Have a personal or library account? Click to login
Behçet’s Disease: A Comprehensive Overview of Symptoms, Pathology, Genetics, and Treatment Cover

Behçet’s Disease: A Comprehensive Overview of Symptoms, Pathology, Genetics, and Treatment

Open Access
|Feb 2026

References

  1. Tong B, Liu X, Xiao J, Su G. Immunopathogenesis of Behcet’s Disease. Front Immunol. 2019;10:665. doi: 10.3389/fimmu.2019.00665/full
  2. Nieto IG, Alabau JLC. Immunopathogenesis of Behçet disease. Curr Rheumatol Rev. 2020;16(1):12–20. doi: 10.2174/1573397115666190415142426
  3. Davatchi F, Shahram F, Chams-Davatchi C, Shams H, Nadji A, Akhlaghi M, et al. Behcet’s disease in Iran: analysis of 6500 cases. Int J of Rheum Dis. 2010;13(4):367–73. doi: 10.1111/j.1756-185X.2010.01549.x
  4. Hadjimi Z, Belguendouz H, Benchabane S, Ghozali NEH, Amri M, Kocheida R, et al. Increased Salivary Cytokines and Nitric Oxide Levels in Behçet’s Disease: Interleukin-32, a Novel Player in Disease Prognosis. Endocr Metab Immune Disord Drug Targets. 2023;23(3):347–55. doi: 10.2174/1871530322666220512120948
  5. Nakamura K, Iwata Y, Asai J, Kawakami T, Tsunemi Y, Takeuchi M, et al. Guidelines for the treatment of skin and mucosal lesions in Behçet’s disease: A secondary publication. J Dermatol. 2020;47(3):223–35. doi: 10.1111/1346-8138.15207
  6. Deuter C, Kotter I, Wallace G, Murray P, Stubiger N, Zierhut M. Behçet’s disease: Ocular effects and treatment. Prog Retin Eye Res. 2008;27(1):111–36. doi: 10.1016/j.preteyeres.2007.09.002
  7. Houman MH, Neffati H, Braham A, Harzallah O, Khanfir M, Miled M, et al. Behçet’s disease in Tunisia. Demographic, clinical and genetic aspects in 260 patients. Clin Exp Rheumatol. 2007;25(4 Suppl 45):S58–64.
  8. Egyptian College of Rheumatology-Behçet’s Disease Study Group (ECR-BDSG), Gheita TA, El-Latif EA, El-Gazzar II, Samy N, Hammam N, et al. Correction to: Behçet’s disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature. Clin Rheumatol. 2019;38(9):2649–50. doi: 10.1007/s10067-019-04653-8
  9. Ghembaza MEA, Bouabdallah N, Lounici A. Behçet disease in Western Algeria. Médecine et Santé Tropicales. 2017;27(1):101–4. doi: 10.1684/mst.2017.0656
  10. Kappen JH, van Dijk EHC, Baak-Dijkstra M, van Daele PLA, Lam-Tse WK, van Hagen PM, et al. Behçet’s disease, hospital-based prevalence and manifestations in the Rotterdam area. Neth J Med. 2015;73(10):471–7.
