Anais
Brasileiros
de
Dermatologia
www.anaisdedermatologia.org.br
INVESTIGATION
Higher
incidence
of
metabolic
syndrome
components
in
vitiligo
patients:
a
prospective
cross-sectional
study
夽,夽夽
Efsun
Tanacan
a,∗,
Nilgun
Atakan
baDepartmentofDermatologyandVeneorology,UfukUniversitySchoolofMedicine,Ankara,Turkey bDepartmentofDermatologyandVeneorology,HacettepeUniversityHospital,Ankara,Turkey
Received5March2019;accepted22July2019 Availableonline12February2020
KEYWORDS
Metabolicsyndrome; Obesity;
Vitiligo
Abstract
Background/Objectives: Toinvestigate the association between vitiligo andmetabolic syn-drome.
Methods: A prospectivecross-sectionalstudy wasconducted between2014and2016.Study (n=155)and control groups (n=155)were evaluated for metabolic syndromeaccording to NationalCholesterolEducationProgramAdultTreatmentPanelIIIandtheInternational Dia-betesFederationcriteria.Studygroupwasdividedintothreegroupsaccordingtotheirvitiligo areaseverityindexandvitiligodiseaseactivityscorevalues(Group1:6.89forVASIscore,Group A:−1---0,GroupB:1---2andGroupC:3---4forvitiligodiseaseactivityscorerespectively).MetS ratesaccordingtobothcriteriawerecomparedbetweenthevitiligodiseaseactivityscoreand vitiligoareaseverityindexgroups.
Results: Metabolicsyndromerateswere37.4%and40%inthestudygroupand19.4%and26.5% inthecontrolgroupaccordingtoNationalCholesterolEducationProgramAdultTreatmentPanel IIIandInternationalDiabetesFederationcriteria,respectively(p<001andp=0.011).Metabolic syndromewasmorefrequentinvitiligoareaseverityindexGroups2and3comparedtovitiligo areaseverityindexGroup1,andinvitiligodiseaseactivityscoreGroupCcomparedtovitiligo diseaseactivityscoreGroupsAandB.
Studylimitations: Singlecenterexperience,absenceofmorespecificoxidative-stressmarkers andlackoflong-termfollow-upofthepatients.
Conclusions: Frequency ofmetabolic syndrome was higher in patients with non-segmental vitiligoandtheratewashigherinactive/severeformofthedisease.
©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/). 夽 Howtocitethisarticle:TanacanE,AtakanN.Higherincidenceofmetabolicsyndromecomponentsinvitiligopatients:aprospective cross-sectionalstudy.AnBrasDermatol.2020;95:165---72.
夽夽StudyconductedattheDepartmentofDermatologyandVeneorology,HacettepeUniversityHospital,Ankara,Turkey. ∗Correspondingauthor.
E-mail:efsunkln@yahoo.com(E.Tanacan). https://doi.org/10.1016/j.abd.2019.07.006
0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).
