www.jped.com.br
ORIGINAL
ARTICLE
Musculoskeletal
manifestations
and
autoantibodies
in
children
and
adolescents
with
leprosy
夽
Luciana
Neder
a,b,
Daniel
A.
Rondon
b,
Silvana
S.
Cury
c,
Clovis
A.
da
Silva
d,∗aMedicalClinicDepartment,UniversidadeFederaldoMatoGrosso(UFMT),Cuiabá,MT,Brazil
bDermatologyService,HospitalUniversitárioJulioMuller,UniversidadeFederaldoMatoGrosso(UFMT),Cuiabá,MT,Brazil cCentralLaboratoryDivision,HospitalUniversitárioJulioMuller,UniversidadeFederaldoMatoGrosso(UFMT),Cuiabá,MT,Brazil dPediatricRheumatologyUnit,FaculdadedeMedicina,UniversidadedeSãoPaulo(FMUSP),SãoPaulo,SP,Brazil
Received21August2013;accepted8January2014 Availableonline5April2014
KEYWORDS
Leprosy; Arthritis; Arthralgia; Neuropathy; Autoantibodies
Abstract
Objective: Toevaluatemusculoskeletal involvementandautoantibodiesinpediatricleprosy patients.
Methods: 50leprosypatientsand47healthychildrenandadolescentswereassessedaccording to musculoskeletal manifestations(arthralgia, arthritis, andmyalgia), musculoskeletal pain syndromes(juvenilefibromyalgia,benignjointhypermobilitysyndrome,myofascialsyndrome, andtendinitis),andapanelofautoantibodiesandcryoglobulins.Healthassessmentscoresand treatmentwereperformedinleprosypatients.
Results: Atleastonemusculoskeletalmanifestationwasobservedin14%ofleprosypatientsand innoneofthecontrols.Fiveleprosypatientshadasymmetricpolyarthritisofsmallhandsjoints. Nervefunctionimpairmentwasobservedin22%ofleprosypatients,type1leprosyreactionin 18%,andsilentneuropathyin16%.Noneofthepatientsandcontrolspresented musculoskele-talpainsyndromes,andthefrequenciesofallantibodiesandcyoglobulinsweresimilarinboth groups (p>0.05).Further analysisofleprosypatientsdemonstratedthatthefrequenciesof nervefunctionimpairment,type1leprosyreaction,andsilentneuropathyweresignificantly observedinpatientswithversuswithoutmusculoskeletalmanifestations(p=0.0036,p=0.0001, andp=0.309,respectively),aswellasmultibacillarysubtypesinleprosy(86%vs.42%,p= 0.045).Themedianofphysicians’visualanalogscale(VAS),patients’VAS,painVAS,and Child-hoodHealthAssessmentQuestionnaire(CHAQ)weresignificantlyhigherinleprosypatientswith musculoskeletalmanifestations(p=0.0001,p=0.002,p=0002,andp=0.001,respectively).
夽
Pleasecitethisarticleas:NederL,RondonDA,CurySS,daSilvaCA.Musculoskeletalmanifestationsandautoantibodiesinchildrenand adolescentswithleprosy.JPediatr(RioJ).2014;90:457---63.
∗Correspondingauthor.
E-mail:[email protected](C.A.Silva). http://dx.doi.org/10.1016/j.jped.2014.01.007
Conclusions: Thiswasthefirststudytoidentifymusculoskeletalmanifestationsassociatedwith nervedysfunction inpediatric leprosypatients. Hansen’sdisease shouldbe includedinthe differentialdiagnosisofasymmetricarthritis,especiallyinendemicregions.
©2014SociedadeBrasileiradePediatria.PublishedbyElsevierEditoraLtda.Allrightsreserved.
PALAVRAS-CHAVE
Hanseníase; Artrite; Artralgia; Neuropatia; Autoanticorpos
Manifestac¸õesmusculoesqueléticaseautoanticorposemcrianc¸aseadolescentescom hanseníase
Resumo
Objetivo: Avaliar o envolvimento musculoesquelético e os autoanticorpos em pacientes pediátricoscomhanseníase.
