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A rare autoimmune bullous skin diseases characterized by painful, flaccid blisters and erosions of the oral mucosa, predominantly involving the buccal area, and with or without extension to the epidermis. Mucosa of the larynx, oesophagus, conjunctiva, nose, genitalia and anus, are less frequently affected.
ORPHA:704Classification level: Disorder
Annual incidence worldwide ranges from 1/143,000 to 1,430,000.
Onset occurs on average at 50-60 years, although childhood onset forms have been described. The disease begins with blisters (bullae) in the mouth, which are often mistaken for aphthae. The blisters are flaccid and are easily broken, often leading to painful lesions or erosions. The disease is classified into three subtypes: mucosal dominant type with blisters in the deep layers of the oral mucosa and limited cutaneous involvement, the mucocutaneous type involving both the mucosa and epidermis, and the cutaneous type with blisters in the deep layers of the epidermis only. Blistering can also affect the oesophagus, rectum, nose or the lining of the eyelids. Skin lesions appear several weeks or several months after the onset of mucosal erosions. Nikolsky's sign can appear on perilesional skin or, in some cases, even on healthy skin. Pemphigus vegetans is a clinical variant characterized by intertriginous lesions developing into vegetating plaques.
The exact etiology of the disease is unknown. Autoantibodies directed against desmosome components cause acantholysis and intraepidermal cleft. In pemphigus vulgaris, autoantibodies bind to desmogleine 1 and 3 (keratinocyte membrane molecules).
Diagnosis should be considered in the presence of bullae on chest or scalp. It can be confirmed by standard histopathological analysis and direct immunofluorescence (DIF) test. Intraepidermal blisters due to suprabasal acantholysis and IgG (mostly IgG1 and IgG4) and/or C3 complement deposits can be detected at the cell surface of keratinocytes. The disease grade is correlated with the level of circulating antibodies.
Differential diagnosis includes the full range of subepidermal diseases, mainly mucous membrane pemphigoid and epidermolysis bullosa aquisita. Oral erosive lichen planus and recurrent buccal aphtosis are characterized by a negative DIF pattern.
Management and treatment
Systemic steroid therapy, given as a 12-month course in absence of relapse, is the treatment of choice. Rituximab can be proposed at first line therapy in association with systemic steroids. Immunosuppressant drugs can be administered in case of relapse or non-responsive disease
The prognosis of pemphigus has markedly improved over the last decades with steroid therapy. Nevertheless, mortality remains an issue (5% of cases). In these cases, death occurs during the first years of disease progression, mostly as a consequence of treatment-related systemic infections and in a smaller proportion, as a consequence of superinfected lesions. Prognosis can be improved by early use of rituximab allowing a rapid tapering of steroids.
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