{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:53:00Z","timestamp":1793141580866,"version":"4.5.0"},"reference-count":46,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"unspecified","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,6,16]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Clinical features of Beh\u00e7et\u2019s disease (BD) exhibit significant variability, not only from patient to patient but also according to gender and geographical region. This study aims to describe the clinical characteristics, identify distinct clusters in a large cohort of paediatric BD patients and compare the clinical manifestations of patients across three geographical regions: Turkey, Europe and Iran.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Patients with paediatric-onset BD (&lt;18 years of age) from Turkey, Iran and European countries (France and Italy) were retrospectively evaluated. A follow-up period of at least 6\u2009months was required for inclusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study included 600 patients (297 females, 49.5%), with cases from Turkey (n=231), Iran (n=306), France (n=44) and Italy (n=19). The most common presentations were mucocutaneous involvement (97.5%), followed by ocular (48.0%), musculoskeletal (43.2%), neurological (11.8%), vascular (11.5%), gastrointestinal (9.0%) and cardiac (2.0%) involvement. Ocular involvement was more prevalent in Iran, gastrointestinal involvement in Europe, and musculoskeletal and vascular involvement in Turkey compared with the other geographical regions. Seven distinct clusters of paediatric BD as vascular (cluster 1 (C1)), mucocutaneous only (C2), ocular (C3), gastrointestinal (C4), mixed (C5), neurologic and ocular (C6), and mucocutaneous-musculoskeletal cluster (C7) were identified, although there was some overlap in system involvements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study supports the notion that BD may tend to present in certain clusters in children as well. Since BD is a complex disease with a multifactorial aetiology, involving the interaction of pathogenic pathways, classification of clusters presents a significant challenge. We have also shown that certain clinical features vary among geographical regions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2024-005335","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T09:35:15Z","timestamp":1751708115000},"page":"e005335","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Clusters in paediatric Beh\u00e7et\u2019s disease: a multicentre international study"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0426-9432","authenticated-orcid":false,"given":"Ummusen","family":"Kaya Akca","sequence":"first","affiliation":[{"name":"Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhad","family":"Shahram","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdem","family":"Karabulut","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Hacettepe University, Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massoomeh","family":"Akhlaghi","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh Tahereh","family":"Faezi","sequence":"additional","affiliation":[{"name":"Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozlem","family":"Akgun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"\u00c7akan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Esen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3710-0569","authenticated-orcid":false,"given":"Caterina","family":"Matucci-Cerinic","sequence":"additional","affiliation":[{"name":"UOC Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini, Genova, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruya","family":"Torun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Dokuz Eyl\u00fcl University, Faculty of Medicine, Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erbil","family":"Unsal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Dokuz Eyl\u00fcl University, Faculty of Medicine, Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0704-1916","authenticated-orcid":false,"given":"Marco","family":"Gattorno","sequence":"additional","affiliation":[{"name":"UOC Rheumatology and Autoinflammatory Diseases, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuray","family":"Aktay Ayaz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fenur","family":"Pa\u00e7 K\u0131saarslan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Erciyes University Faculty of Medicine, Kayseri, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Sozeri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-2363","authenticated-orcid":false,"given":"Ezgi Deniz","family":"Batu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8939-5763","authenticated-orcid":false,"given":"Isabelle","family":"Kon\u00e9-Paut","sequence":"additional","affiliation":[{"name":"Department of Paediatric Rheumatology and National French Reference Centre for Auto-Inflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA), Bic\u00eatre Hospital, Assistance publique-H\u00f4pitaux de Paris, University Paris Saclay, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2883-7868","authenticated-orcid":false,"given":"Seza","family":"Ozen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"2025121606200746000_11.3.e005335.1","doi-asserted-by":"crossref","first-page":"627192","DOI":"10.3389\/fmed.2021.627192","article-title":"Pediatric Beh\u00e7et\u2019s