Métodos: Foramavaliados50pacientescomhanseníasee47crianc¸aseadolescentessaudáveis de acordo commanifestac¸ões musculoesqueléticas(artralgia, artrite e mialgia), síndromes dolorosas musculoesqueléticas (fibromialgia juvenil, síndrome de hipermobilidade articular benigna,síndromemiofascialetendinite)epaineldeautoanticorposecrioglobulinas.Escores deavaliac¸ãodesaúdeetratamentoforamrealizadosnospacientescomhanseníase.
Resultados: Pelo menos uma manifestac¸ão musculoesquelética foi observada em 14% dos pacientescomhanseníaseeemnenhumcontrole.Dentreospacientescomhanseníase,cinco tinham poliartrite assimétrica das pequenas articulac¸ões das mãos. Comprometimento da func¸ãodonervofoiobservadoem22%dospacientescomhanseníase,reac¸ãotipoIhansênicaem 18%eneuropatiasilenciosaem16%.Nenhumdospacientesecontrolesapresentousíndromesde dormusculoesqueléticaeasfrequênciasdosanticorposecrioglobulinasforamsemelhantesnos doisgrupos(p>0,05).Comprometimentosdafunc¸ãonervosa,reac¸ãohansênicatipoIe neuropa-tiasilenciosaforamobservadosempacientescomvssemmanifestac¸õesmusculoesqueléticas (p=0,0036,p=0,0001ep=0,309,respectivamente),bemcomosubtiposdehanseníase multi-bacilar(86%vs42%,p=0,045).Aescalavisualanalógica(EVA)domédico,dospacientes,edador eoQuestionáriodeAvaliac¸ãodeSaúdeInfantilforammaioresempacientescommanifestac¸ões musculoesqueléticas(p=0,0001,p=0,002,p=0002ep=0,001,respectivamente).
Conclusão: Estefoioprimeiro estudoaidentificar manifestac¸ões musculoesqueléticas asso-ciadascomdisfunc¸ãodenervosperiféricosempacientespediátricos.Ahanseníasedeveser incluídanodiagnósticodiferencialdeartriteassimétrica,principalmenteemregiões endêmi-cas.
©2014SociedadeBrasileiradePediatria.PublicadoporElsevierEditoraLtda.Todososdireitos reservados.
Introduction
Leprosyisachronicinfectiousdiseasecausedby
Mycobac-teriumleprae.Itisconsideredamajorpublichealthissuein
developingcountriesandhasbeenrarelydescribedin
pedi-atricpopulation,whichcomprises6% to14% ofallleprosy
cases,1,2withanaverageof7%inBrazil.3
The important clinical signs of leprosy are
hypopig-mented or reddish localized skin lesions with loss of
sensation and peripheral nerves involvement.4,5
Muscu-loskeletal manifestations were described in adult leprosy
patients, especially acute and chronic arthritis6---12 and
arthralgia,8 andtheseinvolvements wererarely described
inthepediatricleprosypopulation.13,14
Autoantibodies were also studied in adult leprosy
patients, especially antinuclear antibody (ANA)9 and
antiphospholipid.15 Moreover, there is no study that has
simultaneously assessed musculoskeletal involvement and
autoantibodiesinpediatricleprosypatients.
Therefore, this was a cross-sectional study that
investigatedthemusculoskeletalinvolvement and
autoan-tibodiesinpediatricleprosypatientsandhealthycontrols.
In addition, the possible associations of
musculoskele-tal manifestations in leprosy children and adolescents
with demographic data, leprosy manifestations, health
assessment scores, autoantibodies, and treatment were
evaluated.
Patients
and
methods
From January of 2010 to October of 2012, 56 leprosy
patients were followed upat the Dermatology Service of
the Hospital Universitário Julio Muller, from the
Universi-dadeFederal doMato Grosso,Cuiabá,Brazil.Fiftyleprosy
patientsagreedtoparticipateinthisstudy.Allpatientswere
diagnosedinaccordancewiththeNationalLeprosyProgram
guidelines5 and theRidley-Jopling classificationcriteria,16
asborderline-borderline(BB),borderline-lepromatous(BL),
lepromatous-lepromatous(LL),borderline-tuberculoid(BT),
tuberculoid-tuberculoid(TT),orindeterminateleprosy(IL).
