Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

Abstract

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.

B Cells, Dendritic Cells, and Macrophages Are Required To Induce an Autoreactive CD4 Helper T Cell Response in Experimental Epidermolysis Bullosa Acquisita

“…Use of different animal models has greatly improved our understanding of the pathogenesis of AIBD (6). Especially, use of autoantibody transfer into mice has unraveled mechanisms leading to blister formation (7)(8)(9)(10)(11)(12)(13)).…”

Clinical features and diagnosis of epidermolysis bullosa acquisita

“…A variety of other diseases, e.g. rheumatoid arthritis, diabetes, cryoglobulinemia, and psoriasis were reported in individual EBA patients [5,37,38]. Recently, an association with hematological malignancies i.e.…”

“…Epidermolysis bullosa acquisita (EBA) is a rare chronic autoimmune blistering disease of skin and mucous membranes characterized by circulating and tissue bound antibodies against type VII collagen [5,6]. Type VII collagen is the major component of anchoring fibrils, which provides attachment of the epidermis and underlying basement membrane zone (BMZ) to the dermis ( Figure 1) [7][8][9].…”

Diffuse bullöse Eruptionen bei einer älteren Frau: Spätmanifestation eines bullösen systemischen Lupus erythematodes

“…Eine sorgfältige Anamnese, bei der das Hauptaugenmerk auf den Charakteristika der Läsionen liegt, relevante serologische Untersuchungsergebnisse und das Ansprechen auf Dapson erleichtern die Unterscheidung dieser beiden Erkrankungen [4]. EBA-Läsionen sind überwiegend mechanobullöser Natur und treten typischerweise auf mechanisch exponierten Körperstellen wie Ellenbogen, Knie, Fußknöchel und Handrücken auf [5]. Zudem sind die Hautläsionen bei EBA resistenter gegen eine Behandlung mit Steroiden und anderen immunmodulatorischen Wirkstoffen, was ein weiteres wichtiges Differenzierungsmerkmal darstellt.…”

“…Die Erkrankung betrifft im Allgemeinen Erwachsene mittleren Alters, doch wurden auch seltene Fälle bei Älteren berichtet [3]. BSLE kann gleichzeitig mit anderen immunbullösen und nicht immunbullösen Krankheiten bestehen [5]. Bei BSLE kann es sich um die Erstmanifestation eines SLE handeln, sodass der diagnostizierende Arzt ein hohes Maß an klinischer Vorsicht wahren sollte [10].…”