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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 .