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Evaluationoftheadultwithpolyarticularpain
Author: RobertHShmerling,MD
SectionEditor: RavinderNMaini,BA,MBBChir,FRCP,FMedSci,FRS
DeputyEditor: MonicaRamirezCurtis,MD,MPH

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Aug2016.|Thistopiclastupdated:Jun10,2015.
INTRODUCTIONPolyarticularpaininanadultisencounteredfrequentlyinclinicalpractice.Thecauses
includevariousselflimitedillnessesandothersthatarepotentiallydisablingandlifethreatening.Thehistoryand
physicalexaminationgenerallyprovidethemostusefuldiagnosticinformationsupportingorconfirmatorydata
areobtainedfromlaboratoryandimagingstudiesor,morerarely,fromtissuebiopsy.Acompletehistoryand
physicalexaminationareappropriateforallpatientspresentingwithpolyarticularjointpain,sincethissymptom
maybetheinitialmanifestationofasystemicillness.
Thelistofcausesofpolyarticularpainislengthy[1,2]andincludes:
Polyarthritis(table1)
Viralarthritis(table2)
Postinfectiousorreactivearthritis
Fibromyalgia
Multiplesitesofbursitisortendinitis
Softtissueabnormalities
Hypothyroidism
Neuropathicpain
Metabolicbonedisease
Depression
Thediagnosticpossibilitiescanbenarrowedsubstantiallydependinguponwhetherornotarthritisispresent
(algorithm1).Amongthoseinwhomtherearesymptomsandsignsofsynovitis,thefurtherevaluationislimitedto
thosediseaseswhichcausepolyarthritis.Intheabsenceofclearcutarthritis,thefocusshiftstononarticular
sourcesofpain.
Despitethelengthylistofdiseasesthatcausepolyarthritis,manypatientswithinflammatoryarthritisappearto
haveonlyoneofafewpossibledisorders.Amongover200patientswithearlysynovitis(definedaslessthan
oneyearduration)evaluatedatoneacademiccenter,60percentwerediagnosedwitheitherrheumatoidarthritis
(RA)oraspondyloarthropathyatpresentationorduringthefollowingyear[3].Theprognosisisrelativelygoodfor
thosewhoremainunclassifiable,withnearlyonehalfofsuchpatientsundergoingremissionandnotrequiringany
pharmacologictherapyatfollowupatoneyear.
Thistopicreviewwilladdresspolyarticularjointpaininadults.Evaluationsoftheadultwithmonoarticularpainand
ofchildrenwithjointpainarepresentedseparately.(See"Overviewofmonoarthritisinadults"and"Evaluationof
thechildwithjointpainand/orswelling".)