The control group included 47 healthy children and
ado-lescent oftheEscolaEstadualde1◦ e2◦ grausBelaVista,
Cuiabá,MatoGrosso,Brazil.Theethicalcommitteesofthe
ClínicasdaUniversidadedeSãoPaulo approvedthisstudy,
andaninformedconsentwasobtainedfromallparticipants
andlegalguardians.
Demographic
data
and
socio-economic
classes
Demographicdataincludedcurrentageandgender.
Brazil-iansocioeconomicclasseswereclassifiedinaccordancewith
theAssociac¸ãoBrasileiradosInstitutosdePesquisade
Mer-cadoscriteria.17
Musculoskeletal
manifestations
Musculoskeletal manifestationswere defined according to
arthralgia(diffusejointpainortendernesswithoutevidence
ofinflammation), arthritis(swellingwithinajoint,or
lim-itation inthe rangeof jointmovement with jointpainor
tenderness),18andmyalgia(musclepainortendernessinone
ormorelimbswithoutevidenceofinflammation).Arthritis
wereclassifiedaccordingtothenumberofjoints
(oligoar-ticularlowerthanfourarthritidesandpolyarticular[equal
toorgreaterthanfivearthritides])andtheduration(acute
[lowerthansixweeks]andchronic[equaltoorgreaterthan
sixweeks]).18
Musculoskeletalpainsyndromes
The following musculoskeletal pain syndromes were
diagnosed during musculoskeletal examination: juvenile
fibromyalgia,19 myofascial syndrome, and tendinitis.20---22
Juvenile fibromyalgia was diagnosed in accordance with
Yunus and Masi criteria.19 Myofascial syndrome was
diag-nosedaccordingtoactivetriggerpoints,whichisdefinedas
painfulpointsintautbandsof musclefibers. Ifpressured,
thesepointsinducereportedpainthatisreproducibleand
thataffectsspecificplacesforeachmuscle.20---22
Otherfindingsinmusculoskeletalphysical
examination
Joint hypermobility (JH) was diagnosed according to the
criteriaproposed by Beighton. Benign jointhypermobility
syndromewasdefinedasJHcombinedwithmusculoskeletal
painandfiveofninecriteria.23
Clinicalassessmentofleprosy
Clinicalassessmentofleprosywasperformedinaccordance
withtheBrazilianLeprosyProgramguidelines.5Nerve
func-tion impairment is a clinically detectable loss of motor,
sensory, or autonomic peripheral nerve function. Type 1
(reversal)leprosyreactionisdefinedasnerveinflammation
withlossofsensoryandmotorfunctionsand/orrednessand
swellinginpre-existingskinlesionandinnewlesions.Silent
neuropathyisdefinedastheimpairmentofnervefunction
without any nerve pain or tenderness. Type 2 (erythema
nodosum leprosum) leprosy reaction is defined as a
sud-denappearanceofsuperficialordeepcropsonnewtender
subcutaneousnodules.5
Healthassessmentscoresandtreatmentinleprosy
patients
All leprosy patients were evaluated regarding physician’s
global assessment, patient’s global assessment, and pain
usingthe10cmVisualAnalogScale(VAS)24andtheChildhood
HealthAssessmentQuestionnaire(CHAQ).25
Dataconcerningleprosytreatmentincluded:prednisone
therapy, mutibacillary therapy (rifampicin, dapsone and
clofazimine),and paucibacillary therapy (rifampicine and
dapsone).5
Autoantibodiesandcryoglobulins
Thelaboratoryexamswereperformedbyatechnicianwho
wasblindedtothe results ofleprosy and musculoskeletal
manifestations.The following serum autoantibodies were
measuredatstudyadmission:ANAbyindirect
immunofluo-rescence on human cell epithelioma (HEp-2) cells (GMK
- United States) and staining reactivity at ≥ 1:80 serum
dilutiondefinedaspositive;anti-double-strandedDNA
(anti-ds DNA) by in-house indirect immunofluorescence using
Crithidialuciliaeassubstrate(GMK --- UnitedStates) with
a cut-off value of 1:10; anti-Ro and anti-La by
fluorome-try(Phadia-Sweden)withacut-off<10.1;anticardiolipin
(aCL)isotypesIgGandIgMbyenzyme-linkedimmunosorbent
assay(ELISA;Phadia-Sweden),withacut-offvalue of20
GPLand/orMPL.Lupusanticoagulant(LAC)wasassessedby
thediluteRussell’svipervenomtimewithacut-offvalue<
1.15and confirmatory testing witha cut-off value < 1.21
(Siemens - Germany). Cryoglobulin was performed by
in-housegelimmunoelectrophoresis.HLAB27andrheumatoid
factor(RF)detectionswereperformedbyin-housereal-time
polymerasechain reactionassay(ArupLaboratories-USA)
and by immunoturbidimetric assays (Wiener - Argentina;
cut-off<20UI/mL)inpatientsandcontrolswitharthralgia
and/orarthritis.
