Kawasaki disease (KD) is a
systemic vasculitis with an unknown etiology affecting young children. Although
intravenous immunoglobulin (
IVIG) plus
acetylsalicylic acid is effective in most cases, approximately 10-20% of patients do not respond to this
therapy. An 8-month-old boy was admitted to a local hospital with the presumptive diagnosis of KD. He received
IVIG twice and four series of
methylprednisolone pulse
therapy from the third to the tenth day of illness. Despite these treatments, his
fever persisted with the development of moderate dilatations of the coronary arteries. A diagnosis of refractory KD was made, and
infliximab with oral
prednisolone was administered without success. Defervescence was finally achieved by
cyclosporine A, an inhibitor of the signaling pathway of the
calcineurin/nuclear factor of activated T cells (NFAT). Whole-genome sequencing of his
deoxyribonucleic acid samples disclosed two single
nucleotide variants (SNVs) in
disease-susceptibility genes in Japanese KD patients, ORAI1 (rs3741596) and BLK (rs2254546). In summary, the refractory nature of the present case could be explained by the presence of combined SNVs in susceptibility genes associated with upregulation of the
calcineurin/NFAT signaling pathway. It may provide insights for stratifying KD patients based on the SNVs in their susceptibility genes.