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HISTORYAlthoughtheinformationobtainedinthehistoryisseldomsufficienttoleadtoaspecificdiagnosis,it
allowssubstantialreductioninreasonableoptions.Anacutepresentationwithmigratoryarthritisandfever,for
example,ischaracteristicofrheumaticfever,disseminatedgonococcalinfection,andviralarthritis.
MusculoskeletalemergenciesTheevaluationofpolyarticularpainbeginsbyrulingoutpotential
musculoskeletalemergencies.Theseconditionsgenerallyhaveanacutepresentationandaremorecommonly
associatedwithmonoarticularoroligoarticularpain.Someoftheseemergencies,however,canbeseenin
patientswithpolyarticularpain,andfailuretomakethecorrectdiagnosiscouldleadtopermanentharmtothe
patient.Importanthistoricalpointsincludethefollowing[2]:
Hotorswollenjointsmaysuggestinfection(althoughbacterialinfectionmorecommonlypresentswithacute
monoarthritis).
Constitutionalsymptoms(fever,weightloss,malaise)arenonspecificbutraisethesuspicionofinfectionor
sepsis.
Jointpaingreaterthanexpectedfromphysicalfindingsmaybeasymptomofacompartmentsyndrome.
Burningpain,numbness,orparesthesiamaysuggestanacutemyelopathy,radiculopathy,orneuropathy.
JointsymptomsItisimportanttoobtainadetailedhistoryofthecharacterofthejointpain,includingpain
quality,timeofonset,exacerbatingorremittingfactors,andduration.
Thequalityofthepainmaybeusefulindistinguishingmusculoskeletalfromneurologiccauses.Thelatteris
suggestedwhenpainisburningorisaccompaniedbynumbnessorparesthesias.Neuropathicpainisalsolikely
tobeconstant,tobeintensifiedatnight,andtobeunrelatedtomotion.However,anindividualpatientmay
experiencemorethanonetypeofpain.Asanexample,patientswithrheumatoidarthritis(RA)frequentlyhave
neuropathicpainduetocarpaltunnelsyndrome.
Thetwomaincategoriesofarthritis,inflammatoryandnoninflammatory,canoftenbedistinguishedbasedupon
thecharacteranddistributionofjointpain:
Withinflammatoryarthritis,symptomstendtoworsenwithimmobilitythisaccountsforthetypicalmorning
stiffnessandgellingthattypicallyaccompaniesinflammatoryarthritis.
Incontrast,thepainofosteoarthritis(OA),themostcommontypeofnoninflammatoryarthritis,isusually
aggravatedbymotionandweightbearingandisrelievedbyrest.
ThejointinvolvementinRAisusuallysymmetrical,whereasasymmetryisfrequentinOA,especiallyinthe
largejoints.Problemssuchasbursitis,tendinitis,orsprainsandstrainsarealsoasymmetricalinmostcases.
Thedurationofsymptomsmayalsobehelpful.Synovitisthathasbeenpresentforlessthansixweekscould
representaviralarthritisorsystemicrheumaticdisease,whereasalongerdurationwouldincreasethelikelihood
ofthelatter.Theabilitytoaccuratelyclassifypatientswithearlyinflammatoryarthritisisdifficult.Inonestudyof
211patientswithrecentonsetsynovitis,36percentcouldnotbeclassifiedandweredesignatedashaving
undifferentiatedarthropathyafterfollowupof33weeks[4].(See"Specificvirusesthatcausearthritis".)
AssociatedsymptomsThepresenceofextraarticularsymptomsmayhelptonarrowthedifferential
diagnosis.Weaknesssuggestsaneurologicormyopathicdisorder.Ontheotherhand,signsandsymptomsof
multisysteminvolvement(suchasfatigue,rash,adenopathy,alopecia,oralandnasalulcers,pleuriticchestpain,
