姜林娣－类风关

RHEUMATOIDARTHRITIS

（RA）

JiangLindi

(ZhongshanHospital)

1WhatisRA?RAisachronicpolyarticularinflammatoryarthritisthatinvolvesnotonlysmalljointsofthehandsandfeetbutalsosystemicorgans.Pathologicchange:chronicsynovitiswithpannus(血管翳)formation.Itwillcausebonydestruction,deformation,disabilityifjointinflammationrepeatedlyoccur.RFispresentintheseraofmorethan75%ofpatients.TheprevalencerateofRAhasbeenestimatedtobe0.32%-0.36%inChina,Womenappeartobeaffectedthreetimesmorecommonlythanmen.2ETIOLOGYInfectiousagents:Epstein-Barrvirus,mycoplasma,macobacteria,retrovirusesTlymphocyteandmacrophageactivationBlymphocyteactivationChangeofthegeneexpressionMolecularmimicry32.GeneticfactorsAhighincidenceamongmonozygotictwins(30%~50%),first-degreerelativeRoleofHLA-DR4inthesusceptibilitytoandseverityofRA70%RApatients，arelativeriskofhavingRAwithHLA-DR4of4to5Thesusceptibilityepitope(sharedepitope共同表位):QKRAA或QRRAAItwasconsideredtoberelatedwiththeseverityofestablishedRA43.Gender:PredominanceinwomenImprovementorremissionofRAduringpregnancy4.Inducedfactors:tiredness,humidity,cold,mulnutrition,psychicalstimuli5

antigen:HLA-DR(QKRAA)、heatshockprotein、IgG、typeIIcollagenantigenprocessingmacrophages+MHCII-peptidecomplexespresentationTcellcytokine（IL-1、2、3、4、6、TNF、r-INF）

BcellactivationimmunedamageRFandotherantibody

collagenase、stromolysincartilageandbonedestructionextra-articularsymptomPATHOLOGY6PATHOLOGICFINDING1.chronicsynovitisInacutephase:effusionandcellinfiltration

Inchronicphase:

thenumberofAtypecellremarkablyincreasesthepannuserodescartilage,bone,ligamentsandtendons.2.extra-articular：vasculitis、rheumatoidnodule7CLINICALFAETURESTheusuallyageatonsetis35-50yearsTheratiooffemaletomaleis3:1TheonsetofRAisusuallyinsidiousSystemicsymptomoffatigue,malaise,fever,weightlossmaybeseen

8

1.Jointmanifestation（1）morningstiffnessstiffnesspersistingforover30minutesisprominentinthemorningorafterdaytimeactivityandsubsidesduringthedayThepersistinglengthofmorningstiffnessisassociatedwiththedegreeofjointinflammation.Thedurationofmorningstiffnessisusedastheindexofdiseaseactivity.9（2）painandtenderness：painfulonrestlocation：small(PIP,MCP),symmetricjointcharacteristic：persisting、dullorswollenpain（3）swelling：synovialproliferation,effusion,swellingofsofttissue（4）articulardeformity：ulnardeviationofthefingers,“swan-neck”deformity,atrophyofskinandmuscle(seefigure1-5)（5）involvementofspecialjoint:atlantoaxialsubluxation，shoulders,temporomandibularjoint,hips.10Figure1-4:尺侧偏移钮扣花畸形掌指关节肿胀受累关节示意11（6）Functionalcapacity

1991ACRcriteriaforclassificationoffunctionalstatusinRAClassI

Completelyabletoperformusualactivitiesofdailyliving(self-care,vocational,andavocational)

ClassII

Abletoperformusualself-careandvocationalactivities,butlimitedinavocationalactivitiesClassIIIAbletoperformusualself-careactivities,butlimitedinvocationalandavocationalactivitiesClassIVLimitedinabilitytoperformusualself-carevocational,andavocationalactivities122.Extra-articularmanifestations（1）Rheumatoidnodules

20%-30%patientsareasthatarerepeatedlysubjectedtofriction,suchastheextensorsurfaceoftheforearm

Theadventindicatesthediseaseisintheactivephase

（2）rheumatoidvasculitis:episcleritis,scleritis13（3）pulmonarymanifestationdiffuseinterstitialfibrosis:abnormalonCTscan,restrictivediffusepatternintrapulmonarynodules:：asymptomatic,infected,cavitaterheumatoidpleuraldisease：exudative,WBC<5000/mm3,lowerlevelofglucose(4）pericarditis:30%pericardialeffusion,asymptomatic（5）gastrointestinal

manifestation:nausea,lossofappetite（6）kidney：drug-induced，amyloiddegeneration14（7）Neurologicmanifestations：Acervicalmyclopathycanresultfromatlantoaxialsubluxation:sensoryabnormityandlossofstrengthperipheralneuropathiescanbeproducedbyproliferatingsynoviumcausingcompressionofnervesandrheumatoidvasculitis:carpaltunnelsyndrome.（8）Hematologicmanifestations：anemia,Felty’ssyndrome