Introduction
Vitiligo is an acquired, progressive disorder of pigmenta-tioncharacterizedbythedevelopmentofwell-definedwhite maculesontheskin.1Itisthemostfrequentcauseof depig-mentationwithanestimatedprevalenceof0.1to2percent inbothadultsandchildren.2Malesandfemalesareequally affectedwithoutprominentethnic,racialorsocio-economic differences.3Vitiligomayoccuratanyagegroupfromearly childhoodtolateadulthood, withapeakincidenceinthe secondandthirddecadesoflife.4
Although, many theories have been debated for the etiology of vitiligo, the exact cause of vitiligo is still unknown.Geneticpredisposition,autoimmunity, biochemi-calsubstances,viralinfection,melanocyteself-destruction, oxidativestress,neuralandmelanocytorrhagyarethemost commonhypothesesintheliterature.5 The clinicalcourse of vitiligo is variationaland lesions mayremain stable or progressslowlyforyears.1VitiligoAreaSeverityIndex(VASI) andVitiligo DiseaseActivityScore(VIDA)may beusedfor the assessment of disease severityand activation.6 Even-though,thereisnocureforthedisease,thephysicianshave sometreatmentmodalitieswhichmayhalttheprogression of lesions and induce varying degrees of repigmentation. Individualized approach based on the patient’s age, skin type,the extent, location and degree of disease activity togetherwiththeeffectofvitiligoonqualityoflifeshould beimplemented.7
Metabolic syndrome(MetS)is an alarming health prob-lemwhichaffectsapproximatelyone-quarteroftheworld’s adultpopulation.8PresenceofMetSprominentlyincreases therisk of developing type 2 diabetes andcardiovascular diseases which leadtoserious complications like myocar-dialinfarction,strokeanddeath.9On theotherhand,the dramaticincreaseofautoimmunediseasesinwestern coun-tries following the outbreak of obesity is remarkable.10 Furthermore, MetS is regarded as a state of chronic low gradeinflammation whichcanresultinincreasedlevelsof proinflammatorymediatorslikeTumorNecrosisFactoralpha (TNF␣), Interleukin-1(IL-1), Interleukin-6 (IL-6) Plasmino-gen Activator Inhibitor-1 (PAI-1), and C-Reactive Protein (CRP).9 Thus, the relationship between MetS and autoim-munediseases wereinvestigatedinmany studies.10 There are also publications in the literature which investigated theassociationbetweenMetSanddermatologicdiseaseslike vitiligoand psoriasis.11---17 Additionally, theroleof vitamin B12metabolisminvitiligowasassessedinsomestudies.18---20 The aim of this study is toinvestigate the association betweenvitiligoandMetS.
Methods
Enrollmentofpatientsandcontrol
We conducted a prospective cross-sectional study at HacettepeUniversity,DepartmentofDermatologyand Vene-orologybetweenOctober 2014andMarch2016.Atotalof 310participantswereincludedinthestudy(n=155forthe studygroupandn=155forthecontrolgroup).Inclusion cri-teriafor thestudygroupwere:(1)Patientswithdiagnosis ofvitiligo(2)≥18yearsofage.Controlgroupwasconsisted
of155 genderandage matchedsubjectswhoadmittedto dermatology clinic for complaintsother than inflammma-toryskin diseases.Exclusioncriteriawere:(1)Presenceof pregnancy or lactation;(2) Patientswhohave used medi-cationsthatcaneffectthemetabolicstatus(likesystemic steroidtherapyorcyclosporine).Writteninformedconsent wasobtainedfromalltheparticipants,andthestudywas approvedbytheinstitutionalethicscommitteeofHacettepe University(GO14/338-03).
Investigationformetabolicsyndrome
StudyandcontrolgroupswereevaluatedforMetScriteria. Mean age,gender, frequency of risk factorsfor metabolic syndrome(presenceofdiabetesmellitus,Hashimoto’s thy-roiditis, hypertension, hyperlipidemia, obesity, rate of smokingandalcohol consumption), laboratory test results [levels of Fasting Plasma Glucose (FPG), High-Density Lipoprotein (HDL), cholesterol, Low-Density Lipoprotein (LDL)cholesterol,total cholesterol,triglycerite(TG),CRP andvitaminB12],vitaminB12deficiency/replacementrates (the percentage patients with lower levels of vitamin B12 levels than reference ranges and/or taking vitamin B12replacement duringthe studyperiod), blood pressure measurements, waistcircumference and Body Mass Index (BMI)werecomparedbetweenthegroups.Vitiligopatients werealsoevaluatedfor frequencyofvitiligosubtypesand meandurationofthedisease.Furthermore,mentionedrisk factors, laboratory tests results and MetS criteria were compared between the vitiligo subtypes (segmental and non-segmentalvitiligo). Venousbloodsamples weretaken fromthesubjectsafter12hoffasting.
