Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. The pathogenic relevance of autoantibodies targeting type VII collagen (COL7) has been well-documented. Therefore, EBA is a prototypical autoimmune disease with a well-characterized pathogenic relevance of autoantibody binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new cases per million and per year. The current treatment of EBA relies on general immunosuppressive therapy, which does not lead to remission in all cases. Therefore, there is a high, so far unmet medical need for the development of novel therapeutic options. During the last 10 years, several novel in vitro and in vivo models of EBA have been established. These models demonstrated a critical role of the genetic background, T cells, and cytokines for mediating the loss of tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor engagement, cytokines, several molecules involved in cell signaling, release of reactive oxygen species, and matrix metalloproteinases are crucial for autoantibody-induced tissue injury in EBA. Based on this growing understanding of the diseases’ pathogenesis, several potential novel therapeutic targets have emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and current treatment options for EBA are discussed in detail. 1. Clinical Presentation of Epidermolysis Bullosa Acquisita In the beginning of the 20th century, the term “epidermolysis bullosa acquisita” (EBA) was used as a descriptive clinical diagnosis for patients with adult onset and features resembling those of hereditary dystrophic epidermolysis bullosa [1]. Almost 70 years later, EBA was distinguished from other bullous diseases on the basis of distinctive clinical and histological features, implementing the first diagnostic criteria for the disease. Specifically, these included (i) clinical lesions resembling epidermolysis bullosa dystrophica, (ii) adult onset of disease, (iii) a negative family history of epidermolysis bullosa dystrophica, and (iv) exclusion of other bullous diseases [2]. Based on the current understanding of EBA pathogenesis, additional/other criteria define EBA diagnosis today (see Section 13). The cutaneous manifestations in EBA patients are heterogeneous. However, EBA patients can be classified into two major clinical subtypes: noninflammatory (classical or mechanobullous) and inflammatory EBA, which is characterized by cutaneous inflammation resembling bullous pemphigoid, linear IgA disease, mucous membrane
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