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Adamantiades-Behçet’s Disease

  • Petros P. SfikakisEmail author
Chapter

Abstract

Adamantiades-Behçet disease (ABD) is a distinct, chronic, relapsing systemic inflammatory disorder. ABD is not the typical autoinflammatory disease and should be viewed as a condition linking autoinflammation and autoimmunity classified among the primary systemic vasculitides. ABD exists worldwide, but it is more prevalent across the ancient trading route known as the “Silk Road”, i.e. in countries of the Mediterranean Basin, the Middle East and the Far East. The clinical spectrum is diverse, with significant differences in the prevalence of clinical manifestations between ethnic groups. Diagnosis is entirely clinical and in the absence of other explanations is based on the presence of recurring oral ulcerations (aphthous or herpetiform) at least three times in a 12-month period, plus at least any two of the following: recurrent genital aphthous ulceration or scarring, inflammation of the anterior and/or the posterior eye pole, skin lesions (erythema nodosum, pseudofolliculitis, papulopustular lesions or acneiform nodules in postadolescent patients not on corticosteroids) and a positive pathergy test (non-specific skin hyperreactivity in response to minor trauma). Intestinal, joint and central nervous system involvement and vascular thrombosis and formation of arterial aneurysms also frequently occur. Morbidity and mortality are significant; ocular involvement results in blindness if left untreated in more than 70% of those affected. Treatment should be individualized balancing the risks of therapy with the putative efficacy of a given approach. For self-limited manifestations, the aim is to control symptoms. The prompt use of immunosuppressive agents, including anti-TNF monoclonal antibodies, is mandatory for vital organ involvement.

