REMOVED: Plasma Steroids and Endocannabinoids Used as Biomarkers to Assess the Pruritus Severity of Patients With Prurigo Nodularis

Abstract

Prurigo nodularis (PN) as an extremely pruritic and hyperplastic chronic dermatosis induces psychologically and physiologically stressful responses. PN-induced responses in the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG) axes and endocannabinoid system (ECS) are abnormal. Extant studies on the PN's pathogenesis mostly focused on the PN's psychological responses. To date, the PN's physiological responses remain not been fully uncovered yet. To investigate the PN-induced physiological responses via the levels of five steroids and two endocannabinoids combined with their ratios in plasma and examine the association between the psychological and physiological responses. Thirty-six patients with PN, 36 age- and gender-matched healthy controls were recruited. The PN's psychological symptoms including pruritus severity, pain and life quality were measured with the visual analog scale, the prurigo score index, numerical rating scale, verbal rating scale and dermatology life quality index. Their concentrations of steroids and endocannabinoids were determined with liquid chromatography-tandem mass spectrometry. Compared to controls, the PN patients showed lower plasma levels in cortisol, cortisone, N-arachidonoyl-ethanolamine (AEA), and the ratio of DHEA to 1-arachydonoyl glycerol (1-AG), which negatively moderately and over correlated with PN's symptoms, especially with the pruritus severity. Additionally, the PN patients exhibited higher levels in the ratios of testosterone and 1-AG to cortisol, which positively moderately and over correlated with pruritus severity. Thus, the seven biomarkers would be sensitive and reliable biomarkers for assessing the pruritus severity of PN because they met the screening criteria that the biomarkers show intergroup differences and showed moderate or over correlation with the pruritus severity of PN. To the best of our knowledge, this is the first study exploring PN-induced physiological responses. The findings suggest that alterations in these three endocrine systems may lead to new insights to psychological mechanisms and responses to prurigo nodularis.