Evaluation of the Diagnostic Value of Oesophageal Biopsies for Direct Immunofluorescence Microscopy in Mucous Membrane Pemphigoid

Authors

  • Kaan Yilmaz Department of Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany
  • Onur Dikmen Department of Dermatology, University of Lübeck, Lübeck, Germany; Charité – Universitätsmedizin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Institute of Pathology, Berlin, Germany
  • Nina van Beek Department of Dermatology, University of Lübeck, Lübeck, Germany
  • Jens U. Marquardt Department of Medicine I, University of Lübeck, Lübeck, Germany
  • Martha M. Kirstein Department of Medicine I, University of Lübeck, Lübeck, Germany
  • Detlef Zillikens Department of Dermatology, University of Lübeck, Lübeck, Germany
  • Enno Schmidt Department of Dermatology, University of Lübeck, Lübeck, Germany; Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany

DOI:

https://doi.org/10.2340/actadv.v103.11947

Keywords:

mucous membrane pemphigoid, autoimmune bullous diseases, autoantibody, direct immunofluorescence microscopy, esophagus, oesophagus, dysphagia

Abstract

Mucous membrane pemphigoid is an autoimmune blistering disorder characterized by predominant involvement of surface-close epithelia and linear depositions of immunoreactants at the dermal-epithelial junction on direct immunofluorescence microscopy. A major diagnostic difficulty is the frequent need for multiple biopsies to facilitate the diagnosis. Although oesophageal involvement is a rare, but life-threatening manifestation, the relevance of oesophageal direct immunofluorescence sampling is unclear. This retrospective monocentric study evaluated 67 non-lesional biopsies from 11 patients with mucous membrane pemphigoid and clinical symptoms suggestive of oesophageal involvement, comprising 31 samples from the oesophagus and 36 samples from other anatomical sites. Five patients (45.5%) exhibited endoscopic findings compatible with oesophageal involvement of mucous membrane pemphigoid. No correlation was identified between the presence of oesophageal lesions and direct immunofluorescence positivity in lesions from the oesophagus (p = 1.0). Oral and cutaneous samples were significantly more frequently positive by direct immunofluorescence than were oesophageal biopsies (p < 0.0001 and p = 0.0195, respectively). Oesophageal samples yielded significantly less IgG reactivity than oral and cutaneous lesions (p < 0.0001 and p = 0.0126, respectively), and less IgA antibody response than oral lesions (p = 0.0036). In conclusion, oesophageal direct immunofluorescence samples were inferior to oral and cutaneous biopsies for the diagnosis of mucous membrane pemphigoid even when oesophageal lesions compatible with mucous membrane pemphigoid were present at the time of biopsy. 

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References

Chan LS, Ahmed AR, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, 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.

https://doi.org/10.1001/archderm.138.3.370

Du G, Patzelt S, van Beek N, Schmidt E. Mucous membrane pemphigoid. Autoimmun Rev 2022; 21: 103036.

https://doi.org/10.1016/j.autrev.2022.103036

Yilmaz K, Hammers CM, Boch K, Zillikens D, Shimanovich I, Schmidt E. Immunoglobulin M mucous membrane pemphigoid. J Dtsch Dermatol Ges 2023; 21: 285-287.

https://doi.org/10.1111/ddg.14973

Tazudeen N, Au S, Pewitt J, Tu E, Aronson IK. IgM ocular cicatricial pemphigoid: a unique insight into the immune system. Dermatol Online J 2015; 21: 13030/qt40z314gz.

https://doi.org/10.5070/D32110028946

Schmidt E, Zillikens D. Pemphigoid diseases. Lancet 2013; 381: 320-332.

https://doi.org/10.1016/S0140-6736(12)61140-4

van Beek N, Kridin K, Buhler E, Kochan AS, Stander S, Ludwig RJ, et al. Evaluation of site- and autoantigen-specific characteristics of mucous membrane pemphigoid. JAMA Dermatol 2022; 158: 84-89.

