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Background: Dystrophic epidermolysis bullosa pruriginosa (DEB‐Pr) is a rare subtype of hereditary epidermolysis bullosa, with a poorly understood pathogenesis and no satisfactory treatment. Objectives: To assess the clinical and biological features, genetic basis and therapeutic management, to better characterize this rare genodermatosis. Methods: We have conducted a retrospective study, reviewing the clinical presentation, genetic diagnosis, immunohistopathological findings and biological characteristics and management of patients with dystrophic epidermolysis bullosa pruriginosa. This study was conducted in the Department of Dermatology at Saint‐Louis Hospital and the Department of Genetics at Necker Hospital (Paris, France). All patients with a diagnosis of DEB‐Pr seen between 2010 and 2020 were included. Results: Seven patients were included, the average age of 50.1 years [range 36–76]. Pruriginous‐lichenified papules, plaques or nodules appeared at 27.6 years on average [range 7–66] on pretibial areas and forearms, associated with milia and toenails dystrophy. All patients received multiple treatments, 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, with no history of atopy. 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 7 distinct causative mutations, six 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. Conclusion: 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. Linked Commentary Z. Ruszczak and S. Abdelhadi. J Eur Acad Dermatol Venereol 2022; 36: 13–16. https://doi.org/10.1111/jdv.17821. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a systemic disease that affects the skin in about 25% of patients. The treatment of cutaneous sarcoidosis is guided by the extent of lesions, associated symptoms and organ involvement. To evaluate rates of response to various potential first-line treatments for cutaneous sarcoidosis during the year following treatment initiation. This retrospective multicentre study included 120 patients with cutaneous sarcoidosis. Treatment response was assessed retrospectively from the patients' medical records. Univariate logistic regression analysis, with an estimation of unadjusted odds ratios (OR) and their 95% CI ,was performed to identify factors associated with complete cutaneous remission (CR), followed by multivariate logistic regression analysis. At one year, 43 of the 120 (36%) included patients had CR. The best response rates were obtained with oral corticosteroids (12/21, 57%), followed by a combination of hydroxychloroquine and topical steroids (6/13, 46%). In multivariate analysis, lupus pernio was the only predictor of a poor cutaneous response. We suggest the use of a combination of hydroxychloroquine and topical steroids as an optimal first-line treatment for cutaneous sarcoidosis, given the known adverse effects of systemic corticosteroids.

Competing Interests: Conflicts of interest: F.A. and O.D. have received hospitality and speakers’ honoraria from Kyowa Kirin.

Cutaneous T-cell lymphomas (CTCLs) are rare malignancies involving primarily the skin. Responses to treatment are usually short-lived in advanced CTCL. The determinants of long-term CTCL control are unclear. Mogamulizumab, an anti-human CCR4 antibody that acts by antibody-dependent cell cytotoxicity against CCR4+ CTCL tumor cells and peripheral memory blood regulatory T cells, has been associated with long-lasting remissions and immune adverse events. Here, we reported skin rashes in 32% of 44 patients with CTCL treated with mogamulizumab, associated with significantly higher overall survival (hazard ratio, 0.16; 0.04-0.73; P = .01). Rash occurred in patients with Sézary syndrome and was associated with longer time to progression. These rashes were characterized by a CD163+ granulomatous and/or CD8+ lichenoid skin infiltrate. High-throughput sequencing analysis of T-cell receptor β genes in skin and blood flow cytometry confirmed the depletion of CTCL tumor cells, as well as the recruitment of new reactive T-cell clones in skin at the time of skin rash. CXCL9 and CXCL11, two macrophage-derived chemokines that recruit CXCR3+ T cells to skin, were overexpressed in skin rashes. A higher frequency of TIGIT+ and PD1+ exhausted reactive blood T cells was observed at baseline in patients with rash, and this frequency decreased with mogamulizumab treatment. These data are consistent with mogamulizumab-induced long-term immune CTCL control by activation of the macrophage and T-cell responses in patients with rash., (© 2022 by The American Society of Hematology.)