Download PDF
Klin Monbl Augenheilkd 2013; 230(8): 796-803
DOI: 10.1055/s-0032-1328748
Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Das okuläre vernarbende Pemphigoid – aktuelle Aspekte zu Klinik und Therapie einer problematischen Erkrankung

Ocular Cicatricial Pemphigoid – State of the Art in Clinic and Therapy for a Problematic Disease
A. Rübsam
Universitäts-Augenklinik, Charité Campus Virchow-Klinik, Berlin
,
J. P. Klein
Universitäts-Augenklinik, Charité Campus Virchow-Klinik, Berlin
,
U. Pleyer
Universitäts-Augenklinik, Charité Campus Virchow-Klinik, Berlin
› Author Affiliations
Further Information

Publication History

eingereicht 05 February 2013

akzeptiert 06 June 2013

Publication Date:
19 August 2013 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Das okuläre Schleimhautpemphigoid (OCP = ocular cicatricial pemphigoid) gehört zu einer Familie von seltenen, chronisch-fortschreitenden Autoimmunerkrankungen, die vorwiegend die Schleimhäute befallen. Es ist eine immunpathologisch heterogene Gruppe mit unterschiedlichen Phänotypen, deren gemeinsames klinisches Korrelat eine subepidermale Blasenbildung durch Störung der Adhäsion zwischen Epidermis und Dermis ist. Entscheidend ist, dass es aufgrund einer chronischen Entzündungsreaktion mit konsekutiver Fibrose zum Funktionsverlust der betroffenen Organe kommt. Die chronisch vernarbende Konjunktivitis stellt eine häufige Manifestation des Schleimhautpemphigoids dar. Die Deutung der subtilen Symptomatik und zügige Einleitung einer stadiengerechten Therapie ist dabei von höchster Wichtigkeit. Ziel ist die Vermeidung visusbedrohender Komplikationen durch eine korneale Beteiligung und u. U. lebensbedrohender Komplikationen durch ösophageale oder tracheale Strikturen im Rahmen einer extraokulären Beteiligung. Bislang liegen keine prospektiven, randomisierten Studien vor, die eine Therapieempfehlung über dem Evidenzgrad III ableiten ließen. Aufgrund der Autoimmunpathogenese und klinischer Erfahrung wird die systemische Immunsuppression, vor allem bei fortgeschrittenen Stadien, als einzige wirkungsvolle Behandlungsmöglichkeit angesehen.

Ziel dieser Übersichtsarbeit ist es, einen Leitfaden für die stadiengerechte Therapie zu bieten. Des Weiteren soll ein Ausblick auf zukünftige Alternativen, insbesondere für schwere und therapieresistente Verlaufsformen gegeben werden.

Abstract

The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages.

The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease.

