{Reference Type}: Journal Article
{Title}: Targeting IL-1 controls refractory pityriasis rubra pilaris.
{Author}: Schmauch E;Severin Y;Xing X;Mangold A;Conrad C;Johannsen P;Kahlenberg JM;Mellett M;Navarini A;Nobbe S;Sarkar MK;Satyam A;Tsoi LC;French LE;Nilsson J;Linna-Kuosmanen S;Kaikkonen MU;Snijder B;Kellis M;Gudjonsson JE;Tsokos GC;Contassot E;Kolios AGA;
{Journal}: Sci Adv
{Volume}: 10
{Issue}: 27
{Year}: 2024 Jul 5
{Factor}: 14.957
{DOI}: 10.1126/sciadv.ado2365
{Abstract}: 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.