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Psoriasis is now classified as an immune-mediated inflammatory disease (IMID) of the skin. It is being recognized that patients with various IMIDs, including psoriasis, are at higher risk of developing "systemic" co-morbidities, e.g., cardiovascular disease (CVD), metabolic syndrome, and overt diabetes. In non-psoriatic individuals, the pathophysiology of obesity, aberrant adipocyte metabolism, diabetes, and CVDs involves immune-mediated or inflammatory pathways. IMIDs may impact these co-morbid conditions through shared genetic risks, common environmental factors, or common inflammatory pathways that are co-expressed in IMIDs and target organs. Given that pathogenic immune pathways in psoriasis are now well worked out and a large number of inflammatory mediators have been identified in skin lesions, in this review we will consider possible mechanistic links between skin inflammation and increased risks of (1) obesity or metabolic alterations and (2) CVD. In particular, we will discuss how well-established risk factors for CVD can originate from inflammation in other tissues.
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PMID:Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions. 2044 52

Recent epidemiological observations reveal that the prevalence of psoriasis increases more rapidly in young women compared with young men, and that the prevalence of psoriasis may decrease in the elderly. Emerging evidence suggests that some potentially modifiable exposures, such as smoking, stress and obesity, may increase a patient's risk of developing psoriasis. The evolving literature suggests that psoriasis is associated with multiple other diseases, including cancer, cardiovascular disease, diabetes and psychiatric disease, and that psoriasis itself may be an independent risk factor for developing atherosclerosis and myocardial infarction. The treatment of moderate-to-severe psoriasis is undergoing a revolution with the advent of biological therapies that target the immunopathogenesis of psoriasis, such as tumor necrosis factor-alpha and T-cell function. The pharmacokinetics, pharmacodynamics, efficacy and safety profiles vary among biologicals and, therefore, drug and patient factors are important in selecting the optimum therapy. In this article, we focus on recent developments in the epidemiology and systemic treatment of psoriasis.
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PMID:Update on the epidemiology and systemic treatment of psoriasis. 2047 6

An observational study was conducted to estimate the incidence of psoriasis in Italy, as well as the utilization of healthcare resources and the association with selected comorbidities in psoriasis patients. The data source was the Health Search/Thales Database, containing computer-based patient records from over 900 primary care physicians (PCPs) throughout Italy. The study cohort comprised all adults receiving a first-ever diagnosis of psoriasis during the years 2001-2005. From a total sample of 511,532 individuals, the incidence of psoriasis was 2.30-3.21 cases per 1,000 person-years. Psoriatic arthritis was present in 8% of psoriasis patients. The comparison with matched controls showed that psoriasis patients were more likely to have comorbidities (e.g., chronic bronchitis, chronic ischemic heart disease, obesity and diabetes mellitus) and to undergo PCP visits and hospitalizations, and to refer for specialist visits. The use of non-steroidal anti-inflammatory drugs appeared to be significantly more prevalent in patients as compared to controls. Topical therapy with corticosteroids and non-steroidal preparations accounted for 45.3% and 47.2% of all cases, respectively. Only a minority of cases used systemic immunosuppressive drugs or acitretin. The incidence rate of psoriasis in our study was particularly high and might reflect an overestimation by PCPs. Our results show the association between psoriasis and multiple comorbidities.
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PMID:Incidence of psoriasis and association with comorbidities in Italy: a 5-year observational study from a national primary care database. 2060 68

Psoriasis and atherosclerosis share immunoinflammatory mechanisms and patients with psoriasis may carry an excess of cardiovascular risk factors (hypercholesterolemia, hypertension, obesity, metabolic syndrome, diabetes mellitus, smoking etc.) and increased risk of atherothrombotic disease. The current review summarises the available evidence in this area of research and calls for increased awareness of cardiovascular risk assessment and treatment in patients with psoriasis.
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PMID:[Psoriasis and atherothrombotic disease]. 2065 88

Recent studies have found that psoriasis is linked to a higher rate of obesity, and that obesity itself is a risk factor for the development of psoriasis. There are two recent reports of chronic severe psoriasis improving with weight loss after Roux-en-Y gastric bypass surgery. We have observed two patients with body mass indices greater than 50 kg/m(2) who had marked improvement in their psoriasis after gastric bypass surgery. The common link between psoriasis and obesity may be a state of chronic inflammation, including elevated levels of T helper 1 (TH-1) cytokines such as tumor necrosis factor. More recent research has shown that the appetite suppressant leptin is also elevated in patients with psoriasis and obesity, and that levels decrease with weight loss. We conclude that weight loss may be a useful adjunctive therapy for obese patients with psoriasis.
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PMID:Gastric bypass surgery improves psoriasis. 2065 27

