小儿风湿性疾病-徐虹

RheumatoidDiseaseinChildren

小儿风湿性疾病Children’sHospitalofFudanUniversityXuHonghxu@RheumatoidDisease

Connectivetissuediseases

（包含有120种与关节、骨骼、肌肉等相关的疾病）

过敏性紫癜（anaphylactoidpurpura）类风湿性关节炎（JRA）SLE（systemiclupuserythematosis）皮肌炎（dermatomyositis）硬皮病（scleroderma）风湿热（rheumaticfever）川崎病(Kawasakidisease)RheumatoidDiseaseinChildrenThemostcommondiseases：JuvenileRheumatiodArthritisHenoch-SchonleinpurpuraKawasakiDisease(MucocutaneousLymphNodeSyndrome,MCLS)RheumaticFever冠状动脉造影CoronaryangiogramHenoch-SchonleinpurpuraAlternativenames:AnaphylactoidpurpuraVascularpurpuraDefinitionHenoch-Schonleinpurpuraisadiseasethathasthesymptomspurplespotsontheskinjointpaingastrointestinalsymptomsglomerulonephritis(atypeofkidneydisorder)HistorystorySchonlein'sPurpura

(In1837,JohanSchonlein)theskinandjointsareaffectedbutthegastrointestinaltractisnot

Henoch'sPurpura(Later,hisstudent,EduardHenoch)purpuraspotsontheskinandacuteabdominalproblemsnotaffectedbyjointdiseaseGeneralconditionsatypeofhypersensitivityvasculitisandinflammatoryresponsewithinthebloodvesselItiscausedbyanabnormalresponseoftheimmunesystemTheexactcauseforthisdisorderisunknown.Thesyndromeisusuallyseeninchildren,butpeopleofanyagemaybeaffectedItismorecommoninboysthaningirlsManypeoplewithHenoch-SchonleinpurpurahadanupperrespiratoryillnessinthepreviousweeksCausesandpathogenesisAninflammatorydiseaseofthesmallbloodvessels(capillaries)

usuallyaself-limiteddiseaseItisthemostcommonformofchildhoodvascularinflammation(vasculitis)andresultsininflammatorychangesinsmallbloodvesselsCommonallergensincludeMedications(suchascertainantibiotics,antihistaminesandthiazidediuretics)Pathogens(bacterium/virus/parasite,suchasgroupAstrep,varicella,parvovirusandhepatitisB)AnacuterespiratoryinfectionCommonallergensincludefoods(suchasberries,shellfish,fish,nuts,eggs,milk,andothers)pollen

animaldander(scalesofshedskin)insectbites

Certainvaccinations,suchasformeasles,yellowfeverandcholera

Pathophysiology

asmall-vesselvasculitischaracterizedbyimmunoglobulinA(IgA),C3,andimmunecomplexdepositioninarterioles,capillaries,andvenulesHSPandIgAnephropathyarerelateddisorders.BothillnesseshaveelevatedserumIgAlevelsandidenticalfindingsonrenalbiopsyPathophysiology

LowerLegDirectimmunofluoresence(DIF)showeddepositsofIgAaboutdermalvessels.RenalbiopsyshoweddepositsofIgAinthemensangiumFrequency:IntheUS:Approximately14casesoccurper100,000school-agedchildren.HSPalsooccursinadults,althoughlesscommonlythaninchildren.

Mortality/Morbidity:

Ingeneral,HSPisabenignself-limiteddisorder.

Fewerthan5%ofcasescausechronicsymptoms.Fewerthan1%ofcasesprogresstoend-stagerenalfailure.Sex:Male-to-femaleratioisabout2:1.

Age:

75%ofpatientsaffectedareaged2-11years.Insomeseries,asmanyas27%ofthepatientsareadults.

ManifestationsHistory:ThemostcommonsymptomsofHSPincludethefollowing:Rash(95-100%),especiallyinvolvingthelegs,maynotbepresentoninitialpresentationSubcutaneousedema(20-50%)Abdominalpainandvomiting(85%)Jointpain(60-80%),especiallyinvolvingkneesandanklesScrotaledema(2-35%)Bloodystools("hematochezia","melena")ManifestationsPhysical:

Palpablepurpura,particularlyonthebuttocksandlegsEdemaofthehands,feet,scalp,andearsArthritis,mostcommonlyinvolvingthekneesandanklesAbdominaltendernessGastrointestinalbleedingAcutescrotaledemathatmaymimictesticulartorsionWithAngioneuroticedemaSwelling–eyes,lip,handOnthebuttocks臀部

inrarecasesthebrainandspinalcord(centralnervoussystem)involvedArthritis,thekneeLabStudiesRoutinelabtestresultsareusuallywithinreferenceranges.Somelabstudieshelpinexcludingotherdiagnosesandinevaluatingrenalfunction:urinalysis/CBCwithplateletcountanddifferential/BUN,creatinine/prothrombintime(PT),activatedpartialthromboplastintime(aPTT)/lipaseLabStudiesHematuriaand/orproteinuriaarepresentin10-20%ofpatientsPlateletcountisusuallyinthereferencerangebutmaybeelevatedAnormallipasemakesacutepancreatitisveryunlikelyWBCcountmaybeinthereferencerangeorelevated.EosinophiliaissometimespresentESRinthereferencerangeorelevatedBUNandcreatininelevelsmaybeelevatedfromrenalinvolvementofHSPorfromdehydrationImagingStudies:Abdominalultrasoundmaybebetterthanbariumenematodiagnoseintussusception,sinceHSP-relatedintussusceptionismoreoftenileoilealinsteadofileocolicasistypicalinidiopathicintussusception.DopplerorradionuclidetesticularscanresultsshownormalorincreasedbloodflowinHSP,incontrasttothedecreasedbloodflowseenintesticulartorsion.

