Objective Coronary artery disease (CAD) is the leading cause of excess deaths in RA. However, identification of features denoting those with CAD risk is lacking. The composition of circulating mononuclear cell (PBMC) subsets in RA cases differs markedly from healthy controls in extent of T-cell activation with clonal expansion and differentiation to memory effector status and presence of inflammatory monocytes. We sought to evaluate whether elevations in these subpopulations in RA denote those with increased risk for subclinical CAD, as measured by coronary artery calcium (CAC). Methods 72 RA patients underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and presence of CAC. Results 33% had CAC and exhibited significant increases of circulating CD4 T cell subsets denoting activation and differentiation to memory effector phenotypes. Analogous increases in CD8 T cell subsets, and intermediate CD14hiCD16+monocytes, were also present compared to those without CAC. The CD4 and CD8 T cell subset increases were highly intercorrelated, while increases in CD14hiCD16+monocytes were independent of the elevated CD4 subsets. After adjustment for relevant confounders, levels of CD4+CD56+CD57+ T cells and CD14hiCD16+monocytes remained associated with the presence of CAC. Conclusions These PBMC subsets are markers for CAC and suggest mechanisms of atherogenesis in RA may operate in part through their increases, raising further questions about the mechanisms underlying the presence of these subset alterations in RA and the potential for shared etiologic pathways between RA and CVD.

Dyslipidemia is highly prevalent in rheumatoid arthritis (RA) and appears to be present very early in the RA disease process, in some studies even before a diagnosis of clinical RA has been made. The association between lipid measures and the risk of cardiovascular disease (CVD) in RA appears to be paradoxical, whereby lower levels of total cholesterol (TC), low-density lipoprotein (LDL-C), and atherogenic ratios are associated with higher CVD risk. This may be due to the lipid-lowering effects of RA-related systemic inflammation. Therefore, standard CVD risk calculators have been shown to underperform in RA. Data also suggest that lipoprotein particle sizes and the apolipoprotein cargo of lipoproteins skew toward atherogenic dyslipidemia in RA and may contribute to the initiation and progression of atherosclerosis. Inflammatory burden in RA may also alter the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol (HDL-C). Adipose tissue is quantitatively increased in RA patients compared with matched non-RA controls and may be more inflamed and metabolically dysfunctional compared with an otherwise similar non-RA patient. In vitro, animal, and a handful of non-RA human, studies suggest that inflamed, metabolically dysfunctional adipose tissue contributes directly to lower HDL-C levels. In turn, lower HDL-C that has been altered functionally by inflammation may lead to expanded adipose mass and further adipose dysfunction and inflammation. In the last part of this review, we speculate how the RA disease state may recapitulate these processes.

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Pyoderma gangrenosum (PG) is a rare entity that is characterized by infiltration of neutrophils into the dermis, causing the formation of rapidly enlarging, painful and necrotic skin ulcers. The pathophysiology of PG is still poorly understood. However, genetic, autoimmune and autoinflammatory mechanisms have been proposed that could potentially explain the etiology of this ulcerating skin disorder. Early diagnosis and treatment are key, as the disease course is rapidly progressive and can leave disfiguring, cribriform scars. However, the diagnosis of PG proves difficult, firstly because there are multiple variants of the disease and secondly because it is a clinical diagnosis and can appear similar to that of other diseases such as vasculitis, skin/soft tissue infections and malignancy. Additionally, there are no official diagnostic criteria to aid in the recognition of PG, which often leads to significant delays in diagnosis. The treatment of PG consists in immunosuppression. However, due to a lack of standardized guidelines, therapeutic regimens are usually dependent upon the individual clinician’s experience and are based on little evidence. Knowledge of the clinical features and pathophysiology of PG can aid in early diagnosis and targeted treatment strategies, which in turn results in improved patient outcomes.

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