w w w . r e u m a t o l o g i a . c o m . b r
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
Original
article
New
guidelines
for
the
diagnosis
of
fibromyalgia
Roberto
E.
Heymann
a,b,∗,
Eduardo
S.
Paiva
a,c,
José
Eduardo
Martinez
a,d,
Milton
Helfenstein
Jr.
a,b,
Marcelo
C.
Rezende
a,e,
Jose
Roberto
Provenza
a,f,
Aline
Ranzolin
a,g,
Marcos
Renato
de
Assis
a,h,
Daniel
P.
Feldman
a,b,
Luiz
Severiano
Ribeiro
a,i,
Eduardo
J.R.
Souza
a,jaSociedadeBrasileiradeReumatologia,Brazil
bUniversidadeFederaldoEstadodeSãoPaulo,SãoPaulo,SP,Brazil
cUniversidadeFederaldoParaná,Curitiba,PR,Brazil
dPontifíciaUniversidadeCatólicadeSãoPaulo,Sorocaba,SP,Brazil
eSantaCasadeCampoGrande,CampoGrande,MS,Brazil
fPontifíciaUniversidadeCatólicadeCampinas,Campinas,SP,Brazil
gHospitaldasClínicasdePernambuco,Recife,PE,Brazil
hFaculdadedeMedicinadeMarília,Marília,SP,Brazil
iHospitaldoServidorPúblicodeMinasGerais,BeloHorizonte,MG,Brazil
jSantaCasadeBeloHorizonte,BeloHorizonte,MG,Brazil
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received1July2016 Accepted25May2017 Availableonline8August2017
Keywords:
Fibromyalgia Pain Diagnosis Diagnosticcriteria Guidelines
a
b
s
t
r
a
c
t
Objective:Toestablishguidelinesbasedonscientificevidenceforthediagnosisof fibromyal-gia.
Materialandmethods:Evidencecollectionwasperformedbasedon9questionsregarding thediagnosisoffibromyalgia,structuredusingthePatient,InterventionorIndicator, Com-parisonandOutcome(P.I.C.O.),withsearchesinthemain,primarydatabasesofscientific information.Afterdefiningthepotentialstudiestosupporttherecommendations,theywere gradedaccordingtoevidenceanddegreeofrecommendation.
©2017PublishedbyElsevierEditoraLtda.ThisisanopenaccessarticleundertheCC BY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
∗ Correspondingauthor.
E-mail:[email protected](R.E.Heymann).
http://dx.doi.org/10.1016/j.rbre.2017.07.002
Novas
diretrizes
para
o
diagnóstico
da
fibromialgia
Palavras-chave:
Fibromialgia Dor Diagnóstico
Critériosdiagnósticos Diretrizes
r
e
s
u
m
o
Objetivo: Estabelecerdiretrizesbaseadasemevidênciascientíficasparaodiagnósticoda fibromialgia.
Materialemétodos:Acoletadeevidênciasfoielaboradaapartirdenovequestõessobre diag-nósticodafibromialgia,estruturadaspormeiodoPICO(Paciente,Intervenc¸ãoouIndicador,
Comparac¸ãoeOutcome),combuscanasprincipaisbasesprimáriasdeinformac¸ão cientí-fica.Apósdefinirosestudospotenciaisparasustentac¸ãodasrecomendac¸ões,essesforam graduadospelaforc¸adaevidênciaegrauderecomendac¸ão.
Resultadoseconclusões: Asquestõesresultaramemnoverecomendac¸õesparao diagnós-ticodafibromialgiacombasenasevidênciasdeliteraturaenaopiniãodosexpertsque participaramdotrabalho.