Statisticalanalysis
Results were presented as mean ± standard deviation or
median(range)forcontinuousvariables,andasnumber(%)
forcategoricalvariables.DatawerecomparedbyStudent’s
t-testorMann-Whitney’stestforcontinuousvariables.For
categorical variables, the differences were assessed by
Fisher’sexacttest.Inallstatisticaltests,thelevelof
signif-icancewassetat5%(p<0.05).
Results
Leprosypatientsandhealthycontrols
Musculoskeletalandleprosymanifestations,and musculoskeletalpainsyndromes
At least one musculoskeletal manifestation (arthralgia,
arthritis,and/or myalgia) was observed in 14% of leprosy
patients,andnone wasobserved inhealthy controls.Five
leprosypatientshadasymmetricpolyarthritisofsmalljoints
ofthehands(metacarpophalangealandproximal
interpha-langealjoints),withmediandurationof12months(ranging
from15daysto36months).Fourpatientswithborderline
Table1 Demographicdata,clinicalmusculoskeletalmanifestations,andmusculoskeletalpainsyndromesinleprosypatients andhealthycontrols.
Variables Leprosypatients(n=50) Controls(n=47) p-value
Demographicdata
Currentage,median(range) 12(3-18) 14(3-18) 0.385
Femalegender,n(%) 25(50) 25(53.1) 0.840
Braziliansocio-economicclasses
Middle/lowermiddleclass,n(%) 46(92) 44(93) 1.000
Clinicalmusculoskeletalmanifestations
Musculoskeletal,n(%) 7(14) 0 0.0012a
Arthralgia,n(%) 1(2) 0 1.000
Myalgia,n(%) 3(6) 0 0.243
Musculoskeletalpainsyndromes
Juvenilefibromyalgia,n(%) 0 0 1.000
Benignjointhypermobilitysyndrome,n(%) 0 0 1.000
Myofascialsyndrome,n(%) 0 0 1.000
Handstendinitis,n(%) 0 0 1.000
aSignificantp-values.
Themostfrequentleprosymanifestationswere
hypopig-mented or reddish localized skin lesions with loss of
sensation,particularlyoftouchandtemperature,observed
in94% of all leprosy patients. Nerve functionimpairment
wasobservedin22%oftheleprosypatients;type1leprosy
reaction, in 18%; and silent neuropathy, in 16%. No
lep-rosypatienthadcutaneousvasculitisandtype2(erythema
nodosumleprosum)leprosyreaction.
None of the patients and controls had juvenile
fybro-mialgia,benign joint hypermobility syndrome, myofascial
syndrome,andtendinitisinthehands(Table1).
Autoantibodiesandcryoglobulins
Thefrequenciesofallantibodies(ANA,anti-dsDNA,anti-Ro,
anti-La,aCL-IgM,aCl-IgG,andLAC)andcyoglobulinswere
similarinleprosy patientsandcontrols(Table2).HLAB27
test were negative in all patients with arthralgia and/or
arthritis.RF waspositive in twooutof five patients with
arthralgiaand/orarthritis.
