Prevalence of metabolic syndrome in South Indian patients with psoriasis vulgaris and the relation between disease severity and metabolic syndrome: a hospital-based case-control study.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints with an increased cardiovascular risk. Previous studies have shown a higher prevalence of metabolic syndrome (MS) in psoriatic patients.
OBJECTIVE: To investigate the prevalence of MS in patients with psoriasis and healthy controls, and to determine the relation between disease severity and the presence of MS.
MATERIALS AND METHODS: We performed a hospital-based case-control study on 118 adult patients with psoriasis vulgaris and 120 controls matched for age, sex and body mass index. MS was diagnosed by the presence of three or more of the South Asian Modified National Cholesterol Education Program's Adult Panel III criteria.
RESULTS: MS was significantly more common in psoriatic patients than in controls (44.1% vs. 30%, P value = 0.025). Psoriatic patients also had a higher prevalence of triglyceridemia (33.9% vs. 20.8%, P value = 0.011), abdominal obesity (34.7% vs. 32.5%, P value = 0.035) and elevated blood sugar. There was no difference in the high density lipoprotein (HDL) levels and presence of hypertension among patients with psoriasis and normal controls. There was no correlation between the severity and duration of psoriasis with MS.
CONCLUSION: MS is frequent in patients with psoriasis. We have found no relationship between disease severity and presence of MS. Hence, we suggest that all patients must be evaluated for the MS, irrespective of the disease severity.

Introduction

Psoriasis is a chronic, immunologically based inflammatory skin disease.[1] Over the last decade, many studies world over have shown that people with psoriasis often have comorbidities like diabetes, hypertension and lipid abnormalities.[2-4] However, there have been very few studies so far on the risk factors and comorbidities associated with psoriasis in Indian patients.[5-7]

Study design

This was a prospective, observational, descriptive, hospital-based case–control study and the protocol was approved by members of the Indian Council of Medical Research (ICMR) and the institutional ethics committee of Sri Ramachandra University prior to the start of the study.

Aim

This study was performed to understand the occurrence of metabolic syndrome (MS) in South Indian psoriasis patients, and to study the relationship between the severity of psoriasis, joint involvement, duration of the disease and the presence of MS in psoriatic patients.

Study population

This was a hospital-based case–control study in which 118 patients with psoriasis vulgaris were recruited from the psoriasis outpatient clinic over a period of 1.5 years from December 2008 to June 2010. One hundred and twenty patients who attended the skin department for other skin ailments were the controls. The inclusion criteria for the cases were age more than 18 years and clinical diagnosis of plaque-type psoriasis. Patients on current treatment and those who received cyclosporine, acitretin, psoralens and methotrexate within the last 6 weeks were excluded from the study.

Materials and Methods

After obtaining the informed consent, all patients were subjected to detailed history taking and clinical examination. A detailed history taking included duration of the disease, joint pains, smoking, alcohol consumption, diet, presence of other systemic illness, past intake of systemic agents for psoriasis and concomitant intake of medicines for other illnesses. Clinical examination included measurement of height, weight, waist circumference and blood pressure. The body mass index (BMI) was determined by weight and height calculations using the following equation: BMI = weight in kg/square of height in meters. According to Indian guidelines, a BMI from 23 to 24.9 is overweight, a BMI greater than or equal to 25 is moderate obesity, and a BMI greater than or equal to 30 is severe obesity.[8] The waist circumference was measured by placing the measuring tape snugly around the abdomen at the level of the iliac crest. A waist circumference of more than 90 cm and 80 cm for men and women, respectively, was considered as abdominal obesity.[9] The blood pressure was taken in the sitting posture and the average of two measurements was recorded.

