Rev. Bras. Reumatol. vol.56 número2

w w w . r e u m a t o l o g i a . c o m . b r

REVISTA

BRASILEIRA

DE

REUMATOLOGIA

Original

article

Brazilian

multicenter

study

of

71

patients

with

juvenile-onset

Takayasu’s

arteritis:

clinical

and

angiographic

features

夽

Gleice

Clemente

_,

_Maria

_Odete

_Hilário

_,

_Claudio

_Len

_,

_Clovis

_A.

_Silva

_,

Adriana

M.

Sallum

_,

_Lúcia

_M.

_Campos

_,

_Silvana

_Sacchetti

_,

_Maria

_Carolina

_dos

_Santos

_,

Andressa

Guariento

Alves

_,

_Virgínia

_P.

_Ferriani

_,

_Flávio

_Sztajnbok

_,

_Rozana

_Gasparello

_,

Sheila

Knupp

Oliveira

_,

_Marise

_Lessa

_,

_Blanca

_Bica

_,

_André

_Cavalcanti

_,

_Teresa

_Robazzi

_,

Marcia

Bandeira

_,

_Maria

_Teresa

_Terreri

a_{SectorofPediatricRheumatology,DepartmentofPediatrics,UniversidadeFederaldeSãoPaulo,SãoPaulo,SP,Brazil}

b_{PediatricRheumatologySector,InstitutodaCrianc¸a,UniversidadedeSãoPaulo,SãoPaulo,SP,Brazil}

c_{SantaCasadeMisericórdiadoSãoPaulo,SãoPaulo,SP,Brazil}

d_{MedicineSchool,UniversidadedeSãoPaulo,RibeirãoPreto,SP,Brazil}

e_{UniversidadedoEstadodoRiodeJaneiro,RiodeJaneiro,RJ,Brazil}

f_{InstitutodePediatriaMartagãoGesteira,UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro,RJ,Brazil}

g_{RheumatologyUnit,UniversidadeFederaldoRiodeJaneiro,RiodeJaneiro,RJ,Brazil}

h_{RheumatologyUnit,UniversidadeFederaldePernambuco,Recife,PE,Brazil}

i_{UniversidadeFederaldaBahia,Salvador,BA,Brazil}

j_{HospitalPequenoPríncipe,Curitiba,PR,Brazil}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received5December2014 Accepted5September2015 Availableonline18February2016

Keywords:

Takayasu’sarteritis Child

Teenager Image

a

b

s

t

r

a

c

t

Objective:TodescribetheclinicalandangiographiccharacteristicsofTakayasu’sarteritisin Brazilianchildrenandadolescents.

Methods:A retrospectivedata collectionwasperformedin 71 childrenandadolescents followedin10BrazilianreferencecentersinPediatricRheumatology.Theevaluationwas carriedoutinthreedifferenttimepoints:fromonsetofsymptomstodiagnosis,fromthe 6thto12thmonthofdiagnosis,andinthelastvisit.

Results:Of71selectedpatients,51(71.8%)weregirls.Themeanageofonsetofsymptoms andoftimetodiagnosiswas9.2(±4.2)yearsand1.2(±1.4)years,respectively.Attheendof thestudy,20patientswereinastateofdiseaseactivity,39inremissionand5hadevolvedto death.Themostcommonsymptomsinbaselineassessment,secondevaluation,andfinal evaluationwere,respectively:constitutional,musculoskeletal,andneurologicalsymptoms.

夽

StudylinkedtotheSectorofPediatricRheumatology,DepartmentofPediatrics,UniversidadeFederaldeSãoPaulo(UNIFESP),São Paulo,SP,Brazil.

∗ _{Correspondingauthor.}

E-mail:teterreri@terra.com.br(M.T.Terreri).

http://dx.doi.org/10.1016/j.rbre.2016.01.004

Adecreaseinperipheralpulseswasthemostfrequentcardiovascularsignal,andanincrease inerythrocytesedimentationratewasthemostfrequentlaboratoryfindinginallthree evaluationperiods.Thetuberculintestwaspositivein41%ofthosetested.Stenosiswas themostfrequentangiographiclesion,abdominalarterywasthemostaffectedsegment, andangiographic typeIVthemostfrequent.Most(90%)participantsweretreatedwith glucocorticoids,85.9%requiredanotherimmunosuppressivedrug,and29.6%underwent angioplasty.

