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Aktuelle Rheumatologie 2017; 42(01): 66-75
DOI: 10.1055/s-0042-118700
Übersichtsarbeit
Georg Thieme Verlag KG Stuttgart · New York

Morbus Behçet: Eine interdisziplinäre Herausforderung aus ophthalmologischer Sicht

Behçet’s Disease: The Ophthalmic Perspective on an Interdisciplinary Challenge
Uwe Pleyer
1   Augenklinik, Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Berlin
,
Ina Kötter
2   Asklepios Klinik Altona, IV. Medizin, Asklepios Rheumazentrum Hamburg, Hamburg
,
Nicole Stübiger
3   Augenklinik, Campus Benjamin Franklin, Charité, Universitätsmedizin Berlin, Berlin
› Author Affiliations
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Publication History

Publication Date:
03 April 2017 (online)

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Zusammenfassung

Der Morbus (M.) Behçet (auch Behçet Erkrankung oder Adamantiades-Behçet-Syndrom) ist ein systemisches entzündliches Krankheitsbild unbekannter Ursache. In der aktuellen Chapel-Hill-Nomenklatur für die Vaskulitiden wird der M. Behçet als Vaskulitis variabler Gefäße klassifiziert, da Arterien und Venen aller Kaliber in unterschiedlichem Ausmaß betroffen sind. Sowohl das angeborene als auch das adaptive Immunsystem sind bei der Pathogenese der Erkrankung beteiligt. Es liegen überwiegend Merkmale einer autoinflammatorischen Erkrankung vor, weswegen aktuell diskutiert wird, dass es sich bei der Erkrankung um ein Mischbild zwischen Autoimmunität und Autoinflammation handelt. Die Krankheit ist durch Exazerbationen und schubartigen Verlauf unterschiedlicher Symptome und Organmanifestationen gekennzeichnet. Sie kann durch geringe Haut- und Schleimhautläsionen in Erscheinung treten oder zu schwerwiegenden Augenbeteiligungen mit Erblindungsfolge führen. Zusätzliche Beteiligungen des Magen-Darm-Traktes, des Nervensystems und der großen Gefäße sind manchmal lebensbedrohlich. Die Behandlung des M. Behçet umfasst ein breites Spektrum von immunmodulatorischen Wirkstoffen mit zunehmender Bedeutung von Biologika. So konnte die IFN-α-Therapie für die intraokulare Entzündung eine signifikante Wirksamkeit belegen. Monoklonale Antikörper gegen Tumornekrosefaktor (TNF)-α und Interleukin-1 wurden in klinischen Studien erfolgreich geprüft und erstere inzwischen in einigen Ländern zugelassen. In dieser Übersichtsdarstellung stellen wir den aktuellen Stand des Wissens zusammen und betonen insbesondere die Rolle des Augenarztes bei der Diagnostik und Behandlung des M. Behçet.

Abstract

Behçet’s disease (BD) (also known as Adamantiades-Behçet syndrome) is a systemic inflammatory disorder of unknown etiology. In the current Chapel Hill Nomenclature for vasculitides, it is classified as variable vessel vasculitis as it affects arterial and venous vessels of all sizes. Both the innate and the adaptive immune system are involved in the pathogenesis of BD. The disorder is largely characterised by the features of an autoinflammatory disease and is therefore currently considered to be at the crossroads between autoimmune and autoinflammatory syndromes. The disease typically involves exacerbations and remissions of symptoms and organ manifestations. It may produce only mild mucocutaneous lesions, but may also lead to severe ocular involvement resulting in blindness. Additional involvement of the gastrointestinal tract, CNS and large vessels may be life-threatening. The treatment of BD includes a broad spectrum of immunomodulatory agents with increasing importance of biologic agents. IFN-α therapy has shown significant efficacy for intraocular inflammation. Monoclonal antibodies against tumour necrosis factor (TNF)-α and interleukin-1 have been successful in clinical trials, and the former has been approved in several countries. This article summarises the current state of knowledge and emphasises the role of ophthalmologists in the management of BD.

