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.

  • Review Article
  • Published:

Behçet syndrome: a contemporary view

Nature Reviews Rheumatology volume 14, pages 107–119 (2018)Cite this article

Subjects

A Corrigendum to this article was published on 24 January 2018

This article has been updated

Key Points

  • Both the disease presentation and evidence from basic studies suggest more than one pathogenetic mechanism is involved in Behçet syndrome. Recognized vascular manifestations in Behçet syndrome include venous claudication, bronchial arterial collaterals (causing haemoptysis) and 'silent' Budd–Chiari syndrome

  • The diagnostic specificity of certain manifestations, such as eye disease or vascular involvement, might be more pathognomonic than other manifestations, such as gastrointestinal ulcerations

  • In considering the clinical and the basic science findings in Behçet syndrome, the weight of evidence suggests Behçet syndrome should not to be grouped with other, seemingly related, conditions

Abstract

The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest multiple pathological pathways are involved in Behçet syndrome. These features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 to be the important genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bone fide disease, especially in non-endemic regions, suggests other factors must also be operative in Behçet syndrome. This consideration is also true for the newly proposed 'MHC-I-opathy' concept. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease (such as Budd–Chiari syndrome and pulmonary artery involvement), 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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The prevalence of Behçet syndrome.
Figure 2: Vascular involvement in Behçet syndrome.
Figure 3: CNS involvement in Behçet syndrome.
Figure 4: Management of Behçet syndrome.

Similar content being viewed by others

Article 16 September 2021

Yusuf Yazici, Gulen Hatemi, … Hasan Yazici

Change history

  • 24 January 2018

    In the original version of this article, the indicated dosage of colchicine, 1.5 mg per day, was incorrectly given as 1.5 mg/kg per day in figure 4. This error has now been corrected in the print, PDF and HTML versions of this article.

References

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

  2. Skef, W. Gastrointestinal Behçet's disease: a review. World J. Gastroenterol. 21, 3801 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 

  4. Yazici, H. & Yazici, Y. Diagnosis and/or classification of vasculitis. Curr. Opin. Rheumatol. 28, 3–7 (2016).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Tunc, R., Saip, S., Siva, A. & Yazici, H. Cerebral venous thrombosis is associated with major vessel disease in Behçet's syndrome. Ann. Rheum. Dis. 63, 1693–1694 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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 

  8. Tugal-Tutkun, I., Onal, S., Ozyazgan, Y., Soylu, M. & Akman, M. Validity and agreement of uveitis experts in interpretation of ocular photographs for diagnosis of Behçet uveitis. Ocul. Immunol. Inflamm. 22, 461–468 (2013).

    Article  PubMed  Google Scholar 

  9. 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).

    Article  PubMed  Google Scholar 

  10. Kural-Seyahi, E. et al. The long-term mortality and morbidity of Behçet syndrome. Medicine 82, 60–76 (2003).

    Article  PubMed  Google Scholar 

  11. Yavuz, S. et al. Activation of neutrophils by testosterone in Behçet's disease. Clin. Exp. Rheumatol. 25 (Suppl. 45), S46–S51 (2007).

    CAS  PubMed  Google Scholar 

  12. Seyahi, E. et al. Pulmonary artery involvement and associated lung disease in Behçet disease. Medicine 91, 35–48 (2012).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Seyahi, E. et al. An outcome survey of 43 patients with Budd-Chiari syndrome due to Behçet's syndrome followed up at a single, dedicated center. Semin. Arthritis Rheum. 44, 602–609 (2015).

    Article  PubMed  Google Scholar 

  15. Melikoglu, M., Kural-Seyahi, E., Tascilar, K. & Yazici, H. The unique features of vasculitis in Behçet's syndrome. Clin. Rev. Allergy Immunol. 35, 40–46 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Çoban, O. et al. Masked assessment of MRI findings: is it possible to differentiate neuro-Behçet's disease from other central nervous system. Neuroradiology 41, 255–260 (1999).

    Article  PubMed  Google Scholar 

  17. Siva, A. et al. Behçet's disease: diagnostic and prognostic aspects of neurological involvement. J. Neurol. 248, 95–103 (2001).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  19. Valenti, S., Gallizzi, R., De Vivo, D. & Romano, C. Intestinal Behçet and Crohn's disease: two sides of the same coin. Pediatr. Rheumatol. 15, 33 (2017).