https://doi.org/10.1001/jamadermatol.2021.4773

Rashid H, Lamberts A, Borradori L, Alberti-Violetti S, Barry RJ, Caproni M, et al. 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 2021; 35: 1750-1764.

https://doi.org/10.1111/jdv.17397

Zehou O, Raynaud JJ, Le Roux-Villet C, Alexandre M, Airinei G, Pascal F, et al. Oesophageal involvement in 26 consecutive patients with mucous membrane pemphigoid. Br J Dermatol 2017; 177: 1074-1085.

https://doi.org/10.1111/bjd.15592

Benoit S, Scheurlen M, Goebeler M, Stoevesandt J. Structured diagnostic approach and risk assessment in mucous membrane pemphigoid with oesophageal involvement. Acta Derm Venereol 2018; 98: 660-666.

https://doi.org/10.2340/00015555-2938

Shimanovich I, Nitz JM, Zillikens D. Multiple and repeated sampling increases the sensitivity of direct immunofluorescence testing for the diagnosis of mucous membrane pemphigoid. J Am Acad Dermatol 2017; 77: 700-705.e3.

https://doi.org/10.1016/j.jaad.2017.05.016

Schmidt E, Rashid H, Marzano AV, Lamberts A, Di Zenzo G, Diercks GFH, et al. 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 2021; 35: 1926-1948.

https://doi.org/10.1111/jdv.17395

Egan CA, Hanif N, Taylor TB, Meyer LJ, Petersen MJ, Zone JJ. Characterization of the antibody response in oesophageal cicatricial pemphigoid. Br J Dermatol 1999; 140: 859-864.

https://doi.org/10.1046/j.1365-2133.1999.02816.x

Schattenkirchner S, Lémann M, Prost C, Caux F, Guigui B, Cadot M, et al. Localized epidermolysis bullosa acquisita of the esophagus in a patient with Crohn's disease. Am J Gastroenterol 1996; 91: 1657-1659.

Hofmann SC, Günther C, Böckle BC, Didona D, Ehrchen J, Gaskins M, et al. S2k Guideline for the diagnosis and treatment of mucous membrane pemphigoid. J Dtsch Dermatol Ges 2022; 20: 1530-1550.

https://doi.org/10.1111/ddg.14905

Schmidt E, Skrobek C, Kromminga A, Hashimoto T, Messer G, Bröcker EB, et al. Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180. Br J Dermatol 2001; 145: 778-783.

https://doi.org/10.1046/j.1365-2133.2001.04471.x

Goletz S, Probst C, Komorowski L, Schlumberger W, Fechner K, van Beek N, et al. A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid. Br J Dermatol 2019; 180: 149-156.

https://doi.org/10.1111/bjd.17202

Boch K, Hammers CM, Goletz S, Kamaguchi M, Ludwig RJ, Schneider SW, et al. Immunoglobulin M pemphigoid. J Am Acad Dermatol 2021; 85: 1486-1492.

https://doi.org/10.1016/j.jaad.2021.01.017

Fine JD, Neises GR, Katz SI. Immunofluorescence and immunoelectron microscopic studies in cicatricial pemphigoid. J Invest Dermatol 1984; 82: 39-43.

https://doi.org/10.1111/1523-1747.ep12259075

Arduino PG, Broccoletti R, Carbone M, Conrotto D, Pettigiani E, Giacometti S, et al. Describing the gingival involvement in a sample of 182 Italian predominantly oral mucous membrane pemphigoid patients: a retrospective series. Med Oral Patol Oral Cir Bucal 2017; 22: e149-e152.

https://doi.org/10.4317/medoral.21431

Alexandre M, Brette MD, Pascal F, Tsianakas P, Fraitag S, Doan S, et al. A prospective study of upper aerodigestive tract manifestations of mucous membrane pemphigoid. Medicine (Baltimore) 2006; 85: 239-252.