Each participant was thoroughly examined by two dermatologists (SA and SM) who classified psoriasis according to the International classification of Diseases, Tenth revision. Extent of involvement was assessed using Psoriasis Area and Severity Index (PASI), a composite score from 0 to 72 that evaluates the erythema, induration, and scaling of the lesions in four body areas (head, trunk, arms and legs).[10] Mild psoriasis was classified as a PASI between 0 and 7, moderate between 8 and 12 and severe >12. Psoriatic arthritis was diagnosed according to the standard criteria.[11] All patients and controls underwent the following laboratory tests at Sri Ramachandra Central Diagnostic Laboratory after overnight fasting. Serum glucose levels was measured by the hexokinase method, and lipid profile which included total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglyceride levels was assessed by enzymatic methods. Patients were considered to have diabetes if their fasting glucose was more than or equal to 126 mg/dl.[12] Liver function tests which comprised aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase and bilirubin levels were also done in all patients. MS was diagnosed using the South Asian Modified National Cholesterol Education Program Adult Treatment Panel III criteria (SAM-NCEP criteria).[13] If three or more of the following were present, the patient was diagnosed as having MS: abdominal obesity (definition of abdominal obesity was modified using Asia Pacific WHO guidelines as waist circumference ≥90 cm for males and ≥80 cm for females), blood pressure >130/85 mmHg, fasting blood glucose ≥100 mg/dl, hypertriglyceridemia >150 mg/dl, or low HDL cholesterol (<40 mg/dl for males and <50 mg/dl for females). Ultrasonogram of abdomen was also obtained in all subjects in both the groups.

Statistical analysis

Analysis was carried out using Statistical Package for the Social Studies (SPSS), South Asia Pvt. Ltd. Version 17.0 software packages. MS was compared between cases and controls and the association between the presence of psoriasis and duration, severity and psoriatic arthritis was tested using t-test, F-test and chi-square test. All P values were two sided and a P value of less than 0.05 was considered statistically significant. Sample size of the population was determined by posting the prevalence of MS in the control group as 30% (from earlier studies) and we estimated a prevalence difference of about 5% in patients with psoriasis. For significance level (α) at 0.05 and power factor (1-β) at 90%, it was necessary to control at least 108 patients per group in order to guarantee the above significance level of power.

Results

Characteristics of the psoriasis cohort

The study included 118 patients and 120 controls. The mean age of patients in the psoriasis group was 46.31 years ± 11.29 (SD). The mean age in the control group was 45.89 years ± 11.11 (SD). Duration of the disease was classified as <1 year, 1–5 years and >5 years. Twenty patients had short duration of the disease, i.e. less than 1 year, 53 patients had the disease between 1 and 5 years and 45 patients had longstanding disease for more than 5 years. Patients had mild psoriasis to severe psoriasis with PASI score ranging from 0.6 to 45.6 with mean and median of 6.2 and 82. Eighty-two (69.4%) patients had mild psoriasis (PASI < 8), 20 (16.9%) had moderate psoriasis (PASI 8–12) and 16 (13.5%) had severe psoriasis (PASI>12). Thirty (25.4%) had psoriatic arthritis. In the psoriasis group, elevated fasting blood sugar was the most common feature of the MS (61%), followed by decreased HDL levels (36.4%), abdominal obesity (34.7%) and triglyceridemia (34%).

There was a significant association between the presence of MS and some of the individual components of MS in patients with psoriasis when compared to the controls [Figure 1]. In the psoriasis group, 52 (44%) patients had MS, while in the control group, only 36 (30%) had MS (P value=0.025). MS was significantly higher after the age of 40 years. There was a significant correlation between the presence of triglyceridemia, abdominal obesity and elevated fasting glucose levels in the psoriasis cohort when compared to the controls (P value = 0.01, 0.035 and 0.005, respectively). There was no obvious difference in the other components of the MS between both the groups [Table 1].

Figure 1

Distribution of MS and its components among cases and controls. (x axis: MS, metabolic syndrome; WC, waist circumference; TGL, triglyceridemia; HT, hypertension; FBS, elevated fasting blood sugars. y axis: percentage)

Table 1

Study population: Descriptive characteristic of cases and controls

Relation between disease severity and metabolic syndrome

Out of 36 patients who had moderate and severe disease, 14 (38.8%) had MS. The P value was 0.449, indicating that MS was not associated with the extent of involvement. There was also no correlation between severity of the disease and raised fasting blood sugar, decreased HDL cholesterol, increased LDL and total cholesterol levels. However, we found that hypertension, abdominal obesity and triglyceridemia were more prevalent in those patients with moderate and severe disease [Table 2].

Table 2

Relation between disease severity and metabolic syndrome

Relation between duration of psoriasis and metabolic syndrome

There was no significant relationship between duration of the disease and the presence of MS (P value = 0.448) [Table 3].

Table 3

Relation between duration of disease and metabolic syndrome

We also analyzed the individual components of MS in patients with psoriasis and those with MS in the control group. We found that increased fasting blood sugar, triglyceridemia and hypertension were more in the psoriasis group than in the control group with MS [Table 4].

