Update on the treatment of Behçet’s syndrome

  • Sinem Nihal Esatoglu
  • Gulen HatemiEmail author
Part of the following topical collections:
  1. Behcet disease
  2. Behcet disease


Behçet’s syndrome (BS) is a complex disease that shows important heterogeneity in clinical findings and physiopathology. Its treatment can be problematic as BS manifestations in different organs may respond differently to the same drug. The cornerstone of therapy for inducing remission is corticosteroids whereas immunomodulatory and immunosuppressive agents such as colchicine, azathioprine, cyclosporine-A, interferon-alpha, and cyclophosphamide are used as steroid-sparing agents and to prevent further relapses. However, a considerable number of patients continue to have mucocutaneous lesions despite therapy, and some patients require more aggressive treatment for refractory major organ involvement. Tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, are increasingly used for various refractory BS manifestations despite the lack of controlled studies. In this review, we aim to focus on both the traditional and new treatment modalities for BS, with more emphasis on recent data on newer agents.


Behçet’s syndrome Treatment Management TNF inhibitors Biologic agents 



We did not receive any funding support.

Compliance with ethical standards

Conflict of interest

GH received research grants, honoraria or speaker’s fees from Abbvie, Celgene, MSD, Pfizer, and UCB Pharma. SNE declares no competing interests.

Statement of human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent



  1. 1.
    Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kotter I, Leccese P, Mahr A, Moots R, Ozguler Y, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H (2018) 2018 update of the EULAR recommendations for the management of Behcet’s syndrome. Ann Rheum Dis 77(6):808–818. CrossRefPubMedGoogle Scholar
  2. 2.
    Aktulga E, Altac M, Muftuoglu A, Ozyazgan Y, Pazarli H, Tuzun Y, Yalcin B, Yazici H, Yurdakul S (1980) A double blind study of colchicine in Behcet’s disease. Haematologica 65(3):399–402PubMedGoogle Scholar
  3. 3.
    Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Hamuryudan V, Uysal O, Senocak M, Yazici H (2001) A double-blind trial of colchicine in Behcet’s syndrome. Arthritis Rheum 44(11):2686–2692CrossRefPubMedGoogle Scholar
  4. 4.
    Davatchi F, Sadeghi Abdollahi B, Tehrani Banihashemi A, Shahram F, Nadji A, Shams H, Chams-Davatchi C (2009) Colchicine versus placebo in Behcet’s disease: randomized, double-blind, controlled crossover trial. Mod Rheumatol 19(5):542–549. CrossRefPubMedGoogle Scholar
  5. 5.
    Leccese P, Ozguler Y, Christensen R, Esatoglu SN, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kotter I, Mahr A, Moots RJ, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H, Hatemi G (2018) Management of skin, mucosa and joint involvement of Behcet’s syndrome: A systematic review for update of the EULAR recommendations for the management of Behcet’s syndrome. Semin Arthritis Rheum.
  6. 6.
    Yazici H, Pazarli H, Barnes CG, Tuzun Y, Ozyazgan Y, Silman A, Serdaroglu S, Oguz V, Yurdakul S, Lovatt GE et al (1990) A controlled trial of azathioprine in Behcet’s syndrome. N Engl J Med 322(5):281–285. CrossRefPubMedGoogle Scholar
  7. 7.
    Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A, Yurdakul S, Zwingenberger K, Yazici H (1998) Thalidomide in the treatment of the mucocutaneous lesions of the Behcet syndrome A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128(6):443–450CrossRefPubMedGoogle Scholar
  8. 8.
    Alpsoy E, Durusoy C, Yilmaz E, Ozgurel Y, Ermis O, Yazar S, Basaran E (2002) Interferon alfa-2a in the treatment of Behcet disease: a randomized placebo-controlled and double-blind study. Arch Dermatol 138(4):467–471CrossRefPubMedGoogle Scholar
  9. 9.
    Azizlerli G, Sarica R, Kose A, Ovul C, Kavala M, Kayabali M, Erkan F, Kural Z (1996) Interferon alfa-2a in the treatment of Behcet’s disease. Dermatology 192(3):239–241. CrossRefPubMedGoogle Scholar
  10. 10.
    Hamuryudan V, Moral F, Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Direskeneli H, Akoglu T, Yazici H (1994) Systemic interferon alpha 2b treatment in Behcet’s syndrome. J Rheumatol 21(6):1098–1100PubMedGoogle Scholar
  11. 11.
    Boyvat A, Sisman-Solak C, Gurler A (2000) Long-term effects of interferon alpha 2A treatment in Behcet’s disease. Dermatology 201(1):40–43. CrossRefPubMedGoogle Scholar
  12. 12.
