类风关文档格式.docx

类风关文档格式.docx

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Etiology:

Despitemanyyearsofintensiveinvestigations,theetiologyofRAremainsobscure.Therecentfindingofanassociationwithcertainallelesofhemajorhistocompatibilitycomplexsuggeststhatgeneticfactorscaninfluencetheexpressionofthedisease,perhapsbytheireffectsontheimmunologicphenomenathatplayanimportantroleindiseasepathogenesis.BesidesthatcertainbacteriaandvirusaresuspectedtobethetriggerofRA.

Rheumaticfactor:

（RF）

RFareantibodieswithspecificitytoantigenicdeterminantsontheFcportionofhumanoranimalIgG.StandardflocculationtestsdetectIgMRFintheseraofapproximately70%ofadultpatientsofRA.RFpositivecanalsobefoundinotherdiseasesoreveninoldhealthypeople.HightiterofRFisgenerallyassociatedwithmoresevereandactivejointdisease,thepresenceofnodules,greaterfrequencyofsystemicmanifestationsofRAandapooreroutcome.Currently,themostpopularnotionthatRFariseasantibodiesto“altered”autologousIgG.AlterationisthoughttooccurwhenanativeIgGantibodymoleculecombineswithitsspecificantigen,whichchangestheconfigurationoftheIgGmoleculerevealingneworpreviouslyhiddenantigenicdeterminants,therebyrenderingitanautoimmunogen.

BesidesRA,IgMRFfrequentlypresentinfollowingdiseases:

Sjogren’ssyndrome,systemiclupuserythematosus,progressivesystemicsclerosis,polymyositis/dermatomyositis,bacterialendocarditis,tuberculosis,syphilis,infectioushepatitis,schistosomiasis,normalindividualespeciallyaged,diffuseinterstitialpulmonaryfibrosis,cirrhosisofliver,chronicactivehepatitisandsarcoidosis.

RFusuallyabsentinosteoarthritis,ankylosingspondylitis,gout,chondrocaleinosis,psoriaticarthritis,enteropathicarthritisReiter’ssyndromeandsuppurativearthritis.

TheexactbiologicalroleofRFisunknown.Antiviralpropertieshavebeenascribedtothem.Itisfoundthattheycanaffecttheinflammatoryresponsebyenhancingcomplementfixation,byalteringthepropertiesofimmunecomplexes,orbyrenderingthembymoresusceptibletophagocyticcells.Theselattercharacteristicsareprobablyimportantinsynovialtissuesandfluids.

Pathology:

Thesynovialmembraneistheprimarysiteofinvolvement.Itbecomesthickened,withprominentvillousformationandeffusionofinflammatoryfluidintothejointcavity.Therearediffuseexudationandinflammatorycellinfiltration.Lininglayerincreasesindepth.Inthesubintimallayer,TcellspredominantlyCD4+cellsconstitute30-50%ofsynovialtissuecellsandclusterinperivasularaccumulations.Themostcharacteristicpathologyintherheumatoidjointisthepannusformation,asheetofinvasivecellulartissue,incontinuitywithsynoviallininglayerandpresumablyderivedfromit,whicherodescartilageandboneatthemarginofthejoint.

Theextra-articularpathologyincludesrheumatoidnodulesandvasculitis.Thenodulesconsistsofaninnercoreoffibrinoidnecrosis,asurrounding“fence”madeuppredominantlyofmacrophagesandanouterareaoflooselyorganizedperivascularchroniclymphoidinfiltration.

Pathogenesis:

RAisautoimmunereactionbynature.ItinvolvesbothTandBlymphocytesaswellassomecytokineslikeTNFα,IL-I.Unknownantigenismodifiedandpresentedbyantigen-presentingcellstoactivateThelpercells,whichinturnsecretemanycytokinestostimulateBcellsresultinginthemassproductionofimmunoglobulinincludingRF.Allthesechangeswillcreateaninflammatoryprocess.

Clinicalfeatures:

1.Articularandothersynovialdisease

TheonsetofRAisfrequentlyheraldedbyprodromalsymptomssuchasfatigue,anorexia,weightloss,weakness,,andgeneralizedachingandstiffness.Approximately20%ofpatientshaveanabruptonsetofpolyarthritis,oftenaccompaniedbyfeverandprostration.Themanifestationsarepain,stiffnesslimitationofmotionandthesignsofinflammation.Morningstiffnesslastingmorethanhalfanhourmaybeoneoftheimportantcluesfordiagnosis.Inearlydiseasejointlimitationisusuallycausedbypainwhilelatermaybecauseofcapsularfibrosis,musclecontractureorbony/fibrousankylosis.Themostcommonlyinvolvedinitiallyarethesmalljointsofhands,wrists,knees,andfeet.Itisusuallybilateral,symmetricalandpolyarticularinvolved.Asthediseasebecomesestablished,thearthritisspreadstotheelbows,shoulders,sternoclavicularjoints,hips,anklesandsubtalarjoints.Lesscommonlythetemporomandibularandcricoarytenoidjointsareaffected.Clinicallysignificantspinalinvolvementisusuallylimitedtotheuppercervicalarticulations.

