{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T21:47:02Z","timestamp":1770673622768,"version":"3.49.0"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Beh\u00e7et\u2019s disease (BD) is a systemic inflammatory disorder characterized by vasculitis affecting blood vessels of any caliber or type. It can present with a wide spectrum of vasculitic lesions, including erythema nodosum-like lesions and retinal vasculitis, and may also lead to larger vessel diseases, such as aortic aneurysm and deep vein thrombosis. The full etiology of BD remains unclear, but it is considered a polygenetic disease with multiple genetic risk factors that promote immune dysregulation and thrombophilia. Inflammation can be triggered by environmental factors, such as bacteria or viruses, and the dysregulation of innate and adaptive immune cell subsets. Neutrophils and lymphocytes are the primary players involved in BD pathogenesis, with specific innate (i.e., neutrophil-derived reactive oxygen species and neutrophil extracellular traps) and adaptive (i.e., anti-endothelial cell antibodies) processes inducing endothelial cell activation and chemotaxis of inflammatory cells, leading to coagulation and vasculitis. These inflammation-induced vasculitic or vasculopathic features are observed in most mucocutaneous BD lesions, although vasculitis <jats:italic>per se<\/jats:italic> is often pathologically evident only during a brief period of the disease process. Due to the multifactorial nature of BD-associated inflammation, broad-spectrum anti-inflammatory medications, including glucocorticoids and immunosuppressive drugs, have been the mainstay for managing BD. In addition, inhibitors of interleukin (IL)-1, tumor necrosis factor (TNF)-\u03b1, and IL-17, which target innate and adaptive immune functions dysregulated in BD, have emerged as promising new therapeutics. In this review, we discuss the muco-cutaneous manifestations of BD by focusing on the underlying vasculitic components in their pathologies, as well as the current array of treatment options.<\/jats:p>","DOI":"10.3389\/fmed.2022.987393","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T08:30:55Z","timestamp":1669969855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Mucocutaneous manifestations of Beh\u00e7et\u2019s disease: Pathogenesis and management from perspectives of vasculitis"],"prefix":"10.3389","volume":"9","author":[{"given":"Doyoung","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumio","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erkan","family":"Alpsoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongsik","family":"Bang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 Revised international Chapel Hill consensus conference nomenclature of vasculitides.","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum."},{"key":"B2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3349\/ymj.2012.53.1.35","article-title":"New insights in the clinical understanding of Beh\u00e7et\u2019s disease.","volume":"53","author":"Cho","year":"2012","journal-title":"Yonsei Med J."},{"key":"B3","doi-asserted-by":"publisher","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":"B4","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1002\/art.24642","article-title":"HLA-B51\/B5 and the risk of Behcet\u2019s disease: a systematic review and meta-analysis of case-control genetic association studies.","volume":"61","author":"de Menthon","year":"2009","journal-title":"Arthritis Rheum."},{"key":"B5","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/ng.2520","article-title":"Genome-wide association analysis identifies new susceptibility loci for Beh\u00e7et\u2019s disease and epistasis between HLA-B*51 and ERAP1.","volume":"45","author":"Kirino","year":"2013","journal-title":"Nat Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nrrheum.2015.147","article-title":"\u2018MHC-I-opathy\u2019-unified concept for spondyloarthritis and Beh\u00e7et disease.","volume":"11","author":"McGonagle","year":"2015","journal-title":"Nat Rev Rheumatol."},{"key":"B7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41572-021-00301-1","article-title":"Beh\u00e7et syndrome.","volume":"7","author":"Yazici","year":"2021","journal-title":"Nat Rev Dis Primers."