Utvrđivanje povezanosti hronične plak psorijaze i osnovnih kriterijuma metaboličkog sindroma

Abstract

Psoriasis is a hereditary chronic skin disorder affecting 1–3 % of the general population worldwide. Presently, psoriasis is considered to be a Th1/Th17 involved inflammatory disease, characterized by chronically elevated pro-inflammatory cytokine levels. The metabolic syndrome (MetS) is a cluster of interrelated common clinical disorders, including insulin resistance, obesity, glucose intolerance, hypertension, and dyslipidemia. Other unexplored confounders, including genetic factors, diet, alcohol, physical activity, drugs and psychosocial factors, may contribute to several aspects of the metabolic syndrome. Previous studies have shown a possible association between psoriasis and the MetS. It has been hypothesized that this association may be explained by the state of chronic low-grade inflammation. There is little information available on the effects of drugs on the metabolic syndrome. Drugs used to treat psoriasis can adversely affect individual components of the MetS such as blood pressure and lipid concentrations. Thus, the objective of this study is to determine the prevalence of the metabolic syndrome, comorbidity and comedication in patients with psoriasis who have never received any systemic antipsoriatic drugs. The psoriatic patients were recruited from the University Clinic of Dermatology, at the Medical Faculty in Skopje between September 2011 and April 2012. The inclusion criteria for the patients were: age > 18 years and clinical diagnosis of plaque-type psoriasis lasting for at least six consecutive months. The study included only untreated patients. Thus, patients receiving systemic antipsoriatic drugs including acitretin, cyclosporine, methotrexate, psoralen-ultraviolet A therapy and biologics, were excluded. In addition, patients with other types of psoriasis (guttate, erythrodermic and pustular psoriasis), and patients with a history of autoimmune disorders were also excluded. Data collection included demographics, weight, height, waist circumference, BMI, blood pressure, smoking and drinking habits, age of psoriasis onset, type and severity of psoriasis, and presence of psoriatic arthropathy. Each control was matched to a case according to age (±1 year) and gender. The severity of psoriasis was assessed according to the Psoriasis Area and Severity Index (PASI) and the body surface area (BSA). The MetS was diagnosed by the presence of three or more of the criteria of the National Cholesterol Education Program’s (ATP III). Odds ratios (OR) were estimated by logistic regression models using the conditional likelihood and 95 % confidence intervals (CI) were computed. The proportion of the metabolic syndrome and its individual components for the patients was compared with their matched healthy controls. Comparisons were made using the Student’s t-test for parametric continuous variables, the Mann-Whitney U test for nonparametric continuous variables, and the Chi-square test for qualitative variables. The potential predictive factors of the MetS were identified with univariate and multivariate logistic regression. The significance was set at p ≤ 0.05 for all tests. One hundred and twenty-two patients with psoriasis (52 male and 70 female, mean age 51.52 years, SD 15.56, range 19–80 years), and 122 age- and gender-matched controls (mean age 51.98, range 19–79 years) participated in the study. No statistically significant difference was noted in age between the groups (p = 0.82). Type I psoriasis occurred in 78 patients (63.9 %). The mean duration of psoriasis was 17.9 years (range 1–65 years). PASI score ranged from 2.4 to 62.0 (mean 14.75), and 56 (45.9 %) had moderate to severe psoriasis. There was no significant difference in the prevalence of the MetS between the patients with psoriasis (24.6 %) and the controls (22.9 %) (OR 1.095, 95 % CI 0.607–1.974, p = 0.764). Among the individual components of the metabolic syndrome, hypertriglyceridemia and abdo-minal obesity were associated with psoriasis. The prevalence of hypertriglyceridemia in the patients with psoriasis and the controls was 41.8 % and 28.7 %, respectively (OR 1.78, 95 % CI 1.04–3.04, p = 0.032). The prevalence of abdominal obesity in the patients with psoriasis and the controls was 56.5 % and 35.2 %, respectively (OR 2.07, 95 % CI 1.24– 3.46, p = 0.005). There were no significant differences regarding the prevalence of hypertension, low HDL cholesterol and fasting plasma glucose between cases and controls. Smoking was significantly more often noted in psoriasis patients compared with controls (OR 1.813, 95 % CI 1.091–3.013, p = 0.021). The patients with psoriasis had a higher mean BMI (26.24, SD 4.42) compared with the controls (24.73, SD 3.86 ), p = 0.005. The patients were divided in two groups, according to the presence or absence of the MetS. The psoriatic patients with the MetS had a higher mean age (p = 0.001), and higher mean BMI (p = 0.001) compared with the patients without the MetS. The presence of the MetS was not associated with the severity of psoriasis (p = 0.674). Furthermore, there were no differences regarding gender, smoking and drinking habits, clinical characteristics of psoriasis, and presence of PsA. Univariate and multivariate logistic regression analyses were conducted to identify the variables predictive of the metabolic syndrome. The analyses identified age (OR 1.049, 95 % CI 1.014–1.085, p = 0.005), BMI (OR 1.268, 95 % CI 1.124–1.430, p < 0.001), and elevated triglycerides (OR 35.59, 95 % CI 12.593–100.6, p < 0.001), as significant predictors of the MetS. The growing body of evidence suggests a possible link between psoriasis and cardiovascular risks. Three elements contribute to the unfavorable cardiovascular risk profile in patients with psoriasis: systemic inflammation, systemic therapies and unhealthy lifestyle. Over the last decade, the association between psoriasis and the MetS has been well researched. A number of small case-control studies, large population-based studies, and meta-analysis, show a strong association between psoriasis and the metabolic syndrome. Several studies, however have not found such a relation. The prevalence of the metabolic syndrome among patients with psoriasis in other studies varies from 4.3 % to 53 %. There are conflicting study results regarding the prevalence of the individual components of the metabolic syndrome. In our study, there was no significant difference in the prevalence of the metabolic syndrome between the patients with psoriasis and the controls (24.6 % vs. 22.9 %, OR 1.095, p = 0.764). Similar to our observation, Mebazaa et al. (J Eur Acad Dermatol Venereol, 2011) detected higher prevalence of the metabolic syndrome in cases than in controls but without statistical differences (35.5 % vs. 30.8 %, p = 0.095). Kim et al. (Ann Dermatol, 2012) and Chen et al. (Arch Dermatol, 2008) findings revealed that the prevalence of the MetS among psoriasis patients was lower than among controls. In our study, among the individual components of the MetS, only hypertriglyceridemia and abdominal obesity were associated with psoriasis. These results are concurrent with some recent studies. Similarly to Gisondi et al. (Br J Dermatol, 2007) , and Kutlu et al.( Indian J Dermatol Venereol Leprol, 2011), we did not find correlation between the severity of psoriasis and the metabolic syndrome. In contrast, Sommer et al. (Arch Dermatol Res, 2006) reported an increased prevalence of the MetS in patients with psoriasis. It is noteworthy, that logistic regression analysis identified age, BMI, and hypertriglyceridemia as variables that favor the occurrence of the metabolic syndrome. There are several possible explanations for the diverse findings between our study and previous studies. Firstly, some studies were not completely matched for age and gender, which might influence the results. In addition, some studies are associated with high risk of selection and detection bias, due to the use of administrative databases. Furthermore, differences in nutritional habits and genetic susceptibility among different populations may affect the prevalence of the metabolic syndrome. Lastly, a selection of untreated patients with psoriasis eliminates the influence of systemic antipsoriatic drugs on the components of the metabolic syndrome. To our knowledge, this is the first case-control study to investigate the metabolic syndrome in untreated patients with psoriasis. Traditional systemic therapies for psoriasis may worsen CVR. Methotrexate increases homocysteine levels, cyclosporine and acitretin induce hyperlipidemia. Thus, the high prevalence of the metabolic syndrome in patients with psoriasis may be, in part, due to the systemic antipsoriatic drugs. Wakkee et al. argue that the effect of systemic drugs on the cardiovascular risk is a sum of anti-inflammatory effect and atherogenic side effect. It is difficult to assess the contribution of systemic antipsoriatic drugs on the development of the metabolic syndrome in patients with psoriasis. A number of concurrent factors, as inflammation and lifestyle factors, contribute to the metabolic syndrome. Furthermore, the influence of other systemic drugs such as NSAIDs (non-steroidal anti-inflammatory drugs), antidepressants and diuretics, needs to be taken into consideration, as these drugs are widely prescribed for patients with psoriasis. Nevertheless, our study confirms that the psoriasis patients compared with the controls, more frequently have three classic risk factors for cardiovascular disease: smoking, obesity and hypertriglyceridemia. Untreated patients with psoriasis have no significantly higher prevalence of the metabolic syndrome than healthy controls. Our data suggest that the systemic antipsoriatic drugs may play an important role in the pathogenesis of the metabolic syndrome. Future research of the impact of drugs on cardiovascular risk in psoriasis is needed.