According to data from the American Heart Association and the World Health Organization, cardiovascular disease (CVD) is the most frequent cause of premature death. Several inflammatory and non-inflammatory skin diseases have been associated with metabolic syndrome and cardiovascular risk (CVR). Here, we classified these conditions into traditionally CVR-associated and those that have been linked to a lesser degree. Psoriasis and hidradenitis suppurativa are commonly associated with CVD, sharing common inflammatory pathways and a higher prevalence of traditional cardiovascular risk factors. Many other diseases could be associated indirectly – with no common pathogenic features with the atheromatous disease – but share a higher prevalence of standard cardiovascular risk and chronic inflammatory state. This review aims to highlight the associated cardiovascular risk that exists for some dermatologic diseases and sensitize cardiologists, dermatologists, and first care providers to implement risk factor control promptly.

Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions.

Introduction: CD14 (monocyte differentiation antigen, LPS binding protein – endotoxin receptor) and CD16 (FcγRIII, Low-affinity receptor for IgG) define three subpopulations of circulating monocytes with different inflammatory and phagocytic capabilities. Contradictory reports exist regarding both in vivo monocyte phenotype-disease association and response of these circulating monocytes to in vitro stimulation. We analyzed phenotypic changes in circulating monocytes when stimulated with LPS (pro-inflammatory stimulus) and IL-4 (alternative inflammatory stimulus). Methods: Mononuclear cells from nine healthy donors were extracted and studied for surface and intracellular markers using flow cytometry. PBMC were extracted using Ficoll technic and immediately analyzed using flow cytometry. Pro-inflammatory interleukin IL-1β and IL-6 were measured by intracellular cytometry. Mononuclear cells were stimulated using LPS and IL-4 as previously described. Changes against non-stimulated populations were statistically analyzed. Results: Compared to non-stimulated and IL-4 stimulated monocytes, LPS-stimulated cells display a singular pattern of markers, with higher levels of intracellular IL-1β and IL-6 directly correlating with CD14+CD163- cell frequency and diminishing membrane CD163 fluorescence. CD14+CD16- classical monocytes show greater percentage of CD163- cells upon LPS stimulation. CD86 levels on monocytes’ surface did not change with LPS or IL-4 stimulation. Conclusions and Discussion: We showed that CD14+CD16- classical monocytes display higher sensitivity to LPS stimulation, with more IL-1β and IL-6 levels than intermediate and non-classical monocytes. This subset also diminishes its CD163 levels on the membrane after LPS stimulation with a contemporary raise in CD163- cells, suggesting that classical monocytes preferentially acquire CD163- defined M1 characteristics upon in vitro LPS stimulation. Intermediate and non-classical monocytes respond with lower levels of interleukins and display surface proteins in an M2-type profile (CD163+).

The soluble interleukin-2 receptor (sIL-2R) is a novel biomarker associated with a variety of immune-mediated diseases. It is produced through the proteolytic cleavage of the membrane-bound interleukin-2 receptor α-chain on activated T lymphocytes; hence, its increase reflects T-cell activation and immune dysregulation. Elevated sIL-2R levels are frequently documented in conditions such as rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, histiocytosis, hemophagocytic lymphohistiocytosis, lymphomas, and graft-versus-host disease, suggesting a potential role in monitoring disease activity and progression. However, sIL-2R levels may increase in the context of immune response to infections and malignancies, requiring careful interpretation. It is essential to determine whether elevated levels of this marker within specific ranges could suggest a specific entity, due to the implications this may have for the management of patients. This case-based review presents five patients with different immune-mediated diseases, highlighting how these different conditions can present with characteristic ranges of sIL-2R elevation. By integrating clinical findings with sIL-2R measurements, we emphasize the biomarker’s utility in guiding diagnosis, as well as monitoring disease activity and determining prognosis, which can enhance clinical decision-making and patient management in rheumatology and related fields.