Yutaro Soejima1, Yohei Kirino2, Mitsuhiro Takeno3, Michiko Kurosawa4, Masaki Takeuchi5, Ryusuke Yoshimi1, Yumiko Sugiyama6, Shigeru Ohno6, Yukiko Asami7, Akiko Sekiguchi8, Toshihisa Igarashi9, Shohei Nagaoka10, Yoshiaki Ishigatsubo11, Hideaki Nakajima1, Nobuhisa Mizuki5. 1. Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. 2. Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. kirino@yokohama-cu.ac.jp. 3. Department of Allergy and Rheumatology, Nippon Medical School, Musashi Kosugi Hospital, 1-396 Kosugi-machi, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. 4. Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan. 5. Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. 6. Yokohama City University Medical Center, Center for Rheumatic Diseases, 4-57 Urafunecho, Minami-ku, Yokohama, 232-0024, Japan. 7. Yokosuka Center for Rheumatic Diseases, Yokosuka City Hospital, 1-3-2 Nagasaka, Yokosuka, 240-0101, Japan. 8. Department of Hematology and Rheumatology, Fujisawa City Hospital, 2-6-1 Fujisawa, Fujisawa, 251-8550, Japan. 9. Department of Rheumatology, Yamato City Hospital, Fukaminishi, Yamato, 242-8602, Japan. 10. Department of Rheumatology, Yokohama Minami Kyosai Hospital, 1-21-1 Mutsuura Higashi, Yokohama, 236-0037, Japan. 11. Yokohama City University, Yokohama, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
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."
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."
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