Dominant Dystrophic Epidermolysis Bullosa Pruriginosa Responding to Naltrexone Treatment

Pallesen, Kristine Appel Uldall; Lindahl, Kim Hein; Bygum, Anette

doi:10.2340/00015555-3304

Cited by 7 publications

(7 citation statements)

References 8 publications

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“…19 Several other therapies have been reported in the literature including intra-lesional steroid injections, cryotherapy, ultraviolet B phototherapy, topical tacrolimus, topical gel-containing ketamine 0.5% and amitriptyline 2% associated with oral sertraline, 20 oral steroids, cyclosporin, mizoribin, 21 thalidomide 22,23 and naltrexone. 24 Some of these treatments were efficacious in isolated cases, but their efficacy was not sustainable. Ultimately, severe pruritus and visible chronic lesions result in a poor quality of life and a heavy burden as reported for patients with DEB.…”

Section: Introductionmentioning

confidence: 99%

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

Darbord

Hickman

Pironon

et al. 2021

Acad Dermatol Venereol

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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. MethodsWe 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 TNFa, IL1b 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. ConclusionOur 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.

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Section: Introductionmentioning

confidence: 99%

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

Darbord

Hickman

Pironon

et al. 2021

Acad Dermatol Venereol

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“…EBP is notoriously resistant to therapy, as attested by the large number of modalities reported in the literature including both topical (corticosteroids, calcineurin inhibitors) and systemic drugs (antihistamines, ciclosporin, thalidomide, naltrexone) . The disabling pruritus associated with EBP (and DEB) has been attributed to immune dysregulation.…”

mentioning

confidence: 99%

Treatment of epidermolysis bullosa pruriginosa‐associated pruritus with dupilumab

Shehadeh

Sarig

et al. 2020

Br J Dermatol

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“…DEB‐Pr is notoriously resistant to be the treatment of pruritus 4,49,50 . Recently, six previous reports have documented successful treatment of DEB‐Pr with dupilumab, a monoclonal antibody targeting the IL‐4 receptor alpha (IL‐4Rα) that provides dual blockade of IL‐4 and IL‐13, which play an important role in the pathogenesis of AD 4,26,51–53 .…”

Section: Discussionmentioning

confidence: 99%

“…48 DEB-Pr is notoriously resistant to be the treatment of pruritus. 4,49,50 Recently, six previous reports have documented successful treatment of DEB-Pr with dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha (IL-4Rα) that provides dual blockade of IL-4 and IL-13, which play an important role in the pathogenesis of AD. 4,26,[51][52][53] In addition, Darbord et al 54 reported mast cell infiltration of the lesional skin, high serum total IgE levels and increased Th2 subsets in circulating T cells in patients with DEB-Pr.…”

Section: Ta B L E 2 (Continued)mentioning

confidence: 99%

New insight of itch mediators and proinflammatory cytokines in epidermolysis bullosa

Nguyen

Shinkuma

Katsumi

et al. 2022

J Cutaneous Imm & Allergy

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Objectives Epidermolysis bullosa (EB) is a hereditary disorder characterized by mechanical stress‐induced blistering. The presence of extracutaneous complications such as cardiomyopathy and renal disease observed in severe EB subtypes and the fact that pruritus is a common symptom across all EB subtypes indicate that EB is not only a skin fragility disease but also a systemic inflammatory disorder. Our study aims to elucidate the basis of the systemic inflammation seen in EB patients. Methods We analyzed serum samples of 20 EB patients by Luminex bead‐based cytokine assays and enzyme‐linked immunosorbent assays. Results The serum levels of sIL‐2R, IL‐6, HGF, M‐CSF, SCGF‐β, IL‐8, IL‐16, IFN‐γ, MIF, MIP‐1α, and thymic stromal lymphopoietin (TSLP) (p < .01, p < .01, p < .01, p < .01, p < .01, p < .05, p < .05, p < .05, p < .05, p < .05, and p = .01, respectively) were found to be significantly elevated in EB patients, whereas TNF‐β (p < .01) was decreased. Th2 cytokines including IL‐4, IL‐5, and IL‐13 were not elevated in EB patients. In contrast, TSLP was significantly increased, and IL‐31 and oncostatin M were not statistically significant but tended to be higher in the patients than in healthy controls. Among proinflammatory cytokines such as IL‐1β, IL‐6, and TNF‐α, IL‐6 was elevated in EB patients. Conclusions The imbalance of several itch mediators and proinflammatory cytokines was identified. Biologics targeting the cytokines found to be elevated in the sera of patients is considered as a beneficial treatment option for EB.

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Dominant Dystrophic Epidermolysis Bullosa Pruriginosa Responding to Naltrexone Treatment

Cited by 7 publications

References 8 publications

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

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

Treatment of epidermolysis bullosa pruriginosa‐associated pruritus with dupilumab

New insight of itch mediators and proinflammatory cytokines in epidermolysis bullosa

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