Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Behçet syndrome

Abstract

Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn’s disease suggest that multiple pathological pathways are involved in Behçet syndrome. These disease features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 as a genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bona fide disease, especially in non-endemic regions, suggests that other factors must also be operative in Behçet syndrome. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease, eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve. New treatment options and a better understanding of the underlying pathogenesis for various manifestations of this condition are required to further improve the management of the disease, which will improve patient quality of life.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Prevalence of Behçet syndrome.
Fig. 2: Schematic representation of skewed helper T cell responses observed in patients with Behçet syndrome.
Fig. 3: Mucocutaneous manifestations of Behçet syndrome.
Fig. 4: Ocular manifestations of Behçet syndrome.
Fig. 5: Pulmonary artery aneurysm in Behçet syndrome as seen on conventional radiography and CT.

References

  1. 1.

    Yazici, H., Seyahi, E., Hatemi, G. & Yazici, Y. Behçet syndrome: a contemporary view. Nat. Rev. Rheumatol. 14, 107–119 (2018). A comprehensive review of epidemiology, pathogenesis and treatment of Behçet syndrome.

    CAS  PubMed  Google Scholar 

  2. 2.

    Ortiz-Fernández, L. & Sawalha, A. H. Genetics of Behçet’s disease: functional genetic analysis and estimating disease heritability. Front. Med. 8, 625710 (2021).

    Google Scholar 

  3. 3.

    Kirino, Y. et al. Genome-wide association analysis identifies new susceptibility loci for Behçet’s disease and epistasis between HLA-B*51 and ERAP1. Nat. Genet. 45, 202–207 (2013). This paper provides information on potential pathways involved in the pathogenesis of Behçet syndrome.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Sota, J. et al. Behçet’s syndrome in Italy: a detailed retrospective analysis of 396 cases seen in 3 tertiary referral clinics. Intern. Emerg. Med. 15, 1031–1039 (2020).

    PubMed  Google Scholar 

  5. 5.

    Zou, J. et al. Cluster analysis of phenotypes of patients with Behçet’s syndrome: a large cohort study from a referral center in China. Arthritis Res. Ther. 23, 45 (2021).

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Soejima, Y. et al. Changes in the proportion of clinical clusters contribute to the phenotypic evolution of Behçet’s disease in Japan. Arthritis Res. Ther. 23, 49 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Yazici, H., Ugurlu, S. & Seyahi, E. Behçet syndrome: is it one condition? Clin. Rev. Allergy Immunol. 43, 275–280 (2012).

    CAS  PubMed  Google Scholar 

  8. 8.

    Seyahi, E. et al. Increased vein wall thickness in Behçet disease. J. Vasc. Surg. Venous Lymphat. Disord. 7, 677–684 (2019). This paper describes how blood vessels are involved in Behçet syndrome.

    PubMed  Google Scholar 

  9. 9.

    Alibaz-Oner, F. et al. Venous vessel wall thickness in lower extremity is increased in male patients with Behçet’s disease. Clin. Rheumatol. 38, 1447–1451 (2019).

    PubMed  Google Scholar 

  10. 10.

    Hatemi, G. et al. Apremilast for Behçet’s syndrome — a phase 2, placebo-controlled study. N. Engl. J. Med. 372, 1510–1518 (2015).

    CAS  PubMed  Google Scholar 

  11. 11.

    Verity, D. H., Marr, J. E., Ohno, S., Wallace, G. R. & Stanford, M. R. Behçet’s disease, the Silk Road and HLA-B51: historical and geographical perspectives. Tissue Antigens 54, 213–220 (1999).

    CAS  PubMed  Google Scholar 

  12. 12.

    Ndiaye, M. et al. Behçet’s disease in black skin. A retrospective study of 50 cases in Dakar. J. Dermatol. Case Rep. 9, 98–102 (2015).

    PubMed  PubMed Central  Google Scholar 

  13. 13.

    Mohammad, A., Mandl, T., Sturfelt, G. & Segelmark, M. Incidence, prevalence and clinical characteristics of Behçet’s disease in southern Sweden. Rheumatology 52, 304–310 (2012).

    PubMed  Google Scholar 

  14. 14.

    Papoutsis, N. G. et al. Prevalence of Adamantiades-Behçet’s disease in Germany and the municipality of Berlin: results of a nationwide survey. Clin. Exp. Rheumatol. 24 (Suppl. 42), S125 (2006).

    CAS  PubMed  Google Scholar 

  15. 15.

    Kappen, J. H. et al. Behçet’s disease, hospital-based prevalence and manifestations in the Rotterdam area. Neth. J. Med. 73, 471–477 (2015).

    CAS  PubMed  Google Scholar 

  16. 16.

    Calamia, K. T. et al. Epidemiology and clinical characteristics of Behçet’s disease in the US: a population-based study. Arthritis Rheum. 61, 600–604 (2009).

    PubMed  PubMed Central  Google Scholar 

  17. 17.

    Yazici, Y., Filopoulos, M. T., Schimmel, E., McCraken, A. & Swearingen, C. Clinical characteristics, treatment and ethnic/racial differences in the manifestations of 518 Behçet’s syndrome patients in the United States [abstract]. Arthritis Rheum. 62 (Suppl.), 1284 (2010).

    Google Scholar 

  18. 18.

    Salvarani, C. et al. Epidemiology and clinical course of Behçet’s disease in the Reggio Emilia area of Northern Italy: a seventeen-year population-based study. Arthritis Rheum. 57, 171–178 (2007).