Leprosypatientswithandwithoutmusculoskeletal manifestations
The frequencies of nerve function impairment, type 1
leprosy reaction, andsilent neuropathy weresignificantly
observedinleprosypatientswithmusculoskeletal
manifes-tationsversusthosewithout(71%vs.14%,p=0.0036;71%vs.
0%,p=0.0001;29%vs.14%,p=0.309;respectively),aswell
asmultibacillarysubtypesinleprosy patientswith
muscu-loskeletalmanifestations(86%vs.42%,p=0.045)(Table3).
Themedianofphysicians’VAS,patients’VAS,painVAS,
andCHAQweresignificantlyhigherinleprosypatientswith
musculoskeletalmanifestationsversusthosewithoutthese
alterations(p=0.0001,p=0.002,p =002,andp=0.001,
respectively). Leprosypatients withmusculoskeletal
man-ifestations were significantlytreated withprednisone and
multibacillary therapies compared with patients without
thesemanifestations(71%vs.0%,p=0.0001;86%vs.42%,p
=0.045)(Table3).
Thefrequenciesofallantibodies(ANA,anti-dsDNA,
anti-Ro, anti-La, aCL-IgM,aCl-IgG, andLAC) and cryoglobulins
were similarin leprosy patients withand without
muscu-loskeletalmanifestations(Table4).
Discussion
To the bestof the authors’ knowledge, this was the first
studyinapediatricleprosypopulationthatclearlyobserved
Table2 Autoantibodiesandcryoglobulinsinleprosypatientsandhealthycontrols.
Variables Leprosypatients(n=50) Controls(n=47) p-value
Autoantibodies
ANA,n(%) 1(2) 0 1.000
Anti-dsDNA,n(%) 0 0 1.000
Anti-Ro,n(%) 0 0 1.000
Anti-La,n(%) 0 0 1.000
aCL-IgM,n(%) 8(16) 6(13) 0.775
aCL-IgG,n(%) 1(2) 0 1.000
LAC,n(%) 1(2) 1(2) 1.000
Cryoglobulins,n(%) 0 0 1.000
Table3 Demographicdata,leprosyclinicalmanifestations,healthassessmentscores,andtreatmentinleprosypatientswith andwithoutmusculoskeletalmanifestations.
Variables Withmusculoskeletal
manifestations(n=7)
Withoutmusculoskeletal manifestations(n=43)
p-value
Demographicdata
Diseaseonset,median(range) 12(3-16) 10(2-18) 0.286
Currentage,median(range) 13(6-18) 12(3-18) 0.280
Femalegender,n(%) 4(57) 21(49) 1.000
Braziliansocio-economicclasses
Middle/lowermiddleclass,n(%) 7(100) 35(81) 0.579
Leprosy
Nervefunctionimpairment,n(%) 5(71) 6(14) 0.0036a
TypeI(reversal)leprareaction,n(%) 5(71) 0 0.0001a
Silentneuropathy,n(%) 2(29) 6(14) 0.309
Erythemanodosumleprosum,n(%) 0 0 1.000
Cutaneousvasculitis,n(%) 0 0 1.000
Multibacillary(BB,BL,orBT),n(%) 6(86) 18(42) 0.045a
Paucibacillary(TTorIL),n(%) 1(14) 25(58) 0.045a
Healthassessmentscores
PhysicianVAS(0-10),median(range) 8(0-10) 0(0-10) 0.0001a
PatientVAS(0-10),median(range) 0(0-10) 0(0-6) 0.002a
PainVAS(0-10),median(range) 0(0-9) 0(0-8) 0.002a
CHAQ(0-3),median(range) 0(0-1) 0(0) 0.001a
Treatment
Prednisone,n(%) 5(71) 0 0.0001a
Multibacillarytherapy,n(%) 6(86) 18(42) 0.045a
Paucibacillarytherapy,n(%) 1(14) 25(58) 0.045a
BB,borderline-borderline;BL,borderline-lepromatous;BT,borderline-tuberculoid;TT,tuberculoid-tuberculoid;IL,indeterminate lep-rosy;VAS,visualanalogscale;CHAQ,ChildhoodHealthAssessmentQuestionnaire.
a Significantp-values.
musculoskeletalmanifestations,especiallyasymmetric
pol-yarthritis,associatedwithseverediseaseandnervefunction
impairment,withoutautoantibodiesproduction.