Conclusion:Thisisthelargeststudyonjuvenile-onsetTakayasuarteritis,andahighnumber ofpatientsundertheageof10years,withpredominanceofconstitutionalsymptomsearly inthedisease,wasobserved.

©2016ElsevierEditoraLtda.Allrightsreserved.

Estudo

multicêntrico

brasileiro

de

71

pacientes

com

arterite

de

Takayasu

juvenil:

características

clínicas

e

angiográficas

Palavras-chave: ArteritedeTakayasu Crianc¸a

Adolescente Imagem

r

e

s

u

m

o

Objetivo: DescreverascaracterísticasclínicaseangiográficasdaarteritedeTakayasuem crianc¸aseadolescentesbrasileiros.

Métodos: Foirealizadacoletaretrospectivadedadosde71crianc¸aseadolescentes acom-panhadosem10centrosbrasileirosdereferênciaemreumatologiapediátrica.Aavaliac¸ão foifeitaem3temposdiferentes:iníciodossintomasatéodiagnóstico,do6◦_ao12◦_mêsde diagnósticoeúltimaconsulta.

Resultados: Dos71pacientesselecionados,51(71,8%)erammeninas.Asmédiasdeidade deiníciodossintomasedetempoatédiagnósticoforam9,2anos(±4,2)e1,2anos(±1,4), respectivamente.Nofinaldoestudo,20pacientesestavamematividadededoenc¸a,39em remissãoe5haviamevoluídoaoóbito.Ossintomasmaisfrequentesnasavaliac¸ãoinicial, segundaavaliac¸ãoeavaliac¸ãofinalforam,respectivamente:osconstitucionais,os muscu-loesqueléticoseosneurológicos.Areduc¸ãodepulsosperiféricosfoiosinalcardiovascular maisfrequenteeaelevac¸ãodavelocidadedehemossedimentac¸ãofoioachadolaboratorial maisfrequentenostrêsperíodosdeavaliac¸ão.Otestetuberculínicofoireagenteem41% daquelesqueorealizaram.Aestenosefoialesãoangiográficamaisencontrada,aartéria abdominalfoiosegmentomaisafetadoetipoangiográficoIVomaisfrequente.Amaioria (90%)fezterapiacomglicocorticoides,85,9%necessitoudeoutroimunossupressore29,6% foisubmetidoàangioplastia.

Conclusão: EsteéomaiorestudodearteritedeTakayasujuvenilenóspudemosobservar elevadonúmerodepacientescomidadeinferiora10anoseapredominânciadesintomas constitucionaisnoiníciodadoenc¸a.

©2016ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Takayasu’s arteritis (TA) is achronic vasculitis that affects

large-and medium-caliber arteriesand is accompaniedby

highmorbidity,duetoanimpairedbloodsupplytoorgansand limbs.Thediseaseisrareandaffectspredominantlyyoung femaleadults,beingmostprevalentinEastAsiancountries. ThismakesTAapoorlycharacterizeddiseaseinthepediatric population, particularlyin Westerncountries. The descrip-tions of the disease in the pediatric population, including infants,hasincreasedinrecentdecades,oftenreaching32% ofpatientsagedunder20years.1–5

Clinical signs and symptoms found in patients with

juvenile-onset TAare similarto those found inadults, for

instance, the presence of constitutional, neurological and musculoskeletalsymptoms,highbloodpressure,adecreaseof peripheralpulsesandpresenceofvascularmurmur.However, theinitialclinicalmanifestationsseemtobemoreinsidious and nonspecificinchildren.4,6–9 _{Thismaycontributetothe} greaterdelayofdiagnosisinthepediatricagegroup,whichis uptofourtimeshigherthanthatforadults.2

Theworldliteratureonjuvenile-onsetATarescarce,being

derived from specific populations with small numbers of

Patients

and

methods

ThisisaBrazilianmulticenterstudyonclinical,angiographic andtherapeuticcharacteristicsofpatientsagedunder19years withadiagnosisofTA.Datacollectionwascarriedoutbetween the2010and2011throughasearchofmedicalrecords.