    PubMed  Google Scholar 

  19. 19.

    Madanat, W. Y. et al. The prevalence of Behçet’s disease in the north of Jordan: a hospital-based epidemiological survey. Clin. Exp. Rheumatol. 35 (Suppl. 108), 51–54 (2017).

    PubMed  Google Scholar 

  20. 20.

    Sakane, T., Takeno, M., Suzuki, N. & Inaba, G. Behçet’s disease. N. Engl. J. Med. 341, 1284–1291 (1999).

    CAS  PubMed  Google Scholar 

  21. 21.

    Greco, A. et al. Behçet’s disease: new insights into pathophysiology, clinical features and treatment options. Autoimmun. Rev. 17, 567–575 (2018).

    CAS  PubMed  Google Scholar 

  22. 22.

    Pineton de Chambrun, M., Wechsler, B., Geri, G., Cacoub, P. & Saadoun, D. New insights into the pathogenesis of Behçet’s disease. Autoimmun. Rev. 11, 687–698 (2012).

    CAS  PubMed  Google Scholar 

  23. 23.

    Ohno, S. et al. HLA-5 and Behçet’s disease. Lancet 2, 1383–1384 (1973).

    CAS  PubMed  Google Scholar 

  24. 24.

    McGonagle, D., Aydin, S. Z., Gül, A., Mahr, A. & Direskeneli, H. ‘MHC-Iopathy’-unified concept for spondyloarthritis and Behçet disease. Nat. Rev. Rheumatol. 11, 731–740 (2015). A hypothesis-generating paper on the potential role of MHC in the pathogenesis of Behçet syndrome.

    CAS  PubMed  Google Scholar 

  25. 25.

    Giza, M., Koftori, D., Chen, L. & Bowness, P. Is Behçet’s disease a ‘class1-opathy’? The role of HLA-B*51 in the pathogenesis of Behçet’s disease. Clin. Exp. Immunol. 191, 11–18 (2018).

    CAS  PubMed  Google Scholar 

  26. 26.

    Moll, J. M., Haslock, I., Macrae, I. F. & Wright, V. Associations between ankylosing spondylitis, psoriatic arthritis, Reiter’s disease, the intestinal arthropathies, and Behçet’s syndrome. Medicine 53, 343–364 (1974).

    CAS  PubMed  Google Scholar 

  27. 27.

    Mizuki, N. et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci. Nat. Genet. 42, 703–706 (2010).

    CAS  PubMed  Google Scholar 

  28. 28.

    Remmers, E. F. et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23RIL12RB2 regions associated with Behçet’s disease. Nat. Genet. 42, 698–702 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Mizuki, Y. et al. The influence of HLA-B51 on clinical manifestations among Japanese patients with Behçet’s disease: a nationwide survey. Mod. Rheumatol. 30, 708–714 (2020).

    CAS  PubMed  Google Scholar 

  30. 30.

    Hou, S. et al. Genetic variations of IL17F and IL23A show associations with Behçet’s disease and Vogt-Koyanagi-Harada syndrome. Ophthalmology 122, 518–523 (2015).

    PubMed  Google Scholar 

  31. 31.

    Hughes, T. et al. Epigenome-wide scan identifies a treatment-responsive pattern of altered DNA methylation among cytoskeletal remodeling genes in monocytes and CD4+ T cells from patients with Behçet’s disease. Arthritis Rheumatol. 66, 1648–1658 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Imamura, Y. et al. Involvement of Th1 cells and heat shock protein 60 in the pathogenesis of intestinal Behçet’s disease. Clin. Exp. Immunol. 139, 371–378 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Direskeneli, H. Innate and adaptive responses to heat shock proteins in Behçet’s disease. Genet. Res. Int. 2013, 249157 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Frassanito, M. A., Dammacco, R., Cafforio, P. & Dammacco, F. Th1 polarization of the immune response in Behçet’s disease: a putative pathogenetic role of interleukin-12. Arthritis Rheum. 42, 1967–1974 (1999).

    CAS  PubMed  Google Scholar 

  35. 35.

    Alipour, S. et al. Hypermethylation of IL-10 gene is responsible for its low mRNA expression in Behçet’s disease. J. Cell. Biochem. 119, 6614–6622 (2018).

    CAS  PubMed  Google Scholar 

  36. 36.

    Nakano, H. et al. GWAS-identified CCR1 and 14 IL10 loci contribute to M1 macrophage-predominant inflammation in Behçet’s disease. Arthritis Res. Ther. 20, 124 (2018).

    PubMed  PubMed Central  Google Scholar 

  37. 37.

    Perazzio, S. F., Andrade, L. E. C. & de Souza, A. W. S. Understanding Behçet’s disease in the context of innate immunity activation. Front. Immunol. 11, 586558 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Shimizu, J. et al. Excessive CD4+ T cells co-expressing interleukin-17 and interferon-ɣ in patients with Behçet’s disease. Clin. Exp. Immunol. 168, 68–74 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Shimizu, J. et al. Skewed TGFβ/Smad signalling pathway in T cells in patients with Behçet’s disease. Clin. Exp. Rheumatol. 30 (3 Suppl. 72), 35–39 (2012).

    Google Scholar 

  40. 40.

