Dramatic Improvement of Treatment-Refractory Prurigo Nodularis Following Initiation of Semaglutide: A Case Report.

Prurigo nodularis (PN) is a chronic inflammatory dermatosis characterized by intensely pruritic hyperkeratotic nodules affecting the trunk and extremities. Despite an expanding therapeutic armamentarium including dupilumab and nemolizumab, a subset of patients remains inadequately controlled. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in the management of type 2 diabetes and obesity, have provided emerging evidence supporting immunomodulatory and anti-inflammatory effects in several chronic inflammatory dermatoses. We report the case of a 64-year-old man with severe, treatment-refractory PN who had failed multiple lines of therapy over four years, including potent topical corticosteroids, dupilumab, and methotrexate. Following initiation of semaglutide for obesity, and with no change to his background PN treatment, a dramatic and progressive clinical improvement was observed. To our knowledge, this is the first reported case of PN improvement under GLP-1 RA therapy. The potential mechanisms underlying this benefit include modulation of low-grade chronic inflammation, direct effects on GLP-1 receptor-expressing immune cells, possible modulation of Th2 immune response, and anti-nociceptive action on pruritus via central and peripheral neuro-immune pathways. This observation highlights the potential of GLP-1 RAs as adjunctive therapy in refractory inflammatory dermatoses and warrants further investigation.