Psoriasis and metabolic syndrome: a review

Psoriasis is the most common chronic dermatosis and affects 1–2% of the population of developed countries. In Russia, psoriasis incidence rate has increased by 11% since 2011. Psoriasis is a chronic inflammatory and immune-mediated skin disease and it is often associated with metabolic syndrome and its components such as obesity, arterial hypertension, insulin resistance and dyslipidemia. The risk of developing metabolic syndrome in patients with psoriasis is 40% higher than in the general population. Psoriasis and metabolic syndrome share some pathogenic mechanisms such as chronic low-grade systemic inflammation and an increased level of pro-inflammatory cytokines. Systemic inflammation causes obesity, cardiovascular diseases, diabetes. These conditions increase the risk of mortality among patients. There is a link between the severity of psoriasis and metabolic syndrome and associated with severe rash, reduction of the remission and higher risk of psoriatic arthritis development. The carriers of the risk allele of FTO gene are associated with severe psoriasis, presence of psoriatic arthritis and obesity. The article presents the issues of epidemiology, etiology and pathogenesis of psoriasis and metabolic syndrome.

Correlation of gefitinib and its metabolites with gefitinib induced rash in patients with non-small cell lung cancer (NSCLC).

e21712 Background: Gefitinib induced rash is the most common adverse reaction and severe rash of gefitinib often leads to discontinuation or termination of treatment. The concentrations of drug and its metabolites may affect drug induced toxicities, however, the association of gefitinib/metabolites with gefitinib-induced rash are poorly investigated. Therefore, we explored the association between concentrations of gefitinib and its four metabolites with gefitinib-induced rash in non-small cell lung cancer (NSCLC) patients. Methods: A total of 180 advanced NSCLC patients carrying EGFR sensitive mutations receiving gefitinib were enrolled. The concentrations of gefitinib, and its four metabolites including M537194, M387783, M523595 and M605211 were determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The associations between concentration of gefitinib/its metabolites and gefitinib-induced rash were analyzed by Mann-Whiney U test. Operating characteristic curves(ROC) were used to determine gefitinib/metabolites cutoff values for gefitinib-induced rash. Results: M605211 was first detected in plasma in NSCLC patients. The concentrations of gefitinib and M605211, M537194 were found to be correlated with the incidence of gefitinib-induced rash ( P= 0.0002, 0.027 and 0.0097, respectively), moreover, the concentration of gefitinib was correlated with severe rash (Grade 0,1 vs. 2+, P= 0.017). Multivariate Logistic regression analysis showed that only gefitinib concentration was independent risk factor for gefitinib-induced rash (grade 0 vs grade1+, OR = 1.006, 95%CI (1.002-1.009), P = 0.00078; grade0,1 vs grade2+, OR = 1.003, 95%CI (1.001-1.005), P = 0.015, respectively). The cutoff values of gefitinib were 160.2 ng/ml (grade 0 vs grade1+, sensitivity = 78.7%, specificity = 47.7%, area under the curve (AUC) = 0.686, P = 0.0002, 95% CI (0.592-0.779)) and 201.7ng/ml (grade0,1 vs grade2+, sensitivity = 69.3%, specificity = 47.6%, AUC = 0.605, P = 0.0168, 95%CI (0.521-0.689)). Conclusions: This research demonstrated that the concentration of gefitinib and its metabolites were associated with gefitinib induced rash in NSCLC patients. Therapeutic drug monitoring of gefitinib concentration may have potential improvement for optimization of treatment with gefitinib. Clinical trial information: NCT01994057.