Pemphigus occurs in three major types, all characterized by blistering and ulceration caused by the action of autoantibodies against adhesion molecules that anchor keratinocytes to one another and to the underlying basement membrane. The target of the IgG autoantibodies is a group of transmembrane proteins called desmogleins. A review by Nousari and Anhalt emphasizes the differences in pathophysiology, clinical features, optimal therapy and prognosis between pemphigus vulgaris, paraneoplastic pemphigus and pemphigus foliaceus.
The most common form of pemphigus—pemphigus vulgaris—usually begins in adults between 30 and 50 years of age as painful oral ulcerations on the posterior buccal mucosa and gums. The disease is progressive and chronic but remains limited to mucous membranes in many patients. Skin lesions in pemphigus vulgaris are fragile vesicobullous outbreaks mainly on the head and neck. The trunk and flexures may become involved as the condition progresses. Certain populations show genetic predisposition to pemphigus vulgaris. The disease is now believed to result from the action of antidesmoglein 3, IgG autoantibodies that bind to stratified squamous epithelium. Immunofluorescent testing for these autoantibodies indicates that patients who progress to skin involvement also produce antibodies against desmoglein 1. Treatment is aimed at reducing the synthesis of these autoantibodies. Combination systemic therapy with corticosteroids and immunosuppressive agents is usually required, although the iatrogenic effects of these potent medications may contribute to morbidity. Prednisone alone in dosages up to 1 mg per kg may control some cases. If the dosage cannot be tapered to 5 to 10 mg on alternate days within a year of treatment, azathioprine or cyclophosphamide must be added. In fulminant cases, plasmapheresis has been used to remove autoantibodies from the circulation. The mortality rate in patients with pemphigus vulgaris is up to 10 percent, with sepsis being the most common cause of death.
In pemphigus foliaceus, blisters occur only on the skin, and only antibodies to desmoglein 1 are found. The condition may be drug induced, particularly by penicillamine. A geographically limited form of pemphigus foliaceus also occurs in clusters, presumably related to an unknown environmental agent. The same therapeutic agents are used, but treatment is usually less aggressive and the prognosis better than in patients with pemphigus vulgaris.
Patients with paraneoplastic pemphigus produce antibodies against a range of structural proteins, including desmogleins. The condition is progressive and involves internal organs, especially the pulmonary system, in addition to skin and mucous membranes. Paraneoplastic pemphigus occurs with neoplasm, usually a B-cell lymphoproliferative disorder, but treatment of the malignant neoplasm does not appear to alter the progression of the condition. Death usually occurs within two years. Combination therapy with steroids and cyclosporine may alleviate symptoms.