The cardiometabolic conditions of psoriatic disease

Abstract

Psoriasis (PsO) and psoriatic arthritis (PsA), together known as psoriatic disease (PsD), are immune-mediated diseases with a chronic and relapsing course that affect the skin, the joints or both. The pathophysiology of PsO is complex and involves abnormal expression of keratinocytes and infiltration of the skin with dendritic cells, macrophages, neutrophils and T lymphocytes. Around 30% of patients with PsO develop arthritis with axial and/or peripheral manifestations. Both PsO and PsA share similar Th1- and Th17-driven inflammation, with increased production of inflammatory cytokines, including TNFα, IFN-γ, IL-17, IL-22, IL-23 in the skin and the synovial membrane. PsD is associated with a high burden of cardiometabolic diseases such as hypertension, diabetes, dyslipidemia, obesity, metabolic syndrome and cardiovascular (CV) complications as compared to the general population. These comorbidities share common immunopathogenic pathways linked to systemic inflammation, and are associated with the extent and severity of the disease. Morever, they can influence treatment outcomes in PsD. In this short review, we summarize the available evidence on the epidemiology, clinical aspects and mechanisms of cardiometabolic conditions in patients with PsD. We also discuss the impact of targeted treatments such as methotrexate and biological agents on these cardiometabolic conditions.

Keywords: cardiovascular risk; metabolic syndrome; obesity; psoriasis; psoriatic arthritis.

Figure 1

Due to disease activity, psoriatic disease (PsD) is associated with the production of Th1 (TNFα, IFNγ) and Th17 (IL-17, IL-22) derived cytokines that have potential effects on the blood vessels. They lead to endothelial activation, vascular dysfunction, altered lipid profile and prothrombotic effects, and ultimately, they promote atherosclerosis and cardiovascular (CV) disease. PsD is strongly associated with specific comorbidities including obesity and metabolic syndrome (MetS). Smoking and genetic factors may contribute to the development of CV diseases in PsD. Obesity is a predisposing factor for the developement of PsD and contributes to disease activity by the release of adipokines. Specific comorbidities, such as MetS and obesity, and therapeutic response are interrelated in PsD : on the one hand, MetS and obesity impair the therapeutic effectiveness of TNF inhibitors (TNFi), while on the other hand, methotrexate and TNFi have been shown to limit the CV burden of PsD.