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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

Health-related

quality

of

life

evaluated

by

Pediatric

Quality

of

Life

Inventory

4.0

in

pediatric

leprosy

patients

with

musculoskeletal

manifestations

Luciana

Neder

a

,

Marlon

van

Weelden

b,c

,

Gabriela

Ribeiro

Viola

d

,

Daniela

Mencaroni

Lourenc¸o

d

,

Claudio

A.

Len

e

,

Clovis

A.

Silva

d,f,∗

aDermatologyService,UniversidadeFederaldoMatoGrosso(UFMT),Cuiabá,MT,Brazil

bVUUniversity,MedicalFaculty,Amsterdam,TheNetherlands

cPediatricDepartment,FaculdadedeMedicina,UniversidadeSãoPaulo(USP),SãoPaulo,SP,Brazil

dPediatricRheumatologyUnit,FaculdadedeMedicina,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil

ePediatricRheumatologyUnit,UniversidadeFederaldeSãoPaulo(UNIFESP),SãoPaulo,SP,Brazil

fDivisionofRheumatology,FaculdadedeMedicina,UniversidadedeSãoPaulo(USP),SãoPaulo,SP,Brazil

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received10April2014

Accepted1December2014

Availableonline20July2015

Keywords:

Leprosy Children

Hansen’sdisease

Health-relatedqualityoflife

Arthritis

a

b

s

t

r

a

c

t

Objective:Toevaluatethehealth-relatedqualityoflife(HRQL)inpediatricleprosypatients.

Methods:Across-sectionalstudyincluded47leprosypatientsand45healthysubjects.The

HRQLwasmeasuredbyPediatricQualityofLifeInventory4.0(PedsQL4.0),andevaluated

physical,emotional,socialandschooldomains.Theleprosypatientswereclassifiedby

RidleyandJoplingclassificationcriteriaandassessedaccordingtoclinicalmusculoskeletal

manifestations,laboratoryandradiographicexaminations.

Results:Themedianofcurrentagewassimilarinleprosypatientsandcontrols[12(6–18)

vs.15(5–18)years,p=0.384],likewisethefrequenciesoffemalegender(p=0.835)and

mid-dle/lowerBraziliansocio-economicclasses(p=1.0).Thedomainschoolactivitiesaccording

thechild-selfreportwassignificantlylowerinleprosypatientscomparedtocontrolsinthe

agegroupof13–18years[75(45–100)vs.90(45–100),p=0.021].Theotherdomainswerealike

inbothgroups(p>0.05).Atleastonemusculoskeletalmanifestation(arthralgia,arthritis

and/ormyalgia)wasobservedin15%ofleprosypatientsandnoneincontrols(p=0.012).

Furthercomparisonbetweenallleprosypatientsshowedthatthemedianofthephysical

capacitydomain[81.25(50–100)vs.98.44(50–100),p=0.036]andschoolactivitiesdomain

bychild-selfreport[60(50–85)vs.80(45–100),p=0.042]weresignificantlylowerinpatients

withmusculoskeletalmanifestationscomparedtopatientswithoutthesemanifestations.

NodifferenceswereevidencedbetweentheotherHRQLparametersinbothgroups,reported

bypatientsandparents(p>0.05).

Conclusions:Reducedphysicalcapacityandschoolactivitiesdomainswereobservedin

pedi-atricleprosypatientswithmusculoskeletalmanifestations.

©2015ElsevierEditoraLtda.Allrightsreserved.

Correspondingauthor.

E-mail:clovisaasilva@gmail.com(C.A.Silva).

http://dx.doi.org/10.1016/j.rbre.2015.05.004

(2)

Qualidade

de

vida

relacionada

à

saúde

avaliada

pelo

Inventário

Pediátrico

de

Qualidade

de

Vida

4.0

em

pacientes

pediátricos

com

hanseníase

e

manifestac¸ões

musculoesqueléticas

Palavras-chave:

Lepra Crianc¸a Hanseniase

Qualidadedevidarelacionadaà

saúde Artrite

r

e

s

u

m

o

Objetivo: Avaliaraqualidadedevidarelacionadaàsaúde(QVRS)empacientespediátricos

comhanseníase.

