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:

Vascular Behçet syndrome: from pathogenesis to treatment

Nature Reviews Rheumatology volume 19, pages 111–126 (2023)Cite this article

Subjects

Abstract

Behçet syndrome is a rare, chronic inflammatory disease of unknown aetiopathogenesis, most commonly presenting with mucocutaneous and ocular manifestations. Vascular involvement, most frequently superficial vein and deep vein thrombosis, can occur in up to 50% of patients with Behçet syndrome. Venous thrombosis at atypical sites (inferior and superior vena cava, suprahepatic veins with Budd–Chiari syndrome, portal vein, cerebral sinuses and right atrium and/or ventricle) and arterial involvement (mostly in situ thrombosis and aneurysms of the pulmonary arteries, as well as aneurysms of the abdominal aorta, and peripheral and visceral arteries) are also unique features of Behçet syndrome. Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, with an impaired immune-inflammatory response rather than traditional cardiovascular risk factors contributing to thrombogenesis. Specifically, neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly promote endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome. This unusual pathogenesis directly determines the treatment approach, which relies mostly on immunosuppressants rather than anticoagulants for treatment of thrombosis and for secondary prevention. This Review discusses the main histopathological, pathogenetic and clinical aspects of vascular Behçet syndrome, addressing their implications for therapeutic management. Future perspectives in terms of pathogenetic studies, disease monitoring and treatment strategies are also discussed.

Key points

  • Vascular involvement occurs in up to 50% of patients with Behçet syndrome, mostly in the form of superficial and deep vein thrombosis.

  • Behçet syndrome is considered a natural model of inflammation-induced thrombosis in humans, as thrombogenesis is mostly due to an impaired immune-inflammatory response rather than traditional cardiovascular risk factors.

  • Neutrophil hyperactivation and neutrophil-mediated mechanisms of damage directly sustain endothelial dysfunction, platelet activation and thrombogenesis in Behçet syndrome.

  • Venous thrombosis at atypical sites (such as Budd–Chiari syndrome, inferior and superior vena cava, and cerebral venous sinus thrombosis), and pulmonary and non-pulmonary artery involvement are also unique features of Behçet syndrome.

  • Thrombosis treatment and secondary prevention in Behçet syndrome currently relies mostly on immunosuppressants rather than on anticoagulants.

  • Research is needed to address the contribution of epigenetic modulators in Behçet syndrome thrombogenesis, to assess the diagnostic performance of vascular imaging to support Behçet syndrome diagnosis, and to identify new pharmacological and non-pharmacological therapeutic approaches.

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

Fig. 1: The main pathogenetic mechanisms in vascular Behçet syndrome.
Fig. 2: Vascular involvement in Behçet syndrome.
Fig. 3: Imaging of venous involvement in Behçet syndrome.
Fig. 4: Imaging of arterial involvement in Behçet syndrome.

Similar content being viewed by others

References

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

    Article  CAS  Google Scholar 

  2. Seyahi, E. Phenotypes in Behçet’s syndrome. Intern. Emerg. Med. 14, 677–689 (2019).

    Article  Google Scholar 

  3. Bettiol, A., Prisco, D. & Emmi, G. Behçet: the syndrome. Rheumatology 59, iii101–iii107 (2020).

    Article  Google Scholar 

  4. 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  Google Scholar 

  5. Alkaabi, J. K. & Pathare, A. Pattern and outcome of vascular involvement of Omani patients with Behcet’s disease. Rheumatol. Int. 31, 731–735 (2011).

    Article  Google Scholar 

  6. 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).

    Article  Google Scholar 

  7. Davatchi, F. et al. Behcet’s disease: epidemiology, clinical manifestations, and diagnosis. Expert. Rev. Clin. Immunol. 13, 57–65 (2017).

    Article  CAS  Google Scholar 

  8. Ames, P. R., Steuer, A., Pap, A. & Denman, A. M. Thrombosis in Behçet’s disease: a retrospective survey from a single UK centre. Rheumatology 40, 652–655 (2001).

    Article  CAS  Google Scholar 

  9. Kara Kivanc, B. et al. Why are male patients with Behçet’s disease prone to thrombosis? A rotational thromboelastographic analysis. Clin. Exp. Rheumatol. 36, 63–67 (2018).

    Google Scholar 

  10. Nasr, H. & Scriven, J. M. Superficial thrombophlebitis (superficial venous thrombosis). Br. Med. J. 350, h2039 (2015).

    Article  CAS  Google Scholar 

  11. Sarr, S. A. et al. Superior vena cava syndrome revealing a Behçet’s disease. Thromb. J. 13, 7 (2015).

    Article  Google Scholar 

  12. Toledo-Samaniego, N. et al. Arterial and venous involvement in Behçet’s syndrome: a narrative review. J. Thromb. Thrombolysis 54, 162–171 (2022).

    Article  Google Scholar 

  13. Emmi, G. et al. Vascular Behçet’s syndrome: an update. Intern. Emerg. Med. 14, 645–652 (2019).

    Article  Google Scholar 

  14. Becatti, M. et al. Behçet’s syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects. Clin. Exp. Immunol. 195, 322–333 (2019).

    Article  CAS  Google Scholar 

  15. Khalid, U. & Saleem, T. Hughes-Stovin syndrome. Orphanet J. Rare Dis. 6, 15 (2011).

    Article  Google Scholar 

  16. Uzun, O., Akpolat, T. & Erkan, L. Pulmonary vasculitis in Behçet disease: a cumulative analysis. Chest 127, 2243–2253 (2005).

    Article  Google Scholar 

  17. Mattioli, I., Bettiol, A., Saruhan-Direskeneli, G., Direskeneli, H. & Emmi, G. Pathogenesis of Behçet’s syndrome: genetic, environmental and immunological factors. Front. Med. 8, 713052 (2021).

    Article  Google Scholar 

  18. Bettiol, A. et al. Treating the different phenotypes of Behçet’s syndrome. Front. Immunol. 10, 2830 (2019).

    Article  CAS  Google Scholar 

  19. Demirkesen, C., Oz, B. & Goksel, S. in Behçet’s syndrome 171–189 (Springer, 2020).

  20. Emmi, G. et al. Thrombosis in vasculitis: from pathogenesis to treatment. Thromb. J. 13, 15 (2015).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Ruf, W. & Ruggeri, Z. M. Neutrophils release brakes of coagulation. Nat. Med. 16, 851–852 (2010).

