Skip to main content

Advertisement

SpringerLink
Log in

Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To assess the prevalence of autoimmune diseases (ADs) associated with ocular cicatricial pemphigoid (OCP) and analyze clinical, laboratory, and treatment associations between these entities.

Methods

A multicentre cross-sectional study of patients with an OCP diagnosis. The population was divided into two groups according to their association with other ADs or not. Clinical, laboratory and treatment variables were described and compared between groups. A multivariable logistic regression analysis was performed to identify variables that could suggest the association between OCP and ADs.

Results

Eighty-eight patients were recruited, with a mean age at diagnosis of 64.3 years (SD 11.9). Biopsy was performed in 86.8% of the patients. There was a median delay of 2 years from the onset of symptoms to diagnosis. Extraocular involvement was evidenced in 11.5%. The group associated with ADs included 24 patients (27.3%). The most prevalent diagnosis was Sjögren´s syndrome. Hypergammaglobulinemia was associated with ADs and OCP, adjusted for age, sex, smoking, skin and mucosal involvement, and erythrocyte sedimentation rate (OR 8.7; 95%CI 1.6–46.8; p = 0.012).

Conclusions

Due to OCP’s autoimmune nature, it could coexist with other ADs. This study observed that more than a quarter of the population presented with this association, and hypergammaglobulinemia could suggest it.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rashid H, Lamberts A, Borradori L, Alberti-Violetti S, Barry RJ, Caproni M et al (2021) European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European academy of dermatology and venereology–part I. J Eur Acad Dermatol Venereol 35(9):1750–1764. https://doi.org/10.1111/jdv.17397

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Schmidt E, Rashid H, Marzano AV, Lamberts A, Di Zenzo G, Diercks GFH et al (2021) European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European academy of dermatology and venereology–part II. J Eur Acad Dermatol Venereol 35(10):1926–1948. https://doi.org/10.1111/jdv.17395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mondino BJ, Brown SI (1981) Ocular cicatricial pemphigoid. Ophthalmology 88(2):95–100. https://doi.org/10.1016/s0161-6420(81)35069-6

    Article  CAS  PubMed  Google Scholar 

  4. Wang K, Seitzman G, Gonzales JA (2018) Ocular cicatricial pemphigoid. Curr Opin Ophthalmol 29(6):543–551. https://doi.org/10.1097/ICU.0000000000000517

    Article  PubMed  Google Scholar 

  5. Ringer A, Grossi GD, Siegrist C, Cuadranti N, Ruffino JP, Argento MC et al (2022) Ocular cicatricial pemphigoid. From a rheumatology and ophthalmology point of view. Rev Colomb Reumatol. 29:57–67. https://doi.org/10.1016/j.rcreu.2020.12.006

    Article  Google Scholar 

  6. Di Zazzo A, Yang W, Coassin M, Micera A, Antonini M, Piccinni F et al (2020) Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis. J Mol Med (Berl) 98(5):751–760. https://doi.org/10.1007/s00109-020-01907-w

    Article  PubMed  Google Scholar 

  7. Schmidt E, Zillikens D (2013) Pemphigoid diseases. Lancet 381(9863):320–332. https://doi.org/10.1016/S0140-6736(12)61140-4

    Article  PubMed  Google Scholar 

  8. Branisteanu DC, Stoleriu G, Branisteanu DE, Boda D, Branisteanu CI, Maranduca MA et al (2020) Ocular cicatricial pemphigoid (Review). Exp Ther Med 20(4):3379–3382. https://doi.org/10.3892/etm.2020.8972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ahmed M, Zein G, Khawaja F, Foster CS (2004) Ocular cicatricial pemphigoid: pathogenesis, diagnosis and treatment. Prog Retin Eye Res 23(6):579–592. https://doi.org/10.1016/j.preteyeres.2004.05.005

    Article  PubMed  Google Scholar 

  10. Georgoudis P, Sabatino F, Szentmary N (2019) Ocular mucous membrane pemphigoid: current state of pathophysiology. Diagnos Treat Ophthalmol Ther 8(1):5–17. https://doi.org/10.1007/s40123-019-0164-z

    Article  Google Scholar 

  11. Taurone S, Spoletini M, Ralli M, Gobbi P, Artico M, Imre L et al (2019) Ocular mucous membrane pemphigoid: a review. Immunol Res 67(2–3):280–289. https://doi.org/10.1007/s12026-019-09087-7