    Article  Google Scholar 

  20. Hatemi, I. et al. Frequency of pathergy phenomenon and other features of Behçet's syndrome among patients with inflammatory bowel disease. Clin. Exp. Rheumatol. 26, S91–95.

  21. Takeuchi, M. et al. Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility. Nat. Genet. 49, 438–443 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 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).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  24. McGonagle, D., Aydin, S. Z., Gül, A., Mahr, A. & Direskeneli, H. 'MHC-I-opathy' — unified concept for spondyloarthritis and Behçet disease. Nat. Rev. Rheumatol. 11, 731–740 (2015).

    Article  CAS  PubMed  Google Scholar 

  25. Schett, G. et al. Enthesitis: from pathophysiology to treatment. Nat. Rev. Rheumatol. 13, 731–741 (2017).

    Article  CAS  PubMed  Google Scholar 

  26. Yurdakul, S. et al. A double-blind trial of colchicine in Behçet's syndrome. Arthritis Rheum. 44, 2686–2692 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Hamuryudan, V. Thalidomide in the treatment of the mucocutaneous lesions of the Behcet syndrome. Ann. Intern. Med. 128, 443 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Melikoglu, M. et al. Short-term trial of etanercept in Behçet's disease: a double blind, placebo controlled study. J. Rheumatol. 32, 98–105 (2005).

    CAS  PubMed  Google Scholar 

  29. Direskeneli, H. Autoimmunity versus autoinflammation in Behcet's disease: do we oversimplify a complex disorder? Rheumatology 45, 1461–1465 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Yazici, H. The place of Behçet's syndrome among the autoimmune diseases. Int. Rev. Immunol. 14, 1–10 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Lule, S. et al. Behçet disease serum is immunoreactive to neurofilament medium which share common epitopes to bacterial HSP-65, a putative trigger. J. Autoimmun. 84, 87–96 (2017).

    Article  CAS  PubMed  Google Scholar 

  32. Gul, A. Behçets disease as an autoinflammatory disorder. Curr. Drug Targets Inflamm. Allergy 4, 81–83 (2005).

    Article  PubMed  Google Scholar 

  33. Franks, W. A. et al. Cytokines in human intraocular inflammation. Curr. Eye Res. 11, 187–191 (1992).

    Article  PubMed  Google Scholar 

  34. Kirino, Y. et al. Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease. Proc. Natl Acad. Sci. USA 110, 8134–8139 (2013).

    Article  PubMed  Google Scholar 

  35. Yazici, H. & Fresko, I. Behçet's disease and other autoinflammatory conditions: what's in a name? Clin. Exp. Rheumatol. 23 (Suppl. 38), S1–S2 (2005).

    PubMed  Google Scholar 

  36. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01965145 (2017).

  37. Rudwaleit, M. in Rheumatology 5th edn (eds Hochberg, M., Silman, A., Smolen, J., Weinblatt, M. & Weisman, M.) 1123–1127 (Mosby Elsevier, 2011).

    Book  Google Scholar 

  38. Remmers, E. F. et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease. Nat. Genet. 42, 698–702 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ombrello, M. J. et al. Behcet disease-associated MHC class I residues implicate antigen binding and regulation of cell-mediated cytotoxicity. Proc. Natl Acad. Sci. USA 111, 8867–8872 (2014).

    Article  CAS  PubMed  Google Scholar 

  40. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Evans, D. M. et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat. Genet. 43, 761–767 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat. Genet. 42, 985–990 (2010).

  43. Ambarus, C., Yeremenko, N., Tak, P. P. & Baeten, D. Pathogenesis of spondyloarthritis: autoimmune or autoinflammatory? Curr. Opin. Rheumatol. 24, 351–358 (2012).

    Article  CAS  PubMed  Google Scholar 

  44. Giza, M., Koftori, D., Chen, L. & Bowness, P. Is Behçet's disease a 'class 1-opathy'? The role of HLA-B*51 in the pathogenesis of Behçet's disease. Clin. Exp. Immunol. 191, 11–18 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Schwartz, D. M., Bonelli, M., Gadina, M. & O'Shea, J. J. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat. Rev. Rheumatol. 12, 25–36 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Tulunay, A. et al. Activation of the JAK/STAT pathway in Behcet's disease. Genes Immun. 16, 170–175 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hatemi, G. & Yazici, H. Behçet's syndrome and micro-organisms. Best Pract. Res. Clin. Rheumatol. 25, 389–406 (2011).

