Chronic pruriuts on non-lesional skin does not affect the epidermal barrier – results from the SOMA.PRU study

Chronic pruritus on non-lesional skin (CPNL) is a hallmark of chronic pruritus of undetermined origin (CPUO) and characterized by persistent pruritus without visible skin lesions. While atopic dermatitis (AD) is well known to involve epidermal barrier disruption, the pathophysiology of CPNL remains poorly understood. Our goal was to compare stratum corneum (SC) morphology and its role as a functional epidermal barrier, the severity of the symptoms, the relationship between persistent itch and primary skin and scratch lesions, and selected inflammatory markers in patients with CPNL, AD, and healthy controls. We assessed corneocyte morphology and corneodesmosome density in skin samples using atomic force microscopy (AFM) and fluorescence microscopy (FLM). Transepidermal water loss (TEWL) and tissue hemoglobin index (THI) were used to evaluate epidermal barrier integrity and skin blood perfusion. Symptom severity was assessed using the Worst and Average Itch-Numerical Rating Scale (NRS), Scratch Sign Score (SSS), and patient-reported sleep disturbance. AD patients demonstrated structural differences in the SC, including reduced corneocyte area, clustering of corneocytes, absence of intermediate filaments, and relocated corneodesmosomes, along with elevated TEWL, THI values and IgE serum levels. In contrast, patients with CPNL displayed corneocyte morphology and skin barrier parameters like healthy controls, despite reporting high itch intensity and frequent sleep disturbance in clinical interviews. These findings indicate that CPNL is not triggered by a disrupted epidermal barrier but may represent different mechanisms.