Dystrophic epidermolysis bullosa (DEB) is a rare inherited skin fragility disorder characterized by blistering and scarring of the skin and mucous membranes in response to minimal mechanical trauma. According to GeneReviews, DEB is caused by pathogenic variants in the gene encoding type VII collagen, a structural protein critical for anchoring the epidermis to the underlying dermis through anchoring fibrils at the dermal-epidermal junction. The condition encompasses two major forms defined by inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB), each further subdivided by clinical severity. DEB is classified within the broader epidermolysis bullosa spectrum of mechanobullous disorders. According to GeneReviews, the prevalence of RDEB and DDEB is each approximately 1.35–1.49 per million live births in registry data, with an overall EB prevalence of approximately 11 per million live births.

DEB is characterized by increased fragility of the skin and mucous membranes, with blistering typically present at or shortly after birth. As described in GeneReviews, the clinical spectrum varies substantially across subtypes. In severe RDEB—the most clinically significant form—widespread blistering leads to chronic wounds, milia formation, and progressive dermal scarring. Repeated blistering and healing cycles in the hands and feet result in pseudosyndactyly, the progressive fusion of digits that severely impairs hand function. Mucosal involvement causes oral and esophageal blistering, leading to dysphagia and nutritional compromise; esophageal strictures are a recognized complication. Corneal erosions and chronic anemia are additional systemic manifestations. GeneReviews notes that individuals with severe RDEB face a markedly elevated cumulative risk of squamous cell carcinoma arising in chronically wounded skin, representing a leading cause of mortality in this population. Milder forms—including DDEB and less severe RDEB subtypes—present with more localized blistering, primarily affecting the hands, feet, and extremities, with less systemic involvement.

DEB results from pathogenic variants in the gene encoding type VII collagen, a homotrimeric structural protein that forms anchoring fibrils at the dermal-epidermal junction. GeneReviews describes distinct genotype-phenotype relationships across subtypes. Severe RDEB is typically caused by biallelic pathogenic variants that result in complete absence of functional type VII collagen protein—commonly nonsense, frameshift, or splice-site variants. Intermediate RDEB generally results from compound heterozygosity for variants that allow production of small amounts of partially functional protein. DDEB typically arises from dominant-negative glycine substitution variants within the triple-helical domain of the type VII collagen molecule; these variants interfere with anchoring fibril assembly even in the presence of the normal protein produced from the second allele. The autosomal recessive inheritance pattern defines RDEB and the autosomal dominant pattern defines DDEB.

Diagnosis of DEB is established through clinical evaluation, histopathologic examination, and molecular genetic testing. According to GeneReviews, DEB may be suspected in individuals presenting with skin fragility manifesting as blistering with minimal trauma, healing with scarring and milia formation, and dystrophic or absent nails—features typically apparent at birth. Skin biopsy with transmission electron microscopy demonstrates absent or markedly reduced anchoring fibrils at the dermal-epidermal junction, and immunofluorescence mapping can detect type VII collagen absence or reduction in skin sections. Molecular genetic testing to identify biallelic (for RDEB) or heterozygous dominant-negative (for DDEB) pathogenic variants in the causative gene confirms the diagnosis, enables subtype classification, and supports cascade testing of at-risk relatives and prenatal diagnosis for affected families.

GeneReviews documents several FDA-approved targeted therapies for DEB. Beremagene geperpavec-svdt (Vyjuvek), a topical gene therapy based on an HSV-1 vector delivering a functional type VII collagen gene to wound tissue, is documented by GeneReviews as FDA-approved for wound treatment in individuals aged six months and older with molecularly confirmed RDEB or DDEB, applied topically once weekly by a health care provider. Prademagene zamikeracel (Zevaskyn), a genetically corrected autologous keratinocyte graft, is documented by GeneReviews as FDA-approved for wound treatment in individuals with RDEB. Birch bark extract containing birch triterpenes (Filsuvez), a botanical drug product, is documented by GeneReviews as FDA- and EMA-approved for wound treatment in individuals aged six months and older with epidermolysis bullosa, applied topically twice daily. International clinical practice guidelines published by DEBRA International address wound care, nutritional management, pain, esophageal stricture, oncological surveillance, and psychosocial support, among other domains.

Prognosis in DEB varies substantially by subtype. GeneReviews documents that severe RDEB carries the greatest disease burden, with progressive scarring, pseudosyndactyly, nutritional compromise, and a markedly elevated lifetime cumulative risk of squamous cell carcinoma. Squamous cell carcinoma in severe RDEB commonly arises in chronically wounded skin and represents a leading cause of premature mortality in this population. Milder RDEB subtypes and DDEB are associated with longer survival and greater preservation of function, though chronic wound burden, pain, and recurrent blistering remain significant throughout life. The availability of targeted therapies documented by GeneReviews represents an evolution in the treatment landscape for DEB, though long-term outcome data across these newer modalities continue to accumulate.

Research in DEB is active across multiple therapeutic modalities. GeneReviews documents that gene therapy, stem cell approaches (including bone marrow transplantation, mesenchymal stem cell infusion, and induced pluripotent stem cell strategies), stop codon readthrough, exon skipping, type VII collagen protein replacement, and revertant mosaicism exploitation are all under active investigation. Antifibrotic, anti-inflammatory, and antipruritic approaches are also being evaluated in ongoing trials. A classified publication digest includes over 100 publications spanning basic science, preclinical research, gene therapy, and biomarker development. Multiple active clinical trials are enrolling participants across interventional and observational designs, including industry-sponsored trials evaluating both systemic and topical investigational agents for wound healing and disease modification.