  11. Melikoğlu MA, Melikoğlu M. The Influence of Age on Behcet’s Disease Activity. Eurasian J Med. 2008;40(2):68–71.
  12. Kılıç G, Körüklü KF, Kumcu MG, Çakır E, Karkucak M, Kılıç E. Gender disparities in Behçet’s syndrome: identifying distinct phenotypes through cluster analysis. Immunol Res. 2024;72(5):975–81. doi: 10.1007/s12026-024-09498-1
  13. Chen KR, Kawahara Y, Miyakawa S, Nishikawa T. Cutaneous vasculitis in Behçet’s disease: A clinical and histopathologic study of 20 patients. J Am Acad Dermatol. 1997;36(5):689–96. doi: : 10.1016/S0190-9622(97)80318-0
  14. Adil A, Goyal A, Quint JM. Behcet Disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Available from: http://www.ncbi.nlm.nih.gov/books/NBK470257/
  15. Al-Obeidi AF, Nowatzky J. Immunopathogenesis of Behçet’s disease. Clinical Immunol. 2023;253:109661. 10.1016/j.clim.2023.109661
  16. Van Der Houwen TB, Van Hagen PM, Van Laar JAM. Immunopathogenesis of Behçet’s disease and treatment modalities. Seminars in Arthritis and Rheumatism. 2022;52:151956. doi: 10.1016/j.semarthrit.2022.151956
  17. Ortiz-Fernández L, Sawalha AH. Genetics of Behçet’s disease: functional genetic analysis and estimating disease heritability. Front Med. 2021;8:625710. doi: 10.3389/fmed.2021.625710/
  18. Mattioli I, Bettiol A, Saruhan-Direskeneli G, Direskeneli H, Emmi G. Pathogenesis of Behçet’s syndrome: genetic, environmental and immunological factors. Front Med. 2021;8:713052. doi: 10.3389/fmed.2021.713052
  19. Sornsamdang G, Shobana J, Chanprapaph K, Chantratita W, Chotewutmontri S, Limtong P, et al. Novel genetic variants of HLA gene associated with Thai Behcet’s disease (BD) patients using next generation sequencing technology. Sci Rep. 2024;14(1):7967. doi: 10.1038/s41598-024-58254-w
  20. Takeno M. The association of Behçet’s syndrome with HLA-B51 as understood in 2021. Curr Opin Rheumatol. 2022;34(1):4–9. doi: 10.1097/BOR.0000000000000846
  21. Kim JN, Kwak SG, Choe JY, Kim SK. The prevalence of Behçet’s disease in Korea: data from Health Insurance Review and Assessment Service from 2011 to 2015. Clin Exp Rheumatol. 2017;35 Suppl 108(6):38–42.
  22. Sakane T, Takeno M, Suzuki N, Inaba G. Behçet’s Disease. N Engl J Med. 1999;341(17):1284–91. doi: 10.1056/NEJM199910213411707
  23. Hatemi G, Seyahi E, Fresko I, Talarico R, Uçar D, Hamuryudan V. One year in review 2021: Behçet’s syndrome. Clin Exp Rheumatol. 2021;39(5):3–13. doi: 10.55563/clinexprheumatol/lnvc9k
  24. Leonardo NM, McNeil J. Behcet’s Disease: Is There Geographical Variation? A Review Far from the Silk Road. Int J Rheumatol. 2015;2015:1–7. doi: 10.1155/2015/945262
  25. Muñoz SA, Kostianovsky A, Allievi A, Orden AO. Behçet disease in Latin American countries: a systematic literature review of demographic and clinical features, and HLA-B*51 allele frequency. Reumatología Clínica (English Edition). 2023;19(7):386–91. doi: 10.1016/j.reumae.2022.12.005
  26. Gu F, Huang X, Huang W, Zhao M, Zheng H, Wang Y, et al. The role of miRNAs in Behçet’s disease. Front Immunol. 2023;14:1249826. doi: 10.3389/fimmu.2023.1249826/full
  27. Villiger RA, Stefanski AL, Grobty V, Adler S, Villiger PM. Behçet’s syndrome: clinical presentation and prevalence in Switzerland. Swiss Med Wkly. 2019; 149:w20072. doi: 10.4414/smw.2019.20072
  28. Leccese P, Padula MC, Santospirito EV, Colucci R, Lascaro N, Padula AA, et al. The relationship between HLA-B*51 subtypes, clinical manifestations and severity of Behçet’s syndrome: a large Italian cohort study. Rheumatology Adv Pract. 2023;7(3):rkad087. doi: 10.1093/rap/rkad087
  29. Alibaz-Oner F, Direskeneli H. Advances in the treatment of Behçet’s disease. Curr Rheumatol Rep. 2021;23(6):47. doi: 10.1007/s11926-021-01011-z
  30. Alpsoy E, Leccese P, Emmi G, Ohno S. Treatment of Behçet’s disease: an algorithmic multidisciplinary approach. Front Med. 2021;8:624795. doi: 10.3389/fmed.2021.624795/full
  31. Kudsi M, Khalayli N, Allahham A. Behcet’s disease: Diagnosed as isolated recurrent oral aphthae; a case report. Ann Med Surg (London). 2022;81. doi: j.amsu.2022.104327
  32. Moots RJ, Fortune F, Jackson R, Thornburn T, Morgan A, Carr DF, et al. Infliximab vs interferon-α in the treatment of Behçet’s syndrome: clinical data from the BIO-BEHÇET’S randomized controlled trial. Rheumatol. 2025;64(5):2882–91. doi: 10.1093/rheumatology/keae585
  33. Hatemi G, Mahr A, Ishigatsubo Y, Song YW, Takeno M, Kim D, et al. Trial of Apremilast for oral ulcers in Behçet’s syndrome. N Engl J Med. 2019;381(20):1918–28. doi: 10.1056/NEJMoa1816594
  34. Geertsema-Hoeve BC, Van Laar JAM, Raaphorst J, Tas SW, Welsing PMJ, Goekoop RJ, et al. Multicentre, 26-weeks, open-label phase 2 trial of the JAK inhibitor filgotinib in Behçet’s disease, idiopathic inflammatory myopathies and IgG4-related disease: DRIMID study protocol. BMJ Open. 2025;15(2):e089827. doi: 10.1136/bmjopen-2024-089827
  35. Interlandi E, Leccese P, Olivieri I, Latanza L. Adalimumab for treatment of severe Behçet’s uveitis: a retrospective long-term follow-up study. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S58–62.