    Article  CAS  Google Scholar 

  23. Soehnlein, O. Multiple roles for neutrophils in atherosclerosis. Circ. Res. 110, 875–888 (2012).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Sahin, S., Akoglu, T., Direskeneli, H., Sen, L. S. & Lawrence, R. Neutrophil adhesion to endothelial cells and factors affecting adhesion in patients with Behçet’s disease. Ann. Rheum. Dis. 55, 128–133 (1996).

    Article  CAS  Google Scholar 

  26. Eksioglu-Demiralp, E. et al. Neutrophil activation in Behçet’s disease. Clin. Exp. Rheumatol. 19, S19–S24 (2001).

    CAS  Google Scholar 

  27. Yavuz, S. et al. Dual effects of testosterone in Behcet’s disease: implications for a role in disease pathogenesis. Genes. Immun. 17, 335–341 (2016).

    Article  CAS  Google Scholar 

  28. Durmazlar, S. P. et al. Significance of serum interleukin-8 levels in patients with Behcet’s disease: high levels may indicate vascular involvement. Int. J. Dermatol. 48, 259–264 (2009).

    Article  CAS  Google Scholar 

  29. Becatti, M. et al. Neutrophil activation promotes fibrinogen oxidation and thrombus formation in Behçet disease. Circulation 133, 302–311 (2016). This study investigated the pathogenesis of thrombo-inflammation in vascular Behçet syndrome, and demonstrated how oxidative stress can induce pro-thrombotic modifications of fibrinogen, a key molecule involved in the coagulation pathway.

    Article  CAS  Google Scholar 

  30. Orem, A. et al. Relationship between lipid peroxidation and disease activity in patients with Behçet’s disease. J. Dermatol. Sci. 16, 11–16 (1997).

    Article  CAS  Google Scholar 

  31. Orem, A., Cimsit, G., Deger, O., Vanizor, B. & Karahan, S. C. Autoantibodies against oxidatively modified low-density lipoprotein in patients with Behçet’s disease. Dermatology 198, 243–246 (1999).

    Article  CAS  Google Scholar 

  32. Orem, A. et al. The evaluation of autoantibodies against oxidatively modified low-density lipoprotein (LDL), susceptibility of LDL to oxidation, serum lipids and lipid hydroperoxide levels, total antioxidant status, antioxidant enzyme activities, and endothelial dysfunction in patients with Behçet’s disease. Clin. Biochem. 35, 217–224 (2002).

    Article  CAS  Google Scholar 

  33. Stoiber, W., Obermayer, A., Steinbacher, P. & Krautgartner, W. D. The role of reactive oxygen species (ROS) in the formation of extracellular traps (ETs) in humans. Biomolecules 5, 702–723 (2015).

    Article  CAS  Google Scholar 

  34. Delgado-Rizo, V. et al. Neutrophil extracellular traps and its implications in inflammation: an overview. Front. Immunol. 8, 81 (2017).

    Article  Google Scholar 

  35. Chen, J., Liu, T., He, J. & Liu, Y. Correspondence on ‘Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease’. Ann. Rheum. Dis. https://doi.org/10.1136/annrheumdis-2020-21947 (2020).

    Article  Google Scholar 

  36. Safi, R. et al. Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behçet’s disease. J. Dermatol. Sci. 92, 143–150 (2018).

    Article  CAS  Google Scholar 

  37. Le Joncour, A. et al. Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease. Ann. Rheum. Dis. 78, 1274–1282 (2019). This study showed the role of NETs as a potential mechanism of neutrophil-induced thrombo-inflammation.

    Article  Google Scholar 

  38. Bettiol, A. et al. Neutrophil-mediated mechanisms of damage and in-vitro protective effect of colchicine in non-vascular Behçet’s syndrome. Clin. Exp. Immunol. 206, 410–421 (2021).

    Article  CAS  Google Scholar 

  39. Li, L. et al. Neutrophil extracellular traps promote aberrant macrophages activation in Behçet’s disease. Front. Immunol. 11, 590622 (2020).

    Article  CAS  Google Scholar 

  40. Nakazawa, D. et al. The responses of macrophages in interaction with neutrophils that undergo NETosis. J. Autoimmun. 67, 19–28 (2016).

    Article  CAS  Google Scholar 

  41. Folco, E. J. et al. Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1ɑ and cathepsin G. Arterioscler. Thromb. Vasc. Biol. 38, 1901–1912 (2018).

    Article  CAS  Google Scholar 

  42. Consolandi, C. et al. Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun. Rev. 14, 269–276 (2015). This study demonstrated how Behçet’s syndrome is characterized by a specific microbiome signature and microbiota dysbiosis.

    Article  Google Scholar 

  43. Brown, J. M. & Hazen, S. L. Microbial modulation of cardiovascular disease. Nat. Rev. Microbiol. 16, 171–181 (2018).

    Article  CAS  Google Scholar 

  44. Emmi, G. et al. Butyrate-rich diets improve redox status and fibrin lysis in Behçet’s syndrome. Circ. Res. 128, 278–280 (2021). This pilot study investigated for the first time the effects of tailored nutritional interventions to reduce redox status and the consequent pro-thrombotic milieu in patients with Behçet syndrome.

    Article  CAS  Google Scholar 

  45. Pagliai, G. et al. Modulation of gut microbiota through nutritional interventions in Behçet’s syndrome patients (the MAMBA study): study protocol for a randomized controlled trial. Trials 21, 511 (2020).

    Article  CAS  Google Scholar 

  46. Kawakami, T. et al. Presence of neutrophil extracellular traps in superficial venous thrombosis of Behçet’s disease. J. Dermatol. 49, 741–745 (2022).

    Article  Google Scholar 

  47. Onur, E. et al. Oxidative stress impairs endothelial nitric oxide levels in Behçets’ disease. Cutan. Ocul. Toxicol. 30, 217–220 (2011).

    Article  CAS  Google Scholar 

  48. Sahin, M. et al. Asymmetric dimethylarginine and nitric oxide levels as signs of endothelial dysfunction in Behcet’s disease. Ann. Clin. Lab. Sci. 36, 449–454 (2006).