Recent studies have found a relationship between obesity and chronic inflammation, confirmed by the association of high levels of tumor necrosis factor (TNF-_), interleukin six (IL-6,) and reactive C-protein with an increase in body mass index (BMI). In obese individuals, this inflammatory condition could contribute to the development or aggravation of psoriasis. Analogous phenomena have already been described in other inflammatory chronic diseases, such as rheumatoid arthritis and Crohn's disease. Epidemiological studies have identified a high prevalence of cardiovascular comorbidities, secondary to the metabolic alterations associated with psoriasis and obesity. A few aspects of this association remain unclear, such as the impact of obesity in the clinical forms of dermatoses, in the response to treatment, and its relationship with comorbidities.
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PMID:Psoriasis and obesity: literature review and recommendations for management. 2067 69

An association between obesity and psoriasis has been reported. For a variety of reasons, obese persons with psoriasis are often more difficult to treat. We sought to review the literature on obesity and psoriasis and to discuss efficacy and safety data that could be utilized by clinicians who are making treatment decisions for obese persons with psoriasis. We performed a literature review using the terms "obesity and psoriasis" and "metabolic syndrome and psoriasis." Evidence from relevant literature was evaluated and categorized according to the criteria of Shekelle et al (published 1999). Numerous reports cite an association between obesity and psoriasis. When compared with non-obese patients with psoriasis, obese patients with psoriasis are more likely to experience certain adverse effects to medications and are less likely to respond favorably to systemic therapies. The amount of category I evidence for objectively determining the best treatment choices for obese patients with psoriasis was scarce and thus did not allow for the development of a treatment algorithm that could be generally applied for all psoriasis patients who are obese. Efficacy and safety concerns affected by obesity are important considerations for clinicians who are making decisions on proper treatment of psoriasis.
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PMID:Obesity and psoriasis: from the Medical Board of the National Psoriasis Foundation. 2069 22

Psoriasis is a chronic inflammatory dermatosis with a relapsing course. The best known comorbidity is psoriatic arthritis. In daily clinical practise it is well known, that patients with psoriasis show more often classic cardiovascular risk factors such as obesity, Diabetes mellitus, hyperlipoproteinemia, hypertension, nicotine abuse often presenting as Metabolic Syndrome and suffer more often from coronary heart disease than patients without psoriasis. This could be demonstrated in numerous clinical and epidemiologic studies. In the last few years there is increasing evidence for psoriasis being an independent cardiovascular risk factor despite of concomitant classic risk factors. This review summarizes the current state of research and discusses possible common immunopathogenetic mechanisms.
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PMID:[Psoriasis as an independent risk factor for development of coronary artery disease]. 2081 62

Several recent studies have found an increased prevalence of non-alcoholic fatty liver disease within psoriasis patients. The exact pathophysiological mechanisms behind these observations are unclear, but are likely related to the high prevalence of obesity and metabolic syndrome within this patient population. Chronic inflammation, mediated by either proinflammatory adipokines or skin-derived cytokines, may contribute to fatty liver disease development by increasing insulin resistance which in turn promotes hepatic lipid accumulation. These same adipokines in addition to hepatic cytokines may act on the skin to influence psoriasis disease severity.
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PMID:Psoriasis and non-alcoholic fatty liver disease. 2084 Mar 46

This article evaluates a patent application from Solvay Pharmaceuticals, which claims spiro azepane-oxazolidinones as novel blockers of the voltage-gated potassium channel Kv1.3 for the treatment of diabetes, psoriasis, obesity, transplant rejection and T-cell mediated autoimmune diseases such as rheumatoid arthritis and MS. The patent describes a new chemotype of Kv1.3 blockers and thus illustrates the growing interest of the pharmaceutical industry in Kv1.3 as a target of immunosuppression and metabolic disorders. This article briefly summarizes the chemistry and biological data provided in the patent and then compares the new compounds to Kv1.3 blockers previously disclosed by both academia and pharmaceutical companies.
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PMID:Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers: WO2010066840. 2095 90


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