Ocular Mucosal Pemphigoid: Diagnosis, Clinic and Therapy

Abstract

Ocular mucosal pemphigoid is a rare, chronically progressive autoimmune disease of the ocular surface. It belongs to a group of diseases whose common clinical correlate is the disruption of cohesion at the basement membrane. Recurrent inflammation with progressive fibrosis of the conjunctiva and damage to limbal stem cells are characteristic. If the course remains uncontrolled, severe morphological and functional damage can occur, up to blindness. Therefore, the critical perception of initially subtle findings and early diagnostic are of great importance. The aim of immune modulative therapy is to control the underlying inflammation and prevent the progression of fibrosis, in order to avoid serious complications.

Conclusion Box

• Ocular MMP is a rare autoimmune disorder that is often problematic and frequently requires (systemic) treatment.

• Supervising these patients requires interdisciplinary cooperation.

• Early clinical signs of ocular MMP may manifest as fibrosis in the area of the nasal fornix and at the plica semilunaris.

• In cases of clinical suspicion, patients should be referred early to a specialised centre for (immuno)diagnostics and treatment.

• Diagnosis should be based on current guidelines, which includes several specific immunologic procedures.

• Even if immunodiagnostic findings are negative, adequate treatment measures should be initiated with clinical follow-up.

• Treatment of ocular MMP is primarily based on systemically administered immunomodulatory agents that can be titrated up or down with a stepwise titration protocol.

• Adjuvant treatment measures must take into account the disorders at the surface of the eye (keratoconjunctivitis sicca; trichiasis, etc., in the event of eyelid malalignment or other conditions).

• In some patients, fibrosis progresses even when the eye is not inflamed.

• As further research into clinical care is required, the authors expressly draw attention to the national (German) registry of ocular MMP.

Fazitbox

• Das okuläre SHP ist eine seltene Autoimmunerkrankung, die oft problematisch verläuft und häufig (systemisch!) behandelt werden muss.

• Die Betreuung dieser Patienten erfordert eine interdisziplinäre Zusammenarbeit.

• Frühe klinische Zeichen des okulären SHP können sich als Fibrose im Bereich des nasalen Fornix und an der Plica semilunaris zeigen.

• Bei klinischem Verdacht sollten die Patienten frühzeitig an ein spezialisiertes Zentrum zur (Immun-)Diagnostik und Behandlung überwiesen werden.

• Das diagnostische Vorgehen sollte sich an der aktuellen LL orientieren, das mehrere spezifische immunologische Verfahren umfasst.

• Auch bei negativen Befunden der Immundiagnostik sind adäquate Maßnahmen der Behandlung einzuleiten und klinisch zu begleiten.

• Die Therapie des okulären SHP beruht primär auf systemisch angewendeten immunmodulatorischen Substanzen, die in einem schrittweisen Ansatz eskaliert/deeskaliert werden können.

• Adjuvante Behandlungsmaßnahmen müssen die Störungen an der Augenoberfläche (Keratoconjunctivitis sicca; Trichiasis u. a. bei Lidfehlstellung u. a.) berücksichtigen.

• Bei einem Teil der Patienten schreitet die Fibrose auch bei einem ruhigen Augenbefund voran.

• Da weiterer Bedarf an klinischer Versorgungsforschung besteht, kann ausdrücklich auf die Existenz eines nationalen Registers zum okulären SHP hingewiesen werden.

Keywords

autoimmune diagnostics - ocular pemphigoid - mucosal pemphigoid - symblepharon - scarring conjunctivitis