  36. Khitri MY, Bartoli A, Maalouf G, Deroux A, Salvarani C, Emmi G, et al. Tocilizumab in Behçet Disease: A Multicenter Study of 30 Patients. J Rheumatol. 2023;50(7):916–23. doi: 10.3899/jrheum.221106
  37. Davatchi F. Diagnosis/classification criteria for Behcet’s disease. Pathol Res Int. 2012;2012:1–5.doi: https://doi.org/10.1155/2012/607921
  38. International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD), Davatchi F, Assaad-Khalil S, Calamia KT, Crook JE, Sadeghi-Abdollahi B, et al. The International Criteria for Behçet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. Acad Dermatol Venereol. 2014;28(3):338–47. doi: 10.1111/jdv.12107
  39. Alibaz-Oner F, Direskeneli H. Update on the Diagnosis of Behçet’s Disease. Diagnostics. 2022;13(1):41. doi: 10.3390/diagnostics13010041
  40. Wei Y, Li N, Zhao L, Yang C, Ma B, Li X, et al. MicroRNAs and autoimmune-mediated eye diseases. Front Cell Dev Biol. 2020;8:818. doi: 10.3389/fcell.2020.00818/full
  41. Emmi G, Bagni G, Lastraioli E, Di Patti F, Bettiol A, Fiorillo C, et al. A unique circulating miRNA profile highlights thrombo-inflammation in Behçet’s syndrome. Ann. Rheum. Dis. 2022;81(3):386–97. doi: 10.1136/annrheumdis-2021-220859
  42. Puccetti A, Pelosi A, Fiore PF, Patuzzo G, Lunardi C, Dolcino M. MicroRNA Expression Profiling in Behçet’s Disease. J. of Immunol Res. 2018;2018:1–18. doi: 10.1155/2018/2405150
  43. Hussein W, Ramadan H, Labib S, Hegazy G, Shaker O, Yusuf S, et al. Expression levels of lncRNA NEAT1, miRNA-21, and IL-17 in a group of Egyptian patients with Behçet’s disease: relation to disease manifestations and activity. Biol: Targets Ther. 2024;18:327–37. doi: 10.2147/BTT.S493191
  44. Hassouna SS, Tayel MY, ElKaffash DM, Abdelhady AM, Elsayed EH. MicroRNA155 expression in relation to BDCAF scored Behçet’s disease in an Egyptian patients’ sample. Open Rheumatol J. 2018;12(1):115–22. doi: 10.2174/1874312901812010115
  45. Lengvári L, Takács K, Lengyel A, Pálinkás A, Wouters CH, Koné-Paut I, et al. Mevalonate kinase deficiency: an updated clinical overview and revision of the SHARE recommendations. Front Immunol. 2024;15:1466844.
  46. Papa R, Doglio M, Lachmann HJ, Ozen S, Frenkel J, et al. A web-based collection of genotype-phenotype associations in hereditary recurrent fevers from the Eurofever registry. Orphanet J Rare Dis. 2017;12(1):167. doi: 10.1186/s13023-017-0720-3
  47. Houten SM, Van Woerden CS, Wijburg FA, Wanders RJA, Waterham HR. Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. Eur J Hum Genet. 2003;11(2):196–200. doi: 10.1038/sj.ejhg.5200933
  48. Feldmann J, Prieur AM, Quartier P, Berquin P, Certain S, Cortis E, et al. Chronic Infantile Neurological Cutaneous and Articular Syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet. 2002;71(1):198–203. doi: 10.1016/S0002-9297(07)60434-0
  49. Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001;29(3):301–5. doi: 10.1038/ng756
  50. Dodé C, Le Dû N, Cuisset L, Letourneur F, Berthelot JM, Vaudour G, et al. New mutations of CIAS1 that are responsible for Muckle-Wells Syndrome and Familial Cold Urticaria: a novel mutation underlies both syndromes. Am J Hum Genet. 2002;70(6):1498–506. doi: 10.1086/340786
  51. Aksentijevich I, Nowak M, Mallah M, Chae JJ, Watford WT, Hofmann SR, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): A new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis & Rheumat. 2002;46(12):3340–8. doi: 10.1002/art.10688
  52. Bertin J, DiStefano PS. The PYRIN domain: a novel motif found in apoptosis and inflammation proteins. Cell Death Differ. 2000;7(12):1273–4. doi: 10.1038/sj.cdd.4400774
  53. Centola M, Wood G, Frucht DM, Galon J, Aringer M, Farrell C, et al. The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators. Blood. 2000;95(10):3223–31.
