r e v b r a s r e u m a t o l . 2014;54(6):486–489
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
www . r e u m a t o l o g i a . c o m . b r
Case
report
Optic
neuritis
in
juvenile
idiopathic
arthritis
patient
Daniela
M.R.
Lourenc¸o
a,
Izabel
M.
Buscatti
a,
Benito
Lourenc¸o
b,
Fernanda
C.
Monti
c,
José
A.
Paz
c,
Clovis
A.
Silva
a,d,∗aUnidadedeReumatologiaPediátrica,DepartamentodePediatria,FaculdadedeMedicinadaUniversidadeSãoPaulo,SãoPaulo,SP,
Brazil
bUnidadedoAdolescente,DepartamentodePediatria,FaculdadedeMedicinadaUniversidadeSãoPaulo,SãoPaulo,SP,Brazil
cUnidadedeNeurologiaPediátrica,DepartamentodeNeurologia,FaculdadedeMedicinadaUniversidadeSãoPaulo,SãoPaulo,SP,Brazil
dDivisãodeReumatologia,FaculdadedeMedicinadaUniversidadeSãoPaulo,SãoPaulo,SP,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received17October2013 Accepted28January2014 Availableonline29October2014
Keywords: Opticneuritis
Juvenileidiopathicarthritis Anti-aquaporin4antibody
a
b
s
t
r
a
c
t
Opticneuritis(ON)wasrarelyreportedinjuvenileidiopathicarthritis(JIA)patients, particu-larlyinthoseunderanti-tumornecrosisfactoralphablockage.However,toourknowledge, theprevalenceofONinJIApopulationhasnotbeenstudied.Therefore,5793patientswere followedupatourUniversityHospitaland630(11%)hadJIA.Onepatient(0.15%)hadON andwasreportedherein.A6-year-oldmalewasdiagnosedwithextendedoligoarticularJIA, andreceivednaproxenandmethotrexatesubsequentlyreplacedbyleflunomide.At11years old,hewasdiagnosedwithasepticmeningitis,followedbyapartialmotorseizurewith sec-ondarygeneralization.Brainmagneticresonanceimaging(MRI)andelectroencephalogram showeddiffusedisorganizationofthebrainelectricactivityandleflunomidewassuspended. Sevendayslater,thepatientpresentedacuteocularpain,lossofacuityforcolor,blurred vision,photophobia,rednessandshortprogressivevisuallossintherighteye.Afundoscopic examdetectedunilateralpapilledemawithoutretinalexudates.OrbitalMRIsuggestedright ON.Theanti-aquaporin4(anti-AQP4)antibodywasnegative.Pulsetherapywith methyl-prednisolonewasadministeredforfivedays,andsubsequentlywithprednisone,hehad clinicalandlaboratoryimprovement.Inconclusion,alowprevalenceofONwasobserved inourJIApopulation.Theabsenceofanti-AQP4antibodyandthenormalbrainMRIdonot excludethepossibilityofdemyelinatingdiseaseassociatedwithchronicarthritis.Therefore, rigorousfollowupisrequired.
©2014ElsevierEditoraLtda.Allrightsreserved.
DOIoforiginalarticle:http://dx.doi.org/10.1016/j.rbr.2014.01.011. ∗ Correspondingauthor.
E-mail:clovisaasilva@gmail.com(C.A.Silva).
