Reduced intraepidermal nerve fibre density in lesional and nonlesional prurigo nodularis skin as a potential sign of subclinical cutaneous neuropathy

Abstract

Background Prurigo nodularis (PN) is a highly pruritic condition characterized by multiple hyperkeratotic nodules. Previous immunohistochemical studies demonstrated increased numbers of dermal nerve fibres. Objectives Given that the sensation of pruritus is transmitted mainly by thin, unmyelinated epidermal nerves, the aim of our study was to investigate the intraepidermal nerve fibre (IENF) density. Methods Biopsies taken from lesional and nonlesional skin of 53 patients (37 women and 16 men; mean ± SD age 60·6 ± 14·9 years) with PN of diverse origin were immunostained for protein gene product 9·5. According to the guideline of the European Federation of Neurological Societies, the IENF density per millimetre was determined and compared with that in 20 healthy volunteers. Results Lesional and uninvolved PN skin biopsies showed significantly decreased IENF density (P < 0·001) regardless of patient age, origin of PN, intensity or quality of pruritus. Conclusions Hypoplasia of epidermal sensory nerves independently of clinical parameters is a new finding in PN and suggests involvement of epidermal nerves in PN pathophysiology. To date, it cannot be ruled out that reduced IENF density is due to repeated scratching. However, the presence of hypoplasia in nonlesional PN skin suggests the presence of a subclinical small fibre neuropathy.