},{"key":"B8","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/ng.625","article-title":"Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Beh\u00e7et\u2019s disease.","volume":"42","author":"Remmers","year":"2010","journal-title":"Nat Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3389\/fimmu.2019.00665","article-title":"Immunopathogenesis of Behcet\u2019s Disease.","volume":"10","author":"Tong","year":"2019","journal-title":"Front Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1002\/art.41637","article-title":"Genetic association of a gain-of-function IFNGR1 polymorphism and the intergenic region LNCAROD\/DKK1 With Beh\u00e7et\u2019s Disease.","volume":"73","author":"Ortiz Fern\u00e1ndez","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/ng.3786","article-title":"Dense genotyping of immune-related loci implicates host responses to microbial exposure in Beh\u00e7et\u2019s disease susceptibility.","volume":"49","author":"Takeuchi","year":"2017","journal-title":"Nat Genet."},{"key":"B12","first-page":"S44","article-title":"The role of heat shock proteins in Beh\u00e7et\u2019s disease.","volume":"21","author":"Direskeneli","year":"2003","journal-title":"Clin Exp Rheumatol."},{"key":"B13","first-page":"489","article-title":"The role of streptococcal hypersensitivity in the pathogenesis of Beh\u00e7et\u2019s Disease.","volume":"18","author":"Kaneko","year":"2008","journal-title":"Eur J Dermatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"581468","DOI":"10.1155\/2014\/581468","article-title":"New diagnostic way for behcet\u2019s disease: skin prick with self-saliva.","volume":"2014","author":"Kaneko","year":"2014","journal-title":"Genet Res Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1038\/sj.jid.5700203","article-title":"Role of IL-12B promoter polymorphism in adamantiades-Behcet\u2019s disease susceptibility: an involvement of Th1 immunoreactivity against Streptococcus Sanguinis antigen.","volume":"126","author":"Yanagihori","year":"2006","journal-title":"J Invest Dermatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1016\/s0140-6736(82)91268-5","article-title":"Detection of RNA complementary to herpes-simplex virus in mononuclear cells from patients with Beh\u00e7et\u2019s syndrome and recurrent oral ulcers.","volume":"2","author":"Eglin","year":"1982","journal-title":"Lancet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/BF02505221","article-title":"Polymerase chain reaction reveals herpes simplex virus DNA in saliva of patients with Beh\u00e7et\u2019s disease.","volume":"288","author":"Lee","year":"1996","journal-title":"Arch Dermatol Res."},{"key":"B18","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0923-1811(00)00080-3","article-title":"The effect of herpesvirus infection on the expression of cell adhesion molecules on cultured human dermal microvascular endothelial cells.","volume":"24","author":"Kim","year":"2000","journal-title":"J Dermatol Sci."},{"key":"B19","first-page":"21","article-title":"Beh\u00e7et\u2019s disease-like symptoms induced by the Herpes simplex virus in ICR mice.","volume":"8","author":"Sohn","year":"1998","journal-title":"Eur J Dermatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"607768","DOI":"10.3389\/fimmu.2021.607768","article-title":"Interrelationship of stress, environment, and herpes simplex virus Type-1 on Beh\u00e7et\u2019s Disease: using a mouse model.","volume":"12","author":"Islam","year":"2021","journal-title":"Front Immunol."},{"key":"B21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1093\/rheumatology\/27.4.300","article-title":"Treatment with acyclovir does not affect orogenital ulcers in Beh\u00e7et\u2019s syndrome: a randomized double-blind trial.","volume":"27","author":"Davies","year":"1988","journal-title":"Br J Rheumatol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.ophtha.2003.07.018","article-title":"Comparison of patients with Beh\u00e7et\u2019s disease in the 1980s and 1990s.","volume":"111","author":"Yoshida","year":"2004","journal-title":"Ophthalmology."},{"key":"B23","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/jdv.14601","article-title":"Incidence, prevalence, and mortality of adamantiades-Beh\u00e7et\u2019s disease in Korea: a nationwide, population-based study (2006-2015).","volume":"32","author":"Lee","year":"2018","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.3906\/sag-2003-147","article-title":"Decreasing incidence and severity of Beh\u00e7et\u2019s disease: a changing trend in epidemiological spectrum possibly associated with oral health.","volume":"50","author":"Mumcu","year":"2020","journal-title":"Turk J Med Sci."