IL-1-targeted therapy in dermatologic conditions

Interleukin-1 (IL-1) plays a key role in inflammasome activation, keratinocyte signaling and neutrophil recruitment, and is a driving force behind many neutrophil-rich and suppurative dermatoses. There is robust evidence supporting the use of IL-1 blockade as a disease-modifying therapy in cryopyrin-associated periodic syndromes and other monogenic periodic fever syndromes, as well as in the treatment of Schnitzler syndrome, where it can rapidly control urticarial and neutrophilic eruptions. Cohort- and series-level data demonstrate high efficacy in IL-1 receptor antagonist deficiency and steroid-refractory pyoderma gangrenosum, whereas benefits appear more heterogeneous in hidradenitis suppurativa, pustular psoriasis and proline-serine-threonine phosphatase-interacting protein 1-associated autoinflammatory diseases. In contrast, conditions such as IL-36 receptor antagonist deficiency, synovitis acne pustulosis hyperostosis osteitis syndrome, Sweet syndrome and vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome are supported only by scattered case reports or theoretical rationale, with highly variable or uncertain responses to IL-1 blockade, highlighting the importance of careful clinical and, where possible, genetic phenotyping. We summarize practical considerations for selecting agents, pediatric and adult dosing and safety. IL-1 antagonists are indispensable for a subset of IL-1-driven disorders and represent a rational rescue option for selected neutrophilic dermatoses.