Métodos: Estudotransversalcom47pacientescomhanseníasee45indivíduossaudáveis.A

QVRSfoimensuradapeloPediatricQualityofLifeInventory4.0(PedsQL4.0)eosdomínios

físico,emocional,socialeescolarforamavaliados.Ospacientescomhanseníaseforam

classificadospeloscritériosdeRidleyeJoplingeavaliadosdeacordocommanifestac¸ões

clínicasmusculoesqueléticas,laboratoriaiseexamesradiográficos.

Resultados: Amédiadeidadeatualfoisimilarempacientescomhanseníaseecontroles

[12(6-18)vs.15(5-18)anos,p=0,384],assimcomofrequênciasdosexofeminino(p=0,835)e

classessocioeconômicasbrasileirasmédia/baixa(p=1,0).Deacordocomaauto-avaliac¸ão

dacrianc¸a relacionadocomasatividadesescolares,estedomíniofoisignificativamente

menornospacientescomhanseníaseemrelac¸ãoaoscontrolesde13-18anos[75(45-100)vs.

90(45-100),p=0,021].Osoutrosdomíniosforamsemelhantesemambososgrupos(p>0,05).

Pelomenosumamanifestac¸ãomusculoesquelética(artralgia,artritee/oumialgia)foi

obser-vadaem 15%dospacientescomhanseníasee nenhumanoscontroles(p=0,012).Uma

comparac¸ãomaisdetalhadaentrepacientescomhanseníasemostrouqueamedianado

domíniodecapacidadefísica[81,25(50-100)vs.98,44(50-100),p=0,036]edeatividades

esco-larespelaauto-avaliac¸ãodacrianc¸a[60(50-85)vs.80(45-100),p=0,042]erasignificantemente

menornospacientescommanifestac¸õesmusculoesqueléticasemcomparac¸ãocomados

pacientessemessasmanifestac¸ões.(1)Nenhumadiferenc¸afoievidenciadaentreosoutros

parâmetrosdeQVRSemambososgruposrelatadospelospacientesepais(p>0,05).

Conclusões: Diminuic¸õesdosdomínioscapacidadefísicaeescolarforamobservadosem

pacientescomhanseníasepediátricaemanifestac¸õesmusculoesqueléticas.

©2015ElsevierEditoraLtda.Todososdireitosreservados.

Introduction

Leprosy, also known as Hansen’s disease, is caused by

the Mycobacterium leprae.1 This isa relevantinfectious

dis-ease in developing countries. Recently in Brazil, 6.7% of

newlydetectedleprosycaseswerediagnosedinchildrenand

adolescents.2

Theclinicalfeaturesofpediatricleprosyincludeseveral

skin lesions, numbness of the skin, damage of

periph-eral nerves, arthralgia and arthritis.3–11 In this regard, we

recentlydetectedthatmusculoskeletalmanifestationswere

associatedwithsevereleprosyinchildrenand adolescents,

especiallyinpatientspresentingnervefunctionimpairment

andneuropathy.12

Furthermore,adultleprosypatientscouldpresentreduced

scoresofhealth-relatedqualityoflife(HRQL),particularlyin

physicalcapacityandsocialparticipationdomains.13–17Toour

knowledge,HRQLwasrarelyreportedinpediatricleprosy,17

andtheimpactofmusculoskeletalmanifestationsonHRQL

wasnotpreviousinvestigated.

Therefore, the objectives of our study were to assess

HRQL in leprosy patients and healthy controls using a

generic instrument for children/adolescents and theirs

legal guardians, and to evaluate the possible influence of

presence of musculoskeletal manifestations in decreasing

HRQL.

