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

Abstract

Observations: Emerging epidemiologic, clinical, and real-world data establish GPP as a distinct disease entity associated with high rates of hospitalization, multisystem involvement, and increased mortality. Accurate diagnosis requires recognition of characteristic cutaneous findings together with laboratory and clinical evidence of systemic involvement, and exclusion of key mimickers such as acute generalized exanthematous pustulosis, as well as recognition of patient-reported systemic symptoms such as fever, malaise, and joint pain. Advances in pathophysiologic understanding have identified dysregulated innate immune signaling centered on the interleukin-36 (IL-36) pathway as the primary driver of neutrophilic inflammation and pustule formation. Randomized clinical trials, real-world evidence, and meta-analyses consistently demonstrate that IL-36 receptor blockade achieves rapid and reliable control of acute GPP flares and provides a rational strategy for flare prevention. In contrast, off-label biologic therapies targeting IL-17, IL-23, or tumor necrosis factor-α show more variable and often delayed efficacy, particularly for acute disease control.

Conclusions and relevance: Contemporary evidence supports a paradigm shift toward disease-specific, pathway-directed management of GPP, with IL-36 pathway inhibition positioned as the cornerstone of modern therapy.  .