    CAS  Google Scholar 

  49. Ozoran, K., Dugun, N., Gurler, A., Tutkak, H. & Tokgoz, G. Plasma von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, and antithrombin III levels in Behçet’s disease. Scand. J. Rheumatol. 24, 376–382 (1995).

    Article  CAS  Google Scholar 

  50. Haznedaroglu, I. C., Ozcebe, O., Celik, I., Dundar, S. V. & Kirazhi, S. Haemostatic markers of procoagulant imbalance in Behçet’s disease. Eur. J. Haematol. 57, 107–108 (1996).

    Article  CAS  Google Scholar 

  51. Butta, N. V., Fernandez-Bello, I., Lopez-Longo, F. J. & Jimenez-Yuste, V. Endothelial dysfunction and altered coagulation as mediators of thromboembolism in Behçet disease. Semin. Thromb. Hemost. 41, 621–628 (2015).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  53. Triolo, G. et al. Enhancement of endothelial cell E-selectin expression by sera from patients with active Behçet’s disease: moderate correlation with anti-endothelial cell antibodies and serum myeloperoxidase levels. Clin. Immunol. 91, 330–337 (1999).

    Article  CAS  Google Scholar 

  54. Sari, R. A., Kiziltunc, A., Tays’y, S., Akdem’yr, S. & Gundogdu, M. Levels of soluble E-selectin in patients with active Behçet’s disease. Clin. Rheumatol. 24, 55–59 (2005).

    Article  Google Scholar 

  55. Turkoz, Y. et al. Serum levels of soluble P-selectin are increased and associated with disease activity in patients with Behçet’s syndrome. Mediators Inflamm. 2005, 237–241 (2005).

    Article  Google Scholar 

  56. Martinez, M. et al. Platelet activation and red blood cell phosphatidylserine exposure evaluated by flow cytometry in patients with Behçet’s disease: are they related to thrombotic events? Pathophysiol. Haemost. Thromb. 36, 18–22 (2007).

    Article  CAS  Google Scholar 

  57. Polat, G. et al. Association of the platelet glycoprotein Ia C807T/G873A gene polymorphism and thrombosis in Behçet patients. Haematologia 32, 121–128 (2002).

    Article  CAS  Google Scholar 

  58. Haim, S. et al. Platelet function in Behçet’s disease. J. Dermatol. 11, 117–120 (1984).

    Article  CAS  Google Scholar 

  59. Akar, S. et al. Circulated activated platelets and increased platelet reactivity in patients with Behçet’s disease. Clin. Appl. Thromb. Hemost. 12, 451–457 (2006).

    Article  CAS  Google Scholar 

  60. Wilson, A. P., Efthimiou, J. & Betteridge, D. J. Decreased prostacyclin sensitivity of platelets in patients with Behçet’s syndrome. Eur. J. Clin. Invest. 18, 410–414 (1988).

    Article  CAS  Google Scholar 

  61. Niccolai, E. et al. Microparticles: bridging the gap between autoimmunity and thrombosis. Semin. Thromb. Hemost. 41, 413–422 (2015).

    Article  CAS  Google Scholar 

  62. Macey, M. et al. Age, gender and disease-related platelet and neutrophil activation ex vivo in whole blood samples from patients with Behçet’s disease. Rheumatol 50, 1849–1859 (2011).

    Article  CAS  Google Scholar 

  63. 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).

    Article  CAS  Google Scholar 

  64. Emmi, G. et al. A unique circulating miRNA profile highlights thrombo-inflammation in Behçet’s syndrome. Ann. Rheum. Dis. 81, 386–397 (2022). This study investigated for the first time the role of circulating miRNA in thrombo-inflammation in Behçet syndrome.

    Article  CAS  Google Scholar 

  65. Bagni, G. et al. Circulating miRNome profiling data in Behçet’s syndrome. Data Brief. 38, 107435 (2021).

    Article  CAS  Google Scholar 

  66. Caramaschi, P. et al. A study on thrombophilic factors in Italian Behcet’s patients. Jt. Bone Spine 77, 330–334 (2010).

    Article  CAS  Google Scholar 

  67. Haznedaroglu, I. C. et al. Impaired haemostatic kinetics and endothelial function in Behçet’s disease. J. Intern. Med. 240, 181–187 (1996).

    Article  CAS  Google Scholar 

  68. Aitchison, R., Chu, P., Cater, D. R., Harris, R. J. & Powell, R. J. Defective fibrinolysis in Behçet’s syndrome: significance and possible mechanisms. Ann. Rheum. Dis. 48, 590–593 (1989).

    Article  CAS  Google Scholar 

  69. Hampton, K. K., Chamberlain, M. A., Menon, D. K. & Davies, J. A. Coagulation and fibrinolytic activity in Behçet’s disease. Thromb. Haemost. 66, 292–294 (1991).

    Article  CAS  Google Scholar 

  70. Lee, Y. J. et al. Coagulation parameters and plasma total homocysteine levels in Behcet’s disease. Thromb. Res. 106, 19–24 (2002).

    Article  CAS  Google Scholar 

  71. Beyan, E., Sadikoglu, B., Ertugrul, E. & Beyan, C. Von Willebrand factor antigen levels in Behçet disease. Am. J. Hematol. 79, 70–72 (2005).

    Article  Google Scholar 

  72. Esmat, S. et al. Lipoprotein (a) and nitrites in Behcet’s disease: relationship with disease activity and vascular complications. Eur. J. Dermatol. 16, 67–71 (2006).

    Google Scholar 

  73. Gurbuz, O., Ozdemir, Y., Cosar, C. B. & Kural, G. Lipoprotein (a) in Behçet’s disease as an indicator of disease activity and in thrombotic complications. Eur. J. Ophthalmol. 11, 62–65 (2001).

    Article  CAS  Google Scholar 

  74. Leiba, M. et al. Thrombophilic factors are not the leading cause of thrombosis in Behçet’s disease. Ann. Rheum. Dis. 63, 1445–1449 (2004).

    Article  CAS  Google Scholar 

  75. Ricart, J. M., Vaya, A., Santaolaria, M., Espana, F. & Aznar, J. Dyslipidaemia in Behçet’s disease as a thrombotic risk factor. Ann. Rheum. Dis. 65, 1248–1249 (2006).

    Article  CAS  Google Scholar 

  76. Lenk, N., Ozet, G., Alli, N., Coban, O. & Erbasi, S. Protein C and protein S activities in Behçet’s disease as risk factors of thrombosis. Int. J. Dermatol. 37, 124–125 (1998).

