Abstract: Background Epidermolysis bullosa (EB) is a rare, genetically and clinically heterogeneous group of skin fragility disorders. No cure is currently available, but many novel and repurposed treatments are upcoming. For adequate evaluation and comparison of clinical studies in EB, well-defined and consistent consensus-endorsed outcomes and outcome measurement instruments are necessary. Objectives To identify previously reported outcomes in EB clinical research, group these outcomes by outcome domains and areas and summarize respective outcome measurement instruments. Methods A systematic literature search was performed in the databases MEDLINE, Embase, Scopus, Cochrane CENTRAL, CINAHL, PsycINFO and trial registries covering the period between January 1991 and September 2021. Studies were included if they evaluated a treatment in a minimum of three patients with EB. Two reviewers independently performed the study selection and data extraction. All identified outcomes and their respective instruments were mapped onto overarching outcome domains. The outcome domains were stratified according to subgroups of EB type, age group, intervention, decade and phase of clinical trial. Results The included studies (n = 207) covered a range of study designs and geographical settings. A total of 1280 outcomes were extracted verbatim and inductively mapped onto 80 outcome domains and 14 outcome areas. We found a steady increase in the number of published clinical trials and outcomes reported over the past 30 years. The included studies mainly focused on recessive dystrophic EB (43%). Wound healing was reported most frequently across all studies and referred to as a primary outcome in 31% of trials. Great heterogeneity of reported outcomes was observed within all stratified subgroups. Moreover, a diverse range of outcome measurement instruments (n = 200) was identified. Conclusions We show substantial heterogeneity in reported outcomes and outcome measurement instruments in EB clinical research over the past 30 years. This review is the first step towards harmonization of outcomes in EB, which is necessary to expedite the clinical translation of novel treatments for patients with EB

Abstract: Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous skin fragility disorder characterized by trauma-induced skin dissociation and the development of painful wounds. So far, mutations in 20 genes have been described as being associated with more than 30 clinical EB subtypes. The era of whole-exome sequencing has revolutionized EB diagnostics with gene panels being developed in several EB centers and allowing quicker diagnosis and prognostication. With the advances of gene editing, more focus has been placed on gene editing-based therapies for targeted treatment. However, their implementation in daily care will still take time. Thus, a significant focus is currently being placed on achieving a better understanding of the pathogenetic mechanisms of each subtype and using this knowledge for the design of symptom-relief therapies, i.e. treatment options aimed at ameliorating and not curing the disease

Abstract: Clinical StudyBetulin-Based Oleogel to Improve Wound Healing inDystrophic Epidermolysis Bullosa: A Prospective ControlledProof-of-Concept StudyAgnes Schwieger-Briel,1,2Dimitra Kiritsi,1Christoph Schempp,1,3Cristina Has,1and Hauke Schumann11Epidermolysis Bullosa Centre, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, Germany2Department of Pediatric Dermatology, University Children's Hospital Zurich, Zurich, Switzerland3Research Centre Skinitial, Department of Dermatology, Medical Center, University of Freiburg, Freiburg, GermanyCorrespondence should be addressed to Agnes Schwieger-Briel; agnes.schwieger@kispi.uzh.chReceived 20 February 2017; Accepted 18 April 2017; Published 22 May 2017Academic Editor: Elizabeth H. KempCopyright © 2017 Agnes Schwieger-Briel et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.Introduction. Skin fragility and recurrent wounds are hallmarks of hereditary epidermolysis bullosa (EB). Treatment options toaccelerate wound healing are urgently needed. Oleogel-S10 contains a betulin-rich triterpene extract from birch bark. In this study,we tested the wound healing properties of topical Oleogel-S10 in patients with dystrophic EB.Methods. We conducted an open,blindly evaluated, controlled, prospective phase II pilot trial in patients with dystrophic EB (EudraCT number 2010-019945-24).Healing of wounds treated with and without topical Oleogel-S10 was compared. Primary efficacy variable was faster reepithelial-ization as determined by 2 blinded experts. The main secondary outcome variable of the study was percentage of wound epithe-lialization.Results. Twelve wound pairs of 10 patients with dystrophic EB were evaluated. In 5 of 12 cases, both blinded reviewersconsidered epithelialization of the intervention wounds as superior. In 3 cases, only one reviewer considered Oleogel-S10 as superiorand the other one as equal to control. Measurements of wound size showed a trend towards accelerated wound healing with theintervention but without reaching statistical significance.Conclusion. Our results indicate a potential for faster reepithelializationof wounds in patients with dystrophic EB when treated with Oleogel-S10 but larger studies are needed to confirm significance

Abstract: Dystrophic epidermolysis bullosa (DEB) is a blistering skin disease caused by mutations in the gene COL7A1 encoding collagen VII. DEB can be inherited as recessive DEB (RDEB) or dominant DEB (DDEB) and is associated with a high wound burden. Perpetual cycles of wounding and healing drive fibrosis in DDEB and RDEB, as well as the formation of a tumor-permissive microenvironment. Prolonging wound-free episodes by improving the quality of wound healing would therefore confer substantial benefit for individuals with DEB. The collagenous domain of collagen VII is encoded by 82 in-frame exons, which makes splice-modulation therapies attractive for DEB. Indeed, antisense oligonucleotide-based exon skipping has shown promise for RDEB. However, the suitability of antisense oligonucleotides for treatment of DDEB remains unexplored. Here, we developed QR-313, a clinically applicable, potent antisense oligonucleotide specifically targeting exon 73. We show the feasibility of topical delivery of QR-313 in a carbomer-composed gel for treatment of wounds to restore collagen VII abundance in human RDEB skin. Our data reveal that QR-313 also shows direct benefit for DDEB caused by exon 73 mutations. Thus, the same topically applied therapeutic could be used to improve the wound healing quality in RDEB and DDEB

Abstract: Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disorder, characterized by trauma-induced blistering followed by soft tissue fibrosis. One of the most feared complications is the early development of aggressive cutaneous squamous cell carcinomas (SCC). For patients with locally advanced or metastasized SCCs treatment with cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), has been proposed and so far, treatment of five DEB patients with cetuximab has been published. With this report, we extend the spectrum of EB patients treated with cetuximab by adding two additional patients. Taking together all DEB cases treated with cetuximab, we propose that cetuximab should be administered as early as possible, since it seems to be more efficient and is accompanied by rather mild adverse effects. We also show that EGFR is frequently expressed in DEB-associated SCCs, although there were noticeable differences in the level of expression, which may influence responsiveness to EGFR-targeting therapies. Although only limited experiences with targeted cancer treatments in EB exist, such reports highlight the treatments' effects in this specific cohort and assist our therapeutic decisions