08/11/2017 Clinical manifestations and diagnosis of bromyalgia in adults - UpToDate

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Clinicalmanifestationsanddiagnosisoffibromyalgiainadults

Author: DonLGoldenberg,MD
SectionEditor: PeterHSchur,MD
DeputyEditor: PaulLRomain,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Oct2017.|Thistopiclastupdated:Sep14,2016.

INTRODUCTIONFibromyalgia(FM)isacommoncauseofchronicwidespreadmusculoskeletalpain,often
accompaniedbyfatigue,cognitivedisturbance,psychiatricsymptoms,andmultiplesomaticsymptoms.The
etiologyofthesyndromeisunknown,andthepathophysiologyisuncertain[1,2].Despitesymptomsofsoft
tissuepainaffectingthemuscles,ligaments,andtendonsthereisnoevidenceoftissueinflammation.

FM,likeotherfunctionalsomaticsyndromes,hasbeenacontroversialcondition[1,2].Patientslookwell,there
arenoobviousabnormalitiesonphysicalexaminationotherthantenderness,andlaboratoryandradiologic
studiesarenormal.Thus,theroleoforganicillnesshadbeenquestioned,andFMwasoftenbeenconsidered
tobepsychogenicorpsychosomatic.However,ongoingresearchsuggeststhatFMisadisorderofpain
regulation,oftenclassifiedasaformofcentralsensitization[3].(See"Pathogenesisoffibromyalgia".)

FMisoftenassociatedwithotherconditionsthatmaycausemusculoskeletalpain,disruptionofsleep,or
psychiatricsymptomsfeaturesoftheseconditionsmayalsomimicFM,andthepresenceofsuchdisorders
shouldbeconsideredinthediagnosticevaluation.(See"Differentialdiagnosisoffibromyalgia".)

TheclinicalmanifestationsanddiagnosisofFMwillbereviewedhere.ThedifferentialdiagnosisofFMis
discussedindetailseparately,asarethepossiblepathogenicmechanismsandtreatmentofFMinadults,and
theclinicalmanifestations,diagnosis,andtreatmentofFMinchildrenandadolescents.(See"Differential
diagnosisoffibromyalgia"and"Pathogenesisoffibromyalgia"and"Initialtreatmentoffibromyalgiainadults"
and"Treatmentoffibromyalgiainadultsnotresponsivetoinitialtherapies"and"Fibromyalgiainchildrenand
adolescents:Clinicalmanifestationsanddiagnosis"and"Fibromyalgiainchildrenandadolescents:Treatment
andprognosis".)

EPIDEMIOLOGYFibromyalgia(FM)isacommoncauseofchronicpainandthemostcommoncauseof
generalized,musculoskeletalpaininwomenbetweenagesof20and55yearsintheUnitedStatesandin
othercountries,theprevalenceisapproximately2to3percentandincreaseswithage[47].FMismore
commoninwomenthanmenandoccursinbothchildrenandadults[48].Itissixtimesmorecommonin
womeninreportsfromspecialtyclinics,althoughthefemalepredominanceisnotasstrikinginthecommunity
andwhenusingsurveycriteriathatdonotrequireatenderpointexamination[6].Thediagnosismaybe
underrecognizedinclinicalpracticeprevalenceestimatesinoneUScountyusingsurveyswithstandardized
criteriawerehigherthanestimatesbaseduponmedicalrecorddocumentationofthediagnosis(6.4versus
1.1percent)[4].Prevalencestudiesinadolescentshavebeenverysimilartothoseinadults[8].

Initiallytermedfibrositis,FMwasdescribedinFranceandEnglandinthemid19thcentury.Bytheendofthe
20thcentury,manyrheumatologistsrecognizedFMasadiscretesyndrome,anddiagnosticclassification
criteriawereproposed,evaluated,andthenvalidated.Usingsuchcriteria,FMhasbeenrecognized
worldwideasexamples,reportsfoundaprevalenceof1.6percentinFrance,2.5percentinBrazil,and3.6
percentinBangladesh[911].

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Atleast10percentofthegeneralpopulationhaschronicwidespreadpain,andthemajorityofthese
individualsdonothaveanyspecificdiseaseorstructuralabnormalitytoaccountforthepainmanyofthese
patientshavesymptomsandfindingscompatiblewithFM.Morethan40percentofpatientsreferredtoa
tertiarypainclinicmeetthediagnosticcriteriaforFM[12].

CLINICALMANIFESTATIONSFibromyalgia(FM)ischaracterizedbywidespreadmusculoskeletalpain
andfatigue,oftenaccompaniedbyothersomaticsymptoms,aswellascognitiveandpsychiatricdisturbances
[1,2,13].Physicalexaminationrevealstendernessinmultiplesofttissueanatomiclocations.Laboratory
testingisnormalintheabsenceofotherillnesses(table1).

SomedisordersareseeningreaterfrequencyinpatientswithFMthaninthegeneralpopulation.Certainof
theseconditionsmayclusterwithFMandhavesomecommonpathophysiologicfeatures,suchasirritable
bowelsyndrome(IBS)andmigraine.Additionally,certainfeaturesofothercommonlyassociateddisorders
maysimulateorexacerbatethesymptomsofFM,suchasmusculoskeletalpaininpatientswithchronicforms
ofarthritisandsleepdisturbanceandfatigueinpatientswithdepression,obstructivesleepapnea,orrestless
legssyndrome.(See'Coexistingdisorders'below.)

SymptomsCharacteristiccomplaintsincludechronicwidespreadmusculoskeletalpainnumbness,
tingling,andotherabnormalsensationsfatigueandpoorsleepcognitiveandpsychiatricsymptoms
headacheandavarietyofothersymptoms:

WidespreadmusculoskeletalpainThecardinalmanifestationofFMiswidespreadmusculoskeletal
paininvolvingbothsidesofthebodyandpresentaboveandbelowthewaist.However,thepainmay
initiallybelocalized,oftenintheneckandshoulders.Commonpatientdescriptionsinclude"IfeelasifI
hurtallover,"or"itfeelsasifIalwayshavetheflu."Patientstypicallydescribepainpredominantly
throughoutthemuscles,butoftenstatethattheirjointshurt,andsometimesdescribejointswelling,
althoughsynovitisisnotpresentonexamination[1,2,14].

