Pathogenesis of Chronic Plaque Psoriasis and Its Intersection With Cardio-Metabolic Comorbidities

Abstract

Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic plaques on the skin. Psoriasis is frequently associated to comorbidities, including psoriatic arthritis, cardiovascular diseases, diabetes mellitus, obesity, non-alcoholic fatty liver disease, and inflammatory bowel diseases. In this review, we discuss the pathophysiological relationship between psoriasis and cardio-metabolic comorbidities and the importance of therapeutic strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis. Pathogenesis of psoriasis and its comorbidities share both genetic predisposition and inflammatory pathways, which include the TNFα and the IL-23/IL-17 pathways. These pathways are selectively addressed by biological treatments, which have substantially changed the outcomes of psoriasis therapy and affect positively comorbidities including reducing cardiovascular risk, allowing a more comprehensive approach to the patient.

Keywords: cardio-metabolic comorbidities; inflammation; pathogenesis; psoriasis; treatment.

Figure 1

Man affected by psoriasis and central obesity.

Figure 2

Genetic and environmental factors predispose to psoriasis and obesity. Obesity is a risk factor for both psoriasis and metabolic syndrome. However, inflammation associated with moderate to severe psoriasis can in turn favor insulin resistance, dyslipidemia, obesity, and non-alcoholic fatty liver disease (NAFLD), hence directly and/or indirectly fuelling atherosclerosis, and configuring the so-called “psoriatic march”. Ultimately, moderate to severe psoriasis directly and indirectly increases the risk of cardiovascular diseases and mortality. Psoriasis also precedes the development of psoriatic arthritis.