There is considerable evidence to show that patients with moderate-to-severe psoriasis have a significantly increased risk of cardiovascular disease and cardiovascular risk factors such as obesity, diabetes mellitus, the metabolic syndrome and smoking compared to the general population. The mechanistic link between psoriasis and this observed increase in cardiovascular co-morbidities has not been fully defined. It is clear, however, that common inflammatory pathways are at play in the pathophysiology of psoriasis, obesity and coronary artery disease. It had been proposed that the control of systemic inflammation in psoriasis could help reduce cardiovascular morbidity, and retrospective studies of methotrexate and anti-TNF-a agents have suggested a cardio-protective effect with use of these agents. More recently, however, there have been concerns regarding a potential excess of cardiovascular events with the newer generation of anti-interleukin-12p40 antibodies. In this article we review the association of psoriasis with cardiovascular disorders and the effects of current psoriasis therapies on cardiovascular risk.
"This also led to investigation into the relationship between anti-IL-12/23 therapies and vascular inflammation. During the phase 2 and 3 trials of ustekinumab, 10 MACE occurred compared to zero MACE in the placebo-treated patients . However, further studies investigating the relationship and specific mode of action of these agents relating to coronary artery atherosclerosis and inflammation are still needed to draw conclusions that are more definitive. "
[Show abstract][Hide abstract] ABSTRACT: Psoriasis is an immune-mediated disease that affects 1%-2% of the European and North American population. While topical agents such as corticosteroids and vitamin D derivatives are prescribed for mild disease, they are generally unable to adequately control patients with more severe disease. Over the past decade, research into the immunopathogenesis of psoriasis, including investigations into the role of tumor necrosis factor-alpha and more recently interleukins (IL) 12/23, has led to the advent of targeted biologic therapies based on the central role of a new subset of T cells, Th17. Because of their increased specificity, biologic agents have revolutionized short- to medium-term treatment outcomes and safety profiles for moderate to severe disease over previously gold standard systemic agents. The immunopathogenesis of the disease is still a focus for researchers and novel targets for future agents are being discovered and investigated in clinical trials. In particular, specifically targeting the IL-23/Th17 pathway has given rise to IL-23p19 and IL-17 antagonists, both of which have shown significant promise in clinical trials. IL-22 is involved in keratinocyte proliferation and is being studied as a treatment target for psoriasis. New small molecule oral agents, including Janus kinase and phosphodiesterase inhibitors are currently in phase 2 and 3 clinical trials.
Dermatology and Therapy 12/2012; 2(1):16. DOI:10.1007/s13555-012-0016-4
"Patients with moderate-to-severe psoriasis have a significantly increased risk of cardiovascular disease and cardiovascular risk factors such as obesity, diabetes mellitus, the metabolic syndrome and smoking compared to the general population. Also, there is a potential excess of cardiovascular events with the newer generation of anti-interleukin-12p40 antibodies used in psoriasis therapies . Psoriatic patients with a body mass index of 27 or more are likely to have vitamin D insufficiency . "
[Show abstract][Hide abstract] ABSTRACT: To evaluate the role of psoriasin, koebnerisin, interleukn (IL)-12 and IL-23 in the pathogenesis of psoriasis and their relations to Psoriasis Area Severity Index (PASI) and obesity. Thirty patients had chronic plaque psoriasis and 30 healthy subjects matched in age and sex were enrolled in this study. Serum from all subjects were used for determination of psoriasin, koebnerisin, IL-12 and IL-23 by ELISA kits. IL-23 and psoriasin were significantly higher in skin psoriasis compared to control and psoriatic arthritis (PsA). There was a correlation between psoriasin and both PASI and obesity. On the other hand, IL-12 was significantly increased in PsA compared to skin psoriasis (p=0.000) and control. Its sensitivity and specificity were 87%, 93%; respectively. To our knowledge, psoriasin is the first biomarker confirm the link between obesity with psoriasis. The risk of development psoriasis is directly related to higher BMI.
[Show abstract][Hide abstract] ABSTRACT: Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.
Journal of the American Academy of Dermatology 10/2013; 70(1). DOI:10.1016/j.jaad.2013.08.042 · 4.45 Impact Factor
Wieteke M Heidema, Ralph R Scholten, Fred K Lotgering, Marc E A Spaanderman
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