    Article  PubMed  Google Scholar 

  48. Behçet, H. Über residivierende aphtose, durch ein virus verursachte geschwüre am mund, am auge und den genitalen [German]. Dermatol. Wochenschrift. 105, 1152–1158 (1937).

    Google Scholar 

  49. Mumcu, G., Inanc, N., Yavuz, S. & Direskeneli, H. The role of infectious agents in the pathogenesis, clinical manifestations and treatment strategies in Behçet's disease. Clin. Exp. Rheumatol. 25 (Suppl. 45), S27–S33 (2007).

    CAS  PubMed  Google Scholar 

  50. Coit, P. et al. Sequencing of 16S rRNA reveals a distinct salivary microbiome signature in Behçet's disease. Clin. Immunol. 169, 28–35 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Seoudi, N., Bergmeier, L. A., Drobniewski, F., Paster, B. & Fortune, F. The oral mucosal and salivary microbial community of Behçet's syndrome and recurrent aphthous stomatitis. J. Oral Microbiol. 7, 27150 (2015).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  54. Xavier, J. M. et al. FUT2: filling the gap between genes and environment in Behçet's disease? Ann. Rheum. Dis. 74, 618–624 (2013).

    Article  CAS  PubMed  Google Scholar 

  55. Maroni, L., van de Graaf, S. F. J., Hohenester, S. D., Oude Elferink, R. P. J. & Beuers, U. Fucosyltransferase 2: a genetic risk factor for primary sclerosing cholangitis and Crohn's disease — a comprehensive review. Clin. Rev. Allergy Immunol. 48, 182–191 (2014).

    Article  CAS  Google Scholar 

  56. Goto, Y., Uematsu, S. & Kiyono, H. Epithelial glycosylation in gut homeostasis and inflammation. Nat. Immunol. 17, 1244–1251 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Coit, P., Direskeneli, H. & Sawalha, A. H. An update on the role of epigenetics in systemic vasculitis. Curr. Opin. Rheumatol. 10.1097/bor.0000000000000451 (2017).

  59. Morton, L. T., Situnayake, D. & Wallace, G. R. Genetics of Behçet's disease. Curr. Opin. Rheumatol. 28, 39–44 (2016).

    Article  CAS  PubMed  Google Scholar 

  60. Maldini, C., LaValley, M. P., Cheminant, M., de Menthon, M. & Mahr, A. Relationships of HLA-B51 or B5 genotype with Behçet's disease clinical characteristics: systematic review and meta-analyses of observational studies. Rheumatology 51, 887–900 (2012).

    Article  PubMed  Google Scholar 

  61. Becatti, M. et al. Neutrophil activation promotes fibrinogen oxidation and thrombus formation in Behçet's disease. Circulation 133, 302–311 (2015).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  63. 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).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  65. 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 

  66. 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 

  67. Mahr, A. et al. Population-based prevalence study of Behçet's disease: differences by ethnic origin and low variation by age at immigration. Arthritis Rheum. 58, 3951–3959 (2008).

    Article  PubMed  Google Scholar 

  68. 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).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Google Scholar 

  70. 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).

    Article  PubMed  Google Scholar 

  71. Madanat, W. Y. et al. The prevalence of Behçet disease in the north of Jordan: a hospital based epidemiological survey. Clin. Exp. Rheumatol 35 (Suppl.), S51–S54 (2017).

    Google Scholar 

  72. Saadoun, D. et al. Mortality in Behçet's disease. Arthritis Rheum. 62, 2806–2812 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Bernabe, E., Marcenes, W., Mather, J., Phillips, C. & Fortune, F. Impact of Behcet's syndrome on health-related quality of life: influence of the type and number of symptoms. Rheumatology 49, 2165–2171 (2010).

    Article  PubMed  Google Scholar 

  74. 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, S107–112.