    Alpsoy E, Yilmaz E, Basaran E (1994) Interferon therapy for Behcet’s disease. J Am Acad Dermatol 31(4):617–619CrossRefPubMedGoogle Scholar
  13. 13.
    O’Duffy JD, Calamia K, Cohen S, Goronzy JJ, Herman D, Jorizzo J, Weyand C, Matteson E (1998) Interferon-alpha treatment of Behcet’s disease. J Rheumatol 25(10):1938–1944PubMedGoogle Scholar
  14. 14.
    Georgiou S, Monastirli A, Pasmatzi E, Gartaganis S, Goerz G, Tsambaos D (1998) Efficacy and safety of systemic recombinant interferon-alpha in Behcet’s disease. J Intern Med 243(5):367–372CrossRefPubMedGoogle Scholar
  15. 15.
    Keskin Y, Seyahi E, Poyraz C, Ugurlu S, Ozyazgan Y, Yazici H (2014) Interferon alfa-associated depression in patients with Behcet’s syndrome: a prospective controlled study. Clin Exp Rheumatol 32(4 Suppl 84):S175PubMedGoogle Scholar
  16. 16.
    Melikoglu M, Fresko I, Mat C, Ozyazgan Y, Gogus F, Yurdakul S, Hamuryudan V, Yazici H (2005) Short-term trial of etanercept in Behcet’s disease: a double blind, placebo controlled study. J Rheumatol 32(1):98–105PubMedGoogle Scholar
  17. 17.
    Arida A, Fragiadaki K, Giavri E, Sfikakis PP (2011) Anti-TNF agents for Behcet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 41(1):61–70. CrossRefPubMedGoogle Scholar
  18. 18.
    Hatemi G, Melikoglu M, Tunc R, Korkmaz C, Turgut Ozturk B, Mat C, Merkel PA, Calamia KT, Liu Z, Pineda L, Stevens RM, Yazici H, Yazici Y (2015) Apremilast for Behcet’s syndrome–a phase 2, placebo-controlled study. N Engl J Med 372(16):1510–1518. CrossRefPubMedGoogle Scholar
  19. 19.
    Hatemi G, Mahr A, Takeno M, Kim DY, Melikoglu M, Cheng S, McCue S, Paris M, Wang Y, Yazici Y (2018) Apremilast for Behçet’s syndrome: a phase iii randomised, placebo-controlled, double-blind study (RELIEF). Ann Rheum Dis 77:91–92CrossRefGoogle Scholar
  20. 20.
    Vitale A, Rigante D, Lopalco G, Emmi G, Bianco MT, Galeazzi M, Iannone F, Cantarini L (2016) New therapeutic solutions for Behcet’s syndrome. Expert Opin Investig Drugs 25(7):827–840. CrossRefPubMedGoogle Scholar
  21. 21.
    Vitale A, Rigante D, Lopalco G, Selmi C, Galeazzi M, Iannone F, Cantarini L (2016) Interleukin-1 Inhibition in Behcet’s disease. Isr Med Assoc J 18(3–4):171–176PubMedGoogle Scholar
  22. 22.
    Cantarini L, Vitale A, Scalini P, Dinarello CA, Rigante D, Franceschini R, Simonini G, Borsari G, Caso F, Lucherini OM, Frediani B, Bertoldi I, Punzi L, Galeazzi M, Cimaz R (2015) Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol 34(7):1293–1301. CrossRefPubMedGoogle Scholar
  23. 23.
    Emmi G, Talarico R, Lopalco G, Cimaz R, Cantini F, Viapiana O, Olivieri I, Goldoni M, Vitale A, Silvestri E, Prisco D, Lapadula G, Galeazzi M, Iannone F, Cantarini L (2016) Efficacy and safety profile of anti-interleukin-1 treatment in Behcet’s disease: a multicenter retrospective study. Clin Rheumatol 35(5):1281–1286. CrossRefPubMedGoogle Scholar
  24. 24.
    Grayson PC, Yazici Y, Merideth M, Sen HN, Davis M, Novakovich E, Joyal E, Goldbach-Mansky R, Sibley CH (2017) Treatment of mucocutaneous manifestations in Behcet’s disease with anakinra: a pilot open-label study. Arthritis Res Ther 19(1):69. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Mirouse A, Barete S, Monfort JB, Resche-Rigon M, Bouyer AS, Comarmond C, Sene D, Domont F, Ferfar Y, Cacoub P, Saadoun D (2017) Ustekinumab for Behcet’s disease. J Autoimmun 82:41–46. CrossRefPubMedGoogle Scholar
  26. 26.