Centersinvolved

FifteenBraziliantertiarymedicalcentersofreferencein Pedi-atricRheumatologywereinvitedtoparticipateinthisstudy. Centerswithatleastthreepatientswithjuvenile-onset TA whofulfilledtheclassificationcriteriaofthedisease10_were included.Thestudyincluded10Braziliancentersofthree dif-ferentgeographicregions,includingthecoordinatingcenter.

Participatingpatients

Patients with incomplete relevant data were excluded (2

patients).Thestudyincluded 71patientsfollowed between

1988 and 2011 with a diagnosis of juvenile-onset TA. The

diagnosiswasestablishedbasedonclinicalfindingsand angi-ographicimagescompatiblewiththedisease,withexclusion ofotherpossiblecauses;andallpatientsmettheclassification criteriaforpediatricTakayasu’sarteritis.10

Questionnaire

A detailed questionnaire containing demographic, clinical, laboratory, angiographic and therapeuticdata wasapplied. Thesedatawerecollectedatthreedifferenttimepoints, in ordertoallowalongitudinalfollow-up ofpatients, making easierthedatacollectionbytheheadofeachparticipating center.Thequestionnairewascomposedof4Excel® spread-sheetsdividedasfollows:baselineassessment(referringto

data from the onset of symptoms to diagnosis

establish-ment);a secondevaluation(for datacollected betweenthe 6thand12thmonthofdiagnosis);finalassessment(referring to data of the last visit and last examination); and treat-ment(referringtotherapyperformedduringfollow-up).This

questionnaire, along with a Word® _{document with}

expla-nations of how to properly fill out the information and

standardize the responses, was emailed by the

coordinat-ingcenter tothedoctorsresponsible foreach participating center.

Patientswereclassifiedaccordingtodiseaseactivityinthe lastsixmonthsofthefinalevaluation:diseaseinactivity,in remission,ordeath.Astherearenovalidatedcriteriafor defin-ingdiseaseactivityforpediatricpatientstodate,wedefined “disease activity” as the presence ofcharacteristic clinical

symptoms/signs of the disease and/or laboratory changes

(increases in erythrocyte sedimentation rate [VHS] and C-reactiveprotein[CRP],withexclusionofotherpossiblecauses forincreasesininflammatorytests)inthelastsixmonths;and “remission”astheabsenceofclinicalsigns/symptomsandof laboratorychanges inthelast 6monthsoffollow-up, with orwithoutpharmacologicalcare.Theangiographic examina-tionswerenotconsideredfortheevaluationofdiseaseactivity, duetothelargenumberofparticipatingcenterswithdifferent

imagingmodalities(conventionalangiography,CTAandMRA) andalsoduetothelargenumberofradiologistsinterpreting theimages.

AngiographictypesweredefinedaccordingtoHata’s angi-ographic classification, developed at the International TA ConferenceinTokyoin1994,asshowninFig.1.11

ThestudywasapprovedbytheEthicsCommitteeofthe

coordinatinginstitutionandbytheotherCommitteesofthe participatingcenters.

Results

Ofthe71patientsselectedforthestudy,51(71.8%)weregirls. Attheonsetofthedisease,36patients(50.7%)werechildren –youngerthan10years;and35(49.3%)wereteenagers–aged 10–19years,accordingtothedefinitionoftheWorldHealth

Organization. Themean ageatonsetofsymptomswas9.2

years(±4.2).Themeansfortimetodiagnosisandprogression timeofthediseasewere1.2(±1.4)yearsand5.4(±3.7)years, respectively.Attheendofthestudy,20patientswerewith theirdiseaseinactivity,39inremission(ofthese,11wereusing corticosteroids),and5died(Table1).Timetilldeathsincethe onsetoffollow-upwasone,two,sixand44months, respec-tively(thisinformationwasnotavailableforonepatient).The causesofdeathwereheartfailure,kidneyfailureandsurgical complications,andwecouldnotidentifythecausamortisof twopatients.