FatigueTheotheruniversalsymptomofFMisfatigue[15].Thisisespeciallynotablewhenarisingfrom
sleep,butisalsomarkedinthemidafternoon.Seeminglyminoractivitiesaggravatethepainandfatigue,
althoughprolongedinactivityalsoheightenssymptoms.Patientsarestiffinthemorningandfeel
unrefreshed,eveniftheyhaveslept8to10hours.PatientswithFMcharacteristicallysleep"lightly,"
wakingfrequentlyduringtheearlymorningandhavedifficultygettingbacktosleep.Acommonquoteis
"NomatterhowmuchsleepIget,itfeelslikeatruckranmeoverinthemorning."

CognitivedisturbancesCognitivedisturbancesarepresentinthemajorityofpatients.Thecognitive
disturbancesareoftenreferredtoas"fibrofog."Patientstypicallydescribeproblemswithattentionand
difficultydoingtasksthatrequirerapidthoughtchanges.Neuropsychologicaltestingreveals
abnormalitiesthataresomewhatdifferentthanthosefoundinpsychiatricdisorders[16].

PsychiatricsymptomsDepressionand/oranxietyarepresentin30to50percentofpatientsatthe
timeofdiagnosis[1722].InaCanadiangeneralpopulationsampleof127,000,those1635subjectswith
FMwerethreetimesmorelikelytohavedepressioncomparedwithsubjectswithoutFM[17].Twentytwo
percentoftheFMgrouphadconcurrentmajordepression.Depressioninthatgroupcorrelatedwith
youngerage,femalegender,unmarriedstatus,foodinsecurity,numberofchronicconditions,and
limitationsinactivities.TwofifthsofthosewithdepressionandFMhadnotdiscussedmentalhealth
concernswithanyhealthprofessionalsinthepreviousyear(see'Coexistingdisorders'below).Mood
disordersarealsoassociatedwithseverityofFMsymptoms[2022].

HeadacheHeadachesarepresentinmorethan50percentandincludemigraineandmuscular
(tension)types[23,24].Inanambulatorytertiaryheadacheclinic,FMwaspresentin174of889patients
(20percent),including44percentofthosewithchronic,tensiontypeheadaches[23].FMcomorbidity
correlatedwithfrequencyofheadaches,anxiety,pericranialtenderness,poorsleep,andphysical
disability.FMisespeciallycommoninpatientswithepisodicmigraine[24].

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ParesthesiasPatientsalsooftenreportparesthesias,includingnumbness,tingling,burning,or
creepingorcrawlingsensations,especiallyinbotharmsandbothlegs.However,unlessaconcurrent
neurologicdisorder,suchascarpaltunnelsyndromeoracervicalradiculopathy,ispresent,adetailed
neurologicevaluationorformaltestingisusuallyunremarkable.

OthersymptomsanddisordersPatientsalsomayhaveavarietyofpoorlyunderstoodpain
symptoms,includingabdominalandchestwallpain,suchassymptomsofcostochondritissymptoms
suggestiveofIBSandpelvicpainandbladdersymptomsoffrequencyandurgencysuggestiveofthe
interstitialcystitis/painfulbladdersyndrome(formerlyfemaleurethralsyndrome)[15].(See"Clinical
manifestationsanddiagnosisofirritablebowelsyndromeinadults"and"Pathogenesis,clinicalfeatures,
anddiagnosisofinterstitialcystitis/bladderpainsyndrome".)

Othercommoncomplaintsincludeoculardryness,multiplechemicalsensitivityand"allergic"symptoms,
palpitations,dyspnea,vulvodynia,dysmenorrhea,sexualdysfunction,weightfluctuations,nightsweats,
dysphagia,dysgeusia,palpitationsandorthostaticintolerance[15,25,26].

Someindividualscommonlyreportthatparticularweatherconditionsorchangesintheweathermay
aggravatesymptoms,butconsistenteffectsofsuchconditionsupondailypainorfatiguehavenotbeen
foundinmoststudies[27].Asanexample,adetailedstudyoftheinfluenceofweatheronsymptomsof
painandfatigueinvolving403womenwithFMfoundastatisticallysignificantbutsmalleffectofweather
uponeitherpainorfatigue[27].

PhysicalfindingsInpatientswithFM,theonefindingthatisusuallypresentonphysicalexaminationis
tendernessinsofttissueanatomiclocations(figure1).However,theextentandseverityofthesefindingsmay
varyovertimeandfromdaytoday.Thetenderpointexaminationrequiresthattheexaminerknowswhereto
palpateandhowmuchpressuretoapply:

Theamountofpressureappropriatefordetectingthesetenderpointsshouldequal4kg/cm,whichis
enoughtowhitenthenailbedoftheexaminer'sfingertip.

Theninepairsoftenderpointsusedforthe1990AmericanCollegeofRheumatology(ACR)
ClassificationCriteria(see'1990ACRclassificationcriteria'below)areatlocationsthatmostprimary
carecliniciansandspecialistsroutinelyevaluateinpatientswithsofttissuecomplaints(figure1).These
locationsincludetheuppermidtrapeziusmuscle,thelateralepicondyle(thesocalledtenniselbow
location),thesecondcostochondraljunction(thesiteofcostochondritis),thegreatertrochanter(thesite
oftrochantericbursitisofthehip),andothersites.

FMpatientsaretypicallynotastenderinthesocalledcontrollocations,suchasoverthethumb,themid
forearm,andtheforehead,whenthesecontrolareasarepalpatedinasimilarfashiontothedefinedFM
tenderpoints.Similarly,thejointexaminationmayrevealsometendernessoverthejointsandjointlines
themselves.

Theneurologicevaluationsometimesrevealsminorsensoryandmotorabnormalities,intheabsenceof
anothercondition[28].