Raynaudphenomenon,ordryeyesandmouth)arecommoninpatientswithsystemicrheumaticdiseases.Fever,
nightsweats,andweightlossmayalsosuggestsystemicillness.
OthercluesfromthehistoryTheremainderofthehistoryshouldfocusontheusualareas,includingpast
medicalhistory,familyhistory,socialhistory,andsystemreview.Particularattentionshouldbepaidtothe
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following:
FunctionalcapacityThisincludesassessingthepatientsabilitytoperformusualactivitiesofdailyliving.
Changesinfunctionalstatusmayleadtodepression,anxiety,andlossofindependence.
HistoryofjointinjuryApastmedicalhistoryofprevioustrauma,fracture,orsurgicalprocedureson
symptomaticjointsmayhelpidentifythecauseofpain.
RiskfactorsfororahistoryofinfectionForexample,exposuretoorpastinfectionwithviralhepatitismay
suggestthediagnosisofviralarthralgia.ExposuretoticksoryoungchildrenmaysuggestLymediseaseor
parvovirusinfection,respectively.
AcompletemedicationlistAreviewofmedicationsmayleadtoaspecificdiagnosis,suchasdruginduced
lupus,ormayaltertreatmentchoices.
PsychologicstateandsocialsupportsystemThemorechronicconditionscangreatlyaffectthelifeofthe
patientandhisorherfamily.
PHYSICALSIGNSAfteracompletehistory,thephysicalexaminationisusedtofurthernarrowthedifferential
diagnosis.Asanexample,acutelowerextremitypainmayhavemanycauseshowever,septicarthritis,crystal
inducedarthritis,orfractureshouldbesuspectedwhenthepainresultsininabilitytobearweight,orisassociated
withsofttissueswellingandothersignsofinflammationextendingfaraboveorbelowtheinvolvedjoint.
JointexaminationAnimportantobjectiveofthephysicalexaminationistoestablishthepresenceorabsence
ofsynovitis[2].Detectingsynovitisincreasesthelikelihoodofaninflammatoryarthritisorsystemicrheumatic
diseases.Thehallmarksofsynovitisinclude:
Softtissueswelling
Warmthoverajoint
Jointeffusion
Lossofmotion
Reducedactiverangeofmotionwithpreservedpassiverangeofmotionsuggestssofttissuedisorderssuchas
bursitis,tendinitis,ormuscleinjury.Ifbothactiveandpassiverangesofmotionaredecreased,softtissue
contracture,inflammatoryornoninflammatoryjointdisease,orastructuralabnormalityofthejointshouldbe
considered[2].
Jointexaminationisalsohelpfultoconfirmtheabsenceofsynovitisorthepresenceofbonyenlargementor
crepitus,asistypicalofosteoarthritis(OA).
GeneralexaminationFindingsongeneralexaminationmaypointtoasystemiccondition.Thesefindings
includelymphadenopathy,parotidenlargement,oralulcerations,heartmurmurs,pericardialorpleuralfriction
rubs,orfineinspiratoryralesduetointerstitiallungdisease.
Feversuggestsasubsetofinfectiousandrheumaticillnessesincluding[1]:
Infectiousarthritis
Postinfectiousorreactivearthritis(postentericinfection,rheumaticfever)
Systemicrheumaticdisease,includingStillsdisease,vasculitis,orsystemiclupuserythematosus(SLE)
Crystalinducedarthritis(goutandpseudogout)
Otherdiseasessuchascancer,sarcoidosis,andmucocutaneousdisorders
Additionalfindingsmaysuggestaspecificdiseaseprocess.Examplesofsuchfindingsinclude:
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Thepresenceofsubcutaneousnodulesmaybeduetorheumatoidnodulesortophi.