Patients with BMI values ≥30kg/m2 were defined as obese. MetSwas definedas thepresence of any three of thefollowing fivetraits:(1)Waist circumference≥102cm in men and≥88cm inwomen; (2) SerumTG ≥150mg/dL or drugtreatment forelevated TG;(3)SerumHDL choles-terol <40mg/dL in men and <50mg/dL in women or drug treatment for low HDL cholesterol; (4) Blood pres-sure ≥130/85mmHg ordrugtreatment for elevatedblood pressure; (5) FPG ≥100mg/dL or drug treatment for elevated blood glucose, according to the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII).21However,TheInternationalDiabetes Feder-ation(IDF)useswaistcircumferenceasanessentialelement in definition with different thresholds set for different race/ethnicity groups.22 We usedboth criteriainorderto objectively compare our results with the results of vari-ous studiesin theliterature. The diagnosis ofvitiligo was madebydermatologistsbasedontheclinicalfindings.VASI and VIDA scores were usedfor the assessment of disease severityand activation.6 Additionally,the vitiligo patients weredividedinto3groupsaccordingtotheirVASIscore val-ues.FirstwecalculatedVASIScoresforall155studygroup patients.ThenwesortedtheVASIscorevalueswith increas-ing orderandafter thatwe divided theVASI scorevalues intothreesubgroupsaccordingtonumberofpatientsineach subgroup(subgroup1=52,subgroup2=52,subgroup3=51). FirstsubgroupconsistedofpatientswithVASIscorevalues <1.94,secondsubgroupconsistedofpatientswithVASIscore values1.94---6.89 andthird subgroup consistedof patients
with VASI score values >6.89. Moreover, the study group were divided into 3 groups according to their VIDA score values(GroupA:−1---0,GroupB:1---2andGroupC:3---4for VIDAscorerespectively).Metabolicsyndromerates accord-ing to both NCEP-ATP III and IDF criteria were compared between the VIDAand VASIgroups. Additionally, VASI and VIDAscores for vitiligo subtypeswere compared. Further-more,meanCRPvalueswerecomparedbetweenVIDAscore groups.Finally,MetSrateswerealsocomparedbetweenthe studyandcontrolgroupsafterexcludingthepatientswith obesity,diabetesmellitus,Hashimoto’sthyroiditis,vitamin B12deficiencyandalcoholconsumption.
Statisticalanalysis
Statistical analyses were performed with the Statistical Packagefor the SocialSciences (SPSS.22,IBM SPSS Statis-tics for Windows, Version 22.0. Armonk, NY: IBM Corp.). TheKolmogorov---Smirnovtestwasusedtoevaluatethe nor-maldistributionofthedata.Normallydistributeddatawere presented as means and standard deviations, while non-parametricdatawerepresentedasmedian(range)values. The independent-samplesttest andMann---WhitneyUtest wereusedtocomparetheparametricandnon-parametric variables between the groups, respectively. Categorical variableswerecomparedusingtheChi-squaretest.The sig-nificancelevelwithap-valueof<0.05wasdetermined.
Results
Demographicfeaturesandclinicalcharacteristics
Thedemographicfeaturesandclinicalcharacteristicsofthe studyandcontrolgroupswereshownintable1.Therewere nostatisticallysignificantdifferencebetweenthegroupsin termsofgender,meanage,ratesofcoexistingdiabetes mel-litus, Hashimoto’s thyroiditis and smoking (p-values were 0.811,0.909,0.723,0.197and0.814respectively).Onthe other hand, rates of hypertension, hyperlipidemia, obe-sity and alcohol consumption were statistically different
betweenthegroups(p-valueswere0.045,0.002,0.025and 0.013respectively).Patientswithvitiligo hadhigherrates ofhypertension(34.2%vs.23.9%),hyperlipidemia(57.4%vs. 39.4%),obesity (23.9%vs.10.3%)andalcohol consumption (32.3%vs.19.4%)comparedtothecontrolgroup.