    Article  CAS  Google Scholar 

  77. Nalcaci, M. & Pekcelen, Y. Antithrombin III, protein C and protein S plasma levels in patients with Behçet’s disease. J. Int. Med. Res. 26, 206–208 (1998).

    Article  CAS  Google Scholar 

  78. Espinosa, G. et al. Vascular involvement in Behçet’s disease: relation with thrombophilic factors, coagulation activation, and thrombomodulin. Am. J. Med. 112, 37–43 (2002).

    Article  CAS  Google Scholar 

  79. Guermazi, S., Hamza, M. & Dellagi, K. Protein S deficiency and antibodies to protein S in patients with Behçet’s disease. Thromb. Res. 86, 197–204 (1997).

    Article  CAS  Google Scholar 

  80. Alkaabi, J. K., Gravell, D., Al-Haddabi, H. & Pathare, A. Haemostatic parameters in patients with Behçet’s disease. Sultan Qaboos Univ. Med. J. 14, e190–e196 (2014).

    Google Scholar 

  81. Demirer, S. et al. Haemostasis in patients with Behçet’s disease. Eur. J. Vasc. Endovasc. Surg. 19, 570–574 (2000).

    Article  CAS  Google Scholar 

  82. Conway, E. M. & Rosenberg, R. D. Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol. Cell. Biol. 8, 5588–5592 (1988).

    CAS  Google Scholar 

  83. Lentz, S. R., Tsiang, M. & Sadler, J. E. Regulation of thrombomodulin by tumor necrosis factor-ɑ: comparison of transcriptional and posttranscriptional mechanisms. Blood 77, 542–550 (1991).

    Article  CAS  Google Scholar 

  84. Navarro, S. et al. Activated protein C levels in Behçet’s disease and risk of venous thrombosis. Br. J. Haematol. 126, 550–556 (2004).

    Article  CAS  Google Scholar 

  85. Koşar, A., Haznedaroglu, I. C., Buyukasik, Y., Kirazli, S. & Dundar, S. V. Activated protein C resistance in Behçet’s disease. Rheumatol. Int. 17, 249–250 (1998).

    Article  Google Scholar 

  86. Gül, A. et al. Coagulation factor V gene mutation increases the risk of venous thrombosis in Behçet’s disease. Br. J. Rheumatol. 35, 1178–1180 (1996).

    Article  Google Scholar 

  87. Verity, D. H. et al. Factor V Leiden mutation is associated with ocular involvement in Behçet disease. Am. J. Ophthalmol. 128, 352–356 (1999).

    Article  CAS  Google Scholar 

  88. Batioglu, F., Atmaca, L. S., Karabulut, H. G. & Beyza Sayin, D. Factor V Leiden and prothrombin gene G20210A mutations in ocular Behçet disease. Acta Ophthalmol. Scand. 81, 283–285 (2003).

    Article  CAS  Google Scholar 

  89. Dagan, E. et al. Vascular Behcet and mutations in thrombogenic genes: methylene tetrahydrofolate reductase, factor V, and prothrombin. Genet. Test. Mol. Biomark. 16, 30–35 (2012).

    Article  CAS  Google Scholar 

  90. Akarsu, M. et al. Increased levels of tissue factor pathway inhibitor may reflect disease activity and play a role in thrombotic tendency in Behçet’s disease. Am. J. Hematol. 68, 225–230 (2001).

    Article  CAS  Google Scholar 

  91. Gul, A., Aslantas, A. B., Tekinay, T., Konice, M. & Ozcelik, T. Procoagulant mutations and venous thrombosis in Behçet’s disease. Rheumatology 38, 1298–1299 (1999).

    Article  CAS  Google Scholar 

  92. Ricart, J. M. et al. Thrombophilic risk factors and homocysteine levels in Behçet’s disease in eastern Spain and their association with thrombotic events. Thromb. Haemost. 95, 618–624 (2006).

    Article  CAS  Google Scholar 

  93. Mejia, J. C., Espinosa, G., Tassies, D., Reverter, J. C. & Cervera, R. Endogenous thrombin potential in Behçet’s disease: relationship with thrombosis and anticoagulant therapy. Clin. Exp. Rheumatol. 32, S67–S71 (2014).

    Google Scholar 

  94. Toydemir, P. B. et al. Effects of factor V gene G1691A, methylenetetrahydrofolate reductase gene C677T, and prothrombin gene G20210A mutations on deep venous thrombogenesis in Behçet’s disease. J. Rheumatol. 27, 2849–2854 (2000).

    CAS  Google Scholar 

  95. Sayar, Z., Moll, R., Isenberg, D. & Cohen, H. Thrombotic antiphospholipid syndrome: a practical guide to diagnosis and management. Thromb. Res. 198, 213–221 (2021).

    Article  CAS  Google Scholar 

  96. Islam, M. A. et al. Prevalence of antiphospholipid antibodies in Behçet’s disease: a systematic review and meta-analysis. PLoS One 15, e0227836 (2020).

    Article  CAS  Google Scholar 

  97. Tokay, S., Direskeneli, H., Yurdakul, S. & Akoglu, T. Anticardiolipin antibodies in Behçet’s disease: a reassessment. Rheumatology 40, 192–195 (2001).

    Article  CAS  Google Scholar 

  98. Mader, R., Ziv, M., Adawi, M., Mader, R. & Lavi, I. Thrombophilic factors and their relation to thromboembolic and other clinical manifestations in Behçet’s disease. J. Rheumatol. 26, 2404–2408 (1999).

    CAS  Google Scholar 

  99. La Regina, M., Orlandini, F., Prisco, D. & Dentali, F. Homocysteine in vascular Behçet disease: a meta-analysis. Arterioscler. Thromb. Vasc. Biol. 30, 2067–2074 (2010).

    Article  Google Scholar 

  100. Choi, B. O. et al. Homozygous C677T mutation in the MTHFR gene as an independent risk factor for multiple small-artery occlusions. Thromb. Res. 111, 39–44 (2003).

    Article  CAS  Google Scholar 

  101. Altinbaş, A. et al. Hyperhomocysteinaemia and activated protein C resistance in Behçet’s disease. J. Intern. Med. 248, 267–268 (2000).

