IMPORTANCERecessive dystrophic epidermolysis bullosa (RDEB) is a devastating, often fatal, inherited blistering disorder caused by mutations in the COL7A1 gene encoding type VII collagen. Support and palliation are the only current therapies.OBJECTIVE To evaluate the safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with RDEB.DESIGN, SETTING, AND PARTICIPANTS Single-center phase 1 clinical trial conducted in the United States of 4 patients with severe RDEB with a measured area of wounds suitable for grafting of at least 100 cm 2 . Patients with undetectable type VII collagen keratinocyte expression were excluded.INTERVENTIONS Autologous keratinocytes isolated from biopsy samples collected from 4 patients with RDEB were transduced with good manufacturing practice-grade retrovirus carrying full-length human COL7A1 and assembled into epidermal sheet grafts. Type VII collagen gene-corrected grafts (approximately 35 cm 2 ) were transplanted onto 6 wounds in each of the patients (n = 24 grafts). MAIN OUTCOMES AND MEASURESThe primary safety outcomes were recombination competent retrovirus, cancer, and autoimmune reaction. Molecular correction was assessed as type VII collagen expression measured by immunofluorescence and immunoelectron microscopy. Wound healing was assessed using serial photographs taken at 3, 6, and 12 months after grafting. RESULTSThe 4 patients (mean age, 23 years [range, 18-32 years]) were all male with an estimated body surface area affected with RDEB of 4% to 30%. All 24 grafts were well tolerated without serious adverse events. Type VII collagen expression at the dermal-epidermal junction was demonstrated on the graft sites by immunofluorescence microscopy in 9 of 10 biopsy samples (90%) at 3 months, in 8 of 12 samples (66%) at 6 months, and in 5 of 12 samples (42%) at 12 months, including correct type VII collagen localization to anchoring fibrils. Wounds with recombinant type VII collagen graft sites displayed 75% or greater healing at 3 months (21 intact graft sites of 24 wound sites; 87%), 6 months (16/24; 67%), and 12 months (12/24; 50%) compared with baseline wound sites. CONCLUSIONS AND RELEVANCEIn this preliminary study of 4 patients with RDEB, there was wound healing in some type VII collagen gene-corrected grafts, but the response was variable among patients and among grafted sites and generally declined over 1 year. Long-term follow-up is necessary for these patients, and controlled trials are needed with a broader range of patients to better understand the potential long-term efficacy of genetically corrected autologous epidermal grafts.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) lack functional type VII collagen owing to mutations in the gene COL7A1 and suffer severe blistering and chronic wounds that ultimately lead to infection and development of lethal squamous cell carcinoma. The discovery of induced pluripotent stem cells (iPSCs) and the ability to edit the genome bring the possibility to provide definitive genetic therapy through corrected autologous tissues. We generated patient-derived COL7A1-corrected epithelial keratinocyte sheets for autologous grafting. We demonstrate the utility of sequential reprogramming and adenovirus-associated viral genome editing to generate corrected iPSC banks. iPSC-derived keratinocytes were produced with minimal heterogeneity, and these cells secreted wild-type type VII collagen, resulting in stratified epidermis in vitro in organotypic cultures and in vivo in mice. Sequencing of corrected cell lines before tissue formation revealed heterogeneity of cancer-predisposing mutations, allowing us to select COL7A1-corrected banks with minimal mutational burden for downstream epidermis production. Our results provide a clinical platform to use iPSCs in the treatment of debilitating genodermatoses, such as RDEB.

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The results demonstrated the clinical benefits associated with continuous topical administration of a zinc oxide/petrolatum-based formulation by this novel diaper.

Background Qualitative data suggest that pruritus is a burdensome symptom in patients with epidermolysis bullosa (EB), but the prevalence of pruritus in children and adults with EB, as well as factors that contribute to pruritus are unknown. Objective To quantitatively identify and to characterize pruritus experienced by EB patients using a comprehensive online questionnaire. Methods A questionnaire was developed to evaluate pruritus in all ages and types of EB. Questions that characterize pruritus were included, and factors that aggravate symptoms were investigated. Patients from seven North American EB centers were invited to participate. Results A total of 146 out of 216 questionnaires were completed (response rate=68%) (73 males, 73 females; median age, 20.0). Using a 5-point Likert scale (1=never, 2=rarely, 3=sometimes, 4=often, 5=always), itchiness was the most bothersome EB complication (mean=3.3). The average daily frequency of pruritus increased with self-reported EB severity. Pruritus was most frequent at bedtime (mean=3.8) and interfered with sleep. Factors that aggravated pruritus included healing wounds, dry skin, infected wounds, stress, heat, dryness, and humidity. Conclusions Pruritus is common in EB patients and can be very bothersome. Future studies will need to investigate the most effective treatments given to EB patients for pruritus.

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Objective:To review the literature addressing the care of neonatal skin.Data Sources:Computerized searches in MEDLINE and CINAHL, as well as references cited in articles reviewed. Key concepts in the searches included neonatal skin differences; neonatal skin and care practices for skin integrity; neonatal skin and toxicity; permeability; and contact irritant sensitization.Study Selection:Articles and comprehensive works relevant to key concepts and published after 1963, with an emphasis on new findings from 1993 to 1999. One hundred two citations were identified as useful to this review.Data Extraction:Data were extracted and organized under the following headings: anatomy and physiology of the skin; physiologic and anatomic differences in neonatal skin; nutritional deficiencies; skin care practices; and care of skin breakdown.Data Synthesis:Newborns’ skin is at risk for disruption of normal barrier function because of trauma. In light of available evidence about differences in neonatal skin development, clinical practice guidelines are suggested for baths, lubrication, antimicrobial skin disinfection, and adhesive removal. In addition, basic care practices are suggested for maintaining skin integrity, reducing exposure to potentially toxic substances, and promoting skin health beyond the neonatal period. Preventive care recommendations are made for reducing trauma, protecting the skin’s immature barrier function, and promoting skin integrity.Conclusions:This review generated evidence with which to create a new and comprehensive practice guideline for clinicians. Evaluation of the guideline is under way at 58 U.S. sites.