Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behçet’s disease in Japan

Author:

Soejima Yutaro,Kirino YoheiORCID,Takeno Mitsuhiro,Kurosawa Michiko,Takeuchi Masaki,Yoshimi Ryusuke,Sugiyama Yumiko,Ohno Shigeru,Asami Yukiko,Sekiguchi Akiko,Igarashi Toshihisa,Nagaoka Shohei,Ishigatsubo Yoshiaki,Nakajima Hideaki,Mizuki Nobuhisa

Abstract

Abstract Background We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Here, we conducted a study to identify clinical clusters of BD. Methods A total of 657 patients registered in the Yokohama City University (YCU) regional BD registry between 1990 and 2018, as well as 6754 patients who were initially registered in the Japanese Ministry of Health, Labour and Welfare (MHLW) database between 2003 and 2014, were investigated. The YCU registry data regarding the clinical manifestations of BD, human leukocyte antigen (HLA) status, treatments, and hospitalizations were analyzed first, followed by similar analyses of the MHLW for validation. A hierarchical cluster analysis was independently performed in both patient groups. Results A hierarchical cluster analysis determined five independent clinical clusters in the YCU cohort. Individual counterparts of the YCU clusters were confirmed in the MHLW registry. Recent phenotypical evolutions of BD in Japan, such as increased gastrointestinal (GI) involvement, reduced complete type according to the Japan Criteria, and reduced HLA-B51 positivity were associated with chronologically changing proportions of the clinical clusters. Conclusions In this study, we identified independent clinical clusters among BD patients in Japan and found that the proportion of each cluster varied over time. We propose five independent clusters namely “mucocutaneous”, “mucocutaneous with arthritis”, “neuro”, “GI”, and “eye.”

Funder

Ministry of Health, Labour and Welfare

Publisher

Springer Science and Business Media LLC

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