Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Beh\xe7et\u2019s disease in Japan

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

doi:10.1186/s13075-020-02406-6

Abstract

BackgroundWe 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.MethodsA 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.ResultsA 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.ConclusionsIn 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.”

Highlights

We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease
Chronological changes of clinical clusters We previously reported that Japanese BD patient phenotypes have been evolving over the past 30 years, with ocular involvement becoming less common while the incidence of intestinal BD continues to rise [9, 13]
Our data strongly support the notion that BD patients can be categorized into several clinical subtypes based on clinical presentations

Summary

Introduction

We hypothesized that Behçet’s disease (BD) consists of several clinical subtypes with different severity, resulting in heterogeneity of the disease. Behçet’s disease (BD) is a rare systemic inflammatory disease that causes periodic ocular and mucocutaneous inflammation [1, 2]. Identifying predictive factors for these unfavorable BD subtypes is essential. One of the primary obstacles facing personalized medicine is the heterogeneity of BD patients [2]. Serious organ involvement such as ocular and vascular lesions in young men [8, 9], genital ulcers in young women [9], and GI symptoms in pediatric patients [9, 10] have been

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