  75. Ilhan, B. et al. Fatigue in patients with Behcet's syndrome: relationship with quality of life, depression, anxiety, disability and disease activity. Int. J. Rheum. Dis. 10.1111/1756-185X.12839 (2016).

  76. Moses Alder, N., Fisher, M. & Yazici, Y. Behçet's syndrome patients have high levels of functional disability, fatigue and pain as measured by a Multi-dimensional Health Assessment Questionnaire (MDHAQ). Clin. Exp. Rheumatol. 26 (Suppl. 50), S110–S113 (2008).

    CAS  PubMed  Google Scholar 

  77. Saygin, C., Uzunaslan, D., Hatemi, G. & Hamuryudan, V. Suicidal ideation among patients with Behçet's syndrome. Clin. Exp. Rheumatol. 33 (Suppl. 94), S30–S35 (2015).

    PubMed  Google Scholar 

  78. Volle, G. et al. Dietary and nondietary triggers of oral ulcer recurrences in Behçet's disease. Arthritis Care Res. 69, 1429–1436 (2017).

    Article  Google Scholar 

  79. Hamuryudan, V. et al. Frequent oral ulceration during early disease may predict a severe disease course in males with Behçet's syndrome. Clin. Exp. Rheumatol. 30 (Suppl. 72), S32–S34 (2012).

    CAS  PubMed  Google Scholar 

  80. Alibaz-Oner, F. et al. Unmet need in Behcet's disease: most patients in routine follow-up continue to have oral ulcers. Clin. Rheumatol. 33, 1773–1776 (2014).

    Article  PubMed  Google Scholar 

  81. Tugal-Tutkun, I., Ozdal, P. C., Oray, M. & Onal, S. Review for diagnostics of the year: multimodal imaging in Behçet uveitis. Ocul. Immunol. Inflamm. 25, 7–19 (2016).

    Article  PubMed  Google Scholar 

  82. Onal, S. et al. Quantitative analysis of structural alterations in the choroid of patients with active Behçet uveitis. Retina 10.1097/iae.0000000000001587 (2017).

  83. Oray, M., Onal, S., Bayraktar, S., Izgi, B. & Tugal-Tutkun, I. Nonglaucomatous localized retinal nerve fiber layer defects in Behçet uveitis. Am. J. Ophthalmol. 159, 475–481.e1 (2015).

    Article  PubMed  Google Scholar 

  84. Chung, Y.-R., Lee, E.-S., Kim, M. H., Lew, H. M. & Song, J. H. Changes in ocular manifestations of Behçet disease in Korean patients over time: a single-center experience in the 1990s and 2000s. Ocul. Immunol. Inflamm. 23, 157–161 (2014).

    Article  PubMed  Google Scholar 

  85. Cingu, A. K., Onal, S., Urgancioglu, M. & Tugal-Tutkun, I. Comparison of presenting features and three-year disease course in Turkish patients with Behçet uveitis who presented in the early 1990s and the early 2000s. Ocul. Immunol. Inflamm. 20, 423–428 (2012).

    Article  PubMed  Google Scholar 

  86. Taylor, S. R. J. et al. Behçet disease: visual prognosis and factors influencing the development of visual loss. Am. J. Ophthalmol. 152, 1059–1066 (2011).

    Article  PubMed  Google Scholar 

  87. Accorinti, M., Pesci, F. R., Pirraglia, M. P., Abicca, I. & Pivetti-Pezzi, P. Ocular Behçet's disease: changing patterns over time, complications and long-term visual prognosis. Ocul. Immunol. Inflamm. 25, 29–36 (2016).

    Article  PubMed  Google Scholar 

  88. Seyahi, E. et al. Clinical and ultrasonographic evaluation of lower-extremity vein thrombosis in Behcet syndrome. Medicine 94, e1899 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Seyahi, E. et al. The estimated pulmonary artery pressure can be elevated in Behçet's syndrome. Respir. Med. 105, 1739–1747 (2011).

    Article  PubMed  Google Scholar 

  90. Esatoglu, S. N. et al. Bronchial artery enlargement may be the cause of recurrent haemoptysis in Behçet's syndrome patients with pulmonary artery involvement during follow-up. Clin. Exp. Rheumatol. 34 (Suppl. 102), 92–96 (2016).

