IL-1-targeted therapy in dermatologic conditions.

Area of Science:

• Dermatology
• Immunology
• Genetics

Background:

• Interleukin-1 (IL-1) is crucial in inflammasome activation, keratinocyte signaling, and neutrophil recruitment.
• IL-1 drives numerous neutrophil-rich and suppurative dermatoses.
• IL-1 blockade shows promise for various inflammatory skin conditions.

Purpose of the Study:

• To review the efficacy of IL-1 blockade in IL-1-driven autoinflammatory and neutrophilic dermatoses.
• To summarize practical considerations for using IL-1 antagonists.
• To highlight the importance of clinical and genetic phenotyping.

Main Methods:

• Literature review of cohort and case series data.
• Analysis of evidence for IL-1 blockade in various dermatological conditions.
• Summary of clinical considerations, dosing, and safety.

Main Results:

• Robust evidence supports IL-1 blockade for cryopyrin-associated periodic syndromes, monogenic periodic fever syndromes, and Schnitzler syndrome.
• High efficacy demonstrated in IL-1 receptor antagonist deficiency and pyoderma gangrenosum.
• Variable efficacy observed in hidradenitis suppurativa, pustular psoriasis, and PSTPIP1-associated autoinflammatory diseases.
• Limited evidence for IL-36 receptor antagonist deficiency, SAPHO, Sweet, and VEXAS syndromes.

Conclusions:

• IL-1 antagonists are essential for specific IL-1-driven disorders.
• IL-1 blockade is a rational rescue therapy for selected neutrophilic dermatoses.
• Careful phenotyping is vital for guiding IL-1 antagonist therapy.