LaboratorytestingandotherstudiesFMdoesnotcauseanyabnormalitiesinroutineclinicallaboratory
testingorimaging.However,abnormalitieshavebeenidentifiedinresearchstudiesusingspecialized
neuroimaging(eg,functionalmagneticresonanceimaging[MRI])andothertechniquesthatrevealdistinctions
betweenpatientswithFMandcontrolsubjects.Researchstudieshavealsofoundthatasubsetofpatients
withFMhaveabnormalitiesonskinbiopsiessuggestiveofsmallfiberneuropathicchangesthemeaningof
thesefindingsisuncertain.(See"Pathogenesisoffibromyalgia",sectionon'Alteredpainprocessing'and
"Pathogenesisoffibromyalgia",sectionon'Peripheralpainmechanisms'.)

DIAGNOSISPatientswithsymptomsofchronicwidespreadpainshouldbesuspectedoffibromyalgia(FM)
andundergoevaluationtoconfirmorexcludethediagnosis(see'Clinicaldiagnosis'belowand'Diagnostic

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evaluation'below).TypicalpatientcomplaintsthatshouldraisesuspicionofFMareIhurtalloverorItfeels
likeIalwayshavetheflu(table2).

ClinicaldiagnosisThediagnosisofFMisbasedprimarilyuponthepatient'ssymptomsofwidespread
pain,typicallyreportedinthemusclesandjoints,andfindingsofmultipletenderpointsincharacteristicsoft
tissuelocations(figure1),intheabsenceofevidenceonphysicalexaminationandlaboratorytestingofjoint
ormuscleinflammationthatwouldexplainthepatientssymptoms.Aspecificnumberoftenderpointsisnot
requiredtomakethediagnosisinclinicalpractice.(See'Diagnosticevaluation'belowand'1990ACR
classificationcriteria'below.)

Othercommonfeaturessupportingthediagnosisincludefatigueandnonrestorativesleep,cognitive
disturbances,andthecoexistenceofotherdisordersoftenseeninassociationwithFM,includingdepression,
anxiety,irritablebowelsyndrome(IBS),bladderirritability,obstructivesleepapnea,andrestlesslegs
syndrome.(See'Symptoms'aboveand'Coexistingdisorders'below.)

FM,likeheadacheorIBS,willcontinuetobeacontroversialdiagnosisbecauseofalackofclinicallyapparent
objectivechanges,andtherehasbeencontroversyregardingtheutilityofthediagnosisofFM.Although
somehavearguedthatprovidingadiagnosticlabeltoeverydaysymptomsincreasesillnessbehavior,there
arenowmorestudiessuggestingthatpatientsimproveafteradiagnosisandthereissignificantsavingof
healthcaredollars[29].

DiagnosticevaluationThediagnosticevaluationincludesathoroughhistoryandphysicalexamination,
togetherwithlimitedlaboratorytestingtoexcludeotherconditions(table2andalgorithm1).Thediagnostic
evaluationisusuallystraightforwardandshouldneverbea"fishing"expeditiontoexcludeeverypotential
causeofpainandfatigue[1,2].

HistoryAthoroughmedicalhistoryshouldbeobtained.Particularattentionshouldfocuson:

SymptomsofFM,includingchronic,widespreadmusculoskeletalpainlastingatleastthreemonths
(oftenformanyyears)ahistoryoftendernesstotouchfatiguesleep,cognitive(eg,problemswith
attentionandclarityofthought),andpsychiatricdisturbancesparesthesiasproblemswithbalance
andsensitivitytonoises,light,odors,andcold(see'Symptoms'above)

AhistoryofconditionsthatmaybeassociatedwithFM,includingdepressivedisordersanxiety
disordersposttraumaticstressdisorderchronicfatiguesyndrome(CFS),alsoknownassystemic
exertionintolerancedisease(SEID)obstructivesleepapnearestlesslegssyndromeotherfactors
thatmaydisruptsleepchronicorrecurrentheadaches(includingmigraine)bladderirritability
Raynaudphenomenonsymptomsofautonomicdysfunction(eg,orthostatictachycardia)andother
painandfunctionalsomaticsyndromessuchasvulvodyniaandtemporomandibularsyndrome(see
'Symptoms'aboveand'Coexistingdisorders'below)

AhistoryofotherconditionsthatmaycausemusculoskeletalpainandcoexistwithormimicFM,
includinginflammatoryrheumatologicdisorders(eg,rheumatoidarthritis[RA],systemiclupus
erythematosus,spondyloarthritis),noninflammatoryrheumaticdiseases(eg,osteoarthritis),localized
painsyndromes,andthyroiddisease(see'Differentialdiagnosis'belowand'Coexistingdisorders'
below)

PhysicalexaminationAthoroughphysicalexaminationshouldbeperformed,withparticularattentionto
acarefuljointandneurologicexamination,bothtoidentifyfindingstypicalofFM(eg,tenderpointsin
characteristiclocations(figure1))andtoexcludeotherillnesspresentingwithsimilarsymptoms,aswell
astodetectfindingssuggestiveofothersimilarorrelatedconditionsthatmaycausemusculoskeletal
painandfatigue(see'Physicalfindings'aboveand'Differentialdiagnosis'belowand'Coexisting
disorders'below).Theneurologicevaluationmaysometimesrevealminorsensoryandmotor
abnormalities,intheabsenceofanothercondition[28].

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WhenevaluatingthetendernessoftheninepairsofspecificFMpoints,thesocalledcontrollocations,
suchasoverthethumb,themidforearm,andtheforehead,shouldalsobepalpatedinasimilarfashion,
asthesecontrollocationsaretypicallynotastender.Ajointexaminationshouldalwaysbedone,looking
foranysynovitisandalsopalpatingfortendernessoverthejointsthemselves.

LaboratorytestingThereisnodiagnosticlaboratorytestorradiographicorpathologicfinding,and
testingshouldbekepttoaminimum.Often,subspecialtyreferralismorecosteffectivethanordering
multiplelaboratoryandimagingstudiesifanotherconditionortypeofdisorderissuspected.Testingis
doneprimarilytoexcludeanassociateddiseaseoranotherillnessthatmaymimicFM(table2),because
FMitselfdoesnotcauseanyabnormalitiesinlaboratorytestingorimaging.Weusethefollowing
approachtolaboratorytesting:

Weobtainacompletebloodcount(CBC)andanerythrocytesedimentationrate(ESR)oraC
reactiveprotein(CRP)forinitiallaboratoryevaluation.SinceFMisnotaninflammatorycondition,
normalacutephasereactantsimmediatelyprovideconfidencethatanoccultinflammatorydisorderis
unlikely.

