Assessment of Diagnostic Strategy for Mucous Membrane Pemphigoid

Abstract

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 PARTICIPANTSThis 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. RESULTSOf 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 RELEVANCEThis 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.

Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid

“…Indirect immunofluorescence has lower sensitivity and higher specificity for diagnosis of MMP and is of more value in patients with DIFnegative MMP including multiple sites than in patients with DIFnegative MMP with only ocular involvement. 25,35,36 In ocular MMP with no extraocular involvement, there are higher chances of biopsy positivity from extraocular sites (100%) compared with a conjunctival biopsy (60%). 15,25,37 In conclusion, findings of this study suggest that likelihood of DIF positivity for confirming the tissue diagnosis of ocular MMP can be increased by taking bilateral conjunctival biopsies as early as possible in the course of the disease.…”

Clinical and Serological Characterization of Orf-Induced Immunobullous Disease

“…In 8 of the 13 cases (62%) known to be described so far, mucosal lesions were present, while predominant mucosal involvement has only been reported in 1 (Table; eTable in the Supplement). The latter patient was consequently diagnosed with orf-induced mucous membrane pemphigoid (MMP) . All patients with mucosal involvement presented with oral lesions followed by involvement of nostrils (3 of 13 [23%]) and conjunctivae (2 of 13 [15%]).…”

“…Two main differences between anti–laminin 332 reactivity in MMP and orf-induced (bullous) pemphigoid can be recognized. Mucosal involvement in anti–laminin 332 MMP, by definition, predominates over skin lesions . By contrast, in orf-induced (bullous) pemphigoid, mucosal lesions are present in about 62% of patients but do not predominate, except in 1 case of orf-induced MMP in which the target antigen remained elusive (case 13, eTable in the Supplement).…”

Association of ocular cicatricial pemphigoid with a history of malignancy and severe vision loss.

“…To the Editor: Mucous membrane pemphigoid (MMP) is a rare autoimmune blistering disorder affecting various mucous membranes and occasionally the skin [1]. Ocular monosite MMP refers to MMP involving solely the ocular surface with the potential to compromise vision and is also known as ocular cicatricial pemphigoid (OCP), [2]. In OCP, subepithelial blisters are formed by antibodies against surface antigens at the basement membrane zone of the conjunctival epithelium [3].…”

“…We determined disease severity, complications, and associated findings. Patients with OCP were placed in the OCP cohort and patients with multisite and monosite (other than ocular) MMP were placed in the MMP cohort [2]. International classification of diseases 9 and 10 codes were used to search for individual patients.…”