Clinicalfindings

Constitutionalsymptoms–fever,astheniaandweightloss– occurredin77.5%ofpatientsandwerethepredominant symp-toms atthe baseline assessment, followed byneurological –headache,stroke,andsyncope (70.4%)and musculoskele-tal – arthritis,arthralgia, and limbpain(64.8%) symptoms; inthesecondevaluation,themostfrequentsymptomswere musculoskeletal(42.2%),followedbyneurological(35.9%)and constitutional(32.8%)symptoms;andinthefinalevaluation,a

predominanceofneurologicalsymptoms(22.7%)wasfound,

Table1–Clinicalanddemographicfeaturesofpatients withjuvenile-onsetTakayasu’sarteritis.

Clinicalanddemographicfeaturesn=71 n(%)

Girls,n(%) 51(71.8)

Ageatonsetmean(SD),years 9.2(±4.2) Timetodiagnosismean(SD),years 1.2(±1.4) Timeofprogressionmean(SD),years 5.4(±3.7)

Diseaseprogressionattheendofstudy

Activity,n(%) 20(31.3)a

Remission,n(%) 39(60.9)a

Inuseofcorticosteroids 11(28.2)

Nosteroids 28(71.8)

Death,n(%) 5(7.8)a

n,numberofpatients.

a _{Valuesfor64patients,becauseinsevenwewerenotableto}

Type

I

IIa

IIb

III

IV

V

Fig.1–Hata’sangiographicclassification.11

followedbymusculoskeletal–arthritis,arthralgia,andlimb pain (19.7%)and constitutional/gastrointestinal (6.1% each) symptoms(Table2).

Themostfrequentcardiovascularsignalwasadecrease/ absenceofperipheralpulsesinthethreeevaluationperiods, followedbyhighbloodpressureinthefirstevaluationandbya bloodpressuredifferenceinthesecondandthirdevaluations (Table2).

Laboratoryfindings

Regarding laboratorytests,ESRelevationwasthemost fre-quentfindinginallthreeevaluations,beingpresentinover 80%ofpatientsatbaselineassessment,withnormalizationof itsvalueinthemajorityofpatientsduringfollow-up. Tuber-culinskintestwasperformedin58patients,and25(43.1%)of themtestedpositive(Table2).

Table2–Clinicalandlaboratorydataofpatientswithjuvenile-onsetTakayasu’sarteritisatthethreeassessmenttime points.

Clinicalandlaboratoryfindings Initial assessment(71)

n(%)

Second assessment(65)a

n(%)

Finalassessment (66)a_n(%)

Constitutional 55(77.5) 21/64(32.8) 4(6.1)

Neurological 50(70.4) 23/64(35.9) 15(22.7)

Musculoskeletal 46(64.8) 27/64(42.2) 13(19.7)

Gastrointestinal 41(57.7) 14/64(21.8) 4(6.1)

Dyspnea/chestpain 38(53.5) 11/64(17.2) 3(4.5)

Visualchanges 15(21.1) 4/64(6.2) 3(4.5)

Limbclaudication 26(36.6) 19/64(29.7) 10(15.2)

Decrease/absenceofpulses 61(85.9) 51/64(79.7) 44(66.7)

Hypertension 60(84.5) 41/64(64.0) 29(43.9)

Heartandarterialbruit 53(74.6) 43/63(68.3) 37(56.1)

BPdifferencebetweenlimbs>10mmHg 48(67.6) 36/51(70.6) 40(60.6)

Heartfailure 13(18.3) 3/64(4.7) 0(0.0)

IncreaseofVHS 54/67(80.6) 40/62(64.5) 20/60(33.3)

Anemia 35/70(50.0) 12/64(18.8) 8/61(13.1)

Leukocytosis 41/69(59.4) 21/64(32.8) 5/61(8.2)

Thrombocytosis 30/67(44.8) 12/63(19.0) 2/59(3.4)

PPD+ 25/58(43.1) 7/26(26.9) 3/17(17.6)

ESR,erythrocytesedimentationrate;PPD,purifiedproteinderivative.