Skinlesionsmaysuggestthatthejointsymptomsareduetopsoriaticarthritis,SLE,viralinfection,orStills
disease.
Eyedisease,includingkeratoconjunctivitissicca,uveitis,conjunctivitis,andepiscleritis,isalsoafeatureof
certainrheumaticillnesses.
Concomitantaxialpainorstiffnesssuggeststhepossibilityofaxialspondyloarthritisoranotherseronegative
spondyloarthritis.Asaresult,spinaltenderness,deformity,andrangeofmotionshouldalwaysbe
ascertainedinpatientswithpolyarticularjointpain.
Inaddition,softtissuetenderpointscharacteristicoffibromyalgiaareparticularlyimportanttoidentifyinpatients
whohavenoobjectiveabnormalitiesinthejoints(see"Clinicalmanifestationsanddiagnosisoffibromyalgiain
adults").However,jointtendernessmayoccurinsomefibromyalgiapatients,andpatientswithvarioustypesof
polyarthritis,includingrheumatoidarthritis(RA),SLE,andLymedisease,mayhavesuperimposedfibromyalgia.
LABORATORYSTUDIESLaboratorystudiesarenotalwaysnecessarytomakeadiagnosisand,infact,can
bemisleading.Asanexample,somepatientswithosteoarthritis(OA)mayhaveabnormalresultsthatactually
reflectotherunrelatedconditions.Inaddition,insomepatientswitharthralgiasandmyalgiaswithoutphysical
findings,managingsymptomsandcarefullyfollowingthepatientoverseveralweeksmaybemoreprudentthan
aninitialbatteryoftests.Laboratorytestingisalsounnecessarywhenamechanicalorextraarticularproblemhas
beenidentified[2].
Whentheinitialhistoryandphysicalexamdonotyieldadiagnosis,however,somediagnostictestingmaybe
indicated.Standardhematologictests,urinalysis,andbiochemicaltests(renalandliverfunction)mayhelpto
identifypatientswithsystemicillnesses.Othermorespecializedtestsarediscussedbelow.
ErythrocytesedimentationrateNonspecificindicatorsofinflammation,suchastheerythrocyte
sedimentationrate(ESR)andCreactiveprotein(CRP),arehelpfulindistinguishingbetweeninflammatoryand
noninflammatoryconditions.However,thesetestsareneverdiagnosticandmaybeabnormalinavastarrayof
infectious,malignant,rheumatic,andotherdiseases[5].TheCRPissometimesamorereliableindicatorofthe
acutephaseresponsethantheESR[6],asthelattermaybeinfluencedbyabnormalredbloodcellmorphology
andahostofotherfactors[5].
Furthermore,therearenumerousexamplesoftheESRyieldingresultsthatarenotconsistentwiththeactual
rheumatologicprocess:
SomepatientswithaninflammatoryrheumaticdiseasehaveanormalESR.Asanexample,inoneseriesof
9,135patientswithactiverheumatoidarthritis(RA),theESRwasnormalin71percent[7].
Innoninflammatoryarthritis,theESRmaybeelevatedbecauseofanotherproblem,suchasrenalfailure,
diabetes,hyperlipoproteinemia,dysproteinemia,oroccultmalignancy.
TheESRmayincreasewithageinthegeneralpopulation[8].Thisphenomenonmaybethebasisfor
apparentESRelevationsinsomeOApatients.
Despitetheselimitations,theESRmayprovideconfirmatoryinformationwhenacertaindiagnosisisfavored
baseduponthehistoryandphysicalfindings.Inanolderpatientwithachingandstiffnessinthehipandshoulder
girdleareas,forexample,theposttestprobabilityofpolymyalgiarheumaticaincreasesiftheESRismarkedly
elevated.However,anormalESRdoesnotprecludethediagnosis.