},{"key":"B25","first-page":"1332","article-title":"Changes of neutrophil migration without modification of in vitro metabolism and adhesion in Beh\u00e7et\u2019s disease.","volume":"24","author":"Carletto","year":"1997","journal-title":"J Rheumatol."},{"key":"B26","first-page":"S85","article-title":"Beh\u00e7et\u2019s disease heterogeneity: cytokine production and oxidative burst of phagocytes are altered in patients with severe manifestations.","volume":"33","author":"Perazzio","year":"2015","journal-title":"Clin Exp Rheumatol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.3389\/fimmu.2019.01085","article-title":"Beh\u00e7et\u2019s syndrome as a model of thrombo-inflammation: the role of neutrophils.","volume":"10","author":"Emmi","year":"2019","journal-title":"Front Immunol."},{"key":"B28","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1172\/JCI84538","article-title":"Neutrophil extracellular traps - the dark side of neutrophils.","volume":"126","author":"S\u00f8rensen","year":"2016","journal-title":"J Clin Invest."},{"key":"B29","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1136\/annrheumdis-2018-214335","article-title":"Critical role of neutrophil extracellular traps (NETs) in patients with Behcet\u2019s disease.","volume":"78","author":"Le Joncour","year":"2019","journal-title":"Ann Rheum Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1093\/rheumatology\/ken109","article-title":"Effects of vitamin D on expression of toll-like receptors of monocytes from patients with Behcet\u2019s disease.","volume":"47","author":"Do","year":"2008","journal-title":"Rheumatology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"586558","DOI":"10.3389\/fimmu.2020.586558","article-title":"Understanding Beh\u00e7et\u2019s Disease in the context of innate immunity activation.","volume":"11","author":"Perazzio","year":"2020","journal-title":"Front Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"852297","DOI":"10.3389\/fimmu.2022.852297","article-title":"The roles of monocytes and macrophages in Beh\u00e7et\u2019s Disease with focus on M1 and M2 Polarization. the roles of monocytes and macrophages in Beh\u00e7et\u2019s Disease with focus on M1 and M2 polarization.","volume":"13","author":"Hirahara","year":"2022","journal-title":"Front Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1111\/j.1346-8138.2003.tb00442.x","article-title":"Serum Levels of IL-4, IL-10, IL-12, IL-13 and IFN-gamma in Beh\u00e7et\u2019s disease.","volume":"30","author":"Aridogan","year":"2003","journal-title":"J Dermatol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.ajo.2006.04.016","article-title":"Intraocular cytokine environment in active Beh\u00e7et uveitis.","volume":"142","author":"Ahn","year":"2006","journal-title":"Am J Ophthalmol."},{"key":"B35","doi-asserted-by":"crossref","first-page":"CR227","DOI":"10.12659\/MSM.881720","article-title":"Expression of Th-17 and ROR\u03b3t mRNA in Beh\u00e7et\u2019s Disease.","volume":"17","author":"Hamzaoui","year":"2011","journal-title":"Med Sci Monit."},{"key":"B36","first-page":"32","article-title":"Up-regulation of Th17 and related cytokines in Beh\u00e7et\u2019s disease corresponding to disease activity.","volume":"31","author":"Na","year":"2013","journal-title":"Clin Exp Rheumatol."},{"key":"B37","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jaci.2011.05.029","article-title":"Critical role of IL-21 in modulating TH17 and regulatory T cells in Beh\u00e7et disease.","volume":"128","author":"Geri","year":"2011","journal-title":"J Allergy Clin Immunol."},{"key":"B38","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1038\/s41598-017-03251-5","article-title":"Enhancement of Th1\/Th17 inflammation by TRIM21 in Beh\u00e7et\u2019s disease.","volume":"7","author":"Ahn","year":"2017","journal-title":"Sci Rep."},{"key":"B39","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between inflammation and thrombosis in cardiovascular pathology.","volume":"18","author":"Stark","year":"2021","journal-title":"Nat Rev Cardiol."