RDEB is caused by pathogenic variants in the COL7A1 gene and is inherited in an autosomal recessive pattern. ClinGen has classified the relationship between COL7A1 variants and RDEB as DEFINITIVE. Individuals with RDEB carry two altered copies of COL7A1—one inherited from each parent—resulting in absent or severely reduced functional type VII collagen. Parents who each carry one altered copy are typically unaffected carriers. Because RDEB requires inheriting pathogenic variants from both parents, it may be more prevalent in families where parents share a common ancestor, as shared ancestry increases the probability that both individuals carry the same rare genetic variant. Carrier status in family members can be assessed through genetic testing of COL7A1.

Diagnosis is established through clinical features, skin biopsy findings, and molecular genetic testing. Suggestive clinical features include skin fragility with blistering from minimal trauma, healing with scarring and milia, absent lingual papillae, and nail dystrophy present at birth or in early infancy. Skin biopsy with immunofluorescence mapping demonstrates absent or reduced type VII collagen at the dermal-epidermal junction, and electron microscopy confirms sub-lamina densa cleavage as the site of blister formation. Molecular genetic testing of COL7A1 identifies the causative variants and confirms the diagnosis. GeneReviews-based diagnostic criteria for dystrophic epidermolysis bullosa have been published and guide evaluation. Subtype classification based on severity and distribution of involvement informs prognosis and treatment selection.

Two FDA-approved targeted therapies are available for wound treatment in RDEB. Beremagene geperpavec-svdt (VYJUVEK) is FDA-approved as a topical treatment for wounds in individuals age six months and older with molecularly confirmed RDEB or dominant DEB; it is applied by a healthcare provider. Prademagene zamikeracel (Zevaskyn) is FDA-approved for wound treatment in pediatric and adult individuals with RDEB and is administered as a surgically applied autologous keratinocyte graft through qualified treatment centers.

Comprehensive supportive care involves a multidisciplinary team across dermatology, gastroenterology, nutrition, hematology, ophthalmology, dentistry, pain management, hand surgery, and palliative care specialties. Wound care focuses on minimizing new blister formation through protective handling, dressings, and soft clothing and footwear. Nutritional management addresses the challenges from oral and esophageal involvement. Anemia is managed through established hematological approaches. Esophageal strictures may require dilation procedures. Hand surgery and rehabilitation therapy address pseudosyndactyly and work to preserve hand function. Regular dermatological evaluation for squamous cell carcinoma is an important component of long-term monitoring. International clinical practice guidelines developed by DEBRA International cover wound and skin care, nutritional management, cancer surveillance, pain care, psychosocial support, and other aspects of ongoing management.

The clinical course of RDEB is chronic, progressive, and associated with significant morbidity from ongoing blistering, scarring, infection, systemic complications, and the development of squamous cell carcinoma. Squamous cell carcinoma is a major determinant of survival in individuals with severe RDEB, arising in areas of longstanding chronic wounds and scarring and representing the most serious long-term complication. The approval of targeted therapies for wound treatment represents a meaningful advance in the clinical management of this condition. Individual outcomes vary based on disease severity, extent of systemic involvement, the burden of complications over time, and access to specialized multidisciplinary care experienced in managing epidermolysis bullosa.

RDEB is an active area of therapeutic and translational research. Multiple clinical trials are currently investigating approaches including novel wound-healing agents, gene correction strategies, systemic disease-modifying therapies, and transplantation-based approaches. ClinicalTrials.gov lists current studies relevant to RDEB and its subtypes for individuals and clinicians seeking information on research participation opportunities.