    Article  Google Scholar 

  102. Mungan, A. G., Can, M., Açikgöz, S., Eştürk, E. & Altinyazar, C. Lipid peroxidation and homocysteine levels in Behçet’s disease. Clin. Chem. Lab. Med. 44, 1115–1118 (2006).

    Article  CAS  Google Scholar 

  103. Buldanlioglu, S. et al. Nitric oxide, lipid peroxidation and antioxidant defence system in patients with active or inactive Behçet’s disease. Br. J. Dermatol. 153, 526–530 (2005).

    Article  CAS  Google Scholar 

  104. Canataroglu, A. et al. Methylenetetrahydrofolate reductase gene C677T mutation and plasma homocysteine level in Behçet’s disease. Rheumatol. Int. 23, 236–240 (2003).

    Article  CAS  Google Scholar 

  105. 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  Google Scholar 

  106. Chen, Y., Cai, J. F., Lin, C. H. & Guan, J. L. Demography of vascular Behcet’s disease with different gender and age: an investigation with 166 Chinese patients. Orphanet J. Rare Dis. 14, 88 (2019).

    Article  Google Scholar 

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

    Article  Google Scholar 

  108. 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  Google Scholar 

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

    Article  Google Scholar 

  110. Desbois, A. C. et al. Immunosuppressants reduce venous thrombosis relapse in Behçet’s disease. Arthritis Rheum. 64, 2753–2760 (2012).

    Article  CAS  Google Scholar 

  111. Seyahi, E., Karaaslan, H., Ugurlu, S. & Yazici, H. Fever in Behçet’s syndrome. Clin. Exp. Rheumatol. 31, 64–67 (2013).

    Google Scholar 

  112. Yazici, H., Seyahi, E., Hatemi, G. & Yazici, Y. Behçet syndrome: a contemporary view. Nat. Rev. Rheumatol. 14, 107–119 (2018).

    Article  CAS  Google Scholar 

  113. Celik, S., Yazici, Y., Sut, N. & Yazici, H. Pulmonary artery aneurysms in Behçet’s syndrome: a review of the literature with emphasis on geographical differences. Clin. Exp. Rheumatol. 33, S54–S59 (2015).

    Google Scholar 

  114. Ideguchi, H. et al. Characteristics of vascular involvement in Behçet’s disease in Japan: a retrospective cohort study. Clin. Exp. Rheumatol. 29, S47–S53 (2011).

    Google Scholar 

  115. Chang, H. K. & Kim, J. W. The clinical features of Behcet’s disease in Yongdong districts: analysis of a cohort followed from 1997 to 2001. J. Korean Med. Sci. 17, 784–789 (2002).

    Article  Google Scholar 

  116. Savey, L. et al. Ethnicity and association with disease manifestations and mortality in Behçet’s disease. Orphanet J. Rare Dis. 9, 42 (2014).

    Article  Google Scholar 

  117. Lee, I. et al. Cardiac Behçet disease presenting as aortic valvulitis/aortitis or right heart inflammatory mass: a clinicopathologic study of 12 cases. Am. J. Surg. Pathol. 32, 390–398 (2008).

    Article  Google Scholar 

  118. 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).

    Google Scholar 

  119. 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  Google Scholar 

  120. 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).

    Article  Google Scholar 

  121. Yazıcı, H. & Seyahi, E. Behçet syndrome: the vascular cluster. Turk. J. Med. Sci. 46, 1277–1280 (2016).

    Article  Google Scholar 

  122. Seyahi, E. Behçet’s disease: how to diagnose and treat vascular involvement. Best. Pract. Res. Clin. Rheumatol. 30, 279–295 (2016).

    Article  Google Scholar 

  123. Hetta, H. F. et al. Possible role of regulatory B cells in different Behçet’s disease phenotypes and therapies: first report from Egypt. J. Inflamm. Res. 14, 737–744 (2021).

    Article  Google Scholar 

  124. Zou, J., Luo, D., Shen, Y. & Guan, J. L. Characteristics and phenotype heterogeneity in late-onset Behçet’s syndrome: a cohort from a referral center in China. Clin. Rheumatol. 40, 2319–2326 (2021).

    Article  Google Scholar 

  125. Attia, D. H. S. Behçet’s disease phenotypes and clinical outcomes: a cohort study in Egyptian patients. Reumatol. Clin. 17, 514–520 (2021).

    Article  Google Scholar 

  126. Saadoun, D. et al. Cerebral venous thrombosis in Behçet’s disease. Arthritis Rheum. 61, 518–526 (2009).

    Article  CAS  Google Scholar 

  127. Hussein, M. A., Eissa, I. M. & Dahab, A. A. Vision-threatening Behcet’s Disease: severity of ocular involvement predictors. J. Ophthalmol. 2018, 9518065 (2018).

    Google Scholar 

  128. Zou, L. et al. Long-term outcomes of endovascular treatment for aortic pseudoaneurysm in patients with Behçet’s disease. Vascular https://doi.org/10.1177/17085381211063038 (2021).

    Article  Google Scholar 

  129. Tutar, B., Kantarci, F., Cakmak, O. S., Yazici, H. & Seyahi, E. Assessment of deep venous thrombosis in the lower extremity in Behçet’s syndrome: MR venography versus Doppler ultrasonography. Intern. Emerg. Med. 14, 705–711 (2019).

    Article  Google Scholar 

  130. 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, 92–96 (2016).

    Google Scholar 

  131. Zhou, J. et al. The clinical features, risk factors, and outcome of aneurysmal lesions in Behcet’s disease. J. Immunol. Res. 2019, 9198506 (2019).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  134. 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  Google Scholar 

  135. Torgutalp, M. et al. Analysis of vascular involvement in 460 patients with Behçet’s syndrome: clinical characteristics and associated factors. Jt. Bone Spine 89, 105277 (2022).

    Article  Google Scholar 

  136. Alibaz-Oner, F. et al. Behçet disease with vascular involvement: effects of different therapeutic regimens on the incidence of new relapses. Medicine 94, e494 (2015).

    Article  CAS  Google Scholar 

  137. Alibaz-Oner, F. et al. Vascular Behçet’s disease: a comparative study from Turkey and France. Clin. Exp. Rheumatol. 40, 1491–1496 (2022).

    Google Scholar 

  138. Alibaz-Oner, F. et al. Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behçet’s disease. J. Vasc. Surg. Venous Lymphat. Disord. 4, 301–306 (2016).

