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Aim of this paper is to discuss, on the basis of an extensive critical review of the recent literature, the case of a 56-yr-old male patient who suffered from cutaneous psoriasis and psoriatic arthritis mutilans (PA) (polyarticular, symmetric, destruent and erosive) with involvement of the hands, feet and spine, associated with android obesity and mild type 2 diabetes mellitus. HLA typing of the patient showed the HLA-A3-Ax, B14-B63 and Cw4-Cw6 haplotypes, some of which are associated or correlated with susceptibility to PA. Cutaneous psoriasis is a chronic inflammatory dermatitis, with onset at any age and affecting approximately 2% of the western populations. In 5-7% of patients, it is associated with articular manifestations or true arthritis. PA is a chronic, inflammatory, seronegative arthropathy which may develop in some psoriasis patients, may involve peripheral and axial (spondarthritis) joints and may lead to severe joint destruction. Genetic, immunologic and environmental (i.e., infectious agents or trauma) factors seem to play an important role in the onset and clinical appearance of PA. Although PA is a clinically monomorphic disease, it may show different heterogenous subgroups with differences in their etiopathogenesis. When PA is suspected, it is mandatory to analyze carefully the patient's familiar history, search attentively for the specific skin features, exclude a septic arthritis (especially if the involvement is monoarticular) and, in the cases of fulminant disease, consider always the possible coexistence of an acquired immunodeficiency syndrome. PA can occasionally be an aggressive, disfigurating and disabling disease and the treatment (incisive and precocious) should be similar to that for rheumatoid arthritis. At present, a definitive therapy does not yet exist, but the majority of PA patients can lead a fairly normal life and they do not show increased mortality rates (excluding the severe cases of erythrodermic or pustulosis psoriasis). However, as a result of the various problems of occupation and morbidity it causes, PA is a disease with great social involvement.
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PMID:[Psoriasis complicated with severe mutilating psoriatic osteoarthropathy. Clinical case and review of the literature]. 1122 Feb 3

Psoriasis is one of the common complex disorders in Western world, affecting 2% to 3% of the population. Recent studies indicate that psoriasis is associated with an increased risk of comorbidity and mortality compared to the general population. It appears that patients with psoriasis have a higher prevalence of metabolic disorders such as diabetes, hypertension, obesity, and hyperlipidemia, as well as a higher frequency of cigarette smoking. These concomitant diseases can complicate the treatment of psoriasis. Even though the etiology of these associations is elusive, physicians should be aware of them and take active steps to reduce the risk profiles of patients with psoriasis and psoriatic arthritis, in order to lessen mortality and comorbidity.
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PMID:Metabolic disorders in patients with psoriasis and psoriatic arthritis. 1697 9

TNF-alpha plays an important role in obesity-linked insulin resistance and diabetes mellitus by activating at least two serine kinases capable of promoting negative regulation of key elements of the insulin signaling pathway. Pharmacological inhibition of TNF-alpha is currently in use for the treatment of rheumatoid and psoriatic arthritis, and some case reports have shown clinical improvement of diabetes in patients treated with the TNF-alpha blocking monoclonal antibody infliximab. The objective of this study was to evaluate the effect of infliximab on glucose homeostasis and insulin signal transduction in an animal model of diabetes. Diabetes was induced in Swiss mice by a fat-rich diet. Glucose and insulin homeostasis were evaluated by glucose and insulin tolerance tests and by the hyperinsulinemic-euglycemic clamp. Signal transduction was evaluated by immunoprecipitation and immunoblotting assays. Short-term treatment with infliximab rapidly reduced blood glucose and insulin levels and glucose and insulin areas under the curve during a glucose tolerance test. Furthermore, infliximab increased the glucose decay constant during an insulin tolerance test and promoted a significant increase in glucose infusion rate during a hyperinsulinemic-euglycemic clamp. In addition, the clinical outcomes were accompanied by improved insulin signal transduction in muscle, liver, and hypothalamus, as determined by the evaluation of insulin-induced insulin receptor, insulin receptor substrate-1, and receptor substrate-2 tyrosine phosphorylation and Akt and forkhead box protein O1 serine phosphorylation. Thus, pharmacological inhibition of TNF-alpha may be an attractive approach to treat severely insulin-resistant patients with type 2 diabetes mellitus.
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PMID:Infliximab restores glucose homeostasis in an animal model of diet-induced obesity and diabetes. 1776 68

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

Psoriasis is a chronic, inflammatory, immune-mediated skin disease associated with substantial comorbidity. Traditional comorbid conditions include psychological/psychiatric disorders, psoriatic arthritis and inflammatory bowel disease. Increasingly, an association with metabolic dysfunction, including obesity and the metabolic syndrome, and cardiovascular disease, with consequent effects on morbidity and mortality, has been recognized in psoriasis. The underlying inflammatory mechanisms of both psoriasis and psoriasis-associated comorbidities involve mediation by proinflammatory T-helper type 1 cytokines. For effective management of psoriasis and related comorbidities, an integrated approach targeting both cutaneous and systemic inflammation may be beneficial, and strategies to improve overall management of the patient should be encouraged to reduce the disease burden. This paper discusses the emerging role of biological agents in this approach, and offers an appreciation of the role of existing anti-psoriasis and adjunctive therapies.
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PMID:Long-term prognosis in patients with psoriasis. 1870 Sep 9

