Stress and psoriasis: Exploring the link through the prism of hypothalamo-pituitary-adrenal axis and inflammation.

BACKGROUND: Psoriasis is an immune-mediated, chronic inflammatory disease affecting mainly the skin. Chronic stress leads to the blunted hypothalamic-pituitary-adrenal axis (HPA) that might induce pro-inflammatory conditions. Hence, we assessed the blood levels of the HPA hormones and interleukin-17 (IL-17) and the effect of stress and emotional distress to understand the link between stress and psoriasis better. METHODS: This cross-sectional study included 45 patients with psoriasis and 45 age and gender-matched apparently healthy volunteers (n = 45). IL-17, cortisol, and adrenocorticotrophic hormone (ACTH) levels were assessed in both groups. Psoriasis Area Severity Index (PASI) was used to assess disease severity. Presumptive Stressful Life Events scale [PSLE], Perceived Stress scale [PSS] and Daily Hassles and Uplifts Scale [DHUS] scoring were used to assess stress levels and emotional distress. RESULTS: Patients with psoriasis had higher levels of IL-17 and ACTH and lower levels of cortisol, as compared to controls. Stress scores (PSS, PSLE & DHUS) were significantly elevated in cases, as compared to the controls. IL-17, ACTH and stress scores showed a significant positive correlation with one another and a significant negative correlation with cortisol levels. They also showed a significant positive correlation with PASI, while cortisol levels showed a significant negative correlation. CONCLUSION: Psoriasis patients having high ACTH, IL-17 and stress scores had lower levels of cortisol, indicating a dysregulated HPA axis with the pro-inflammatory state. This might lead to exacerbation of psoriatic flares, which needs investigation in further prospective studies.

Interleukin-9 serves as a key link between systemic inflammation and angiogenesis in psoriasis.

BACKGROUND: Psoriasis is a T helper cell-mediated chronic immune-mediated inflammatory disease affecting mainly the skin, although systemic pathological effects are also observed. Cytokine-mediated interaction between T lymphocytes and keratinocytes lead to excessive proliferation of keratinocytes, which in turn leads to formation of a proinflammatory milieu and finally to psoriatic plaque formation. AIM: To measure interleukin (IL)-9, IL-17 and vascular endothelial growth factor (VEGF) levels in patients with psoriasis compared with controls, and to evaluate the effect of methotrexate (MTX) monotherapy on the aforesaid cytokine levels in psoriasis. METHODS: This cohort study included 54 patients with psoriasis and 54 age- and sex-matched healthy controls (HCs). IL-9, IL-17 and VEGF levels were measured by using commercially available ELISA kits. Patients with psoriasis who were on MTX monotherapy were followed up for a period of 3 months. RESULTS: Patients with psoriasis had increased levels of IL-9, IL-17 and VEGF at baseline, compared with the HC group. After 3 months of MTX monotherapy, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI) and levels of cytokines (IL-9, IL-17 and VEGF) were significantly decreased compared with baseline. PASI and DLQI at baseline also showed a positive correlation with IL-9, IL-17 and VEGF. CONCLUSION: Our results suggest the existence of a proinflammatory milieu in psoriasis, with increased levels of IL-9, IL-17 and the proangiogenic growth factor VEGF, showing an increasing trend with increasing disease severity and impaired quality of life (QoL). MTX treatment helps to reduce levels of IL-9, IL-17 and VEGF, thereby limiting disease progression and improving QoL in psoriasis.

Asymmetric dimethylarginine and angiopoietin-like protein-2 are independent predictors of cardiovascular risk in pre-dialysis non-diabetic chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular (CVD) morbidity and mortality. Hence, this study was carried out to assess the biomarkers of endothelial dysfunction and inflammation as predictors of CVD risk in Indian patients with CKD. METHODS: In this case control study, we recruited 43 patients with CKD and 43 healthy control volunteers. Circulating levels of endothelial dysfunction markers [asymmetric dimethylarginine (ADMA), angiopoietin-like protein-2 (ANGPTL2), matrix metallopeptidase 9 (MMP-9)] and systemic inflammation [high-sensitivity C-reactive protein (hs-CRP)] were assessed in the study population. All study participants underwent brachial artery flow mediated dilation (FMD) to estimate endothelial dysfunction. Disease severity (e-GFR) was assessed by a nephrologist. RESULTS: CKD patients showed markedly elevated levels of ADMA, ANGPTL2, MMP-9, and hs-CRP. FMD and eGFR were significantly decreased in cases, as compared to the controls. ADMA, ANGPTL2, MMP-9 and hs-CRP showed significant positive correlation with one another and significant negative correlation with FMD and disease severity. We also observed a significant negative correlation of FMD with disease severity and duration of CKD. In the multiple linear regression model, ADMA and ANGPTL2 were found to be independent predictors of FMD. CONCLUSION: In CKD patients, there is significantly increased endothelial dysfunction and systemic inflammation, which showed a positive correlation with disease severity. Thus, the markers of endothelial dysfunction such as ADMA and ANGPTL2 can be used as predictors of CVD risk in CKD.

Assessment of bone turnover markers to predict mineral and bone disorder in men with pre-dialysis non-diabetic chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. METHODS: We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls. 25-hydroxyvitamin D, intact parathyroid hormone, and bone-specific alkaline phosphatase were assayed. Bone mineral density (BMD) was estimated using dual-energy X-ray absorptiometry. RESULTS: CKD is associated with significantly higher levels of bone-specific alkaline phosphatase and intact parathyroid hormone and lower levels of 25-hydroxyvitamin D and bone mineral density, when compared to controls. In the multivariate linear regression model, bone-specific alkaline phosphatase emerged as an independent predictor of reduced BMD. Receiver Operator Characteristic analysis for prediction of reduced BMD in CKD showed both intact parathyroid hormone and bone-specific alkaline phosphatase have significant predicting power. CONCLUSION: The combination of bone-specific alkaline phosphatase and intact parathyroid hormone has more significant predicting power and is a more reliable index for non-invasive assessment of bone health in men with chronic kidney disease, than either marker when used alone.