    Article  PubMed  Google Scholar 

  12. Besagar S, London AO, Jairam MP, Trief D, Dagi Glass LR (2021) Chronic early-stage ocular cicatricial pemphigoid. Ophthalmic Plast Reconstr Surg 37(6):e209–e213. https://doi.org/10.1097/IOP.0000000000002021

    Article  PubMed  Google Scholar 

  13. Chiganer EH, Albera P (2017) Penfigoide ocular cicatricial: hallazgos de biopsia conjuntival y su relación con la inflamación y cicatrización ocular. Rev Mex Oftalmol 91(3):134–141

    Google Scholar 

  14. Cervera R, Khamashta MA, Hughes GR (1990) “Overlap” syndromes. Ann Rheum Dis 49:947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rauz S, Maddison PG, Dart JKG (2005) Evaluation of mucous membrane pemphigoid with ocular involvement in young patients. Ophthalmology 112(7):1268–1274. https://doi.org/10.1016/j.ophtha.2005.01.039

    Article  PubMed  Google Scholar 

  16. Neumann R, Tauber J, Foster CS (1991) Remission and recurrence after withdrawal of therapy for ocular cicatricial pemphigoid. Ophthalmology 98(6):858–862. https://doi.org/10.1016/s0161-6420(91)32209-7

    Article  CAS  PubMed  Google Scholar 

  17. Laskaris G, Sklavounou A, Stratigos J (1982) Bullous pemphigoid, cicatricial pemphigoid, and pemphigus vulgaris. Oral Surg Oral Med Oral Pathol 54(6):656–662

    Article  CAS  PubMed  Google Scholar 

  18. Williams GP, Radford C, Nightingale P, Dart JKG, Rauz S (2011) Evaluation of early and late presentation of patients with ocular mucous membrane pemphigoid to two major tertiary referral hospitals in the United Kingdom. Eye (Lond) 25(9):1207–1218. https://doi.org/10.1038/eye.2011.175

    Article  CAS  PubMed  Google Scholar 

  19. Lee J, Seiffert-Sinha K, Attwood K, Sinha AA (2019) 2019 A Retrospective study of patient-reported data of bullous pemphigoid and mucous membrane pemphigoid from a US-based registry. Front Immunol 10:2219. https://doi.org/10.3389/fimmu.2019.02219.eCollection

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rojas M, Ramírez-santana C, Acosta-ampudia Y, Monsalve DM, Su A, Ríos-serna LJ et al (2022) New insights into the taxonomy of autoimmune diseases based on polyautoimmunity. J Autoimmun 126:102780. https://doi.org/10.1016/j.jaut.2021.102780

    Article  CAS  PubMed  Google Scholar 

  21. Rojas-villarraga A, Amaya-amaya J, Rodriguez-rodriguez A (2012) Introducing polyautoimmunity: secondary autoimmune diseases no longer exist. Autoimmune Dis 2012:254319. https://doi.org/10.1155/2012/254319

    Article  PubMed  PubMed Central  Google Scholar 

  22. Botello A, Herrán M, Salcedo V, Rodríguez Y, Anaya JM, Rojas M (2020) Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: a systematic review and meta-analysis. Clin Endocrinol (Oxf) 93(4):375–389. https://doi.org/10.1111/cen.14304

    Article  PubMed  Google Scholar 

  23. Molano-gonzález N, Rojas M, Monsalve DM, Pacheco Y, Acosta-ampudia Y, Rodríguez Y et al (2019) Cluster analysis of autoimmune rheumatic diseases based on autoantibodies. New insights for polyautoimmunity. J Autoimmun 98:24–32. https://doi.org/10.1016/j.jaut.2018.11.002

    Article  CAS  PubMed  Google Scholar 

  24. Anaya JM (2017) The autoimmune tautology. A summary of evidence. Joint Bone Spine 84(3):251–253. https://doi.org/10.1016/j.jbspin.2016.11.012

    Article  CAS  PubMed  Google Scholar 

  25. Cojocaru M, Cojocaru IM, Silosi I (2010) Multiple autoimmune syndrome. Maedica (Bucur) 5(2):132–134

    CAS  PubMed  Google Scholar 

  26. Olsen KE, Holland EJ (1998) The association between ocular cicatricial pemphigoid and rheumatoid arthritis. Cornea 17(5):504–507. https://doi.org/10.1097/00003226-199809000-00007