Schlüsselwörter

Autoinflammation - Morbus Behçet - Biologika - Therapie - Uveitis

Key words

autoinflammation - Behçet’s disease - biologics - treatment - uveitis
 

  • Literatur

  • 1 Jennette JC, Falk RJ, Bacon PA. et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 2 International Study Group for Behçet’s Disease. Criteria for diagnosis of Behçet’s disease. Lancet 1990; 335: 1078–1080
    PubMed
  • 3 International Team for the Revision of the International Criteria for Behçet's Disease (ITR-ICBD):. Davatchi F, Assaad-Khali S, Calamia KT. et al. The International Criteria for Behçet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatl Venerol 2014; 28: 338-347
    PubMedSearch in Google Scholar
  • 4 McGonagle D, Aziz A, Dickie LJ. et al. An integrated classification of pediatric inflammatory diseases, based on the concepts of autoinflammation and the immunological disease continuum. Pediatr Res 2009; 65: 38R-45R
    CrossrefPubMedSearch in Google Scholar
  • 5 Gül A. Pathogenesis of Behçet’s disease: autoinflammatory features and beyond. Semin Immunopathol 2015; 37: 413-418
    CrossrefPubMedSearch in Google Scholar
  • 6 Hatemi G, Silman A, Bang D. et al. EULAR recommendations for the management of Behçet disease. Ann Rheum Dis 2008; 67: 1656-1662
    CrossrefPubMedSearch in Google Scholar
  • 7 Kneifel CE, Köhler AK, Altenburg A. et al. Epidemiology of ocular involvement in Adamantiades-Behçetʼs disease. Ophthalmologe 2012; 109: 542-547
    CrossrefPubMedSearch in Google Scholar
  • 8 Deuter CM, Kötter I, Wallace GR. et al. Behçet’s disease: ocular effects and treatment. Prog Retin Eye Res 2008; 27: 111-136
    CrossrefPubMedSearch in Google Scholar
  • 9 Tugal-Tutkun I, Onal S, Altan-Yaycioglu R. et al. Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol 2004; 138: 373-380
    CrossrefPubMedSearch in Google Scholar
  • 10 Benezra D, Cohen E. Treatment and visual prognosis in Behçet’s disease. Br J Ophthalmol 1986; 70: 589-592
    CrossrefPubMedSearch in Google Scholar
  • 11 Cochereau-Massin I, Wechsler B, Le Hoang P. et al. Ocular prognosis in Behçet’s disease. J Fr Ophthalmol 1992; 15: 343-347
    PubMedSearch in Google Scholar
  • 12 Pazarli H, Ozyazgan Y, Oguz V. et al. Involvement of the fundus oculi in our Behçet patients. Bull Soc Ophthalmol 1985; 85: 317-320
    PubMedSearch in Google Scholar
  • 13 Zierhut M, Saal JG, Pleyer U. et al. Behçet’s disease: epidemiology and eye manifestations in German and Mediterranean patients. German J Ophthalmol 1995; 4: 246-251
    PubMedSearch in Google Scholar
  • 14 Mamo JG. The rate of visual loss in Behçet’s disease. Arch Ophthalmol 1970; 84: 451-452
    CrossrefPubMedSearch in Google Scholar
  • 15 Stübiger N, Pleyer U. Typical and atypical ocular manifestations of Behçet’s disease. Ophthalmologe 2012; 109: 558-562
    CrossrefPubMedSearch in Google Scholar
  • 16 Kötter I, Zierhut M, Eckstein AK. et al. Human recombinant interferon alfa-2a for the treatment of Behçet’s disease with sight threatening posterior or panuveitis. Br J Ophthalmol 2003; 87: 423-431
    CrossrefPubMedSearch in Google Scholar
  • 17 Stübiger N, Kötter I, Zierhut M. Complete regression of retinal neovascularisation after therapy with interferon alfa in Behçet’s disease. Br J Ophthalmol 2000; 84: 1437-1438
    PubMedSearch in Google Scholar
  • 18 Pleyer U, Hazirolan D, Winterhalter S. et al. Behçet’s disease – ophthalmological and general aspects part I: etiology, pathogenesis and diagnostics. Ophthalmologe 2012; 109: 1129-1141
    CrossrefPubMedSearch in Google Scholar
  • 19 Stübiger N, Besch D, Deuter CM. et al. Multifocal ERG changes in patients with ocular Behçet’s disease during therapy with interferon alpha2a. Adv Exp Med Biol 2003; 528: 529-532
