Sang Eun Lee

Background Pruritus is a highly burdensome symptom in patients with epidermolysis bullosa, especially recessive dystrophic epidermolysis bullosa (RDEB); however, only a few studies have assessed the molecular pathogenesis of RDEB‐associated pruritus. Interleukin (IL)‐31 is a key cytokine implicated in pruritus associated with dermatologic diseases such as atopic dermatitis and prurigo nodularis. Objective To investigate the role and cellular source of IL‐31 in RDEB‐associated pruritus. Methods Serum and skin samples were obtained from 11 RDEB patients and 11 healthy controls. Pruritus visual analogue scale scores were determined. Serum levels of IL‐31 and thymic stromal lymphopoietin (TSLP) were examined by enzyme‐linked immunosorbent assay (ELISA). The expression of IL‐31 and other pruritus mediators in the skin were examined through immunofluorescence staining, and their correlation with pruritus severity was analysed. Results Serum IL‐31 and TSLP were elevated in RDEB patients. IL‐31 expression was increased in RDEB skin and positively correlated with pruritus severity. Most of the IL‐31‐expressing cells were mast cells, and some were CD206(+) M2‐like macrophages. The number of substance P(+) cells was also increased in the patients' skin, and most of them were mast cells. The number of substance P(+) mast cells was correlated with the number of IL‐31(+) dermal infiltrates. The number of IL‐4Rα‐ and IL‐13‐expressing cells and expression of TSLP and periostin increased in RDEB skin, but without a correlation to pruritus score. Conclusion The increased production of skin IL‐31 from mast cells and M2‐like macrophages may be the mechanism underlying pruritus in RDEB.