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AntibodytestsAntibodytestscanidentifyexposuretopotentialpathogens(groupAstreptococcus,viruses
suchasparvovirusorhepatitisBandC,Borreliaburgdorferi)(see"Specificvirusesthatcausearthritis").In
addition,certainautoantibodiesareassociatedwithalimitedgroupofillnessesandmayadddiagnosticspecificity
toaclinicalsuspicionofrheumaticdisease(suchasantinativeDNAorantiSminsystemiclupuserythematosus
[SLE])(see"Antibodiestodoublestranded(ds)DNA,Sm,andU1RNP").Theseantibodytestsshouldnotbe
orderedroutinelybutshouldbereservedforcasesinwhichthereisareasonableclinicalsuspicion[9](see
below).Theindiscriminateuseofpanelsofthesetestswillresultinahighfrequencyoffalsepositiveresultsand
inadditionalexpensiveandunnecessarytesting[911].
AntinuclearantibodyTheantinuclearantibody(ANA)testhashighsensitivitybutlowspecificityforSLE.
Therefore,unlessanothercauseisevident,itisgenerallyappropriatetoorderanANAinpatientswith
polyarthritissinceanegativetestessentiallyrulesoutadiagnosisofSLE.ApositiveANAmayoccur,however,in
manyrheumaticandnonrheumaticillnesses.Thus,apatientwithfewornoclinicalfeaturesofSLEisunlikelyto
havethedisease,eveninthepresenceofapositiveANA.(See"Measurementandclinicalsignificanceof
antinuclearantibodies".)
AdditionalinformationmayhelpclarifythemeaningofapositiveANA.ThehighertheANAtiter,themorelikely
thatthepatienthaseitherSLEoranotherANAassociateddisease[2].Additionalserologictests,suchasanti
doublestranded(ds)DNAantibodies,maybediagnosticoratleastmayfurtherlimitthedifferentialdiagnosis.
RheumatoidfactorRheumatoidfactorshouldbeorderedwhenRAissuspectedduetosignsorsymptoms
ofinflammatoryarthritishowever,thetesthaslimiteddiagnosticvalue[12].Approximatelyonethirdofpatients
withRAremainseronegativethroughouttheircourse[12].Furthermore,patientswithotherinflammatoryor
infectiousdiseases(suchasSLE,infectiveendocarditis,vasculitis,viralinfection)mayhaveapositivetest(table
3).HighrheumatoidfactortitershaveabetterpredictivevalueforthediagnosisofRAandmayalsopredictpoor
outcomes.(See"Originandutilityofmeasurementofrheumatoidfactors".)
AntibodiestocitrullinatedpeptidesAnticitrullinatedpeptide/proteinantibodies(ACPA)arefrequently
foundinpatientswithRA.ACPA,detectedbyanticycliccitrullinatedpeptide(antiCCP)antibodytesting,are
morespecificthanrheumatoidfactorfordiagnosingRAandmaypredicterosivediseasemoreeffectively[13,14].
(See"Biologicmarkersinthediagnosisandassessmentofrheumatoidarthritis",sectionon'Anticitrullinated
peptideantibodies'.)
SerumuricacidconcentrationSerumuricacidlevelsareusuallyelevatedingout,but,sinceasymptomatic
hyperuricemiahasahighprevalenceinthegeneralpopulation,thefindingofhyperuricemiahaslittlediagnostic
value.Inaddition,normaluricacidlevelsarefairlycommonduringanattackofgout,includinginpatientswith
polyarticularinvolvement[15,16],althoughthefindingofauricacidlevelbelowthelowerlimitofthenormal
referencerangewouldmakethediagnosisofgoutmuchlesslikely.
SynovialfluidanalysisSynovialfluidanalysismaybediagnosticinpatientswithbacterialinfectionsor
crystalinducedsynovitis.Synovialfluidanalysisisalsovaluabletopermitclassificationintoaninflammatoryor
noninflammatorycategory,toidentifyhemarthrosis,andtoidentifycrystalsandinfectiousorganisms.Patients
withestablishedrheumaticdiseasepresentaparticularchallengeasitmaybedifficulttodistinguishaflareofthe
underlyingdiseasefromanew,concomitantdisorder,includinginfectiousarthritis.WhiletheAmericanCollegeof
Rheumatology(ACR)clinicalguidelinessuggestthatsynovialfluidanalysisbeperformedinthefebrilepatient
withanacuteflareofestablishedarthritis[2],suchtestingcanberecommendedforanypatient,withorwithout
priorrheumaticdisease,whenthediagnosisisuncertainafterhistory,physicalexamination,andstandard
laboratorytests.Thisisespeciallyimportantwhencrystalinducedarthritisorsepticarthritisaresuspected.(See
"Jointaspirationorinjectioninadults:Techniqueandindications".)