©2017PublicadoporElsevierEditoraLtda.Este ´eumartigoOpenAccesssobuma licenc¸aCCBY-NC-ND(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Consideredoneofthemostcommonclinicalrheumatologic conditions, fibromyalgia (FM) has variable epidemiological data. In studies performed in the USA and inEurope, the prevalencefoundwasupto5%inthegeneralpopulation,1–5
surpassing10%ofvisitsinrheumatologyclinics.6InBrazil,FM
ispresentinupto2.5%ofthegeneralpopulation, predomi-nantlyamongwomen,especiallyfrom35to44yearsofage.7,8
FM is certainly not a new syndrome, as corroborating reportshavebeenpublishedsince1592.9Theterm
“fibromyal-gia”wasfirstusedinareviewbyHench10in1976,althoughits
recognitionasasyndromeoccurredafterthepublicationof astudybyYunusetal.in1981,11whodescribedand
charac-terizedtheclinicalpattern ofFM.However,itsdiagnosis in thedailyroutineandthechoiceofpatientsforclinicalstudies werechallengingduetothelackofanobjectiveclinicalor lab-oratorymarker.Tominimizethesubjectivityofclinical judg-ment,severaldiagnosticcriteriawereelaboratedfrom1980, thoughwithoutunanimity,whichgeneratedmore diagnos-ticconfusion.In1990,theAmericanCollegeofRheumatology (ACR)preparedclassificationcriteriathatwereacceptedbythe scientificcommunity,12substantiallyhelpingtohomogenize
thediagnosisofFMandtopromotestudiesonFM.
Despiteadvancesintheuseofthesecriteria, many crit-icisms have appeared over the years, especially regarding overvaluingwidespreadpainabovesymptomssuchasfatigue, sleepdisordersandmorningstiffness,amongothers. Count-ingandsearchingfortenderpointsbecameanotherreasonfor discussionbecausemanyphysicianslackedadequatetraining torecognizethem.
Inresponsetothesecriticisms,in2010,theACRprepared newpreliminarydiagnosticcriteria, whichincludedseveral symptomsand excluded palpation oftenderpoints. These criteriaweresubsequentlychangedandarestillunder analy-sisbytherheumatologicmedicalcommunity.13,14
Giventhevarietyinclinicalpatternsandtheinexistence oflaboratorymarkersorcharacteristicimagingexamination, thediagnosisofFMisbasedonclinicaljudgmentandvaries withtheexperienceofeachphysician.
Material
and
methods
Thisguidelinefollowedasystematicreviewpattern,retrieving evidencebasedontheevidence-basedmedicinemovement, inwhichclinicalexperienceisintegratedwiththecapacityto criticallyanalyzeandrationallyapplyscientificinformation, thusimprovingthequalityofmedicalcare.
NineclinicalquestionsrelevanttothediagnosisofFMwere elaborated,withtheparticipationofallmembersofthe Com-mitteeforPain,Fibromyalgia,andSoft-TissueRheumatismof theBrazilianSocietyofRheumatology(SociedadeBrasileirade Reumatologia).Theformulationstructureofeachquestionis summarizedbytheP.I.C.O.acronym,whereinPcorresponds toPatient–withFibromyalgia;Itointervention–diagnostic criteriaorACRcriteria,widespreadpain,tenderpoints,sleep disorders,fatigue,thermography;CtoComparison–clinical evaluationand otherdiagnostic criteria;and OtoOutcome –diagnostic accuracy.15 Thus,thedescriptorstobeusedin
the search strategies forscientificevidence were obtained. Searches were performed from August 2015 to September 2016inthemainprimarydatabasesofscientificinformation (Medline/PubMed, Embase, Lilacs/Scielo, Cochrane Library, PremedlineviaOVID),inadditiontoamanualsearchinthe Brazilian Digital Library of Theses and Dissertations (Bib-liotecaDigitalBrasileiradeTeseseDissertac¸ões–BDTD)ofthe BrazilianInstituteforInformationinScienceandTechnology (InstitutoBrasileirodeInformac¸ãoemCiênciaeTecnologia– IBICT;Table1).
Initially,thestudieswereselectedbytitle,thenbyabstract, and lastlybyfulltext, whichwassubjectedtocritical eval-uationandextractionofresultsonoutcomes.Theretrieved evidencewasconsideredeligibleifmeetingthePICOmethod criteria. Observationalstudies(cross-sectionalor cohort)or before-and-afterstudieswerepreferentiallyconsidered, with-outtimeorlanguagerestrictionsandwithavailablefulltext. Thecriticalevaluationsofthecohortstudieswereperformed using the Newcastle-Ottawa Scale (NOS)16 and the
cross-sectionalstudiesusingQuadas.17
Table1–Searchstrategiesandarticlesretrievedandselectedaccordingtoeachguidelinequestion.