http://dx.doi.org/10.1016/j.rbre.2014.01.003
rev bras reumatol.2014;54(6):486–489
487
Neurite
óptica
em
paciente
com
artrite
idiopática
juvenil
Palavras-chave: Neuriteóptica
Artriteidiopáticajuvenil Anticorpoantiaquaporina4
r
e
s
u
m
o
A neuriteóptica(NO) raramenteérelatadaem pacientescomartrite idiopáticajuvenil (AIJ),especialmentenaquelesqueutilizamtratamentocombloqueadordefatordenecrose tumoral-alfa.Noentanto,atéondesesabe,a prevalênciadeNO empacientescomAIJ aindanãofoiestudada.Acompanharam-se5.793pacientesnoHospitalUniversitáriodesta instituic¸ão.Destes,630(11%)tinhamAIJ,eapenasum(0,15%)apresentavaNO.Opaciente comNO,de6anosdeidadeedosexomasculino,foidiagnosticadocomAIJoligoarticular estendida.Foramintroduzidosnaproxenoemetotrexato,posteriormentesubstituídospor leflunomida.Aos11anosdeidade,elefoidiagnosticadocommeningiteasséptica,seguida deconvulsãomotoraparcialcomevoluc¸ãoparageneralizac¸ãosecundária.Aressonância magnéticadoencéfaloe oeletroencefalogramaevidenciaramdesorganizac¸ãodifusada atividadeelétricadoencéfalo.Alefluomidafoisuspensa.Após7dias,opaciente apresen-toudorocularaguda,baixaacuidadevisualparacores,visãoturva,fotofobia,hiperemiae amauroseprogressivanoolhodireito.Noexamedefundodeolho,foidetectadoedemade papilaunilateralsemexsudatosretinianos.Aressonânciamagnéticadeórbitasugeriu neu-ropatiaópticaàdireita.Oanticorpoantiaquaporina4(anti-AQP4)foinegativo.Opaciente foisubmetidoapulsoterapiacommetilprednisolonaporcincodias,seguidadeprednisona, apresentandomelhoraclínicaelaboratorial.Emsuma,foiobservadabaixaprevalênciade NOempacientescomAIJ.Aausênciadoanticorpoantiaquaporina4earessonância mag-néticanormaldoencéfalonãoexcluemapossibilidadededoenc¸adesmielinizanteassociada aestaartritecrônica.Logo,éimportantequesejafeitoumacompanhamentorigoroso.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Opticneuritis(ON)ischaracterizedbyacutevisuallossand opticnerveinflammation.Themostcommonclinical mani-festationsofthisdiseasearesuddenvisionloss,disturbance ofcolorvisionandperiorbital,andretro-orbitalpainmainly duringeyemovement.1Thisvisualabnormalitymaybe asso-ciatedwithinfections,vaccinations,drugsandautoimmune diseases,particularlymultiplesclerosis(MS)and neuromieli-tisoptic(NMO).2,3
Of note, ON was rarely reported in juvenile idiopathic arthritis (JIA) patients, particularly in those under tumor necrosis factor alpha (TNF-␣) blockage.3–6 However, to our
knowledge,theprevalenceofONinJIApopulationhasnot beenstudied.
Therefore,from January1983toJuly2013,5793patients werefollowedupatthePediatricRheumatologyUnitofthe Children’sInstitute,FaculdadedeMedicinadaUniversidade deSãoPaulo.Outofthose,630(11%)fulfilledtheInternational LeagueofAssociationsforRheumatism(ILAR)classification criteriaforJIA.7Onlyone(0.15%)hadacutevisuallossdueto ONduringthediseasecourseandwasreportedherein.