Keywords

TNF Infliximab Uveitis Thrombosis Oral ulcer Genital ulcer Vasculitis 

References

  1. 1.
    Arida A, Vaiopoulos G, Markomichelakis N, Kaklamanis P, Sfikakis PP. Are clusters of patients with distinct clinical expression present in Behçet’s disease? Clin Exp Rheumatol. 2009;27(2 Suppl 53):S48–51.PubMedGoogle Scholar
  2. 2.
    Arida A, Fragiadaki K, Giavri E, Sfikakis PP. Anti-TNF agents for Behçet disease: analysis of published data on 369 patients. Semin Arthritis Rheum. 2011;41:61–70.CrossRefGoogle Scholar
  3. 3.
    Arida A, Sfikakis PP. Anti-cytokine biologic treatment beyond anti-TNF in Behçet’s disease. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S149–55.PubMedGoogle Scholar
  4. 4.
    Burillo-Sanz S, Montes-Cano MA, García-Lozano JR, Ortiz-Fernández L, Ortego-Centeno N, García-Hernández FJ, Espinosa G, Graña-Gil G, Sánchez-Bursón J, Rosa Juliá M, Solans R, Blanco R, Barnosi-Marín AC, Gómez De la Torre R, Fanlo P, Rodríguez-Carballeira M, Rodríguez-Rodríguez L, Camps T, Castañeda S, Alegre-Sancho JJ, Martín J, González-Escribano MF. Mutational profile of rare variants in inflammasome-related genes in Behçet disease: a next generation sequencing approach. Sci Rep. 2017;7(1):8453.CrossRefGoogle Scholar
  5. 5.
    Criteria for diagnosis of Behcet’s disease: international study group for Behcet’s disease. Lancet. 1990;335:1078–80.Google Scholar
  6. 6.
    Curnow SJ, Pryce K, Modi N, Knight B, Graham EM, Stewart JE, Fortune F, Stanford MR, Murray PI, Wallace GR. Serum cytokine profiles in Behçet’s disease: is there a role for IL-15 in pathogenesis? Immunol Lett. 2008;121(1):7–12.CrossRefGoogle Scholar
  7. 7.
    Dalghous AM, Freysdottir J. Fortune F Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet's disease (BD) and recurrent aphthous stomatitis is Th1-associated, although Th2-association is also observed in patients with BD. Scand J Rheumatol. 2006;35(6):472–5.CrossRefGoogle Scholar
  8. 8.
    Diri E, Mat C, Hamuryudan V, Yurdakul S, Hizli N, Yazici H. Papulopustular skin lesions are seen more frequently in patients with Behçet’s syndrome who have arthritis: a controlled and masked study. Ann Rheum Dis. 2001;60(11):1074–6.CrossRefGoogle Scholar
  9. 9.
    Elezoglou AV, Sfikakis PP, Vaiopoulos G, Kapsimali V, Kaklamanis PG. Serum levels of soluble TNF-alpha receptor-II (P75), circulating gamma delta T-cells and Adamantiades-Behçet’s disease activity. Adv Exp Med Biol. 2003;528:261–5.CrossRefGoogle Scholar
  10. 10.
    Elezoglou A, Kafasi N, Kaklamanis PH, Theodossiadis PG, Kapsimali V, Choremi E, Vaiopoulos G, Sfikakis PP. Infliximab treatment-induced formation of autoantibodies is common in Behçet’s disease. Clin Exp Rheumatol. 2007;25(4 Suppl 45):S65–9.PubMedGoogle Scholar
  11. 11.
    Emmi G, Silvestri E, Bella CD, Grassi A, Benagiano M, Cianchi F, Squatrito D, Cantarini L, Emmi L, Selmi C, Prisco D, D'Elios MM. Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-α in early phases of the disease. Medicine (Baltimore). 2016;95(49):e5516.CrossRefGoogle Scholar
  12. 12.
    Gül A, Inanç M, Ocal L, Aral O, Koniçe M. Familial aggregation of Behçet’s disease in Turkey. Ann Rheum Dis. 2000;59(8):622–5.CrossRefGoogle Scholar
  13. 13.
    Gul A, Ohno S. HLA-B*51 and Behçet Disease. Ocul Immunol Inflamm. 2012;20:37–43.CrossRefGoogle Scholar
  14. 14.
    Hatemi G, Fresko I, Tascilar K, Yazici H. Increased enthesopathy among Behçet’s syndrome patients with acne and arthritis: an ultrasonography study. Arthritis Rheum. 2008;58(5):1539–45.CrossRefGoogle Scholar
  15. 15.
    Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A, Houman MH, Kotter I, Olivieri I, Salvarani C, Sfikakis PP, Siva A, Stanford MR, Stubiger N, Yurdakul S, Yazici H. EULAR recommendations for the management of Behcet disease. Ann Rheum Dis. 2008;67:1656–62.CrossRefGoogle Scholar