Thegreatadvantageofthepresentstudydesignwasthe
systematicevaluationofleprosyandmusculoskeletal
mani-festations,painsyndromes,andapanelofautoantibodies,
including standardized definitions18---23 and excluding
peri-articularpain,20---22 in a leprosypopulation of onestate in
MidwesternBrazil.Additionally,ahealthycontrolgroupwith
thesameage,gender,andsocio-economicclass,usingthe
sameprotocol,wasincluded.
Importantly, musculoskeletal involvement is the third
most frequent manifestation in adult leprosy patients.10
Arthritiswasdescribedin4%to79%8,10ofthesepatients,and
maybedividedintofoursubtypes:Charcots joints,septic
arthritis,acutearthritis,andchronicarthritis.10Asymmetric
polyarthritisgenerallyinvolvesmetacarpophalangealjoints
andproximalanddistalinterphalangealjoints,7asobserved
Table4 Autoantibodiesandcryoglobulinsinleprosypatientswithandwithoutmusculoskeletalmanifestations.
Variables Withmusculoskeletal
manifestations(n=7)
Withoutmusculoskeletal manifestations(n=43)
p-value
Autoantibodies
ANA,n(%) 0 1(2) 1.000
Anti-dsDNA,n(%) 0 0 1.000
Anti-Ro,n(%) 0 0 1.000
Anti-La,n(%) 0 0 1.000
aCL-IgM,n(%) 3(43) 5(12) 0.071
aCL-IgG,n(%) 0 1(2) 1.000
LAC,n(%) 1(14) 0 0.140
Cryoglobulins,n(%) 0 0 1.000
inthepresentfivepediatricleprosypatients.Furthermore,
chronic polyarthritis of the hands mimicking rheumatoid
arthritiswasalsoreportedinayoungmiddle-agedmalewith
type1leprosyreaction.10
This jointinvolvement is generallyignored in children
andadolescentswithleprosy,andchronicpolyarthritismay
mimicpediatric autoimmune diseases, especially juvenile
idiopathic arthritis,7,13 acute leukemia,26 and childhood
systemic lupus erythematosus.27 Of note, these
muscu-loskeletal manifestationswere rarely reportedin the two
leprosycasesthatinvolvedperipheralandhandjoints,13and
alsoinonecaseassociatedwitherythemanodusumthatwas
previouslyevidencedbythisgroup.14
Musculoskeletal pain syndromes were not observed in
this population of leprosy patients and controls, as also
described in the present healthy and obese adolescents,
withaprevalencerangingfrom0%to10%.20---22Additionally,
notendinitisofthehandassociatedwithjointinvolvement
wasobserved.
Interestingly, none of the present patients had joint
hypermobility,althoughthisabnormalityhasbeenreported
inupto20% ofpediatricpopulation.20,21 Thisalterationis
morefrequentinschoolchildren,withreducedprevalencein
adolescentsandadults.Infact,thepresentleprosypatients
andhealthycontrols weremainly adolescents,whichmay
havecontributedtotheabsenceofjointhypermobility,as
alsoobservedinanotherstudybytheauthors.22
Autoantibodieswererarelyobservedinthepresent
pedi-atric leprosy patients. IgM anticardiolipin was the most
frequentautoantibodiesobservedinleprosypatients
with-out autoimmune thrombosis (13%), as also observed in
adultleprosy.Thisfactdifferedfromthe presentpatients
with childhood systemic lupus erythematosus, juvenile
dermatomyositis,28 andRASopathies,29 whichpresentedup
to93%,59%,and52%ofavarietyoforgan-specificandnon
organ-specificautoantibodies,respectively.
