Pemphigus vulgaris and pemphigus foliaceus

Abstract

The blistering diseases of the skin grouped under the term pemphigus comprise unique organospecific autoimmune disorders in which the epidermis is injured by autoantibodies. The clinical syndromes manifested depend on the specificity of the autoantibodies Present in the patient, i.e., pemphigus vulgaris (PV) autoantibodies produce suprabasilar acantholysis while pemphigus foliaceus autoantibodies cause subcorneal acantholysis. The antigens recognized by these autoantibodies appear to be desmosomal-associated glycoproteins. The etiology of all forms of pemphigus is unknown except for the endemic form of pemphigus foliaceus known as fogo selvagem (PS). FS is thought to be initiated by exposure to environmental factors) present in certain regions of Brazil in which the disease is endemic. This review examines the relevant clinical, histological, and immunologic characteristics of PV and FS. PV is a potentially lethal disease that affects predisposed individuals sharing the HLA-DRw4 and -DRw6 phenotypes and a unique-DQ β-restriction fragment length of the major histocompatibility complex (MHC) polymorphism. Patients develop mucosal erosions and vesicles and bullae in the skin. The majority of patients possess autoantibodies directed against a cell surface antigen of squamous epithelia. The epidermal lesions show suprabasilar acantholysis. Experimental data strongly implicate PV autoantibodies as the cause of the epidermal lesions by mechanisms under current investigation. The IgG fraction from the sera of these patients induces similar lesions when injected into experimental animals. Similarly, F(ab′) 2 but not Fab′ fragments from PV IgG are pathogenic. These findings suggest that cross-linking of a keratinocyte surface antigen by the autoantibodies may be the initial step in the development of acantholysis in the epidermis of patients with PV. FS is a superficial erosive dermatosis that affects young adults and children living in remote villages of certain regions of Brazil where there are more than 15,000 registered cases. Epidemiological data strongly implicate an environmental factor(s) as the cause of FS. If this is established, it would represent a major step forward in the understanding of human autoimmunity. The disease involves only the skin and produces subcorneal vesicles that can lead to exfoliated erythroderma. The majority of patients have autoantibodies against a keratinocyte surface antigen, desmoglein I. These autoantibodies induce epidermal subcorneal vesicles when injected intraperitoneally into experimental animals. FS IgG as well as the F(ab′) 2 and Fab′ fragments are pathogenic when tested in the experimental animal model. This suggests that the autoantibodies in this disease may trigger subcorneal acantholysis by impairing the function of a cell adhesion molecule of the keratinocyte. The mechanisms by which pemphigus autoantibodies precipitate acantholysis continue under investigation in different laboratories. Current experiments suggest that activation of proteases such as plasminogen activator may be implicated in this process. Experimental data from other investigators suggest that complement activation may be an amplifying mechanism of acantholysis. Finally, it has been postulated that pemphigus autoantibodies may impair the assembly of desmosomes, thereby inducing acantholysis. The advances in the immunopathology of pemphigus have proved important in establishing the rationale for the treatment of these patients. All therapies are focused on lowering and eliminating pemphigus autoantibodies from the circulation of the patient. Thus, these therapies for PV and FS (as a prototype of pemphigus foliaceus) include systemic steroid and immunosuppressive agents. As we advance in the understanding of the etiology and pathogenesis of pemphigus, we will be able to develop new approaches in the management of these patients.