},{"key":"B40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3109\/08830189709116846","article-title":"Vasculitis in Beh\u00e7et\u2019s disease.","volume":"14","author":"Ehrlich","year":"1997","journal-title":"Int Rev Immunol."},{"key":"B41","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/ard.55.2.128","article-title":"Neutrophil adhesion to endothelial cells and factors affecting adhesion in patients with Beh\u00e7et\u2019s disease.","volume":"55","author":"Sahin","year":"1996","journal-title":"Ann Rheum Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/0046-8177(93)90086-v","article-title":"Ultrastructure of endothelial cell necrosis in classical erythema nodosum.","volume":"24","author":"Honma","year":"1993","journal-title":"Hum Pathol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/s0046-8177(87)80387-8","article-title":"The pathogenesis of vascular changes in erythema nodosum-like lesions of Beh\u00e7et\u2019s syndrome: an electron microscopic study.","volume":"18","author":"Bang","year":"1987","journal-title":"Hum Pathol."},{"key":"B44","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.jvsv.2018.11.006","article-title":"Increased vein wall thickness in Beh\u00e7et disease.","volume":"7","author":"Seyahi","year":"2019","journal-title":"J Vasc Surg Venous Lymphat Disord."},{"key":"B45","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/rheumatology\/keaa264","article-title":"Femoral vein wall thickness measurement: a new diagnostic tool for Beh\u00e7et\u2019s disease.","volume":"60","author":"Alibaz-Oner","year":"2021","journal-title":"Rheumatology."},{"key":"B46","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1136\/ard.53.4.265","article-title":"Antibodies to endothelial cells in Beh\u00e7et\u2019s disease: cell-binding heterogeneity and association with clinical activity.","volume":"53","author":"Cervera","year":"1994","journal-title":"Ann Rheum Dis."},{"key":"B47","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/s0923-1811(02)00062-2","article-title":"Activation of extracellular signal regulated kinase 1\/2 in human dermal microvascular endothelial cells stimulated by anti-endothelial cell antibodies in sera of patients with Beh\u00e7et\u2019s disease.","volume":"30","author":"Lee","year":"2002","journal-title":"J Dermatol Sci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1006\/clim.1999.4687","article-title":"Enhancement of endothelial cell E-selectin expression by sera from patients with active Beh\u00e7et\u2019s disease: moderate correlation with anti-endothelial cell antibodies and serum myeloperoxidase levels.","volume":"91","author":"Triolo","year":"1999","journal-title":"Clin Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/jid.2011.397","article-title":"Identification of HnRNP-A2\/B1 as a target antigen of anti-endothelial cell IgA antibody in Beh\u00e7et\u2019s disease.","volume":"132","author":"Cho","year":"2012","journal-title":"J Invest Dermatol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1002\/art.11074","article-title":"Human alpha-enolase from endothelial cells as a target antigen of anti-endothelial cell antibody in Beh\u00e7et\u2019s disease.","volume":"48","author":"Lee","year":"2003","journal-title":"Arthritis Rheum."},{"key":"B51","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.bbrc.2014.07.126","article-title":"Identification of prohibitin as an antigen in Behcet\u2019s disease.","volume":"451","author":"Xun","year":"2014","journal-title":"Biochem Biophys Res Commun."},{"key":"B52","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.bbrc.2014.12.064","article-title":"Identification of heat shock protein 27 as a novel autoantigen of Beh\u00e7et\u2019s disease.","volume":"456","author":"Chen","year":"2015","journal-title":"Biochem Biophys Res Commun."},{"key":"B53","doi-asserted-by":"publisher","first-page":"8162","DOI":"10.1038\/srep08162","article-title":"Annexin A2 as a target endothelial cell membrane autoantigen in Beh\u00e7et\u2019s disease.","volume":"5","author":"Chen","year":"2015","journal-title":"Sci Rep."},{"key":"B54","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ebiom.2016.03.009","article-title":"HnRNP A1 is involved in deep vein thrombosis patients with Beh\u00e7et\u2019s Disease.","volume":"6","author":"Chen","year":"2016","journal-title":"EBioMedicine."