Disease","volume":"8","author":"Yildiz","year":"2021","journal-title":"Front Med"},{"key":"2025121606200746000_11.3.e005335.2","doi-asserted-by":"crossref","DOI":"10.3390\/jcm11051278","article-title":"Paediatric Beh\u00e7et\u2019s Disease: A Comprehensive Review with an Emphasis on Monogenic Mimics","volume":"11","author":"Kul Cinar","year":"2022","journal-title":"J Clin Med"},{"key":"2025121606200746000_11.3.e005335.3","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S232660"},{"key":"2025121606200746000_11.3.e005335.4","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1097\/BOR.0b013e328363ea8b","article-title":"Pediatric-onset Beh\u00e7et disease","volume":"25","author":"Ozen","year":"2013","journal-title":"Curr Opin Rheumatol"},{"key":"2025121606200746000_11.3.e005335.5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/rheumatology\/kew486","article-title":"Exploring the variability in Beh\u00e7et\u2019s disease prevalence: a meta-analytical approach","volume":"57","author":"Maldini","year":"2018","journal-title":"Rheumatology (Oxford)"},{"key":"2025121606200746000_11.3.e005335.6","doi-asserted-by":"publisher","DOI":"10.1002\/art.37708"},{"key":"2025121606200746000_11.3.e005335.7","doi-asserted-by":"publisher","DOI":"10.1080\/1547691X.2017.1346008"},{"key":"2025121606200746000_11.3.e005335.8","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.01067","article-title":"Beh\u00e7et\u2019s Disease: An Overview of Etiopathogenesis","volume":"10","author":"Leccese","year":"2019","journal-title":"Front Immunol"},{"key":"2025121606200746000_11.3.e005335.9","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.02830","article-title":"Treating the Different Phenotypes of Beh\u00e7et\u2019s Syndrome","volume":"10","author":"Bettiol","year":"2019","journal-title":"Front Immunol"},{"key":"2025121606200746000_11.3.e005335.10","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208491"},{"key":"2025121606200746000_11.3.e005335.11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/jdv.12107","article-title":"The International Criteria for Beh\u00e7et\u2019s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria","volume":"28","author":"Davatchi","year":"2014","journal-title":"Acad Dermatol Venereol"},{"key":"2025121606200746000_11.3.e005335.12","first-page":"347","article-title":"Disease patterns of patients with Beh\u00e7et\u2019s disease demonstrated by factor analysis","volume":"17","author":"Krause","year":"1999","journal-title":"Clin Exp Rheumatol"},{"key":"2025121606200746000_11.3.e005335.13","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker423"},{"key":"2025121606200746000_11.3.e005335.14","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s11739-019-02248-4","article-title":"Beh\u00e7et\u2019s syndrome in Italy: a detailed retrospective analysis of 396 cases seen in 3 tertiary referral clinics","volume":"15","author":"Sota","year":"2020","journal-title":"Intern Emerg Med"},{"key":"2025121606200746000_11.3.e005335.15","first-page":"2393","article-title":"Target organ associations in Turkish patients with Beh\u00e7et\u2019s disease: a cross sectional study by exploratory factor analysis","volume":"29","author":"Tunc","year":"2002","journal-title":"J Rheumatol"},{"key":"2025121606200746000_11.3.e005335.16","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1080\/14397595.2021.1891670","article-title":"Distinct clinical characteristics of pediatric Beh\u00e7et\u2019s syndrome: A study from a referral center in China","volume":"31","author":"Zou","year":"2021","journal-title":"Mod Rheumatol"},{"key":"2025121606200746000_11.3.e005335.17","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s13075-021-02429-7","article-title":"Cluster analysis of phenotypes of patients with Beh\u00e7et\u2019s syndrome: a large cohort study from a referral center in China","volume":"23","author":"Zou","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"2025121606200746000_11.3.e005335.18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s13075-020-02406-6","article-title":"Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Beh\u00e7et\u2019s disease in Japan","volume":"23","author":"Soejima","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"2025121606200746000_11.3.e005335.19","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/mr\/roac044","article-title":"Cluster analysis of paediatric Beh\u00e7et\u2019s disease: Data from The Pediatric Rheumatology Academy-Research Group","volume":"33","author":"Demir","year":"2023","journal-title":"Mod Rheumatol"},{"key":"2025121606200746000_11.3.e005335.20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/RHU.0000000000001996","article-title":"Characteristics of Patients With Beh\u00e7et Disease From the Van Province, Eastern Turkey: Definition of Disease Clusters in a Tertiary Referral Center","volume":"29","author":"Oguz","year":"2023","journal-title":"J Clin Rheumatol"},{"key":"2025121606200746000_11.3.e005335.21","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s12519-023-00785-9","article-title":"Clinical heterogeneity and five phenotypes identified in pediatric Beh\u00e7et\u2019s syndrome: a cohort study from Shanghai Beh\u00e7et\u2019s syndrome database","volume":"20","author":"Hu","year":"2024","journal-title":"World J Pediatr"},{"key":"2025121606200746000_11.3.e005335.22","first-page":"S48","article-title":"Are clusters of patients with distinct clinical expression present in Beh\u00e7et\u2019s disease?","volume":"27","author":"Arida","year":"2009","journal-title":"Clin Exp Rheumatol"},{"key":"2025121606200746000_11.3.e005335.