    Shimizu, J., Kaneko, F. & Suzuki, N. Skewed helper T-cell responses to IL-12 family cytokines produced by antigen-presenting cells and the genetic background in Behçet’s disease. Genet. Res. Int. 2013, 363859 (2013). This paper discusses the important part that T cells play in the pathogenesis of Behçet syndrome.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Shimizu, J. et al. Possible association of proinflammatory cytokines including IL1β and TNFα with enhanced Th17 cell differentiation in patients with Behçet’s disease. Clin. Rheumatol. 35, 1857–1863 (2016).

    PubMed  Google Scholar 

  42. 42.

    Ahmadi, M. et al. Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behçet’s disease. J. Cell. Physiol. 234, 3985–3994 (2019).

    CAS  PubMed  Google Scholar 

  43. 43.

    Salmaninejad, A. et al. Behçet’s disease: an immunogenetic perspective. J. Cell. Physiol. 234, 8055–8074 (2019).

    CAS  PubMed  Google Scholar 

  44. 44.

    Hamzaoui, K., Hamzaoui, A. & Houman, H. CD4+CD25+ regulatory T cells in patients with Behçet’s disease. Clin. Exp. Rheumatol. 24 (5 Suppl. 42), 71–78 (2006).

    Google Scholar 

  45. 45.

    Koh, A., De Vadder, F., Kovatcheva-Datchary, P. & Bäckhed, F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165, 1332–1345 (2016).

    CAS  PubMed  Google Scholar 

  46. 46.

    Shimizu, J. et al. Bifidobacteria abundance-featured gut microbiota compositional change in patients with Behçet’s disease. PLoS ONE 11, e0153746 (2016).

    PubMed  PubMed Central  Google Scholar 

  47. 47.

    Shimizu, J. et al. Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behçet’s disease. Clin. Rheumatol. 38, 1437–1445 (2019).

    PubMed  Google Scholar 

  48. 48.

    Consolandi, C. et al. Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun. Rev. 14, 269–276 (2015).

    PubMed  Google Scholar 

  49. 49.

    Zi, Y. et al. A metagenomic study of the gut microbiome in Behçet’s disease. Microbiome 6, 135 (2018).

    Google Scholar 

  50. 50.

    Ambrose, N., Pierce, I. T., Gatehouse, P. D., Haskard, D. O. & Firmin, D. N. Magnetic resonance imaging of vein wall thickness in patients with Behçet’s syndrome. Clin. Exp. Rheumatol. 32 (4 Suppl. 84), 99–102 (2014). This paper reviews the importance and utility of a non-invasive imaging method such as MRI in the management of vascular involvement in Behçet syndrome.

    Google Scholar 

  51. 51.

    Ahn, J. K., Lee, Y. S., Jeon, C. H., Koh, E. M. & Cha, H. S. Treatment of venous thrombosis associated with Behçet’s disease: immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation. Clin. Rheumatol. 27, 201–205 (2008).

    PubMed  Google Scholar 

  52. 52.

    Sertoglu, E. et al. The relationship of serum VEGF and sVEGFR-1 levels with vascular involvement in patients with Behçet’s disease. Scand. J. Clin. Lab. Invest. 78, 443–449 (2018).

    CAS  PubMed  Google Scholar 

  53. 53.

    Khan, E. et al. A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s syndrome. Sci. Rep. 6, 38104 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Emmi, G. et al. Stem-cell-derived circulating progenitors dysfunction in Behçet’s syndrome patients correlates with oxidative stress. Front. Immunol. 10, 2877 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Yasar Bilge, N. S., Akay, O. M., Gunduz, E., Bilgin, M. & Kasifoglu, T. Circulating endothelial cells in Behçet’s disease: is there a relationship with vascular involvement? Clin. Exp. Rheumatol. 37 (Suppl. 121), 105–110 (2019).

    PubMed  Google Scholar 

  56. 56.

    Demirkesen C., Oz B. & Göksel S. in Behçet Syndrome (eds Yazici, Y., Hatemi, G., Seyahi, E. & Yazici, H.) 171–189 (Springer, 2020).

  57. 57.

    Ureten, K. et al. Neutrophil CD64 expression in Behçet’s disease. J. Rheumatol. 32, 849–852 (2005).

    CAS  PubMed  Google Scholar 

  58. 58.

    Canete, J. D. et al. Distinct synovial immunopathology in Behçet disease and psoriatic arthritis. Arthritis Res. Ther. 11, R17 (2009).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Hayasaki, N. et al. Neutrophilic phlebitis is characteristic of intestinal Behçet’s disease and simple ulcer syndrome. Histopathology 45, 377–383 (2004).

    CAS  PubMed  Google Scholar 

  60. 60.

    Melikoglu, M. et al. Characterization of the divergent wound-healing responses occurring in the pathergy reaction and normal healthy volunteers. J. Immunol. 177, 6415–6421 (2006).

    CAS  PubMed  Google Scholar 

  61. 61.

    Ergun, T., Gürbüz, O., Harvell, J., Jorizzo, J. & White, W. The histopathology of pathergy: a chronologic study of skin hyperreactivity in Behçet’s disease. Int. J. Dermatol. 37, 929–933 (1998).

    CAS  PubMed  Google Scholar 

  62. 62.

    Kobayashi, M. et al. Neutrophil and endothelial cell activation in the vasa vasorum in vasculo-Behçet disease. Histopathology 36, 362–371 (2000).

    CAS  PubMed  Google Scholar 

  63. 63.

