Rheumatoid-Arthritis-(RA)类风湿关节炎

RheumatoidArthritis(RA)OutlineIntroduction(RA)AetiologyPathologyDiagnosisTreatmentPrognosisIntroduction

toRARheumatoidArthritis(RA)isachronic,systemicautoimmunediseaseInflammation/DeformityofthejointsSystemicproblemsVasculitisRheumatoidnodulesLungdisease,Heartdisease,BlooddisordersOsteoporosis………1%worldwide,3%ofAustralianpopulation*RatioofincidencebetweenFemaleandMaleis3:1Canoccuratanyage,onsetofmostcasesbetween30&60years

*(2004)inNicholasJVardaxis:PathologyforHealthScience,8th,MacmillanPublishersAustraliaPTYLTD,566-570.ISBN0-7329-2012-4

Introduction

toRASynoviumisaconnectivetissuemembranethatlinesthecavitybetweenjointsandsecretesalubricatingfluid.

Introduction

toRAThesynoviumbecomesinflamed,producesexcessfluidandthecartilagebecomesroughandpitted.

Primarysymptoms

ofRAThediseaseusuallybeginsinthejoints:Typically:PainofjointsSwellingofjointsMorningjointstiffness(lastingmorethan1hour)

WidespreadmuscleachesLowgradefever(Interleukin-1)Weakness(Cytokines)

FatigueSecondarysymptoms

ofRASjogren'ssyndromePleuritisPericarditisAnaemiaFelty'ssyndromeRheumatoidnodulesVasculitisInflammationoftheglandsofeyesandmouthInflammationofthelungliningInflammationofthepericardiumReducednumberofredbloodcellsReducednumberofwhitebloodcellscausinghypertrophyofspleenFirmlumpsundertheskinaroundjointsInflammationofblood-vesselsMoresymptomscausedbyeffectsonotherorgansCharacteristics

ofRABeginsinsmalljointsinasymmetricalpattern.Laterstagesaffectremainderofwholebody.ColourX-rayImaging

ofRA

Jointswellingandbonedeformation

X-rayImaging

ofRABoneerosionandjointdestructionAetiology

ofRAUnknowncauseAutoimmunediseaseGeneticallyinherited(HLA-Dw4/DRw4)*1Suspectedcauses:Viralinfection(HHV-6)

BacterialinfectionFungalinfectionEnvironmentalfactors*2HormonalfactorsSmokingtobacco*3*1Stastny,P.1978.AssociationoftheB-cellalloantigenDRw4withrheumatoidarthritis.N.Engl.J.Med.298:869.*2AlbaniS.1992.Geneticandenvironmentalfactorsintheimmunepathogenesisofrheumatoidarthritis729-40

PMID:1280844*3UhligT.1999.

Currenttobaccosmoking,formaleducation,andtheriskofrheumatoidarthritis47-54PMID:9918239Pathogenesis

ofRAHumoral-mediatedimmuneresponseRFANAanti-CCPFcportionofautologousIgGImmunecomplexTypeIIIhypersensitivitydevelopsPlateletaggregationanddegranulationMicrothrombusformationandvasoactiveaminereleaseComplementactivationAnaphylatoxinandHistaminereleaseConnectiveTissuedamageandinflammationPathogenesis

ofRATcell-mediatedimmuneresponseHelperT4TypeIVdelayedhypersensitivityGrossdeformity-degenerativenecrosisofconnectivetissueLymphokinesMacrophages,LymphocytesFibroblastsandBoneresorption

FormationofFollicles(laterstage)

DisuseatrophyofboneandmusclesFibrosisandcalcificationAnkylosisDiagnosis

ofRAClinicalpresentationBloodtestsSerologicaltestsBiochemicalexaminationRadiographicexaminationArthroscopicexaminationtypicalsymptomswhitecells,redcells,ESRRF,ANA,ACPAsynovialfluidboneerosion,jointdestructioninteriorofjointTreatment

ofRAGoal:ReducejointinflammationandpainMaximizejointfunctionPreventjointdestructionanddeformity

LifelongtreatmentTreatment

ofRA

PharmaceuticalinterventionFirst-linedrugs(NSAIDs)Celecoxib,RofecoxibSecond-linedrugs(DMARDs)GoldsaltMethotrexate

"First-line"drugs

ofRAReducepainandinflammation--NSAIDs(celecoxib,rofecoxib)selectivelyinhibitCOX-2(cyclo-oxygenaseisoforms2)COX-2pathwayInflammatoryandmitogenicstimuliArachidonicAcidPGH2PGE2kidneyPro-inflammatoryprostaglandinsConsequencesofCOX-2inhibitionbyNSAIDs

InflammationFeverPainPhospholipaseA2COX-2CelecoxibRofecoxib"Second-line"drugsofRAAuranofin(goldsalt)Sulphydrylsystemsvariousenzymesystems,phagocyticactionofmacrophagesandleukocytes,immuneresponseMethotrexateImmunosuppressantaction:inhibitionofTcellactivationandsuppressionofintercellularadhesionmoleculePromotediseaseremissionandpreventprogressivejointdestruction—disease-modifyingantirheumaticdrugs(DMARDs)expressionbyTcellsNewerMedications

forRAAnakinra

EtanerceptBiologicalMedications:Anakinraisaninterleukin-1(IL-1)receptorantagonist.

Arecombinant,nonglycosolatedhumanIL-1receptorantagonistEtanerceptisaTumorNecrosisFactor-alpha(TNFα)Inhibitor(immunosuppressant)Arecombinant-DNAdrug

Modeofaction

AnakinraEtanerceptInflammationstimuliInterleukin-1InflammationImmunologicreactionBoneresorptionCartilagedegradationMonocytesMacrophagesTransportofwhitebloodcellstositesofinflammationInitiateandAmplifyinflammationTNFαInflammationstimuliOtherTreatment

ofRAAlternativeMedicineNaturopathyChiropracticeAcupunctureMassageTraditionalChinesemedicineFishoil

Anti-inflammatoryeffectsProper,regularexerciseMaintainjointmobilityandstrengthenthemusclesaroundthejointseg.Swimming

SurgeryRestorejointmobilityorrepairdamagedjointsPsychologicalhelpMinimizationofemotionalstresscanhelpimproveoverallhealth.Prognosis

followingdiagnosisofRA3to7yearsshorterlifespanNearlyall