  54. Lange-Sperandio B, Möhring K, Gutzler F, Mehls O. Variable expression of vasculitis in siblings with familial Mediterranean fever. Pediatr Nephrol. 2004;19(5):539–43. doi: 10.1007/s00467-004-1440-1
  55. Cattan D, Notarnicola C, Molinari N, Touitou I. Inflammatory bowel disease in non-Ashkenazi Jews with familial Mediterranean fever. The Lancet. 2000;355(9201):378–9. doi: 10.1016/S0140-6736(99)02134-0
  56. Koné Paut I, Dubuc M, Sportouch J, Minodier P, Garnier JM, Touitou I. Phenotype-genotype correlation in 91 patients with familial Mediterranean fever reveals a high frequency of cutaneomucous features. Rheumatology. 2000;39(11):1275–9. doi: 10.1093/rheumatology/39.11.1275
  57. Boursier G, Rittore C, Milhavet F, Cuisset L, Touitou I. Mevalonate Kinase-Associated Diseases: Hunting for Phenotype-Genotype Correlation. J Clin Med. 2021;10(8):1552. doi: 10.3390/jcm10081552
  58. Arslan Taş D, Erken E, Yildiz F, Dinkçi S, Sakalli H. Mevalonate kinase gene mutations and their clinical correlations in Behçet’s disease. Int J of Rheum Dis. 2014;17(4):435–43. doi: 10.1111/1756-185X.12243
  59. Koné-Paut I, Sanchez E, Le Quellec A, Manna R, Touitou I. Autoinflammatory gene mutations in Behçet’s disease. Ann Rheum Dis. 2007;66(6):832–4. doi: 10.1136/ard.2006.068841
  60. Yıldız F, Dinkçi S, Erken E. Mevalonate kinase gene polymorphisms in ankylosing spondylitis patients: A cross-sectional study. Arch Rheumatol. 2023;38(2):238–48. doi: 10.46497/ArchRheumatol.2023.9468
  61. Kuiper JJ, Prinz JC, Stratikos E, Kuśnierczyk P, Arakawa A, Springer S, et al. EULAR study group on ‘MHC-I-opathy’: identifying disease-overarching mechanisms across disciplines and borders. Ann Rheum Dis. 2023;82(7):887–96. doi: 10.1136/ard-2022-222852
  62. Guasp P, Alvarez-Navarro C, Gomez-Molina P, Martín-Esteban A, Marcilla M, Barnea E, et al. The peptidome of Behçet’s disease–associated HLA–B*51:01 includes two subpeptidomes differentially shaped by endoplasmic reticulum aminopeptidase 1. Arth & Rheum. 2016;68(2):505–15. doi: 10.1002/art.39430
  63. McGonagle D, Aydin SZ, Gül A, Mahr A, Direskeneli H. ‘MHC-I-opathy’—unified concept for spondyloarthritis and Behçet disease. Nat Rev Rheumatol. 2015;11(12):731–40. doi: 10.1038/nrrheum.2015.147
  64. Chang HK, Kim JU, Cheon KS, Chung HR, Lee KW, Lee IH. HLA-B51 and its allelic types in association with Behçet’s disease and recurrent aphthous stomatitis in Korea. Clin Exp Rheumatol. 2001;19(5 Suppl 24):S31–35.
  65. Burillo-Sanz S, Montes-Cano MA, García-Lozano JR, Olivas-Martínez I, Ortego-Centeno N, García-Hernández FJ, et al. Behçet’s disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes. Sci Rep. 2019;9(1):2777. doi: 10.1038/s41598-019-39113-5
DOI: https://doi.org/10.34763/jmotherandchild.20252901.d-25-00026 | Journal eISSN: 2719-535X | Journal ISSN: 2719-6488
Language: English
Page range: 1 - 10
Submitted on: Jul 15, 2025
|
Accepted on: Nov 3, 2025
|
Published on: Feb 1, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2026 Arbnora Batalli, Thomas Liehr, Gazmend Temaj, published by Institute of Mother and Child
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 30 (2026): Issue 1 (January 2026)