DiagnosisanddifferentiationDiagnosisisclinicalandnotbasedonlaboratoryevaluationAphysicalexaminationrevealsskinlesionsandjointtendernessAurinalysisshowsmicroscopicbloodintheurineAskinbiopsyshowsvasculitisDiagnosisanddifferentiationAnormalplateletcountrulesoutidiopathicthrombocytopenicpurpura(ITP)Anormalplateletcountandnormalcoagulationstudies(ie,PT,aPTT,fibrinsplitproducts)ruleoutthromboticthrombocytopenicpurpura(TTP)OtherProblemstobeConsidered

EssentialmixedcryoglobulinemiaWaldenströmmacroglobulinemiaSystemiclupuserythematosusRickettsialdiseasesBowelinfarction/perforationTreatment

Anti-inflammatorymedications,suchasaspirinoribuprofen,torelievejointpainandswellingStoppingmedicationthatmaybetheunderlyingcauseCorticosteroids

Ifsymptomspersist,therapywithcorticosteroidssuchasprednisone,triedtotreatabdominalpain,subcutaneousedema,andnephritisTreatment

Patientswithsevereabdominalpain,significantgastrointestinalbleeding,ormarkedrenalinsufficiencymayrequirehospitalization.

TreatmentinHSPN(HSPnephritis)manydifferentmodalitiesinseverecasesIVororalsteroidswithorwithout:

Azathioprine（硫唑嘌呤）Cyclophosphamide（CTX）Cyclosporine（环孢素A）Dipyridamole(潘生丁)Plasmapheresis（血浆置换）high-doseIVimmunoglobulinG(IVIg)PrognosisHSPisgenerallyabenigndiseasewithanexcellentprognosisMorethan80%ofpatientshaveasingleisolatedepisodelastingafewweeksApproximately10-20%ofpatientshaverecurrencesFewerthan5%ofpatientsdevelopchronicHSPAbdominalpainresolvesspontaneouslywithin72hoursinmostpatientsGeneralconditionsAchronicsystemicdiseasePrimarilyofthejointsMarkedbyinflammatorychangesinthesynovialmembranes（滑膜）

andarticularstructuresWidespreadfibrinoiddegenerationofthecollagenfibersinmesenchymaltissues,andbyatrophyandrarefactionofbonystructures（纤维化和骨质疏松）EtiologyisunknownAutoimmunemechanismshavebeenimplicatedGeneralconditions

Arthritiscanbeshort-term-lastingforjustafewweeksormonths,thengoingawayforeveroritcanbechronicandlastformonthsoryears.Inrarecases,itcanlastalifetimeCausesandpathogenesisCausesunknownexactlyResearchindicatesthatitisanautoimmunediseaseWhitebloodcellslosetheabilitytotellthedifferencebetweenthebody'sownhealthycellsandharmfulinvaderslikebacteriaandvirusesTheimmunesystem,whichissupposedtoprotectthebodyfromtheseharmfulinvaders,insteadreleaseschemicalsthatcandamagehealthytissuesandcauseinflammationandpainClinicalmanifestationsSignsandSymptomsThefirstsignsofarthritiscanbesubtleorobvious.Signsmayincludelimping(跛行)

orasorewrist,finger,orkneeJointsmaysuddenlyswellandremainenlarged.Stiffnessintheneck,hips,orotherjointsRashesmaysuddenlyappearanddisappeardevelopingin1areaandthenanother.HighfeversthattendtospikeintheeveningsandsuddenlydisappeararecharacteristicofsystemicjuvenilerheumatoidarthritisHighfeversinSystemicJRAClinicalmanifestationsTypicallyappearsbetweentheagesof6monthsand16yearsNotasingledisease,butagroupofdiseasesWhattheyallhaveincommonischronicjointinflammation.thefirstsignsareoftenjointpainorswellingandreddenedorwarmjointsThediseasesareverydifferentintheirsymptoms,theirtreatments,andtheiroutcomesThereare3majortypesofjuvenilerheumatoidarthritis(accordingtoonsetwithinthefirst6months)ClinicalmanifestationsPolyarticulararthritis(多关节型)affectsmoregirlsthanboysSymptomsincludeswellingorpain

in5ormorejointsThe

smalljoints

ofthehandsareaffectedaswellastheweight-bearingjointssuchastheknees,hips,ankles,feet,andneckInaddition,

alow-gradefever

mayappear,aswellasbumpsornodulesonthebodyonareassubjectedtopressurefromsittingorleaningswellingofsmalljointsofthehandsalotofstiffnesswhentheyfirstwakeupinthemorning.Oncetheirjointswarmup,theycanusuallymovemoreeasily.ClinicalmanifestationsPauciarticularJRA

(少关节型)affects4orfewerjointsSymptomsincludepain,stiffness,orswellinginthejointsThe

kneeandwristjoints

arethemost

commonlyaffectediridocyclitis

or

iritisor

uveitis

mayoccurwithorwithoutactivejointsymptoms(canbedetectedearlybyanophthalmologist)ClinicalmanifestationsSystemicJRA（全身型）affectsthewholebodySymptomsinclude

highfevers

thatoftenincreaseinthe

eveningsandthenmaysuddenlydroptonormalDuringtheonsetoffever,thechildmayfeelveryill,appearpale,ordeveloparashThe

rash

maysuddenlydisappearandthenquicklyappearagainThe

spleenandlymphnodes

mayalsobecomeenlarged

Eventuallymanyofthebody's

joints

areaffectedbyswelling,pain,andstiffnessLabStudiesAbnormalitiesinthenumbersandappearancesofCBCcanbeusefulinthediagnosisofmanymedicalconditionsAbloodculturemaybetakentoruleoutinfectionsBonemarrowexaminationisatesttoruleoutconditionssuchasleukemiaLabStudiesErythrocytesedimentationrateoftenincreasesinpeoplewheninflammationisoccurringinthebodyRheumatoidfactor（RA类风湿因子）

isanantibody,commoninrheumatoidarthritis

RareinpersonswithsystemicJRAamarkerforpersistenceofpolyarticularJRAintoadulthoodLabStudiesANA(antinuclearantibody)isatestperformedonthebloodtodetectautoimmunity.ItisalsousefulinpredictingwhichchildrenarelikelytohaveeyediseasewithJRATestforcertainviralinfectionssuchasLymediseasethatmaycausesimilarsymptomsoroccuralongwiththearthritis.

ImagingStudiesRadiographyofaffectedjoints

Whenonlyasinglejointisaffected,radiographyisimportanttoexcludeotherdiseases,suchasosteomyelitis骨髓炎orsepticarthritisBonescanning:Whenphysicalfindingsdonotdocumentdefinitearthritis,considerbonescanningasameansofidentifyingapotentialfocusofosteomyelitisorotherabnormalityImagingStudiesMRIishelpfulwhenconsideringtraumainthedifferentialdiagnosisCTscanningoflongbones:Performwhenconsideringosteoidosteomainachildwithlowerextremitypain(oftenatnight)andunremarkablefindingsonphysicalexamination.ImagingStudiesEchocardiographyThisisperformedinachildwithpossiblesystemicJRAandwithfevers.Inapersonwhohasnonspecificrash,adenopathy,andpossiblemucocutaneouschanges,toexcludecoronaryarterialdilationresultingfrom(possiblyatypical)Kawasakidisease.InanindividualwhohasfindingssuggestiveofSLE(eg,nephritis,pleuriticchestpain,thrombocytopenia)OthersSynovialbiopsyThisproceduremaybehelpfultoexcludeotherdiagnosesparticularlywhenthekneeisaffected(eg,villonodularsynovitis绒毛膜结节样滑膜炎

granulomatousarthritis)DiagnosisanddifferentiationDiagnosisToeffectivelymanageandminimizetheeffectsofarthritis,anearlyandaccuratediagnosisisessential

AdetailedphysicalexaminationisacriticaltoolindiagnosingJRAPhysicalfindingsareimportanttodetectabnormalitiessuggestiveofotherpossiblediagnosesDiagnosisanddifferentiationThediagnosisofJRAisbasedonthephysicalfindingofarthritis(orsynovitis)inatleastonejointthatpersistsforatleast6weeksWithothercausesbeingexcludedandwithonsetwhentheindividualisyoungerthan16yearsArthritisonexaminationisdefinedaseitherjointswellingorthecombinationoflimitedmotionwithpain(onmotionortopalpation)DiagnosisanddifferentiationDIFFERENTIALSAcuteLymphoblasticLeukemiaAutoimmuneChronicActiveHepatitisCrohnDiseaseEndocarditis,BacterialFeverintheToddlerKawasakiDiseaseSystemicLupusErythematosusTreatmentThegoalsoftreatment:TorelievepainandinflammationToslowdownorpreventthedestructionofjointsTorestoreuseandfunctionofthejointstopromoteoptimalgrowth,physicalactivity,andsocialandemotionaldevelopmentCombinationofmedication,physicaltherapy,andexercise(physician,rheumatologist,andphysicaltherapist)TreatmentInitialtreatmentlimitedtotheuseofsalicylatesthenothernonsteroidalanti-inflammatorydrugs(NSAIDs)resultedinmanypatientsbecomingwheelchairboundOtherpatientsunderwentsynovectomiestoremoveexcesstissuer