Mucous Membrane Pemphigoid (MMP)

• Mucous membrane pemphigoid (MMP) is a rare chronic autoimmune subepithelial blistering disease.
• MMP leads to erosive lesions of mucous membranes and skin.
• MMP typically results in scarring of at least some sites of involvement.

Historical Perspective

• In 1794, Wichmann described a chronic blistering disorder with ocular involvement.
• In 1949, Civatte separated MMP from pemphigus based on histopathologic findings.
• Lever affirmed the distinction, naming the disorder "benign mucous membrane pemphigoid" which is now considered a misnomer.
• In 2002, an international consensus conference agreed upon the designation as MMP.
• MMP nomenclature includes patients with disease affecting any mucosal surface and emphasizes the mucosal predominant character.
• In 2015, a consensus statement provided definitions for disease extent, activity, outcome measures, end points, and therapeutic response.

Epidemiology

• MMP has an estimated incidence of 1 to 2 cases per million annually.
• Females are affected 1.5 to 2.0 times as often as males.
• MMP has a mean age of onset in the early to middle 60s.
• HLADQB1∗0301 allele is significantly increased in frequency in patients with oral, ocular, and generalized bullous pemphigoid.
• Amino acid residues at positions 57 and 71 to 77 of the DQB1 protein may represent a disease-susceptibility marker.

Clinical Features

Cutaneous Findings

• Patients typically describe the onset of painful, erosive, and/or blistering lesions on one or more mucosal surfaces.

• The mouth is the most frequent site of involvement; often the first (and only) site affected.

• Lesions in the mouth often involve the gingiva, buccal mucosa, and palate.

• Erosive lesions of the gingiva resulting in tissue retraction and loss are a frequent manifestation.

• Severe disease may cause adhesions between the buccal mucosa and alveolar process, around the uvula and tonsillar fossae, and between the tongue and the floor of the mouth.

• Gingival involvement can result in tissue loss and dental complications.

• Ocular lesions typically manifest as conjunctivitis that progresses insidiously to scarring and may become sight threatening.

• Early ocular disease can be quite subtle and nonspecific.

• Disease is usually bilateral, starting unilaterally and progressing to both eyes within several years.

• Chronic ocular involvement can result in scarring characterized by shortened fornices, symblepharons, and, in severe disease, ankyloblepharons.

• Conjunctival scarring can cause entropion and trichiasis that result in corneal irritation, superficial punctate keratopathy, corneal neovascularization, corneal ulceration, and/or blindness.

• Additional ocular complications include scarring of the lacrimal ducts, decreased tear secretion, and loss of mucosal goblet cells.

• The nasopharyngeal, laryngeal, esophageal, and anogenital mucosae may also be affected.

• Nasopharyngeal lesions can result in discharge, epistaxis, excessive crust formation, impaired airflow, chronic sinusitis, scarring, and tissue loss.

• Laryngeal involvement may present as hoarseness, sore throat, and/or loss of phonation.

• Esophageal involvement may result in stricture formation, dysphagia, odynophagia, weight loss, and/or aspiration.

• Involvement of the genital and/or rectal mucosae can be a source of substantial pain and morbidity.

• The skin is involved in 25% to 35% of patients.

• Most frequently affected areas are the scalp, head, neck, and upper trunk.

• Lesions typically consist of small vesicles or bullae situated on erythematous and/or urticarial bases.

• Brunsting-Perry pemphigoid was considered a variant form of MMP.

• Brunsting-Perry pemphigoid predominates in men, lacks mucous membrane involvement.

• Brunsting-Perry pemphigoid is only in selected cases associated with IgG autoantibodies against BP230 or BP180.

• Some patients with the same clinical, histologic, and immunopathologic features have autoantibodies directed against type VII collagen and blister planes beneath the lamina densa.

• A subset of such patients may have a localized form of epidermolysis bullosa acquisita.

• Rare patients with this phenotype and autoantibodies directed against laminin-332 and/or other skin autoantigens also have been described.