Targeting IL-1 controls refractory Pityriasis rubra pilaris

Abstract

Abstract Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease which lacks efficacious standard-of-care treatments. Molecular studies of skin lesions revealed that IL-1β is central to the pathogenesis of PRP. Treatment of three patients with the IL-1-targeting biologics anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature. We identified an NF-κB-mediated IL-1β-CCL20 axis central to the inflammatory response in PRP. Our results reveal the central role of IL-1β signaling in the pathogenesis of PRP and highlights its prominence as a therapeutic target.