Patients

and

methods

A cross-sectional study was performed with 56 leprosy

patients,whichwerefollowed-upattheDermatologyUnitofa

tertiaryhospitalinBrazil.Outofthem,theHRQLof47leprosy

patients wassystematically evaluated.All patients fulfilled

theleprosydiagnosisaccordingtoNationalLeprosyProgram

guidelines4 and Ridley and Jopling classification criteria.18

Controlgroupincluded45healthychildrenandadolescents

of local school in Brazil. This study was approved by the

LocalEthicalCommittee.Patientsandcontrolsandtheirlegal

guardianssignedtheinformedconsentform.

Methods

Demographicdata

Demographicdataincludedcurrent ageandgender.

Brazil-ian socio-economic classes were classified according to

the Associac¸ão Brasileira dos Institutos de Pesquisa de

Mercados.19

Clinicalassessmentofleprosy

Clinical assessment of Hansen’s disease was performed

(3)

The leprosy patients were also classified by Ridley and

Jopling classification criteria: borderline–borderline (BB),

borderline–lepromatous(BL),lepromatous–lepromatous(LL),

borderline–tuberculoid (BT), tuberculoid–tuberculoid (TT) or

indeterminateleprosy(IL).18

Clinicalmusculoskeletalmanifestations

Musculoskeletal manifestations were defined according to:

arthralgia(diffusejointpainortendernesswithoutevidenceof

inflammation),arthritis(swellingwithinajoint,orlimitation

inthe range ofjoint movement with joint pain or

tender-ness)andmyalgia(musclepainortendernessinoneormore

limbswithoutevidenceofinflammation).Arthritiswere

clas-sifiedaccordingtothenumberofjoints[oligoarticular(lower

orequalto4arthritis)andpolyarticular(greaterorequalto5

arthritis)]andduration[acute(lessthan6weeks)andchronic

(overor equalto6weeks)], articulardistribution

[symmet-ricor asymmetric], patternofjoint involvement[addictive,

migratoryand intermittent] and type of joint involvement

[peripheral(largeorsmalljoints)andaxial].

HRQLassessment

TheHRQLwasdeterminedbythegenericinstrument:

Pedi-atricQualityofLife Inventory4.0(PedsQL 4.0) validated to

Brazilian Portuguese language, using different versions for

threeagegroups5–7,8–12and13–18years.20,21 Two

instru-mentswereusedinthepresentstudy:PedsQL4.0child-self

reportandPedsQL4.0parentsreport.ThePedsQL4.0

question-naireincludesproblemsinfour multidimensionaldomains

presentedinthepreviousmonth,suchasphysicalcapacity,

emotionalaspects,socialaspectsand schoolactivities.The

23itemswerescored usingafive-pointscale inthegroups

of8–12years,13–18yearsandparents(0–never,1–almost

never,2–sometimes,3–oftenand4–almostalways)and

forchildrenattheageof5–7yearswithathree-pointscale

(0–never,2–sometimesand3–often).Thesumofthetotal

scorevariedfrom0to100.Ahigherscoreindicatedabetter

HRQL.20,21

Laboratoryandradiographicexaminations

Blinded laboratory exams were performed for the clinical

andHRQL assessments.Antinuclear antibodies(ANA)were

measuredatstudyentrybyindirectimmunofluorescenceon

humancellepithelioma(HEp-2)cells(GMK,USA)and

stain-ingreactivityat≥1:80.Anticardiolipin(aCL)isotypesIgGand

IgMbyenzyme-linkedimmunosorbentassay(ELISA)(Phadia,

Sweden),cut-off valueof20GPL and/orMPL.HLAB27and

rheumatoidfactor(RF)detectionswerecarriedoutbyin-house

real-timepolymerisechainreactionassay(ArupLaboratories,

USA)andbyimmunoturbidimetricassays(Wiener,Argentina,

cut-off<20UI/ml)respectivelyinpatientsandcontrolswith

arthralgiaand/orarthritis.Conventional jointradiographies

were carried out in patients and controls with arthralgia

and/orarthritis,andclassifiedas:decreasedjointspace,

ero-sionsandankylosis.

