Nerve Fibres in Psoriatic Skin and Their Relation to Vasculature and Clinical Parameters

Emerging evidence supports the neurogenic origin of psoriasis, yet the morphology and distribution of nerve fibres in psoriatic skin remain poorly characterised due to methodological inconsistencies and limited 3D data. The aim of this study was to provide a comprehensive 3D quantification of nerve fibre morphology in psoriatic skin and assess its spatial relation to vasculature and clinical parameters. High-resolution confocal microscopy was used to analyse 69 (70 μm thick) skin sections from 23 psoriasis patients, capturing full-thickness epidermis and dermis. Nerve fibres were segmented by location (epidermal, papillary and reticular) and quantified volumetrically alongside vascular networks. The results show that nerve fibres occupied ~0.1% of total skin volume and predominantly localised near vasculature in the dermis, with epidermal nerves branching from perivascular plexuses. Epidermal nerve fibre volume negatively correlated with erythema, age and epidermal thickness (p < 0.05). No significant correlation was observed between dermal nerve fibre volumes and vascular density or clinical severity scores. This study presents a detailed 3D neurovascular map of psoriatic skin, revealing a distinct topography of nerve-vessel relationships. The findings highlight that epidermal nerve fibres (not total nerve density) show the strongest association with clinical markers. These results provide a critical baseline for evaluating nerve-targeted therapies and modelling neurovascular responses in laser-based psoriasis treatments.