    PubMed  Google Scholar 

  91. Siva, A. & Saip, S. The spectrum of nervous system involvement in Behçet's syndrome and its differential diagnosis. J. Neurol. 256, 513–529 (2009).

    Article  PubMed  Google Scholar 

  92. Gündüz, T. et al. Cognitive impairment in neuro-Behcet's disease and multiple sclerosis: a comparative study. Int. J. Neurosci. 122, 650–656 (2012).

    Article  PubMed  Google Scholar 

  93. Akman-Demir, G. et al. Behçet's disease patients with multiple sclerosis-like features: discriminative value of Barkhof criteria. Clin. Exp. Rheumatol. 33 (Suppl. 94), S80–S84 (2015).

    PubMed  Google Scholar 

  94. Kikuchi, H., Takayama, M. & Hirohata, S. Quantitative analysis of brainstem atrophy on magnetic resonance imaging in chronic progressive neuro-Behçet's disease. J. Neurol. Sci. 337, 80–85 (2014).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  96. Hatemi, I. et al. Characteristics, treatment, and long-term outcome of gastrointestinal involvement in Behcet's syndrome. Medicine 95, e3348 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Esatoglu, S. N. et al. Fecal calprotectin level looks promising in identifying active disease in Behçet's syndrome patients with gastrointestinal involvement: a controlled and pilot study [abstract]. Ann. Rheum. Dis. 75, AB0574 (2016).

    Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  99. Hatemi, G. et al. Current status, goals, and research agenda for outcome measures development in Behcet syndrome: report from OMERACT 2014. J. Rheumatol. 42, 2436–2441 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Hatemi, G. et al. Developing a core set of outcome measures for Behçet disease: report from OMERACT 2016. J. Rheumatol. 44, 1750–1753 (2017).

    Article  PubMed  Google Scholar 

  101. Cush, J. New EULAR guidelines on Behçet's. RheumNow http://rheumnow.com/content/new-eular-guidelines-beh%C3%A7ets (2016).

  102. Tasli, L., Mat, C., De Simone, C. & Yazici, H. Lactobacilli lozenges in the management of oral ulcers of Behçet's syndrome. Clin. Exp. Rheumatol. 24 (Suppl. 42), S83–S86 (2006).

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  104. Alpsoy, E. et al. Interferon alfa-2a in the treatment of Behçet disease: a randomized placebo-controlled and double-blind study. Arch. Dermatol. 138, 467–471 (2002).

    Article  CAS  PubMed  Google Scholar 

  105. Grayson, P. C. et al. Treatment of mucocutaneous manifestations in Behçet's disease with anakinra: a pilot open-label study. Arthritis Res. Ther. 19, 69 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mirouse, A. et al. Ustekinumab for Behçet's disease. J. Autoimmun. 82, 41–46 (2017).

    Article  CAS  PubMed  Google Scholar 

  107. Gül, A. et al. Interleukin-1β-regulating antibody XOMA 052 (gevokizumab) in the treatment of acute exacerbations of resistant uveitis of Behçet's disease: an open-label pilot study. Ann. Rheum. Dis. 71, 563–566 (2011).

    Article  CAS  PubMed  Google Scholar 

  108. Tugal-Tutkun, I. et al. Safety and efficacy of gevokizumab in patients with behçet's disease uveitis: results of an exploratory phase 2 study. Ocul. Immunol. Inflamm. 25, 62–70 (2016).

    Article  CAS  Google Scholar 

  109. Dick, A. D. et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 120, 777–787 (2013).

    Article  PubMed  Google Scholar 

  110. Deroux, A., Chiquet, C. & Bouillet, L. Tocilizumab in severe and refractory Behcet's disease: four cases and literature review. Semin. Arthritis Rheum. 45, 733–737 (2016).

    Article  CAS  PubMed  Google Scholar 

  111. Eser Ozturk, H., Oray, M. & Tugal-Tutkun, I. Tocilizumab for the treatment of Behçet uveitis that failed interferon alpha and anti-tumor necrosis factor-alpha therapy. Ocul. Immunol. Inflamm. 10.1080/09273948.2017.1355471 (2017).

