%0 Journal Article
%T Targeting IL-1 controls refractory pityriasis rubra pilaris.
%A Schmauch E
%A Severin Y
%A Xing X
%A Mangold A
%A Conrad C
%A Johannsen P
%A Kahlenberg JM
%A Mellett M
%A Navarini A
%A Nobbe S
%A Sarkar MK
%A Satyam A
%A Tsoi LC
%A French LE
%A Nilsson J
%A Linna-Kuosmanen S
%A Kaikkonen MU
%A Snijder B
%A Kellis M
%A Gudjonsson JE
%A Tsokos GC
%A Contassot E
%A Kolios AGA
%J Sci Adv
%V 10
%N 27
%D 2024 Jul 5
%M 38959302
%F 14.957
%R 10.1126/sciadv.ado2365
%X Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with a poorly understood pathogenesis. Through a molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP skin samples, compared to psoriasis, atopic dermatitis, healed PRP, and healthy controls, we identified IL-1β as a key mediator, orchestrating an NF-κB-mediated IL-1β-CCL20 axis, including activation of CARD14 and NOD2. Treatment of three patients with the IL-1 antagonists anakinra and canakinumab resulted in rapid clinical improvement and reversal of the PRP-associated molecular signature with a 50% improvement in skin lesions after 2 to 3 weeks. This transcriptional signature was consistent with in vitro stimulation of keratinocytes with IL-1β. With the central role of IL-1β underscoring its potential as a therapeutic target, our findings propose a redefinition of PRP as an autoinflammatory keratinization disorder. Further clinical trials are needed to validate the efficacy of IL-1β antagonists in PRP.