(A) Interpretation of epidemiologic clues from Japan’s unparalleled historical record of KD. Left: The first record of KD-like cases in Japan appeared in the 1950s, following large influxes of people from other regions, including repatriation of Japanese individuals from China and Korea as well as US military occupation following WWII and the Korean War. The subsequent 3 epidemics of KD in 1979, 1982, and 1986 are consistent with the introduction of a causative agent into a highly genetically susceptible population. The plateau period from 1988 to 1992 suggests a steady-state exposure to the KD trigger. Right: The 4.5-fold increase in cases in older children occurring from the mid-1990s to 2019 suggests increasing exposure of large populations to an environmental trigger, possibly a wind-borne aerosol. Post-WWII development or increasing intensity of some human activities could create an aerosol that might amplify this exposure, consistent with the rise in KD cases. Incidence in infants remained essentially unchanged over three decades, suggesting a different mode of exposure to the KD trigger in this youngest age group. In 2020, reduced exposure due to isolation measures taken during the COVID-19 pandemic resulted in a decrease in KD incidence that was mirrored by other countries around the globe. (B) Correlation of the seasonal pattern of KD across prefectures in Japan, 1988–2019. For infants less than 6 months of age (left) there is little coherence in seasonal patterns across Japan, in contrast to children 3 years and older (right), for whom there is striking synchrony of KD seasonal patterns across all of Japan. KD incidence and correlation data were adapted with permission from JAMA Network (16).