    Emmi, G. et al. Behçet’s syndrome as a model of thrombo-inflammation: the role of neutrophils. Front. Immunol. 10, 1085 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Le Joncour, A. et al. Critical role of neutrophil extracellular traps (NETs) in patients with Behçet’s disease. Ann. Rheum. Dis. 78, 1274–1282 (2019).

    PubMed  Google Scholar 

  65. 65.

    International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 335, 1078–1080 (1990).

    Google Scholar 

  66. 66.

    Davatchi, F. 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. J. Eur. Acad. Dermatol. Venereol. 28, 338–347 (2013).

    Google Scholar 

  67. 67.

    Blake, T. et al. Birmingham Behçet’s service: classification of disease and application of the 2014 International Criteria for Behçet’s Disease (ICBD) to a UK cohort. BMC Musculoskelet. Disord. 18, 101 (2017).

    PubMed  PubMed Central  Google Scholar 

  68. 68.

    Behçet’s Disease Research Committee of Japan. Behçet’s disease guide to diagnosis of Behçet’s disease. Jpn. J. Ophthalmol. 18, 291–294 (1974).

    Google Scholar 

  69. 69.

    Suzuki Kurokawa, M. & Suzuki, N. Behcet’s disease. Clin. Exp. Med. 4, 10–20 (2004).

    CAS  PubMed  Google Scholar 

  70. 70.

    Kutlubay, Z. et al. Papulopustular lesions according to age, sex and localization in Behçet’s syndrome patients compared with healthy and diseased controls [abstract FRI0351]. Ann. Rheum. Dis. 76 (Suppl. 2), 619 (2017).

    Google Scholar 

  71. 71.

    Main, D. M. & Chamberlain, M. A. Clinical differentiation of oral ulceration in Behçet’s disease. Br. J. Rheumatol. 31, 767–770 (1992).

    CAS  PubMed  Google Scholar 

  72. 72.

    Oh, S. H., Han, E. C., Lee, J. H. & Bang, D. Comparison of the clinical features of recurrent aphthous stomatitis and Behçet’s disease. Clin. Exp. Dermatol. 34, e208–e212 (2009).

    CAS  PubMed  Google Scholar 

  73. 73.

    Hatemi G. et al. Pentoxifylline gel for oral ulcers in patients with Behçet’s syndrome [abstract 1720]. Presented at the 2019 ACR/ARP Annual Meeting. https://acrabstracts.org/abstract/pentoxifylline-gel-for-oral-ulcers-in-patients-with-behcets-syndrome/ (2019).

  74. 74.

    Mat, M. C., Goksugur, N., Engin, B., Yurdakul, S. & Yazici, H. The frequency of scarring after genital ulcers in Behçet’s syndrome: a prospective study. Int. J. Dermatol. 45, 554–556 (2006).

    PubMed  Google Scholar 

  75. 75.

    Kanakis, M. A., Vaiopoulos, A. G., Vaiopoulos, G. A. & Kaklamanis, P. G. Epididymo-orchitis in Behçet’s disease: a review of the wide spectrum of the disease. Acta Med. Iran. 55, 482–485 (2017).

    PubMed  Google Scholar 

  76. 76.

    Demirkesen, C. et al. Clinicopathologic evaluation of nodular cutaneous lesions of Behçet syndrome. Am. J. Clin. Pathol. 116, 341–346 (2001).

    CAS  PubMed  Google Scholar 

  77. 77.

    Tunc, R., Keyman, E., Melikoglu, M., Fresko, I. & Yazici, H. Target organ associations in Turkish patients with Behçet’s disease: a cross sectional study by exploratory factor analysis. J. Rheumatol. 29, 2393–2396 (2002).

    PubMed  Google Scholar 

  78. 78.

    Leccese, P. et al. Management of skin, mucosa and joint involvement of Behçet’s syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet’s syndrome. Semin. Arthritis Rheum. 48, 752–762 (2019).

    PubMed  Google Scholar 

  79. 79.

    Fatemi, A. et al. Prospective study of articular manifestations in Behçet’s disease: five-year report. Int. J. Rheum. Dis. 20, 97–102 (2017).

    CAS  PubMed  Google Scholar 

  80. 80.

    Diri, E. et al. Papulopustular skin lesions are seen more frequently in patients with Behçet’s syndrome who have arthritis: a controlled and masked study. Ann. Rheum. Dis. 60, 1074–1076 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Hatemi, G. et al. The pustular skin lesions in Behçet’s syndrome are not sterile. Ann. Rheum. Dis. 63, 1450–1452 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Hatemi, G., Fresko, I., Tascilar, K. & Yazici, H. Increased enthesopathy among Behçet’s syndrome patients with acne and arthritis: an ultrasonography study. Arthritis Rheum. 58, 1539–1545 (2008).

    PubMed  Google Scholar 

  83. 83.

    Hatemi, G. et al. Reply to letter by Priori et al commenting on whether Behçet’s syndrome patients with acne and arthritis comprise a true subset. Arthritis Rheum. 62, 305–306 (2010).

    PubMed  Google Scholar 

  84. 84.

    Buyuktas, D. et al. Fatigue is correlated with disease activity but not with the type of organ involvement in Behçet’s syndrome: a comparative clinical survey. Clin. Exp. Rheumatol. 33 (6 Suppl. 94), 107–112 (2105).

    Google Scholar 

  85. 85.

    Kone-Paut, I. et al. French recommendations for the management of Behçet’s disease. Orphanet. J. Rare Dis. 16 (Suppl. 1), 352 (2021).

    PubMed  PubMed Central  Google Scholar 

  86. 86.