    Article  CAS  PubMed  Google Scholar 

  27. Anzaar F, Cabrita F, Ahmed M, Foster CS (2012) The frequency of other autoimmune disorders in patients with ocular cicatricial pemphigoid. Acta Ophthalmol 90(3):e253–e254. https://doi.org/10.1111/j.1755-3768.2011.02174.x

    Article  PubMed  Google Scholar 

  28. Nayar M, Wojnarowska F, Venning V, Taylor CJ, Oxford F (1991) Association of autoimmunity and cicatricial pemphigoid: Is there an immunogenetic basis? J Am Acad Dermatol 25(6 Pt 1):1011–1015. https://doi.org/10.1016/0190-9622(91)70299-h

    Article  CAS  PubMed  Google Scholar 

  29. Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ et al (2002) The first international consensus on mucous membrane pemphigoid. Arch Dermatol 138(3):370–379. https://doi.org/10.1001/archderm.138.3.370

    Article  PubMed  Google Scholar 

  30. Foster CS (1986) Cicatricial pemphigoid. Trans Am Ophthalmol Soc 84:527–663

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Cifuentes-González C, Amaris-Martínez S, Reyes-Guanes J, Uribe-Reina P, de-la-Torre A (2022) Ocular cicatricial pemphigoid, sjögren’s syndrome, and hashimoto’s thyroiditis as a multiple autoimmune syndrome: a case report. Eur J Ophthalmol 32(4):NP52–NP55. https://doi.org/10.1177/1120672121996637

    Article  PubMed  Google Scholar 

  32. Zakka LR, Keskin DB, Reche P, Ahmed AR (2010) Relationship between target antigens and major histocompatibility complex (MHC) class II genes in producing two pathogenic antibodies simultaneously. Clin Exp Immunol 162(2):224–236. https://doi.org/10.1111/j.1365-2249.2010.04239.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zakka LR, Reche PA, Ahmed AR (2012) The molecular basis for the presence of two autoimmune diseases occurring simultaneously-preliminary observations based on computer analysis. Autoimmunity 45(3):253–263. https://doi.org/10.3109/08916934.2011.632454

    Article  CAS  PubMed  Google Scholar 

  34. Haider N, Neuman R, Foster CS, Ahmed AR (1992) Report on the sequence of DQB1*0301 gene in ocular cicatricial pemphigoid patients. Curr Eye Res 11(12):1233–1238. https://doi.org/10.3109/02713689208999549

    Article  CAS  PubMed  Google Scholar 

  35. Zaltas MM, Ahmed R, Foster CS (1989) Association of HLA DR4 with ocular cicatricial pemphigoid. Curr Eye Res 8(2):189–193. https://doi.org/10.3109/02713688908995191

    Article  CAS  PubMed  Google Scholar 

  36. Winchester R (1989) Genetics of autoimmune diseases. Curr Opin Immunol 1:701–707

    Article  CAS  PubMed  Google Scholar 

  37. Beuvon C, Martin M, Baillou C, Roblot P, Puyade M (2021) Etiologies of polyclonal hypergammaglobulinemia: a scoping review. Eur J Intern Med 90:119–121. https://doi.org/10.1016/j.ejim.2021.05.023

    Article  PubMed  Google Scholar 

  38. Dispenzieri A, Gertz MA, Therneau TM, Kyle RA (2001) Retrospective cohort study of 148 patients with polyclonal gammopathy. Mayo Clin Proc 76(5):476–487. https://doi.org/10.4065/76.5.476

    Article  CAS  PubMed  Google Scholar 

  39. Paricaud K, Moulis G, Combis MS, Sailler L, Arlet P (2014) Causes of protidemia above 100 g/L. Eur J Intern Med 25(10):e123. https://doi.org/10.1016/j.ejim.2014.10.005

    Article  PubMed  Google Scholar 

  40. Sun DP, Chen WM, Wang L, Wang Z, Liang JH, Zhu HY et al (2021) Clinical characteristics and immunological abnormalities of Castleman disease complicated with autoimmune diseases. J Cancer Res Clin Oncol 147(7):2107–2115. https://doi.org/10.1007/s00432-020-03494-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Miyagawa S, Hashimoto T, Ohno H, Nakagawa A, Watanabe K, Nishikawa T et al (1995) Atypical pemphigus associated with monoclonal IgA gammopathy. J Am Acad Dermatol 32(2 Pt 2):352–357. https://doi.org/10.1016/0190-9622(95)90402-6