Leprosyisachronicgranulomatousinfectionthatoccurs
mainlywithcutaneous and neurologicalmanifestations,4,5
asobservedinthepresent patientswithandwithout
mus-culoskeletal involvement. This disease may affect daily
life activities and health-related quality of life in adult
patients,30asobservedherein.
Remarkably, type 1 leprosy reactions with nerve
func-tionimpairmentwererelatedtoseveredisease,5andthese
abnormalities were also associated with musculoskeletal
manifestations, indicating a simultaneous involvement of
nerves and joints that needed immunosuppressant and
multibacillary treatment. Moreover, these patients could
presentpermanentjointdamagewithswanneck
deformi-ties, mallet finger, and/or ulnar drift,10 which requires a
rigorousandprolongedfollow-up.
In conclusion, this was the first study to identify a
high frequency of musculoskeletal manifestations
associ-atedwithnerve dysfunctionin pediatricleprosy patients.
Hansen’sdiseaseshouldbeincludedinthedifferential
diag-nosisofasymmetricarthritis,especiallyinendemicregions.
Funding
This study was supported by the Doutorado Inter
Institu-cional(DINTER)ofthePediatricDepartment(UFMT-FMUSP),
by theConselhoNacionaldeDesenvolvimento Científicoe
Tecnológico(CNPq,undergrantNo.302724/2011-7toCAS),
byaFedericoFoundationgranttoCAS,andbytheNúcleo
deApoioàPesquisa‘‘SaúdedaCrianc¸aedoAdolescente’’
oftheUniversidadedeSão(NAP-CriAd-SP).
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgments
The authors would liketothank all thecolleagues of the
UniversityHospitalofCuiabá,Brazil,andDr.UlyssesDória
Filhoforassistanceinstatisticalanalysis.
References
1.LastóriaJC,Abreu MA.SBD-RESPinactivesearchforleprosy cases.AnBrasDermatol.2011;86:613---8.
2.PiresCA,MalcherCA,AbreuJúniorJM,AlbuquerqueTG, Cor-rêaIR,DaxbacherEL.Leprosyinchildrenunder15years:the importanceofearlydiagnosis.RevPaulPediatr.2012;30:292---5.
3.WorldHealthOrganization(WHO).WklyEpidemiolRec.:Global leprosysituation,2012;2012.p.317---28.
4.Australia. Northern Territory Government. Department of Health and Families. Guidelines for the control of Lep-rosy in the Northern Territory. Australia; 2010. [cited 31 Aug 2013]. Available from: http://www.health.nt.gov.au/ library/scripts/objectifyMedia.aspx?file=pdf/10/90.pdf 5.Brasil.Ministério da SaúdeSecretariade Políticasde Saúde.
Departamento de Atenc¸ão Básica. Guia para o controle da hanseníase.Brasília:.MinistériodaSaúde.2002.
6.Cossermelli-MessinaW,FestaNetoC,CossermelliW.Articular inflammatorymanifestationsinpatientswithdifferentformsof leprosy.JRheumatol.1998;25:111---9.
7.MiladiMI,Feki I,BahloulZ,JlidiR, MhiriC.Chronic inflam-matoryjointdiseaserevealing borderlineleprosy. JointBone Spine.2006;73:314---7.
8.PereiraHL,RibeiroSL,PenniniSN,SatoEI.Leprosy-relatedjoint involvement.ClinRheumatol.2009;28:79---84.
9.RibeiroSL,PereiraHL,MangueiraCL,FerreiraCE,RossetoE, Scheinberg M. The development ofarthritis and antinuclear antibodiescorrelatewithserum25-hydroxyvitaminDlevelsin patientswithleprosy.AnnRheumDis.2012;71:2062---3.
10.ChauhanS,WakhluA,AgarwalV.Arthritisinleprosy. Rheuma-tology(Oxford).2010;49:2237---42.
11.Kaur MR, Grindulis K, Maheshwari M, Ellis CJ, Bhat J, Tan CY. Delayed diagnosis of leprosy due to presentation with a rheumatoid-like polyarthropathy. Clin Exp Dermatol. 2007;32:784---5.
