RHEUMATOIDARTHRITIS RA JiangLindi ZhongshanHospital WhatisRA RAisachronicpolyarticularinflammatoryarthritisthatinvolvesnotonlysmalljointsofthehandsandfeetbutalsosystemicorgans Pathologicchange chronicsynovitiswithpannus 血管翳 formation Itwillcausebonydestruction deformation disabilityifjointinflammationrepeatedlyoccur RFispresentintheseraofmorethan75 ofpatients TheprevalencerateofRAhasbeenestimatedtobe0 32 0 36 inChina Womenappeartobeaffectedthreetimesmorecommonlythanmen ETIOLOGY Infectiousagents Epstein Barrvirus mycoplasma macobacteria retrovirusesTlymphocyteandmacrophageactivationBlymphocyteactivationChangeofthegeneexpressionMolecularmimicry 2 GeneticfactorsAhighincidenceamongmonozygotictwins 30 50 first degreerelativeRoleofHLA DR4inthesusceptibilitytoandseverityofRA70 RApatients arelativeriskofhavingRAwithHLA DR4of4to5Thesusceptibilityepitope sharedepitope共同表位 QKRAA或QRRAAItwasconsideredtoberelatedwiththeseverityofestablishedRA 3 Gender PredominanceinwomenImprovementorremissionofRAduringpregnancy4 Inducedfactors tiredness humidity cold mulnutrition psychicalstimuli antigen HLA DR QKRAA heatshockprotein IgG typeIIcollagenantigenprocessingmacrophages MHCII peptidecomplexespresentationTcellcytokine IL 1 2 3 4 6 TNF r INF BcellactivationimmunedamageRFandotherantibodycollagenase stromolysincartilageandbonedestructionextra articularsymptom PATHOLOGY PATHOLOGICFINDING 1 chronicsynovitisInacutephase effusionandcellinfiltrationInchronicphase thenumberofAtypecellremarkablyincreasesthepannuserodescartilage bone ligamentsandtendons 2 extra articular vasculitis rheumatoidnodule CLINICALFAETURES Theusuallyageatonsetis35 50yearsTheratiooffemaletomaleis3 1TheonsetofRAisusuallyinsidiousSystemicsymptomoffatigue malaise fever weightlossmaybeseen 1 Jointmanifestation 1 morningstiffnessstiffnesspersistingforover30minutesisprominentinthemorningorafterdaytimeactivityandsubsidesduringthedayThepersistinglengthofmorningstiffnessisassociatedwiththedegreeofjointinflammation Thedurationofmorningstiffnessisusedastheindexofdiseaseactivity 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 Figure1 4 尺側偏移鈕扣花畸形掌指關節腫脹受累關節示意 6 Functionalcapacity1991ACRcriteriaforclassificationoffunctionalstatusinRAClassICompletelyabletoperformusualactivitiesofdailyliving self care vocational andavocational ClassIIAbletoperformusualself careandvocationalactivities butlimitedinavocationalactivitiesClassIIIAbletoperformusualself careactivities butlimitedinvocationalandavocationalactivitiesClassIVLimitedinabilitytoperformusualself carevocational andavocationalactivities 2 Extra articularmanifestations 1 Rheumatoidnodules20 30 patientsareasthatarerepeatedlysubjectedtofriction suchastheextensorsurfaceoftheforearmTheadventindicatesthediseaseisintheactivephase 2 rheumatoidvasculitis episcleritis scleritis 3 pulmonarymanifestationdiffuseinterstitialfibrosis abnormalonCTscan restrictivediffusepatternintrapulmonarynodules asymptomatic infected cavitaterheumatoidpleuraldisease exudative WBC 5000 mm3 lowerlevelofglucose 4 pericarditis 30 pericardialeffusion asymptomatic 5 gastrointestinalmanifestation nausea lossofappetite 6 kidney drug induced amyloiddegeneration 7 Neurologicmanifestations Acervicalmyclopathycanresultfromatlantoaxialsubluxation sensoryabnormityandlossofstrengthperipheralneuropathiescanbeproducedbyproliferatingsynoviumcausingcompressionofnervesandrheumatoidvasculitis carpaltunnelsyndrome 8 Hematologicmanifestations anemia Felty ssyndrome LABORATORYFINDING 1 Anemia ahypochromicnormocyticanemia2 