biostudies-literatureUnknown10(27)Schmauch EPityriasis 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 Science advanceseado2365https://www.ebi.ac.uk/biostudies/studies/S-EPMC11221491biostudies-literatureTargeting IL-1 controls refractory pityriasis rubra pilaris.PMC11221491Kahlenberg JMMellett MSnijder BGudjonsson JESatyam ANilsson JXing XNavarini AJohansen PTsoi LCTsokos GCKolios AGASarkar MKKellis MNobbe SFrench LESeverin YKaikkonen MULinna-Kuosmanen SContassot EMangold AConrad CSchmauch EfalseTargeting IL-1 controls refractory pityriasis rubra pilaris.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 2024-01-01T00:00:00Z2024 Jul2026-06-02T21:18:35.078Z2025-04-04T12:21:35.411ZS-EPMC112214913895930210.1126/sciadv.ado2365