12.Al-RaqumHA,UppalSS,ElAbdalghaniRA,LasheenI.Firstreport ofleprosypresentingasacutepolyarthritisinthesettingoftype Idowngradingleprareaction.ClinRheumatol.2006;25:101---5.
13.TerreriMT,LuttiD,LenC,GoldenbergJ,HilárioMO.Leprosy: anunusualcauseofarthritisinchildren.Areportoftwocases. JTropPediatr.1997;43:186---7.
14.MoraesAJ,SoaresPM,ZapataAL,LotitoAP,SallumAM,Silva CA. Panniculitis in childhood and adolescence. Pediatr Int. 2006;48:48---53.
16.RidleyDS, JoplingWH. Classification ofleprosyaccordingto immunity.Afive-groupsystem.IntJLeprOtherMycobactDis. 1966;34:255---73.
17.Almeida PM,Wickerrhauser H. Critério de classe econômica da Associac¸ão Brasileira de Anunciantes (ABA) e Associac¸ão Brasileira dos Institutos de Pesquisa de Mercado (ABIPEME). 1991.
18.PettyRE,SouthwoodTR,MannersP,Baum J,GlassDN, Gold-enberg J, et al. International League of Associations for Rheumatologyclassificationofjuvenileidiopathicarthritis: sec-ondrevisionEdmonton,2001.JRheumatol.2004;31:390---2.
19.Yunus MB,Masi AT. Juvenile primary fibromyalgia syndrome. Aclinicalstudyofthirty-three patientsand matchednormal controls.ArthritisRheum.1985;28:138---45.
20.ZapataAL,Moraes AJ,LeoneC,Doria-FilhoU,SilvaCA.Pain andmusculoskeletalpainsyndromesinadolescents.JAdolesc Health.2006;38:769---71.
21.ZapataAL,Moraes AJ,LeoneC,Doria-FilhoU,SilvaCA.Pain andmusculoskeletalpainsyndromesrelatedtocomputerand videogameuseinadolescents.EurJPediatr.2006;165:408---14.
22.JanniniSN,Dória-FilhoU,DamianiD,SilvaCA.Musculoskeletal paininobeseadolescents.JPediatr(RioJ).2011;87:329---35.
23.BeightonP,SolomonL, Soskolne CL.Articularmobilityin an Africanpopulation.AnnRheumDis.1973;32:413---8.
24.GianniniEH,RupertoN,RavelliA,LovellDJ,FelsonDT,Martini A.Preliminarydefinitionofimprovementinjuvenilearthritis. ArthritisRheum.1997;40:1202---9.
25.MachadoCS,RupertoN,SilvaCH,FerrianiVP,RoscoeI,Campos LM,etal.TheBrazilianversionoftheChildhoodHealth Assess-mentQuestionnaire(CHAQ)andtheChildHealthQuestionnaire (CHQ).ClinExpRheumatol.2001;19:S25---9.
26.Tamashiro MS, Aikawa NE, Campos LM, Cristofani LM, Odone-Filho V, Silva CA. Discrimination of acute lym-phoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset. Clinics (Sao Paulo). 2011;66: 1665---9.
27.Cavalcante EG,Aikawa NE, Lozano RG, LotitoAP,Jesus AA, Silva CA. Chronic polyarthritis as the first manifestation of juvenilesystemiclupuserythematosuspatients.Lupus.2011;20: 960---4.
28.AikawaNE,JesusAA,Liphaus BL,SilvaCA,Carneiro-Sampaio M,VianaVS,etal.Organ-specificautoantibodiesand autoim-mune diseases in juvenile systemic lupus erythematosus and juvenile dermatomyositis patients. ClinExp Rheumatol. 2012;30:126---31.
29.Quaio CR, Carvalho JF, da Silva CA, Bueno C, Brasil AS, Pereira AC,etal. Autoimmunediseaseand multiple autoan-tibodiesin42patientswithRASopathies.AmJMedGenetA. 2012;158A:1077---82.