Inearlystage,swellingoftheproximalinterphalangeal（PIP）jointsproducesaspindle-shapedappearanceofthefingers.Bilateralsndsymmertricalswellingofthemetacarpophalangeal（MCP）joints,particularlythesecondandthird,isverycommonandremainslongafterPIPjointinflammationhassubsided.Thedistalinterphalangeal（DIP）jointsaremoreoftenspared.Asthediseaseprogresses,laxityofsofttissuesincreasesandunderthepressureofregularuse,typicalhanddeformitiesdevelop.Ulnardeviationofthefingersisparticularlycommon,oftenaccompaniedbypalmarsubluxationoftheproximalphalanges.HyperextensionofthePIPjointsinconjunctionwithflexionattheDIPjointconstitutestheswanneckdeformity.TheboutonnieredeformityisaflexiondeformityofthePIPjoints.InvolvementofthethumbscauseshyperextensionoftheinterphalangealjointsandflexionattheMCPjointswitharesultantlossofpinch.

WristdiseaseisalmostinvariableaccompanimentofRA.Activesynovitiscanbeobservedatthedorsumofthewristasaboggy.Softtissueswelling,synovitishypertrophyandtenosynovitisonthevolaraspectmaycompressthemediannervebeneaththetransversecarpalligament,producingacarpaltunnelsyndromewithparesthesiaanddysesthesiaofthethumb,second,third,andradialaspectofthefourthdigits.Thethenareminencemayatrophy.

Hipjointsarelessinvolved.Afrequentcomplaintisdiscomfortinthegroin;

lessoftenthepainisreferredtothebuttocksorlowerback.Swellingandtendernessaredifficulttonoteandhipdiseasemayberecognizedonlybecauseofgaitabnormalitiesorlimitationofjointmotion.

Thekneeisamongthemostfrequentlyaffectedjointsandisresponsibleformuchdisability.Synovialhypertrophyandchroniceffusioncanbepronounced.Aregularaccompanimentofkneeinvolvementisquadricepsatrophy,oftenofgreatseverity.

Feetandanklearthritiscreateanumberofvexingproblemsduetopainandlimitationofflexionandextension.

Symptomsofintermittentneckpainandstiffnessarefrequent.Thespinalcordmaybecompromisedbyanteriordislocationofthefirstcervicalvertebrae.Verticalsubluxatoncaninducetorsionandcompressionofthevertebralarterieswithsymptomsofvertebrobasilarinsufficiencyandsyncopeondownwardgaze.

Extra-articulardisease:

Rheumatoidnoduleappearsatsometimeinapproximately20-25%ofthepatients.Theyareoftenassociatedwithseropositive（RF）andperhapswithamoresevereanddestructivearthritis.Nodulesareroundorovalmassinsubcutaneousordeeperconnectivetissues,varyingfromlessthan0.5cmtoseveralcentimetersindiameter.Peri-articularstructuresandareassubjectedtomechanicalpressurearecommonsitesespeciallytheolecranonbursae,extensorsurfaceoftheforearmandtheAchillestendon.

Vasculitis:

thepathogenesisofrheumatoidvasculitisisuncertain,indirectevidencesuggeststheparticipationofimmunecomplexes.Theymaytakemanyformsascapillarritis,venulitisorinrarecasewidespreadnecrotizingarteritis.Theyproducethesymptomsofdigitalgangrene,skinulcerandnecrosis,sensorimotorneuropathyandvisceralinfarction.

Cardiacmanifestations:

pericarditisoccursinabout40%atautopsy.Lesscommonaregranulomatouslesions,similartorheumatoidnodules,involvingtheepicarduim,myocardiumandvalves;

focalinterstitialmyocarditis;

andarteritisofcoronaryvessels;

occasionallyvalvularinsufficiencyorconductionabnormalitiesarerecognizedduringlife.

Pleuropulmonarymanifestations:

Rheumatoidpleuraldiseaseisusuallyasymptomatic.Pleuraleffusionmayhappenin10%ofthepatientswithhydrothorax.Solitaryormultiplenodulesareoccasionallyseeninthechestfilmespeciallythosewithsubcutaneousnodules.Diffuseinterstitialfibrosisisnotrare.InlatestageitmayprogresstothehoneycombappearanceinCTscanwithamarkeddecreaseinpulmonaryfunction.

PatientswithhightiterofRFprobablydevelopsecondarySjogren’ssyndrome.Theremaybecornealandconjunctivallesions.

LymphnodeenlargementiscommoninRApatients.Palpablesplenomegalyoccursinupto10%ofpatients.Felty’ssyndromereferstothoseRApatientswhohavebothsplenomeaglyandleukopenia.RecurrentGrampositiveinfectionarecommonandfrequentlyrespondpoorlytoantibiotics.

Labfi