Keratin-associated epidermolysis bullosa simplex: phenotypes and challenges in clinical trials – a narrative review and systematic update

• Published in: Orphanet journal of rare diseases Vol. 20; no. 1; pp. 313 - 14
• Main Authors: Wally, Verena, Welponer, Tobias, Wiesinger, Hans-Peter, Diem, Anja, Thiel, Konstantin, Geroldinger, Martin, Zimmermann, Georg, Hummel, Julia I., Dorfer, Sonja, Hofbauer, Josefina Piñón, Bauer, Johann W., Laimer, Martin
• Format: Journal Article
• Language: English
• Published: London BioMed Central 20.06.2025; BioMed Central Ltd; BMC
• Subjects: Blisters; Care and treatment; Case reports; Clinical trials; Clinical Trials as Topic; Epidermolysis bullosa; Epidermolysis bullosa simplex; Epidermolysis Bullosa Simplex - genetics; Epidermolysis Bullosa Simplex - metabolism; Epidermolysis Bullosa Simplex - pathology; Health aspects; Human Genetics; Humans; Keratin; Keratins - metabolism; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Pharmacology/Toxicology; Phenotype; Physiological aspects; Review; Social aspects; Austria; Blisters; Clinical trials; Case reports; Epidermolysis bullosa simplex
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-025-03822-0

Introduction Clinical research on innovative therapies for the rare genodermatosis epidermolysis bullosa (EB) faces significant challenges, including small sample sizes, disease heterogeneity with intra- and inter-individual variability, limited understanding of pathogenic mechanisms and natural disease course, as well as the lack of patient-centred core outcomes. Moreover, existing tools and techniques to assess disease activity and dynamics are heterogeneous, inconsistent, and may fail to consider or inaccurately emphasize particularities of individual patients and distinct EB subtypes. Methods In order to exemplify the differences between keratin-associated subtypes of EB simplex (k-EBS), we summarized respective clinical characteristics in a narrative way. In addition, we performed a systematic review of the literature published over the last 5 years, with the aim to give an overview on outcomes and their assessments used in these patient populations. Results This review summarises the methodological scope, strengths and limitations of outcome assessments in clinical trials for the k-EBS, a group of inherited skin fragility diseases characterised by their distinct phenotype of epidermal blistering. Conclusions By presenting an overview of the clinical spectrum of k-EBS, we identified key gaps in current assessment methodologies and propose alternative approaches to optimise the evaluation of skin blistering, with the aim of enhancing the accuracy, reliability, and patient-relevance of clinical outcomes.