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:[email protected](C.A.Silva).
http://dx.doi.org/10.1016/j.rbre.2015.05.004
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
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)
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
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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