The Distinctive Immunologic Pathogenesis Differentiates Atopic Comorbidity Status in Prurigo Nodularis

Abstract

Background: Prurigo nodularis (PN) is a chronic pruritic skin disorder with a large number of hyperkeratoticnodules. The precise mechanisms of its pathogenesis remain unknown. PN has been linked to atopic dermatitis(AD), but its association remains unclear. Objective: We aimed to investigate the clinical, histological, and immunohistochemical characteristics of patientswith PN and PN underlying AD (PN-AD). Methods: Eight patients were recruited for PN, PN-AD, and eight normal subjects, respectively. Skin tissues wereobtained from patients and healthy subjects for histological and immunohistochemical analyses. Results: Histological examination showed increased epidermal thickness and dermal inflammatory cell counts in thePN-AD and PN groups compared to normal subjects. Immunohistochemical analyses revealed that the expression ofinterleukin (IL)-4, IL-13, IL-18, IL-31, IL-33, interferon (IFN)-γ, stromal-derived factor (SDF) 1-α and thymicstromal lymphopoietin (TSLP) was increased in the tissues of PN-AD and PN groups, in which the stainingintensities of IL-4, IL-13, SDF1-α and TSLP in the PN-AD group were higher than those in the PN group, but thedifferences were not statistically significant. Conversely, the staining intensities of IL-18, IL-33 and IFN-γ weresignificantly higher in the PN group than those in the PN-AD group. Conclusion: The pathogenesis of PN may differ from that of PN-AD, in which IL-18, IL-33 and IFN-γ may beassociated, implying that epidermal injury is the initial cause of IL-18 and IL-33 induction, which then increasesIFN-γ, resulting in the inflammatory process of PN.