Generalized pustular psoriasis (GPP) is a rare, severe variant of pustular psoriasis characterized by extensive, repeated bouts of neutrophil-rich pustule development in the epidermis, as well as fever and systemic inflammation. GPP is a unique entity from plaque psoriasis, according to recent clinical, histologic, and genetic findings, with different cytokine pathways predominating in the manifestation of each illness. For a study, researchers examine the existing knowledge of GPP, explain fresh therapeutic prospects, and discuss how the disease’s distinct pathophysiology may inspire future treatment efforts.

The innate immune system is regulated by the interleukin-36 (IL-36) signaling cascade, and its dysfunction appears to be crucial to the pathophysiology of GPP. A positive feedback loop of unregulated signaling and excess production of inflammatory cytokines had been found to produce chemokine induction and neutrophil recruitment in the epidermis as a result of the altered expression of multiple IL-36 pathway members. Given the potentially fatal nature of GPP episodes, pharmacological therapies that result in illness resolution as quickly as possible where necessary. 

Early findings suggested that therapeutics targeting multiple components of the IL-36 inflammatory cascade were attractive study topics. However, there were no GPP-specific treatment medicines available in the United States or Europe at the moment. Understanding the inflammatory pathways, related risk factors, and involvement of neutrophils in the appearance and persistence of GPP flares was a critical priority in designing effective therapies. 

Reference:link.springer.com/article/10.1007/s40257-021-00655-y