Constitutionalsymptoms:fever,astheniaandweightloss;neurologicalsymptoms:headache,stroke,syncope;musculoskeletalsymptoms: arthritis,arthralgia,limbpain;gastrointestinalsymptoms:abdominalpain,diarrhea,vomiting;visualchange:conjunctivalhyperemia,visual blurring,blindness,decreasedvisualacuity,uveitis.

a _{6patientswerelosttofollow-upafterthediagnosisandoneofthemreturnedafter5years.}

Table3–Angiographicclassificationofpatientswith juvenile-onsetTakayasu’sarteritis,accordingtoHata’s classification.11

Angiographicclassification n(%)

TypeI 8(11.9)

TypeIIa 4(6.0)

TypeIIb 1(1.5)

TypeIII 9(13.4)

TypeIV 27(40.3)

TypeV 18(26.9)

Thefrequencyofangiographictypesdescribedwasrelatedto67 patients,consideringthatfourpatientslackedfullinitial angiogra-phicdata.

During the baselineassessment, 47 patients underwent conventionalangiography,34MRAand16TCA.Imagingtests werenotperformedonaconsiderablenumberofpatientsin thesecond and thirdevaluations;inview ofthat, onlythe firststudieswereevaluated.Accordingtothestudyofimages takenatbaseline,achangeinabdominalaortawasthemost frequentfinding,and waspresentin67.2%ofpatients, fol-lowedbyrenalarteries(55.2%)andbysubclavianarteriesand descendingthoracicaorta (26.9%each);The mostfrequent typeofarterialinjurywasstenosis(89.6%)followedby obstruc-tion(28.4%),swelling(17.9%)andaneurysm(14.9%);andthe mostfrequentangiographictypewastypeIV,followedbytype V(Table3).Therewasnosignificantdifferencewithrespect toangiographictypesamongchildrenandadolescentswhen typesI, IIaand IIbwere gathered inagroup,and typesIII andIVinanothergroup,beingsubsequentlycomparedamong themselvesandagainstVgroup(p=0.624).

Astodrugtherapyperformedbypatientsduring follow-up,themajority(90.0%)madeuseoforalglucocorticoids,or intheformofpulsetherapy.Sixty-one(85.9%)patientsused

other immunosuppressive drugs (methotrexate,

cyclophos-phamide, azathioprine and mycophenolate) and only four

have used biological therapy (infliximab). Thirty patients

(42.3%) used methotrexateand 18 (25.4%) used

cyclophos-phamide as initial immunosuppressive medication.Of the

25 patients with apositive tuberculin skintest, 10 (40.0%) requiredthe introduction oftriple therapy dueto astrong suspicionoftuberculosis(clinicalfindings,chestradiography, bacilloscopy,orbiopsyorsputumculture),nine(36.0%)used isoniazidfortreatmentoflatenttuberculosis,andtwo(8.0%) hadbeentreatedforlatenttuberculosisinfection,andwere treatedwithtripletherapyatdifferentfollow-uptimes.Four (16.0%)patients, who were weakreactors,did notundergo treatmentwithtripletherapynorforlatentTB.Twopatients withanegativeresultfortuberculintestunderwenttreatment fortuberculosis(1)andforlatenttuberculosis(2),intheface oftheirpositiveepidemiology.Twenty-sevenpatients(38.0%) underwentsomekindofinterventionaltherapy,and angio-plastywasthe mostperformed procedure, in21 (77.8%)of thesepatients.Attheendofthisstudy,thediseaseevolution inthegroupofpatientswhounderwentsurgicalprocedures wasasfollows:7(25.9%)wereinastateofdiseaseactivity,16 (59.3%)wereinremission,and2(7.4%)hadevolvedtodeath. Two(7.4%)ofthesepatientshadnodataavailable(Table4).

Table4–Pharmacologicalandinterventionisttherapy carriedoutduringfollow-upofpatientswith

juvenile-onsetTakayasu’sarteritis.