Serologictests,suchasantinuclearantibodyandrheumatoidfactor,shouldbeobtainedonlyifthe
historyandphysicalexaminationsuggestaninflammatory,systemicrheumaticdisease.Thesetests
areoftenpositiveinotherwisehealthypeopleandhaveverypoorpredictivevalueunlessthereis
significantclinicalsuspicionofasystemicrheumaticdisease.(See"Measurementandclinical
significanceofantinuclearantibodies",sectionon'ClinicallimitationsofANAtesting'.)

Inpatientswithanysuspicionofthyroiddiseaseorinflammatorymusclediseaseweorderthyroid
functiontestsoracreatinekinase,respectively.

ThereisnoevidencethatorderingviraltestssuchasantibodiestotheEpsteinBarrvirusorordering
vitaminDlevelsarehelpfulinthediagnosisofFM.LowvitaminDlevelsarecommoninpatientswith
chronicpain.

AdditionalevaluationFindingsontheinitialevaluationwilldeterminewhatadditionalevaluationmaybe
needed.Asexamples:

Patientswithsymptomsofobstructivesleepapneaandrestlesslegsorrepetitivelimbmovementsshould
bereferredforaformalsleepevaluation,whichmayincludeanovernightpolysomnogram[30,31].Sleep
apneahasbeenobservedmoreofteninmaleswithFM[31].(See"Clinicalpresentationanddiagnosisof
obstructivesleepapneainadults"and"Clinicalfeaturesanddiagnosisofrestlesslegssyndrome/Willis
Ekbomdiseaseandperiodiclimbmovementdisorderinadults".)

Patientssuspectedofanundiagnosedpsychiatricdisorder,suchasdepressionoranxiety,should
undergofurtherevaluationandtreatmentbyanexpertexperiencedintheseconditions[19].(See
"Unipolardepressioninadults:Assessmentanddiagnosis"and"Bipolardisorderinadults:Assessment
anddiagnosis"and"Generalizedanxietydisorderinadults:Epidemiology,pathogenesis,clinical
manifestations,course,assessment,anddiagnosis".)

Autonomicnervoussystemdysfunction,whichmaypresentwithsymptomsoforthostasis,tachycardia,or
palpitations,hasbeennotedinpatientswithFM[32].However,therearenoappropriatescreeningtests
otherthanbloodpressureandheartratereadingswhenpatientsarerecumbentandstanding.Inselected
individualswhoexhibitthesefindings,referraltoanexpert,suchasacardiologistorneurologist,is
indicatedforfurtherevaluationand,ifneeded,moreformaltestssuchastilttabletesting.(See"Upright
tilttabletestingintheevaluationofsyncope",sectionon'Tilttabletestingprocedure'and"Postural
tachycardiasyndrome"and"Mechanisms,causes,andevaluationoforthostatichypotension"and"Sinus
tachycardia:Evaluationandmanagement"and"Overviewofpalpitationsinadults".)

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ClassificationcriteriaandproposeddiagnosticcriteriaInanattempttoprovidesomehomogeneityin
patientpopulationsinclinicalstudies,variousclassificationcriteriaforFMhavebeendevelopedandtested.
Additionalcriteriasetshavebeenproposedandundergonesomeevaluationasclassificationcriteriaand
potentiallyforclinicaluseasdiagnostictools.

1990ACRclassificationcriteriaTheAmericanCollegeofRheumatology(ACR)ClassificationCriteria
forFibromyalgiawerepublishedin1990andhavebeenusedinmostclinicalandtherapeutictrials[33].They
arelessusefulfordiagnosingFMinroutineclinicalpractice.

TheACRcriteriawerebaseduponexpertrheumatologists'opinionsregardingtheoptimalhistoricaland
physicalfindingsthatcoulddifferentiatepatientswithFMfromthosewithotherrheumaticdiseasesandforms
ofchronicpain.Thesecriteriawerethenfieldtestedinanumberofacademicrheumatologyclinicsandoffice
practices.

Thefinal1990ACRFMclassificationcriteriaincluded:

Symptomsofwidespreadpain,occurringbothaboveandbelowthewaistandaffectingboththerightand
leftsidesofthebody
Physicalfindingsofatleast11of18definedtenderpoints(figure1)

Thesesimplecriteriahadgreaterthan85percentsensitivityandspecificityfordifferentiatingpatientswithFM
fromthosewithotherrheumaticdiseases.

Inofficepractice,thediagnosisofFMcanbemadeeveniffewerthan11of18tenderpointsarepresent,
providedthatthehistoryisconsistentwithFMandthatthemajordifferentialdiagnoseshavebeenexcluded
(see'Clinicaldiagnosis'above).Thetenderpointsrepresentheightenedpainperceptionratherthansitesof
inflammationortissuepathology.Thus,theyareproxiesfordetectingwidespreadpain,andtheexactnumber
necessarytodiagnoseFMclinicallyissomewhatarbitrary.Itisimportanttorecognizethattheclassification
criteriawerevalidatedforlargepatientpopulationsandshouldbeusedprimarilyinclinicalresearchand
epidemiologicstudiesofFM.

2010ACRpreliminarydiagnosticcriteriaSomeinvestigatorshaveadvocatednotusingthetender
pointexaminationaspartoftheFMdiagnosticcriteriaandrelyingonlyuponsymptoms[34]inpractice,
tenderpointcountsareoftennotobtained,andmostclinicianshavenotbeentrainedinthetenderpoint
examination,whichhasraisedconcernsabouttheaccuracyofthediagnosisbynonspecialists.The2010
ACRpreliminarydiagnosticcriteria(2010criteria)forFM(table3)provideanalternativeapproachto
diagnosisandclassification,whichdoesnotrequireatenderpointexamination,butdoesprovideascalefor
measurementoftheseverityofsymptomsthatarecharacteristicofFM[34].Thesecriteriaalsorecognizethe
importanceofcognitiveproblemsandsomaticsymptomsinpatientswithFMthatwerenotconsideredinthe
1990ACRclassificationcriteria.

