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The skin
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Epidermolysis bullosa is another exceptionally heterogeneous group of disorders in which genetic differences are supported by the clinical and histological features and where expert clinical and laboratory diagnosis is particularly important. Thus, the neonatal letalis form (now partly treatable by steroids) is autosomal recessive, while the mild simplex types, without scarring, are autosomal dominant; at least one form results from a molecular defect in keratin. The dystrophic forms with scarring may follow either pattern, but most severe cases are autosomal recessive. A defect in type 7 collagen has been found in most families. Junctional forms are due to defects in the basement membrane zone. Prenatal diagnosis of the letalis and dystrophic forms is usually possible by DNA analysis on chorion biopsy, where the molecular defect is known. This has largely superseded the use of fetal skin biopsy.
Dermatology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Epidermolysis bullosa is a group of rare genetic conditions of mucocutaneous skin fragility. Presentation and clinical course is highly variable dependent on the type (simplex, junctional or dystrophic) and the underlying genetic mutation.
Musculoskeletal disorders and connective tissue disorders
Published in Steve Hannigan, Inherited Metabolic Diseases: A Guide to 100 Conditions, 2018
The symptoms of epidermolysis bullosa vary depending on the form of the disorder. In the simplex form, blisters occur on the outer layers of the skin. This form can be divided into two subtypes, namely the Weber-Cockayne variant and the Dowling-Meara variant. In the Weber-Cockayne variant the blisters are usually found on the feet and hands. The Dowling-Meara variant presents shortly after birth or later, and the blisters occur over much of the body. Individuals afected by this variant may also have growth problems resulting from diiculties with feeding due to blisters in the mouth and severe gastro-oesophageal relux. Later complications include thickened hard skin over the palms and soles (hyperatosis).
Surgical management of hand deformities in patients with recessive dystrophic epidermolysis bullosa
Published in Journal of Plastic Surgery and Hand Surgery, 2020
Xianyu Zhou, Yan Zhang, Mengmeng Zhao, Yuluo Jian, Jinny Huang, Xusong Luo, Jun Yang, Di Sun
Epidermolysis bullosa (EB) is a group of rare genetic disorders characterized by increased skin fragility, blistering and scarring in response to minor mechanical injury [1]. Based on the location of the fragility and the level of skin cleavage, EB is classified into four major types: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome [2]. DEB is caused by a mutation in the COL7A1 gene. This gene encodes type VII collagen, which makes up the anchoring fibrils in the sublamina densa. The defective anchoring fibrils allow easy epidermal detachment from the dermis, thus resulting in blisters [3,4]. DEB is categorized into two main subtypes: autosomal dominant DEB (DDEB) and recessive DEB (RDEB). These two subtypes are further mainly classified into DDEB generalized, DDEB acral, DDEB pretibial, DDEB pruriginosa, RDEB generalized severe, RDEB generalized intermediate, RDEB inversa, RDEB localized, RDEB pretibial and RDEB pruriginosa [2,5]. For DEB patients, mortality rates during infancy or early childhood are low if meticulous pediatric and dermatologic intensive care was provided.
The NK1 receptor antagonist serlopitant for treatment of chronic pruritus
Published in Expert Opinion on Investigational Drugs, 2019
Sonja Ständer, Mary C. Spellman, Paul Kwon, Gil Yosipovitch
Serlopitant is an oral once-daily NK1 receptor antagonist (Box.1). The clinical development for serlopitant was initiated by Merck in January 2005 and included 13 phase I studies and 2 phase II studies in patients with overactive bladder (N = 557) and alcohol dependence (N = 162) [38,39]. In 2012, the serlopitant clinical development program was licensed to Menlo Therapeutics, formerly Tigercat Pharma, where phase II clinical studies have been completed in patients with chronic pruritus, pruritus associated with PN, pruritus associated with atopic dermatitis, pruritus associated with psoriasis, and chronic cough [39–43]. In addition, an exploratory phase II investigator-initiated study was completed in patients with epidermolysis bullosa by researchers at Stanford University [44]. Serlopitant is currently being developed for the treatment of pruritus associated with PN, pruritus associated with psoriasis, and chronic pruritus of unknown origin (CPUO).
Current developments in gene therapy for epidermolysis bullosa
Published in Expert Opinion on Biological Therapy, 2022
Thomas Kocher, Igor Petkovic, Johannes Bischof, Ulrich Koller
The blistering skin disease epidermolysis bullosa is a heterogeneous disorder with numerous involved genes and respective mutations causing certain EB subtypes [1]. The presence of dominant or recessive inherited mutations, the diversity of mutation types and the divergent localization of the affected protein within patient skin of the respective EB subtype complicate the selection of an appropriate gene therapeutic strategy. Depending on these factors, either an RNA or DNA-based gene repair strategy can be the better choice. Splicing-modulation therapies showed promise in pre-clinical or/and clinical settings for various genetic diseases including Huntington’s disease, Duchenne muscular dystrophy, Spinal muscular atrophy and epidermolysis bullosa [42,43,138–141].