New insight of itch mediators and proinflammatory cytokines in epidermolysis bullosa

Abstract

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.

Measuring the impact of pruritus on epidermolysis bullosa patients: evaluation using an itch-specific instrument

“… 10 There is evidence that sera of EB patients contain higher level of itch mediators particularly thymic stromal lymphopoietin (TSLP), interleukin (IL-6) and IFN-γ. 11 …”

Successful treatment of multicentric Castleman's disease associated with dystrophic epidermolysis bullosa using anti‐interleukin‐6 receptor antibody

“…2 Several studies have reported that serum IL-6 levels are higher in Dystrophic Epidermolysis Bullosa patients than in healthy controls. 4 IL-6 induces systemic inflammation and acute-phase protein production. 5 This case, possibly the first of its kind to be treated with tocilizumab, emphasizes the role of IL-6 in inflammatory responses in severe forms of EB 5 and its association with recurrent fever in EB patients.…”