The2010criteriamaybeusedinpatientswithsymptomspresentatasimilarlevelforatleastthreemonths,
andnootherdisorderthatwouldotherwiseexplainthepain.Theycombineawidespreadpainindex(WPI)
andasymptomseverity(SS)scaleformakingthediagnosisofFM(table3).TheWPIisameasureofthe
numberofpainfulbodyregionsfromadefinedlistof19areas.TheSSscoreincludesanestimateofthe
degreeoffatigue,wakingunrefreshed,andcognitivesymptoms,andthenumberofsomaticsymptomsin
general.TheSScanalsobeusedfortheassessmentofpatientswithcurrentorpreviousFMorfor
longitudinalevaluation.

The2010criteriashowedgoodcorrelationwiththe1990ACRcriteria(see'1990ACRclassificationcriteria'
above),andsincetheycanbeselfadministered,thesenewcriteriawillbemorepracticalforpopulation
basedstudiesofchronicwidespreadpain.Theseandsimilarcriteriamaybeparticularlyusefulforclinicians
whoareinexperiencedinperformingtenderpointexaminations,asadditionaldatapointsindifficultcases,
andmaybeusefulintheprimarycaresettingtodeterminetheneedforrheumatologyreferralfordiagnosis
[35].However,thesequestionnairebasedcriteriaalonecannotbeusedforestablishingthediagnosisofFM,
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andtheyrequireadditionalvalidationindifferentpatientpopulations(eg,primarycaresettingsandpatients
withotherrheumaticdiseases).

Amodificationofthe2010criteria,the2011modificationofthe2010ACRpreliminarycriteria(2011modified
criteria),wasthendeveloped[36].Thesecriteriacanbeselfadministeredandwererecommendedprimarily
forepidemiologicstudies[36].Inonestudy,these2011modifiedcriteriahadsensitivityandspecificityforFM
of90.2and89.5percent,respectively,amongpatientsreferredtoarheumatologist,typicallyforwidespread
pain,fromaprimarycarepractice[37].Furthermodificationofthescoringincreasedthesensitivityand
specificityto93.1and91.7percent,respectively.Applyingthe1990,the2010,orthe2011modifiedFM
criteriachangedtheprevalenceofFMasmuchasfourfold[6].TheprevalenceofFMwas1.7withthe1990
criteriaand1.2withthe2010criteria,but5.4withthe2011modifiedcriteria.Thesemodifiedcriteriaidentified
agreaterproportionofmenwithFMandweremoreinfluencedbysomaticsymptomsthanbypain[6].

DIFFERENTIALDIAGNOSISThemultiplenonspecificsymptomsoffibromyalgia(FM)canmimicmany
otherconditions,andconsiderationofthedifferentialdiagnosisisimportantinmakingthediagnosisofFM.
Thehistoryandphysicalexamination,aswellaslimitedlaboratorytesting,areusuallysufficientto
differentiateFMfromtheseotherconditions,suchassystemicinflammatoryarthropathies,spondyloarthritis,
systemicautoimmune(connectivetissue)disorders,polymyalgiarheumatica,inflammatorymyopathy,and
hypothyroidism(table4).AdetaileddiscussionofthedifferentialdiagnosisofFMispresentedseparately.
(See"Differentialdiagnosisoffibromyalgia".)

COEXISTINGDISORDERSSeveralgroupsofdisordersmayoccurinassociationwithfibromyalgia(FM)
moreoftenthanexpectedbychancealone.Somefeaturesoftheseconditionsmaysimulateorexacerbate
thesymptomsofFM,suchasmusculoskeletalpaininpatientswithchronicformsofarthritisandsleep
disturbanceandfatigueinpatientswithdepression,obstructivesleepapnea,orrestlesslegssyndrome.
Recognitionandeffectivetreatmentofthesecomorbiditiescanpotentiallycontributetosymptomaticreliefin
patientswithFM.Theseconditionsinclude:

FunctionalsomaticsyndromesandrelateddisordersFMisoftenpresentinpatientstogetherwith
othercommonfunctionalsomaticsyndromes,includingchronicfatiguesyndrome(CFS),alsoknownas
systemicexertionintolerancedisease(SEID)irritablebowelsyndrome(IBS)migraineand
temporomandibulardisorder(TMD),aswellaschronicbladderandpelvicpainsyndromes[15,3841].
TheprevalenceofFMineachofthesedisordersvariesfrom20to50percent[3841],and30to70
percentofpatientswithFMmeetcriteriaforCFS/SEIDandIBS[15,42,43].

Demographic,clinical,andpotentialpathophysiologiccharacteristicsofCFS/SEID,IBS,andother
functionalsomaticsyndromesareverysimilartothoseofFM,andpatientswithFMmayreceivemultiple
diagnosesaccordingtosubspecialtyreferralpatterns,iftheclinicianscaringforthepatientarediagnostic
"splitters."Ontheotherhand,theexactlabelmaybelessimportantifthesefunctionalillnessesare
consideredaspartofaspectrum.Eachoftheseconditionsisdiagnosedusingcriteriabaseduponthe
patientssymptomswhenotherdiseaseshavebeenexcluded,andtheytendtobecontroversialbecause
oftheabsenceofaspecificdiagnostictestorofobjectivepathophysiologicabnormalities.Screening
questionsthatcanbeusefulindeterminingwhetheradditionalevaluationforoneofthemiswarranted
include[44]:

CFS/SEIDHaveyouhadunexplained,persistent,orrelapsingfatigueforatleastsixmonths?(See
"Clinicalfeaturesanddiagnosisofchronicfatiguesyndrome(systemicexertionintolerance
disease)".)

IBSHaveyouhadabdominaldiscomfortorpainaccompaniedoraffectedbyconstipationor
diarrheaforthreeormoremonthsinthepastyear?(See"Clinicalmanifestationsanddiagnosisof
irritablebowelsyndromeinadults".)

