The study was approved by the Ethic Committee of Yokohama City University (A141127010).

All patients were Japanese except for four patients (one Filipino, one Syrian, one Korean, and one Chinese patient). These patients had been treated in any of the seven hospitals within the Kanagawa district located in mid-Japan, from July 1991 to December 2015. The patients who participated in the study met the 1987 revised diagnostic criteria of the Behçet’s disease research committee, the Ministry of Health, Labor and Welfare of Japan. To determine whether the trends were transient or continuous in the same area, this study enrolled patients newly diagnosed with BD after 2008 and compared them with the previous cohorts reported by Ideguchi et al. These findings suggest the involvement of altered environmental factors in the phenotypical changes in BD in these countries. However, to our knowledge, such chronological changes in the BD phenotype have been reported only in Japan and Korea, where the majority of the residents have been native and genetically homogenous, with infrequent influx of immigrants from other ethnic groups. Similarly, a recent paper from Korea also reported reduction in the complete type, declining male propensity, and shifting patterns of organ involvement, during the last 30 years. We previously reported that newly diagnosed complete-type BD (patients having all four of the major symptoms of oral ulcers, genital ulcers, and eye and skin lesions) in Kanagawa district, Japan had been declining since the year 2000, compared with the previous data (33 % of patients diagnosed before 2000 had complete BD compared to 23 % of patients between 20). It is thus possible that environmental factors modify the clinical courses and phenotypes of BD.Įpidemiological studies from Japan and Korea have shown that the prevalence of BD, particularly of patients with serious manifestations, is decreasing. Moreover, dysbiosis in the intestinal flora has been reported in many inflammatory diseases including BD. Microbes such as Streptococcus sanguinis and herpes simplex have been implicated in BD pathogenesis, and genetic evidence supporting association with microbiomes in the development of BD is growing. A definitive environmental factor associated with BD is still unknown. Behçet’s disease (BD) is an inflammatory disease of unknown cause, affecting multiple organs such as eyes, skin, mucosa, and brain.

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