183 Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity

Abstract

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of hereditary epidermolysis bullosa, with a poorly understood pathogenesis and no satisfactory treatment. Our objective was to assess the clinical, biological features and genetic basis, to better characterize this rare genodermatosis. We conducted a retrospective study, reviewing the clinical presentation, genetic diagnosis, biological analyses and management of patients with DEB-Pr seen between 2010 and 2020. Seven patients were included, average age of 50.1 years. Pruriginous lichenified papules or nodules appeared at 27.6 years on average on pretibial areas and forearms, associated with milia and toenails dystrophy. All patients received multiple therapies but none could sustainably reduce pruritus. Immunohistopathological analysis of lesion skin revealed subepidermal blister with fibrosis, milia and mast cell infiltration. Serum TNFα, IL1β and IL6 levels were elevated in 2/6 patients. Total serum IgE levels were increased in 7/7 patients. Immunophenotyping of circulating T-cells revealed an increased Th2 subset in 4/4 patients, with reduced Th1 and Th17 subpopulations. Genetic analysis of COL7A1 identified 8 distinct causative mutations, 6 of which were new. Intra-familial clinical variability was documented in 5/7 patients and was associated with the co-inheritance of a recessive COL7A1 mutation or an FLG2 mutation in 2 families. Our study confirms the stereotyped presentation of DEB-Pr with large intra-familial variability in disease expression. Mast cell infiltration, elevated IgE and increased Th2 subset without atopy strongly support a role of Th2-mediated immunity in DEB-Pr, and further argue for new targeted therapeutic options such as dupilumab.