69 - Epidermolysis bullosa

Abstract

Epidermolysis bullosa (EB) comprises a group of rare, genetically inherited mechanobullous skin disorders. Underlying mutations impair the structural and functional integrity of the epidermis and dermoepidermal basement membrane zone (BMZ) of skin and mucous membranes, affecting key molecular pathways like cell adhesion and differentiation, tissue repair, and barrier function. The clinical hallmarks include increased mucocutaneous fragility with trauma-induced blistering, erosions, and scarring. Based upon the level of blister formation within the BMZ, EB is subclassified into four major types: simplex (intraepidermal), junctional (lamina lucida), dystrophic (dermal), and Kindler EB (mixed). Considerable genetic heterogeneity as well as secondary epigenetic, biochemical, and environmental factors constitute for the wide phenotypical variety of the disease. The index genes involved are also expressed in other epithelialized (gastrointestinal, respiratory, urogenital tract) or mesenchymal (skeletal muscle) organs rendering particularly the more severe EB variants a systemic disease with high morbidity and mortality. Current treatment strategies are mainly symptomatic, including skin and wound care; control of infection, pain, and pruritus; and nutritional supplementation, as well as prevention and management of complications such as anemia or osteoporosis. In addition, approaches of molecular therapies hold some promising translational perspectives.