Question Strategy Result
1.Arethe1990ACRcriteriaessentialfor
thediagnosisofFM?
FibromyalgiaAND(ACRORAmericanCollegeof
Rheumatology)AND(sensitiv*[Title/Abstract]OR
sensitivityandspecificity[MeSHTerms]OR
diagnos*[Title/Abstract]OR
diagnosis[MeSH:noexp]ORdiagnostic*
[MeSH:noexp]OR
diagnosis,differential[MeSH:noexp]OR
diagnosis[Subheading:noexp])
Retrieved:283Selected:5
2.Iswidespreadpainessentialforthe
diagnosisofFM?
((FibromyalgiaANDPainANDwidespreadAND
(sensitiv*[Title/Abstract]ORsensitivityand
specificity[MeSHTerms]OR
diagnos*[Title/Abstract]OR
diagnosis[MeSH:noexp]ORdiagnostic*
[MeSH:noexp]OR
diagnosis,differential[MeSH:noexp]OR
diagnosis[Subheading:noexp]))OR(Fibromyalgia
ANDPainANDspecificity[Title/Abstract])))
Retrieved:382Selected:6
3.Shouldtenderpointsbeconsideredin
thediagnosisofFM?
(tenderpoint*ORpressureORpainthreshold)
ANDFibromyalgiaAND(sensitiv*[Title/Abstract]
ORsensitivityandspecificity[MeSHTerms]OR
diagnos*[Title/Abstract]OR
diagnosis[MeSH:noexp]ORdiagnostic*
[MeSH:noexp]OR
diagnosis,differential[MeSH:noexp]OR
diagnosis[Subheading:noexp])
Retrieved:588Selected:13
4.Aresleepdisorders,fatiguedisorders
andcognitivedisordersalso
considered?
(sleepORfatigueORmentaldisordersOR
cognitiveORcognitionORstress)AND
FibromyalgiaAND(sensitiv*[Title/Abstract]OR
sensitivityandspecificity[MeSHTerms]OR
diagnos*[Title/Abstract]OR
diagnosis[MeSH:noexp]ORdiagnostic*
[MeSH:noexp]OR
diagnosis,differential[MeSH:noexp]OR
diagnosis[Subheading:noexp])
Retrieved:1419Selected:6
5.Canthe2010criteriabeconsideredin
thediagnosisofFM?
FibromyalgiaAND(sensitiv*[Title/Abstract]OR
sensitivityandspecificity[MeSHTerms]OR
diagnos*[Title/Abstract]OR
diagnosis[MeSH:noexp]ORdiagnostic*
[MeSH:noexp]OR
diagnosis,differential[MeSH:noexp]OR
diagnosis[Subheading:noexp])Limits:published
inthelast3yearsSortby:PublicationDate
Retrieved:659Selected:7
6.Isthermographyindicatedinthe
diagnosisofFM?Note:useincomplex
pain,almostnothingonFM
(FibromyalgiaAND(thermographyOR
temperatureORthermotestORcapillaroscopy
ORheatORhotORcoldORsensoryORthermal
ORsomatosensory)OR(thermograph*OR
telethermography)AND(painORtriggerOR
tender))
Retrieved:857Selected:10
7.Whenshouldwerequest
polysomnographyforthediagnosisof
FM?Note:thequestionofsleep
complements
FibromyalgiaAND(Polysomnography*OR
CircadianRhythm)
Retrieved:62Selected:4
8.IsthediagnosisofFMadiagnosisof
exclusion?
Note:Theanswertothisquestioncan
naturallyarisewiththeotheranswers
FibromyalgiaAND(exclu*ORdifferential) Retrieved:766Selected:7
9.Shouldweassessmooddisordersin
patientswithFM?How?