Statisticalanalysis

Statisticalanalyseswereperformedusingthestatistics

pro-gramSPSS.Thenon-parametricMann–Whitneytestwasused

tocomparethecontinuousvariablesandpresentedasmedian

(range).DifferencesinfrequencieswereassessedbyFisher’s

exacttestforcategoricalvariables.Valuesofpweresetat5%

(p<0.05)inallstatisticaltests.

Results

Themedianofcurrentagewassimilarinleprosypatientsand

healthycontrols[12(6–18)vs.15(5–18)years,p=0.384],

like-wisethefrequenciesoffemalegender(47%vs.51%,p=0.835).

No differences were evidenced in middle/lower Brazilian

socio-economicclassesinbothgroups(91%vs.93%,p=1.0).

Table1–Demographicdata,classificationcriteria, clinicalmanifestations,laboratory,radiographyand treatmentsinleprosypatients.

Variables Leprosy

patients(n=47)

Demographicdata

Currentage,years 12(3–18)

Femalegender 25/47(53)

Braziliansocioeconomicclasses

Middle/lowermiddlesclass 46(92)

RidleyandJoplingclassificationcriteria

Borderline–borderline 21(45)

Indeterminate 0(0)

Tuberculoid 26(55)

Lepromatous 0(0)

WorldHealthOrganization(WHO)classification

Multibacillary 21(45)

Paucibacillary 26(55)

Clinicalmanifestation

Hypopigmentedorreddishskin lesionswithlossofsensation

47(100)

Erythemanodosumleprosum 0(0) Peripheralsilentneuropathy 2(4)

Arthralgia 1(2)

Myalgia 3(6)

Arthritis 5(11)

Laboratory Autoantibodies

Antinuclearantibodies(ANA) 1(2)

Rheumatoidfactor 2/5(20)

IgManticardiolipin(aCL) 7(15)

IgGaCL 1(2)

Radiography

Jointradiographiesabnormalities 0(0)

Treatments

Prednisone 8(17)

Rifampicin,dapsoneandclofazimin 21(45) Rifampicinanddapsone 26(55)

(4)

Table2–PediatricQualityofLifeInventory4.0(PedsQL 4.0)scoresofthreeagegroupsaccordingtoreportsof patientswithleprosyandhealthycontrolsandtheir parents.

Variables Leprosy (n=47)

Controls (n=45)

p

5–7years (n=4) (n=6)

Physical (Patients)

100(81–100) 98.44(88–100) 0.719

(Parents) 98.44(90.63–100) 98.44(90.63–100) 1.0 Emotional

(Patients)

65(60–80) 75(50–90) 0.515

(Parents) 65(60–80) 72.50(60–85) 0.504 Social

(Patients)

85(70–90) 82.50(80–90) 0.909

(Parents) 95(80–100) 90(70–95) 0.321 School

(Patients)

95(80–100) 75(50–100) 0.128

(Parents) 92.50(75–95) 67.50(45–95) 0.130

8–12years (n=20) (n=12)

Physical (Patients)

95.94(63–100) 100(88–100) 0.504

(Parents) 100(68.75–100) 100(90.63–100) 0.982 Emotional

(Patients)

70(55–100) 75(45–100) 0.708

(Parents) 70(55–100) 72.50(65–95) 0.569 Social

(Patients)

90(75–100) 90(45–100) 0.270

(Parents) 95(35–100) 100(45–100) 0.691 School

(Patients)

80(60–95) 85(40–100) 0.346

(Parents) 80(50–100) 87.50(45–100) 0.281

13–18years (n=23) (n=27)

Physical (Patients)

93.75(50–100) 93.75(50–100) 0.597

(Parents) 100(50–100) 93.75(53.13–100) 0.179 Emotional

(Patients)

70(30–95) 75(40–100) 0.358

(Parents) 75(35–100) 80(25–100) 0.769 Social

(Patients)

90(45–100) 95(75–100) 0.506

(Parents) 100(75–100) 100(65–100) 0.631 School

(Patients)

75(45–100) 90(45–100) 0.021

(Parents) 80(35–95) 80(35–100) 0.473

Resultsarepresentedinmedian(range)byMann–Whitneytest.

