PSORIASIS UNCOVERED - COMORBID CONDITIONS WITH SPECIAL REFERENCE TO METABOLIC SYNDROME

Very interesting article, we should take care that the management of psoriasis should be shifted towards comprehensive disease management. Obesity may increase risk of liver and renal toxicity to Methotrexate and cyclosporine, Obesity may decrease the short-term clinical response to all systemic treatment, Decreasing body weight improves the response of obese patients to low dose cyclosporine therapy, Drugs indicated in co morbidities may exacerbate psoriasis; e.g ACEI, anticoagulants, diuretics, B blockers, and psycholeptics. Drugs used to treat psoriasis can aggravate metabolic syndrome and co morbidities; e.g Cyclosporine may lead to hypertension, or impairment of kidneys, also Acitretine may change glucose tolerance, induce hyperlipidaemia or hepatopathy, also methotrexate may have hepatopathic effects. PSORIASIS UNCOVERED COMORBID CONDITIONS WITH SPECIAL REFERENCE TO METABOLIC SYNDROME


Introduction
Psoriasis is a chronic immune-inflammatory-mediated disease affecting approximately 1-3% of the general population [1,2].Psoriasis is not just a disease of skin and joints, but is a systemic disease that is connected with a range of comorbiditiesespecially metabolic syndrome and cardiovascular disease.Comorbid conditions linked with psoriasis are associated with increasing rates of morbidity and mortality [3].Metabolic syndrome is a cluster of risk factors including central obesity, atherogenic dyslipidaemia, hypertension and glucose intolerance.It is a strong predictor of cardiovascular diseases, diabetes and stroke [4].Similarities exist among psoriasis, metabolic syndrome and atherosclerosis, with all three conditions characterized by an inflammatory process driven by Th1 cytokines [5,6].Increasing population-based studies have suggested a relationship between psoriasis and metabolic syndrome [7].Purpose of our study was to determine the prevalence of comorbidities in patients with psoriasis vulgaris, with special emphasis on metabolic syndrome, as it remains largely unelucidated in the Indian population.
Severity of psoriasis was assessed by percent body surface area (%BSA) and psoriasis area severity index (PASI).BSA is calculated using the "rule of nines".BSA is the arithmetic mean of the affected skin surface based on the assumption that the head (H) presents 10%, the upper extremities (U) 20%, the trunk (T) 30%, and the lower extremities (L) 40% of the total body surface [8].PASI is a composite score from 0 to 72.PASI assesses the degree of erythema (E), infiltration (I), and desquamation (D) in the above-mentioned sites (H, U, T, L) [9].These features are appraised in these sites using a fourpoint scale: 0: no symptoms; 1: slight symptoms; 2: moderate symptoms; 3: marked symptoms; 4: very marked symptoms.The scores used to describe the coverage of skin disease in the distinct areas are: 0: 0%; 1: < 10%; 2: 10-29%; 3: 30-49%; 4: 50-69%; 5: 70-89%; 6: 90-100%.Therefore, PASI takes both coverage (A) and severity (E, I and D) into consideration.It is calculated by: PASI = 0.  [10].If three or more of the following were present, the patient was diagnosed as having metabolic syndrome: abdominal obesity (definition of abdominal obesity was modified using Asia Pacific WHO guidelines as waist circumference ≥90cm for males and ≥80cm 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).ECG was done in all patients and angiogram wherever required.Statistical comparisons were performed using the Student's t-test.The data were considered statistically significant if p values were less than 0.05 (p<0.05).

Results
The study group included 120 patients, with 86 (71.7%) males and 34 (28.3%)females with a male to female ratio of 2.53:1.Age of the patients ranged from 18 years to 62 years with a mean age of 37.34 years.Duration of the disease ranged from 2 months to 30 years, with a mean duration of 6.67 years.Mean age at onset was 31.41 years, with minimum age 12 years and maximum age 60 years at onset.Severity of psoriasis was moderate to severe in 68 (56.7%) of the patients and mild in 52 (43.3%) of the patients with a Median PASI of 13.05.PASI score ranged from 5 to 70.BSA involved ranged from 6% to 80%, with a Median BSA of 20%.Central obesity was the most prevalent comorbidity, affecting 70 (58.3%)patients with psoriasis, followed by hypertension, dyslipidaemia, diabetes mellitus, metabolic syndrome, ischaemic heart disease and stroke (Tabl.I).Waist circumference ≥90cm in men and ≥ 80cm in women was observed in 42 (35%) and 28 (23.3%)patients respectively.Obesity measured by BMI was present in 64 (53.3%) patients.Metabolic syndrome was seen in 30 (25%) patients of psoriasis.Distribution of risk factors and different components of Metabolic Syndrome are given in Table II.On analyzing psoriatic patients with and without metabolic syndrome, we found that patients with metabolic syndrome had longer mean disease duration than psoriatic patients without metabolic syndrome, which was significant.There was no significant difference regarding psoriasis severity, gender or prevalance of smoking between psoriatic patients with and without metabolic syndrome (Tabl III).Metabolic syndrome in psoriasis was seen more commonly in the patients aged above sixty years, however we also observed early onset of metabolic syndrome in psoriasis (Tabl.IV).

