Is psoriasis a new cutaneous marker for metabolic syndrome? A study in Indian patients.

Sir,

Psoriasis is a chronic, inflammatory, immune-mediated skin disease, characterized by erythematous scaly patches and may be associated with arthritis. Recently, the chronic inflammatory nature of psoriasis is thought to predispose patients to other diseases with an inflammatory component, the most notable being the metabolic syndrome. Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), that are overproduced in patients with psoriasis are likely to contribute to the increased risk for development of metabolic syndrome.[1] Establishment of a significant association between psoriasis and metabolic syndrome would underline the need for early screening of psoriasis patients for cardiovascular risk factors, stroke and type 2 diabetes. There have been few studies in Indian patients. To demonstrate the relationship of psoriasis with these co-morbidities, we assessed the presence of metabolic syndrome in patients with psoriasis and in control subjects.

Fifty patients having psoriatic lesions attending outpatient clinic of dermatology department were included. Controls comprised of fifty age and sex matched individuals from the general healthy population without psoriasis. The study was approved by the institutional ethics committee. Patients were thoroughly questioned for the history of the disease, past treatment taken, familial involvement, diet and smoking by filling a questionnaire. Waist circumference, blood pressure, fasting blood sugar, triglyceride and HDL levels were the parameters studied in both the groups.

Metabolic syndrome was diagnosed by the criteria proposed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) which recommends that the metabolic syndrome be identified as the presence of three or more of these components: Waist circumference > 90 cm in men or > 80 cm in women, triglycerides > 150 mg/dl, HDL < 40 mg/dl in men or < 50 mg/dl in women, blood pressure > 130/85 mm Hg, fasting glucose > 100 mg/dl or previously diagnosed type 2 diabetes.[2] Data was analysed with SPSS for Windows 10.0.1. Qualitative variables were compared between the two groups (cases and controls) using Chi-square test/Fischer's exact test as appropriate.

Fifty patients included 27 males and 23 females in the psoriatic cases, while the controls had 29 males and 21 females. The age of the patients varied from 14-60 years with a mean of 32.76 years, with maximum number of patients lying between 21 to 30 years. Most common type of psoriasis encountered was chronic plaque psoriasis, seen in 42 out of 50 patients [Table 1]. The simultaneous occurrence of three or more of these conditions known as metabolic syndrome was approximately thrice as compared to controls. Dyslipidemia was observed in 16% of psoriatics as compared to 4% in controls, a significantly higher prevalence (P < 0.05) O.R.-4.57. Hypertension was observed in 26% of cases and 10% of controls (P < 0.05) O.R.-3.16. Central obesity was observed in 38% of cases and 14% of controls, which was significant (P < 0.01) O.R.-3.76. Diabetes was found in 16% of cases as compared to 6% of controls, which was not significantly higher (P < 0.1) [Figure 1]. Thus surprisingly in our study, no significant association was observed between psoriasis and diabetes. A diagnosis of metabolic syndrome was made in 30% of cases and 8% of controls, which was statistically significant (P < 0.005). The increased prevalence of metabolic syndrome appeared not to be due to the confounding factors, such as smoking and alcohol consumption (P < 0.5 which is not significant).

Table 1

Characteristics of the study population (cases of psoriasis)

Figure 1

Prevalence of metabolic syndrome and individual components in psoriasis

Conflicting results have been reported by other Indian studies.[34] Nisa and Quazi[3] reported a significantly higher prevalence of metabolic syndrome in psoriatic patients including hypertriglyceridema, hypertension and impaired fasting plasma glucose levels, whereas Pereira et al.,[4] reported a significantly higher prevalence of impaired fasting glucose but no association between psoriasis and dyslipidemia and metabolic syndrome. These could be due to ethnic, dietary and lifestyle changes in different parts of the country. Thus there is a need for further large multicentric epidemiological studies to obtain accurate nationwide estimates of the prevalence of the metabolic syndrome in psoriatic patients in various parts of India. A large study in the American population including 6549 participants revealed a high incidence of metabolic syndrome in patients with psoriasis, with abdominal obesity, followed by hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, but not diabetes.[5] Another large study in the UK population involving 44164 patients with psoriasis observed that they were at moderately higher risk than the general population of subsequently developing diabetes, hypertension, obesity, hyperlipidaemia, myocardial infarction, angina, atherosclerosis, peripheral vascular disease and stroke.[6]

Inflammatory cytokines such as intracellular adhesion molecule-1 and TNF-α, IL-12 play a role in the pathogenesis of psoriasis, and also in the pathogenesis of metabolic syndrome, obesity, atherosclerosis and myocardial infarction.[1] Increased adiposity has been found to be associated with raised levels of circulating cytokines, including leptin and resistin, which may promote activation of T-cells and monocytes, driving both Th-1 and Th-17 immune responses. In addition, psoriasis and obesity share similar mediators of inflammation, such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) and obesity may potentiate some of the TNF-α and IL-6 driven inflammation seen in psoriasis.[7] This raises the question whether treatment of psoriasis would lower the risk of cardiovascular disease by reducing inflammation.

A study assessing the risk of mortality in patients with psoriasis indicated that the relative risk of cardiovascular mortality is highest in younger patients less than 40 years, with severe psoriasis.[8] It would be interesting to observe whether therapeutic intervention by use of anti-inflammatory drugs including methotrexate and TNF-alpha antagonists would diminish the risk of cardiovascular disease and mortality in psoriasis. Thus our study showed that patients with psoriasis are prone to developing a distinct cluster of concomitant diseases, including hypertension, dyslipidemia, and obesity. Hence psoriasis should now be considered as a systemic inflammatory disease and all patients should be evaluated and monitored for the presence of diseases, such as ischemic heart disease, hypertension, diabetes mellitus and obesity.

It is important to emphasize that association alone, and not causality, was proven. Another limitation was that the sample size was not large enough to represent the general population. Further prospective studies are needed to establish this novel observation. If this observation is accurate, psoriasis may take a role as a new risk factor for ischemic heart disease.

Thus patients with psoriasis should be regularly screened and advised lifestyle modification such as diet, exercise and stress reduction to reduce the incidence of cardiovascular disease. Future prospective large randomized, controlled, population-based or multicenter studies should be undertaken to confirm the association and causality between psoriasis and cardiovascular risk factors.