Treatment Total,n(%)

Corticosteroids 64/71(90.1)b

Methotrexate 52/71(73.2)

Cyclophosphamide 36/68(52.9)b

Azathioprine 7/63(11.1)b

Mycophenolate 3/66(4.5)b

Infliximab 4/64(6.3)b

Antiplatelet 36/68(52.9)b

Anticoagulant 7/65(10.8)b

Antihypertensive 58/70(82.9)b

LatentTBtreatmenta _13/67(19.4)b

TBtreatmenta _13/52(25.0)b

Angioplastywithorwithoutstent 21/71(29.6)

Bypass 10/71(14.1)

Nephrectomy 5/71(7.0)

a _{Onepatientwas treatedforlatent tuberculosis(TB)andfor}

tuberculosisindifferenttimesduringthemonitoring. b _{Mostpercentageswerecalculatedwithdifferentdenominators,}

accordingtothequestionnairedataofeachpatient.

Discussion

Thisstudywasconductedinamixed-racecountry,withlarge geographicdimensionsandwithalargenumberofpatients withjuvenile-onsetTA.Thisallowedusabetterknowledge ofthedisease inthisagegroup.Weobservedahigh num-berofpatientsunder10inourseriesandahighfrequencyof constitutionalsymptomsatpresentationofthedisease.

Thepredominanceoffemalesinourstudyisconsistent with studiesindifferent populations, bothinthe pediatric population,wherethisfrequencyvariesbetween58and83%, asintheadultpopulation,thatshowsanevenhigher propor-tionofwomen.4,5,12–16_{Thehighnumberofchildrenunder10} years inthisstudy,whichincluded patientsupto18 years of age atdiagnosis, draws attention and differs from Park et al. series, where 108 children and adults with TAwere evaluated.14_{Inthisstudy,childrenupto10yearsat} diagno-sisaccountedfor6.5%ofallpatients,andadolescentsaged between10and20yearsaccountedfor19%.Themeanageat diseaseonsetwasalsolowerthanthatfoundinsomestudies, wherethismeanreachedupto14years,buthigherthanthe meanfoundbyHahnetal.in31childrenofSouthAfrica(8.4 years).5,12,13_{Wecouldnotjustifythevariationinageamong} thedifferentpopulations;thus,wehypothesizedthatgenetic andenvironmentalfactorsmayinfluencetheearlieronsetof thediseaseinsomeregions.Themortalityrateof8%found inourcohortwassimilartothatinotherstudiesonpediatric populations(range:7–22%).6,12,13_{Ourpatientsdiedinashort} time,whichreflectstheseverityofthisvasculitis.

Constitutionalsymptomswere presentinalmost80%of

lowerdegreeofinflammationofthediseaseafterits

treat-ment.Otherstudiesalsoshowedthesesymptomsinpeople

withjuvenile-onsetTA,buttheirassessmentwascarriedout separately:fever was present in 4–26%of patients; loss of

weight in 4–47.5%; and fatigue (which was evaluated in a

recentUSstudy),occurredin38%ofpatientsatthe presenta-tionofthedisease.4,5,12,13_{Thehighfrequencyofconstitutional}

symptoms inthe presentation ofTA isa well-known fact,

particularlyinpediatricpopulations;andbecauseoftheir non-specificcharacter,thiscausesadelayindiagnosis,whichin somepatientsmeanta4-yearsetback.

Neurological symptomswere alsovery prevalent in our

series,withimprovementduringfollow-up,similarlyto car-diovascularsigns(lowerperipheralpulsesandbloodpressure), findingsconsistentwiththeliterature.4,6,12,13,17_Thedecreases inperipheralpulsesandblood pressure,especiallythefirst ofthesesigns,didnotshowsignificantimprovementduring follow-up,asthesearesecondarymanifestationsofstructural arterialchanges,athinghardlymodifiablewiththerapy.

