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Recent epidemiological studies have suggested that psoriasis represents a risk factor for thrombotic vascular diseases. In order to evaluate the possible role of hemostatic changes in the development of thrombotic episodes in psoriasis, some parameters of the hemostatic "balance" were investigated in 22 male psoriatic patients and compared to those of 22 male control subjects. Incidence of known risk factors for vascular diseases (diabetes, hypertension, smoking, dyslipidemia) was comparable in the two study groups. There were no statistically significant differences in platelet count, circulating platelet aggregates, platelet production of malondialdehyde (MDA), total plasma antithrombin and fibrinolytic activities. In patients with psoriasis the incidence of spontaneous platelet hyperaggregability and plasma levels of beta-thromboglobulin were significantly higher than in control subjects. Platelet regeneration time, measured as MDA recovery after aspirin ingestion, was significantly shorter in psoriatic patients. These data suggest that an in vivo platelet activation occurs in patients with psoriasis and could contribute to the development of thrombotic complications. The release of mitogenic and inflammatory substances by activated platelets may play a role in the histogenesis of psoriatic lesions.
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PMID:Platelet activation in psoriasis. 316 Dec 5

Psoriasis is an immune-mediated chronic inflammatory disorder of the skin. Association with kidney disease has been debated for a long time. Secondary renal amyloidosis in psoriatic arthropathy and drug-induced renal lesions secondary to methotrexate or cyclosporine are accepted accompaniments of psoriasis. IgA nephropathy is also known to occur in psoriatics. We report three interesting cases of renal involvement in long-standing established psoriasis on topical therapy alone. The patients presented with hypertension, significant proteinuria, hypoalbuminemia, and dyslipidemia. Kidney biopsies revealed "mesangioproliferative glomerulonephritis with IgA nephropathy," "focal proliferative glomerulonephritis," and "membranous glomerulonephropathy." The former two had marked active urinary sediment. Patients improved on prednisolone and angiotensin-converting enzyme inhibitors. Contrary to the belief that renal involvement in psoriasis is coincidental, we propose that kidney disease may be a common accompaniment of psoriasis, which may be labeled as "psoriatic nephropathy" or "psoriatic kidney disease." The exact mechanism of this entity is yet to be elucidated.
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PMID:Psoriatic nephropathy--does an entity exist? 1571 45

Psoriasis is a chronic inflammatory skin disease that is associated with an increased cardiovascular risk profile. The systemic inflammation present in psoriasis, various systemic treatments for psoriasis and an increased prevalence of unhealthy life style factors may all contribute to this unfavorable risk profile. The purpose of this article is to provide an overview of what is known about these risk factors in psoriasis, the way they influence the cardiovascular risk of psoriasis patients, and what can be done to reduce this risk. Genetic studies demonstrate that psoriasis and cardiovascular disease share common pathogenic features in which, for example inflammatory cytokines like TNF-alpha and IL-1 play an important role. The chronic inflammation in psoriasis has an unfavorable effect on the cardiovascular risk profile. Multiple cardiovascular risk factors seem to be influenced; the blood pressure, oxidative stress, dyslipidemia, endothelial cell dysfunction, homocysteine levels and blood platelet adhesion. Moreover, classic cardiovascular risk factors like smoking and obesity that have an increased prevalence among patients with psoriasis, indirectly also worsen the cardiovascular risk profile by stimulating the psoriasis activity. Systemic treatments in psoriasis reduce the cardiovascular risk by diminishing the inflammation, but it should be taken into account that most therapies also have adverse cardiovascular effects like dyslipidemia, hyperhomocysteinemia and hypertension. As a consequence preventive measures may be indicated at least during long-term treatments. Prospective research is warranted to accurately estimate the increased cardiovascular risk in psoriasis, to determine the underlying processes and to consider preventive measures according to the absolute risk of cardiovascular disease. The present overview provides data to advice health care providers to pay more attention to the cardiovascular risk profile in psoriasis patients.
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PMID:Unfavorable cardiovascular risk profiles in untreated and treated psoriasis patients. 1694 72