    Tugal-Tutkun, I., Onal, S., Altan-Yaycioglu, R., Huseyin Altunbas, H. & Urgancioglu, M. Uveitis in Behçet disease: an analysis of 880 patients. Am. J. Ophthalmol. 138, 373–380 (2004).

    PubMed  Google Scholar 

  87. 87.

    Tugal-Tutkun, I. et al. An algorithm for the diagnosis of Behçet disease uveitis in adults. Ocul. Immunol. Inflamm. https://doi.org/10.1080/09273948.2020.1736310 (2020).

  88. 88.

    Onal, S. et al. Quantitative analysis of structural alterations in the choroid of patients with active Behçet uveitis. Retina 38, 828–840 (2018).

    PubMed  Google Scholar 

  89. 89.

    Khairallah, M. et al. Optical coherence tomography angiography in patients with Behçet uveitis. Retina 37, 1678–1691 (2017).

    PubMed  Google Scholar 

  90. 90.

    Tugal-Tutkun, I., Gupta, V. & Cunningham, E. T. Differential diagnosis of Behçet uveitis. Ocul. Immunol. Inflamm. 21, 337–350 (2013).

    PubMed  Google Scholar 

  91. 91.

    Tascilar, K. et al. Vascular involvement in Behçet’s syndrome: a retrospective analysis of associations and the time course. Rheumatology 53, 2018–2022 (2014).

    CAS  PubMed  Google Scholar 

  92. 92.

    Seyahi, E. et al. Pulmonary artery involvement and associated lung disease in Behçet disease: a series of 47 patients. Medicine 91, 35–48 (2012).

    PubMed  Google Scholar 

  93. 93.

    Ozguler, Y. et al. Clinical course of acute deep vein thrombosis of the legs in Behçet’s syndrome. Rheumatology 59, 799–806 (2020).

    PubMed  Google Scholar 

  94. 94.

    Uygunoğlu, U. & Siva, A. Nervous system involvement in Behçet’s syndrome. Curr. Opin. Rheumatol. 31, 32–39 (2019).

    PubMed  Google Scholar 

  95. 95.

    Uygunoğlu, U. & Siva, A. Behçet’s syndrome and nervous system involvement. Curr. Neurol. Neurosci. Rep. 18, 35 (2018).

    PubMed  Google Scholar 

  96. 96.

    Alis, D. et al. Apparent diffusion coefficient characteristics of parenchymal neuro-Behçet’s disease. Int. J. Rheum. Dis. 22, 1452–1458 (2019).

    PubMed  Google Scholar 

  97. 97.

    Akman-Demir, G., Serdaroglu, P. & Tasçi, B. Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. The Neuro-Behçet Study Group. Brain 122, 2171–2182 (1999).

    PubMed  Google Scholar 

  98. 98.

    Kasahara, Y. et al. Intestinal involvement in Behçet’s disease: review of 136 surgical cases in the Japanese literature. Dis. Colon. Rectum 24, 103–106 (1981).

    CAS  PubMed  Google Scholar 

  99. 99.

    Jung, Y. S. et al. Clinical course of intestinal Behçet’s disease during the first five years. Dig. Dis. Sci. 58, 496–503 (2013).

    PubMed  Google Scholar 

  100. 100.

    Jung, Y. S. et al. Prognostic factors and long-term clinical outcomes for surgical patients with intestinal Behçet’s disease. Inflamm. Bowel Dis. 17, 1594–1602 (2011).

    PubMed  Google Scholar 

  101. 101.

    Lee, C. R. et al. Colonoscopic findings in intestinal Behçet’s disease. Inflamm. Bowel Dis. 7, 243–249 (2001).

    CAS  PubMed  Google Scholar 

  102. 102.

    Cheon, J. H. & Kim, W. H. An update on the diagnosis, treatment, and prognosis of intestinal Behçet’s disease. Curr. Opin. Rheumatol. 27, 24–31 (2015).

    CAS  PubMed  Google Scholar 

  103. 103.

    Bayraktar, Y., Ozaslan, E. & Van Thiel, D. H. Gastrointestinal manifestations of Behçet’s disease. J. Clin. Gastroenterol. 30, 144–154 (2000).

    CAS  PubMed  Google Scholar 

  104. 104.

    Kural-Seyahi, E. et al. The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine 82, 60–76 (2003). The largest and longest followed cohort of patients with Behçet syndrome including findings related to the natural history of this condition.

    PubMed  Google Scholar 

  105. 105.

    Hatemi, G. et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome. Ann. Rheum. Dis. 77, 808–818 (2018). The latest treatment guidelines for Behçet syndrome.

    PubMed  Google Scholar 

  106. 106.

    Hatemi, G. et al. Trial of apremilast for oral ulcers in Behçet’s syndrome. N. Engl. J. Med. 381, 1918–1928 (2019). This paper presents data on the first approved treatment for oral ulcers in Behçet syndrome in the USA.

    CAS  PubMed  Google Scholar 

  107. 107.

    Mirouse, A. et al. Long-term outcome of ustekinumab therapy for Behçet’s disease. Arthritis Rheumatol. 71, 1727–1732 (2019).

    CAS  PubMed  Google Scholar 

  108. 108.

    Fagni, F. et al. Long-term effectiveness and safety of secukinumab for treatment of refractory mucosal and articular Behçet’s phenotype: a multicentre study. Ann. Rheum. Dis. 79, 1098–1104 (2020).

    CAS  PubMed  Google Scholar 

  109. 109.