(MoodDisordersORdepressionORdepressive)
ANDFibromyalgiaAND(sensitiv*[Title/Abstract]
ORsensitivityandspecificity[MeSHTerms]OR
diagnos*[Title/Abstract]OR
diagnosis[MeSH:noexp]ORdiagnostic*
[MeSH:noexp]OR
diagnosis,differential[MeSH:noexp]OR
diagnosis[Subheading:noexp])
Articles identified in the databases (n=7847)
Selected
Included
Eligibility
Retrieve
d
Manual and gray literature search (n=4)
Articles retrieved after removing duplicates (n=5563)
Selected articles (n=271)
Articles excluded for failing to meet the eligibility
criteria (n=5349)
Full-text article accessed (n=216)
Articles excluded (n=162)
REASONS: intermediate outcomes; narrative or systematic reviews; duplicates;
language: post-hoc analysis; lack of data to be extracted, case reports; comments or letters; case-control studies; redundant or repeated results; repeated case studies Included studies
(n=53)
Fig.1–Flowchart.
or systematic reviews; that were post hoc analyses, com-mentsorletters,casereports,orcase-controlstudies;thathad redundantorrepeatedresults;thatwereduplicates;thatwere repeatedcasestudies;orthatwherenotconducivetodata extractionwereexcluded.
Afterdefiningthepotentialstudiessupportingthe recom-mendations,theywereselectedbasedonevidenceanddegree ofrecommendationaccordingtotheOxfordclassification.18
Therecommendations were then written and re-evaluated byall participantsduring4videoconferencemeetings held betweenJanuary2015and July2016andwere approvedby atleast70%ofparticipants.Questionswithout thislevelof agreementweresubjectedtonewquestioningandcorrection sessionsviatheInternetuntiltheywereacceptedbyatleast 70%ofthemembers.
Fig.1showsthesearchandselectionstagesofthearticles fortheseguidelines.
Guidelines
for
the
diagnosis
of
fibromyalgia
Arethe1990ACRcriteriaessentialforthediagnosisof fibromyalgia(FM)?
TheclassificationofFMaccording tothe 1990ACRcriteria (1990ACR)primarilydependsonthepresenceofwidespread pain (axial plus upper and lower segments plus left- and right-sided) and on the physical examination of tender points.12
Thesecriteriawereexclusivelypreparedtoincludepatients in scientific studies. The 2010 ACR preliminary diagnostic criteria of FM are based on the number of tender areas of the body and on the presence and severity of fatigue,
non-restorativesleep,cognitivedifficulties,andtheextentof somaticsymptoms(D).12,13,19
Overtime,itbecameevidentthattenderpointshavenot been usedorhavebeen erroneouslyassessedbyuntrained physiciansinclinical practice,particularly inprimarycare, causingfailuresinthefinaldiagnosis.Therefore,thediagnosis wasoftenevaluatedonlybasedonpatientcomplaints.20
The1990ACRcriteria,whenpositive,inapopulationwith 49%pre-testprobabilityforFM(prevalence),madeadefinitive diagnosisin92%cases(post-testprobability)(B).12,21
FMdiagnosisusingthe1990ACRcriteriahad25%false neg-ativeswhencomparedwithclinicaldiagnosis.Theuseofthe WidespreadPainIndex(WPI>7)combinedwiththeSymptom SeverityScale(SS>5),bothbasedonpatientsymptoms(pain, fatigue,sleep,cognition,andsomaticsymptoms),enableda 90.8%diagnosticaccuracy(90.9%sensitivityand85.9% speci-ficity)whencomparedwiththe1990ACRcriteria(B).13
At49%pre-testprobability,combiningthepositivityofthe 1990and2010ACRcriteriaenableddiagnosticcertaintyin99% cases(B).13,21
Recommendation
FM diagnosis may be performed without using the 1990 ACR criteria,althoughits applicationwiththe2010criteria increasesthediagnosticaccuracy.
IswidespreadpainisessentialforthediagnosisofFM?