Chronic plaque psoriasis is an immune-mediated, inflammatory skin disease with a heavy burden on quality of life of patients. The disease has a chronic relapsing course and may be life long. Comorbid disorders include psoriatic arthritis, obesity, dyslipidemia, hypertension and an increased rate of cardiovascular disease. Conventional systemic treatments include methotrexate, cyclosporine and acitretin, which are associated with end organ toxicity that precludes long term therapy. Biological drugs are designed to selectively interfere with the immune mechanisms that induce psoriasis. Efalizumab is effective for skin psoriasis but not psoriatic arthritis. Anti-TNF-alpha agents (etanercept, infliximab and adalimumab) are active on both psoriasis and psoriatic arthritis. Infliximab is the most effective and rapid agent, but its safety profile may be less favourable. Moreover, efficacy can reduce over time. Etanercept is moderately active but has a better safety profile, and can be discontinued and re-used without loss of efficacy. The long term safety of all these agents has not been established.
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PMID:Biologic therapies in psoriasis: a new therapeutic approach. 1785 41

Previous reports have shown a possible association between psoriasis and obesity, ischaemic heart disease, hypertension or diabetes mellitus. However, most of these studies were uncontrolled and were based on small sample sizes. We therefore investigated the association between psoriasis and the metabolic syndrome in a case control study. Case patients were defined as patients with a diagnosis of psoriasis vulgaris. Control patients were subjects who underwent hernioplasty or appendectomy. We used data mining techniques utilizing the database of the southern district of Clalit Health Services. The proportions of patients with diseases that belong to the metabolic syndrome were compared between case and control patients by univariate analyses. chi2 tests were used to compare categorical parameters between the groups. Logistic regression models were used to measure the association between psoriasis and the metabolic syndrome. A total of 340 patients with psoriasis and 6643 controls were included in the study. The mean age of case patients was 47.7 years (SD 10.7 years). There were 50.3% men and 49.7% women. Ischaemic heart disease was present in 23.5% of the patients with psoriasis, compared with 17.2% of the controls (p=0.003). Diabetes mellitus was present in 27.9% of the patients with psoriasis, compared with 19.5% of the controls (p <0.001). Hypertension was present in 44.4% of the patients with psoriasis, compared with 37.2% of the controls (p=0.007). Obesity was present in 29.4% of the patients with psoriasis, compared with 23.5% of the controls (p=0.012). Dyslipidaemia was present in 50.9% of the patients with psoriasis, compared with 44.2% of the controls (p=0.015). The association between psoriasis and the metabolic syndrome was pronounced after the age of 50 years and in men. Multivariate models adjusting for age and gender demonstrated that psoriasis was associated with an increased risk for ischaemic heart disease (odds ratio (OR) 1.4 95% confidence interval (CI) 1.0-1.8), diabetes mellitus (OR 1.5 95% CI 1.2-2.0), hypertension (OR 1.3 95% CI 1.0-1.7), obesity (OR 1.3 95% CI 1.0-1.7) and dyslipidaemia (OR 1.2 95% CI 1.0-1.6). Our findings demonstrate a possible association between psoriasis and the metabolic syndrome. Further studies are needed to establish this observation.
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PMID:Psoriasis and the metabolic syndrome. 1798 88