Demographicdata,classificationcriteria,clinical manifes-tations,laboratoryabnormalities,radiographyandtreatments inleprosypatientsweredescribedinTable1.

Table2includesPedsQL4.0scoresforthreeagegroupsof

childrenand adolescentswithleprosyandhealthy controls

andtheirparents.Thedomainschoolactivitiesaccordingthe

child-selfreportwas significantlylower inleprosypatients

comparedtohealthycontrolsintheagegroupof13–18years

[75 (45–100) vs. 90 (45–100), p=0.021] (Table 2). The other

domainswerealikeinbothgroups(p>0.05).Alldomainswere

alsosimilarintheparentevaluations(p>0.05,Table2).

At least one musculoskeletal manifestation (arthralgia,

arthritis and/or myalgia) was observed in 15% of leprosy

patients and none in healthy controls (p=0.012). Five

lep-rosypatientshad acute orchronic peripheral,asymmetric,

Table3–PediatricQualityofLifeInventory4.0(PedsQL 4.0)scoresofchildrenandadolescents,andtheir parentsaccordingtothepresenceofmusculoskeletal manifestations.

Variables With musculoskeletal

manifestations (n=7)

Without musculoskeletal

manifestations (n=40)

p

Children

Physical 81.25(50–100) 98.44(50–100) 0.036

Emotional 65.00(30–80) 70(45–100) 0.270 Social 90.00(65–100) 90(45–100) 0.336 School 60.00(50–85) 80(45–100) 0.042

Parents

Physical 90.63(50–100) 100(68.75–100) 0.143 Emotional 65.00(35–80) 72.50(50–100) 0.107 Social 95.00(80–100) 100(35–100) 0.735 School 70(50–95) 82.50(35–100) 0.094

Resultsarepresentedinmedian(range)byMann–Whitneytest.

migratorypolyarthritisofsmalljointsofthehands (metacar-pophalangeal and proximal interphalangeal joints), with medianduration of12 months(ranged from 15 daysto 36 months).Fourofthemhadborderline–borderlineleprosyform andhadchronicpolyarthritiswithmorningstiffness, mimick-ingjuvenileidiopathicarthritis(JIA).ANAandHLAB27test were negative inall patients witharthralgia and/or arthri-tis.RFwaspositivein2of5patientswitharthralgiaand/or arthritis.Noneofthemhadconventionaljointradiographies abnormalities.

Furthercomparisonbetweenallleprosypatientsshowed that the median of the physical capacity domain [81.25 (50–100) vs. 98.44 (50–100), p=0.036] and school activities domainbychild-selfreport[60(50–85)vs.80(45–100),p=0.042] were significantly lower in patients with musculoskeletal manifestationscomparedwithout thesemanifestations.No differenceswereevidencedbetweentheotherHRQL parame-tersinbothgroups,reportedbypatientsandparents(p>0.05, Table3).

Discussion

ToourknowledgethiswasthefirstreportthatstudiedHRQL

inpediatricleprosypatientswithmusculoskeletal

manifes-tations,andobservedreducedscoresinphysicalandschool

domains.

The major advantage of this study was the systematic

assessment ofthe HRQLin children and adolescents with

leprosyinawell-knownendemicareaofthisinfectious

dis-easeinBrazil.Moreover,ahealthycontrolgroupwithsimilar

age, gender and socio-economic classwas included in the

presentstudy.Theimportanceofthesesimilaritiesobserved

hereinwasalsoreportedinseveralstudiesthatfounda

rela-tionbetweenHRQLandlowsocio-economicclass,genderand

age.22–24Themainlimitationswerethesmallnumberof

lep-rosypatientsevaluatedhereinandtheuseofonlyoneHRQL

(5)