Table 4

Analysis of the components of metabolic syndrome in cases versus controls

Discussion

Gerald Reaven, an endocrinologist from Stanford University, first described the MS in 1988. It was originally described as the clustering of four conditions that when present together in one individual increased the risk of cardiovascular disease. The four conditions were glucose intolerance; hypertension, dyslipidemia and central obesity.[14] There have been many studies linking psoriasis to the individual components of the MS since 1950s.[15]

In 2006, an article authored by Mallbris et al. discussed the metabolic disorders in patients with psoriasis and psoriatic arthritis.[16] In the same year, Sommer et al. showed that MS was more prevalent in psoriasis patients.[17] Since then, there have been many studies from various parts of the world showing the same findings.[1819]

MS and psoriasis share certain common immunological mechanisms. The intra-abdominal fat acts as an endocrine organ capable of secreting adipocytokines that promote inflammation, affect glucose metabolism and vascular endothelial biology.[20] Visceral adiposity is associated with an elevation of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and plasminogen activator inhibitor type1 (PAI-1). These have also been found to be elevated in psoriasis.[2122] Leptin, another hormone secreted by the adipocytes, has a role in acute and chronic inflammation via regulation of cytokine expression that modulates the type 1 and 2 T-helper cells. Hyperleptinemia has been associated with the development of MS. Elevated leptin levels have also been observed in psoriasis. However, the exact effect in psoriasis is yet to be explored.[23]

Our study supports the previous observations by Gisondi and other authors that MS has a higher prevalence in patients with psoriasis.[71824] We observed that 44% of patients with psoriasis had MS. This is much higher when compared to the findings of other studies conducted abroad.[18] An Indian study from Kashmir has shown a prevalence of 28%.[7] This gross difference is probably due to racial factors and the use of South Asian modified NCEP ATP III criteria. The overall prevalence of MS is about 30-40% in the Indian population, with a higher prevalence in South India.[2526] The prevalence of MS in the control population was similar to that of the Indian population. Increased blood sugar was the most important factor contributing to increased prevalence of MS in psoriatic group in our study. The possible explanation is that psoriasis and diabetes share common genetic loci. CDKALI gene has been associated with both psoriasis and type 2 diabetes mellitus. Similarly, PTPN22 has been associated with many diseases, including psoriasis and type 1 diabetes mellitus.[2728]

There have been varying findings on the relationship between the severity of psoriasis and the presence of MS. A Korean study has shown that MS is significantly more prevalent in patients who had moderate and severe disease.[29] Other studies have shown that MS is present irrespective of the extent of involvement.[718] However, they showed a positive correlation between some of the individual components such as triglyceridemia and higher PASI score in these western studies. Our observation is consistent with the latter. Studies have shown that TNFα levels, IL-12 and IL-18 correlate with severity of psoriasis.[3031] These cytokines also play a role in the development of MS.[32] An increased level of these cytokines in moderate and severe disease is a possible explanation for a higher occurrence of abdominal obesity and triglyceridemia in more severe disease in our study.

We did not observe any difference between the presence of MS and the duration of the disease. Mallbris et al., in their study, have shown that patients with new onset psoriasis had increased total cholesterol and HDL than controls, proving the presence of lipid abnormalities even in those with shorter duration of disease.[33] On the contrary, an Indian study by Nisa et al. has shown a positive association between longer duration of psoriasis and MS. However, the individual components of MS and the duration were not analyzed.[7] From the discrepancies in earlier studies, it is unclear whether MS is a risk factor for psoriasis or psoriasis is a risk factor for MS.

This is the first study on the association of MS in South Indian patients with psoriasis and the second such study from India. We have confirmed an association between psoriasis and the presence of MS in our South Indian rural population. Though the sample may not be representative of the entire country, it gives an insight into the pattern of comorbidities of psoriasis in our country, prompting quick therapeutic intervention at the onset of disease itself. Secondly, this being a cross-sectional study, the direction of association, whether psoriasis is a risk factor for MS or MS is a risk factor for psoriasis, cannot be determined.

In conclusion, all patients must be screened for cardiovascular risk factors as per the proposed guidelines at the disease onset irrespective of the disease severity and more so in those patients where systemic therapy is being considered.