    Shapiro LS, Farrell J, Borhani Haghighi A (2012) Tocilizumab treatment for neuro-Behcet’s disease, the first report. Clin Neurol Neurosurg 114(3):297–298. CrossRefPubMedGoogle Scholar
  27. 27.
    Atienza-Mateo B, Calvo-Rio V, Beltran E, Martinez-Costa L, Valls-Pascual E, Hernandez-Garfella M, Atanes A, Cordero-Coma M, Miquel Nolla J, Carrasco-Cubero C, Loricera J, Gonzalez-Vela MC, Vegas-Revenga N, Fernandez-Diaz C, Demetrio-Pablo R, Dominguez-Casas LC, Luis Martin-Varillas J, Palmou-Fontana N, Hernandez JL, Gonzalez-Gay MA, Blanco R (2018) Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behcet’s disease: multicentre retrospective study. Rheumatology (Oxford) 57(5):856–864. CrossRefGoogle Scholar
  28. 28.
    Diamantopoulos AP, Hatemi G (2013) Lack of efficacy of tocilizumab in mucocutaneous Behcet’s syndrome: report of two cases. Rheumatology (Oxford) 52(10):1923–1924. CrossRefGoogle Scholar
  29. 29.
    Hirano T, Ohguro N, Hohki S, Hagihara K, Shima Y, Narazaki M, Ogata A, Yoshizaki K, Kumanogoh A, Kishimoto T, Tanaka T (2012) A case of Behcet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol 22(2):298–302. CrossRefPubMedGoogle Scholar
  30. 30.
    Emmi G, Silvestri E, Squatrito D, Emmi L, Cantarini L, Prisco D (2016) Tocilizumab-induced exacerbation of mucosal ulcers in a patient with multi-refractory Behcets disease. Semin Arthritis Rheum 46(1):e1–2. CrossRefPubMedGoogle Scholar
  31. 31.
    Cantarini L, Lopalco G, Vitale A, Coladonato L, Rigante D, Lucherini OM, Lapadula G, Iannone F (2015) Paradoxical mucocutaneous flare in a case of Behcet’s disease treated with tocilizumab. Clin Rheumatol 34(6):1141–1143. CrossRefPubMedGoogle Scholar
  32. 32.
    Deroux A, Chiquet C, Bouillet L (2016) Tocilizumab in severe and refractory Behcet’s disease: four cases and literature review. Semin Arthritis Rheum 45(6):733–737. CrossRefPubMedGoogle Scholar
  33. 33.
    Vitale A, Emmi G, Lopalco G, Fabiani C, Gentileschi S, Silvestri E, Gerardo DS, Iannone F, Frediani B, Galeazzi M, Lapadula G, Rigante D, Cantarini L (2017) Long-term efficacy and safety of golimumab in the treatment of multirefractory Behcet’s disease. Clin Rheumatol 36(9):2063–2069. CrossRefPubMedGoogle Scholar
  34. 34.
    Lopalco G, Emmi G, Gentileschi S, Guerriero S, Vitale A, Silvestri E, Becatti M, Cavallo I, Fabiani C, Frediani B, Iannone F, Cantarini L (2017) Certolizumab Pegol treatment in Behcet’s disease with different organ involvement: a multicenter retrospective observational study. Mod Rheumatol 27(6):1031–1035. CrossRefPubMedGoogle Scholar
  35. 35.
    Di Scala G, Bettiol A, Cojan RD, Finocchi M, Silvestri E, Emmi G (2018) Efficacy of the anti-IL 17 secukinumab in refractory Behcet’s syndrome: a preliminary study. J Autoimmun.
  36. 36.
    Henderson LK, Masson P, Craig JC, Roberts MA, Flanc RS, Strippoli GF, Webster AC (2013) Induction and maintenance treatment of proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 61(1):74–87. CrossRefPubMedGoogle Scholar
  37. 37.
    Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM, Sclerodema Lung Study III (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4(9):708–719. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Smith RM (2015) Update on the treatment of ANCA associated vasculitis. Presse Med 44(6 Pt 2):e241–249. CrossRefPubMedGoogle Scholar
  39. 39.
    Adler YD, Mansmann U, Zouboulis CC (2001) Mycophenolate mofetil is ineffective in the treatment of mucocutaneous Adamantiades-Behcet’s disease. Dermatology 203(4):322–324. CrossRefPubMedGoogle Scholar
  40. 40.
    Kose O, Simsek I, Pay S (2011) Mycophenolate sodium in the treatment of mucocutaneous Behcet’s diseases. Int J Dermatol 50(7):895–896. CrossRefPubMedGoogle Scholar
  41. 41.
