Psoriasis as a systemic inflammatory disease: an immune set-point framework for comorbidities and relapse

Psoriasis is increasingly recognized as a systemic immune-mediated disorder that extends beyond cutaneous inflammation. Although skin lesions are its most visible manifestation, growing evidence indicates that psoriasis reflects a broader disruption of immune homeostasis accompanied by sustained systemic inflammatory activation. Persistent immune activation, altered myeloid programming, and dysregulated immunometabolic pathways together establish a state of chronic inflammatory priming. This systemic inflammatory state contributes to multi-organ comorbidities and also favors disease relapse through durable immune memory and trained immunity. In this review, we propose that psoriasis reflects maladaptive reprogramming of the systemic immune set-point, such that both spatial multi-organ involvement and temporal disease recurrence arise from shared immunologic mechanisms. Viewing psoriasis in these terms has important implications for comorbidity assessment, long-term maintenance strategies, and the pursuit of disease modification.