Metabolicsyndromecomponents
Comparison of the laboratory test results, waist cir-cumference, BMI, blood pressure values and MetS rates betweenthe study and thecontrol groups were shown in
table 2. There were nostatistically significant difference between the groups for mean HDL cholesterol, TG, vita-min B12, waist circumference and BMI values (p-values were 0.970, 0.630, 0.953, 0.08 and 0.054 respectively). However, there were statistically significant differences between the groups for mean FPG, LDLcholesterol, CRP, SystolicBloodPressure (SBP) andDiastolic BloodPressure (DBP) values(p-values were 0.013, 0.031, 0.05, 0.02 and 0.05respectively).StudygrouphadhigherFPG(93±20.82 vs. 87.78±11.40), LDL cholesterol (134.09±31.11 vs. 113.56±24.11), CRP (0.36±0.24 vs. 0.26±0.14), SBP (115±15.50vs.109.29±14.67)andDPB(74.83±10.07vs. 71.38±9.17) values comparedto the control group. Fur-thermore, the rates of vitamin B12 deficiency rate was similarbetweenthegroups(41.1%vs.42.1%,p=0.854).On theother hand rates of vitamin B12replacement therapy andMetS(accordingtobothNCEP-ATPIIIandIDF)were sta-tisticallysignificantlydifferentbetweenthegroups.Vitamin B12replacementtherapyratewas16.1%inthestudygroup and 7.7% in the control group (p=0.036). MetS rate was 37.4% in the study group and 19.4% in the control group accordingtotheNCEP-ATPIIIcriteria(p<001).Additionally, MetSratewas40%inthestudygroupand26.5%inthecontrol groupaccordingtoIDFcriteria(p=0.011).
Vitiligoseverity
Non-segmental vitiligo was the most frequent subtype in our study with 144 patients (92.9%). Segmental vitiligo
Table1 Demographicfeaturesandclinicalcharacteristicsofthestudyandcontrolgrouppatients
Variables Studygroup
(n=155) Controlgroup (n=155) p-Value Gender(n,%) 0.811 Female 72(46.5%) 71(45.8%) Male 83(53.5%) 84(54.2%)
Age(mean±SD,range)(years) 37.04±12.07 (18---69)
37.37±12.60 (18---73)
0.909 Frequencyofriskfactorsformetabolicsyndrome,n(%)
Diabetesmellitus 5(3.2%) 3(1.9%) 0.723 Hashimoto’sthyroiditis 27(17.4%) 18(11.6%) 0.197 Hypertension 53(34.2%) 37(23.9%) 0.045 Hyperlipidemia 89(57.4%) 61(39.4%) 0.002 Obesity 37(23.9%) 16(10.3%) 0.025 Smoking 59(38.1%) 56(36.1%) 0.814 Alcoholconsumption 50(32.3%) 30(19.4%) 0.013
Table2 Comparisonofthelaboratorytestresults,waistcircumference,BMI,bloodpressurevaluesandmetabolicsyndrome ratesbetweenthestudyandthecontrolgroups
Variables Studygroup
(n=155) Controlgroup (n=155) p-Value FPG(mg/dL)(mean±SD) 93±20.82 87.78±11.40 0.013 HDLcholesterol(mg/dL)(mean±SD) 50.08±10.90 50.13±12.37 0.970 LDLcholesterol(mg/dL)(mean±SD) 134.09±31.11 113.56±24.11 0.031 TG(mg/dL)(mean±SD) 127.00±75.90 123.45±71.85 0.630 CRP(mg/L)(mean±SD) 0.36±0.24 0.26±0.14 0.05 VitaminB12(pg/mL)(mean±SD) 245.12±100.86 245.91±130.00 0.953
VitaminB12deficiencyrate,n(%) 62(41.1%) 64(42.1%) 0.854
VitaminB12replacementrate,n(%) 25(16.1%) 12(7.7%) 0.036
Waistcircumference(cm)(mean±SD) 94.20±13.06 91.72±11.85 0.08
BMI(kg/m2)(mean±SD) 26.28±4.71 25.35±3.71 0.054
Systolicbloodpressure(mmHg)(mean±SD) 115±15.50 109.29±14.67 0.02 DiastolicBloodpressure(mmHg)(mean±SD) 74.83±10.07 71.38±9.17 0.05 Metabolicsyndromerate,n(%)
NCEP-ATPIIIcriteria 58(37.4%) 30(19.4%) <0.001
IDFcriteria 62(40%) 41(26.5%) 0.011
FPG,FastingPlasmaGlucose;HDL,High-DensityLipoprotein;LDL,Low-DensityLipoprotein;TG,Triglyceride;CRP,C-ReactiveProtein; BMI,Body-MassIndex,NCEP-ATPIII,NationalCholesterolEducationProgramAdultTreatmentPanelIII;IDF,TheInternationalDiabetes Federation.