    Calguneri M, Ozturk MA, Ertenli I, Kiraz S, Apras S, Ozbalkan Z (2003) Effects of interferon alpha treatment on the clinical course of refractory Behcet’s disease: an open study. Ann Rheum Dis 62(5):492–493CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Kotter I, Vonthein R, Zierhut M, Eckstein AK, Ness T, Gunaydin I, Grimbacher B, Blaschke S, Peter HH, Stubiger N (2004) Differential efficacy of human recombinant interferon-alpha2a on ocular and extraocular manifestations of Behcet disease: results of an open 4-center trial. Semin Arthritis Rheum 33(5):311–319CrossRefPubMedGoogle Scholar
  43. 43.
    Ozyazgan Y, Ucar D, Hatemi G, Yazici Y (2015) Ocular involvement of Behcet’s syndrome: a comprehensive review. Clin Rev Allergy Immunol 49(3):298–306. CrossRefPubMedGoogle Scholar
  44. 44.
    Cunningham ET Jr, Tugal-Tutkun I, Khairallah M, Okada AA, Bodaghi B, Zierhut M (2017) Behcet Uveitis. Ocul Immunol Inflamm 25(1):2–6. CrossRefPubMedGoogle Scholar
  45. 45.
    Knickelbein JE, Armbrust KR, Kim M, Sen HN, Nussenblatt RB (2017) Pharmacologic treatment of noninfectious Uveitis. Handb Exp Pharmacol 242:231–268. CrossRefPubMedGoogle Scholar
  46. 46.
    Masuda K, Nakajima A, Urayama A, Nakae K, Kogure M, Inaba G (1989) Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behcet’s disease. Lancet 1(8647):1093–1096CrossRefPubMedGoogle Scholar
  47. 47.
    Ozyazgan Y, Yurdakul S, Yazici H, Tuzun B, Iscimen A, Tuzun Y, Aktunc T, Pazarli H, Hamuryudan V, Muftuoglu A (1992) Low dose cyclosporin A versus pulsed cyclophosphamide in Behcet’s syndrome: a single masked trial. Br J Ophthalmol 76(4):241–243CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    BenEzra D, Cohen E, Chajek T, Friedman G, Pizanti S, de Courten C, Harris W (1988) Evaluation of conventional therapy versus cyclosporine A in Behcet’s syndrome. Transplant Proc 20(3 Suppl 4):136–143PubMedGoogle Scholar
  49. 49.
    Kötter I, Vonthein R, Schoenfisch B et al (2016) AB0545 interferon alpha2a versus cyclosporin A for the treatment of severe ocular behcet’s disease – a prospective, randomised, single blind, national multicenter trial (INCYTOB). Ann Rheum Dis 75:1091CrossRefGoogle Scholar
  50. 50.
    Yamada Y, Sugita S, Tanaka H, Kamoi K, Kawaguchi T, Mochizuki M (2010) Comparison of infliximab versus ciclosporin during the initial 6-month treatment period in Behcet disease. Br J Ophthalmol 94(3):284–288. CrossRefPubMedGoogle Scholar
  51. 51.
    Ozguler Y, Leccese P, Christensen R, Esatoglu SN, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kotter I, Mahr A, Moots RJ, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H, Hatemi G (2018) Management of major organ involvement of Behcet’s syndrome: a systematic review for update of the EULAR recommendations. Rheumatology (Oxford).
  52. 52.
    Markomichelakis N, Delicha E, Masselos S, Fragiadaki K, Kaklamanis P, Sfikakis PP (2011) A single infliximab infusion vs corticosteroids for acute panuveitis attacks in Behcet’s disease: a comparative 4-week study. Rheumatology (Oxford) 50(3):593–597. CrossRefGoogle Scholar
  53. 53.
    Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB (2016) Adalimumab in patients with active noninfectious Uveitis. N Engl J Med 375(10):932–943. CrossRefPubMedGoogle Scholar
  54. 54.
    Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brezin AP (2016) Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet 388(10050):1183–1192. CrossRefPubMedGoogle Scholar
  55. 55.
    Fabiani C, Sota J, Rigante D, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, Bitossi A, Orlando I, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2018) Efficacy of adalimumab and infliximab in recalcitrant retinal vasculitis inadequately responsive to other immunomodulatory therapies. Clin Rheumatol.
  56. 56.
    Fabiani C, Vitale A, Emmi G, Bitossi A, Lopalco G, Sota J, Guerriero S, Orlando I, Capozzoli M, Fusco F, Rana F, Iannone F, Frediani B, Galeazzi M, Vannozzi L, Tosi GM, Cantarini L (2018) Long-term retention rates of adalimumab and infliximab in non-infectious intermediate, posterior, and panuveitis. Clin Rheumatol.
  57. 57.
