Systemic Psoriasis: From Molecular Mechanisms to Global Management Strategies.

Psoriasis is a chronic, immune-mediated inflammatory disorder marked by a complex interplay between genetic predisposition, cytokine dysregulation, and environmental triggers. Originally perceived as a superficial dermatological condition, it is now recognized as a systemic disease with far-reaching health implications. Advances in molecular genetics have uncovered over 80 susceptibility loci, with key variants such as HLA-C*06:02, IL23R, and CARD14 contributing to the multifactorial nature of the disorder. Central to its pathogenesis is the aberrant activation of the IL-23/Th17 axis, resulting in excessive production of proinflammatory cytokines that promote rapid keratinocyte proliferation and sustained inflammation. Epigenetic modifications further influence gene expression, while interactions with environmental factors, such as mechanical stress, ultraviolet exposure, and air pollution, exacerbate the inflammatory cascade. Recent progress in targeted therapeutic strategies, notably biologic agents and small molecule inhibitors, has transformed the treatment landscape by specifically modulating these pathogenic pathways. Such innovations are paving the way toward personalized medicine, aiming to optimize therapeutic outcomes and reduce the overall disease burden. This review offers a comprehensive synthesis of current knowledge on the genetic, immunologic, and molecular mechanisms underlying psoriasis. The review emphasizes recent advances in targeted therapies underlining the potential for translational applications that address both cutaneous manifestations and systemic inflammation. It also explores global disparities in psoriasis care and the need for inclusive approaches that bridge disparities and promote equitable, innovative disease management strategies.