Publication History

Received: 28 February 2025

Accepted: 23 March 2025

Article published online:
16 June 2025

• References/Literatur

• 1 Hübner F, Recke A, Zillikens D. et al. Prevalence and Age Distribution of Pemphigus and Pemphigoid Diseases in Germany. J Investig Dermatol Symp Proc 2016; 136: 2495-2498
• 2 Beek N, Weidinger A, Schneider SW. et al. Incidence of pemphigoid diseases in Northern Germany in 2016 – first data from the Schleswig‐Holstein Registry of Autoimmune Bullous Diseases. J Eur Acad Dermatol Venereol 2021; 35: 1197-1202
• 3 Jinagal J, Gupta B, Hanumanthu V. et al. Ocular Cicatricial Pemphigoid in Young Patients. Cornea 2024; 43: 1015-1021
• 4 Chan LS, Razzaque Ahmed A, 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
• 5 Ringer A, Smichowski AM, Gómez R. et al. Study Working Group of Rheumatological Ocular Diseases, Argentinian Society of Rheumatology. Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?. Int Ophthalmol 2024; 44: 99
• 6 Hofmann SC, Günther C, Böckle BC. et al. S2 k Guideline for the diagnosis and treatment of mucous membrane pemphigoid. J Dtsch Dermatol Ges 2022; 20: 1530-1550
• 7 Elder MJ, Bernauer W, Leonard J. et al. Progression of disease in ocular cicatricial pemphigoid. Br J Ophthalmol 1996; 80: 292-296
• 8 Mondino BJ, Brown SI. Ocular Cicatricial Pemphigoid. Ophthalmology 1981; 88: 95-100
• 9 Lopez SN, Cao J, Casas de Leon S. et al. Utility of direct immunofluorescence using buccal mucosal biopsies in those with suspected isolated ocular mucous membrane pemphigoid. Ophthalmology 2022; 129: 1171-1176
• 10 Di Zazzo A, Cutrupi F, De Antoniis MG. et al. Tissue Remodeling in Ocular Mucous Membrane Pemphigoid. Invest Ophthalmol Vis Sci 2023; 64: 17
• 11 Singh S, Donthineni PR, Shanbhag SS. et al. Drug induced cicatrizing conjunctivitis: A case series with review of etiopathogenesis, diagnosis and management. Ocul Surf 2022; 24: 83-92
• 12 Rübsam A, Klein J, Pleyer U. Das okuläre vernarbende Pemphigoid – aktuelle Aspekte zu Klinik und Therapie einer problematischen Erkrankung. Klin Monbl Augenheilkd 2013; 230: 796-803
• 13 Haralanova V, Meier K, Pleyer U. [Diagnostics of ocular mucous membrane pemphigoid]. Ophthalmologie 2023; 120: 484-495
• 14 Foster CS. Cicatricial pemphigoid. Trans Am Ophthalmol Soc 1986; 84: 527-663
• 15 Bocanegra-Oyola N, Pardo-Pizza D, Cifuentes-González C. et al. A. Clinical Characteristics of Ocular Mucous Membrane Pemphigoid: A Systematic Review and Meta-Analysis. Ocul Immunol Inflamm 2024; 32: 2388-2404
• 16 Dart J, Setterfield J, Groves RW. et al. Autoantibody Detection for Diagnosis in Direct Immunofluorescence-Negative Mucous Membrane Pemphigoid: Ocular and Other Sites Compared. Ophthalmology 2021; 128: 372-382
• 17 Sodha D, Patzelt S, Djalilian AR. et al. The Role of Serology in the Diagnosis of Ocular Predominant Mucous Membrane Pemphigoid and the Search for an Ocular-Specific Autoantigen. Ocul Immunol Inflamm 2024; 32: 2521-2534
• 18 Shi L, Li X, Qian H. Anti-laminin 332-type mucous membrane pemphigoid. Biomolecules 2022; 12: 1461
• 19 Carreno-Galeano JT, Dohlman TH, Kim S. et al. A Review of Ocular Graft-versus-Host Disease: Pathophysiology, Clinical Presentation and Management. Ocul Immunol Inflamm 2021; 29: 1190-1199
• 20 Chronopoulos A, Mockenhaupt M, Pleyer U. [Ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis]. Ophthalmologe 2021; 118: 519-532
• 21 Yaïci R, Roth M, Juergens L. et al. Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland. Klin Monbl Augenheilkd 2023; 240: 1077-1083
• 22 Pleyer U, Geerling G, Schrader S. et al. [If Artificial Tears Arenʼt Enough. The Importance of Inflammatory Processes in Dry Eye Disease. Practical Aspects of an Anti-Inflammatory Therapy of Dry Eye Disease]. Klin Monbl Augenheilkd 2020; 237: 655-668
• 23 Abbott KS, Palestine AG, Hauswirth SG. et al. Treatment of Ocular Surface Disease in Ocular Cicatricial Pemphigoid. Ocul Immunol Inflamm 2024; 32: 2479-2485
• 24 Nunziata S, Petrini D, DellʼAnno S. et al. Customized Scleral Lenses: An Alternative Tool for Severe Dry Eye Disease-A Case Series. J Clin Med 2024; 13: 3935
• 25 Queisi MM, Zein M, Lamba N. et al. Update on ocular cicatricial pemphigoid and emerging treatments. Surv Ophthalmol 2016; 61: 314-317
• 26 Rübsam A, Stefaniak R, Worm M. et al. Rituximab preserves vision in ocular mucous membrane pemphigoid. Expert Opin Biol Ther 2015; 15: 927-933
• 27 DʼAgostino GM, Rizzetto G, Marani A. et al. Bullous Pemphygoid and Novel Therapeutic Approaches. Biomedicines 2022; 10: 2844
• 28 Khan HM, Wirth MA, Dolman PJ. et al. Long-term outcomes of fornix reconstruction and cicatricial entropion repair in ocular mucous membrane pemphigoid and drug-related secondary pemphigoid. Can J Ophthalmol 2024; 59: e200-e205
• 29 Saini C, Chen TC, Young LH. et al. Restoration of Vision in Severe, Cicatricial, Ocular Surface Disease With the Boston Keratoprosthesis Type II. Am J Ophthalmol 2022; 243: 42-54
• 30 Ortiz-Morales G, Loya-Garcia D, Colorado-Zavala MF. et al. The evolution of the modified osteo-odonto-keratoprosthesis, its reliability, and long-term visual rehabilitation prognosis: An analytical review. Ocul Surf 2022; 24: 129-144
• 31 Ruiz-Lozano RE, Colorado-Zavala MF, Ramos-Dávila EM. et al. Ocular Mucous Membrane Pemphigoid: The Effect of Risk Factors at Presentation on Treatment Outcomes. Ophthalmology 2024; 131: 1064-1075