Background: Epidemiological studies show a U-shaped tendency in Kawasaki disease (KD)-related coronary artery abnormalities (CAAs) across age categories. Since studies suggest seasonal variations in KD onset, this study aimed to clarify the epidemiologic features of CAAs, considering the seasons of KD-occurrence. Methods: We analyzed 2,106 (males = 1,215, females = 891) consecutive KD cases from October 1999 through September 2017 using our electronic database of annual surveys, targeting all hospitals with pediatric departments across Wakayama, Japan. The primary outcome was the presence=absence of CAAs measured by echocardiography 1 month after KD onset. Odds ratios (ORs) and 95% confidence intervals (CIs) of combined patient age and sex for CAAs were calculated using logistic regression models adjusted for four seasons. Results: The median age was 25 (range, 1-212) months. The proportion of males decreased with increasing age. The youngest age group (<6 months) showed an inverse summer=autumn to winter=spring ratio (>1.0) in KD-occurrence. CAAs were observed in 2.8% of cases (males = 3.4%, females = 2.1%), which significantly lessened in summer than in other seasons. Moreover, 50% (n = 4=8) of cases with giant aneurysms experienced KD in autumn. Adjusted ORs for CAAs among males aged ≥60 months (3.0; 95%, CI 1.2-7.5) and females aged <6 months (3.6; 95%, CI 1.1-11.8) were significantly higher than those among males aged 12-35 months. Conclusions: Cumulative 18-year data of consecutive KD cases from one area suggest the influence of interactions between patient age and sex on the development of KD-related CAAs. The season of KD-occurrence may reflect the diversity of agents.

Key Points Question Are age and sex associated with unresponsiveness to intravenous immunoglobulin (IVIG) and the development of coronary artery abnormalities (CAAs) among patients with Kawasaki disease (KD)? Findings This cohort study using data from 2414 patients in Japan identified an association between the proportion of patients with initial unresponsiveness to IVIG and increasing age. Differences in the risk factors were observed between initial unresponsiveness to IVIG and the development of CAAs in infants with KD. Meaning This study suggests that residual risks other than initial unresponsiveness to IVIG must be addressed to prevent CAA complications among patients with KD, particularly in infants.