    Fabiani C, Sota J, Vitale A, Rigante D, Emmi G, Vannozzi L, Bacherini D, Lopalco G, Guerriero S, Gentileschi S, Capozzoli M, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2018) Cumulative retention rate of adalimumab in patients with Behcet’s disease-related uveitis: a four-year follow-up study. Br J Ophthalmol 102(5):637–641. CrossRefPubMedGoogle Scholar
  58. 58.
    Martin-Varillas JL, Calvo-Rio V, Beltran E, Sanchez-Burson J, Mesquida M, Adan A, Hernandez MV, Garfella MH, Pascual EV, Martinez-Costa L, Sellas-Fernandez A, Cordero-Coma M, Diaz-Llopis M, Gallego R, Salom D, Ortego N, Garcia-Serrano JL, Callejas-Rubio JL, Herreras JM, Garcia-Aparicio A, Maiz O, Blanco A, Torre I, Diaz-Valle D, Pato E, Aurrecoechea E, Caracuel MA, Gamero F, Minguez E, Carrasco-Cubero C, Olive A, Vazquez J, Ruiz-Moreno O, Manero J, Munoz-Fernandez S, Martinez MG, Rubio-Romero E, Toyos-Saenz de Miera FJ, Lopez Longo FJ, Nolla JM, Revenga M, Gonzalez-Vela C, Loricera J, Atienza-Mateo B, Demetrio-Pablo R, Hernandez JL, Gonzalez-Gay MA, Blanco R (2018) Successful optimization of adalimumab therapy in refractory uveitis due to Behcet’s disease. Ophthalmology 125(9):1444–1451. CrossRefPubMedGoogle Scholar
  59. 59.
    Vitale A, Emmi G, Lopalco G, Gentileschi S, Silvestri E, Fabiani C, Urban ML, Frediani B, Galeazzi M, Iannone F, Rigante D, Cantarini L (2017) Adalimumab effectiveness in Behcet’s disease: short and long-term data from a multicenter retrospective observational study. Clin Rheumatol 36(2):451–455. CrossRefPubMedGoogle Scholar
  60. 60.
    Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V, Androudi S (2013) Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 120(4):777–787. CrossRefPubMedGoogle Scholar
  61. 61.
    Tugal-Tutkun I, Pavesio C, De Cordoue A, Bernard-Poenaru O, Gul A (2018) Use of gevokizumab in patients with Behcet’s disease uveitis: an international, randomized, double-masked, placebo-controlled study and open-label extension study. Ocul Immunol Inflamm.
  62. 62.
    Lightman S, Taylor SR, Bunce C, Longhurst H, Lynn W, Moots R, Stanford M, Tomkins-Netzer O, Yang D, Calder VL, Haskard DO (2015) Pegylated interferon-alpha-2b reduces corticosteroid requirement in patients with Behcet’s disease with upregulation of circulating regulatory T cells and reduction of Th17. Ann Rheum Dis 74(6):1138–1144. CrossRefPubMedGoogle Scholar
  63. 63.
    Davatchi F, Shams H, Rezaipoor M, Sadeghi-Abdollahi B, Shahram F, Nadji A, Chams-Davatchi C, Akhlaghi M, Faezi T, Naderi N (2010) Rituximab in intractable ocular lesions of Behcet’s disease; randomized single-blind control study (pilot study). Int J Rheum Dis 13(3):246–252. CrossRefPubMedGoogle Scholar
  64. 64.
    Fabiani C, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, Gentileschi S, Bacherini D, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2017) Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behcet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):191–197. CrossRefPubMedGoogle Scholar
  65. 65.
    Fabiani C, Vitale A, Emmi G, Vannozzi L, Lopalco G, Guerriero S, Orlando I, Franceschini R, Bacherini D, Cimino L, Soriano A, Frediani B, Galeazzi M, Iannone F, Tosi GM, Salvarani C, Cantarini L (2017) Efficacy and safety of adalimumab in Behcet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):183–189. CrossRefPubMedGoogle Scholar
  66. 66.
    Lopalco G, Rigante D, Giannini M, Galeazzi M, Lapadula G, Iannone F, Cantarini L (2016) Safety profile of anakinra in the management of rheumatologic, metabolic and autoinflammatory disorders. Clin Exp Rheumatol 34(3):531–538PubMedGoogle Scholar
  67. 67.
    Gjoni M, Ozguler Y, Karatemiz G, Ugurlu S, Hatemi G, Melikoglu M, Fresko I, Ozyazgan Y, Seyahi E (2007) Behçet sendromunda anti IL-1 tedavisi: tek merkez deneyimi. RAED J 9(Suppl):S64. CrossRefGoogle Scholar
  68. 68.