    Article  Google Scholar 

  139. Ugurlu, S. et al. Venous claudication in Behçet’s disease. J. Vasc. Surg. 62, 698–703.e691 (2015).

    Article  Google Scholar 

  140. Aksoy, A. et al. Predictors for the risk and severity of post-thrombotic syndrome in vascular Behçet’s disease. J. Vasc. Surg. Venous Lymphat. Disord. 9, 1451–1459 (2021).

    Article  Google Scholar 

  141. Desbois, A. C. et al. Behcet’s disease in Budd-Chiari syndrome. Orphanet J. Rare Dis. 9, 104 (2014).

    Article  Google Scholar 

  142. Sakr, M. A. et al. Characteristics and outcome of primary Budd-Chiari syndrome due to Behçet’s syndrome. Clin. Res. Hepatol. Gastroenterol. 44, 503–512 (2020).

    Article  Google Scholar 

  143. Akyol, L. et al. Budd-Chiari syndrome in Behçet’s disease: a retrospective multicenter study. Clin. Rheumatol. 41, 177–186 (2022).

    Article  Google Scholar 

  144. Martens, P. & Nevens, F. Budd-Chiari syndrome. United European Gastroenterol. J. 3, 489–500 (2015).

    Article  Google Scholar 

  145. Rossi, G. M., Emmi, G. & Vaglio, A. Hemoptysis in Behçet’s syndrome: from bedside to bench? Intern. Emerg. Med. 13, 467–469 (2018).

    Article  Google Scholar 

  146. Gokturk, A. et al. Increased frequency of obstructive sleep apnea syndrome in Behçet’s syndrome patients with superior vena cava syndrome. Clin. Exp. Rheumatol. 37, 132–136 (2019).

    Google Scholar 

  147. Yesilot, N. et al. Cerebral venous thrombosis in Behçet’s disease compared to those associated with other etiologies. J. Neurol. 256, 1134–1142 (2009).

    Article  CAS  Google Scholar 

  148. Uluduz, D. et al. Behçet’s disease as a causative factor of cerebral venous sinus thrombosis: subgroup analysis of data from the VENOST study. Rheumatology 58, 600–608 (2019).

    Article  CAS  Google Scholar 

  149. Uluduz, D. et al. Clinical characteristics of pediatric-onset neuro-Behçet disease. Neurology 77, 1900–1905 (2011).

    Article  CAS  Google Scholar 

  150. Duman, T. et al. A multicenter study of 1144 patients with cerebral venous thrombosis: the VENOST study. J. Stroke Cerebrovasc. Dis. 26, 1848–1857 (2017).

    Article  Google Scholar 

  151. Prisco, D., Silvestri, E., Di Scala, G. & Emmi, G. Behçet’s disease as a cause of cerebral sinus vein thrombosis: an emerging role. Rheumatology 58, 563–564 (2019).

    Article  Google Scholar 

  152. Aguiar de Sousa, D., Mestre, T. & Ferro, J. M. Cerebral venous thrombosis in Behçet’s disease: a systematic review. J. Neurol. 258, 719–727 (2011).

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  154. Yıldızeli, Ş. et al. Outcomes of patients with Behçet’s syndrome after pulmonary endarterectomy. Thorac. Cardiovasc. Surg. 66, 187–192 (2018).

    Article  Google Scholar 

  155. Tuzun, H. et al. Surgical treatment of pulmonary complications in Behçet’s syndrome. Semin. Thorac. Cardiovasc. Surg. 30, 369–378 (2018).

    Article  Google Scholar 

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

    Article  Google Scholar 

  157. Saadoun, D. et al. Long-term outcome of arterial lesions in Behçet disease: a series of 101 patients. Medicine 91, 18–24 (2012).

    Article  Google Scholar 

  158. Geri, G. et al. Spectrum of cardiac lesions in Behçet disease: a series of 52 patients and review of the literature. Medicine 91, 25–34 (2012).

    Article  Google Scholar 

  159. Mogulkoc, N., Burgess, M. I. & Bishop, P. W. Intracardiac thrombus in Behçet’s disease: a systematic review. Chest 118, 479–487 (2000).

    Article  CAS  Google Scholar 

  160. Emmungil, H. et al. A rare but serious manifestation of Behçet’s disease: intracardiac thrombus in 22 patients. Clin. Exp. Rheumatol. 32, S87–S92 (2014).

    Google Scholar 

  161. Fei, Y. et al. Major vascular involvement in Behçet’s disease: a retrospective study of 796 patients. Clin. Rheumatol. 32, 845–852 (2013).

    Article  Google Scholar 

  162. Vural, U., Kizilay, M. & Aglar, A. A. Coronary involvement in Behçet’s disease: what are its risks and prognosis? (Rare cases and literature review). Braz. J. Cardiovasc. Surg. 34, 749–758 (2019).

    Article  Google Scholar 

  163. Tunaci, A., Berkmen, Y. M. & Gökmen, E. Thoracic involvement in Behçet’s disease: pathologic, clinical, and imaging features. AJR Am. J. Roentgenol. 164, 51–56 (1995).

    Article  CAS  Google Scholar 

  164. Bonneville, F. Imaging of cerebral venous thrombosis. Diagn. Interv. Imaging 95, 1145–1150 (2014).

    Article  CAS  Google Scholar 

  165. Bradbury, A. W., Milne, A. A. & Murie, J. A. Surgical aspects of Behçet’s disease. Br. J. Surg. 81, 1712–1721 (1994).

    Article  CAS  Google Scholar 

  166. Mehdipoor, G., Davatchi, F., Ghoreishian, H. & Arjmand Shabestari, A. Imaging manifestations of Behcet’s disease: key considerations and major features. Eur. J. Radiol. 98, 214–225 (2018).

    Article  Google Scholar 

  167. Erkan, F., Gül, A. & Tasali, E. Pulmonary manifestations of Behçet’s disease. Thorax 56, 572–578 (2001).

    Article  CAS  Google Scholar 

  168. Cho, S. B. et al. Detection of cardiovascular system involvement in Behçet’s disease using fluorodeoxyglucose positron emission tomography. Semin. Arthritis Rheum. 40, 461–466 (2011).

    Article  Google Scholar 

  169. Trad, S. et al. 18F-fluorodeoxyglucose-positron emission tomography scanning is a useful tool for therapy evaluation of arterial aneurysm in Behçet’s disease. Jt. Bone Spine 80, 420–423 (2013).