Psoriasis is a common inflammatory skin condition. Around 25% of patients develop joint involvement in the form of psoriatic arthritis as well. Recent epidemiologic studies demonstrated an increased cardiovascular morbidity among psoriasis patients. Although the association of psoriasis with cardiovascular diseases such as hypertension, myocardial infarction, and heart failure, is now widely accepted, the pathogenetic link remains yet unclear. High prevalence of the metabolic syndrome as well as adverse effects of systemic anti-psoriatic therapies may contribute to the observed association. Several pilot studies suggest that insulin resistance may contribute to the development of cardiovascular diseases in psoriasis patients who exhibit metabolic parameters like patients developing diabetes. Retrospective data provide evidence that continuous systemic therapy may reduce the risk of cardiovascular mortality in psoriasis patients. The consequences for the management of psoriasis at this point are two-fold: as co-morbidity goes along with co-medication, potential drug interactions need to be kept in mind when choosing a systemic anti-psoriatic therapy. Moreover, as psoriasis itself is a risk factor for cardiovascular morbidity, patients must avoid other known risk factors such as obesity or smoking. Dermatologists need to communicate this additional risk to their patients and support them accordingly.
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PMID:Cardiovascular morbidity in psoriasis: epidemiology, pathomechanisms, and clinical consequences. 1883 72

Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic T cell-mediated inflammatory diseases that manifest not only in the skin and joints but also in the form of cardiometabolic disturbances, which include insulin resistance, dyslipidemia, and obesity. Thus, PsO and PsA patients are predisposed to metabolic syndrome (MetS), diabetes, and cardiovascular disease. In recent years, the introduction of targeted therapy in the form of tumor necrosis factor-alpha (TNF-alpha) antagonists, such as infliximab, etanercept, and adalimumab has been an important and effective addition to the treatment armamentarium for PsO and PsA. Although TNF-alpha antagonists have produced promising results clinically in reducing cutaneous and joint manifestations of PsO and PsA, their effects on MetS components in these patients are presently unclear. This review summarizes the current limited evidence on the effects of TNF-alpha antagonists on MetS components in PsO and PsA patients and extrapolates from related literature in rheumatoid arthritis, which is also a T cell-mediated inflammatory disease, for additional information.
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PMID:Effects of tumor necrosis factor-alpha blockade on metabolic syndrome components in psoriasis and psoriatic arthritis and additional lessons learned from rheumatoid arthritis. 1922 18

Psoriasis is a chronic inflammatory, immune-mediated skin disease affecting 2 to 3% of the general population and may cause significant quality-of-life impairment. Psoriasis and psoriatic arthritis are associated with increased atherothrombotic diseases, including myocardial infarction, deep venous thrombosis, and reduced life span. Both disease-specific and non-disease-specific risk factors are likely to fuel one another in deleterious vicious circles. Disease-specific risk factors are those that are a direct consequence of psoriasis inflammation and include hyperhomocysteinemia, elevated C-reactive protein, elevated blood inflammatory cytokines, and platelet hyperactivity. Non-disease-specific risk factors include insulin resistance/diabetes, obesity, dyslipidemia, hypertension, metabolic syndrome, and habitual tobacco smoking. The presence of cardio-metabolic comorbidities has also relevant implication in the therapy and global approach to patients with psoriasis. Traditional systemic antipsoriatic agents frequently negatively affect cardio-metabolic comorbidities and may have important interactions with drugs commonly used by psoriasis patients. Thus, patients with psoriasis should be treated effectively and encouraged to aggressively correct their modifiable cardiovascular risk factors.
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PMID:Psoriasis and atherothrombotic diseases: disease-specific and non-disease-specific risk factors. 1945

This article will review how epidemiological studies have advanced our knowledge of both genetic and environmental risk factors for rheumatic diseases over the past decade. The major rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, osteoarthritis, gout, and fibromyalgia, and chronic widespread pain, will be covered. Advances discussed will include how a number of large prospective studies have improved our knowledge of risk factors, including diet, obesity, hormones, and smoking. The change from small-scale association studies to genome-wide association studies using gene chips to reveal new genetic risk factors will also be reviewed.
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PMID:What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases. 1949 May 99

Psoriasis is a disease mediated by Th1 and Th17 cytokines that has different phenotypes (plaque, guttate, pustular, and erythrodermic type). Aside from the well known psoriatic arthritis, associated disorders may occur more frequently than expected, including Crohn's disease, anxiety/depression, and metabolic syndrome. This is based on a constellation of different factors, including abdominal obesity, atherogenic dyslipidemia, hypertension, and glucose intolerance, and is a strong predictor of type 2 diabetes, cardiovascular disease, and stroke. People with moderate to severe psoriasis have more risk for cardiac disease, presumably due to the inflammatory nature of psoriasis, causing inflammatory changes in coronary arteries. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue. Since cardiovascular risk factors are higher in psoriatic patients, dermatologists treating moderate to severe psoriasis should screen for their presence, thus approaching psoriasis as a potential multisystem disorder.
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PMID:Clinical aspects and comorbidities of psoriasis. 1966 31


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