    Article  CAS  PubMed  Google Scholar 

  42. Conrady CD, Joos ZP, Patel BCK (2016) Review: the lacrimal gland and its role in dry eye. J Ophthalmol 2016:7542929. https://doi.org/10.1155/2016/7542929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Xu HH, Werth VP, Parisi E, Sollecito TP (2013) Mucous membrane pemphigoid. Dent Clin North Am 57(4):611–630. https://doi.org/10.1016/j.cden.2013.07.003

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ringer A, Smichowski AM, Pérez MJM, Gandino IJ (2023) The Latin-American rheumatology community needs to put the eye on ocular cicatricial pemphigoid. Reumatol Clin (Engl Ed). https://doi.org/10.1016/j.reuma.2023.09.006

    Article  PubMed  Google Scholar 

  45. Smichowski AM, Caputo VD, Romeo C, Rivero E, Morales NS, Casado G (2021) Ocular cicatricial pemphigoid: methotrexate as an initial treatment? Reumatol Clin (Engl Ed) 18:30–32

    Article  PubMed  Google Scholar 

Download references

Funding

The authors have not disclosed any funding. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Rheumatology Unit, National University of Rosario, Hospital Provincial del Centenario, Rosario, Santa Fe, Argentina

    Ariana Ringer, Brian Abdala & Serenela Chulibert

  2. Rheumatology and Internal Medicine Unit, Consultorios Médicos y Laboratorio de Análisis Bioquímicos e Inmunológicos (CM/LABI), Rosario, Santa Fe, Argentina

    Ariana Ringer & Carlos Siegrist

  3. Rheumatology Unit, Hospital Militar Central, 601 Cirujano Mayor Doctor Cosme Argerich, Ciudad Autónoma de Buenos Aires, Argentina

    Andrea María Smichowski

  4. Rheumatology Unit, Hospital Nacional Alejandro Posadas, El Palomar, Provincia de Buenos Aires, Argentina

    Ramiro Gómez

  5. Consultorio de Enfermedades Autoinmunes (CEA), Ciudad Autónoma de Buenos Aires, Argentina

    Belén Virasoro, Alex Kostianovsky & Sebastián Andrés Muñoz

  6. Internal Medicine Unit, Hospital General de Agudos Juan Antonio Fernández, Ciudad Autónoma de Buenos Aires, Argentina

    Liliana Martínez, Emmanuel Bertiller & Ignacio Javier Gandino

  7. Ophtalmology Unit, Hospital Provincial del Centenario, Rosario, Provincia de Santa Fe, Argentina

    German Grossi & Eduardo Rubín

  8. Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Sophia Lutgen

Authors
  1. Ariana Ringer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrea María Smichowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramiro Gómez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Belén Virasoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Liliana Martínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Emmanuel Bertiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carlos Siegrist
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Brian Abdala
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Serenela Chulibert
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. German Grossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Eduardo Rubín
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alex Kostianovsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Sebastián Andrés Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sophia Lutgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ignacio Javier Gandino
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

The Study Working Group of Rheumatological Ocular Diseases, Argentinian Society of Rheumatology.

Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ariana Ringer, Ignacio Gandino, Andrea María Smichowski, Ramiro Gómez, Belén Virasoro, Liliana Martínez, Jose Maximiliano Martinez, Emmanuel Bertiller, Carlos Siegrist, Brian Abdala, Serenela Chulibert, German Grossi, Eduardo Rubín, Alex Kostianovsky, Sebastián Andrés Muñoz and Sophia Lutgen. The first draft of the manuscript was written by Ariana Ringer, Ignacio Gandino and Andrea María Smichowski and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript

Corresponding author

Correspondence to Ariana Ringer.

Ethics declarations

Conflict of interest

The authors have not disclosed any competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ringer, A., Smichowski, A.M., Gómez, R. et al. Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?. Int Ophthalmol 44, 99 (2024). https://doi.org/10.1007/s10792-024-02939-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10792-024-02939-8

Keywords

Search

Navigation