    Lopalco, G. et al. Certolizumab Pegol treatment in Behçet’s disease with different organ involvement: a multicenter retrospective observational study. Mod. Rheumatol. 27, 1031–1035 (2017).

    CAS  PubMed  Google Scholar 

  110. 110.

    Vitale, A. et al. Long-term efficacy and safety of golimumab in the treatment of multirefractory Behçet’s disease. Clin. Rheumatol. 36, 2063–2069 (2017).

    PubMed  Google Scholar 

  111. 111.

    Senusi, A. et al. New mouthwash: an efficacious intervention for oral ulceration associated with Behçet’s disease. Br. J. Oral. Maxillofac. Surg. 58, 1034–1039 (2020).

    PubMed  Google Scholar 

  112. 112.

    Ozguler, Y. et al. Management of major organ involvement of Behçet’s syndrome: a systematic review for update of the EULAR recommendations. Rheumatology 57, 2200–2212 (2018).

    PubMed  Google Scholar 

  113. 113.

    Emmi, G. et al. Adalimumab-based treatment versus disease-modifying antirheumatic drugs for venous thrombosis in Behçet’s syndrome: a retrospective study of seventy patients with vascular involvement. Arthritis Rheumatol. 70, 1500–1507 (2018).

    CAS  PubMed  Google Scholar 

  114. 114.

    Hamuryudan, V., Oz, B., Tüzün, H. & Yazici, H. The menacing pulmonary artery aneurysms of Behçet’s syndrome. Clin. Exp. Rheumatol. 22 (4 Suppl. 34), 1–3 (2004).

    Google Scholar 

  115. 115.

    Liu, X., Yang, P., Wang, C., Li, F. & Kijlstra, A. IFN-α blocks IL-17 production by peripheral blood mononuclear cells in Behçet’s disease. Rheumatology 50, 293–298 (2011).

    CAS  PubMed  Google Scholar 

  116. 116.

    Hamuryudan, V. et al. Pulmonary artery involvement in Behçet’s syndrome: effects of anti-TNF treatment. Semin. Arthritis Rheum. 45, 369–373 (2015).

    CAS  PubMed  Google Scholar 

  117. 117.

    Desbois, A. C. et al. Efficacy of anti-TNF alpha in severe and refractory major vessel involvement of Behçet’s disease: a multicenter observational study of 18 patients. Clin. Immunol. 197, 54–59 (2018).

    CAS  PubMed  Google Scholar 

  118. 118.

    Aksoy, A. et al. Efficacy of TNFα inhibitors for refractory vascular Behçet’s disease: a multicenter observational study of 27 patients and a review of the literature. Int. J. Rheum. Dis. 23, 256–261 (2020).

    PubMed  Google Scholar 

  119. 119.

    Noel, N. et al. Long-term outcome of neuro-Behçet’s disease. Arthritis Rheumatol. 66, 1306–1314 (2014).

    PubMed  Google Scholar 

  120. 120.

    Zeydan, B. et al. Infliximab is a plausible alternative for neurologic complications of Behçet disease. Neurol. Neuroimmunol. Neuroinflamm. 3, e258 (2016).

    PubMed  PubMed Central  Google Scholar 

  121. 121.

    Atienza-Mateo B. et al. Tocilizumab in Behçet’s disease with refractory ocular and/or neurological involvement: response according to different clinical phenotypes. Clin. Exp. Rheumatol. (in the press).

  122. 122.

    Zierhut, M., Abu El-Asrar, A. M., Bodaghi, B. & Tugal-Tutkun, I. Therapy of ocular Behçet disease. Ocul. Immunol. Inflamm. 22, 64–76 (2014).

    CAS  PubMed  Google Scholar 

  123. 123.

    Kotter, I., Hamuryudan, V., Ozturk, Z. E. & Yazici, H. Interferon therapy in rheumatic diseases: state-of-the-art 2010. Curr. Opin. Rheumatol. 22, 278–283 (2010).

    PubMed  Google Scholar 

  124. 124.

    Sfikakis, P. P. et al. Anti-TNF therapy in the management of Behçet’s disease–review and basis for recommendations. Rheumatology 46, 736–741 (2007).

    CAS  PubMed  Google Scholar 

  125. 125.

    Coskun, E. et al. Intravitreal dexamethasone implant for treatment of refractory Behçet posterior uveitis: one-year follow-up results. Ocul. Immunol. Inflamm. 23, 437–443 (2015).

    CAS  PubMed  Google Scholar 

  126. 126.

    Reddy, A. K., Burkholder, B. M., Khan, I. R. & Thorne, J. E. Iluvien implantation for uveitis and uveitic macular edema. Ocul. Immunol. Inflamm. 26, 315–316 (2018).

    PubMed  Google Scholar 

  127. 127.

    Hisamatsu, T. et al. The 2nd edition of consensus statements for the diagnosis and management of intestinal Behçet’s disease: indication of anti-TNFα monoclonal antibodies. J. Gastroenterol. 49, 156–162 (2014).

    CAS  PubMed  Google Scholar 

  128. 128.

    Watanabe, K. et al. Evidence-based diagnosis and clinical practice guidelines for intestinal Behçet’s disease 2020 edited by Intractable Diseases, the Health and Labour Sciences Research Grants. J. Gastroenterol. 55, 679–700 (2020).

    PubMed  PubMed Central  Google Scholar 

  129. 129.