  16. 16.
    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. Apremilast for Behçet’s syndrome–a phase 2, placebo-controlled study. N Engl J Med. 2015;372(16):1510–8.CrossRefGoogle Scholar
  17. 17.
    Kalra S, Silman A, Akman-Demir G, Bohlega S, Borhani-Haghighi A, Constantinescu CS, Houman H, Mahr A, Salvarani C, Sfikakis PP, Siva A, Al-Araji A. Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations. J Neurol. 2014;261(9):1662–76.CrossRefGoogle Scholar
  18. 18.
    Koné-Paut I, Shahram F, Darce-Bello M, Cantarini L, Cimaz R, Gattorno M, Anton J, Hofer M, Chkirate B, Bouayed K, Tugal-Tutkun I, Kuemmerle-Deschner J, Agostini H, Federici S, Arnoux A, Piedvache C. Ozen S; PEDBD group. Consensus classification criteria for paediatric Behçet’s disease from a prospective observational cohort: PEDBD. Ann Rheum Dis. 2016;75(6):958–64.CrossRefGoogle Scholar
  19. 19.
    Kural-Seyahi E, Fresko I, Seyahi N, Ozyazgan Y, Mat C, Hamuryudan V, Yurdakul S, Hl Y. The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore). 2003;82:60–76.CrossRefGoogle Scholar
  20. 20.
    Lopalco G, Lucherini OM, Lopalco A, Venerito V, Fabiani C, Frediani B, Galeazzi M, Lapadula G, Cantarini L. Iannone F Cytokine signatures in mucocutaneous and ocular Behçet’s disease. Front Immunol. 2017;8:200.  https://doi.org/10.3389/fimmu.2017.00200. eCollection 2017.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Markomichelakis NN, Theodossiadis PG, Pantelia E, Papaefthimiou S, Theodossiadis GP, Sfikakis PP. Infliximab for chronic cystoid macular edema associated with uveitis. Am J Ophthalmol. 2004;138(4):648–50.CrossRefGoogle Scholar
  22. 22.
    Markomichelakis N, Delicha E, Masselos S, Fragiadaki K, Kaklamanis P, Sfikakis PP. A single infliximab infusion vs corticosteroids for acute panuveitis attacks in Behçet’s disease: a comparative 4-week study. Rheumatology (Oxford). 2011;50(3):593–7.CrossRefGoogle Scholar
  23. 23.
    Markomichelakis N, Delicha E, Masselos S, Sfikakis PP. Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: a pilot study in 15 patients. Am J Ophthalmol. 2012;154(3):534–41.CrossRefGoogle Scholar
  24. 24.
    Markomichelakis NN, Aissopou EK, Maselos S, Tugal-Tutkun I, Sfikakis PP. Biologic treatment options for retinal neovascularization in Behçet’s disease. Ocul Immunol Inflamm. 2017;12:1–7.  https://doi.org/10.1080/09273948.2017.1332228. [Epub ahead of print].CrossRefGoogle Scholar
  25. 25.
    McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Med. 2006;3(8):e297.CrossRefGoogle Scholar
  26. 26.
    Mendoza-Pinto C, García-Carrasco M, Jiménez-Hernández M, Jiménez Hernández C, Riebeling-Navarro C, Nava Zavala A, Vera Recabarren M, Espinosa G, Jara Quezada J, Cervera R. Etiopathogenesis of Behcet’s disease. Autoimmun Rev. 2010;9:241–5.CrossRefGoogle Scholar
  27. 27.
    Mizuki N, Meguro A, Ota M, Ohno S, Shiota T, Kawagoe T, Ito N, Kera J, Okada E, Yatsu K, Song YW, Lee EB, Kitaichi N, Namba K, Horie Y, Takeno M, Sugita S, Mochizuki M, Bahram S, Ishigatsubo Y, Inoko H. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci. Nat Genet. 2010;42:703–6.CrossRefGoogle Scholar
  28. 28.
    Özdemir FT, Demiralp EE, Aydın SZ, Atagündüz P, Ergun T, Direskeneli H. Immune and inflammatory gene expressions are different in Behçet’s disease compared to those in Familial Mediterranean Fever. Eur J Rheumatol. 2016;3(4):146–52.CrossRefGoogle Scholar
  29. 29.
