patients resulted in significantly decreased IVIG retreatment, offering early real-world confirmation that the Japanese trial findings may extend to diverse populations when the right patients are selected.

Infliximab Emerges as a Preferred Option for IVIG-Resistant Disease

Approximately 10–20% of children with Kawasaki disease have persistent or recurrent fever after initial IVIG, a group at markedly elevated risk for coronary artery damage. The KIDCARE trial (Burns et al. 2021), the largest randomised trial conducted in this population, enrolled 103 patients across 30 US hospitals and found that infliximab produced fever resolution within 24 hours in 77% of patients compared with 51% for a second IVIG dose (OR 3.12, 95% CI 1.36–7.52). Infliximab-treated patients had shorter fever duration (mean 1.5 vs. 2.5 days), shorter hospitalisation (3.2 vs. 4.5 days), and fewer serious adverse events, with haemolytic anaemia occurring exclusively in IVIG-treated patients.

A 2023 Bayesian network meta-analysis by Pan and colleagues, pooling 10 studies with 704 IVIG-resistant patients, confirmed that infliximab demonstrated the strongest antipyretic activity among available second-line therapies. The 2022 large NMA by Lei and colleagues, analysing 56 RCTs with 6,486 participants, found that in the refractory-stage setting, IVIG plus pulse steroid therapy demonstrated the best fever resolution rate, while IVIG plus ciclosporin showed the lowest coronary lesion incidence—though confidence intervals were wide for these comparisons. A 2025 cost-effectiveness analysis found that infliximab was also less costly than second IVIG, driven by shorter hospitalisation.

Aspirin Dose Has Little Impact on Coronary Outcomes

The role of aspirin dosing in the acute phase of Kawasaki disease has undergone substantial re-evaluation. Multiple systematic reviews and meta-analyses, including Zheng et al. (2019, 6 studies, n=2,737), Abdelgawad et al. (2024, 12 studies, n=68,495), and a network meta-analysis (2021, 6 studies, n=1,944), have consistently found no significant difference in coronary artery outcomes between high-dose (80–100 mg/kg/day), medium-dose (30–50 mg/kg/day), and low-dose (3–5 mg/kg/day) aspirin regimens. The largest of these analyses reported an odds ratio of 0.96 (95% CI 0.55–1.67) comparing low-dose to high-dose aspirin for coronary aneurysm incidence.

Despite this body of evidence, the 2024 AHA scientific statement continues to recommend medium-to-high-dose aspirin during the acute phase, noting the need for further data before endorsing routine low-dose use. However, several major centres have already transitioned to low-dose aspirin protocols, and a 2025 preprint from Lurie Children’s Hospital reported comparable coronary and retreatment outcomes after switching from high-dose to low-dose aspirin in practice. The primary concern with higher aspirin doses is the association with adverse effects including gastrointestinal symptoms, anaemia, and the theoretical risk of Reye syndrome.

What the Evidence Does Not Show

No validated risk-stratification tool exists for identifying IVIG-resistant patients in ethnically diverse populations. The Japanese scoring systems (Kobayashi, Egami, Sano) perform poorly outside of Japan, and the 2024 AHA statement could not define clear high-risk criteria for North American patients beyond young age and baseline coronary artery dilation.

The optimal corticosteroid regimen—including dose, formulation, duration, and which specific patients benefit most—has not been determined by an adequately powered trial in a non-Japanese population. The forthcoming Kawasaki Disease Coronary Artery Aneurysm Prevention (KDCAAP) trial may address some of these questions, but results are not yet available.

Long-term coronary outcomes for patients treated with infliximab versus second IVIG remain unknown; the KIDCARE trial reported only short-term results. Similarly, the long-term cardiovascular impact of different aspirin dosing strategies in acute Kawasaki disease has not been studied in a prospective trial. Finally, there is insufficient evidence to guide optimal imaging frequency and modality for serial coronary artery surveillance after the acute phase, particularly for identifying patients at risk of inducible myocardial ischaemia.

Evidence Grade + Bottom Line