    Vaiopoulos, A. G., Sfikakis, P. P., Kanakis, M. A., Vaiopoulos, G. & Kaklamanis, P. G. Gastrointestinal manifestations of Behçet’s disease: advances in evaluation and management. Clin. Exp. Rheumatol. 32, S140–S148 (2014).

    PubMed  Google Scholar 

  130. 130.

    Tanida, S. et al. Adalimumab for the treatment of Japanese patients with intestinal Behçet’s disease. Clin. Gastroenterol. Hepatol. 13, 940–948 (2015).

    CAS  PubMed  Google Scholar 

  131. 131.

    Suzuki, Y. et al. Long-term safety and effectiveness of adalimumab in 462 patients with intestinal Behçet’s disease: results from a large real-world observational study. Intest. Res. 19, 301–312 (2021).

    PubMed  Google Scholar 

  132. 132.

    Lee, H. J. & Cheon, J. H. Optimal diagnosis and disease activity monitoring of intestinal Behçet’s disease. Intest. Res. 15, 311–317 (2017). A summary of the diagnostic approach to intestinal involvement in Behçet syndrome.

    PubMed  PubMed Central  Google Scholar 

  133. 133.

    Senusi, A. A., Ola, D., Mather, J., Mather, J. & Fortune, F. Behçet’s syndrome and health-related quality of life: influence of symptoms, lifestyle and employment status. Clin. Exp. Rheumatol. 35 (Suppl. 108), 43–50 (2017).

    PubMed  Google Scholar 

  134. 134.

    Fabiani, C. et al. Quality of life impairment in Behçet’s disease and relationship with disease activity: a prospective study. Intern. Emerg. Med. 12, 947–955 (2017).

    PubMed  Google Scholar 

  135. 135.

    Khabbazi, A., Ebrahimzadeh Attari, V., Asghari Jafarabadi, M. & Malek Mahdavi, A. Quality of life in patients with Behçet disease and its relation with clinical symptoms and disease activity. Rheumatol. Clin. 17, 1–6 (2021).

    Google Scholar 

  136. 136.

    Can Sandikci, S., Colak, S., Omma, A. & Enecik, M. E. An evaluation of depression, anxiety and fatigue in patients with Behçet’s disease. Int. J. Rheum. Dis. 22, 974–979 (2019).

    PubMed  Google Scholar 

  137. 137.

    Saygin, C., Uzunaslan, D., Hatemi, G. & Hamuryudan, V. Suicidal ideation among patients with Behçet’s syndrome. Clin. Exp. Rheumatol. 33 (6 Suppl. 94), 30–35 (2015).

    Google Scholar 

  138. 138.

    Senusi, A., Seoudi, N., Bergmeier, L. A. & Fortune, F. Genital ulcer severity score and genital health quality of life in Behçet’s disease. Orphanet. J. Rare Dis. 10, 117 (2015).

    PubMed  PubMed Central  Google Scholar 

  139. 139.

    Talarico, R. et al. Sexual dysfunction in Behçet’s syndrome. Rheumatol. Int. 40, 9–15 (2020).

    CAS  PubMed  Google Scholar 

  140. 140.

    Yetkin, D. O., Celik, O., Hatemi, G. & Kadioglu, P. Sexual dysfunction and depression in premenopausal women with mucocutaneous Behçet’s disease. Int. J. Rheum. Dis. 16, 463–468 (2013).

    CAS  PubMed  Google Scholar 

  141. 141.

    Sut, N., Seyahi, E., Yurdakul, S., Senocak, M. & Yazici, H. A cost analysis of Behçet’s syndrome in Turkey. Rheumatology 46, 678–682 (2007).

    CAS  PubMed  Google Scholar 

  142. 142.

    Mumcu, G. et al. The assessment of work productivity and activity impairment in Behçet’s disease. Turk. J. Med. Sci. 47, 535–541 (2017).

    PubMed  Google Scholar 

  143. 143.

    Mehta, P., Ambrose, N. & Haskard, D. O. Work-related disability in Behçet’s syndrome: a British case series. Clin. Exp. Rheumatol. 32 (4 Suppl. 84), 173–174 (2014).

    Google Scholar 

  144. 144.

    Hatemi, G. et al. The OMERACT core set of domains for outcome measures in Behçet syndrome. Arthritis Care Res. https://doi.org/10.1002/acr.24511 (2020).

    Article  Google Scholar 

  145. 145.

    Hatemi, G. et al. Outcome measures used in clinical trials for Behçet syndrome: a systematic review. J. Rheumatol. 41, 599–612 (2014).

    PubMed  PubMed Central  Google Scholar 

  146. 146.

    Gilworth, G. et al. Development of the BD-QoL: a quality of life measure specific to Behçet’s disease. J. Rheumatol. 31, 931–937 (2004).

    PubMed  Google Scholar 

  147. 147.

    Ozguler, Y. et al. Patients’ experiences with Behçet’s syndrome: structured interviews among patients with different types of organ involvement. Clin. Exp. Rheumatol. 37 (Suppl. 121), 28–34 (2019).

    PubMed  Google Scholar 

  148. 148.

    Lawton, G., Bhakta, B. B., Chamberlain, M. A. & Tennant, A. The Behçet’s disease activity index. Rheumatology 43, 73–78 (2004).

    CAS  PubMed  Google Scholar 

  149. 149.