    Papo M, Bielefeld P, Vallet H, Seve P, Wechsler B, Cacoub P, Le Hoang P, Papo T, Bodaghi B, Saadoun D (2014) Tocilizumab in severe and refractory non-infectious uveitis. Clin Exp Rheumatol 32(4 Suppl 84):S75–79PubMedGoogle Scholar
  69. 69.
    Santos-Gomez M, Calvo-Rio V, Blanco R, Beltran E, Mesquida M, Adan A, Cordero-Coma M, Garcia-Aparicio AM, Valls Pascual E, Martinez-Costa L, Hernandez MV, Hernandez Garfella M, Gonzalez-Vela MC, Pina T, Palmou-Fontana N, Loricera J, Hernandez JL, Gonzalez-Gay MA (2016) The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol 34(6 Suppl 102):S34–S40PubMedGoogle Scholar
  70. 70.
    Alokaily F, Al Saati A, Jawad A (2017) Successful treatment of Behcet’s uveitis with Tocilizumab. Saudi J Ophthalmol 31(1):42–44. CrossRefPubMedGoogle Scholar
  71. 71.
    Eser Ozturk H, Oray M, Tugal-Tutkun I (2017) Tocilizumab for the Treatment of Behcet Uveitis that Failed Interferon Alpha and Anti-Tumor Necrosis Factor-Alpha Therapy. Ocul Immunol Inflamm.
  72. 72.
    Fabiani C, Sota J, Rigante D, Vitale A, Emmi G, Vannozzi L, Franceschini R, Bacherini D, Frediani B, Galeazzi M, Tosi GM, Cantarini L (2017) Rapid and sustained efficacy of golimumab in the treatment of multirefractory uveitis associated with Behcet’s disease. Ocul Immunol Inflamm.
  73. 73.
    Ozguler Y, Hatemi G, Cetinkaya F, Tascilar K, Ugurlu S, Seyahi E, Yazici H (2018) Interferon-alpha for the management of lower extremity deep vein thrombosis in Behcet’s syndrome: a case series. Ann Rheum Dis 77:1496Google Scholar
  74. 74.
    Seyahi E, Cakmak OS, Tutar B, Arslan C, Dikici AS, Sut N, Kantarci F, Tuzun H, Melikoglu M, Yazici H (2015) Clinical and ultrasonographic evaluation of lower-extremity vein thrombosis in Behcet syndrome: an observational study. Medicine (Baltimore) 94(44):e1899. CrossRefGoogle Scholar
  75. 75.
    Alibaz-Oner F, Aldag B, Aldag M, Unal AU, Mutis A, Toptas T, Ergun T, Direskeneli H (2016) Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behcet’s disease. J Vasc Surg Venous Lymphat Disord 4(3):301–306. CrossRefPubMedGoogle Scholar
  76. 76.
    Emmi G, Vitale A, Silvestri E, Boddi M, Becatti M, Fiorillo C, Fabiani C, Frediani B, Emmi L, Di Scala G, Goldoni M, Bettiol A, Vaglio A, Cantarini L, Prisco D (2018) Adalimumab-based treatment versus disease-modifying antirheumatic drugs for venous thrombosis in Behcet’s syndrome: a retrospective study of seventy patients with vascular involvement. Arthritis Rheumatol.
  77. 77.
    Seyahi E, Caglar E, Ugurlu S, Kantarci F, Hamuryudan V, Sonsuz A, Melikoglu M, Yurdakul S, Yazici H (2015) An outcome survey of 43 patients with Budd-Chiari syndrome due to Behcet’s syndrome followed up at a single, dedicated center. Semin Arthritis Rheum 44(5):602–609. CrossRefPubMedGoogle Scholar
  78. 78.
    Desbois AC, Biard L, Addimanda O, Lambert M, Hachulla E, Launay D, Ackermann F, Perard L, Hot A, Maurier F, Mausservey C, Bernard F, Noel N, Alric L, Mirault T, Cohen F, Boussouar S, Resche-Rigon M, Cacoub P, Saadoun D (2018) 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. CrossRefPubMedGoogle Scholar
  79. 79.
    Seyahi E (2016) Behcet’s disease: how to diagnose and treat vascular involvement. Best Pract Res Clin Rheumatol 30(2):279–295. CrossRefPubMedGoogle Scholar
  80. 80.
    Saba D, Saricaoglu H, Bayram AS, Erdogan C, Dilek K, Gebitekin C, Ozkan H, Ozer ZG (2003) Arterial lesions in Behcet’s disease. Vasa 32(2):75–81. CrossRefPubMedGoogle Scholar
  81. 81.
    Hamuryudan V, Yurdakul S, Moral F, Numan F, Tuzun H, Tuzuner N, Mat C, Tuzun Y, Ozyazgan Y, Yazici H (1994) Pulmonary arterial aneurysms in Behcet’s syndrome: a report of 24 cases. Br J Rheumatol 33(1):48–51CrossRefPubMedGoogle Scholar
  82. 82.
