The impact of vitamin D on the onset and progress of Kawasaki disease

Abstract

Background: The seasonal epidemic of Kawasaki disease (KD) in winter in Japan suggests that low vitamin D status may affect KD through the immune system. We aimed to evaluate the effect of vitamin D on the onset and clinical course of KD. Methods: We conducted a case-control study to compare 25-hydroxyvitamin D (25(OH)D) levels in KD patients admitted to our hospital between March 2018 and June 2021, with those in healthy controls from published Japanese data. In patients with KD, we evaluated the association of 25(OH)D levels with intravenous immunoglobulin resistance and coronary artery lesions. Results: We compared 290 controls and 86 age-group-adjusted patients with KD. The 25(OH)D levels in KD patients were lower than those in the controls (median: 17 vs. 29 ng/mL, P < 0.001). In winter, 25(OH)D levels in KD patients were lower than those in summer (median: 13 vs. 19 ng/mL). The adjusted odds ratios for the onset of KD were 4.9 (95% CI: 2.5-9.6) for vitamin D insufficiency (25(OH)D: 12-20 ng/mL) and 29.4 (95% CI: 12.5-78.2) for vitamin D deficiency (25(OH)D < 12 ng/mL). Among 110 KD patients, 25(OH)D levels at diagnosis of KD were not associated with intravenous immunoglobulin resistance or coronary artery lesions. Conclusions: The 25(OH)D levels in patients with KD were lower than those in the controls, especially in winter. Lower 25(OH)D levels in winter were associated with an increased risk of KD onset. It remains to be elucidated whether the observed association has a causal relationship.Key words 25-hydroxyvitamin D, coronary aneurysm, intravenous immunoglobulin, Kawasaki disease, vitamin D deficiency.Kawasaki disease (KD) is an acute systemic vasculitis of unknown cause that primarily affects infants and children. 1 Seasonal and regional epidemics have been reported and, in Japan, KD is most prevalent in winter, with a small peak in summer. 2 These epidemics have suggested that some infections trigger KD. 2 Vitamin D is an essential nutrient that is synthesized in the skin upon exposure to ultraviolet rays, in addition to absorption from food. 3 Vitamin D was initially reported to play an important role in bone metabolism and calcium homeostasis but recently, it has been recognized that it regulates innate and adaptive immunity. 3,4 Vitamin D status was defined based on serum 25-hydroxyvitamin D (25(OH)D) levels because of its relatively long half-life. 4 We hypothesized that lower 25(OH)D levels, especially in winter, predispose host immunity to exacerbate the onset and progression of KD. To test this hypothesis, we first conducted a case-control study comparing KD patients and previously reported healthy controls. Second, in patients with KD, we evaluated whether 25(OH)D levels at diagnosis were associated with the clinical course of KD, such as intravenous immunoglobulin (IVIG) resistance or coronary artery lesions (CALs). We have also considered the effect of breastfeeding as a possible confounding factor, which has been reported to be associated with a lower risk of KD and often leads to reduced ...

The effect of vitamin D status on the occurrence of Kawasaki Disease: a meta-analysis

“…Of these KD patients, 272 had CAL, 423 did not suffer from CAL complications, and the remaining did not report their complications. The study included mostly Han Chinese participants (72.6%), with one sample (12.7%) from Japan [ 16 ] and two samples (14.7%) from Italy [ 13 , 18 ]. This distribution is consistent with the higher incidence of KD observed in Northeast Asian countries like China, Japan, Korea, and Taiwan compared to other developed nations such as the United States and Europe.…”

“…A growing body of evidence from various studies demonstrates the crucial role of vitamin D in the systemic inflammatory response and the release of anti-inflammatory cytokines [ 39 , 40 ]. Researchers posit that vitamin D can regulate the immune system and hence, influence the occurrence and development of KD [ 16 ]—an autoimmune disease—and its therapeutic treatment through immune system regulation [ 22 ]. This hypothesis is backed by animal, cell, and human studies which indicate that activated vitamin D (25(OH)D) plays an integral role in regulating immunologic processes [ 41 ].…”