TMDHaveyouhadrecurrentfacial/jawpainand/orlimitationinjawopeningoccurringinthepast
sixmonths?(See"Temporomandibulardisordersinadults".)
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TensionandmigraineheadacheHaveyouhadrecurrentheadaches(atleastfiveformigraine,at
least10fortensiontype)lasting30minutesoccurringinthepastsixmonths?(See"Overviewof
chronicdailyheadache".).

InterstitialcystitisHaveyouhadsymptomsforoverninemonthsofbladderpain,urinaryurgency
andfrequency(voidingmorethaneighttimesduringthedayormorethantwotimesduringthe
night),andanegativeurineculture?(See"Pathogenesis,clinicalfeatures,anddiagnosisof
interstitialcystitis/bladderpainsyndrome".)

VulvodyniaHaveyouexperiencedunexplainedpelvic/vaginalpainfrequentlyduringthepastsix
months?

PsychiatricdisordersPsychiatricdisorders,includingdepressivedisorders,anxietydisorders,and
posttraumaticstressdisorder,aremoreprominentinFMthaninotherrheumaticdiseases,suchas
rheumatoidarthritis(RA).Approximately25percentofpatientswithFMhaveconcurrentmajor
depression,and50percenthavealifetimehistoryofdepression[1822].Thegreaterincidenceof
psychiatricdisordersisespeciallystrikingintertiaryreferralpatientpopulations[45].Aninformal
evaluationforpsychopathologyshouldbepartoftheinitialevaluationofanypatientwithFM,withamore
formalassessmentbyamentalhealthprofessionalinselectedpatients.(See"Unipolardepressionin
adults:Assessmentanddiagnosis"and"Generalizedanxietydisorderinadults:Epidemiology,
pathogenesis,clinicalmanifestations,course,assessment,anddiagnosis"and"Posttraumaticstress
disorderinadults:Epidemiology,pathophysiology,clinicalmanifestations,course,assessment,and
diagnosis".)

SleepdisordersMostpatientswithFMhavenonrestorativesleepasacharacteristicoftheirillness
sleepdisturbancesarealsoverycommoninpatientswithFM,althoughthemostcommonisa
nonspecificinterruptioninstage4sleep[46].Nonrestorativesleepabnormalitiescorrelatewithseverity
ofFMsymptomsandqualityoflife[47].However,primarysleepdisturbances,includingsleepapnea,
restlesslegsyndrome,andperiodiclimbmovementdisorders(PLMD)arealsoquitecommon[30,31].
Theseconditionscancontributesignificantlytothesymptomsoffatigueandnonrestorativesleep
experiencedbypatientswithFM,andsymptomreliefinpatientswiththesecomorbiditiesrequires
recognitionoftheseconditionsandappropriatetreatmentinterventions.Thus,acarefulsleephistory
shouldbeobtainedinpatientswithFMsymptoms.PatientswithpossiblesleepapneaorPLMD(also
termednocturnalmyoclonus)shouldbereferredtoasleepclinicforfurtherevaluationandtreatment.
(See"Clinicalpresentationanddiagnosisofobstructivesleepapneainadults"and"Clinicalfeaturesand
diagnosisofrestlesslegssyndrome/WillisEkbomdiseaseandperiodiclimbmovementdisorderin
adults".)

InflammatoryrheumaticdiseasesTheprevalenceofFMisincreasedinpatientswithchronic
inflammatoryarthritisandsystemicautoimmunerheumaticdiseases,includingRA[4850].Thirtyfour
percentofRApatientshadchronicwidespreadpainconsistentwithFM,andthiswasmorecommonin
women[35].Inalargeearlyarthritiscohort,theincidenceofFMvariedfrom3.6to6.8casesper100
personyears.TheincidenceofFMwashighestduringthefirstyearofarthritisanddidnotcorrelatewith
jointinflammationbutdidcorrelatewithgeneralizedpainandpoormentalhealth.Patientswithactive
inflammatorydiseaseandcoexistentFMmayreportgreatersymptomintensitythanpatientswithoutFM,
anditisimportanttodistinguishsymptomsofFMfromthoseofchronicrheumaticdiseasesbecauseof
thedifferentimplicationsfortreatment[49,51](see"Differentialdiagnosisoffibromyalgia").RAdisease
activityscores,suchasthediseaseactivityscorewitha28jointcount(DAS28),canbeoverestimatedin
patientswithcoexistingFM[52,53].Variousclinical,psychosocial,andillnessseverityvariables,
includingsocialdisadvantage,psychologicaldistress,comorbidity,andRAdiseaseseverity,predictthe
developmentofFMinpatientswithRA.

FMisalsocommoninpsoriaticarthritisandotherformsofseronegativespondyloarthritis[52,53].FMhas
beenespeciallyprominentinsystemiclupuserythematosusandSjgrenssyndrome,withprevalence
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ratesof30to50percent[5456].

ItisalsonowclearthatchronicwidespreadpainandFMmaycomplicateosteoarthritis[57,58]and
regionalpaindisorders,suchaschroniclowbackpain[59]andchronicelbowpain[60].

FIBROMYALGIAANDPRIMARYCAREThediagnosisoffibromyalgia(FM),likethatofheadaches,
chroniclowbackpain,anddepression,cangenerallybemadeintheprimarycaresetting,althoughmany
barriersexistforatimelydiagnosisofFMinprimarycare.Despiteimprovedawarenessamongprimarycare
clinicians,manycontinuetobeuncomfortablewithadiagnosisoffibromyalgia.Therearenoobjective
physical,laboratory,orimagingabnormalities,andthediagnosisisbasedonsubjectivereportingof
symptoms.FMpatientsratedreceivingadiagnosisassomewhatdifficultonaverageandhaddifficulties
communicatingtheirsymptomstothephysician[61].Mostpatientsratedtheirchronicwidespreadpainas
moderateorsevere,andFMsymptomswereonaverage"fairly"to"very"disruptiveandhada"moderate"to
"strong"impactonpatients'lives.However,patientswaitedonaveragealmostayearafterexperiencing
symptomsbeforepresentingtoaclinician,andbeforereceivingadiagnosisofFMtherewasanaverage
durationof2.3yearsandpatientspresentingto3.7differentphysicians.