VHSelevationwasthemostfrequentlaboratoryfindingin allthreeevaluations,reaching80%ofpatientsatthe presen-tationofthedisease,whichisconsistentwiththehighrate ofincreaseininflammatorymarkersfoundinotherstudies inpediatricpatients.5,12,17_{Anotherfrequentlaboratory} find-inginourpatientswasatuberculinskintestpositivity,which wasalsofoundinotherpopulationswithTAwhere tubercu-losis(TB)isendemic,suchasMexicoandSouthAfrica.12,18

ThehighfrequencyofTBfoundinourchildrenwasmuch

higherthanthatreportedinhealthyBrazilianchildrenbythe BrazilianInstitute of Geographyand Statistics, thus show-ing an association between Mycobacterium tuberculosis and TA.19_{ItisstilluncleartherelationshipbetweenTBandTA,} but oneexplanation isthat the heatshock protein65-kDa foundinmycobacteriacross-reactwiththehomologous pro-teinpresent inthe vascular wallofthe host,triggering an

immuneresponse.

Regarding angiographic changes,stenosis was the most

prevalenttypeofinjury,being foundinmostpatients;this finding is consistent with studies on adults and children, where this is the predominant type of injury.4,15 _The fre-quencyofaneurysmsfoundinourpatientswashigherthan the related instudies based on adultpopulations, ranging between5and12%.14,15,20,21 _{Theabdominalaortaandrenal} arteries were the most affected arterial segments, a find-inginlinewithotherstudiesconductedinchildren.4,13,17,22 Therecent studybySzugieet al.foundahigherfrequency ofinvolvementoftheabdominalaortaanddescending tho-racicaorta;but therenalarterieswereanalyzedseparately, andpossiblytheirfrequencywouldchangeiftheyhadbeen analyzedtogether.5 _{With respectto angiographic type,the} mostcommonwastypeIV,followedbytypeV,afindinga lit-tledifferentfromthatinIndianchildren,wheretherewasa higherprevalenceoftypeV,followedbytypeIV.Ontheother hand,ourfindingsaresimilartothoseinchildreninSouth Africa,whereinfradiafragmaticcommitment(corresponding totypeIV)was themostpredominantfinding,followed by diffuseinvolvement(correspondingtotypeV).12,13 Angiogra-phictypespresentedbyadolescentswereevaluatedseparately fromthetypespresentedbychildren;thus,weintendedtosee iftherewasmorelikenesswiththedistributioninadults,in

whom typesIandVaccountforvirtuallyall cases.16 How-ever, the difference between our adolescents versus adults remained.

Thevastmajorityofpatientsneededglucocorticoidsand

immunosuppressive drugs during follow-up, as shown in

other studies,and asignificant portionunderwent surgery, highlightingthechronicandrelapsingnatureofthedisease.23 Withthistreatment,morethan60%ofpatientswerein remis-sionattheendofthestudy;andthisnumbercouldpossibly bemoreencouragingwithashortertimetodiagnosis.

Thisstudyenabledustoanalyzeasignificantnumberof patientswithjuvenile-onsetTA,makingthisthelargeststudy in this agegroup so far.Because ofthe detailed question-naire which produced datafrom three differentevaluation periods, we could describe clinical and laboratory charac-teristics regardingpresentationand evolution ofTA inour population.

Themajorlimitationofthisstudystemmedfromits retro-spectivenatureandfromthelargenumberofevaluatorsfor datacollection,aswellastheuseofdifferentradiologistsfor interpretationoftheangiographicimagestaken.Tominimize possiblediscrepanciesinassessmentsfromthevarious cen-tersinvolved,aWord®_{documentwithexplanationsofhowto} properlyfilloutthedataandstandardizetheresponseswas senttothedoctorsresponsibleforeachcenter.

In our series, that included patients up to 18 years of age,weobservedahighnumberofpatientsunder10years

and high frequencyofconstitutional symptoms atTA

pre-sentation. These findings confirm the importance of the

clinical suspicionwithrespecttothisvasculitis inchildren andadolescents,whenthesepopulationspresentlong-term

constitutional symptomsofunknown cause,aswell asthe

importanceofcheckingbloodpressureandperipheralpulses inourroutinephysicalexaminations.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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