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Background: Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death., Objectives: EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited., Methods: Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and < 9 months that was 10-50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel - both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days., Results: A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met; Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01-2·05; P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe)., Conclusions: Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well -tolerated., Competing Interests: Conflicts of interest: J.S.K. has received grants and/or fees for consultancy in the last 12 months from Amryt. E.S. has received grants for consultancy in the last 12 months from Amryt, Kamari Pharma Ltd, and BiomX, and as CMO of Sol-Gel Technologies Ltd. F.S., C.B. and M.F.F. have received grants and/or fees for consultancy in the last 12 months from Amryt. T.C., S.L. and M.S. are employees of Amryt Research Ltd. C.D. is a paid contractor for Amryt Research Ltd. A.L.B. has received grants and/or fees for consultancy in the last 12 months from Amryt, Amicus/Scioderm, Castle Creek, Fibrocell, ProQR/Wings and Phoenix Tissue Repair. D.F.M. has received grants and/or fees for consultancy in the last 12 months from Amryt and Amicus, and is a co-owner of the patent for topical sirolimus for epidermolysis bullosa simplex. A complete list of investigators in the EASE trial is provided in the Supporting Information., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Epidermolysis bullosa (EB) is a group of rare and currently incurable genetic blistering disorders. As more pathogenic-driven therapies are being developed, there is an important need for EB-specific validated outcomes measures designed for use in clinical trials., Objectives: To test the reliability and construct validity of an instrument for scoring clinical outcomes of research for EB (iscorEB), a new combined clinician- and patient-reported outcomes tool., Methods: We conducted an observational study consisting of independent 1-day assessments (six assessors) at two academic hospitals. The assessments consisted of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity (BEBS) and global severity assessment for physicians; and iscorEB patient (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's Dermatology Life Quality Index for patients. Construct validity and intraclass correlation coefficients (ICCs) for interobserver, intraobserver and test-retest reliability were calculated., Results: Overall, 31 patients with a mean age of 19·5 years (1·8-45·2) were included. Disease severity was mild in 42% of cases, moderate in 29% and severe in 29%. The interobserver ICC was 0·96 for both the clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver reliability was 0·91 and 0·70 for the skin and mucosal domains of iscorEB-c, respectively. Cronbach's alpha for iscorEB-c was 0·89. The test-retest reliability of iscorEB-p was 0·97 and Cronbach's alpha was 0·84. The clinical score differentiated between subjects with mild, moderate and severe disease, and both clinical and patient subscores discriminated between recessive dystrophic EB and other EB subtypes., Conclusions: iscorEB has robust reliability and construct validity, including strong ability to distinguish EB types and severities. Further studies are planned to test its responsiveness to change., (© 2018 British Association of Dermatologists.)

Background: Reduced bone mass and fractures are known complications of generalized forms of epidermolysis bullosa (EB). However, the aetiology - inadequate bone acquisition, premature bone loss, or a combination - is unclear., Objectives: To determine patterns of bone mineral acquisition in children with EB and to identify clinical and laboratory correlates of change in areal bone mineral density (aBMD)., Methods: Seventeen subjects ≥ 6 years of age with generalized EB were studied at two visits at least 12 months apart with clinical and laboratory evaluations and dual energy X-ray absorptiometry scans of the lumbar spine. Wilcoxon signed-rank tests were used to determine if changes from baseline to follow-up were significant. Wilcoxon rank-sum tests were used to compare subjects with gains in aBMD Z-score with those who experienced no change or decreases to determine if baseline laboratory or clinical characteristics differed between the two groups., Results: Subjects gained height and weight at follow-up, but there was no significant improvement in mean Z-scores for height, weight or body mass index. Laboratory values did not change significantly. Mean bone mineral content and aBMD of the lumbar spine increased significantly at follow-up, but mean aBMD Z-scores remained static. No differences in clinical characteristics or laboratory values were seen between subjects with increased aBMD Z-scores vs. those whose scores decreased or did not change., Conclusions: Low bone mass in children with generalized EB is due primarily to inadequate gains in aBMD. Interventions to improve overall health and to help build bone mass in this patient population are warranted., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Desmoplakin is the major linker in desmosomes in epithelia and myocardium, anchoring intermediate filaments by the C-terminus to plakoglobin and plakophilin in the desmosomal plaque. Mutations in the gene DSP encoding desmoplakin have been associated with various phenotypes affecting skin and/or heart. One of these phenotypes, lethal acantholytic epidermolysis bullosa (LAEB), is characterized by extensive postnatal shedding of epidermis leading to early demise and is caused by recessive mutations in the gene DSP resulting in truncation of the desmoplakin C-terminus. Here we describe two infants born to the same consanguinous parents who suffered extensive epidermal dislodgment and died shortly after birth. In addition, universal alopecia, anonychia, malformed ears and cardiomyopathy were observed. As the clinical diagnosis was LAEB, DSP mutation analysis was performed. A homozygous deletion (c.2874del5) abrogating the donor splice site of exon 20 was found. The deletion is predicted to cause read-through in intron 20 with subsequent recognition of a premature termination codon, resulting in desmoplakin lacking its rod domain and C-terminus (p.Lys959MetfsX5). Electron microscopic analysis of skin biopsies showed absence of the desmosomal inner dense plaque and lack of tonofilament insertion. This is the second report of LAEB. These findings suggest DSP mutations as the aetiology of LAEB and cardiomyopathy as part of the phenotype. Furthermore, they indicate that in addition to the desmoplakin C-terminus, the rod domain is dispensable for intrauterine development but is essential for the inner dense plaque of desmosomes., (© 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.)