    Seyahi E, Melikoglu M, Akman C, Hamuryudan V, Ozer H, Hatemi G, Yurdakul S, Tuzun H, Oz B, Yazici H (2012) Pulmonary artery involvement and associated lung disease in Behcet disease: a series of 47 patients. Medicine (Baltimore) 91(1):35–48. CrossRefGoogle Scholar
  83. 83.
    Tuzun H, Seyahi E, Guzelant G, Oz B, Batur S, Demirhan O, Hamuryudan V (2018) Surgical treatment of pulmonary complications in Behcet’s syndrome. Semin Thorac Cardiovasc Surg.
  84. 84.
    Yildizeli SO, Yanartas M, Tas S, Direskeneli H, Mutlu B, Ceyhan B, Yildizeli B (2018) Outcomes of patients with Behcet’s syndrome after pulmonary endarterectomy. Thorac Cardiovasc Surg 66(2):187–192. CrossRefPubMedGoogle Scholar
  85. 85.
    Esatoglu SN, Seyahi E, Ugurlu S, Gulsen F, Akman C, Cantasdemir M, Numan F, Tuzun H, Melikoglu M, Yazici H, Hamuryudan V (2016) Bronchial artery enlargement may be the cause of recurrent haemoptysis in Behcet’s syndrome patients with pulmonary artery involvement during follow-up. Clin Exp Rheumatol 34(6 Suppl 102):92–96PubMedGoogle Scholar
  86. 86.
    Uygunoglu U, Siva A (2018) Behcet’s syndrome and nervous system involvement. Curr Neurol Neurosci Rep 18(7):35. CrossRefPubMedGoogle Scholar
  87. 87.
    Zeydan B, Uygunoglu U, Saip S, Demirci ON, Seyahi E, Ugurlu S, Hamuryudan V, Siva A, Kantarci OH (2016) Infliximab is a plausible alternative for neurologic complications of Behcet disease. Neurol Neuroimmunol Neuroinflamm 3(5):e258. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Noel N, Bernard R, Wechsler B, Resche-Rigon M, Depaz R, Boutin D, Piette JC, Drier A, Dormont D, Cacoub P, Saadoun D (2014) Long-term outcome of neuro-Behcet’s disease. Arthritis Rheumatol 66(5):1306–1314. CrossRefPubMedGoogle Scholar
  89. 89.
    Yoon DL, Kim YJ, Koo BS, Kim YG, Lee CK, Yoo B (2014) Neuro-behcet’s disease in South Korea: clinical characteristics and treatment response. Int J Rheum Dis 17(4):453–458. CrossRefPubMedGoogle Scholar
  90. 90.
    Shugaiv E, Tuzun E, Mutlu M, Kiyat-Atamer A, Kurtuncu M, Akman-Demir G (2011) Mycophenolate mofetil as a novel immunosuppressant in the treatment of neuro-Behcet’s disease with parenchymal involvement: presentation of four cases. Clin Exp Rheumatol 29(4 Suppl 67):S64–67PubMedGoogle Scholar
  91. 91.
    Addimanda O, Pipitone N, Pazzola G, Salvarani C (2015) Tocilizumab for severe refractory neuro-Behcet: three cases IL-6 blockade in neuro-Behcet. Semin Arthritis Rheum 44(4):472–475. CrossRefPubMedGoogle Scholar
  92. 92.
    Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behcet treated by tocilizumab: a case report. Clin Exp Rheumatol 30(3 Suppl 72):S73–75PubMedGoogle Scholar
  93. 93.
    Tascilar K, Melikoglu M, Ugurlu S, Sut N, Caglar E, Yazici H (2014) Vascular involvement in Behcet’s syndrome: a retrospective analysis of associations and the time course. Rheumatology (Oxford) 53(11):2018–2022. CrossRefGoogle Scholar
  94. 94.
    Saadoun D, Wechsler B, Resche-Rigon M, Trad S, Le Thi Huong D, Sbai A, Dormont D, Amoura Z, Cacoub P, Piette JC (2009) Cerebral venous thrombosis in Behcet’s disease. Arthritis Rheum 61(4):518–526. CrossRefPubMedGoogle Scholar
  95. 95.
    Roriz M, Crassard I, Lechtman S, Saadoun D, Champion K, Wechsler B, Chabriat H, Sene D (2018) Can anticoagulation therapy in cerebral venous thrombosis associated with Behcet’s disease be stopped without relapse? Rev Neurol (Paris) 174(3):162–166. CrossRefGoogle Scholar
  96. 96.