Schlüsselwörter

Keratopathie - okuläres Pemphigoid - Symblephara - Therapie

Key words

keratopathy - ocular cicatricial pemphigoid - symblephara - therapy
 

  • Literatur

  • 1 Chan LS, Ahmed AR, Anhalt GJ et al. The first international consensus on mucous membrane pemphigoid: definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators. Arch Dermatol 2002; 138: 370-379
    CrossrefPubMedGoogle Scholar
  • 2 Zillikens D, Wever S, Roth A et al. Incidence of autoimmune subepidermal blistering dermatoses in a region of central Germany. Arch Dermatol 1995; 131: 957-958
    CrossrefPubMedGoogle Scholar
  • 3 Chan LS. Mucous membrane pemphigoid. Clin Dermatol 2001; 19: 703-711
    CrossrefPubMedGoogle Scholar
  • 4 Mutasim DF, Pelc NJ, Anhalt GJ. Cicatricial pemphigoid. Dermatol Clin 1993; 11: 499-510
    PubMedGoogle Scholar
  • 5 Cheng YS, Rees TD, Wright JM et al. Childhood oral pemphigoid: a case report and review of the literature. J Oral Pathol Med 2001; 30: 372-377
    CrossrefPubMedGoogle Scholar
  • 6 Suelves AM, Zhao TZ, Siddique SS et al. Profile of local interleukin expression in a cohort of ocular cicatricial pemphigoid patients. Invest Ophthalmol Vis Sci 2012; 53: 8112-8117
    CrossrefPubMedGoogle Scholar
  • 7 Chan LS. Ocular and oral mucous membrane pemphigoid (cicatricial pemphigoid). Clin Dermatol 2012; 30: 34-37
    CrossrefPubMedGoogle Scholar
  • 8 Bedane C, McMillan JR, Balding SD et al. Bullous pemphigoid and cicatricial pemphigoid autoantibodies react with ultrastructurally separable epitopes on the BP180 ectodomain: evidence that BP180 spans the lamina lucida. J Invest Dermatol 1997; 108: 901-907
    CrossrefPubMedGoogle Scholar
  • 9 Chan LS, Majmudar AA, Tran HH et al. Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid. J Invest Dermatol 1997; 108: 848-853
    CrossrefPubMedGoogle Scholar
  • 10 Ghohestani RF, Nicolas JF, Rousselle P et al. Identification of a 168-kDa mucosal antigen in a subset of patients with cicatricial pemphigoid. J Invest Dermatol 1996; 107: 136-139
    CrossrefPubMedGoogle Scholar
  • 11 Pleyer U, Bruckner-Tuderman L, Friedmann A et al. The immunology of bullous oculo-muco-cutaneous disorders. Immunol Today 1996; 17: 111-113
    CrossrefPubMedGoogle Scholar
  • 12 Fleming TE, Korman NJ. Cicatricial pemphigoid. J Am Acad Dermatol 2000; 43: 571-591 quiz 591–594
    CrossrefPubMedGoogle Scholar
  • 13 Pleyer U, Muller B. [Ocular cicatricial pemphigoid]. Ophthalmologe 2001; 98: 584-597 quiz 598
    CrossrefPubMedGoogle Scholar
  • 14 Mondino BJ, Brown SI. Ocular cicatricial pemphigoid. Ophthalmology 1981; 88: 95-100
    CrossrefPubMedGoogle Scholar
  • 15 Tauber J, Jabbur N, Foster CS. Improved detection of disease progression in ocular cicatricial pemphigoid. Cornea 1992; 11: 446-451
    CrossrefPubMedGoogle Scholar
  • 16 Patten JT, Cavanagh HD, Allansmith MR. Induced ocular pseudopemphigoid. Am J Ophthalmol 1976; 82: 272-276
    PubMedGoogle Scholar
  • 17 Messmer EM, Valet VM, Kampik A. Differences in basement membrane zone components of normal conjunctiva, conjunctiva in glaucoma and normal skin. Acta Ophthalmol 2012; 90: e476-e481
    CrossrefPubMedGoogle Scholar
  • 18 Baun O, Heegaard S, Kessing SV et al. The morphology of conjunctiva after long-term topical anti-glaucoma treatment. A quantitative analysis. Acta Ophthalmol Scand 1995; 73: 242-245
    PubMedGoogle Scholar
  • 19 Gibran SK. Unilateral drug-induced ocular pseudopemphigoid. Eye (Lond) 2004; 18: 1270
