Prurigo nodularis and the microbiome.

Prurigo nodularis (PN) is a chronic skin condition that profoundly impacts quality of life. Histopathological studies of itchy hyperkeratotic nodules show dense infiltrates of T lymphocytes, mast cells, and eosinophils. A robust inflammatory response is implicated, coupled with key changes in neuronal plasticity that affect nerve fiber architecture and function. The microbial community in PN lesions exhibits a distinct composition, marked by decreased α-diversity and a prominent increase in Staphylococcus aureus (S aureus). This alteration appears to contribute to the disease's pathophysiology, causing further disruption of the skin barrier, immune dysregulation, and neuronal plasticity. There is ample evidence that virulence factors of S aureus promote Th2, Th17, and Th22 cytokine production, which are key to PN. In addition, S aureus V8 protease (Endoproteinase Glu-C) has recently been identified to trigger robust itch by activating protease-activated receptor 1 (PAR1) on sensory neurons. This review underscores the complex interplay between the altered microbiome and the itch-scratch cycle of PN, providing insights into potential therapeutics targeting the skin microbiome. A multidisciplinary approach is crucial for providing relief to individuals suffering from this skin condition.