Temporal Clusters of Kawasaki Disease Cases Share Distinct Phenotypes That Suggest Response to Diverse Triggers

Burns, Jane C.; DeHaan, Laurel L.; Shimizu, Chisato; Bainto, Emelia V.; Tremoulet, Adriana H.; Cayan, Daniel R.; Burney, Jennifer A.

OBJECTIVE: To test the hypothesis that cases of Kawasaki disease within a temporal cluster have a similar pattern of host response that is distinct from cases of Kawasaki disease in different observed clusters and randomly constructed clusters. STUDY DESIGN: We designed a case-control study to analyze 47 clusters derived from 1332 patients with Kawasaki disease over a 17-yr. period (2002-2019) from a single clinical site and compared the cluster characteristics with two control groups of synthetic KD clusters. We defined a “true” KD cluster as at least 5 patients within a 7-day moving window. The observed and synthetic KD clusters were compared with respect to demographic and clinical characteristics and median values for standard laboratory data using univariate analysis and a multivariate, Rotated Empirical Orthogonal Function Analysis (REOFs). RESULTS: In a univariate analysis, the median values for age, coronary artery Z score, white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and age-adjusted hemoglobin for several of the true KD clusters exceeded the 95th percentile for the two synthetic clusters. REOFs revealed distinct patterns of demographic and clinical measures within clusters. CONCLUSIONS: Cases of Kawasaki disease within a cluster were more similar with respect to demographic and clinical features, and levels of inflammation than would be expected by chance. These observations suggest that different triggers and/or different intensity of exposures result in clusters of cases of Kawasaki disease that share a similar response pattern. Analyzing cases within clusters or cases who share demographic and clinical features may lead to new insights into the etiology of KD.