Case
report
A 6-year-old male was diagnosed with extended oligoar-ticular JIA based on chronic arthritis of left knee with progression to the wrists and ankles. The initial labora-toryexamsrevealedhemoglobin12.9g/dL,hematocrit38.1%, white blood cell count 17,700mm3 (73% neutrophils, 23%
lymphocytes, 0% eosinophils and 4% monocytes), platelet count 401,000mm3, erythrocyte sedimentation rate (ESR)
30mm/1st,C-reactiveprotein(CRP)98.4mg/dL(normalrange 5.0), rheumatoid factor and antinuclear antibody (ANA) were negative. Naproxen (20mg/kg/day) and methotrexate (0.5mg/kg/week)wereintroducedandsubsequentlychanged for leflunomide (20mg/day) due to gastric intolerance. At 11 years old, no arthritis or limitations were present and he had been treated withleflunomide (20mg/day). Atthat moment,hepresentedheadacheand vomitswithoutfever, followedafterfourdaysbyapartialmotorseizureaffecting therightarmwithsecondarygeneralization.Thelaboratory findings showedcerebral spinalfluid(CSF):slightly muddy, 127cells/mm2 (32%lymphocytes, 19%monocytes,1%
plas-mocytes,43%neutrophils,2%eosinophils,1%basophilsand 2%macrophages),redblood cells0/mm2,protein61mg/dL,
488
rev bras reumatol.2014;54(6):486–489showedthickeningandhyperintensityonT2associatedwith enhancementoftheintraorbital,intracanalicularand cister-nalsegmentsoftherightopticnerve,stronglysuggestedright ON.ImmunologicaltestsshowedantinuclearantibodiesANA 1:160(finespeckled pattern), negativeanti-double-stranded DNA,anti-Sm,anti-RNP,IgGandIgManticardiolipin,anti-Ro and anti-La negatives. The serum anti-aquaporin 4 (anti-AQP4)antibodybyindirectimmunofluorescencewasnegative. Pulsetherapywithmethylprednisolone(1.0g/day)was admin-isteredforfiveconsecutivedaysandsubsequentlyprednisone (60mg/day).Aftera30-daytreatmentwithprednisone, clin-ical, laboratory and fundoscopic, the exams were normal. Currently,heisoncorticosteroidtapering.
Discussion
ONwithreversible visualloss inJIApopulation was infre-quentlydescribedinourpediatricrheumatologyservicefor 30consecutiveyears.
Ofnote,thisophthalmicdiseaseoccursmostcommonly in young patients8 and without gender predominance.9–11 The diagnosis is based on clinical features secondary to opticnervedamage,9–11resultinginsuddenvisionloss,color vision impairment and periorbital pain in eye movement. Papilledemamaybeobservedinthefundoscopicexaminone thirdofpatients,1asaresultofpapillitis,perineuritisor neu-roretinitis.Inourpatient,thepresenceofswollendiskwithout macular starexudatessuggests apapillitis associatedwith aretrobulbarneuritis.Interestingly,retrobulbarneuritisand papillitis are mainly related withMS, whereas perineuritis andneuroretinitisaremoreoftenassociatedwithinfectious orinflammatoryetiologies.
The orbital MRI is not required to confirm the diagno-sis.However,itisnecessarytoexcludeotherdisorders,that canmimicON,suchascompressiveorinflammatoryorbital lesions.12,13Importantly,nearly50%ofthepatientswith iso-latedONdevelopMSoveraperiodof15years.Consequently, brainMRIshouldbeperformedtofindearly symptomsfor demyelinatingbrainlesionsandcloselymonitorthedisease evolution.12,14
In addition, our patient had negative anti-AQP4 anti-body.Thisautoimmunemarkertargetingthecentralnervous system has high specificity for the spectrum of NMO diagnosis.15 However, 53% of sensitivity was detected by indirect immunofluorescence method.16 Ten percent of seronegativepatientsthatpresentrecurrentONwilldevelop NMOwithinfiveyears.14Therefore,therigorousfollow-upof ourpatientisoftheutmostimportance.
InJIApopulation, ONwasrarelyreported, usually asso-ciatedwith TNF-␣ inhibitors,4 witha medianof8 months
treatment.3,6 Furthermore,thisocularabnormalitywasalso describedinadultpatientswithinflammatoryarthritis.17The etiologyforONinourpatientisunclearandpossiblyrelated toautoimmunity.Toourknowledge,noONcasewasreported underleflunomidetherapy.
IntravenousmethylprednisoloneisanoptionofON treat-ment, as indicated herein.19 A recent review, including randomized trials in adult populations, evidenced similar recoveryofnormalvisualacuityinpatientstreatedwith intra-venousororalcorticosteroids.18
Inconclusion,alowprevalenceofONwasobservedinour JIApopulation. Theabsence ofanti-AQP4 antibodyand the normalbrainMRIdonotexcludethepossibilityof demyelinat-ingdiseaseassociatedwiththischronicarthritis.Therefore, rigorousfollowupisrequired.