Table3 MetabolicsyndromeratesforVASIandVIDAgroupsaccordingtoNCEP-ATPIIIandIDFcriteria
Groups NCEP-ATPIII
metabolic syndromepositive (58/155)(37.4%)
p-Value IDFmetabolic syndromepositive (62/155)(40%) p-Value VASIGroups,n(%) 0.006 0.013 Group1(<1.94) 10/155(6.45%) 12/155(7.7%) Group2(1.94---6.89) 23/155(14.8%) 25/155(16.1) Group3(>6.89) 25/155(16.1%) 25/155(16.1%) VIDAGroups,n(%) < 0.001 <0.001 GroupA(−1---0) 1/155(0.6%) 1/155(0.6%) GroupB(1---2) 3/155(1.9%) 4/155(2.6%) GroupC(3---4) 54/155(34.8%) 57/155(36.8%)
NCEP-ATPIII,NationalCholesterolEducationProgramAdultTreatmentPanelIII;IDF,TheInternationalDiabetesFederation;VASI,Vitiligo areaseverityindex;VIDA,VitiligoDiseaseActivityScore.
Table4 Theratesofmetabolicsyndromebetweenthestudyandcontrolgroupsaftertheexclusionofthepatientswithobesity, diabetesmellitus,Hashimoto’sthyroiditis,vitaminB12deficiencyandalcoholconsumptionaccordingtobothNCEP-ATPIIIand IDFcriteria
Group NCEP-ATPIIImetabolicsyndromepositive IDFmetabolicsyndromepositive p-Value
StudyGroup,n(%) 34/86(39.5%) 35/86(40.7%) <0.001
ControlGroup,n(%) 10/115(8.7%) 18/115(15.6%) <0.001
NCEP-ATPIII,NationalCholesterolEducationProgramAdultTreatmentPanelIII;IDF,TheInternationalDiabetesFederation.
was observed in the remaining 11 patients (7.1%). The mean duration of vitiligo was 121.20±115.04 months. In addition,meanVASIscorewas4.054±5.54(0.093to43.3) andmedianVIDAscorewas3(−1to4).Table3showedthe MetSratesforVASIandVIDAgroupsaccordingtoNCEP-ATPIII and IDF criteria. When we compared the vitiligo patient groupsaccordingtoVASIscoreintermsofMetSrates(both
for NCEP-ATPIII and IDF criteria), we found statistically significant difference between the groups (p-values were 0.006 for NCEP-ATPIII criteria and 0.013 for IDF criteria). MetS was more frequent in Groups 2 and 3 according to bothcriteriacomparedtoGroup1(6.45%,14.8%and16.1% according to NCEP-ATPIII criteria, 7.7%, 16.1% and 16.1% accordingtoIDFcriteriaforGroups1,2and3respectively).
Similarly, we found statistically significant difference betweenthegroupsaccordingtoVIDAscores(p<0.001for bothcriteria).Metabolicsyndromerateswasmorefrequent inGroup C comparedtoGroupA andBaccordingtoboth criteria used (0.6%, 1.9% and 34.8% according to NCEP-ATPIII criteria and 0.6%, 2.6% and 36.8% according to IDF criteria).Furthermore,meanCRPvalueswerestatistically significantlydifferentbetweentheVIDAgroups(p=0.006). MeanCRPvalueinGroupCwashigherthanthemeanCRP valuesinGroupAandB(meanCRPvalueswere0.20±0.08, 0.22±0.07and0.48±0.26respectivelyfortheGroupsA,B andC).Table4showedtheratesofMetSbetweenthestudy andcontrolgroupsaftertheexclusionofthepatientswith obesity,diabetesmellitus,Hashimoto’sthyroiditis,vitamin B12deficiencyandalcohol consumptionaccording toboth NCEP-ATPIII and IDF criteria. MetS was still statistically significantly more frequent in the study group according tothebothcriteriacomparedtothecontrolgroup (39.5% vs.8.7%forNCEP-ATPIIIcriteriaand40.7%vs.15.6%forIDF criteriarespectively,p<0.001forbothcriteria).