},{"key":"B55","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1055\/s-0035-1556727","article-title":"Endothelial dysfunction and altered coagulation as mediators of thromboembolism in Beh\u00e7et Disease.","volume":"41","author":"Butta","year":"2015","journal-title":"Semin Thromb Hemost."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1055\/s-0041-1740637","article-title":"Plasma homocysteine in Behcet\u2019s Disease: a systematic review and meta-analysis.","volume":"122","author":"Merashli","year":"2022","journal-title":"Thromb Haemost."},{"key":"B57","doi-asserted-by":"publisher","first-page":"624848","DOI":"10.3389\/fimmu.2021.624848","article-title":"Antineutrophil cytoplasmic antibody-associated vasculitis update: genetic pathogenesis.","volume":"12","author":"Li","year":"2021","journal-title":"Front Immunol."},{"key":"B58","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41584-018-0145-y","article-title":"Pathogenesis and therapeutic interventions for ANCA-associated vasculitis.","volume":"15","author":"Nakazawa","year":"2019","journal-title":"Nat Rev Rheumatol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.1002\/art.39239","article-title":"Promotion of hypercoagulability in antineutrophil cytoplasmic antibody-associated vasculitis by C5a-induced tissue factor-expressing microparticles and neutrophil extracellular traps.","volume":"67","author":"Huang","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1136\/annrheumdis-2013-203430","article-title":"Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease.","volume":"73","author":"Kambas","year":"2014","journal-title":"Ann Rheum Dis."},{"key":"B61","first-page":"66","article-title":"Revised diagnostic criteria for Beh\u00e7et\u2019s disease in 1987.","volume":"28","author":"Mizushima","year":"1988","journal-title":"Ryumachi."},{"key":"B62","first-page":"1078","article-title":"Criteria for diagnosis of Beh\u00e7et\u2019s disease.","volume":"335","year":"1990","journal-title":"Lancet."},{"key":"B63","doi-asserted-by":"publisher","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","year":"2014","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1093\/rheumatology\/kep350","article-title":"Prognosis of Behcet\u2019s syndrome among men with mucocutaneous involvement at disease onset: long-term outcome of patients enrolled in a controlled trial.","volume":"49","author":"Hamuryudan","year":"2010","journal-title":"Rheumatology."},{"key":"B65","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s40257-021-00609-4","article-title":"Beh\u00e7et Disease: an update for dermatologists.","volume":"22","author":"Alpsoy","year":"2021","journal-title":"Am J Clin Dermatol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1111\/j.1365-2133.1985.tb02082.x","article-title":"Immunological studies on aphthous ulcer and erythema nodosum-like eruptions in Behcet\u2019s disease.","volume":"113","author":"Kaneko","year":"1985","journal-title":"Br J Dermatol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/0008-8749(92)90207-6","article-title":"Streptococcal-related antigens stimulate production of IL6 and interferon-gamma by T cells from patients with Behcet\u2019s disease.","volume":"140","author":"Hirohata","year":"1992","journal-title":"Cell Immunol."},{"key":"B68","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1111\/j.1348-0421.1992.tb02083.x","article-title":"Antibody response to oral streptococci in Beh\u00e7et\u2019s disease.","volume":"36","author":"Yokota","year":"1992","journal-title":"Microbiol Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1046\/j.1365-2249.1997.3611265.x","article-title":"Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behcet\u2019s disease (BD) in Japan.","volume":"108","author":"Kaneko","year":"1997","journal-title":"Clin Exp Immunol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1365-2133.2006.07536.x","article-title":"The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Beh\u00e7et disease.","volume":"156","author":"Shaker","year":"2007","journal-title":"Br J Dermatol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1046\/j.1468-3083.2003.00625.x","article-title":"Histological and immunofluorescence findings of non-follicular papulopustular lesions in patients with Beh\u00e7et\u2019s disease.","volume":"17","author":"Alpsoy","year":"2003","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/0030-4220(84)90058-6","article-title":"Pathomorphologic features of the ulcerative stage of oral aphthous ulcerations.","volume":"58","author":"Schroeder","year":"1984","journal-title":"Oral Surg Oral Med Oral Pathol."