PMID- 33522943 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 23 IP - 1 DP - 2021 Feb 1 TI - Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behcet's disease in Japan. PG - 49 LID - 10.1186/s13075-020-02406-6 [doi] LID - 49 AB - BACKGROUND: We hypothesized that Behcet'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." FAU - Soejima, Yutaro AU - Soejima Y AD - Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. FAU - Kirino, Yohei AU - Kirino Y AUID- ORCID: 0000-0002-9488-661X AD - 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. FAU - Takeno, Mitsuhiro AU - Takeno M AD - Department of Allergy and Rheumatology, Nippon Medical School, Musashi Kosugi Hospital, 1-396 Kosugi-machi, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. FAU - Kurosawa, Michiko AU - Kurosawa M AD - Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan. FAU - Takeuchi, Masaki AU - Takeuchi M AD - Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. FAU - Yoshimi, Ryusuke AU - Yoshimi R AD - Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. FAU - Sugiyama, Yumiko AU - Sugiyama Y AD - Yokohama City University Medical Center, Center for Rheumatic Diseases, 4-57 Urafunecho, Minami-ku, Yokohama, 232-0024, Japan. FAU - Ohno, Shigeru AU - Ohno S AD - Yokohama City University Medical Center, Center for Rheumatic Diseases, 4-57 Urafunecho, Minami-ku, Yokohama, 232-0024, Japan. FAU - Asami, Yukiko AU - Asami Y AD - Yokosuka Center for Rheumatic Diseases, Yokosuka City Hospital, 1-3-2 Nagasaka, Yokosuka, 240-0101, Japan. FAU - Sekiguchi, Akiko AU - Sekiguchi A AD - Department of Hematology and Rheumatology, Fujisawa City Hospital, 2-6-1 Fujisawa, Fujisawa, 251-8550, Japan. FAU - Igarashi, Toshihisa AU - Igarashi T AD - Department of Rheumatology, Yamato City Hospital, Fukaminishi, Yamato, 242-8602, Japan. FAU - Nagaoka, Shohei AU - Nagaoka S AD - Department of Rheumatology, Yokohama Minami Kyosai Hospital, 1-21-1 Mutsuura Higashi, Yokohama, 236-0037, Japan. FAU - Ishigatsubo, Yoshiaki AU - Ishigatsubo Y AD - Yokohama City University, Yokohama, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. FAU - Nakajima, Hideaki AU - Nakajima H AD - Department of Stem Cell and Immune Regulation, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. FAU - Mizuki, Nobuhisa AU - Mizuki N AD - Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210201 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (HLA-B Antigens) RN - 0 (HLA-B51 Antigen) SB - IM CIN - Nat Rev Rheumatol. 2021 Apr;17(4):188. PMID: 33619366 MH - *Arthritis MH - *Behcet Syndrome/diagnosis/epidemiology/genetics MH - Databases, Factual MH - HLA-B Antigens/genetics MH - HLA-B51 Antigen MH - Humans MH - Japan/epidemiology PMC - PMC7851921 OTO - NOTNLM OT - Behcet's disease OT - Cluster analysis OT - Intestinal manifestation COIS- Y. Kirino: Amgen (speaking and consultation fees); M. Takeno: Amgen (advisor for the clinical trial of Apremilast); and S. Nagaoka: Chugai, Bristol-Myers Squibb, Gilead (consultation fees). EDAT- 2021/02/02 06:00 MHDA- 2021/06/22 06:00 PMCR- 2021/02/01 CRDT- 2021/02/01 12:16 PHST- 2020/08/10 00:00 [received] PHST- 2020/12/25 00:00 [accepted] PHST- 2021/02/01 12:16 [entrez] PHST- 2021/02/02 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/02/01 00:00 [pmc-release] AID - 10.1186/s13075-020-02406-6 [pii] AID - 2406 [pii] AID - 10.1186/s13075-020-02406-6 [doi] PST - epublish SO - Arthritis Res Ther. 2021 Feb 1;23(1):49. doi: 10.1186/s13075-020-02406-6.