AUTOIMMUNE INJURY OF SQUAMOUS EPITHELIUM BY PEMPHIGUS AUTOANTIBODIES

The term pemphigus refers to a group of bullous diseases that are characterized by the presence of both intraepidermal blister formation and autoantibodies specific for epithelial cells (Lever, 1965). Pemphigus vulgaris, the commonest form, is a potentially lethal disease in which the blister occurs just above the basal cell layer. Pemphigus vegetans is an uncommon variant in which vegetating lesions are predominantly localized to flexural areas. Pemphigus fohaceus is a less serious disorder in which the blister is very superficial, occurring just below the stratum corneum. Brazilian pemphigus foliaceus (Fogo Selvagem) is a form of pemphigus foliaceus that occurs in an endemic fashion in Brazil. Pemphigus erythematosus (the Senear-Usher syndrome) is a clinical syndrome in which pemphigus foliaceus occurs in a patient with the clinical and serological features of lupus erythematosus (Senear & Usher, 1926). All forms of pemphigus are characterized by epidermal cell-cell detachment (acantholysis) leading to intraepidermal vesicle formation, and the presence of IgG antibodies directed against antigenic determinants present on the cell surfaces of differentiating keratinocytes (Beutner & Jordon, 1964). The underlying mechanisms which trigger this autoantibody formation are essentially unknown. The key problem that needs to be resolved is whether there is a breakdown in the self-tolerance of an unaltered antigen (the pemphigus antigen), or whether there is a change in the antigenicity of the antigen itself. There do appear to be genetic factors which predispose to the development of the disease. Although pemphigus vulgaris is found in all ethnic and racial groups, it has a higher incidence in Jews, and is associated with an increased prevalence of the HLA-DRw4 phenotype (Brautbar et al., 1980; Park, Terasaki & Ahmed, i979)Pemphigus has been associated with autoimmune disorders such as lupus erythematosus, rheumatoid arthritis, myasthenia gravis, pernicious anaemia, Hashimoto's thyroiditis and with benign thymomas (Diaz, Glamb & Silva, 1980; Maize, Green & Provost, 1982). Usually the course of pemphigus is not affected by the presence of these disorders. Pemphigus has also been associated with various malignancies, but the incidence of malignancy is not high, and temporal relationships are rare. Recently, penicillamine has been implicated as a potential causative factor in the induction of pemphigus foliaceus in some patients (Degos et al., 1969; Tan & Rowell, 1976). It has been estimated that pemphigus foliaceus will occur in about 7"^ of patients receiving long-term penicillamine therapy (Marsden et al., 1976), which makes the association seem more than fortuitous.