Mucous membrane pemphigoid (ORPHA:46486)
A rare autoimmune bullous skin disease characterized clinically by blistering of the mucous membranes followed by scarring, and immunologically characterized by IgG, IgA and/or C3 deposits on the epidermal basement membrane. The disease principally involves the oral mucosa, but may also affect ocular, pharyngolaryngeal, genital, and esophageal mucous membranes.
Epidemiology
Annual incidence was estimated to be 1/500,000 to 1/770,000 in Germany and France. A slight female predominance is reported.
Clinical description
The average age of onset is 60-70 years. The disease is rare in children. Mucous membrane pemphigoid is a chronic disease with periods of more rapid evolution. The disease manifests as fragile bullous lesions that give way to superficial erosions. The principle sites affected are the oral (80-90% of cases), ocular (50-70% of cases), pharyngolaryngeal (8-20% of cases), genital (15% of cases) and esophageal mucous membranes. Some forms affect only one mucosal membrane, in particular the buccal (erosive gingivitis) or ocular mucosae. An exclusively cutaneous form has also been observed in some cases. The ocular manifestations are initially inflammatory but then lead to retractile scarring of the conjunctive membrane, associated with corneal metaplasia resulting in vision loss.
Etiology
Whilst the etiology is unknown, several different antigens are implicated in the auto-antibody response including BPAg1, BPAg2, integrin subunits alpha-6/beta-4, laminin 5 and 6, and type VII collagen.
Diagnostic methods
Immunological studies reveal the presence of auto-antibodies against several antigens such as PB180, the alpha Laminin-5 subunit and the beta subunit of the integrin alpha-6 beta-4 complex. Histologically, the cutaneous or mucosal blisters are subepithelial, without evidence of acantholysis, and are indistinguishable from those of bullous pemphigoid. Diagnosis can be confirmed by direct (DIF) or indirect immunofluorescence analysis. Immunoelectron microscopy can differentiate bullous from cicatricial pemphigoid by the precise location of immune deposits along the basement membrane.
Differential diagnosis
Differential diagnosis includes the full range of autoimmune bullous disorders. Pemphigus vulgaris is differentiated by the DIF pattern with a labelling of the intercellular substance. Bullous pemphigoid is characterized by a predominant cutaneous involvement. Epidermolysis bullosa acquisita is a difficult to differentiate and relies on ELISA (enzyme-linked immunosorbent assay) anti collagene VII, a different localization of immune deposits along the basement membrane zone as imaged by immunoelectron microscopy, or DIF on salt separated skin. Oral erosive lichen planus and recurrent aphtosis do not show any immune deposits on DIF.
Management and treatment
Management should be multidisciplinary with close follow-up in specialized centers, in particular for the management of the ocular manifestations. The choice of therapeutic strategy (anti-inflammatory drugs, immunosuppressive therapy, intravenous immunoglobulins or local treatments) depends in the severity of the ocular disease.
Prognosis
The prognosis also revolves around the ocular manifestations, which may lead to blindness due to scarring of the conjunctive membrane and corneal metaplasia.

                            Last update: 
                            June 2020


                            - Expert reviewer(s): 
                            Pr Christophe BEDANE