Targeting IL-1 controls refractory pityriasis rubra pilaris

• DOI: 10.1126/sciadv.ado2365
• Publication Date: 2024-07-03T17:59:13Z
• Authors: Eloi Schmauch; Yannik Severin; Xianying Xing; Aaron Mangold; Curdin Conrad; Pål Johansen; J. Michelle Kahle...; Mark Mellett; Alexander Navarini; Stefan Nobbe; Mrinal K. Sarkar; Abhigyan Satyam; Lam C. Tsoi; Lars E. French; Jakob Nilsson; Suvi Linna-Kuosmanen; Minna U. Kaikkonen; Berend Snijder; Manolis Kellis; Johann E. Gudjonsson; George C. Tsokos; Emmanuel Contassot; Antonios G. A. Ko...
• Keywords: Pityriasis rubra pilaris; Refractory (planetary science)

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with poorly understood pathogenesis. Through molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP samples, compared to psoriasis, atopic dermatitis, healed PRP, healthy controls, we identified IL-1β as key mediator, orchestrating NF-κB-mediated IL-1β-CCL20 axis, including activation of CARD14 NOD2. Treatment three patients the IL-1 antagonists anakinra canakinumab resulted rapid clinical improvement reversal PRP-associated molecular signature 50% lesions after 2 3 weeks. This transcriptional was consistent vitro stimulation keratinocytes IL-1β. With central role underscoring its potential therapeutic target, our findings propose redefinition autoinflammatory keratinization disorder. Further trials are needed validate efficacy PRP.