    Article  Google Scholar 

  170. Xi, X. Y. et al. Multiple cardiovascular involvements in Behçet’s disease: unique utility of 18F-FDG PET/CT in diagnosis and follow-up. Eur. J. Nucl. Med. Mol. Imaging 46, 2210–2211 (2019).

    Article  Google Scholar 

  171. Kuzu, A., Köksoy, C., Ozaslan, C., Gürler, A. & Tüzüner, A. Evaluation of peripheral vascular system disorders in vascular symptom-free Behçet’s disease. Cardiovasc. Surg. 4, 381–383 (1996).

    Article  CAS  Google Scholar 

  172. Kisacik, B. et al. Investigation of the veins in patients with Behçet’s disease with no known vascular event by Doppler ultrasonography. Rheumatol. Int. 32, 303–306 (2012).

    Article  Google Scholar 

  173. Alibaz-Oner, F., Karatay, E., Akpinar, I. N., Ergun, T. & Direskeneli, H. Evaluation of asymptomatic venous disease by venous Doppler ultrasonography in patients with Behcet’s disease without overt thrombosis. Clin. Rheumatol. 33, 277–280 (2014).

    Article  Google Scholar 

  174. 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, S99–S102 (2014).

    Google Scholar 

  175. Alibaz-Oner, F. et al. Venous vessel wall thickness in lower extremity is increased in male patients with Behcet’s disease. Clin. Rheumatol. 38, 1447–1451 (2019). This is the first controlled Doppler ultrasonography study showing increased venous vessel wall thickness of lower-extremity veins in male patients with Behçet syndrome compared with male healthy controls or male patients affected by ankylosing spondylitis.

    Article  Google Scholar 

  176. Seyahi, E. et al. Increased vein wall thickness in Behçet disease. J. Vasc. Surg. Venous Lymphat. Disord. 7, 677–684.e672 (2019). This study showed an increased vein wall thickness of proximal deep and superficial lower-extremity veins in patients with Behçet syndrome without any clinical and radiological vascular involvement.

    Article  Google Scholar 

  177. Kaymaz, S. et al. Ultrasonographic measurement of the vascular wall thickness and intima-media thickness in patients with Behçet’s disease with symptoms or signs of vascular involvement: a cross-sectional study. Arch. Rheumatol. 36, 258–266 (2021).

    Article  Google Scholar 

  178. Tezcan, D. et al. Diagnostic performance of lower extremity venous wall thickness and laboratory findings in the diagnosis of the Behçet disease. J. Clin. Rheumatol. 28, e521–e527 (2022).

    Article  Google Scholar 

  179. Agackiran, S. K. et al. Pulmonary arterial wall thickness is increased in Behçet’s disease patients with major organ involvement: is it a sign of severity? Rheumatology https://doi.org/10.1093/rheumatology/keac452 (2022).

    Article  Google Scholar 

  180. Alibaz-Oner, F. et al. Femoral vein wall thickness measurement: a new diagnostic tool for Behçet’s disease. Rheumatology 60, 288–296 (2021).

    Article  Google Scholar 

  181. Alibaz-Oner, F. et al. Femoral vein wall thickness measurement may be a distinctive diagnostic tool to differentiate Behçet’s disease with intestinal involvement and Crohn’s Disease. Dig. Dis. Sci. 66, 2750–2755 (2021).

    Article  Google Scholar 

  182. Kiafar, M. et al. Diagnosis of Behçet’s disease: clinical characteristics, diagnostic criteria, and differential diagnoses. BMC Rheumatol. 5, 2 (2021).

    Article  Google Scholar 

  183. Atalay, E. et al. A new tool supporting the diagnosis of childhood-onset Behçet’s disease: venous wall thickness. Rheumatology https://doi.org/10.1093/rheumatology/keac314 (2022).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  185. 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). Arthritis Rheum. 58, 854 (2008).

    Google Scholar 

  186. Sharquie, K. E., Najim, R. A. & Abu-Raghif, A. R. Dapsone in Behçet’s disease: a double-blind, placebo-controlled, cross-over study. J. Dermatol. 29, 267–279 (2002).

    Article  CAS  Google Scholar 

  187. Shahram, F. et al. Comparison of existing disease activity indices in the follow-up of patients with Behçet’s disease. Mod. Rheumatol. 19, 536–541 (2009).

    Article  Google Scholar 

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

    Article  Google Scholar 

  189. 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).

    Google Scholar 

  190. Kahn, S. R., Partsch, H., Vedantham, S., Prandoni, P. & Kearon, C. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J. Thromb. Haemost. 7, 879–883 (2009).

    Article  CAS  Google Scholar 

  191. Hatemi, G. et al. Core set of domains for outcome measures in Behçet’s syndrome. Arthritis Care Res. 74, 691–699 (2022).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Google Scholar 

  194. 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).

    Article  Google Scholar 

  195. 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).

    Article  CAS  Google Scholar 

  196. Alpsoy, E., Leccese, P., Emmi, G. & Ohno, S. Treatment of Behçet’s disease: an algorithmic multidisciplinary approach. Front. Med. 8, 624795 (2021).

    Article  Google Scholar 

  197. 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).

    Article  Google Scholar 

  198. Ahn, J. K., Lee, Y. S., Jeon, C. H., Koh, E. M. & Cha, H. S. Treatment of venous thrombosis associated with Behcet’s disease: immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation. Clin. Rheumatol. 27, 201–205 (2008). This retrospective study suggests that immunosuppressive therapy is essential for the treatment of deep venous thrombosis associated with Behçet syndrome.

    Article  Google Scholar 

  199. Vautier, M. et al. Direct oral anticoagulant for venous thrombosis in Behçet’s syndrome. Autoimmun. Rev. 20, 102783 (2021). This is an observational study on the role of anticoagulation for the treatment of vascular thrombosis in Behçet syndrome.

    Article  CAS  Google Scholar 

  200. Hamzaoui, A. et al. Vena cava thrombosis in Behçet’s disease. Anadolu Kardiyol. Derg. 14, 292–293 (2014).

    Article  Google Scholar 

  201. Oblitas, C. M. et al. Chronic Budd-Chiari syndrome in Behçet’s disease successfully managed with transjugular intrahepatic portosystemic shunt: a case report and literature review. Clin. J. Gastroenterol. 13, 572–578 (2020).