Comparisonofsegmentalandnon-segmental vitiligopatients
Comparison of demographic features, clinical character-istics, laboratory tests, metabolic syndrome components togetherwithVASIandVIDAscoresbetweenthesegmental andnon-segmentalvitiligopatientswereshownintable5. Patientswerecomparableformostoftheparametres. How-ever, significantlyhighervalueswerefound for CRP,waist circumference, BMI, obesity rate for NCEP-ATPIII criteria, VASIandVIDAscoresinthenon-segmentalvitiligopatients (0.001, <0.001, 0.001, 0.05, <0.001 and <0.001, respec-tively).
Discussion
Vitiligo is an acquired pigmentary disorder of unknown origin and it is the most common depigmenting disorder worldwide.1,2Itmayhaveaprominentphychosocialimpact onthepatientsanditmaylowertheirqualityoflife.23 How-ever,astheexactcauseofthediseasehasnotbeenrevealed yet,nocurativetreatmentisavailablefornow.7Thus, mana-gement protocols are mostlyconservative and they focus on cosmetic conserns.7 On the other hand, recent stud-ieshavehighlightedamuchgreaterdangerforhealth:the associationofvitiligoandtheMetS.11,13,17AsPietrzaketal. mentionedintheirmanuscript,iftheexistenceofmetabolic disturbancesinvitiligoareproved,thefuturemanagement ofvitiligopatientswillchange.11 MetSincreasestheriskof developing type2diabetes mellitus 5foldandthe riskof developingcardiovasculardisease2foldoverthenext5to 10years.9Furthermore,patientswiththeMetSareat2to 4 fold increasedrisk of stroke, 3 to4 fold increasedrisk ofmyocardialinfarction,and2foldtheriskofdyingfrom theseeventscomparedtopopulationwithoutthesyndrome regardless ofa previous historyof cardiovascularevents.9 Therefore,itiscrucialtopreventtheseriouscomplications of MetS by lifestyle changes and control of risk factors. Additionally,optimalmanagementofMetSmayimprovethe clinicalcourseofvitiligo.
Alterations in cytokine concentrations, autoimmunity andgeneticpredispositionarethoughttobethemain fac-torsbehindthepathogenesisofvitiligo.13,17Besides,vitiligo does not only affect the skin but it has many systemic manifestations.13,17 Productionofautoantibodiesinvitiligo mayalsoresultin the developmentof autoimmunological comorbidities, like alopecia areata, autoimmune thyroid disease,Addison’s disease, perniciousanemia, typeI dia-betes mellitus, and myasthenia gravis according to some studies.5,11 Moreover, increasedlevels of proinflammatory cytokinessuchasTNF-␣, IL-1and IL-6mayleadtoinsulin resistanceandatherosclerosis.11Karadagetal.claimedthat insulinresistance andlipidprofile changesmight occur in patients with vitiligo in their study (decreased levels of HDL cholesterol and increased levels of LDL cholesterol and insulin resistance).24 Furthermore, another study by Karadagetal.demonstratedhigherlevelsofhomocysteine in vitiligo patients comparedto controls.18 Homocysteine inhibits tyrosinase, an enzyme participating in melanine synthesisand it is a markerfor cardiovascular diseases.18 Additionally, Silverberg et al. found that vitiligo patients havehigherhomocysteineandlowervitaminB12serum con-centrations in their study.25 According to recent studies, melanocytesarepresent notonlyin theskinandhair fol-licles,but alsoin theretinal pigment epitheliumcells, in somecellsoftheinnerear,insomepartsofthecentral ner-voussystemandintheadiposetissue.11,26,27Melanocytesin adiposetissuearethoughttotakepartinanti-inflammatory reactionsand inthe reductionor bindingof reactive oxy-gen species.11,26,27 Randhawa et al. found higherrates of melanogenesisinobesepatients.27Hoggardetal.andHoch etal.foundhigherlevelsofa-MelanocyteStimulating Hor-mone(a-MSH), thatbinds tothe Melanocortin 1Receptor (MC1R) on human adipocytes and stimulates