    Protogerou AD, Sfikakis PP, Stamatelopoulos KS, Papamichael C, Aznaouridis K, Karatzis E, Papaioannou TG, Ikonomidis I, Kaklamanis P, Mavrikakis M, Lekakis J. Interrelated modulation of endothelial function in Behcet’s disease by clinical activity and corticosteroid treatment. Arthritis Res Ther. 2007;9(5):R90.CrossRefGoogle Scholar
  30. 30.
    Remmers EF, Cosan F, Kirino Y, Ombrello MJ, Abaci N, Satorius C, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’ disease. Nat Genet. 2010;42:698–702.CrossRefGoogle Scholar
  31. 31.
    Saadoun D, Wechsler B, Desseaux K, Le Thi HD, Amoura Z, Resche-Rigon M, Cacoub P. Mortality in Behcet’s disease. Arthritis Rheum. 2010;62:2806–12.CrossRefGoogle Scholar
  32. 32.
    Sfikakis PP. The first decade of biologic TNF antagonists in clinical practice: lessons learned, unresolved issues and future directions. Curr Dir Autoimmun. 2010;11:180–210.CrossRefGoogle Scholar
  33. 33.
    Sfikakis PP, Theodossiadis PG, Katsiari CG, Kaklamanis P, Markomichelakis NN. Effect of infliximab on sight-threatening panuveitis in Behçet’s disease. Lancet. 2001;358:295–6.CrossRefGoogle Scholar
  34. 34.
    Sfikakis PP. Behçet’s disease: a new target for anti-tumour necrosis factor treatment. Ann Rheum Dis. 2002;61(Suppl 2):ii51–3.CrossRefGoogle Scholar
  35. 35.
    Sfikakis PP, Kaklamanis PH, Elezoglou A, Katsilambros N, Theodossiadis PG, Papaefthimiou S, Markomichelakis N. Infliximab for recurrent, sight-threatening ocular inflammation in Adamantiades-Behçet disease. Ann Intern Med. 2004;140(5):404–6.CrossRefGoogle Scholar
  36. 36.
    Sfikakis PP, Markomichelakis N, Alpsoy E, Assaad-Khalil S, Bodaghi B, Gul A, et al. Anti-TNF therapy in the management of Behcet’s disease: review and basis for recommendations. Rheumatology (Oxford). 2007;46:736–41.CrossRefGoogle Scholar
  37. 37.
    Sfikakis PP, Arida A, Panopoulos S, Fragiadaki K, Pentazos G, Laskari K, Tektonidou M, Markomichelakis N. Drug-free long-term remission in severe Behcet’s disease following withdrawal of successful anti-TNF treatment. Arthritis Rheumatol. 2017;  https://doi.org/10.1002/art.40235. [Epub ahead of print].CrossRefGoogle Scholar
  38. 38.
    Sugita S, Kawazoe Y, Imai A, Kawaguchi T, Horie S, Keino H, Takahashi M, Mochizuki M. Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet’s disease. J Immunol. 2013;190(11):5799–808.CrossRefGoogle Scholar
  39. 39.
    Vaiopoulos AG, Sfikakis PP, Kanakis MA, Vaiopoulos G, Kaklamanis PG. Gastrointestinal manifestations of Behçet’s disease: advances in evaluation and management. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S140–8.PubMedGoogle Scholar
  40. 40.
    Wu Z, Zhang S, Li J, Chen S, Li P, Sun F, Wen X, Zheng W, Zhang F, Li Y. Association between MEFV mutations M694V and M680I and Behçet’s disease: a meta-analysis. PLoS One. 2015;10(7):e0132704.  https://doi.org/10.1371/journal.pone.0132704. eCollection 2015.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Yazici H, Fresko I, Yurdakul S. Behcet’s syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol. 2007;3:148–55.CrossRefGoogle Scholar
  42. 42.
    Yazici H, Pazarli H, Barnes CG, Tuzun Y, Ozyazgan Y, Silman A, Serdaroglu S, Oguz V, Yurdakul S, Lovatt GE, et al. A controlled trial of azathioprine in Behcet’s syndrome. N Engl J Med. 1990;322:281–5.CrossRefGoogle Scholar
  43. 43.
    Yazici H, Seyahi E, Yurdakul S. Behcet’s syndrome is not so rare: why do we need to know? Arthritis Rheum. 2008;58:3640–3.CrossRefGoogle Scholar
  44. 44.
    Zouboulis CC, Keitel W. A historical review of early descriptions of Adamantiades- Behcet’s disease. J Invest Dermatol. 2002;119:201–5.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.First Department of Propedeutic & Internal MedicineNational & Kapodistrian University of Athens, Medical SchoolAthensGreece

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