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Thewhitecellcount,differentialcount,cultures,Gramstain,andpolarizedlightmicroscopyarethemostvaluable
studies[2,17].Noninflammatoryfluidsgenerallyhavefewerthan2000whitebloodcells/mm3,withfewerthan75
percentpolymorphonuclearleukocytes(table4)[17].TheACRguidelinessuggestthatunexplainedinflammatory
fluid,particularlyinafebrilepatient,shouldbeassumedtobeinfecteduntilprovenotherwise.(See"Synovialfluid
analysis".)
IMAGINGSTUDIESImagingstudiesareexpensiveandarenotrequiredroutinelyintheevaluationof
polyarticularpain.Evenwhenuseful,itisseldomnecessarytoobtainradiographsofallinvolvedjointsthose
jointswiththehighestyieldinthedifferentialdiagnosisshouldbechosen.Asanexample,ifRAisthesuspected
diagnosis,erosionsarebestvisualizedinthewrist,hand,andfoot.
Inacuteconditions,radiographsusuallylackdiagnosticspecificityandaregenerallynothelpfulforpatientswith
newonsetofrheumatoidarthritis(RA),systemiclupuserythematosus(SLE),gout,tendinitis,orbursitis.In
severalacutesettings,however,plainfilmsmaybeuseful.Chondrocalcinosis,forexample,maybeseenin
calciumpyrophosphatedepositiondisease(see"Clinicalmanifestationsanddiagnosisofcalciumpyrophosphate
crystaldeposition(CPPD)disease").Ontheotherhand,abnormalitiesofthesacroiliac(SI)jointsaretheearliest
radiographicfindinginankylosingspondylitisandservetopointtowardseronegativespondyloarthropathyasthe
causeofperipheralpolyarthritis.Magneticresonanceimaging(MRI)ismoresensitivethanplainfilmradiography
indetectingearlySIjointabnormalities.(See"Diagnosisanddifferentialdiagnosisofankylosingspondylitisand
nonradiographicaxialspondyloarthritisinadults".)
Plainradiographsmayalsobehelpfulinthediagnosisofthefollowingchronicconditions:
InOA,plainfilmscanbeusednotonlytoconfirmthediagnosisbutalsotoassesstheseverity.Radiographs
can,however,benormalinOA,andthefindingofradiographicOAmaynotberelatedtothepatients
symptoms[2].
InRA,marginalerosionsinthejointcanbediagnostic.MRIandultrasoundmaybeabletodetecterosions
beforeplainradiographs[18].
Chronicgoutmayalsocausejointerosions,buttheseoftenhaveanoverhangingedgesuggestiveof
reparativechangesthatdistinguishesthemfromerosionsduetoRA[2].Ultrasoundmayprovidemore
specificinformationthanconventionalradiographsforthediagnosisofgout[19].
Radionuclidescansandotherimagingproceduresareoccasionallyusefulinidentifyinginvolvementofboth
relativelyinaccessiblejoints(eg,hip,SI)andbone(eg,malignancy,infection,Pagetdisease).
TISSUEBIOPSYInsomeinstances,thecorrectdiagnosisinapatientwithpolyarticularpainwilldependupon
atissuebiopsy.Asanexample,synovialbiopsymaybeusefulinthediagnosisoftuberculosis,fungalinfection,
andsarcoidosis.Biopsyofothertissuesmayhelpestablishthepresenceofrheumatoidnodules,Whipple's
disease,vasculitis,andhemochromatosis.
DISEASECOURSEAlthoughitmaynotbepossibletomakeadefinitivediagnosisatthetimeofapatient's
initialpresentationwithpolyarticularpain,someprogresshasbeenmadeinpredictingthediseasecoursefor
thosewithdefinitepolyarthritisofrecentonset.Acombinationofclinical,laboratory,andimagingdatacanhelpto
differentiatepatientslikelytohaveselflimiteddiseasefromthoselikelytohavepersistentarthritis.Prediction
modelsbaseduponpatientswithearlyarthritishaveidentifiedanumberoffeaturesassociatedwithpersistent
