Psoriasis and Systemic Inflammatory Diseases: Potential Mechanistic Links between Skin Disease and Co-Morbid Conditions

Abstract

Psoriasis is now classified as an immune-mediated inflammatory disease (IMID) of the skin. It is being recognized that patients with various IMIDs, including psoriasis, are at higher risk of developing "systemic" co-morbidities, e.g., cardiovascular disease (CVD), metabolic syndrome, and overt diabetes. In non-psoriatic individuals, the pathophysiology of obesity, aberrant adipocyte metabolism, diabetes, and CVDs involves immune-mediated or inflammatory pathways. IMIDs may impact these co-morbid conditions through shared genetic risks, common environmental factors, or common inflammatory pathways that are co-expressed in IMIDs and target organs. Given that pathogenic immune pathways in psoriasis are now well worked out and a large number of inflammatory mediators have been identified in skin lesions, in this review we will consider possible mechanistic links between skin inflammation and increased risks of (1) obesity or metabolic alterations and (2) CVD. In particular, we will discuss how well-established risk factors for CVD can originate from inflammation in other tissues.

Lipin-2 Reduces Proinflammatory Signaling Induced by Saturated Fatty Acids in Macrophages

“…For example, in those patients who have an inflammatory process already ongoing, saturated fatty acids could produce an exacerbated inflammatory state in macrophages, generating more proinflammatory cytokines and contributing to the maintenance of inflammation. In the same line of thought, it has been described that obese patients with psoriasis are more difficult to treat than non-obese individuals (43,44). Several trials have demonstrated that psoriatic patients have partially recovered after weight loss and that increases in weight worsen the symptoms (43, 44).…”

Adiponectin regulates psoriasiform skin inflammation by suppressing IL-17 production from γδ-T cells

“…Psoriasis has been long considered to be a skin-tropic and not life-threatening disease; however, it is now increasingly recognized that psoriasis inflammation is not limited to the skin but goes far beyond the skin, accompanying systemic inflammation 9,10 . Immune cells and cytokines, when released into the systemic circulation, may alter the function of endothelial and haematopoietic cells, leading to the increase in the risk of insulin resistance and atherosclerosis.…”

Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity and psoriasis: diabetes meets dermatology

“…Psoriasis is widely viewed as an immune-mediated inflammatory disease that is associated with the expansion and activation of T helper (Th)1, Th17 and Th22 cells, and the increased expression and levels of cytokines detectable locally in skin lesions and, frequently, systemically in the circulation [1]. Patients with psoriasis exhibit increased rates of cardiovascular disease, obesity and type 2 diabetes-conditions characterised by enhanced local and/or systemic inflammation.…”