15LABORATORYFINDING1.Anemia:ahypochromicnormocyticanemia2.ElevatedESRandCRParedemonstratedanactiveconditionofthedisease3.Jointfluidexamination:WBCintherange5000to20000/mm3，with50~70%aspolymorphonuclearleukocytes,apoormucinclot,normallevelofglucose166.RF

RFisanIgG,IgA,IgMantibodydirectedagainsttheFcfragmentRFisPresentintheseraofmorethan60%-70%patientsDespitetheextremelystrongassociationofRF’swithRA,theyclearlydonotcausethedisease.RFproductionoccurscommonlyinotherdisorders:syphilis,sarcoidosis,infectiveendocarditis,tuberculosis,leprosy,viralinfectionandparasiticinfections,otherautoimmunedisease(SLE,PSS,DM),healthypeople(10%).177.X-raychangesClassIswollenofsofttissue,juxta-articularosteoporosisClassIIjointspacenarrowingClassIIIbonycystsandbonyerosionsClassIVsubluxation,fibrousandbonyankylosis8.PathologicfindingRheumatoidnoduleandsynovialbiopsy181988RevisedARACriteriaforClassificationofRA

Criterion

definition1.Morningstiffnesslastingatleast1hr

2.Arthritisofthreeatleastthreejointareassimultaneouslyormorejointareashavingsofttissueswellingorfluid

3.Arthritisofhandjointsatleastonejointareaswollenoraboveinwrist,MCP,PIPjoint

4.Symmetricarthritissimultaneousinvolvementofthesameareasonbothsidesofthebody

5.Rheumatoidnodules6.Serumrheumatoidfactor7.Radiographicchangesincludingerosionsorunequivocalbonydecalcification19DifferentialDiagnosisOsteoarthritis:occursin40ormorepainincreasethroughdayorwithuseinvolveDIP,weight-bearingjointsradiologicfindings:subchondralsclerosis,osteophyteslabfindings:normal20RAAS

HLA-DR4HLA-B27women,30-50yearsyoungmaleSmalljoint,symmetriclowerextremity,asymmetricpolyarticularoligoarthropathywrist,fingersacroilitis,lumbarspinesynovitisperiarticularsofttissueinflammationulnardeviationmarginalbridgingsundesmophytes,swan-neckdeformitybamboospineRF(+)RF(-)

21TREATMENTTheprimaryobjective:ReductionofinflammationandpainPreventionofjointdeformityPreservationofmusclestrengthandjointfunctionMinimizingundesirabledrugsideeffectsandimprovementofqualityoflife22Generalapproach：Acutephase:restandrestrictionofmotionInactivephase:exercisetherapy23DrugtherapyNSAIDs(nonsteroidalanti-inflammatorydrugs)GlucocorticoidsDMARDs(diseasemodifyinganti-inflammatorydrugs)24NSAIDsNSAIDsisusedasthefirstdrugoftreatingRANSAIDshaveanalgesicandanti-inflamatoryeffectsbutarebelievednottobecapableofpreventingerosionsoralteringprogressionofthedisease.NSAIDs:ibuprofen,naproxen,sulindac,diclofenacNSAIDsshareacommonspectrumofclinicaltoxicities:gastrointestinaltract,kidney,hematopoieticsystem,centralnervoussystemandliver.25CellmembranephospholipidsInhibitedbyglucocorticoidsphospholipaseArachidonicacidInhibitedbyNSAIDsO2+CyclooxygenaseCyclicendoperoxides(PGG2,PGH2)ThromboxaneB2PGE2PGF2ThromboxaneA26-Keto-PGE1ToxicoxygenradicalsPGI226AdvanceTwoisoformsofCOXhavebeendiscovered:COX-1andCOX-2COX-1isexpressedconstitutivelyingastricmucosa,Kidney,platelets.COX-2expressionisinduciblebycytokinesandgrowthfactorsinmacrophages,monocytes,synoviocytes.COX-2playedakeyroleininflammatoryconditionsSelectiveCOX-2inhibitorshavebeendeveloped27DMARDs

(disease-modifyingantirheumaticdrugs)DMARDshavethepotentialtoinhibittheabnormalimmuneresponseanddelaytheprogressionofthedisease.DMARDsshouldbesuggestedwithin3to6months.Thetimeofactionwillberetarded3-6monthaftertakingDMARDs.Carefulmonitoringfortoxicityisrequired.28DMARDsMTX:gastrointestinalandoralulceration,liverfailure,7.5-15mg/qwDP:hematocytopenia,proteinuria,myastheniagravis,Good-pasture’ssyndromeSASP:headache,gastrointestinalupset,2-3g/dAntimalarials:re