    Forbess, C., Swearingen, C. & Yazici, Y. Behçet’s Syndrome Activity Score (BSAS): a new disease activity assessment tool, composed of patient-derived measures only, is strongly correlated with the Behçet’s Disease Current Activity Form (BDCAF). Ann. Rheum. Dis. 67, 360 (2008).

    Google Scholar 

  150. 150.

    Mumcu, G., Inanc, N., Taze, A., Ergun, T. & Direskeneli, H. A new mucocutaneous activity index for Behçet’s disease. Clin. Exp. Rheumatol. 32 (4 Suppl. 84), 80–86 (2014).

    Google Scholar 

  151. 151.

    Senusi, A., Higgins, S. & Fortune, F. The influence of oral health and psycho-social well-being on clinical outcomes in Behçet’s disease. Rheumatol. Int. 38, 1873–1883 (2018).

    PubMed  PubMed Central  Google Scholar 

  152. 152.

    Cheon, J. H. et al. Development, validation, and responsiveness of a novel disease activity index for intestinal Behçet’s disease. Inflamm. Bowel. Dis. 17, 605–613 (2011).

    PubMed  Google Scholar 

  153. 153.

    Karaca, M., Hatemi, G., Sut, N. & Yazici, H. The papulopustular lesion/arthritis cluster of Behçet’s syndrome also clusters in families. Rheumatology 51, 1053–1060 (2012).

    PubMed  Google Scholar 

  154. 154.

    Kim, S. W. et al. Identification of genetic susceptibility loci for intestinal Behçet’s disease. Sci. Rep. 7, 39850 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. 155.

    Kirino, Y. et al. Continuous evolution of clinical phenotype in 578 Japanese patients with Behçet’s disease: a retrospective observational study. Arthritis Res. Ther. 18, 217 (2016).

    PubMed  PubMed Central  Google Scholar 

  156. 156.

    Yazici, Y., Hatemi, G., Seyahi, E. & Yazici, H. (eds) Behçet Syndrome (Springer, 2019).

Download references

Author information

Affiliations

Authors

Contributions

Introduction (H.Y.); Epidemiology (Y.Y.); Mechanisms/pathophysiology (N.A. and N.S.); Diagnosis, screening and prevention (Y.Y., G.H., B.B. and J.H.C.); Management (G.H., B.B. and J.H.C.); Quality of life (Y.Y. and G.H.); Outlook (H.Y.); Overview of Primer (Y.Y., H.Y. and G.H.).

Corresponding author

Correspondence to Yusuf Yazici.

Ethics declarations

Competing interests

Y.Y. has received consulting fees from Amgen and research support from Amgen, BMS and Genentech. G.H. has received research grant, lecture fees and fees for serving on an advisory board from Celgene; consulting fees from Bayer, Johnson & Johnson and UCB Pharma; and lecture fees from Abbvie, Amgen, Novartis and UCB Pharma. B.B. has received consulting fees from AbbVie/Allergan, Alimera, Horus Pharma, Novartis, Santen and Thea. All other authors declare no competing interests.

Additional information

Informed consent

The authors affirm that patients provided informed consent for publication of the images in Fig. 3.

Peer review information

Nature Reviews Disease Primers thanks E. Giacomo, M. Stanford, P. Yang, I. Kötter, S. Hou, L. Cantarini and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Apremilast

A small-molecule inhibitor of PDE4.

Epididymitis

Inflammation of the epididymis, a tube at the back of the testicle that carries sperm.

Endocarditis

Inflammation of the inner layer of the heart.

Reiter’s syndrome

An inflammatory syndrome typically presenting with conjunctivitis, urethritis and arthritis.

MAGIC syndrome

A rare condition with oral and genital ulcers and cartilage inflammation.

Sweet syndrome

A skin condition with neutrophilic infiltrations and fever.

Erythema multiforme

A group of hypersensitivity disorders characterized by symmetrical red, patchy lesions, primarily on the arms and legs.

Pyoderma gangrenosum

Non-infectious inflammatory, neutrophilic skin disease characterized by ulcerating lesions.

Erythema nodosum

An inflammatory panniculitis characterized by inflammation of the fat cells under the skin, resulting in tender red nodules or lumps that are usually seen on both shins.

Superficial thrombophlebitis

Blood clots of the small blood vessels on the skin.

Panniculitis

Inflammation of the subcutaneous fat.

Enthesopathy

A disorder of the entheses, which are the connective tissues between bones and tendons or ligaments.

Episcleritis

An inflammatory condition affecting the episcleral tissue between the conjunctiva (the clear mucous membrane lining the inner eyelids and sclera) and the sclera (the white part of the eye) that occurs in the absence of an infection.

Uveitis

Inflammation of the uvea, which is the pigmented layer that lies between the inner retina and the outer fibrous layer composed of the sclera and cornea in the eye.

Hypopyon

Accumulation of inflammatory cells in the anterior chamber of the eye.

Papillitis

Inflammation of the optic nerve head.

Retrobulbar optic neuritis

A form of optic neuritis in which the optic nerve that is at the back of the eye becomes inflamed.

Budd–Chiari syndrome

A condition caused by the occlusion of the hepatic veins.

Hemiparesis

Weakness of one side of the body.

Dysarthria

Inability to speak due to damage to the part of the brain responsible for speaking.

Ataxia

A neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormalities, speech changes and abnormalities in eye movements.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yazici, Y., Hatemi, G., Bodaghi, B. et al. Behçet syndrome. Nat Rev Dis Primers 7, 67 (2021). https://doi.org/10.1038/s41572-021-00301-1

Download citation

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing