r e v b r a s r e u m a t o l . 2014;54(5):400–403
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
www . r e u m a t o l o g i a . c o m . b r
Case
report
Kikuchi-Fujimoto
disease
prior
to
childhood-systemic
lupus
erythematosus
diagnosis
Sofia
S.
Martins
a,
Izabel
M.
Buscatti
a,
Pricilla
S.
Freire
a,
Erica
G.
Cavalcante
a,
Adriana
M.
Sallum
a,
Lucia
M.A.
Campos
a,
Clovis
A.
Silva
a,b,∗aPediatricRheumatologyUnit,FaculdadedeMedicina,UniversidadedeSãoPaulo,SãoPaulo,SP,Brazil
bDivisionofRheumatology,FaculdadedeMedicina,UniversidadedeSãoPaulo,SãoPaulo,SP,Brazil
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t
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c
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e
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n
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o
Articlehistory:
Received27September2012 Accepted21March2013 Availableonline20August2014
Keywords:
KikuchiFujimotodisease Childhoodsystemiclupus erythematosus
Lymphadenitis Overlap
Herpessimplexvirustype1and type2
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b
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Kikuchi-Fujimotodisease(KFD)isaself-limitinghistiocyticnecrotizinglymphadenitisof unknownorigin.Ofnote,KFDwasinfrequentlyreportedinadultsystemiclupus erythe-matosus(SLE),withrareoccurrenceinchildhood-SLE(C-SLE)patients.Toourknowledge, theprevalenceofKFDinthepaediatriclupuspopulationwasnotstudied.Therefore,in aperiodof29consecutiveyears,5,682patientswerefollowedatourinstitutionand289 (5%)mettheAmericanCollegeofRheumatologyclassificationcriteria forSLE, onehad isolatedKFD(0.03)andonlyonehadKFDassociatedtoC-SLEdiagnoses,whichcasewas reportedherein.A12year-oldfemalepatienthadhighfever,fatigueandcervicaland axil-larylymphadenopathy.Theantinuclearantibodies(ANA)werenegative,withpositiveIgM andIgGherpessimplexvirustype1andtype2serologies.Fluorine-18-fluoro-deoxy-glucose positronemissiontomography/computedtomography(PET/CT)imagingdemonstrated dif-fuselymphadenopathy.Theaxillarylymphnodebiopsyshowednecrotizinglymphadenitis withhistiocytes,withoutlymphoproliferativedisease,compatiblewithKFD.After30days, shepresentedspontaneousregressionandnotherapywasrequired.Ninemonthslater,she developedmalarrash,photosensitivity,oralulcers,lymphopeniaandANA1:320 (homoge-neousnuclearpattern).AtthatmomenttheSystemicLupusErythematosusDiseaseActivity Index2000(SLEDAI-2K)scorewas10andshewastreatedwithprednisone(1.0mg/kg/day) andhidroxychloroquineshowingprogressiveimprovementofherssignsandsymptoms. Inconclusion,KFDisabenignandrarediseaseinourpaediatriclupuspopulation.Wealso wouldliketoreinforcetherelevanceofautoimmunediseasesdiagnosisduringthefollow-up ofpatientswithKFD.
©2014ElsevierEditoraLtda.Allrightsreserved.
DOIoforiginalarticle:http://dx.doi.org/10.1016/j.rbr.2013.03.003. ∗ Correspondingauthor.
E-mail:clovis.silva@icr.usp.br(C.A.Silva).
http://dx.doi.org/10.1016/j.rbre.2013.03.003
r e v b r a s r e u m a t o l . 2014;54(5):400–403
401
Doenc¸a
de
Kikuchi-Fujimoto
antes
do
diagnóstico
de
lúpus
eritematoso
sistêmico
juvenil
Palavras-chave:
Doenc¸adeKikuchi-Fujimoto Lúpuseritematososistêmico juvenil
Linfadenite Superposic¸ão
Vírusdoherpessimplestipo1e tipo2
r
e
s
u
m
o
Adoenc¸adeKikuchi-Fujimoto(DKF)éumalinfadenitenecrosantehistiocítica autolimi-tantedeorigemdesconhecida.ÉdignodenotaqueaDKFeraapenaspoucofrequentemente comunicadaempacientescomlúpuseritematososistêmico(LES),comraraocorrênciaem pacientescomLESjuvenil(LESJ).Atéondevainossoconhecimento,aindanãofoiestudada aprevalênciadeDKFnapopulac¸ãopediátricalúpica.Assim,emumperíodode29anos consecutivos,5.682pacientesforamacompanhadosemnossainstituic¸ãoe289(5%) sat-isfaziamoscritériosdeclassificac¸ãodoAmericanCollegeofRheumatologyparaLES;um sofriaDKFisolado(0,03%)eapenasumpadeciadeDKFassociadaadiagnósticosdeLESJ; estecasofoidescritonopresenteartigo.Umajovemcom12anosdeidadeapresentava-se comfebrealta,fadigaelinfadenopatiacervicaleaxilar.Osanticorposantinucleares(ANA) estavamnegativos,comimunologiapositivaparaIgMeIgGantivírusdoherpessimples tipos1 e2.Asimagensobtidasportomografiaporemissão depósitronscom flúor-18-fluoro-desoxi-glicose/tomografiacomputadorizada(PET/TC)demonstraramlinfadenopatia difusa.Abiópsiadoslinfonodosaxilaresdemonstroulinfadenitenecrosantecompresenc¸a dehistiócitos,semdoenc¸alinfoproliferativa,compatívelcomDKF.Transcorridos30dias,a pacienteapresentouregressãoespontânea,nãohavendonecessidadedetratamento.Nove mesesdepois,apacienteexibiaerupc¸ãomalar,fotossensibilidade,úlcerasorais,linfopenia eANA1:320(padrãonuclearhomogêneo).Nessaocasião,aaplicac¸ãodoSystemicLupus Ery-thematosusDiseaseActivityIndex2000(SLEDAI-2K)(ÍndicedeAtividadedeDoenc¸a/LES2000) teveumescoreiguala10,eajovemfoitratadacomprednisona(1,0mg/kg/dia)e hidroxi-cloroquina,demonstrandomelhoraprogressivadossinaisesintomas.Emconclusão,DKF édoenc¸abenignaeraraemnossapopulac¸ãolúpicapediátrica.Tambémqueremos enfa-tizararelevânciadodiagnósticodedoenc¸asautoimunesduranteoacompanhamentode pacientescomDKF.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
KikuchiorKikuchi-Fujimotodisease (KFD)isaself-limiting histiocyticnecrotizinglymphadenitisofunknownorigins.1–6 The most common clinical manifestations of this dis-ease are localized or diffused painful lymphadenopathy withconcomitantfeverand fatigue.Thissystemicdisorder may be associatedwith infectious diseases, neoplasia and autoimmunerheumaticdiseases,especiallysystemic lupus erythematosus(SLE).4
Ofnote,KFDwasinfrequentlyreportedinadultSLE,1–6with rarecasesinchildhood-SLE(C-SLE).7–9However,toour knowl-edge,theprevalenceofKFDinpediatriclupuspopulationhas notbeenstudied.
Therefore,fromJanuary1983toMay2012,5,682patients werefollowed atour PediatricRheumatologyUnit,and289 (5%)ofthemmettheAmericanCollegeofRheumatology(ACR) classificationcriteriaforSLE.10Ofthetotalpopulation,two hadKFD(0.03%).FromtheseKFDpatients,onlyonehadKFD associatedtoC-SLE(0.02oftotalpopulation,0.3ofC-SLE pop-ulation),andthiscasewasreportedherein.
Case
report
A12-year-oldfemalepatienthadhighgraduatedfever(over 39◦C) daily,fatigue,and painful cervical and axillarlymph
nodes enlargement(diameter of1.0-2.0cm, fibroelastic).At that moment, the laboratory findings showed hemoglobin 11.2g/dL,whitebloodcellcount(WBC)4,700/mm3(80%
neu-trophils,15%lymphocytesand5%monocytes)andplatelets 198,000/mm3.C-reactiveprotein(CRP)was224.8mg/dL
(nor-malrange<5.0),anderythrocytesedimentationrate(ESR)was 57mm/1sthour.Theantinuclearantibodies(ANA)were
402
r e v b r a s r e u m a t o l . 2014;54(5):400–403lymphnodes(1.0cmofdiameter)withoutswellingand pain-less.Thelaboratory findings showed hemoglobin 13.1g/dL, WBC 7,100/mm3 (77% neutrophils, 16% lymphocytes, 1%
eosinophilsand 6%monocytes)andplatelets 264,000/mm3.
CRPwas 5.4mg/dL,ESR 35mm/1st hour, C3154mg/dL and
C424mg/dL.Immunologicaltestsshowedantinuclear anti-bodies ANA 1:320 (homogeneous nuclear pattern), positive anti-Ro antibodies and negativeanti-double-stranded DNA (anti-dsDNA),anti-Sm,anti-RNP,IgGandIgManticardiolipin andanti-Laantibodies.Urinalysisdemonstrated leukocytes 20,000/mL and erythrocytes 2,000/mL, urea 26mg/dL, cre-atinine 0.81mg/dL and proteinuria 0.057g/24h. Therefore, the diagnosis of C-SLE was confirmed according to ACR classificationcriteria.10AtthismomenttheSystemicLupus Ery-thematosusDiseaseActivity Index2000(SLEDAI-2K) scorewas 10,andshewastreatedwithprednisone(1.0mg/kg/day)and hydroxychloroquine sulphate (6.0mg/kg/day) showing pro-gressiveimprovementofherssignsandsymptoms.
Discussion
KFDwasinfrequentlydescribed inourpediatric rheumato-logy service, and the histiocytic necrotizing lymphadenitis wasrarelydiagnosedinC-SLEpopulation,particularlyprior tolupusdiagnosis.
This disease occurs most commonly in young females,2,4,5,7,11 and the main clinical manifestations of KFD in pediatric and adult populations are cervical lym-phadenopathy, usually painful, associated to fever and constitutionalsymptoms,1,2,4,6,7 asobservedin ourpatient. Interestingly,thecervicallymphadenopathyinKFDis gener-allyunilateral(79%)andgeneralizedlymphadenomegaly,as evidencedinthepresentcase,wasrarelyreported(5%).4
Of note, the diagnosis was confirmed by lymph nodes biopsy showing necrotizing histiocytic lymphadenitis.3–6 This procedure is also required to evaluate the possibility ofcomorbidities, especially infectious, lymphoproliferative, autoimmune and hemaphagocytic diseases.4 Herpes virus type1andtype2infectionsmayhavetriggeredKFDinthe currentcase,howeverwedidnotrepeatthesevirusserologies confirmingtheprimaryinfection.Inaddition,onestudydid notobserveanyassociationofthisinfectionwithKFD.12
ThelaboratoryexamsarealmostunchangedatKFD diag-nosis,exceptelevatedESRandCRPlevels,11asalsoobserved herein.Onerelevantpoint assessedinour patientwasthe PET/CTimagingfindings.Ourpatienthaddiffuseadenopathy thatwasnotobservedinthephysicalexamination.Indeed, thisimaginghasahighsensitivityandspecificityforoccult adenomegaly,13 and may help to identify the reticuloen-dotelialsystem involvement.Moreover,the combination of PETandCTmightbeapromisingnoninvasivediagnostictool, especiallyinchildrenwithfeverofunknownorigin.This radio-logicexaminationallowsforlocalizingtheinflammationsite moreaccurately.14
KFD has been infrequently reported with autoimmune diseases, especially SLE, mixed connective tissue disease, anti-phospholipidsyndrome,thyroiditis,polymyositis, sclero-derma,autoimmunehepatitisandStill’sdisease,4andrarely associatedwithC-SLE.7–9KFDwasreportedin4%7to13%in
SLEpopulation.4Importantly,KFDoccurredmainly simulta-neously to SLEdiagnosis,4 in contrast ofthe present case. Additionally,ourpatienthadnegativeautoantibodiesatKFD diagnostic, thus suggesting separated condition of C-SLE. Conversely,otherauthorssuggestthatKFDandSLEhad over-lap manifestations with the same histologic findings and autoimmune mecanisms.9 Moreover, adenopathy occurred frequentlyinouractiveC-SLEpatients,mainlyatbeginning ofthedisease.15,16
Itisimportanttoemphasizethatmostofcasesofisolated KFD areself-limited, withgoodoutcome and notreatment is required, as demonstrated here. Infact, KFD symptoms andsignsmayregressinaperiodofsixmonthswithoutany therapy.7
In conclusion,KFDwas abenignand rare disease asso-ciatedwithpediatriclupuspopulation.Ourstudyreinforces therelevanceofautoimmunediseasesdiagnosisduringthe follow-upofpatientswithKFD.
Funding
ThisstudywassupportedbyFundac¸ãodeAmparoàPesquisa do Estado de São Paulo (FAPESP – grants 2008/58238-4 to CAS and 2011/12471-2 to CAS), by Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPQ – grant 302724/2011-7toCAS),byFedericoFoundationtoCASandby NúcleodeApoioàPesquisa“SaúdedaCrianc¸aedo Adoles-cente”daUSP(NAP-CriAd).
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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