Funding
ThisstudywassupportedbyFundac¸ãodeAmparoàPesquisa doEstadodeSãoPaulo(FAPESP,Brazil–grants 2008/58238-4 to CAS and 2011/12471-2to CAS), by Conselho Nacional doDesenvolvimentoCientíficoeTecnológico(CNPQ,Brazil– grant302724/2011-7toCAS),byFedericoFoundation, Switzer-land toCASand byNúcleo deApoio àPesquisa“Saúde da Crianc¸aedoAdolescente”daUSP(NAP-CriAd),Brazil.
Conflict
of
interest
Theauthorsdeclarenoconflictofinterest.
r
e
f
e
r
e
n
c
e
s
1.SteffenH.Opticnerveneuritis.Ophthalmologe. 2013;110:783–9.
2.CardosoLMCD,ZachariasLC,MonteiroMLR.Neuropatia ópticaautoimune:relatodecaso.ArqBrasOftalmol. 2006;69:593–5.
3.SimsekI,ErdemH,PayS,SobaciG,DincA.Opticneuritis occurringwithanti-tumornecrosisfator␣therapy.Ann
RheumDis.2007;66:1255–8.
4.TristanoAG.Neurologicaladverseeventsassociatedwith anti-tumornecrosisfactor␣treatment.JNeurol.
2010;257:1421–31.
5.TranTH,MileaD,CassouxN,BodaghiB,BourgeoisP,LeHoang P.Opticneuritisassociatedwithinfliximab.JFrOphtalmol. 2005;28:201–4.
6.TauberT,TuretzJ,BarashJ,AvniI,MoradY.Opticneuritis associatedwithetanercepttherapyforjuvenilearthritis.J AAPOS.2006;10:26–9.
7.PettyRE,SouthwoodTR,MannersP,BaumJ,GlassDN, GoldenbergJ,etal.Revisionoftheproposedclassification criteriaforjuvenileidiopathicarthritis:Durban,1997.J Rheumatol.1998;25:1991–4.
8.Pedro-EgbeCN,FiebaiB,EjimaduCS.Visualoutcome followingopticneuritis:a5-yearreview.NigerJClinPract. 2012;15:311–4.
9.MoralesDS,SiatkowskiRM,HowardCW,WarmanR.Optic neuritisinchildren.JPediatrOphthalmolStrabismus. 2000;37:254–9.
10.ShatriahI,AdlinaAR,AlshaarawiS,Wan-HitamWH.Clinical profileofMalaychildrenwithopticneuritis.PediatrNeurol. 2012;46:293–7.
11.StübgenJP.Aliteraturereviewonopticneuritisfollowing vaccinationagainstvirusinfections.AutoimmunRev. 2013;12:990–7.
12.McKinneyAM,LohmanBD,SarikayaB,BensonM,BensonMT, LeeMS.Accuracyofroutinefat-suppressedFLAIRand diffusion-weightedimagesindetectingclinicallyevident acuteopticneuritis.ActaRadiol.2013;54:455–61.
rev bras reumatol.2014;54(6):486–489
489
14.deSezeJ.Atypicalformsofopticneuritis.RevNeurol. 2012;168:697–701.
15.McKeonA,LennonVA,LotzeT,TenenbaumS,NessJM,Rensel M,etal.CNSaquaporin-4autoimmunityinchildren. Neurology.2008;71:93–100.
16.TillemaJM,McKeonA.ThespectrumofNeuromyelitisOptica (NMO)inchildhood.JChildNeurol.2012;27:
1437–47.
17.MohanN,EdwardsET,CuppsTR,OliverioPJ,SandbergG, CraytonH,etal.Demyelinationoccurringduringanti-tumor necrosisfactoralphatherapyforinflammatoryarthritides. ArthritisRheum.2001;44:2862–9.
18.GalRL,VedulaSS,BeckR.Corticosteroidsfortreatingoptic neuritis.CochraneDatabaseSystRev.2012;18:4.