Theglobalprevalenceofleprosyisincreasingaroundthe

world2 and continuesto be high endemic in a number of

developingcountries,includingBrazil.3In2012,the

propor-tionofchildrenandadolescentsamongnewlydetectedcases

inBrazilwas6.7%.2Themainclinicalinvolvementsofleprosy

arehypopigmentedorreddishlocalizedskinlesionswithloss

ofsensation and peripheralnerves involvements.3

Muscu-loskeletalisthethirdmostinvolvedcommonlyorgan/system

inadultleprosy,7andarthritiswasobservedinupto65%.6,25,26

In pediatric leprosy population, we recentlyobserved that

musculoskeletal manifestation was associated with nerve

dysfunction.Therefore,Hansen’sdiseaseshouldbeincluded

in the differential diagnosis of non-erosive asymmetric

arthritis.12

Moreover,thescoresofHRQLmaybedecreasedinchildren

andadolescentswithchronicdiseasescomparingtohealthy

subjects,27asobservedinourstudy.Interestingly,around60%

oftheadultpatientswithleprosyexperiencedalimitationin

theexecutionofdailyactivitiesandalso60%leprosypatients

hadproblemsinsocialparticipation.16

Furthermore,adultleprosypatientspresentedproblemsin

mobility,interpersonalrelationship,marriage,employment,

leisure activities and social attendance.13 In patients with

10–29years,therewasobservedalowerHRQLscores

compar-ingtohealthycontrols,inseveralcategories,suchaspsychical,

vitality,socialfunctioningandemotionalrole.17

The present study investigated HRQLin three different

groupsofageofpediatricleprosyusingPedsQL4.0score.In

contrastwithotherquestionnaires,suchasSF-36instrument,

whichassessesphysicalandmentalcomponentsinadults,

PedsQL4.0evaluatesemotionaldomainandschoolactivities,

whicharerelevanttothepediatricpopulation.Asignificant

lowerchild-reportedHRQLscoreswasobservedinpediatric

leprosypatientswithmusculoskeletalmanifestationsin

com-parison with patients without these manifestationsin the

domainsphysicalcapacityandschoolactivities.These

find-ingscouldberelatedtoneuropathyand/orarticularchronic

painwithwritingdifficulties,whichinduceschronichealth

problemsandpoorschoolperformance.28Ontheotherhand,

nodifferences were evidenced inthe emotionaland social

domains,probablyduetothepredominanceofskinlocalized

manifestationsin ourpopulation, without findings of

stig-matizeddisease.Indeed, noneofour patient had asevere

lepromatoussubtype,whichischaracterizedbynodules

(lep-romas) and a peculiar facies with diffuse infiltration and

eyelashloss,namedleoninefacies.3,4

Therefore,adetailedinvestigationofallleprosypatients

withmusculoskeletalmanifestationsisrequired.Theneedto

establishpreventiveprograms,includingamultiprofessional

andamultidisciplinaryteam,isoftheutmostimportancefor

thispopulation.

Inconclusion,thiswasthefirststudytoidentifyreduced

physicalcapacityandschoolactivitiesdomainsinpediatric

leprosypatientswithmusculoskeletalmanifestations.

Funding

ThisstudywassupportedbyFundac¸ãodeAmparoàPesquisa

doEstadodeSãoPaulo(FAPESP–grants2008/58238-4toCAS),

byConselhoNacionaldoDesenvolvimentoCientíficoe

Tec-nológico (CNPQ – grant 302724/2011-7 to CAS),by Federico

FoundationtoCASandbyNúcleodeApoioàPesquisa“Saúde

daCrianc¸aedoAdolescente”daUSP(NAP-CriAd).Wethank

Dr.VarniforprovidingthePediatricQualityofLifeInventory

4.0(PedsQL4.0)instrument.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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Imagem

Table 1 – Demographic data, classification criteria, clinical manifestations, laboratory, radiography and treatments in leprosy patients.
Table 2 includes PedsQL 4.0 scores for three age groups of children and adolescents with leprosy and healthy controls and their parents

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