https://doi.org/10.1097/01.md.0000231954.08350.52

Chan LS, Yancey KB, Hammerberg C, Soong HK, Regezi JA, Johnson K, et al. Immune-mediated subepithelial blistering diseases of mucous membranes. Pure ocular cicatricial pemphigoid is a unique clinical and immunopathological entity distinct from bullous pemphigoid and other subsets identified by antigenic specificity of autoantibodies. Arch Dermatol 1993; 129: 448-455.

https://doi.org/10.1001/archderm.1993.01680250060007

Hecht E, Pitz S, Renieri G. [In-vivo confocal microscopy for the diagnosis of mucous membrane pemphigoid]. Klin Monbl Augenheilkd 2015; 232: 1077-1081.

https://doi.org/10.1055/s-0035-1546137

Cozzani E, Di Zenzo G, Calabresi V, Carrozzo M, Burlando M, Longanesi L, et al. Autoantibody profile of a cohort of 78 Italian patients with mucous membrane pemphigoid: correlation between reactivity profile and clinical involvement. Acta Derm Venereol 2016; 96: 768-773.

Dart JK. The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on. Eye (Lond) 2017; 31: 301-332.

https://doi.org/10.1038/eye.2016.284

Grootenboer-Mignot S, Descamps V, Picard-Dahan C, Nicaise-Roland P, Prost-Squarcioni C, Leroux-Villet C, et al. Place of human amniotic membrane immunoblotting in the diagnosis of autoimmune bullous dermatoses. Br J Dermatol 2010; 162: 743-750.

https://doi.org/10.1111/j.1365-2133.2009.09566.x

Maglie R, Borgi A, Caproni M, Antiga E. Indirect immunofluorescence in mucous membrane pemphigoid: which substrate should be used? Br J Dermatol 2019; 180: 1266-1267.

https://doi.org/10.1111/bjd.17694

Hayakawa T, Furumura M, Fukano H, Li X, Ishii N, Hamada T, et al. Diagnosis of oral mucous membrane pemphigoid by means of combined serologic testing. Oral Surg Oral Med Oral Pathol Oral Radiol 2014; 117: 483-496.

https://doi.org/10.1016/j.oooo.2013.12.402

Jindal A, Rao R, Bhogal BS. Advanced diagnostic techniques in autoimmune bullous diseases. Indian J Dermatol 2017; 62: 268-278.

Setterfield J, Shirlaw PJ, Kerr-Muir M, Neill S, Bhogal BS, Morgan P, et al. Mucous membrane pemphigoid: a dual circulating antibody response with IgG and IgA signifies a more severe and persistent disease. Br J Dermatol 1998; 138: 602-610.

https://doi.org/10.1046/j.1365-2133.1998.02168.x

Carey B, Joshi S, Abdelghani A, Mee J, Andiappan M, Setterfield J. The optimal oral biopsy site for diagnosis of mucous membrane pemphigoid and pemphigus vulgaris. Br J Dermatol 2020; 182: 747-753.

https://doi.org/10.1111/bjd.18032

Xu HH, Werth VP, Parisi E, Sollecito TP. Mucous membrane pemphigoid. Dent Clin North Am 2013; 57: 611-630.

https://doi.org/10.1016/j.cden.2013.07.003

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Published

2023-08-25

How to Cite

Yilmaz, K., Dikmen, O., van Beek, N., Marquardt, J. U., Kirstein, M. M., Zillikens, D., & Schmidt, E. (2023). Evaluation of the Diagnostic Value of Oesophageal Biopsies for Direct Immunofluorescence Microscopy in Mucous Membrane Pemphigoid. Acta Dermato-Venereologica, 103, adv11947. https://doi.org/10.2340/actadv.v103.11947

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Vol. 103 (2023)

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Copyright (c) 2023 Kaan Yilmaz, Onur Dikmen, Nina van Beek, Jens U. Marquardt, Martha M. Kirstein, Detlef Zillikens, Enno Schmidt

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