Bullous Diseases of the Skin and Mucous Membranes

Autoimmune bullous diseases (AIBDs) comprise about a dozen clinically and immunopathologically heterogeneous disorders. They can be divided into three groups: pemphigus diseases, pemphigoid diseases, and dermatitis herpetiformis. The common denominators of AIBDs are the occurrence of blisters and erosions on the skin and/or surface-close mucous membranes, with accompanying characteristic patterns of deposition of IgG, IgA, and/or complement C3 in these tissues. While in pemphigus and pemphigoid diseases autoantibodies target structural proteins of the epidermal/epithelial desmosomes and the dermal–epidermal junction, respectively, autoantibodies in dermatitis herpetiformis are directed against transglutaminase 2 and 3. Within the last decade, considerable progress has been made in both the diagnosis and the understanding of the pathophysiology of AIBDs. In pemphigus, cellular events of the keratinocytes themselves are sufficient for intraepidermal/-epithelial splitting after the binding of autoantibodies. In pemphigoid diseases, Fc receptor-mediated mechanisms such as local complement activation and the subsequent influx of inflammatory cells induce subepidermal splitting due to the release of reactive oxygen species and specific proteases. C5a, IL-17A, and LTB4 have recently been described as key mediators in this process. In pemphigoid diseases, treatment typically relies on the long-term use of corticosteroids in combination with immunomodulants or immunosuppressants; the anti-CD20 antibody rituximab induces complete remission in 80% to 90% of pemphigus patients.