Hereditary epidermolysis bullosa (EB) is a clinically and genetically heterogeneous group of inherited mechanobullous disorders affecting approximately 1 in 50,000 births. The unifying feature is skin and mucosal fragility leading to blister formation with minimal mechanical trauma. The classification is based on the ultrastructural level of skin cleavage, which corresponds to specific mutated structural proteins of the dermo-epidermal junction.
EB simplex (EBS) accounts for 70% of cases. Cleavage is intraepidermal (basal keratinocytes). Most cases are autosomal dominant with mutations in keratin 5 (KRT5) or keratin 14 (KRT14). Subtypes include EBS-Weber-Cockayne (localized to hands/feet, mild), EBS-Köbner (generalized intermediate), and EBS-Dowling-Meara (generalized severe with herpetiform clusters). Junctional EB (JEB) is autosomal recessive with cleavage in the lamina lucida due to mutations in laminin-332 (LAMA3, LAMB3, LAMC2) or α6β4 integrin (ITGA6, ITGB4); severity ranges from lethal Herlitz JEB (often fatal in infancy) to non-Herlitz forms.
Dystrophic EB (DEB) involves sublamina densa cleavage from mutations in type VII collagen (COL7A1). Dominant DEB (DDEB) is mild-moderate with scarring blisters. Recessive DEB (RDEB) ranges from severe generalized (RDEB-sev gen, with mutilating scarring, mitten-deformity pseudosyndactyly, growth failure, esophageal strictures, malnutrition, anemia, and aggressive squamous cell carcinoma) to intermediate forms. Kindler EB (KEB) involves mixed cleavage levels from FERMT1 (kindlin-1) mutations and presents with blistering, photosensitivity, and progressive poikiloderma. Diagnosis combines clinical history, immunofluorescence antigen mapping (decreased or absent staining of specific protein), transmission electron microscopy (TEM, gold standard for cleavage level), and genetic testing. Management is multidisciplinary: meticulous wound care with non-adherent dressings, infection prevention, nutritional optimization, anemia management, contracture prevention, and squamous cell carcinoma surveillance. Beremagene geperpavec (B-VEC, Vyjuvek), a topical herpes simplex virus-based gene therapy delivering COL7A1, was FDA-approved 2023 for RDEB.