},{"key":"B73","first-page":"178","article-title":"Leg ulcers in Beh\u00e7et\u2019s disease.","volume":"158","author":"Jung","year":"2008","journal-title":"Br J Dermatol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"7678","DOI":"10.4049\/jimmunol.175.11.7678","article-title":"T cell-regulated neutrophilic inflammation in autoinflammatory diseases.","volume":"175","author":"Keller","year":"2005","journal-title":"J Immunol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1111\/j.1365-4632.2009.03905.x","article-title":"Significance of serum interleukin-8 levels in patients with Behcet\u2019s disease: high levels may indicate vascular involvement.","volume":"48","author":"Durmazlar","year":"2009","journal-title":"Int J Dermatol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1046\/j.1365-4362.1998.00401.x","article-title":"A randomized, controlled and blinded study of papulopustular lesions in Turkish Beh\u00e7et\u2019s patients.","volume":"37","author":"Alpsoy","year":"1998","journal-title":"Int J Dermatol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1111\/j.1468-3083.2009.03256.x","article-title":"A histopathological approach: when papulopustular lesions should be in the diagnostic criteria of Beh\u00e7et\u2019s disease?","volume":"23","author":"Kalkan","year":"2009","journal-title":"J Eur Acad Dermatol Venereol."},{"key":"B78","first-page":"747","article-title":"Beh\u00e7et\u2019s syndrome. Immunopathologic and histopathologic assessment of pathergy lesions is useful in diagnosis and follow-up.","volume":"109","author":"Jorizzo","year":"1985","journal-title":"Arch Pathol Lab Med."},{"key":"B79","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0190-9622(97)80318-0","article-title":"Cutaneous vasculitis in Beh\u00e7et\u2019s disease: a clinical and histopathologic study of 20 patients.","volume":"36","author":"Chen","year":"1997","journal-title":"J Am Acad Dermatol."},{"key":"B80","first-page":"33","article-title":"Ultrastructure of vascular changes in cutaneous manifestations of Beh\u00e7et\u2019s disease.","volume":"68","author":"Bang","year":"1988","journal-title":"Acta Derm Venereol."},{"key":"B81","first-page":"808","article-title":"2018 update of the EULAR recommendations for the management of Beh\u00e7et\u2019s syndrome.","volume":"77","author":"Hatemi","year":"2018","journal-title":"Ann Rheum Dis."},{"key":"B82","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1136\/ard.2007.080432","article-title":"EULAR recommendations for the management of Beh\u00e7et disease.","volume":"67","author":"Hatemi","year":"2008","journal-title":"Ann Rheum Dis."},{"key":"B83","doi-asserted-by":"crossref","first-page":"127","DOI":"10.2147\/JEP.S265645","article-title":"Experimental therapeutic solutions for Behcet\u2019s Disease.","volume":"13","author":"Bozca","year":"2021","journal-title":"J Exp Pharmacol."},{"key":"B84","first-page":"75","article-title":"Comparing the effect of phenytoin syrup and triamcinolone acetonide ointment on aphthous ulcers in patients with Behcet\u2019s Syndrome.","volume":"14","author":"Fani","year":"2012","journal-title":"Iran Red Crescent Med J."},{"key":"B85","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/1346-8138.15207","article-title":"Guidelines for the treatment of skin and mucosal lesions in Beh\u00e7et\u2019s disease: a secondary publication.","volume":"47","author":"Nakamura","year":"2020","journal-title":"J Dermatol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1001\/archderm.135.5.529","article-title":"The use of sucralfate suspension in the treatment of oral and genital ulceration of Beh\u00e7et disease: a randomized, placebo-controlled, double-blind study.","volume":"135","author":"Alpsoy","year":"1999","journal-title":"Arch Dermatol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/j.1756-185X.2010.01531.x","article-title":"Pimecrolimus versus placebo in genital aphthous ulcers of Behcet\u2019s disease: a randomized double-blind controlled trial.","volume":"13","author":"Chams-Davatchi","year":"2010","journal-title":"Int J Rheum Dis."