The1990ACRcriteriaconsistentirelyofsignsand symp-tomsofwidespreadpain,whereas56%ofthe2010ACRcriteria arelinkedtomusculoskeletalpain.23
TheWPI(0–19), with acut-off point >8, enabled an FM diagnosiswith83.2%sensitivity,87.6%specificity,and85.4% accuracy.Basedona49%FMprevalence(pre-testprobability), thepresenceofWPI>8increasedthediagnosticprobabilityto 86%(B).21
Thesymptoms and impact related to widespread pain, asmeasuredusingtheinstrumentstheFibromyalgiaImpact Questionnaire (FIQ), the Multidimensional Pain Inventory (MPI),the SF-36Health SurveyShortForm (SF-36),and the PainProcessingInventory(PPI),inpatientswithanaverage of15tenderpoints,weresignificantlymorefrequentthanin patientswithanaverageof6tenderpoints(B).24
TheWPIinpatientswithFMwassignificantlyhigherthan inotherclinicalconditions,includingSystemicLupus Erythe-matosus,Osteoarthritis,andRheumatoidArthritis.TheWPIof patientsdiagnosedwithFMandwithpositive2010ACR crite-riawassignificantlyhigher,onaverage,thanthatofpatients withnegativecriteria.Amongthepatientswithpositive2010 ACRcriteriaforFM,93.7%metthewidespreadpaincriterion (accordingtothe1990ACR).Ofthe2010ACRpatientsnegative forFM,32.8%werepositiveforthewidespreadpaincriterion (B).14
In2016,areviewofthe2010/2011criteriawasproposedto correctclassificationerrorsobservedinpatientswithregional painbyaddingacomplementarycriterionofwidespreadpain (B).25
Recommendation
Thepresenceofwidespreadpainisessentialforthediagnosis ofpatientswithsuspectedFM.
ShouldtenderpointsbeconsideredinthediagnosisofFM?
Overtime, it became evident that in primarycare clinical practice,tenderpointshavenotbeenusedor,atleast,have beenusedinadequatelybyuntrainedphysicians,impairing thefinaldiagnosis.Therefore,thediagnosisisoftenevaluated onlybasedonpatientcomplaints.20
Theincidencerates ofthe presenceoftenderpoints at a higher number than 11 were 22.4%, 24.7% and 89.9% in patientswithRheumatoidArthritis,Osteoarthritis,andFM, respectively, with a linear association between the num-berof tenderpoints and the RheumatologyDistress Index (RDI)(B).26
Regardless of the diagnostic method used todefine FM (clinicalorthroughaquestionnairecombiningevaluationof regionalpainandfatigue),asubstantialnumberofpositive diagnosesoccurredattenderpointcountsrangingfrom6to 18,andthediagnosiswasstronglynegativeatvalueslower than2–3(B).21
Patients with FMwere identified through tenderpoints (morethan11)with84%sensitivityand87%specificity,which provided84%diagnosticcertaintywhenpositive(B).27
Regardless of the FM diagnosis,70% ofelderly patients older than 70 years, with widespread pain, had at least 1 positive tender point, 41.5% had more than 3 tender points,andless than10% hadmorethan10tenderpoints.