    Article  Google Scholar 

  202. Shi, J. et al. Cerebral venous sinus thrombosis in Behçet’s disease: a retrospective case-control study. Clin. Rheumatol. 37, 51–57 (2018).

    Article  Google Scholar 

  203. Le Thi Huong, D. et al. Arterial lesions in Behçet’s disease. A study in 25 patients. J. Rheumatol. 22, 2103–2113 (1995).

    Google Scholar 

  204. Hamuryudan, V. et al. Pulmonary arterial aneurysms in Behçet’s syndrome: a report of 24 cases. Br. J. Rheumatol. 33, 48–51 (1994).

    Article  CAS  Google Scholar 

  205. Saba, D. et al. Arterial lesions in Behçet’s disease. Vasa 32, 75–81 (2003).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  208. Chan, E., Sangle, S. R., Coghlan, J. G. & D’Cruz, D. D. Pulmonary artery aneurysms in Behçet’s disease treated with anti-TNFα: a case series and review of the literature. Autoimmun. Rev. 15, 375–378 (2016).

    Article  Google Scholar 

  209. Yang, S. S. et al. Peripheral arterial involvement in Behcet’s disease: an analysis of the results from a Korean referral center. Rheumatol. Int. 33, 2101–2108 (2013).

    Article  Google Scholar 

  210. Koksoy, C. et al. Surgical treatment of peripheral aneurysms in patients with Behcet’s disease. Eur. J. Vasc. Endovasc. Surg. 42, 525–530 (2011).

    Article  CAS  Google Scholar 

  211. Zhong, H. et al. Efficacy and safety of tocilizumab in Behçet’s syndrome with refractory arterial lesions: a single-centre observational cohort study in China. Rheumatology 61, 2923–2930 (2022).

    Article  CAS  Google Scholar 

  212. Liu, J. et al. A pilot study of tofacitinib for refractory Behçet’s syndrome. Ann. Rheum. Dis. 79, 1517–1520 (2020).

    Article  CAS  Google Scholar 

  213. Chung, S. W. et al. Surgical experience of Behcet’s disease involving the peripheral artery. Ann. Vasc. Surg. 69, 246–253 (2020).

    Article  Google Scholar 

  214. Gaudric, J. et al. Factors influencing the recurrence of arterial involvement after surgical repair in Behçet disease. J. Vasc. Surg. 72, 1761–1769 (2020).

    Article  Google Scholar 

  215. Park, M. C., Hong, B. K., Kwon, H. M. & Hong, Y. S. Surgical outcomes and risk factors for postoperative complications in patients with Behcet’s disease. Clin. Rheumatol. 26, 1475–1480 (2007).

    Article  Google Scholar 

  216. Tüzün, H. et al. Management of aneurysms in Behçet’s syndrome: an analysis of 24 patients. Surgery 121, 150–156 (1997).

    Article  Google Scholar 

  217. Elgengehy, F. T. et al. Vasculitis damage index in Behçet’s disease. Adv. Rheumatol. 61, 33 (2021).

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank G. Bagni and M. Tesi for their assistance in drawing Figs. 1 and 2, respectively. The authors also thank F. Bello and A. Biscarini for their help in collecting images for Figs. 3 and 4.

Author information

Authors and Affiliations

  1. Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy

    Alessandra Bettiol, Domenico Prisco & Giacomo Emmi

  2. Internal Interdisciplinary Medicine Unit, Behçet Center, Careggi University Hospital, Firenze, Italy

    Alessandra Bettiol, Domenico Prisco & Giacomo Emmi

  3. Vasculitis Clinic, Marmara University, School of Medicine, Department of Internal Medicine, Division of Rheumatology, Istanbul, Turkey

    Fatma Alibaz-Oner & Haner Direskeneli

  4. Division of Rheumatology, Department of Internal Medicine, Istanbul University-Cerrahpasa, School of Medicine, Istanbul, Turkey

    Gulen Hatemi & Emire Seyahi

  5. Behçet’s Disease Research Centre, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Gulen Hatemi & Emire Seyahi

  6. Sorbonne Universités AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Département de Médecine Interne et Immunologie Clinique, F-75013, Paris, France

    David Saadoun

  7. Centre National de Références Maladies Autoimmunes Systémiques Rares, Centre National de Références Maladies Autoinflammatoires et Amylose Inflammatoire; Inflammation-Immunopathology-Biotherapy Department (DMU 3iD); INSERM 959, Groupe Hospitalier Pitie-Salpetriere, AP-HP, Paris, France

    David Saadoun

  8. Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia

    Giacomo Emmi

Authors
  1. Alessandra Bettiol
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fatma Alibaz-Oner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haner Direskeneli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gulen Hatemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Saadoun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emire Seyahi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Domenico Prisco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Giacomo Emmi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

G.E. and A.B. researched data for the article. All authors contributed substantially to discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Giacomo Emmi.

Ethics declarations

Competing interests

F.A.-O. has received honoraria, consulting or speaker fees from Pfizer, AbbVie and Amgen. H.D. has received honoraria, consulting and speaker fees from AbbVie, Pfizer, Roche, Novartis, UCB Pharma, Amgen and Celltrione. G.E. has received honoraria and speaker fees from Novartis, Roche, Sobi, AstraZeneca, Boehringer Ingelheim, Janssen, Sanofi and GSK. G.H. has received research grants, honoraria and speaker fees from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Celltrion, Janssen, Novartis, Pfizer, Silk Road Therapeutics and UCB Pharma. D.S. has received honoraria, consulting or speaker fees from Novartis, Amgen, Celltrion, Celgene, Roche Chugai, Viatris, Sanofi and AbbVie. E.S. has received honoraria, consulting or speaker fees from Novartis, Pfizer and AbbVie. A.B. and D.P. declare no competing interests.

Peer review

Peer review information

Nature Reviews Rheumatology thanks J.-L. Guan, J. van Laar and N. Ambrose for their contribution to the peer review of this work.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bettiol, A., Alibaz-Oner, F., Direskeneli, H. et al. Vascular Behçet syndrome: from pathogenesis to treatment. Nat Rev Rheumatol 19, 111–126 (2023). https://doi.org/10.1038/s41584-022-00880-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41584-022-00880-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research