  112. Hamuryudan, V. et al. Pulmonary artery aneurysms in Behçet syndrome. Am. J. Med. 117, 867–870 (2004).

    Article  PubMed  Google Scholar 

  113. Tuzun, H. et al. Management and prognosis of nonpulmonary large arterial disease in patients with Behçet disease. J. Vasc. Surg. 55, 157–163 (2012).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  115. Seyahi, E. & Yazici, H. To anticoagulate or not to anticoagulate vascular thrombosis in Behçet's syndrome: an enduring question. Clin. Exp. Rheumatol. 34 (Suppl. 95), S3–S4 (2016).

    PubMed  Google Scholar 

  116. Alibaz-Oner, F. et al. Behçet disease with vascular involvement. Medicine. 94, e494 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Akman-Demir, G. et al. Cyclosporine for Behçet's uveitis: is it associated with an increased risk of neurological involvement? Clin. Exp. Rheumatol. 26 (Suppl. 50), S84–S90 (2008).

    CAS  PubMed  Google Scholar 

  118. Hirohata, S. et al. Cerebrospinal fluid interleukin-6 in progressive Neuro-Behçet's syndrome. Clin. Immunol. Immunopathol. 82, 12–17 (1997).

    Article  CAS  PubMed  Google Scholar 

  119. Akman-Demir, G. et al. Interleukin-6 in neuro-Behçet's disease: association with disease subsets and long-term outcome. Cytokine 44, 373–376 (2008).

    Article  CAS  PubMed  Google Scholar 

  120. Hatemi, I., Hatemi, G., Pamuk, O. N., Erzin, Y. & Celik, A. F. TNF-alpha antagonists and thalidomide for the management of gastrointestinal Behçet's syndrome refractory to the conventional treatment modalities: a case series and review of the literature. Clin. Exp. Rheumatol. 33 (Suppl. 94), S129–S137 (2015).

    PubMed  Google Scholar 

  121. Soysal, T. et al. Bone marrow transplantation for Behcet's disease: a case report and systematic review of the literature. Rheumatology 53, 1136–1141 (2014).

    Article  CAS  PubMed  Google Scholar 

  122. Yazici, H. Behçet's syndrome in the 2000s: “Where is the wisdom we have lost in knowledge?” Clin. Exp. Rheumatol. 34, (Suppl. 102) S23–S25 (2016).

    Google Scholar 

  123. Yurdakul, S. & Yazici, Y. in Behçet's Syndrome 1st edn (eds Yazici, Y. & Yazici, H.) 35–52 (Springer, 2010).

    Book  Google Scholar 

Download references

Acknowledgements

The authors thank H. Direskeneli (Marmara University, Turkey) for his valuable comments during manuscript preparation.

Author information

Authors and Affiliations

  1. Academic Hospital, Internal Medicine (Rheumatology), Nuhkuyusu cad. Uskudar, Istanbul, 34668, Turkey

    Hasan Yazici

  2. Department of Internal Medicine, Division of Rheumatology, University of Istanbul, Cerrahpaşa Medical Faculty, 181 Kocamustafapaşa, Istanbul, 34098, Fatih, Turkey

    Emire Seyahi & Gulen Hatemi

  3. Department of Medicine (Rheumatology), New York University School of Medicine, NYU Hospital for Joint Diseases, 333 East 38th Street, New York, 10016, NY, USA

    Yusuf Yazici

Authors
  1. Hasan Yazici
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emire Seyahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gulen Hatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yusuf Yazici
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched the data for the article, contributed substantially to the discussions of its content, wrote the manuscript and reviewed the manuscript before submission.

Corresponding author

Correspondence to Hasan Yazici.

Ethics declarations

Competing interests

E.S. has received honoraria or speaker's fees from Pfizer, MSD, Mustafa Nevzat and UCB Pharma. G.H. has received honoraria, speaker fees and/or research grants from Abbvie, BMS, Celgene, Mustafa Nevzat, MSD, Pfizer and UCB Pharma. Y.Y. has received research grants from BMS, Celgene and Genentech, and has received consulting fees from Celgene. H.Y. declares no competing interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yazici, H., Seyahi, E., Hatemi, G. et al. Behçet syndrome: a contemporary view. Nat Rev Rheumatol 14, 107–119 (2018). https://doi.org/10.1038/nrrheum.2017.208

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2017.208

This article is cited by

Search

Advanced 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