ElevatedESRandCRParedemonstratedanactiveconditionofthedisease3 Jointfluidexamination WBCintherange5000to20000 mm3 with50 70 aspolymorphonuclearleukocytes apoormucinclot normallevelofglucose 6 RFRFisanIgG IgA IgMantibodydirectedagainsttheFcfragmentRFisPresentintheseraofmorethan60 70 patientsDespitetheextremelystrongassociationofRF swithRA theyclearlydonotcausethedisease RFproductionoccurscommonlyinotherdisorders syphilis sarcoidosis infectiveendocarditis tuberculosis leprosy viralinfectionandparasiticinfections otherautoimmunedisease SLE PSS DM healthypeople 10 7 X raychanges ClassIswollenofsofttissue juxta articularosteoporosisClassIIjointspacenarrowingClassIIIbonycystsandbonyerosionsClassIVsubluxation fibrousandbonyankylosis8 PathologicfindingRheumatoidnoduleandsynovialbiopsy 1988RevisedARACriteriaforClassificationofRA Criteriondefinition1 Morningstiffnesslastingatleast1hr2 Arthritisofthreeatleastthreejointareassimultaneouslyormorejointareashavingsofttissueswellingorfluid3 Arthritisofhandjointsatleastonejointareaswollenoraboveinwrist MCP PIPjoint4 Symmetricarthritissimultaneousinvolvementofthesameareasonbothsidesofthebody5 Rheumatoidnodules6 Serumrheumatoidfactor7 Radiographicchangesincludingerosionsorunequivocalbonydecalcification DifferentialDiagnosis Osteoarthritis occursin40ormorepainincreasethroughdayorwithuseinvolveDIP weight bearingjointsradiologicfindings subchondralsclerosis osteophyteslabfindings normal RAASHLA DR4HLA B27women 30 50yearsyoungmaleSmalljoint symmetriclowerextremity asymmetricpolyarticularoligoarthropathywrist fingersacroilitis lumbarspinesynovitisperiarticularsofttissueinflammationulnardeviationmarginalbridgingsundesmophytes swan neckdeformitybamboospineRF RF TREATMENT Theprimaryobjective ReductionofinflammationandpainPreventionofjointdeformityPreservationofmusclestrengthandjointfunctionMinimizingundesirabledrugsideeffectsandimprovementofqualityoflife Generalapproach Acutephase restandrestrictionofmotionInactivephase exercisetherapy Drugtherapy NSAIDs nonsteroidalanti inflammatorydrugs GlucocorticoidsDMARDs diseasemodifyinganti inflammatorydrugs NSAIDs NSAIDsisusedasthefirstdrugoftreatingRANSAIDshaveanalgesicandanti inflamatoryeffectsbutarebelievednottobecapableofpreventingerosionsoralteringprogressionofthedisease NSAIDs ibuprofen naproxen sulindac diclofenacNSAIDsshareacommonspectrumofclinicaltoxicities gastrointestinaltract kidney hematopoieticsystem centralnervoussystemandliver Cellmembranephospholipids Inhibitedbyglucocorticoids phospholipase Arachidonicacid InhibitedbyNSAIDs O2 Cyclooxygenase Cyclicendoperoxides PGG2 PGH2 ThromboxaneB2 PGE2 PGF2 ThromboxaneA2 6 Keto PGE1 Toxicoxygenradicals PGI2 Advance TwoisoformsofCOXhavebeendiscovered COX 1andCOX 2COX 1isexpressedconstitutivelyingastricmucosa Kidney platelets COX 2expressionisinduciblebycytokinesandgrowthfactorsinmacrophages monocytes synoviocytes COX 2playedakeyroleininflammatoryconditionsSelectiveCOX 2inhibitorshavebeendeveloped DMARDs disease modifyingantirheumaticdrugs DMARDshavethepotentialtoinhibittheabnormalimmuneresponseanddelaytheprogressionofthedisease DMARDsshouldbesuggestedwithin3to6months Thetimeofactionwillberetarded3 6monthaftertakingDMARDs Carefulmonitoringfortoxicityisrequired DMARDs MTX gastrointestinalandoralulceration liverfailure 7 5 15mg qwDP hematocytopenia proteinuria myastheniagravis Good pasture ssyndromeSASP headache gastrointestinalupset 2 3g dAntimalarials retinallesion lossofvisionhydroxychloroquine200mg qd Glucocorticoid GCisthemostpowerfulanti inflammtoryandimm