melanogen-esis in their studies.28,29 Thus, Pietrzak et al. concluded thatdecreased number of melanocytes together withthe decreased melanogenesis in the adipose tissue might be the common reason behind the oxidative stress both in vitiligoandMetS.11Pageetal.suggestedtestingagonistsof melaninproductiontopreventdevelopmentofMetSintheir studies.26Likewise,Noeletal.indicatesstatinsas immune-modulatingmedicationsforvitiligointheircase reports.30 AfterthepublicationofarticlebyPietrzaketal.,the asso-ciation between vitiligo and MetS attracted attention of moreresearchers.13,17 Atas etal. demonstratedincreased risk of developing MetS in patients withvitiligo and they foundpoorclinical featuresofthe diseasesuchasactive, extended and segmental vitiligo with an increased dura-tionoftimeasindependentpredictorsofdevelopingMetS.13 Furthermore,Sharma et al. found significant presence of MetS in vitiligo patients. However, they did not demon-strateanassociationbetweenMetSandseverity/activityof vitiligo.17
We have demonstrated higher rates of hypertension, hyperlipidemia,obesity,alcohol consumption,vitaminB12 replacementandMetS(forbothcriteria)invitiligopatients comparedto controls in our study. Additionally, levels of meanFPG,LDLcholesterol,CRPandsystolic/diastolicblood pressurewerestatisticallysignificantlyhigherinthestudy group. Furthermore, frequency of MetS increased as the severity/activityofvitiligoincreasedinourstudy.Therates ofmetabolicsyndromewerestatisticallysignificantlyhigher
Table5 Comparison ofdemographic features, clinical characteristics, laboratory tests, metabolic syndromecomponents togetherwithVASIandVIDAscoresbetweenthesegmentalandnon-segmentalvitiligopatients
Variables Non-segmentalvitiligo
patients (n=144) Segmentalvitiligo patients (n=11) p-Value Gender(n,%) 0.730 Male 78(54.2%) 5(45.5%) Female 66(45.8) 6(54.5%)
Age(mean±SD,range)(years) 37.06±12.10(18---69) 37.01±12.20(18---69) 0.910 Frequencyofriskfactorsformetabolicsyndrome,n(%)
Diabetesmellitus 5(3.4%) 0(0%) 0.69 Hashimoto’sthyroiditis 26(18.1%) 1(9.1%) 0.39 Hypertension 49(34%) 4(36.4%) 0.55 Hyperlipidemia 84(58.3%) 5(45.5%) 0.30 Obesity 36(25%) 1(9.1%) 0.67 Smoking 57(39.6%) 2(18.2%) 0.20 Alcoholconsumption 45(31.3%) 5(45.5%) 0.33 FPG(mg/dL)(mean±SD) 93.4±1.79 88.18±1.80 0.42 HDLcholesterol(mg/dL)(mean±SD) 50.01±0.91 50.73±3.5 0.83 LDLcholesterol(mg/dL)(mean±SD) 134.97±3.32 124.25±10.09 0.35 TG(mg/dL)(mean±SD) 127.88±6.21 119.09±28.69 0.71 CRP(mg/L)(mean±SD) 0.37±0.02 0.24±0.02 0.001 VitaminB12(pg/mL)(mean±SD) 244.86±8.67 248.45±23.70 0.91
VitaminB12deficiencyrate,n(%) 53(36.8%) 4(36.4%) 0.62
VitaminB12replacementrate,n(%) 31(21.5%) 1(9.1%) 0.46
Waistcircumference(cm)(mean±SD) 95.79±1.02 82.09±2.70 <0.001
BMI(kg/m2)(mean±SD) 26.62±0.39 21.90±.66 0.001
Systolicbloodpressure(mmHg)(mean±SD) 115.90±1.2 114.09±5.9 0.71 Diastolicbloodpressure(mmHg)(mean±SD) 75.00±0.83 72.72±3.25 0.47 Metabolicsyndromerate,n(%)
NCEP-ATPIIIcriteria 57(39.6%) 1(9.1%) 0.05 IDFcriteria 60(41.7%) 2(18.2%) 0.20 VASIGroups,n(%) <0.001 Group1(<1.94) 40(27.8%) 11(100%) Group2(1.94---6.89) 51(35.4%) 0(0%) Group3(>6.89) 53(36.8%) 0(0%) VIDAGroups,n(%) <0.001 GroupA(−1---0) 19(13.2%) 6(54.5%) GroupB(1---2) 35(24.3%) 3(27.3%) GroupC(3---4) 90(62.5%) 2(18.2%)
FPG,FastingPlasmaGlucose;HDL,High-DensityLipoprotein;LDL,Low-DensityLipoprotein;TG,Triglyceride;CRP,C-ReactiveProtein; BMI,Body-MassIndex;NCEP-ATPIII,NationalCholesterolEducationProgramAdultTreatmentPanelIII;IDF,TheInternationalDiabetes Federation;NCEP-ATPIII,NationalCholesterolEducationProgramAdultTreatmentPanelIII;IDF,TheInternationalDiabetesFederation; VASI,VitiligoAreaSeverityIndex;VIDA,VitiligoDiseaseActivityScore.
