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      Skin Autofluorescence, as a Measure of AGE Accumulation in Individuals Suffering from Chronic Plaque Psoriasis

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          Abstract

          Background

          Psoriasis is currently regarded as a chronic systemic inflammatory disease associated with increased cardiovascular risk. Advanced glycation end products (AGEs) contribute to the development of atherosclerosis.

          Objectives

          The aim of the study was the assessment of skin autofluorescence (SAF), as a measure of AGE accumulation, in individuals suffering from chronic plaque psoriasis without any comorbid conditions.

          Methods

          A study group consisted of 70 patients with chronic plaque psoriasis without any comorbid conditions and 59 healthy controls, matched by age and gender. AGE accumulation was assessed by SAF (AGE Reader, DiagnOptics BV) which is a validated and noninvasive technique. Relations between SAF and some clinical and laboratory data were assessed.

          Results

          SAF was positively correlated with age both in patients with psoriasis and controls ( R = 0.722, p < 0.00001 and R = 0.613, p < 0.00001, respectively). There was significantly increased SAF in patients with psoriasis with elevated levels of C-reactive protein (CRP) and increased erythrocyte sedimentation rate (ESR) compared to controls ( p < 0.00001; p < 0.00001, respectively, after adjustment to age). Increased SAF was found in psoriatic patients with prediabetes (HbA1c 5.7–6.4%) compared to controls ( p < 0.0012, after adjustment to age).

          Conclusion

          Systemic inflammation (increased CRP level), prediabetes, and aging may influence enhanced AGE accumulation in patients with psoriasis without any comorbidities. SAF may be considered as a useful, noninvasive method to identify patients with psoriasis at increased cardiovascular risk.

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          Most cited references34

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          Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and co-morbid conditions.

          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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            The 'psoriatic march': a concept of how severe psoriasis may drive cardiovascular comorbidity.

            There is increasing awareness that psoriasis is more than 'skin deep'. Several recent reviews focussed on biomarkers indicating the systemic dimension of psoriasis and the aspect of comorbidity psoriasis shares with other chronic inflammatory diseases, such as Crohn's disease and rheumatoid arthritis. Of emerging significance is the relationship to cardiovascular disease, as this contributes substantially to the patients' increased mortality. In this viewpoint, we examine currently available evidence favouring the concept of a causal link between psoriasis and cardiovascular disease: systemic inflammation may cause insulin resistance, which in turn triggers endothelial cell dysfunction, leading to atherosclerosis and finally myocardial infarction or stroke. While this 'psoriatic march' is not yet formally proven, it raises clinically and academically relevant questions, and gains support by recent observations of numerous investigators. © 2011 John Wiley & Sons A/S.
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              Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients.

              Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P < 0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.
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                Author and article information

                Contributors
                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi
                0962-9351
                1466-1861
                2018
                27 September 2018
                : 2018
                : 4016939
                Affiliations
                1Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Poland
                2Department of Paediatric Nephrology, Wroclaw Medical University, Poland
                3Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
                Author notes

                Academic Editor: Calogero Caruso

                Author information
                http://orcid.org/0000-0003-2732-3494
                Article
                10.1155/2018/4016939
                6180958
                30363704
                6453d869-9a4c-456a-b72c-20d96dc9e4c7
                Copyright © 2018 Karolina Kopeć-Pyciarz et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 June 2018
                : 26 August 2018
                Categories
                Research Article

                Immunology
                Immunology

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