Summary Background Chronic wounds, a common morbidity in recessive dystrophic epidermolysis bullosa (RDEB), lack definitive therapies. Objectives To assess allogeneic epidermal skin grafts in terms of wound healing and durability over time. Methods In a prospective, open‐label clinical trial for postallogeneic haematopoietic cell transplantation (post‐alloHCT) patients with RDEB, up to nine chronic wounds per patient were grafted over 1 year. Epidermal grafts measuring 5 cm2 were obtained from related alloHCT donors in the outpatient setting using the CELLUTOMETM Epidermal Harvesting System. Wounds were photographed and symptom inventories completed at baseline and 6, 12 and 52 weeks after grafting. The trial was registered at ClinicalTrials.gov (NCT02670837). Results Between August 2016 and January 2019, eight patients with RDEB received a total of 35 epidermal allografts at a median of 1157 days (range 548–2884) post‐alloHCT. The median (interquartile range) percentage reductions in wound surface area were 75% (52–94), 95% (72–100) and 100% (97–100) at 6, 12 and 52 weeks postgraft, respectively, each significantly reduced from baseline (P < 0·001). Donor harvest sites healed quickly without scarring. Biopsy evaluation at 1 year of an epidermal allograft site revealed wildtype type VII collagen (immunofluorescence), anchoring fibrils (electron microscopy), and full‐thickness skin whole‐DNA donor chimerism of 42% (compared with 16% in concurrently biopsied native skin). This strategy subsequently supported release of RDEB pseudosyndactyly. Conclusions The immune tolerance established by alloHCT supports successful adoptive transfer of donor epidermal grafts. Persistence of donor grafts in a single patient beyond 1 year and observed migration of donor‐grafted cells into adjacent wound suggest that epidermal allografts include nonterminally differentiated cells and/or trigger recruitment of donor bone‐marrow‐derived cells to mediate wound healing.
Few studies have evaluated quality of life (QOL) impact on patients with autoimmune blistering diseases (AIBD). AIBD subtypes may have unique disease-specific patient-reported outcomes. Our cross-sectional analysis included 79 patients with AIBD (pemphigus n¼30, bullous pemphigoid (BP) n¼26, and mucous membrane pemphigoid (MMP) n¼23). Disease severity index was calculated for pemphigus (PDAI), BP (BPDAI), and MMP (MMPDAI). We assessed QOL using AIBD QOL (ABQOL), treatment of AIBD QOL (TABQOL) and QOL from pruritus (Itch-yQoL) questionnaires. Mean scores for ABQOL in pemphigus, BP, and MMP were 16, 16.19 and 16.43, while for TABQOL were 14.2, 13.31 and 13.35, respectively. Mean scores for ItchyQoL were 51.97 (low-moderate), 62 (moderate) and 45.74 (mild), respectively. Correlation was measured by Pearson correlation coefficient (PCC). A positive correlation between QOL and PDAI was demonstrated with ABQOL (PCC¼0.4) and ItchyQOL (PCC¼0.39) (p<0.033). Most bothersome from the ABQOL were embarrassment, sexual difficulties and social life impact, while the ItchyQoL confirmed impact of pruritus in symptom and emotional components; skin bleeding, embarrassment and skin condition drives me crazy. Comparing QOL with BPDAI noted impacts in ABQOL, TABQOL and ItchyQOL (p<0.003). ABQOL demonstrated effects on clothing changes, painful skin, embarrassment, and ItchyQOL skin bleeding, concern for what others think, and feeling self-conscious. Correlating QOL with MMPDAI was not significant suggesting existing tools may not be sensitive enough to capture true QOL impact of MMP. Regarding TABQOL, patients in all subtypes described treatments as time consuming while patients with BP were concerned for getting sick and medication dosage drop. ItchyQoL positively correlated with ABQOL in both pemphigus and BP (PCC¼0.71, p¼<0.001). These data highlight a novel finding that pemphigus patients with cutaneous involvement suffer from significant burdens of pruritus approaching that of BP. Overall, these results provide unique insight into QOL impact in patients with AIBD.
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