inthestudygroup,evenaftertheexclusionofthepatients withobesity,diabetesmellitus,Hashimatothyroiditis, vita-min B12deficiency and alcohol consumption according to bothNCEP-ATPIIIandIDFcriteria.Moreover,meanCRPvalue inGroupCwashigherthanthemeanCRPvaluesinGroup A and B which was most probably due to the increased rates of systemicinflammation with theactivation of the disease.Our findings arealmost consistent with the find-ings of the studies conducted by Atas et al. and Sharma etal.13,17 However,unlikeSharma etal.’s study,we found asignificantrelationshipbetweenvitiligoseverityand pres-enceofMetS.17ThehighervitaminB12replacementratein
vitiligopatientswasconsistentwiththefindingsofthestudy by Karadag et al.18 Furthermore, non-segmental vitiligo might be more associated with chronic inflammation and MetSaccordingtothefindingsofthisstudy.Similarly, seg-mental vitiligo wasreported tobemostlyassociatedwith geneticandautoimmunefactors,whileMetSwasreported tobemorefrequentinnon-segmentalvitiligopatientsinthe literature.1,3,5,13 Additionally, higher VASI and VIDAscores in the non-segmental vitiligo patients indicated a more extendedandactivediseasewhichmightbeanother rea-son for the co-existenceof chronic inflammation in these patients.1,3,5,13
The main strengths of our study were its prospective design, relativelylarge number of patientsincluded, high numberofparametersandhomogeneity oflaboratorytest results.Ontheotherhand,themainlimitationsofthestudy were single center experience, absence of more specific oxidative-stressmarkers, small number of patients in the segmental vitiligo group and lack of long-term follow-up of thepatients. Bothmetabolicsyndrome andvitiligo are dynamic syndromes withchanging severityover the years andweonlytriedtodemonstratethecross-sectional asso-ciationof diseaseseveritywiththepresenceof metabolic syndromefeatures.Furtherprospectivestudiesmaybe car-riedouttoconfirmtheresultsofthisstudy.
Inconclusion,frequencyof MetSwashigherinpatients with non-segmental vitiligo and the rate was higher in active/severe form of the disease. Thus, controlling risk factors,makinglifestylechangesandproviding multidisci-plinaryapproachforMetSmaybebeneficialinpatientswith vitiligo.Specifictherapiesforthemanagementofsystemic inflammationandoxidativestress shouldbethetargetsof physicianswhodealwithvitiligo.
Financial
support
Nonedeclared.
Authors’
contributions
EfsunTanacan:Statisticanalysis;approvalofthefinal ver-sion of the manuscript; conception and planning of the study;elaborationandwritingofthemanuscript;obtaining, analysis,andinterpretation ofthedata; effective partici-pationinresearchorientation;intellectualparticipationin thepropaedeuticand/ortherapeuticconductofthestudied cases;criticalreviewoftheliterature;criticalreviewofthe manuscript.
Nilgun Atakan Approval of the final version of the manuscript; conception and planning of the study; effec-tiveparticipationinresearchorientation;criticalreviewof theliterature;criticalreviewofthemanuscript.
Conflicts
of
interest
Nonedeclared.
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