By Robert Jordon, M.D.
Professor and Chairman, Department of Dermatology,
University of Texas
Houston, Texas
Historical Perspective
The term pemphigus was most likely in use in the ancient world, but the first recorded instance was by Hippocrates (460-370 BC) who described pemphigoid fever as “pemphigodes pyertoi.” Galen (AD 13 1-201) named a pustular disease of the mouth as “febris pemphigodes.” In 1637, Zacutus again uses the term “febris pemphigodes” to describe patients with blisters of short duration. DeSauvages (1760) described patients with high fever and blisters of short duration as having “pemphigus maior.” None of the above conditions is considered to be true pemphigus, as their disease was of short duration and all patients recovered.
The first recorded cases that probably represent true pemphigus were by McBride (1777) and Wichmann (1791). Two of McBride’s cases died of “bloody ichor” and “putrid ulcers.” Wichmann applied the term “pemphigus” to his patients and accurately describes flaccid bullae and painful oral ulcerations.
Pemphigus foliaceus was first recognized by Cazenave in 1844, as a special, superficial, rapidly spreading form of pemphigus. Neumann, in 1886, describes a form of the disease with “warty granulations” as pemphigus vegetans. Senear and Usher, in 1926, describe pemphigus erythematosus, combining features of both pemphigus and lupus erythematosus. Auspitz (1881) first described disruption of epidermal cells in patients with pemphigus, but not as a specific finding. Civatte, in 1943, clearly delineated this histopathologic hallmark and labeled it acantholysis. He describes acantholysis (loss of cohesion) and intraepidermal bulla formation in pemphigus vulgaris, pemphigus vegetans, and pemphigus foliaceus. These important pathologic findings clearly separated pemphigus from other blistering skin diseases. In 1953, Lever defined the disease entity bullous pemphigoid both clinically and histopathologically, clearly distinguishing it from pemphigus. This “pemphigus-like” disease affected primarily elderly patients and was characterized by subepidermal bulla formation.
The next breakthrough occurred in 1964 with the reporting of autoantibodies in the sera of pemphigus patients, reactive with an “intercellular substance” of skin and mucosa, by Beutner and Jordon using indirect immunofluorescence. They later showed these same autoantibodies fixed in pathologic sections using direct immunofluorescence methods. In 1967, they also demonstrated autoantibodies in sera and skin specimens from patients with bullous pemphigoid but reactive with the basement membrane zone. These latter findings clearly separate bullous pemphigoid from pemphigus, and establish it as a distinct bullous skin disease.
Pemphigus Concept Today
Pemphigus Vulgaris: Pemphigus vulgaris, and its variant Pemphigus vegetans, are autoimmune bullous diseases with serum autoantibodies that react with cell surface antigens, resulting in loss of cohesion of epidermal cells. These antibodies react primarily with a l3OkD desmosomal protein identified as desmoglein III. Some patients with cutaneous lesions may also have autoantibodies to desmoglein I. Clinical features include flaccid blisters which rupture easily forming denuded weeping areas of skin or oral mucosa.
Histopathologically, the disease is characterized by suprabasal intraepidermal bulla formation with marked acantholysis and an inflammatory infiltrate of eosinophils. Immunopathologically, IgG and C3 deposits are found in intercellular/cell surface areas in skin lesions. Diagnosis is based upon the clinical presentation and characteristic histopathologic and immunopathologic findings.
Pemphigus Foliaceus: Pemphigus foliaceus, its localized variant pemphigus erythematosus, and the endemic form of Pemphigus foliaceus (fogo selvagem) are autoimmune bullous diseases with serum autoantibodies, again reactive with cell surface antigens. These antibodies react primarily with a l8OkD desmosomal protein identified as desmoglein I. Clinical features include superficial vesicles, which rupture easily leaving denuded areas of skin. Oral lesions are absent in this form of pemphigus. Histopathologically, pemphigus foliaceus is characterized by intraepidermal separation high in the epidermis, in or near the granular layer. Acantholysis is present, but may be minimal. Immunopathologically, IgG deposits are again found in intercellular/cell surface areas, but higher in the epidermis than occurs in Pemphigus vulgaris. Diagnosis is again based upon the clinical presentation and characteristic histopathologic and immunopathologic findings.
