To the Editor: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis that causes severe wounds with a poorly understood natural history.1Bruckner-Tuderman L. Mellerio J.E. Wound healing in epidermolysis bullosa.Br J Dermatol. 2017; 177: e193-e195Crossref PubMed Scopus (7) Google Scholar It is understood that some wounds heal within weeks to months and that some heal and relapse.1Bruckner-Tuderman L. Mellerio J.E. Wound healing in epidermolysis bullosa.Br J Dermatol. 2017; 177: e193-e195Crossref PubMed Scopus (7) Google Scholar In a previous survey of 1226 wounds in 85 patients with RDEB, 76% healed within 8 weeks, and 24% were present for longer than 8 weeks.2Eng V. Solis D. Gorell E. et al.Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: a global cross-sectional survey.J Am Acad Dermatol. 2020; https://doi.org/10.1016/j.jaad.2020.03.028Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar Respondents were able to classify these wounds into 2 groups.2Eng V. Solis D. Gorell E. et al.Patient-reported outcomes and quality of life in recessive dystrophic epidermolysis bullosa: a global cross-sectional survey.J Am Acad Dermatol. 2020; https://doi.org/10.1016/j.jaad.2020.03.028Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar To explore these wound types, a retrospective evaluation and cross-sectional patient survey was performed at Stanford University. In cohort 1, serial wound photographs obtained over a mean of 36 weeks (maximum, 72 weeks) were evaluated. Surface area was quantified by using digital software (ImageJ, National Institutes of Health; VECTRA, Canfield; and Tissue Analytics, Net Health). Wounds that underwent investigational treatments were excluded. A cutoff of 12 weeks was hypothesized to define chronic open wounds.3Kyaw B.M. Jarbrink K. Martinengo L. Car J. Harding K. Schmidtchen A. Need for improved definition of “chronic wounds” in clinical studies.Acta Derm Venereol. 2018; 98: 157-158Crossref PubMed Scopus (30) Google Scholar Wounds that healed within 12 weeks but subsequently reblistered in the same location were defined as recurrent. Wounds were classified based on patient self-report and review by 2 dermatologists. In cohort 2, patients completed a survey on wound characteristics and patient-reported outcomes on up to 3 wounds of each type, with a 75% (30/40) response rate (Supplemental Methods; available via Mendeley at https://data.mendeley.com/datasets/f666xk8frd/1). A subset (n = 22) completed both evaluations, with a 78% concordance between participants and investigators for wound type and Spearman correlation coefficient of 0.70 for wound surface area. Both cohorts had similar demographics (Supplemental Table I; available via Mendeley at https://data.mendeley.com/datasets/f666xk8frd/1). Overall, 251 wounds were evaluated; 37% (93/251) were chronic open wounds, and 63% (158/251) were recurrent (Supplemental Table II; available via Mendeley at https://data.mendeley.com/datasets/f666xk8frd/1). Chronic open wounds had a larger mean surface area than recurrent wounds (cohort 1: 118.4 vs 26.0 cm2, P < .01; Cohort 2: 66.3 vs 44.7 cm2, P < .01). Fig 1 illustrates the relatively stable surface area of chronic wounds over time in contrast to the dynamic changes of recurrent wounds. Chronic open wounds were significantly more painful than recurrent wounds (Supplemental Table II). No chronic open wounds healed during the study period. Cohort 2 participants reported recurrent wound healing in 6.3 ± 13 weeks and reblistering in 3.2 ± 6 weeks. The mean time between photographs in cohort 1 was 15 ± 19 weeks; thus, time to healing and reblistering was not captured in this group. This study defines 2 distinct RDEB wound types: chronic open wounds and recurrent wounds. This characterization is important when designing therapeutic trials and ensuring similarity of treatment arms. A previous clinical trial failed wherein 50% of wounds in the placebo arm healed, likely because of the inclusion of recurrent wounds that healed on their own within weeks.4Murrell D.F. Paller A.S. Bodemer C. et al.Wound closure in epidermolysis bullosa: data from the vehicle arm of the phase 3 ESSENCE Study.Orphanet J Rare Dis. 2020; 15: 190Crossref PubMed Scopus (1) Google Scholar In RDEB, chronic open wounds lead to complications such as infection and aggressive squamous cell carcinoma.1Bruckner-Tuderman L. Mellerio J.E. Wound healing in epidermolysis bullosa.Br J Dermatol. 2017; 177: e193-e195Crossref PubMed Scopus (7) Google Scholar Their chronicity is likely multifactorial, related to sustained trauma, bacterial colonization, the itch-scratch cycle, inflammation, impaired cell proliferation, and stem cell depletion.5Cianfarani F. Zambruno G. Castiglia D. Odorisio T. Pathomechanisms of altered wound healing in recessive dystrophic epidermolysis bullosa.Am J Pathol. 2017; 187: 1445-1453Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Additional study is underway with frequent monitoring of wounds to evaluate time to healing and reblistering in recurrent wounds. Future studies are needed to explore the optimal cutoff between recurrent and chronic open wounds to develop prognostic predictors for both types of wounds and develop early clinical interventions to reduce wound burden.