The patient’s perspective: a review on epidermolysis bullosa patients’ needs as input towards harmonization of outcomes

Abstract

Epidermolysis Bullosa (EB) comprises a heterogenous group of rare genetic skin disorders, characterized by blistering. EB is classified in four major types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB), originating from various pathogenic variants and resulting in phenotypic diversity. Despite recent advancements in EB research and therapy, no cure exists, and treatments primarily focus on symptomatic relief. However, the variability in symptoms across EB types poses challenges for consistent assessment of therapeutic targets for clinical trials. A semi-systematic literature search was conducted, encompassing PubMed (MEDLINE), the Orphanet Journal of Rare Diseases, and EB patient organization websites. Studies reporting patient perspectives, including symptoms, impaired abilities, and daily life functions, as well as emotional and social impacts, were included. Pain and itch emerged as the most prevalent and impactful symptoms across major EB types, with itch particularly pronounced in recessive DEB. In EBS patients, pain, and blisters under the soles of the feet led to impaired mobility and reduced quality of life. KEB patients experienced the burden of blisters and fragile skin. DEB and JEB patients experienced wound burdens characterized by size, pain, and slow healing. Impaired sleep and reduced mobility were identified as the most impactful factors reducing quality of life across EB types. However, current outcome domains in EB clinical trials inadequately represent patient-reported outcomes, notably itch, pain, mobility impairments, and sleep difficulties. Specific symptoms, such as neuropathic pain in EBS, scalp blistering, hair loss in JEB, swallowing difficulties, and skin cancer in DEB, are underrepresented in measured outcomes. Our findings offer an overview of needs and disease burden experienced by EB patients of the major types and may serve as a basis for defining core outcome sets in future COSEB meetings. Ultimately, we aim to contribute to the harmonization of outcome domains in EB to enhance the comparability and efficiency of future research and clinical trial design.