and/orerosivedisease,including[2023]:
Durationofsymptomspriortopresentation
Olderage
Malegender
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HighBMI
Durationofmorningstiffness
Numberoftenderorswollenjoints
Involvementoflowerextremities
Elevatedacutephasereactants
Rheumatoidfactor
Anticycliccitrullinatedpeptideantibody
Erosivechangeonbaselineradiograph
Humanleukocyteantigen(HLA)DRB1sharedepitopealleles
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandare
comfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
BeyondtheBasicstopics(see"Patienteducation:Arthritis(BeyondtheBasics)")
SUMMARYWhenthehistoryandphysicalexaminationareusedinconcertwithselectedsequentiallaboratory
andimagingstudies,thecauseofpolyarticularjointpaincanbeidentifiedinmostcases.TheAmericanCollege
ofRheumatology(ACR)guidelinesmakethefollowinggeneralrecommendationsaftercompletionofathorough
historyandphysicalexamination(algorithm1)[2]:
Inthepresenceofsynovitisandsymptomsgreaterthansixweeksinduration,considerrheumatoidarthritis
(RA)andothersystemicrheumaticdiseases(table1).Acompletebloodcount,erythrocytesedimentation
rate(ESR),rheumatoidfactor,anticycliccitrullinatedpeptide(antiCCP),antinuclearantibody(ANA),
plasmacreatinineconcentration,andurinalysisshouldbeobtained.Jointaspirationshouldbeconsideredif
aneffusionispresentandifthediagnosisisuncertain,especiallyifsepticorcrystalinducedarthritisis
suspected.
Inthepresenceofsynovitisandsymptomslessthansixweeksinduration,acompletebloodcount,
measuresofliverfunctiontests,and,insomecases,serologictestingforhepatitisBandCandparvovirus
maybehelpful(table2).
Intheabsenceofsynovitis,thephysicalexaminationfindingoftenderpointssuggestsfibromyalgiaor
multiplesitesofbursitisortendinitisfurtherdiagnostictestingisnotneeded.(See"Clinicalmanifestations
anddiagnosisoffibromyalgiainadults"and"Bursitis:Anoverviewofclinicalmanifestations,diagnosis,and
management".)
Intheabsenceofsynovitisandtenderpoints,considertheremainderofthedifferentialdiagnosis(algorithm
1)andconsiderliverfunctiontests,hepatitisBandCserology,radiographs,andserumlevelsofthyrotropin
(TSH),calcium,albumin,andalkalinephosphatase.
Insomepatientspresentingwithpolyarticularpain,thedifferentialmaybereducedtotwoorthreereasonable
possibilities.Closefollowupmaysoonrevealthecorrectdiagnosis.
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ACKNOWLEDGMENTTheeditorialstaffatUpToDatewouldliketoacknowledgeRobertPinals,MD,who
contributedtoanearlierversionofthistopicreview.
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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persistent(erosive)arthritis.ArthritisRheum200246:357.
21.AlvesC,LuimeJJ,vanZebenD,etal.DiagnosticperformanceoftheACR/EULAR2010criteriafor
rheumatoidarthritisandtwodiagnosticalgorithmsinanearlyarthritisclinic(REACH).AnnRheumDis2011
70:1645.
22.HaYJ,ParkYB,SonMK,etal.Predictivefactorsrelatedtoprogressiontowardrheumatoidarthritisin
Koreanpatientswithundifferentiatedarthritis.RheumatolInt201232:1555.
23.deRooyDP,vanderLindenMP,KnevelR,etal.Predictingarthritisoutcomeswhatcanbelearnedfrom
theLeidenEarlyArthritisClinic?Rheumatology(Oxford)201150:93.
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GRAPHICS
Majorcausesofinflammatorypolyarthritis
Infectiousarthritis