    PubMedGoogle Scholar
  • 20 Tauber J, Melamed S, Foster CS. Glaucoma in patients with ocular cicatricial pemphigoid. Ophthalmology 1989; 96: 33-37
    PubMedGoogle Scholar
  • 21 Meyer-ter-Vehn T, Schmidt E, Zillikens D et al. [Mucous membrane pemphigoid with ocular involvement. Part II: therapy]. Ophthalmologe 2008; 105: 405-419
    CrossrefPubMedGoogle Scholar
  • 22 Letko E, Bhol K, Foster SC et al. Influence of intravenous immunoglobulin therapy on serum levels of anti-beta 4 antibodies in ocular cicatricial pemphigoid. A correlation with disease activity. A preliminary study. Curr Eye Res 2000; 21: 646-654
    CrossrefPubMedGoogle Scholar
  • 23 Hoang-Xuan T, Robin H, Demers PE et al. Pure ocular cicatricial pemphigoid. A distinct immunopathologic subset of cicatricial pemphigoid. Ophthalmology 1999; 106: 355-361
    CrossrefPubMedGoogle Scholar
  • 24 van Beek N, Rentzsch K, Probst C et al. Serological diagnosis of autoimmune bullous skin diseases: prospective comparison of the BIOCHIP mosaic-based indirect immunofluorescence technique with the conventional multi-step single test strategy. Orphanet J Rare Dis 2012; 7: 49
    CrossrefPubMedGoogle Scholar
  • 25 Setterfield J, Shirlaw PJ, Bhogal BS et al. Cicatricial pemphigoid: serial titres of circulating IgG and IgA antibasement membrane antibodies correlate with disease activity. Br J Dermatol 1999; 140: 645-650
    CrossrefPubMedGoogle Scholar
  • 26 Saw VPJ, Dart JKG. Management of ocular mucous Membrane Pemphigoid. In: Reinhard T, Larkin F, eds. Cornea and External Eye Disease. Heidelberg: Springer Verlag; 2008
    CrossrefGoogle Scholar
  • 27 Lee YJ, Kim SW, Seo KY. Application for tacrolimus ointment in treating refractory inflammatory ocular surface diseases. Am J Ophthalmol 2013; 155: 804-813
    CrossrefPubMedGoogle Scholar
  • 28 Letko E, Ahmed AR, Foster CS. Treatment of ocular cicatricial pemphigoid with tacrolimus (FK 506). Graefes Arch Clin Exp Ophthalmol 2001; 239: 441-444
    CrossrefPubMedGoogle Scholar
  • 29 Radford CF, Rauz S, Williams GP et al. Incidence, presenting features, and diagnosis of cicatrising conjunctivitis in the United Kingdom. Eye (Lond) 2012; 26: 1199-1208
    CrossrefPubMedGoogle Scholar
  • 30 Elder MJ, Bernauer W, Leonard J et al. Progression of disease in ocular cicatricial pemphigoid. Br J Ophthalmol 1996; 80: 292-296
    CrossrefPubMedGoogle Scholar
  • 31 Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc 1986; 84: 527-663
    PubMedGoogle Scholar
  • 32 Fern AI, Jay JL, Young H et al. Dapsone therapy for the acute inflammatory phase of ocular pemphigoid. Br J Ophthalmol 1992; 76: 332-335
    CrossrefPubMedGoogle Scholar
  • 33 Elder MJ, Leonard J, Dart JK. Sulphapyridine–a new agent for the treatment of ocular cicatricial pemphigoid. Br J Ophthalmol 1996; 80: 549-552
    CrossrefPubMedGoogle Scholar
  • 34 Sacher C, Hunzelmann N. Cicatricial pemphigoid (mucous membrane pemphigoid): current and emerging therapeutic approaches. Am J Clin Dermatol 2005; 6: 93-103
    CrossrefPubMedGoogle Scholar
  • 35 Tauber J, Sainz de la Maza M, Foster CS. Systemic chemotherapy for ocular cicatricial pemphigoid. Cornea 1991; 10: 185-195
    CrossrefPubMedGoogle Scholar
  • 36 McCluskey P, Chang JH, Singh R et al. Methotrexate therapy for ocular cicatricial pemphigoid. Ophthalmology 2004; 111: 796-801
    CrossrefPubMedGoogle Scholar
  • 37 Chang JH, McCluskey PJ. Ocular cicatricial pemphigoid: manifestations and management. Curr Allergy Asthma Rep 2005; 5: 333-338