RecognitionanddiagnosisofFMleadstoadecreaseinresourceuse,includingsubsequenttestingand
overallhealthcarecosts,despiteconcernsthatdiagnosticlabelssuchasFMwouldpromoteillnessbehavior
anddriveuphealthcarecosts.Thiswasshowninastudyinvolvingmorethan2000patients,81percent
women,whowerenewlydiagnosedwithFM[29].Duringthe10yearsbeforediagnosis,thepatientswithFM
hadconsiderablyhighermeanannualratesofvisits,medicationprescription,andtesting,comparedwith
controls(25versus12visitsand11versus4.5prescriptions).FollowinganFMdiagnosis,visitsformost
symptomsandhealthcareusagedeclined,althoughwithintwotothreeyearsvisitlevelsrose.Adecreasein
costsascomparedwiththepredictedtrendhasalsobeenobservedinthefouryearsafterdiagnosis[62].
Costsbeforediagnosiswereusedinatrendanalysistopredictlatercosts,assumingthediagnosishadnever
beenmade,andthesepredictedcostswerecomparedwiththeobservedcostsafterdiagnosis.Theaverage
differencebetweenthepredictedandobservedcostintheprimarycarepopulationintheUnitedKingdomthat
wasstudiedwas66.21persixmonthsperpatient.Anotherreportdescribedbothimprovedqualityoflifeand
decreasedcostofhealthcareafteradiagnosisofFM,suggestinganeedforearlydiagnosisandtreatment
[63].

EarlierdetectionofFMinprimarycaremaybeadvancedwithnewdiagnostictools[64].TheFibroDetect
includes14questionsassessingpatients'painandfatigue,personalhistoryandattitudes,symptoms,and
impactonlives.Thepredictiveaccuracyofthetoolincreasedto0.86forFMandnonFMpatientdetection,
withasensitivityof90percentandaspecificityof67percentforacutoffof6onthescore.

ElectronicmedicalrecordswereusedtoidentifyvariablesassociatedwiththediagnosisofFM[65].
SignificantdifferencesbetweentheFMandnoFMcohortswereobservedfornearlyallthedemographic,
clinical,andhealthcareresourcevariables.Theseresultssupporttheuseofelectronicmedicalrecordsdata
inclinicalresearchforidentifyingvariablesassociatedwithFM.

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasics
andBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easyto
readmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmore
detailed.Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowant
indepthinformationandarecomfortablewithsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremail
thesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsby
searchingonpatientinfoandthekeyword(s)ofinterest.)

Basicstopic(see"Patienteducation:Fibromyalgia(TheBasics)")
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BeyondtheBasicstopic(see"Patienteducation:Fibromyalgia(BeyondtheBasics)")

SUMMARYANDRECOMMENDATIONS

Fibromyalgia(FM)ischaracterizedbywidespreadmusculoskeletalpainandfatigue,oftenaccompanied
bycognitiveandpsychiatricdisturbances.Physicalexaminationrevealstendernessinmultiplesofttissue
anatomiclocations.Laboratorytestingisnormalintheabsenceofotherillnesses(table1).(See'Clinical
manifestations'above.)

WediagnoseFMinpatientswhopresentwithchronicmyalgiasandarthralgiasbutnoevidenceofjointor
muscleinflammationonphysicalexaminationorlaboratorytestingthatwouldexplainthesymptomsand
findings.Thephysicalexaminationshouldrevealmultipletenderpointsatsofttissuelocations(figure1).
Inclinicalpractice,aspecificnumberoftenderpointsarenotrequiredtomakethediagnosis,andFM
maybediagnosedwithoutatenderpointevaluation.(See'Diagnosis'aboveand'Clinicaldiagnosis'
above.)

Testingshouldbekepttoaminimum,sincetherearenodiagnosticlaboratorytestsforFM.Weadvise
obtainingacompletebloodcount(CBC)andtestingforanacutephasereactant,suchastheerythrocyte
sedimentationrate(ESR)orCreactiveprotein(CRP),toexcludesystemicinflammatorydisease.
Additionallaboratorytestingshouldbebaseduponclinicalsuspicionofaspecificdisorder,suchasa
thyroidstimulatinghormonetestoracreatinekinase,ifhypothyroidismorinflammatorymyopathyare
suspected,respectively.(See'Diagnosticevaluation'above.)

Additionalevaluationshouldbeconsideredforassociatedconditionsifclinicallysuspected,including
sleepdisorders,suchasobstructivesleepapneaorrestlesslegssyndrome,andpsychiatricdisorders,
suchasdepressionoranxiety.(See'Additionalevaluation'above.)

FMmaycoexistwithotherdisorders,suchasotherfunctionalsomaticsyndromes(eg,irritablebowel
syndrome[IBS]andchronicheadache),sleepandpsychiatricdisorders,inflammatoryrheumaticdisease
syndromes,andnoninflammatorymusculoskeletalpain,includingosteoarthritis.Itisimportanttoidentify
whethertheseconditionsarepresentinpatientswithFMbecauseofthetreatmentimplications.(See
'Coexistingdisorders'above.)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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GRAPHICS

Manifestationsoffibromyalgia

History
Morecommoninwomen,age20to65

Chronic,generalizedpain

Fatigue

Sleepandmooddisturbances

Headaches

Irritablebowelsyndrome

Physicalexamination
Multipletenderareasofmuscleandtendons

Noinflammatorymuscleorjointdisease

Laboratorytests
Unremarkable

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Tenderpointsinfibromyalgia

The18"tenderpoints"importantforthediagnosisoffibromyalgia.Notethebilateral
symmetryofthelabeledregions.Tendernessonpalpationofatleast11ofthesesitesina
patientwithatleastathreemonthhistoryofdiffusemusculoskeletalpainisrecommended
asadiagnosticstandardforfibromyalgia.

Adaptedfrom:GoldenbergDL.Diagnosticandtherapeuticchallengesoffibromyalgia.HospPract
(OffEd)198924:39.