Crystalinducedarthritis

Bacterial

Systemicrheumaticillnesses

Lymedisease

Systemiclupuserythematosus

Bacterialendocarditis

Systemicvasculitis

Viral

Systemicsclerosis

Otherinfections

Postinfectious(reactive)arthritis
Rheumaticfever

Polymyositis/dermatomyositis
Still'sdisease

Behet'sdisease

Reactivearthritis

Relapsingpolychondritis

Entericinfection

Autoinflammatorydisorders

Otherseronegativespondyloarthritides
Ankylosingspondylitis

Othersystemicillnesses
Sarcoidosis

Psoriaticarthritis

Palindromicrheumatism

Inflammatoryboweldisease

FamilialMediterraneanfever

Rheumatoidarthritis

Malignancy

Inflammatoryosteoarthritis

Hyperlipoproteinemias

Graphic74266Version4.0

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Virusesthatcausearthralgia

Commonlyseen
HepatitisBandC
Rubellaandvaccine
Parvovirus
Alphaviruses
Denguevirus

Occasionallyseen
EpsteinBarrvirus
Humanimmunodeficiencyvirus
Mumps
HepatitisA
Coxsackievirus
Echovirus
Adenovirus
Varicellazoster
Herpessimplex
Cytomegalovirus
Graphic73403Version5.0

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Evaluationofpolyarthritisorpolyarthralgia

Aninitialapproachtothepatientwithpolyarticularjointsymptoms.
CCP:citrullinecontainingpeptideCBC:completebloodcellcountESR:erythrocytesedimentationrateRF:rheumatoid
factorANA:antinuclearantibodies.
AdaptedfromAmericanCollegeofRheumatologyAdHocCommitteeonClinicalGuidelines,ArthritisRheum199639:1.
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Themajornonrheumaticdiseasesassociatedwithrheumatoidfactor(RF)
positivity
Condition
Aging(>age60)

FrequencyofRF,percent
5to25

Infection
Bacterialendocarditis*

25to50

HepatitisBorhepatitisC*

20to75

Tuberculosis

Syphilis*

Upto13

Parasiticdiseases

20to90

Leprosy*

5to58

Otherviralinfection*

15to65

Pulmonarydisease
Sarcoidosis*

3to33

Interstitialpulmonaryfibrosis

10to50

Silicosis

30to50

Asbestosis

30

Miscellaneousdiseases
Primarybiliarycholangitis*

45to70

Malignancy*

5to25

Aftermultipleimmunizations

10to15

*Referstodisordersthatmaycausesymptomssuggestiveofrheumatoidarthritis.Thebestdocumentedexamplesofviral
infection(inadditiontohepatitisBandC)arerubella,mumps,influenza,andHIV.Chagas'disease,Leishmaniasis,
onchocerciasis,andschistosomiasisaremajorparasiticdiseases.Bcellneoplasmsarethemostcommonmalignancies.
Reprintedbypermissionfromthepublisherfrom:ShmerlingRH,DelbancoTL.Therheumatoidfactor:Ananalysisofclinical
utility,AmJMed199191:528.Copyright1991byExcerptaMedicaInc.
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Categoriesofsynovialfluidbaseduponclinicalandlaboratoryfindings
Measure

Normal

Noninflammatory

Inflammatory

Septic

Hemorrhagic

Volume,mL(knee)

<3.5

Often>3.5

Often>3.5

Often
>3.5

Usually>3.5

Clarity

Transparent

Transparent

Translucent
opaque

Opaque

Bloody

Color

Clear

Yellow

Yellowto
opalescent

Yellowto
green

Red

Viscosity

High

High

Low

Variable

Variable

Whitebloodcell,permm 3

<200

0to2000

>2000

>2000

200to2000

Polymorphonuclear
leukocytes,percent

<25

<25

50

75

50to75

Culture

Negative

Negative

Negative

Often
positive

Negative

Graphic76506Version6.0

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ContributorDisclosures

RobertHShmerling,MD Nothingtodisclose RavinderNMaini,BA,MBBChir,FRCP,FMedSci,


FRS Speaker'sBureau:Genentech[HistoryofantiTNFtherapy].PatentHolder:Inventorsshareofroyalties
awardedbyTheKennedyTrustforRheumatologyResearch,UK,onantiTNFtherapypatents,byAbbvie,
Centocor/Janssen,Hospira,andCelltrion. MonicaRamirezCurtis,MD,MPH Nothingtodisclose
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconformto
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