INDIVIDUAL ARTICLE: Generalized Pustular Psoriasis: A Contemporary Review of Diagnosis, Pathophysiology, and IL-36...

Area of Science:

• Dermatology
• Immunology
• Genetics

Background:

• Generalized pustular psoriasis (GPP) is a severe, distinct disease entity.
• GPP is associated with high hospitalization rates, multisystem involvement, and mortality.
• Accurate diagnosis involves recognizing cutaneous findings, systemic symptoms, and excluding mimickers.

Purpose of the Study:

• To review the current understanding of GPP pathophysiology and management.
• To highlight the role of IL-36 pathway inhibition in GPP treatment.

Main Methods:

• Review of epidemiologic, clinical, and real-world data.
• Analysis of randomized clinical trials, real-world evidence, and meta-analyses.
• Examination of pathophysiologic understanding of GPP.

Main Results:

• Dysregulated IL-36 innate immune signaling drives neutrophilic inflammation and pustule formation in GPP.
• IL-36 receptor blockade demonstrates rapid and reliable control of acute GPP flares.
• IL-36 blockade provides a rational strategy for GPP flare prevention.

Conclusions:

• Contemporary evidence supports a paradigm shift in GPP management.
• Disease-specific, pathway-directed therapy is recommended for GPP.
• IL-36 pathway inhibition is the cornerstone of modern GPP therapy.