Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors

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Abstract
Background Although some patients with psoriasis vulgaris also complain of severe pruritus, the data available regarding pruritus in psoriasis are sparse. Objectives To clarify the mechanism and mediators involved in the pruritus of psoriasis vulgaris, we compared itch‐associated factors in lesional skin from psoriatic patients vs. skin without pruritus quantitatively using a panel of histological and immunohistological parameters. Patients and methods Biopsied specimens were obtained from 38 patients with psoriasis vulgaris who were divided into two groups according to the presence or absence of pruritus. Results When compared with psoriatic patients devoid of pruritus, lesional skin from patients with pruritus showed the following characteristic features: (i) a rich innervation both in the epidermis and in the papillary dermis; (ii) an increase in neuropeptide substance P‐containing nerve fibres in perivascular areas; (iii) decreased expression of neutral endopeptidase in the epidermal basal layer as well as in the endothelia of blood vessels; (iv) many mast cells showing degranulating processes in the papillary dermis; (v) a strong immunoreactivity for nerve growth factor (NGF) throughout the entire epidermis and an increased NGF content in lesional skin homogenates; (vi) an increase in the expression of high‐affinity receptors for NGF (Trk A) in basal keratinocytes and in dermal nerves; (vii) an increased population of interleukin‐2‐immunoreactive lymphocytes; and (viii) a strong expression of E‐selectin on vascular endothelial cells. A significant correlation was observed between the severity of pruritus and protein gene product 9.5‐immunoreactive intraepidermal nerve fibres, NGF‐immunoreactive keratinocytes, expression of Trk A in the epidermis and the density of immunoreactive vessels for E‐selectin. These findings indicate that possible pruritogenic mediators in psoriatic lesional skin are neurogenic factors including innervation, neuropeptide substance P, neuropeptide‐degrading enzymes and NGF, activated mast cells, one or more cytokines and endothelial–leucocyte adhesion molecules. Conclusions These data document for the first time itch‐related local markers in psoriasis, and suggest complex and multifactorial mechanisms of pruritus in the disease. These results provide the groundwork for further studies to evaluate the efficacy of antipruritic treatment for psoriatic patients.