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2020.01.013"},{"key":"2025121606200746000_11.3.e005335.24","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-016-3187-z"},{"key":"2025121606200746000_11.3.e005335.25","doi-asserted-by":"publisher","DOI":"10.14744\/TurkPediatriArs.2019.15045"},{"key":"2025121606200746000_11.3.e005335.26","doi-asserted-by":"crossref","DOI":"10.1186\/s12969-017-0213-x","article-title":"A national cohort study on pediatric Beh\u00e7et\u2019s disease: cross-sectional data from an Italian registry","volume":"15","author":"Gallizzi","year":"2017","journal-title":"Pediatr Rheumatol Online J"},{"key":"2025121606200746000_11.3.e005335.27","doi-asserted-by":"publisher","DOI":"10.3109\/09273948.2011.555592"},{"key":"2025121606200746000_11.3.e005335.28","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.208"},{"key":"2025121606200746000_11.3.e005335.29","first-page":"S135","article-title":"Paediatric rheumatology Paediatric Beh\u00e7et\u2019s disease in Iran: report of 204 cases","volume":"36","author":"Shahram","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"2025121606200746000_11.3.e005335.30","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1080\/14397595.2018.1558752","article-title":"Behcet\u2019s disease in Iran: Analysis of 7641 cases","volume":"29","author":"Davatchi","year":"2019","journal-title":"Mod Rheumatol"},{"key":"2025121606200746000_11.3.e005335.31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s11739-013-1036-5","article-title":"Beh\u00e7et\u2019s syndrome pathophysiology and potential therapeutic targets","volume":"9","author":"Emmi","year":"2014","journal-title":"Intern Emerg Med"},{"key":"2025121606200746000_11.3.e005335.32","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000846"},{"key":"2025121606200746000_11.3.e005335.33","doi-asserted-by":"crossref","first-page":"713052","DOI":"10.3389\/fmed.2021.713052","article-title":"Pathogenesis of Beh\u00e7et\u2019s Syndrome: Genetic, Environmental and Immunological Factors","volume":"8","author":"Mattioli","year":"2021","journal-title":"Front Med"},{"key":"2025121606200746000_11.3.e005335.34","first-page":"261","article-title":"Sensitivity and specificity of pathergy test results in Israeli patients with Beh\u00e7et\u2019s disease","volume":"45","author":"Friedman-Birnbaum","year":"1990","journal-title":"Cutis"},{"key":"2025121606200746000_11.3.e005335.35","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1365-2230.2006.02284.x","article-title":"Pathergy reaction in different body areas in Beh\u00e7et\u2019s disease","volume":"32","author":"Ozdemir","year":"2007","journal-title":"Clin Exp Dermatol"},{"key":"2025121606200746000_11.3.e005335.36","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2340\/00015555597779","article-title":"The usefulness of the nonspecific skin hyperreactivity (the pathergy test) in Beh\u00e7et\u2019s disease in Turkey","volume":"59","author":"T\u00fcz\u00fcn","year":"1979","journal-title":"Acta Derm Venereol"},{"key":"2025121606200746000_11.3.e005335.37","doi-asserted-by":"publisher","DOI":"10.1136\/ard.43.1.74"},{"key":"2025121606200746000_11.3.e005335.38","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-009-1008-9"},{"key":"2025121606200746000_11.3.e005335.39","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1080\/14397595.2021.1886623","article-title":"Long-term outcome and predictors of remission in Beh\u00e7et\u2019s disease in daily practice","volume":"31","author":"Malek Mahdavi","year":"2021","journal-title":"Mod Rheumatol"},{"key":"2025121606200746000_11.3.e005335.40","first-page":"S19","article-title":"Onset signs, clinical course, prognosis, treatment and outcome of adult patients with Adamantiades-Beh\u00e7et\u2019s disease in Greece","volume":"21","author":"Zouboulis","year":"2003","journal-title":"Clin Exp Rheumatol"},{"key":"2025121606200746000_11.3.e005335.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(10)90010-0"},{"key":"2025121606200746000_11.3.e005335.42","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213225"},{"key":"2025121606200746000_11.3.e005335.43","doi-asserted-by":"publisher","DOI":"10.1046\/j.1442-9071.2001.00445.x"},{"key":"2025121606200746000_11.3.e005335.44","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(99)90120-3"},{"key":"2025121606200746000_11.3.e005335.45","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-005-0070-8"},{"key":"2025121606200746000_11.3.e005335.46","first-page":"S84","article-title":"Cyclosporine for Beh\u00e7et\u2019s uveitis: is it associated with an increased risk of neurological involvement?","volume":"26","author":"Akman-Demir","year":"2008","journal-title":"Clin Exp Rheumatol"}],"container-title":["RMD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/rmdopen-2024-005335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T14:20:23Z","timestamp":1765894823000},"score":1,"resource":{"primary":{"URL":"https:\/\/rmdopen.bmj.com\/lookup\/doi\/10.1136\/rmdopen-2024-005335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,7,5]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/rmdopen-2024-005335"],"URL":"https:\/\/doi.org\/10.1136\/rmdopen-2024-005335","relation":{},"ISSN":["2056-5933"],"issn-type":[{"value":"2056-5933","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}