Statins in Psoriasis: Immunometabolic Mechanisms and Cardiovascular Implications

Background and Objectives: Psoriasis is a chronic immune-mediated disease associated with systemic inflammation, metabolic dysfunction, and increased cardiovascular risk. Beyond lipid lowering, statins exert pleiotropic effects involving the mevalonate pathway, inflammatory signaling, oxidative stress, and endothelial function. This review critically examines the mechanistic rationale and clinical evidence for systemic and topical statins in psoriasis, emphasizing the distinction between psoriasis-specific findings and mechanisms extrapolated from other biological systems. Materials and Methods: A narrative review of the literature was conducted using PubMed searches, supplemented by screening the reference lists of relevant publications. Experimental, translational, and clinical studies addressing statin-related immunometabolic mechanisms, cardiovascular implications, and topical or systemic interventions in psoriasis were selected for relevance and critically synthesized. Results: Experimental studies have identified effects on keratinocyte inflammatory signaling, immune-cell recruitment, and psoriasis-like inflammation, whereas several proposed pleiotropic pathways remain extrapolations from other systems. Clinical studies, conducted predominantly in patients with plaque psoriasis, have reported heterogeneous outcomes and do not establish consistent improvement in disease severity. Preliminary topical studies suggest potential cutaneous activity, but small samples, heterogeneous formulations, comparator differences, and methodological limitations preclude firm conclusions regarding efficacy. No validated statin-responsive psoriasis endotype or predictive biomarker has been identified. Conclusions: Current evidence does not support the use of systemic statins solely for psoriasis treatment or topical statins as routine antipsoriatic therapy. Statins remain indicated for cardiovascular risk management in patients with psoriasis when clinically appropriate, while topical formulations warrant further controlled investigation. Future studies should integrate clinical outcomes with inflammatory, metabolic, and molecular profiling to determine whether specific patient subgroups may benefit from statin-based interventions.