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.