    PubMedSearch in Google Scholar
  • 20 Chalam KV, Sambhav K. Optical Coherence Tomography Angiography in Retinal Diseases. J Ophthalmic Vis Res 2016; 11: 84-92
    CrossrefPubMedSearch in Google Scholar
  • 21 Hazirolan D, Pleyer U. Think global – act local: intravitreal drug delivery systems in chronic noninfectious uveitis. Ophthalmic Res 2013; 49: 59-65
    CrossrefPubMedSearch in Google Scholar
  • 22 Karacorlu M, Mudun B, Ozdemir H. et al. Intravitreal triamcinolone acetonide for the treatment of cystoid macular edema secondary to Behçet disease. Am J Ophthalmol 2004; 138: 289-291
    CrossrefPubMedSearch in Google Scholar
  • 23 Ohguro N, Yamanaka E, Otori Y. et al. Repeated intravitreal triamcinolone injections in Behçet disease that is resistant to conventional therapy: one-year results. Am J Ophthalmol 2006; 141: 218-220
    CrossrefPubMedSearch in Google Scholar
  • 24 Oh EK, Lee EK, Yu HG. Long-term results of fluocinolone acetonide intravitreal implant in Behçet intractable posterior uveitis. Can J Ophthalmol 2014; 49: 273-278
    CrossrefPubMedSearch in Google Scholar
  • 25 Coşkun E, Celemler P, Kimyon G. et al. Intravitreal dexamethasone implant for treatment of refractory behçet posterior uveitis: one-year follow-up results. Ocul Immunol Inflamm 2015; 23: 437-443
    CrossrefPubMedSearch in Google Scholar
  • 26 Mirshahi A, Namavari A, Djalilian A. et al. Intravitreal bevacizumab (Avastin) for the treatment of cystoid macular edema in Behçet disease. Ocul Immunol Inflamm 2009; 17: 59-64
    CrossrefPubMedSearch in Google Scholar
  • 27 Markomichelakis N, Delicha E, Masselos S. et al. Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: a pilot study in 15 patients. Am J Ophthalmol 2012; 154: 534-541
    CrossrefPubMedSearch in Google Scholar
  • 28 Hamam RN, Barikian AW, Antonios RS. et al. Intravitreal Adalimumab in active noninfectious uveitis: a pilot Study. Ocul Immunol Inflamm 2016; 24: 319-326
    CrossrefPubMedSearch in Google Scholar
  • 29 Toker E, Kazokoğlu H, Acar N. High dose intravenous steroid therapy for severe posterior segment uveitis in Behçet’s disease. Br J Ophthalmol 2002; 86: 521-523
    CrossrefPubMedSearch in Google Scholar
  • 30 Pleyer U, Hazirolan D, Winterhalter S. et al. Behcet’s disease – ophthalmological and general aspects: Part 2: Therapy. Ophthalmologe 2013; 110: 273-284
    CrossrefPubMedSearch in Google Scholar
  • 31 Nussenblatt RB, Palestine AG, Chan CC. et al. Effectiveness of cyclosporin therapy for Behçet’s disease. Arthritis Rheum 1985; 28: 671-679
    CrossrefPubMedSearch in Google Scholar
  • 32 Kötter I, Günaydin I, Batra M. et al. CNS involvement occurs more frequently in patients with Behçet’s disease under cyclosporin A (CSA) than under other medications – results of a retrospective analysis of 117 cases. Clin Rheumatol 2006; 25: 482-486
    CrossrefPubMedSearch in Google Scholar
  • 33 Yazici H, Pazarli H, Barnes CG. et al. A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med 1990; 322: 281-285
    CrossrefPubMedSearch in Google Scholar
  • 34 Masuda K, Nakajima A, Urayama A. et al. Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet’s disease. Lancet 1989; 1: 1093-1096
    PubMedSearch in Google Scholar
  • 35 Yurdakul S, Mat C, Tüzün Y. et al. A double-blind trial of colchicine in Behçet’s syndrome. Arthritis Rheum 2001; 44: 2686-2692
    CrossrefPubMedSearch in Google Scholar
  • 36 Adler YD, Mansmann U, Zouboulis CC. Mycophenolate mofetil is ineffective in the treatment of mucocutaneous Adamantiades-Behçet’s disease. Dermatology 2001; 203: 322-324
    CrossrefPubMedSearch in Google Scholar