    Park YE, Cheon JH (2018) Updated treatment strategies for intestinal Behcet’s disease. Korean J Intern Med 33(1):1–19. CrossRefPubMedGoogle Scholar
  97. 97.
    Hatemi I, Hatemi G, Celik AF (2018) Gastrointestinal involvement in Behcet disease. Rheum Dis Clin North Am 44(1):45–64. CrossRefPubMedGoogle Scholar
  98. 98.
    Hisamatsu T, Hayashida M (2017) Treatment and outcomes: medical and surgical treatment for intestinal Behcet’s disease. Intest Res 15(3):318–327. CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Park J, Cheon JH, Park Y, Park SJ, Kim TI, Kim WH (2018) Efficacy and tolerability of methotrexate therapy for refractory intestinal Behcet’s disease: a single center experience. Intest Res 16(2):315–318. CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Ma D, Zhang CJ, Wang RP, Wang L, Yang H (2014) Etanercept in the treatment of intestinal Behcet’s disease. Cell Biochem Biophys 69(3):735–739. CrossRefPubMedGoogle Scholar
  101. 101.
    Hatemi I, Hatemi G, Pamuk ON, Erzin Y, Celik AF (2015) TNF-alpha antagonists and thalidomide for the management of gastrointestinal Behcet’s syndrome refractory to the conventional treatment modalities: a case series and review of the literature. Clin Exp Rheumatol 33(6 Suppl 94):S129–137PubMedGoogle Scholar
  102. 102.
    Chen J, Chen S, He J (2017) A case of refractory intestinal Behcet’s disease treated with tocilizumab, a humanised anti-interleukin-6 receptor antibody. Clin Exp Rheumatol 35(6):116–118PubMedGoogle Scholar
  103. 103.
    Esatoglu SN, Hatemi G, Salihoglu A, Hatemi I, Soysal T, Celik AF (2015) A reappraisal of the association between Behcet’s disease, myelodysplastic syndrome and the presence of trisomy 8: a systematic literature review. Clin Exp Rheumatol 33(6 Suppl 94):S145–151PubMedGoogle Scholar
  104. 104.
    Soysal T, Salihoglu A, Esatoglu SN, Gulturk E, Eskazan AE, Hatemi G, Hatemi I, Ongoren Aydin S, Erzin YZ, Baslar Z, Tuzuner N, Ferhanoglu B, Celik AF (2014) Bone marrow transplantation for Behcet’s disease: a case report and systematic review of the literature. Rheumatology (Oxford) 53(6):1136–1141. CrossRefGoogle Scholar
  105. 105.
    Beales IL (1998) Gastrointestinal involvement in Behcet’s syndrome. Am J Gastroenterol 93(12):2633. CrossRefPubMedGoogle Scholar
  106. 106.
    Cantarini L, Stromillo ML, Vitale A, Lopalco G, Emmi G, Silvestri E, Federico A, Galeazzi M, Iannone F, De Stefano N (2016) Efficacy and safety of intravenous immunoglobulin treatment in refractory Behcet’s disease with different organ involvement: a case series. Isr Med Assoc J 18(3–4):238–242PubMedGoogle Scholar
  107. 107.
    Wechsler B, Sable-Fourtassou R, Bodaghi B, Huong DL, Cassoux N, Badelon I, Fain O, LeHoang P, Piette JC (2004) Infliximab in refractory uveitis due to Behcet’s disease. Clin Exp Rheumatol 22(4 Suppl 34):S14–16PubMedGoogle Scholar
  108. 108.
    Seider N, Beiran I, Scharf J, Miller B (2001) Intravenous immunoglobulin therapy for resistant ocular Behcet’s disease. Br J Ophthalmol 85(11):1287–1288CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Rewald E, Jaksic JC (1990) Behcet’s syndrome treated with high-dose intravenous IgG and low-dose aspirin. J R Soc Med 83(10):652–653CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Shutty B, Garg KJ, Swender D, Chernin L, Tcheurekdjian H, Hostoffer R (2012) Optimal use of ivig in a patient with Behcet syndrome and common variable immunodeficiency. Ann Allergy Asthma Immunol 109(1):84. CrossRefPubMedGoogle Scholar
  111. 111.
    Capittini C, Emmi G, De Amici M, Aronico N, Scudeller L, Antoniazzi E, Di Stefano M, Tinelli C (2016) Longitudinal analysis of serum cytokines in a Behcet’s patient during 9 months of IVIG infusions: how does CXCL8 bridge the immune and neuroendocrine systems? Immunol Lett 180:79–80. CrossRefPubMedGoogle Scholar

Copyright information

© Società Italiana di Medicina Interna (SIMI) 2019

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical SchoolIstanbul University-CerrahpasaIstanbulTurkey

Personalised recommendations