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INVESTIGATIVE REPORT See also In-this-Issue, p. 775
ActaDV ActaDV Advances in dermatology and venereology Acta Dermato-Venereologica
Advanced Glycation End Products are Increased in the Skin and Blood of Patients with Severe Psoriasis
Anastasia PAPAGRIGORAKI 1, Micol DEL GIGLIO 1, Chiara COSMA 2, Martina MAURELLI 1, Giampiero GIROLOMONI 1 and Annunziata LAPOLLA 3
1
Department of Medicine, Section of Dermatology and Venereology, University of Verona, Verona, 2 Department of Laboratory Medicine, Hospital-University of Padua, and 3 Department of Medicine, Section of Endocrinology, University of Padua, Padua, Italy
Psoriasis is frequently associated with metabolic comorbidities. Advanced glycation end products( AGEs) are highly oxidant, biologically active compounds that accumulate in tissues in association with hyperglycaemia, hyperlipidaemia and oxidative stress. This is a cross-sectional case-control study involving 80 patients with mild / severe psoriasis and 80 controls matched for age, sex and body mass index( 40 with severe eczema, 40 healthy individuals). Patients and healthy individuals with a smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension or who were under systemic treatment were excluded from the study. Skin AGEs were measured in normalappearing skin by a standard fluorescence technique, and blood AGEs( total AGEs, pentosidine and AGEs receptor) by enzyme-linked immunosorbent assay. Levels of cutaneous AGEs( p < 0.04), serum AGEs( p < 0.03) and pentosidine( p < 0.05) were higher in patients with severe psoriasis. Cutaneous AGEs correlated well with serum AGEs( r = 0.93, p < 0.0001) and with Psoriasis Area and Severity Index score( r = 0.91, p < 0.0001). Receptor levels were lower( p < 0.001) in severe psoriasis, and inversely correlated with disease severity( r = – 0.71, p < 0.0002). Patients with severe psoriasis have accumulation of skin and serum AGEs, independent of associated metabolic disorders.
Key words: psoriasis; eczema; advanced-glycation-end-products; inflammation.
Accepted Mar 27, 2017; Epub ahead of print Mar 30, 2017 Acta Derm Venereol 2017; 97: 782 – 787.
Corr: Anastasia Papagrigoraki, Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, IT-37126 Verona, Italy. E-mail: papanastassia @ yahoo. it
Psoriasis is a common chronic inflammatory immunemediated disease that affects 2 – 3 % of the Western population. Ten to 20 % of patients with psoriasis have severe disease, defined by an involved body surface area greater than 10 %( 1, 2). Severe psoriasis is strongly associated with metabolic disorders, including obesity, metabolic syndrome, arterial hypertension, dyslipidaemia and type II diabetes( 3 – 9). Advanced glycation end products( AGEs) are a group of highly oxidant, biologically active compounds that accumulate in tissues, mostly in association with hyperglycaemia, hyperlipidaemia and oxidative stress. AGEs form through several pathways, including oxidation of sugars, lipids and amino acids, to create reactive aldehydes that bind covalently to proteins. A well-characterized and easily detected member of this large class of compounds is pentosidine( 10 – 12). AGEs are part of the normal metabolism, but, if expressed in excess, may alter cellular structure and function, and promote oxidative stress with formation and release of free radicals( 13 – 15). Accumulation of AGEs occurs permanently in physiological terms through ageing, and it is markedly amplified in diabetes as a consequence of persistent hyperglycaemia, but is also documented in patients with obesity, metabolic syndrome, rheumatoid arthritis, and fatty liver disease( 16 – 18). AGEs elicit biological function through activating membrane receptor( RAGE; receptor for advanced glycation end-products), which is expressed on the surface of inflammatory and epithelial cells, and promotes innate immunity. RAGE exists as several variants, and has emerged as a central regulator for vascular inflammation and atherosclerosis( 19 – 21).
The primary objective of this study was to investigate whether psoriasis is associated with accumulation of AGEs in the skin and serum, and whether skin and serum AGEs correlate with psoriasis severity.
MATERIALS AND METHODS Patients
This cross-sectional case-control study involved a series of 80 patients with chronic plaque psoriasis( cases) and 80 controls matched for age, sex and body mass index( BMI). Inclusion criteria for cases were adult age between 18 and 60 years, clinical diagnosis of chronic plaque psoriasis, and lack of any systemic treatment for psoriasis for at least 6 months before enrolment. Patients affected by psoriatic arthritis were not included. The control group included healthy subjects and patients with chronic eczema, mostly atopic dermatitis. Psoriasis or eczema mean duration was ≤ 3 years at enrolment. Disease duration and patients’ age were selected in order to avoid bias associated with age-related changes in levels of AGEs. Patients and healthy individuals with smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension, any systemic inflammatory, metabolic or autoimmune disease or under systemic treatment, including corticosteroids, acitretin, cyclosporine, methotrexate, phototherapy or biologics, were also excluded from the study. All subjects, after being informed of the study purpose and procedures involved, signed informed consent and were visited by a dermatologist who registered demographic, biometric and other relevant data on a digital case report form. Relevant data collected included age, sex, weight, height, BMI, doi: 10.2340 / 00015555-2661 Acta Derm Venereol 2017; 97: 782 – 787
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.