  • 37 Pleyer U, Stübiger N. New pharmacotherapy options for noninfectious posterior uveitis. Expert Opin Biol Ther 2014; 14: 1783-1799
    CrossrefPubMedSearch in Google Scholar
  • 38 Arida A, Fragiadaki K, Giavri E. et al. Anti-TNF agents for Behçet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 2011; 41: 61-70
    CrossrefPubMedSearch in Google Scholar
  • 39 Vallet H, Riviere S, Sanna A. et al. Efficacy of anti-TNF alpha in severe and/or refractory Behçet’s disease: Multicenter study of 124 patients. J Autoimmun 2015; 62: 67-74
    CrossrefPubMedSearch in Google Scholar
  • 40 Okada AA, Goto H, Ohno S. et al. Multicenter study of infliximab for refractory uveoretinitis in Behçet disease. Arch Ophthalmol. 2012; 130: 592-598
    CrossrefPubMedSearch in Google Scholar
  • 41 Calvo-Río V, Blanco R, Beltrán E. et al. Anti-TNF-α therapy in patients with refractory uveitis due to Behçet’s disease: a 1-year follow-up study of 124 patients. Rheumatology (Oxford) 2014; 53: 2223-2231
    CrossrefPubMedSearch in Google Scholar
  • 42 Takeuchi M, Kezuka T, Sugita S. et al. Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behçet’s disease: a multicenter study. Ophthalmology 2014; 121: 1877-1884
    CrossrefPubMedSearch in Google Scholar
  • 43 Cobo-Ibáñez T, Muñoz-Fernández S, Hidalgo-Barrero V et al. Medium long-term treatment with infliximab and methotrexate in posterior and/or chronic uveitis refractory to conventional treatment. Med Clin (Barc). 2006: 126: 34–35
    PubMed
  • 44 Benitez-del-Castillo JM, Martinez-de-la-Casa JM, Pato-Cour E. et al. Long-term treatment of refractory posterior uveitis with anti-TNF-alpha (infliximab). Eye (Lond) 2005; 19: 841-845
    CrossrefPubMedSearch in Google Scholar
  • 45 Hazirolan D, Stübiger N, Pleyer U. Light on the Horizont: Biologicals in Behçet Uveitis. Acta Ophthalmol 2013; 91: 297-306
    CrossrefPubMedSearch in Google Scholar
  • 46 Cantarini L, Lopalco G, Caso F. et al. Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet’s disease. Autoimmun Rev 2015; 14: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 47 Kötter I, Günaydin I, Zierhut M. et al. The use of interferon alpha in Behçet disease: review of the literature. Semin Arthritis Rheum 2004; 33: 320-335
    CrossrefPubMedSearch in Google Scholar
  • 48 Krause L, Altenburg A, Pleyer U. et al. Longterm visual prognosis of patients with ocular Adamantiades-Behçet’s disease treated with interferon-alpha-2a. J Rheumatol 2008; 35: 896-903
    PubMedSearch in Google Scholar
  • 49 Gueudry J, Wechsler B, Terrada C. et al. Long-term efficacy and safety of low-dose interferon alpha2a therapy in severe uveitis associated with Behçet disease. Am J Ophthalmol 2008; 146: 837-844
    CrossrefPubMedSearch in Google Scholar
  • 50 Deuter CM, Zierhut M, Möhle A. et al. Long-term remission after cessation of interferon-α treatment in patients with severe uveitis due to Behçet’s disease. Arthritis Rheum 2010; 62: 2796-2805
    CrossrefPubMedSearch in Google Scholar
  • 51 Stübiger N, Winterhalter S, Pleyer U. et al. Janus-faced? Effects and side-effects of interferon therapy in ophthalmology. Ophthalmologe 2011; 108: 204-212
    CrossrefPubMedSearch in Google Scholar
  • 52 Aydinoglu-Candan Ö, Araz-Erşan B, Gul A. et al. Anti-interferon alpha antibodies and autoantibodies in patients with Behçet’s disease uveitis treated with recombinant human interferon alpha-2a. Graefes Arch Clin Exp Ophthalmol 2015; 253: 457-465
    CrossrefPubMedSearch in Google Scholar
  • 53 Hatemi G, Melikoglu M, Tunc R. et al. Apremilast for Behçet’s syndrome – a phase 2, placebo-controlled study. N Engl J Med 2015; 372: 1510-1518
    CrossrefPubMedSearch in Google Scholar