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

Abstract

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.

FIGURE 1

Neurovascular architecture in psoriatic skin, highlighting nerve and vascular interactions across epidermal, papillary and reticular dermal layers. Left panel: Schematic representation of psoriatic skin layers, showing the distribution of free nerve endings (green) and vascular structures (red) in the epidermis, papillary dermis and reticular dermis. (A) Free nerve endings (green) in the epidermis that split off from perivascular nerves in the papillae. (B) Papillary perivascular nerves surrounding capillaries in the papillary dermis, (C) Superficial reticular vascular plexus with accompanying nerve fibres (yellow arrows) and leukocyte infiltrates (line drawing), and pgp9.5+ fibroblasts (orange arrows). (D) Neurovascular plexus in the deep reticular dermis, showing thick nerve bundles (grey arrow) running parallel to deep vascular plexus and fine nerve fibres surrounding the vasculature (arteries) (white arrows). Orange arrows show pgp9.5+ fibroblasts in some patients but not in all. Brown arrow shows innervation typically seen at the erector pili near hair follicles.

FIGURE 2

Immunofluorescent histological images of skin sections, oriented with the epidermis at the top and the reticular dermis at the bottom. The psoriatic vasculature, characterised by tortuous and elongated vessels, is visible in red. Thin green fibres indicate (peri)vascular nerves, including those innervating the erector pili muscles (patient 6 S1, patient 11 S2) and the hair follicle (patient 11 S3). Variations in epidermal thickness are also evident, with vertical vasculature marking the transition between the epidermis and the horizontal vasculature of the reticular dermis.

FIGURE 3

Correlation analyses of nerve fibre and vascular volume percentages across different skin layers in psoriatic tissue sections. (a) Papillary nerve fibre volume positively correlates with epidermal nerve fibre volume (R ² = 0.24, p = 0.02). (b) A significant inverse relationship is observed between epidermal nerve fibre volume and epidermal thickness (R ² = 0.18, p = 0.04). (c) No significant correlation is found between papillary nerve fibre volume and papillary vascular volume (R ² = 0.03, p = 0.46). (d) Reticular nerve fibre volume shows no significant correlation with reticular vascular volume (R ² = 0.01, p = 0.58). (e) Comparison of papillary nerve fiber volume with reticular nerve fiber volume shows no significant correlation (R ² = 0.04, p = 0.39. (f) The total nerve volume does not correlate significantly with total vascular volume (R ²  = 0.03, p = 0.45).

FIGURE 4

Nerve fibre volumes in different skin layers compared by biopsy location (elbow, extremities, trunk) and correlations with Physician Global Assessment (PGA). (a–d) Nerve fibre volume (%) in the epidermis (a), papillary dermis (b), reticular dermis (c) and total nerve fibre volume (d) are shown for different biopsy locations. No significant differences in nerve volume were observed between these locations. (e–h) Linear regression plots between nerve fibre volumes in the epidermis (e), papillary dermis (f), reticular dermis (g) and total nerve volume (h) with clinical severity as indicated by the Physician Global Assessment (PGA). Despite the trends, none of the correlations reached statistical significance (p > 0.05).