Discussion
Recent studies on western population show that psoriasis is associated with metabolic disorders such as hypertension, type II diabetes mellitus, dyslipidemia, abdominal obesity, insulin resistance, and cardiac disorders and the risk of metabolic syndrome is increased in patients with psoriasis [11][12][13][14][15][16][17][18][19].Metaanalysis of studies has shown that psoriatics had increased odds (two-fold) of developing metabolic syndrome compared with the general population.Metabolic syndrome has a high prevalence among psoriasis.Possible biologic mechanisms for this may be due to: chronically elevated free fatty acid (FFA) levels which lead to adipocyte dysfunction which in turn inhibit insulin secretion and up-regulation of proinflammatory adipokines like adiponectin, leptin, resistin and visfatin [7].
© Our Dermatol Online 1.2014 15 Studies on the Indian population with relation to psoriasis and its comorbidities and metabolic syndrome are limited.The prevalence of metabolic syndrome in psoriasis was 25% in our study, which is consistent with other Indian studies, which have shown a prevalence ranging from 18.2% -44.1% [4,[20][21][22][23].This wide variation in the prevalence of metabolic syndrome could be due to ethnic, dietary and lifestyle changes in different parts of the country.Prevalence of different metabolic syndrome components in our study is compared with other Indian studies in Table V. Association with smoking was seen in 15% of our patients which is consistent with a study by Madanagobalane et al [20].Association with smoking may be partly explained by the action of nicotine in promoting Th1 mediated inflammation [6].Smoking induces an overproduction of IL-1β, TNF-α and TGF-β, which have been associated with psoriasis severity [24].In our study 38.3% of patients were alcoholic, other Indian studies have reported an association of 9.1% to 17.7% [20,23].Alcoholism has been related with psoriasis, and studies have reported 1.3-1.6 fold increased risk in development of psoriasis in alcoholics [25].Hypertriglyceridemia and low HDL levels were seen in 43.3% and 33.3% of our patients which is consistent with a study by Madanagobalane et al [20].
Pro-inflammatory cytokines TNF-α and IL-6 over expressed in psoriasis contributes to dyslipidaemia [26].Obesity was observed in 58.3% of our patients which is much higher than other Indian studies which have reported an association of 14.6% to 38% [21,22].Leptin produced by adipose tissue and increased TNF-α acts as a potential link between obesity and psoriasis [27,28].Diabetes mellitus was seen in 26.7% of our patients, while other Indian studies have reported a prevalence ranging from 16% to 61% [20,22].Chronically elevated FFA levels inhibit insulin secretion, and TNF-α and IL-6 contributes to insulin resistance [7,26].Fifty six (46.7%) patients were hypertensive in our study which is consistent with another Indian study by Nisa et al. [21].Henselar et al in 40,000 dermatological patients found 1.9 fold greater likelihood of hypertension in psoriatics compared to other dermatological conditions [11].
Our study showed a significant relationship between duration of psoriasis and metabolic syndrome, which is consistent with a study by Nisa et al. [21].
There was no significant relationship between psoriasis severity and metabolic syndrome in our study, which is consistent with other Indian studies [20,21].However, Langan et al found a robust dose-response relationship between psoriasis severity and prevalence of metabolic syndrome [29].This observation was supported by the translational data that T-helper inflammatory cytokines are increased in skin and sera of psoriatic patients and these exert systemic effects on insulin regulation and lipid metabolism [30].

Characteristic
Onset of metabolic syndrome in psoriasis was seen at a younger age in our study which is consistent with a study reported by Nisa et al. [21].Relative risk of cardiovascular mortality is highest in younger patients less than forty years, with severe psoriasis [15].So early therapeutic intervention would diminish the risk of cardiovascular disease and mortality in psoriasis.
Our results showed that psoriasis predisposes to the development of a distinct cluster of concomitant diseases, including hypertension, dyslipidemia, obesity and metabolic syndrome.Hence all patients with psoriasis should be monitored for associated co-morbid conditions.For effective management of psoriasis and related co-morbidities, an integrated approach targeting both cutaneous and systemic manifestations may be beneficial.
Limitation of this study was that the sample size was not large enough to represent the general population.Further large prospective, randomized, controlled, population-based studies should be undertaken to confirm the association and causality between psoriasis and metabolic syndrome.

Conclusion
Approach psoriasis as a potentially multisystem disorder and alert patients to the potentially negative effects of psoriasis as it relates to other aspects of their health.Can we now consider psoriasis as a cutaneous marker for metabolic syndrome?