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Original Investigation
April 28, 2021

Assessment of Diagnostic Strategy for Mucous Membrane Pemphigoid

Author Affiliations
  • 1University of Groningen, University Medical Center Groningen, Department of Dermatology, Center of Blistering Diseases, European Reference Network-Skin Member, the Netherlands
  • 2University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, the Netherlands
JAMA Dermatol. Published online April 28, 2021. doi:10.1001/jamadermatol.2021.1036
Key Points

Question  What is the optimal diagnostic strategy for mucous membrane pemphigoid?

Findings  This comparative diagnostic accuracy study of a cohort of 787 patients with suspected mucous membrane pemphigoid found high sensitivity of a mucosal direct immunofluorescence microscopic (DIF) biopsy—which is superior to serologic analysis; DIF on oral mucosa can be performed on both perilesional and normal buccal mucosa and additional DIF biopsy of another mucosal site or skin may increase the diagnostic yield.

Meaning  Performing DIF on a mucosal biopsy is recommended for diagnosing mucous membrane pemphigoid, and additional sequential biopsies from different sites, including the skin, is recommended in patients with a negative DIF result.


Importance  An accurate diagnosis of mucous membrane pemphigoid (MMP) is essential to reduce diagnostic and therapeutic delay.

Objective  To assess the diagnostic accuracy of direct immunofluorescence microscopy on mucosal biopsy specimens and immunoserology in a large cohort of patients with suspected MMP.

Design, Setting, and Participants  This retrospective cohort study was carried out in a single tertiary care center for blistering diseases between January 2002 and March 2019. Eligible participants were patients with suspected MMP and paired data on at least a mucosal biopsy specimen for direct immunofluorescence microscopy (DIF) and indirect immunofluorescence microscopy (IIF) on a human salt-split skin substrate (SSS). In addition, an optional DIF test on a skin biopsy specimen and one or more performed routine immunoserologic tests were analyzed. Data analysis was conducted from April 2019, to June 2020.

Main Outcomes and Measures  Diagnostic accuracy of DIF, IIF SSS, and immunoblot for BP180 and BP230.

Results  Of the 787 participants, 121 (15.4%) received the diagnosis of MMP (50 men [41.3%], 71 women [58.7%]; mean [SD] age at diagnosis, 60.1 [17.7] years). Sixty-seven of the patients with MMP (55.4%) had monosite involvement, of which oral site was the most frequently affected (51 [42.1%]). No significant difference was found between the sensitivity of DIF on a perilesional buccal biopsy and a normal buccal biopsy (89.3% vs 76.7%). Three patients with solitary ocular involvement showed a positive DIF of only the oral mucosa. In 6 patients with a negative mucosal DIF, a skin biopsy confirmed diagnosis of MMP. Overall, IIF SSS was less sensitive (44.6%), but highly specific (98.9%). The sensitivity of immunoblot (66.1%) was higher compared to SSS, but with lower specificity (91.3%).

Conclusions and Relevance  This comparative diagnostic accuracy study of a cohort of 787 patients found a high sensitivity of a mucosal DIF biopsy for diagnosis of MMP, and lower sensitivity of serologic analysis. A biopsy can be taken from either perilesional or normal buccal mucosa. An additional DIF biopsy of another mucosal site or of affected or unaffected skin may increase the diagnostic yield and is recommended in patients with negative DIF results and high clinical suspicion.

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