},{"key":"B88","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1007\/s10165-009-0200-2","article-title":"Colchicine versus placebo in Beh\u00e7et\u2019s disease: randomized, double-blind, controlled crossover trial.","volume":"19","author":"Davatchi","year":"2009","journal-title":"Mod Rheumatol."},{"key":"B89","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1002\/1529-0131(200111)44:11<2686::AID-ART448>3.0.CO;2-H","article-title":"A double-blind trial of colchicine in Beh\u00e7et\u2019s syndrome.","volume":"44","author":"Yurdakul","year":"2001","journal-title":"Arthritis Rheum."},{"key":"B90","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s10753-015-0237-7","article-title":"Effect of colchicine on platelet-platelet and platelet-leukocyte interactions: a pilot study in healthy subjects.","volume":"39","author":"Shah","year":"2016","journal-title":"Inflammation."},{"key":"B91","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00431-009-1040-y","article-title":"Beh\u00e7et disease: treatment of vascular involvement in children.","volume":"169","author":"Ozen","year":"2010","journal-title":"Eur J Pediatr."},{"key":"B92","doi-asserted-by":"publisher","first-page":"624795","DOI":"10.3389\/fmed.2021.624795","article-title":"Treatment of Beh\u00e7et\u2019s Disease: an algorithmic multidisciplinary approach.","volume":"8","author":"Alpsoy","year":"2021","journal-title":"Front Med."},{"key":"B93","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/rheumatology\/kei165","article-title":"A double-blind trial of depot corticosteroids in Beh\u00e7et\u2019s syndrome.","volume":"45","author":"Mat","year":"2006","journal-title":"Rheumatology."},{"key":"B94","doi-asserted-by":"publisher","first-page":"80","DOI":"10.55563\/clinexprheumatol\/ra8ize","article-title":"Apremilast for oral ulcers associated with active Beh\u00e7et\u2019s syndrome over 68 weeks: long-term results from a phase 3 randomised clinical trial.","author":"Hatemi","year":"2021","journal-title":"Clin Exp Rheumatol."},{"key":"B95","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1056\/NEJMoa1816594","article-title":"Trial of apremilast for oral ulcers in Beh\u00e7et\u2019s Syndrome.","volume":"381","author":"Hatemi","year":"2019","journal-title":"N Engl J Med."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1093\/mr\/roab098","article-title":"Beneficial effects of apremilast on genital ulcers, skin lesions, and arthritis in patients with Beh\u00e7et\u2019s Disease: a systematic review and meta-analysis.","volume":"32","author":"Iizuka","year":"2021","journal-title":"Mod Rheumatol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"19","DOI":"10.2165\/00126839-200304010-00002","article-title":"Efficacy of rebamipide as adjunctive therapy in the treatment of recurrent oral aphthous ulcers in patients with Beh\u00e7et\u2019s disease: a randomised, double-blind, placebo-controlled study.","volume":"4","author":"Matsuda","year":"2003","journal-title":"Drugs R D."},{"key":"B98","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1159\/000246336","article-title":"Effect of prophylactic benzathine penicillin on mucocutaneous symptoms of Beh\u00e7et\u2019s disease.","volume":"192","author":"Calg\u00fcneri","year":"1996","journal-title":"Dermatology."},{"key":"B99","doi-asserted-by":"publisher","first-page":"444","DOI":"10.3349\/ymj.1997.38.6.444","article-title":"Streptococcal infection in the pathogenesis of Beh\u00e7et\u2019s disease and clinical effects of minocycline on the disease symptoms.","volume":"38","author":"Kaneko","year":"1997","journal-title":"Yonsei Med J."},{"key":"B100","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/1756-185X.13298","article-title":"Management of vascular Beh\u00e7et\u2019s disease.","author":"Alibaz-Oner","year":"2019","journal-title":"Int J Rheum Dis."},{"key":"B101","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s11739-018-1991-y","article-title":"Vascular Beh\u00e7et\u2019s syndrome: an update.","volume":"14","author":"Emmi","year":"2019","journal-title":"Intern Emerg Med."