Pemphigus and pemphigoid as paradigms of organ-specific, autoantibody-mediated diseases.

Abstract

The blistering skin diseases pemphigus and pemphigoid can be considered paradigms of antibody-mediated, organ-specific autoimmune diseases. These diseases not only demonstrate mechanisms whereby autoantibodies can mediate tissue damage, but are also examples ofhow autoantibodies from patients can be used as tools to further our understanding ofthe molecular structure of normal tissue. In this Perspectives article, I will briefly describe the clinical, histologic, and immunopathologic features of these diseases. I will then discuss in more detail the newer data regarding the pathophysiology of these diseases, as well as the molecules defined by the autoantibodies from these patients. Clinical and histologic featuresThe clinical and histologic aspects of pemphigus and pemphigoid are well established (Table I) (1). There are two major types of pemphigus, called pemphigus vulgaris (PV)' and pemphigus foliaceus (PF). Patients with PV almost always develop, and often present with, mucous membrane erosions. Skin lesions, which are seen as flaccid blisters or erosions, tend to gradually enlarge at the edges. PV, ifleft untreated, is almost always fatal. The histology ofa PV lesion shows that the blister (or erosion) forms because of separation of epidermal cells from each other (a process called acantholysis) just above the basal cell layer. In contrast to PV patients, PF patients rarely have mucous membrane lesions. They usually present with scaly and crusted skin lesions, which, unlike PV lesions, do not tend to form extensive and enlarging erosions, but are fixed and well demarcated. Fogo selvagem (also called Brazilian PF) is a form of PF that is endemic in rural areas of Brazil and often affects children and young adults (2). The histology of a PF lesion demonstrates blister formation due to acantholysis in the superficial epidermis at the granular layer. With these histologic findings in mind, both major types of pemphigus, PV and PF, can May 1989May , 1443May -1448 In contrast to the flaccid blisters, erosions, and crusted lesions seen in pemphigus patients, bullous pemphigoid (BP) patients classically present with tense blisters on normal-appearing or erythematous skin. Whereas pemphigus lesions are due to intraepidermal blisters, histology of a BP lesion indicates a subepidermal blister with an infiltrate containing eosinophils in the superficial dermis and at the epidermal basement membrane zone (BMZ). Clinically and histologically similar to BP, herpes gestationis (also called pemphigoid gestationis) is a subepidermal, autoantibody-associated blistering disease that occurs during the second or third trimester of pregnancy, and spontaneously resolves in the months after delivery. ImmunopathologyOver 20 years ago, Beutner and Jordon established that BP and pemphigus were associated with autoantibodies (3). Both direct immunofluorescence of patients' lesional and perilesional skin and indirect immunofluorescence with patients' sera on normal skin substrates, have demonstrated antibody binding to the same ar...

T Cell Recognition of Desmoglein 3 Peptides in Patients with Pemphigus Vulgaris and Healthy Individuals

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“…diet (garlic), viruses also act as triggering factors for pemphigus lesions. 5,6 A combination of corticosteroids, immunosuppressive agents, pulse therapy, photophoresis and plasmaphoresis may reduce its progression. 7 Early lesions in the mouth can be best attended by appropriate periodontal therapy with maintenance of optimal oral hygiene.…”

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“…Le si6ge du d6collement peut ~tre affirm6 par l'examen anatomopathologique. La caract6risation du type de dermatose bulleuse n6cessite en fait la mise en 6vidence d'anticorps fix6s par immunofluorescence (IF) directe apr6s biopsie muqueuse ou cutan6e -et du si6ge des d6p6ts d'IgG ou IgA (sous 4pi-dermiques ou 6pidermiques intercellulaires) -et d' anticorps dans le sang circulant par IF indirecte [7].…”