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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
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