},{"key":"B102","doi-asserted-by":"publisher","first-page":"e1899","DOI":"10.1097\/MD.0000000000001899","article-title":"Clinical and ultrasonographic evaluation of lower-extremity vein thrombosis in behcet syndrome: an observational study.","volume":"94","author":"Seyahi","year":"2015","journal-title":"Medicine."},{"key":"B103","first-page":"2164329","article-title":"Successful treatment and secondary prevention of venous thrombosis secondary to Beh\u00e7et Disease with rivaroxaban.","volume":"2016","author":"Boban","year":"2016","journal-title":"Case Rep Hematol."},{"key":"B104","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1056\/NEJM199002013220501","article-title":"A controlled trial of azathioprine in Beh\u00e7et\u2019s syndrome.","volume":"322","author":"Yazici","year":"1990","journal-title":"N Engl J Med."},{"key":"B105","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S0190-9622(97)80354-4","article-title":"Efficacy of cyclosporine on mucocutaneous manifestations of Beh\u00e7et\u2019s disease.","volume":"36","author":"Avci","year":"1997","journal-title":"J Am Acad Dermatol."},{"key":"B106","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.1346-8138.2002.tb00263.x","article-title":"Dapsone in Beh\u00e7et\u2019s disease: a double-blind, placebo-controlled, cross-over study.","volume":"29","author":"Sharquie","year":"2002","journal-title":"J Dermatol."},{"key":"B107","doi-asserted-by":"crossref","first-page":"443","DOI":"10.7326\/0003-4819-128-6-199803150-00004","article-title":"Thalidomide in the treatment of the mucocutaneous lesions of the Beh\u00e7et syndrome. a randomized, double-blind, placebo-controlled trial.","volume":"128","author":"Hamuryudan","year":"1998","journal-title":"Ann Intern Med."},{"key":"B108","first-page":"98","article-title":"Short-term trial of etanercept in Beh\u00e7et\u2019s disease: a double blind, placebo controlled study.","volume":"32","author":"Melikoglu","year":"2005","journal-title":"J Rheumatol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1093\/rheumatology\/kem034","article-title":"Anti-TNF therapy in the management of Behcet\u2019s disease\u2013review and basis for recommendations.","volume":"46","author":"Sfikakis","year":"2007","journal-title":"Rheumatology."},{"key":"B110","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/s10067-007-0685-z","article-title":"Treatment of venous thrombosis associated with Behcet\u2019s disease: immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation.","volume":"27","author":"Ahn","year":"2008","journal-title":"Clin Rheumatol."},{"key":"B111","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1001\/archderm.138.4.467","article-title":"Interferon alfa-2a in the treatment of Beh\u00e7et disease: a randomized placebo-controlled and double-blind study.","volume":"138","author":"Alpsoy","year":"2002","journal-title":"Arch Dermatol."},{"key":"B112","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s00296-019-04259-y","article-title":"The right place of interleukin-1 inhibitors in the treatment of Beh\u00e7et\u2019s syndrome: a systematic review.","volume":"39","author":"Bettiol","year":"2019","journal-title":"Rheumatol Int."},{"key":"B113","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1002\/art.40912","article-title":"Long-term outcome of ustekinumab therapy for Beh\u00e7et\u2019s Disease.","volume":"71","author":"Mirouse","year":"2019","journal-title":"Arthritis Rheumatol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.jaut.2018.09.002","article-title":"Efficacy of the anti-IL 17 secukinumab in refractory Beh\u00e7et\u2019s syndrome: a preliminary study.","volume":"97","author":"Di Scala","year":"2019","journal-title":"J Autoimmun."},{"key":"B115","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1136\/ard.2008.093260","article-title":"Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up.","volume":"67","author":"Molloy","year":"2008","journal-title":"Ann Rheum Dis."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.987393\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T08:31:28Z","timestamp":1669969888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.987393\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,2]]},"references-count":115,"alternative-id":["10.3389\/fmed.2022.987393"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.987393","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,2]]},"article-number":"987393"}}