    CrossrefPubMedGoogle Scholar
  • 38 Pleyer U. [Editorial on “Clinical findings with mycophenolate mofetil in immunosuppressive therapy of ocular pemphigoid” by Zurdel J, Aboalchamat B, Zierhut M et al. in Klin Monatsbl Augenheilkd 2001; 218:222–228]. Klin Monatsbl Augenheilkd 2001; 218: 201-203
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Nottage JM, Hammersmith KM, Murchison AP et al. Treatment of mucous membrane pemphigoid with mycophenolate mofetil. Cornea 2013; 32: 810-815
    CrossrefPubMedGoogle Scholar
  • 40 Pleyer U, Ruokonen P, Schmidt N et al. [Mycophenol acid in ocular automimmune disorders–can we optimise this therapy?]. Klin Monatsbl Augenheilkd 2008; 225: 66-69
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Mondino BJ, Brown SI. Immunosuppressive therapy in ocular cicatricial pemphigoid. Am J Ophthalmol 1983; 96: 453-459
    PubMedGoogle Scholar
  • 42 Saw VP, Dart RJ, Galatowicz G et al. Tumor necrosis factor-alpha in ocular mucous membrane pemphigoid and its effect on conjunctival fibroblasts. Invest Ophthalmol Vis Sci 2009; 50: 5310-5317
    CrossrefPubMedGoogle Scholar
  • 43 Heffernan MP, Bentley DD. Successful treatment of mucous membrane pemphigoid with infliximab. Arch Dermatol 2006; 142: 1268-1270
    CrossrefPubMedGoogle Scholar
  • 44 Canizares MJ, Smith DI, Conners MS et al. Successful treatment of mucous membrane pemphigoid with etanercept in 3 patients. Arch Dermatol 2006; 142: 1457-1461
    CrossrefPubMedGoogle Scholar
  • 45 John H, Whallett A, Quinlan M. Successful biologic treatment of ocular mucous membrane pemphigoid with anti-TNF-alpha. Eye (Lond) 2007; 21: 1434-1435
    CrossrefPubMedGoogle Scholar
  • 46 Papaliodis GN, Chu D, Foster CS. Treatment of ocular inflammatory disorders with daclizumab. Ophthalmology 2003; 110: 786-789
    CrossrefPubMedGoogle Scholar
  • 47 Rubbert-Roth A, Tak PP, Zerbini C et al. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR). Rheumatology (Oxford) 2010; 49: 1683-1693
    CrossrefPubMedGoogle Scholar
  • 48 Le Roux-Villet C, Prost-Squarcioni C, Alexandre M et al. Rituximab for patients with refractory mucous membrane pemphigoid. Arch Dermatol 2011; 147: 843-849
    CrossrefPubMedGoogle Scholar
  • 49 Foster CS, Ahmed AR. Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid: a preliminary study. Ophthalmology 1999; 106: 2136-2143
    CrossrefPubMedGoogle Scholar
  • 50 Letko E, Miserocchi E, Daoud YJ et al. A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies. Clin Immunol 2004; 111: 303-310
    CrossrefPubMedGoogle Scholar
  • 51 Sami N, Letko E, Androudi S et al. Intravenous immunoglobulin therapy in patients with ocular-cicatricial pemphigoid: a long-term follow-up. Ophthalmology 2004; 111: 1380-1382
    CrossrefPubMedGoogle Scholar
  • 52 Krenzky AMVF, Bennett WW. Immunosuppressants, Tolerogens and Immunostimulants. In: Brunton L, Lazo J, Parker KL, eds. Goodman & Gilmanʼs The pharmacological Basis of Therapeutics. New York: The McGraw-Hill Companies; 2005: 1405-1432
    Google Scholar
  • 53 Messmer EM, Hintschich CR, Partscht K et al. [Ocular cicatricial pemphigoid. Retrospective analysis of risk factors and complications]. Ophthalmologe 2000; 97: 113-120
    CrossrefPubMedGoogle Scholar
  • 54 Megahed M. Histopathology of blistering Diseases: With clinical, Electron microscopic, immunological and Molecular biological Correlations. Heidelberg: Springer-Verlag; 2004: 405
    CrossrefGoogle Scholar