**2. Epidemiology**

KD is a systemic vasculitis that mainly affects children younger than 5 years of age. Currently, more than 60 countries in Asia, the Middle East, the Americas, Africa, and Europe have reported KD cases [4]. The incidence of KD is high in Japan, Korea,

and Taiwan, but low in North America and European countries. These incidences reported in different regions of the world can be affected by the survey/surveillance methods used, clinical diagnostic and treatment practices, physician awareness of KD, and data sources used to estimate incidence [5].

According to a nationwide epidemiological survey of KD in Japan, more than 15,000 patients were reported annually until 2019, which was before Coronavirus disease 2019 (COVID-19) pandemic [6]. The annual number of patients with KD in Japan was 17,364 in 2019; however, it decreased to 11,173 in 2020. The incidence rate (per 100,000 children aged 0–4 years per year) was 370.8 (410.1 in boys, and 329.4 in girls) in 2019, and 238.8 (267.3 in boys, and 208.9 in girls) in 2020. Although infectious factors or foreign antigens can trigger KD, the cause of this syndrome remains unclear. Several children diagnosed with COVID-19 have developed multisystem inflammatory syndrome in children (MIS-C), which shows KD-like symptoms [7, 8]. On the other hand, the decline in the incidence of KD remains small, despite the extreme reduction in common pediatric infectious diseases during the COVID-19 pandemic period in Japan, KD may be triggered by unidentified respiratory pathogens that can be acquired both within and outside the household [9].

Genetic factors appear to be involved in KD pathogenesis, as suggested by the highest incidence among Asians and Pacific Islanders, and in boys versus girls. In a genomewide linkage study, several functional polymorphisms such as *inositol 1,4,5-trisphosphate 3-kinase C (ITPKC)* and *caspase-3 (CASP3)* have been identified as common susceptibility genes for KD. Siblings of children with KD have an increased risk of developing the disease [10]. Sibling pairs with KD within a short time interval may be due to environmental triggers, including infectious antigens. Both genetic and environmental factors are thought to interact with each other during the onset of KD; therefore, a detailed study of these contributing factors may help elucidate the pathogenesis of KD.