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Hintsforearlyandcosteffectivediagnosisoffibromyalgia

Chronicwidespreadmusculoskeletalpainforthreemonths

Absenceofothersystemicconditionaccountingforpain

Excesstendernessinsofttissues

Characteristicsymptoms:
"Ihurtallover"
"ItfeelslikeIalwayshavetheflu"
Fatigue,sleepandmooddisturbances
IBS,irritablebladder,multipleothersomaticcomplaints

Exclusionofstructuralorsystemicdisease
Nota"fishing"expedition
Avoid"screening"rheumatologytests
Mostefficientwithearlysubspecialtyreferral

IBS:irritablebowelsyndrome.

CourtesyofDonLGoldenberg,MD.

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Recommendeddiagnosticworkupforfibromyalgia

EstablishingthediagnosisisanessentialcomponentofFMmanagement.
DiagnosticcriteriaforFMincludetheACRandtheCanadianConsensus
Guidelines.Acompletehistory,physicalexam,andlaboratorytestingshouldbe
donetoexcludediseasesthatmaymimicorcomplicateFM.Eachpatientshould
beassessedforathreemonthhistoryofchronicwidespreadpainpatientself
reportshouldbeusedasanindexofpain.Thepresenceoftenderpointsshould
beconfirmed.However,tendernessissubjectiveanddependsuponthe
examiner'sstrengthofpalpation.

CBC:completebloodcountESR:erythrocytesedimentationrateCRP:Creactive
proteinTSH:thyroidstimulatinghormoneCK:creatinekinaseFM:fibromyalgia
ACR:AmericanCollegeofRheumatology.

Adaptedfrom:GoldenbergDL,BurckhardtC,CroffordL.Managementoffibromyalgia
syndrome.JAMA2004292:2388.

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AmericanCollegeofRheumatologypreliminarydiagnosticcriteriafor
fibromyalgiaandmeasurementofsymptomseverity

Criteria
Apatientsatisfiesdiagnosticcriteriaforfibromyalgiaifthefollowingthreeconditionsaremet:

1)Widespreadpainindex(WPI)7andsymptomseverity(SS)scalescore5orWPI3to6andSSscalescore
9.

2)Symptomshavebeenpresentatasimilarlevelforatleastthreemonths.

3)Thepatientdoesnothaveadisorderthatwouldotherwiseexplainthepain.

Ascertainment
1)WPI

Notethenumberareasinwhichthepatienthashadpainoverthelastweek.Inhowmanyareashasthepatient
hadpain?Scorewillbebetween0and19.

Neck

Jaw,left

Jaw,right

Shouldergirdle,left

Shouldergirdle,right

Upperarm,left

Upperarm,right

Lowerarm,left

Lowerarm,right

Chest

Abdomen

Upperback

Lowerback

Hip(buttock,trochanter),left

Hip(buttock,trochanter),right

Upperleg,left

Upperleg,right

Lowerleg,left

Lowerleg,right

2)SSscalescore

Fortheeachofthethreesymptomsbelow,indicatethelevelofseverityoverthepastweekusingthefollowing
scale:

0=no 1=slightormildproblems, 2=moderate,considerableproblems, 3=severe,pervasive,

problem generallymildor oftenpresentand/oratamoderate continuous,lifedisturbing
intermittent level problems

Fatigue(0to3)

Wakingunrefreshed(0to3)

Cognitivesymptoms(0to3)

Consideringsomaticsymptomsingeneral, *indicatewhetherthepatienthas:

Nosymptoms(0)

Fewsymptoms(1)

Amoderatenumberofsymptoms(2)

Agreatdealofsymptoms(3)

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TheSSscalescoreisthesumoftheseverityofthethreesymptoms(fatigue,wakingunrefreshed,cognitive
symptoms)plustheextent(severity)ofsomaticsymptomsingeneral.Thefinalscoreisbetween0and12.

*Somaticsymptomsthatmightbeconsidered:musclepain,irritablebowelsyndrome,fatigue/tiredness,thinkingor
rememberingproblem,muscleweakness,headache,pain/crampsintheabdomen,numbness/tingling,dizziness,
insomnia,depression,constipation,painintheupperabdomen,nausea,nervousness,chestpain,blurredvision,fever,
diarrhea,drymouth,itching,wheezing,Raynaudphenomenon,hives/welts,ringinginears,vomiting,heartburn,oral
ulcers,lossof/changeintaste,seizures,dryeyes,shortnessofbreath,lossofappetite,rash,sunsensitivity,hearing
difficulties,easybruising,hairloss,frequenturination,painfulurination,andbladderspasms.
Asanalternativetosomaticsymptomsingeneral,onepointeachmaybeaddedtotheSSscalescoreifthefollowing
symptomsoccurredduringtheprevioussixmonths:headaches,painorcrampsinlowerabdomen,anddepression(03).
[1]

Reference:
1.WolfeF,ClauwDJ,FitzcharlesM,etal.Fibromyalgiacriteriaandseverityscalesforclinicalandepidemiological
studies:AmodificationoftheACRpreliminarydiagnosticcriteriaforfibromyalgia.JRheumatol201138:1113.
WolfeF,ClauwDJ,FitzcharlesMA,etal.TheAmericanCollegeofRheumatologypreliminarydiagnosticcriteriafor
fibromyalgiaandmeasurementofsymptomseverity.ArthritisCareRes201062:600.Copyright2010American
CollegeofRheumatology.ReproducedwithpermissionofJohnWiley&Sons.

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Differentialdiagnosisoffibromyalgia

Diagnosis Helpfulfeatures

Rheumatoidarthritis Symmetricalpolyarthritis,systemicfeatures(dermatitis,nephritis),elevatederythrocyte
orlupus sedimentationrate,serologicabnormalities(rheumatoidfactor,antiDNAantibodies)

Polymyalgia Elderly,elevatederythrocytesedimentationrate,stiffness>pain,respondswellandquicklyto
rheumatica steroids

Myositis Muscleweakness,elevatedmuscleenzymes

Hypothyroidism Abnormalthyroidfunctiontests

Hyperparathyroidism Hypercalcemia

Neuropathies Clinicalandelectricalevidenceofneuropathy

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Contributor Disclosures
Don L Goldenberg, MD Consultant/Advisory Boards: Pzer [Fibromyalgia (pregabalin)]. Peter H Schur,
MD Nothing to disclose Paul L Romain, MD Nothing to disclose

Contributor disclosures are reviewed for conicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conict of interest policy

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