Diagnosis and classification of pemphigus and bullous pemphigoid.

Pemphigus and bullous pemphigoid represent the two major groups of autoimmune blistering diseases. Pemphigus has three major variants: pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus and is characterized by autoantibodies directed against the cell surface of keratinocytes, producing acantholysis that in turn leads to intraepithelial blisters in the skin and/or mucous membranes. In bullous pemphigoid, the autoantibodies are present at the dermo-epidermal junction and attack the hemidesmosomes, causing subepidermal blister formation. The classification of the major variants of both the pemphigus group and bullous pemphigoid can be based on the combination of clinical, histopathological and immunopathological criteria. Many tools are available for the diagnosis of these entities including biopsy, direct and indirect immunofluorescence, immunoprecipitation, immunoblotting and ELISA. However, currently there are no generally accepted criteria for the diagnosis of these disorders. The present review provides a proposal for diagnostic criteria.

Kershenovich R ，Hodak E ，Mimouni D 《-》

Enzyme-linked immunosorbent assay in autoimmune blistering diseases: preliminary experience of the Dermatology Department of Cagliari.

Atzori L ，Deidda S ，Aste N 《GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIA》

Diagnosis of autoimmune bullous diseases.

Autoimmune bullous disorders (AIBDs) are a heterogeneous group of rare diseases clinically characterized by erosions and/or blisters on the skin and mucous membranes. AIBDs can be categorized into two groups: pemphigus diseases, characterized by intraepidermal blistering and autoantibodies against desmosomal proteins such as desmoglein (Dsg) 1, Dsg3, members of the plakin family, and subepidermal AIBDs, comprised of pemphigoid diseases and dermatitis herpetiformis. Autoantibodies in dermatitis herpetiformis target transglutaminases 2 and 3, while in pemphigoid disease, autoantibodies are directed against structural proteins of the dermal-epidermal junction. Although analysis of a perilesional biopsy with direct immunofluorescence (IF) microscopy is still the diagnostic gold standard, several assays have become widely available that allow serological diagnosis in the majority of patients. Standard serological diagnosis includes indirect IF on monkey esophagus and salt-split human skin. Assays to further characterize autoantibody specificity include ELISA systems based on recombinant forms of the immunodominant regions of the target antigens as well as multivariant indirect IF microscopy tests with several miniature substrates. These serological assays are complemented by various in-house assays using immunoblotting and ELISA, which are only available in specialized laboratories. Here we review new developments in the diagnosis of AIBDs and describe state-of-the-art diagnostic procedures for this group of diseases.

van Beek N ，Zillikens D ，Schmidt E 《-》

Dual diagnosis of Pemphigus and pemphigoid. Retrospective review of thirty cases in the literature.

Pemphigus and pemphigoid are two distinct groups of autoimmune blistering diseases. There are many reports of the simultaneous presence of clinical and serological features of both diseases in the same patient. This study is a retrospective review of the present literature on reports of patients with features of both pemphigus and pemphigoid. We recommend that these patients be considered as having a dual diagnosis. A review of the English language, peer-reviewed literature was conducted on patients described with features of pemphigus and pemphigoid. Available data on clinical profile, histology, immunopathology, treatment, follow-up and outcome were studied in 30 patients. They were divided into three groups: (1) bullous pemphigoid and pemphigus vulgaris, (2) mucous membrane or cicatricial pemphigoid and pemphigus vulgaris and (3) bullous pemphigoid and pemphigus foliaceus. In all three groups, most patients had a clinical phenotype resembling both diseases. In 17 patients with bullous pemphigoid and pemphigus vulgaris, 83% had a skin biopsy consistent with bullous pemphigoid, 70% had direct immunofluorescence studies typical of bullous pemphigoid and sera of 83% had antibodies typical of pemphigus vulgaris on indirect immunofluorescence. In 10 patients with mucous membrane or cicatricial pemphigoid and pemphigus vulgaris, a histology of mucous membrane pemphigoid was reported in 60% of the patients, direct immunofluorescence studies typical of mucous membrane pemphigoid were reported in 70% of the patients and in 80%, autoantibodies characteristic of pemphigus vulgaris were observed. In 3 patients with bullous pemphigoid and pemphigus foliaceus, the histologies were consistent with bullous pemphigoid, direct immunofluorescence was typical of pemphigus foliaceus and their sera had both autoantibodies. The majority of the 30 patients required long-term high-dose corticosteroids and immunosuppressive agents to control their disease. Three patients with bullous pemphigoid and pemphigus vulgaris (18%) died due to effects of prolonged immunosuppression. We characterize a group of patients who have clinical, histological and immunopathological features of bullous or mucous membrane or cicatricial pemphigoid with serological features of pemphigus. These patients did not achieve a prolonged clinical remission by conventional therapy. It is possible that early identification of these patients may improve their prognosis.

Sami N ，Ahmed AR 《DERMATOLOGY》

IgG4, complement, and the mechanisms of blister formation in pemphigus and bullous pemphigoid.

Autoimmune bullous diseases are at the forefront of the research field on autoimmune diseases. Pemphigus and pemphigoid were historical entities in the world of descriptive dermatology for a long time. Recently, however, dermatologists and skin biologists have elegantly explained the novel pathomechanism of pemphigus and pemphigoid diseases. IgG4 is the major subclass of autoantibodies in autoimmune bullous diseases and is known to have little activity to activate complement. It is quite acceptable for pemphigus, because acantholysis in pemphigus has been demonstrated to be complement-independent. On the other hand, subepidermal blister formation in bullous pemphigoid has been believed to be complement-dependent. Therefore, the role of IgG4 autoantibodies on blister formation in bullous pemphigoid remains controversial. Here, we examine the progress of research on the mechanisms of blister formation in autoimmune bullous diseases. We focus on the complement-dependent and independent blistering in bullous pemphigoid using comparisons between pemphigus diseases. In addition, we review the current understanding of the role of IgG4 antibodies in bullous pemphigoid.

Dainichi T ，Chow Z ，Kabashima K 《-》