Background and objectives: Prurigo nodularis (PN) is a severe, intensely pruritic subtype of chronic prurigo for which the molecular basis and interplay between pathophysiologic mechanisms and clinical manifestations are poorly understood.
Methods: LOTUS-PN was a longitudinal observational study that included 54 participants from 11 centers and was designed to improve disease understanding. Protein expression, histology and RNA analyses were performed.
Results: Histologically, all patients had typical PN characteristics. Immunohistochemically, and on the mRNA level, expression in lesional versus non-lesional samples for IL-31 (p < 0.01) was significantly higher. In addition, immunohistochemistry showed higher expression of IL-31RA (p < 0.05), OSM (p < 0.05) and OSMRß (p < 0.01). PN lesional skin showed higher expression of Th2 and Th17/Th22 pathway markers. A correlation analysis of gene expression highlighted two groups of intra-marker correlations dividing the Th2 markers, the first containing barrier and regulatory genes and the other containing markers of general inflammation that correlated negatively and positively with Th17/Th22 genes, respectively. Correlations between gene expression and NRS scores were weak and involved genes associated with general inflammation (MMP12) and Th2 (IL10, CCL18, IL4R).
Conclusions: Our study confirms the role of Th2 signature in PN and the dominant role of IL31. Correlation analysis of gene expression showed differing relationships between subsets of the Th2 axis with Th1 and Th17/Th22 markers, highlighting the potential of different components of the Th2 pathway to interact with and modulate other immune axes.
Keywords: OSMR pathway; chronic prurigo; neuroimmune itch pathways; prurigo nodularis; pruritus.
© 2025 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.