Psoriasis is a chronic and debilitating inflammatory disease associated with serious comorbidities. Psoriasis can have a significant impact on a patient's quality of life and is associated with loss of productivity, depression, and an increased prevalence of malignancy. Emerging comorbidities of psoriasis include cardiovascular disease and metabolic syndrome. Psoriasis patients have an increased prevalence of the core components of metabolic syndrome, including obesity, dyslipidemia, and insulin resistance. The relationship between psoriasis and comorbidities such as metabolic syndrome and cardiovascular disease is likely linked to the underlying chronic inflammatory nature of psoriasis. The molecular mechanisms involved in psoriasis-associated dysregulation of metabolic function are believed to be due, in large part, to the action of increased levels of proinflammatory factors, such as tumor necrosis factor-alpha, that are central to the pathogenesis of psoriasis. Recent studies investigating the effects of tumor necrosis factor antagonists on the treatment of cardiovascular disease and metabolic syndrome support this concept.
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PMID:Psoriasis comorbidities. 1827 20

Psoriasis is a chronic immune-inflammatory-mediated disease that can predispose patients to other inflammatory conditions. For example, individuals with psoriasis are at increased risk for insulin resistance, obesity, dyslipidemia, and hypertension--components that characterize the metabolic syndrome. The metabolic syndrome is an important driver of adverse cardiovascular outcomes. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and other factors that are overproduced in patients with psoriasis likely contribute to the increased risk for development of metabolic syndrome. This article reviews the association of psoriasis with metabolic syndrome, as well as the impact of biologic agents that are currently used to treat psoriasis (ie, TNF antagonists) on risk factors for metabolic syndrome.
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PMID:Psoriasis and the metabolic syndrome. 1856 88

Nicotinic acid has been used for several decades to treat dyslipidemia. In mice, the lipid-lowing effect of nicotinic acid is mediated by the Gi coupled receptor PUMA-G. In humans, high (GPR109A) and low (GPR109B) affinity nicotinic acid receptors have been characterized. Here we identify monomethylfumarate as a GPR109A agonist. Monomethylfumarate is the active metabolite of the psoriasis drug Fumaderm. We show that monomethylfumarate activates GPR109A in a calcium based aequorin assay, cAMP assay and demonstrate competitive binding with nicotinic acid. We show that GPR109A is highly expressed in neutrophils and epidermal keratinocytes, and that its expression is increased in human psoriatic lesions. Our findings provide evidence that GPR109A is a target for the drug Fumaderm and suggest that niacin should be investigated to treat psoriasis in addition to its role in treating lipid disorders.
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PMID:The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. 1872 46

The metabolic syndrome is a combination of diabetes mellitus type 2, hypertension, central obesity and combined hyperlipidemia. The metabolic syndrome and its components have been largely associated with psoriasis. We report the case of a 66-year-old man affected with metabolic syndrome and psoriasis in which a multidisciplinary approach with endocrinologists and nutritionists led to an improvement of both conditions. After only 4 months of diet and an appropriate therapeutic regimen we observed an improvement of the hyperglycaemia, dyslipidemia, significant lose of weight, BMI switching from obesity to overweight and improvement of plaque psoriasis in absence of other treatments. We report this case to emphasise the need of a major control of the metabolic syndrome and associated comorbidities in psoriatic patients. Moreover we suggest that diet counselling and regular nutritional visits should be recommended in some patients to obtain dual benefits.
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PMID:Does metabolic syndrome influence psoriasis? 1902 21

Epidemiologic data document not only a higher prevalence of joint involvement among psoriasis patients than previously thought, but also an association with numerous other diseases, including depression, smoking, alcoholism, Crohn's disease, and metabolic syndrome. The resulting increased cardiovascular mortality is of particular clinical importance, and its pathogenetic link as a complication of the psoriatic inflammation is well recognized. Thus, we need to re-invent the management of psoriasis: Dermatologists are not only the sentinel regarding the early diagnosis of psoriatic arthritis, but also of metabolic complications such as dyslipidemia or diabetes. Moreover, they need to keep in mind interactions between (systemic) anti-psoriatic drugs and the co-medication of their patients as well as possible consequences of these co-medications on the course of psoriasis. To successfully accomplish this mission, a comprehensive management concept and ground-breaking research are urgently needed.
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PMID:[Co-morbidities in psoriasis vulgaris]. 1915 62


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