Natural History Study of Recessive Dystrophic Epidermolysis Bullosa Wounds and Patient Reported Outcomes Using Mobile Application Home Photography

Abstract

Abstract Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, blistering genetic disease where wounding and wound pain are the most commonly reported problems by patients. The natural history of RDEB wounds has not been prospectively studied, thus limiting the design of clinical trial endpoints. Objective: To determine differences in spontaneous wound closure between chronic open vs recurrent RDEB wounds. Methods: We conducted a prospective observational study in which participants used a mobile application to upload weekly photographs of multiple target wounds for up to 6 months and reported associated wound pain and itch (Photo Cohort). We also utilized a separate dataset of placebo-treated wounds from a previously completed trial (Validation Cohort) to validate the differences in characteristics and spontaneous closure rates between chronic open vs recurrent wounds. 13 RDEB participants from a single academic center were enrolled in the prospective Photo Cohort while data from 57 trial participants was leveraged in the Validation Cohort . Results: For the Photo Cohort, 734 photos were collected from 69 wounds, of which 42 (73.7%) were chronic open wounds. Chronic open wounds were larger, more painful, and much less likely to experience spontaneous wound closure (17% vs 100% P<0.001) with much higher time-to-closure (25.7 weeks vs. 5.7 weeks, P<0.0001) than recurrent wounds during follow-up. Baseline wound size was the sole predictor of spontaneous wound closure in the Photo Cohort (12.8, 95% CI: 3.3-48, P<0.01., Findings in the Validation Cohort recapitulated those in the Photo Cohort (26% chronic open wounds had spontaneous closure vs 86% recurrent wounds, P<0.001, and time-to-closure of 14.6 weeks vs. 8 weeks for recurrent wounds). In multivariable models, wounds of the recurrent type had a 29-fold greater likelihood to close spontaneously compared with chronic open wound type (P=0.0045). Conclusions: Chronic open wounds tend to be larger, more painful, have a much lower probability of spontaneous closure, and longer time-to-closure than recurrent wounds. The distinction between wound types can be leveraged to predict spontaneous wound closure and guide wound selection and observation in RDEB clinical trials.