Furthermore,10%ofpatientswithoutwidespreadpainhad>3 positivetenderpoints.Atenderpointcounthigherthan3was alreadyassociatedwiththedecreasedphysicalperformance ofpatients, asmeasuredbytheShortPhysicalPerformance Battery(SPPB)(B).28
There are reasons for using criteria that are not based solelyontenderpointcounts.Althoughthereisa standard-ized protocol for counting tender points, it isnot used in clinical practice, and its examinationis susceptible to the variablepressure exertedbytheexaminerinmostresearch studies.TheneedforinvolvingamultidisciplinaryteaminFM isanotherobstaclerelatedtothecapacitytomeasuretender points.Thus,therelevanceandspecificityoftenderpointsin thediagnosisofFMarelimited(B).29
Themanual countoftenderpoints wascorrelated with stressordepressionvariables,asmeasuredusingthescales theBriefSymptomInventory(BSI),theGlobalSeverityIndex (GSI),andtheBeckDepressionInventory(BDI),defininga lin-earrelationshipbetweenthenumberofpositivetenderpoints andthestressintensityand/ordepression(B).30
Themeannumberoftenderpointsinpatientsdiagnosed withFMmaybe3–4timeshigherthanthatinhealthypeople. Usingadolorimeter,witha4.0kg/cm2cut-offpointforpain
threshold,eachtenderpointwillprovidegoodsensitivityand specificitysignificantforthediagnosisofFM.Thecombined useofeachpositivetenderpointmayincreasethepost-test probabilityofthediagnosisofFM(B).31
A study showed that most tender points examined in FM could betrigger points, observed throughspontaneous intramuscularelectricalactivity.Therefore,asignificant cor-relationwasdetectedbetweentheintensityofspontaneous widespreadpainandthetotalnumberofactivetriggerpoints andtenderpointspre-determinedinFM(B).32
Thetenderpointcountandtheresultfromthevisual ana-log painscale,theBDIintheevaluationofdepression, and theFIQintheevaluationofdiseaseseveritywerecorrelated inpatientswithFMandameanof15positivetenderpoints (B).33
Patients with widespread pain and less than 11 tender pointshadlowerdiseaseseverity,fewersleepdisordersand somaticsymptoms,andlowerriskforanxietyanddepression (theDukeAnxiety-Depression(Duke-AD)score)(B).34
Insixmonthsoffollow-up,32%patientsdiagnosedwith atypical FM(numberoftenderpointsrangingfrom 6to10) developednumbersoftenderpoints>11.Inthesameperiod, 36%patientsinitiallydiagnosedwithtypicalFM(numbersof tenderpoints>11)werediagnosedwithatypicalFM. Symp-tomsrelatedtosleepquality,anxiety,depression, andtotal FIQscore mayinitially beincreasedinpatientswith num-bersoftenderpoints>11whencomparedwithpatientswith 6–10tenderpoints.After6monthsoffollow-up,that differ-encemaydisappear.Thesesymptomsimprovedinbothtypes ofpatientsafter6monthsoffollow-up,albeitwithfurther therapeuticimprovementinpatientswithnumbersoftender points>11(B).35
Pain-related symptoms, measured by the SF-36 scores (bodilypain,painintensity, fatigue,and morningtiredness) weresignificantlyworseinpatientswithnumbersoftender points≥11 thaninpatientswithnumbers oftenderpoints
of Motor and Process Skills score <1.5) in patients with widespreadpainandnumbersoftenderpoints≥11(B).36
Recommendation
Tenderpointsmaybeusefulforthediagnosisoffibromyalgiawhen evaluatedin combinationwith other functional disorderscovered inthe2010criteria.Thetenderpointcountmaybecorrelated withtheintensityofsomesymptoms,particularlyemotional stress.
Aresleepdisorders,fatigue,andcognitivesymptomsalso importantfordiagnosis?
Patients with FMhave higher risks for somaticsymptoms (67%), depression (55%), panic syndrome (35%), and ago-raphobia (30%) than patients with rheumatoid arthritis. Furthermore,theyhaveworsepain,sleepquality,andquality oflifeindices(B).37
InpatientswithFM,painintensityandworsesleep qual-ity are associatedwithhigh fatigue scores. Dailypain is a moreimportantpredictorofdailyfatiguethandepressionor sleep quality. Thereis acyclical and dysfunctionalpattern ofintensifiedpainandnon-restorativesleepunderlyingthe experienceoffatigueinFM(B).38
Inpatients diagnosedwithFM,in aone-yearfollow-up, sleep quality was permanently low when measured using the Pittsburgh Sleep QualityIndex. Sleepquality and pain intensityatthebeginningofthediagnosismaypredictpain intensityafteroneyear(B).39
TheevaluationofpatientswithFMusingthemeasuring instrumentsFIQ,theHospitalAnxietyandDepressionScale, theBrief Pain Inventory,theFatigue AssessmentScale,the HealthAssessmentQuestionnaire,theGeneralHealth Ques-tionnaire, the Chronic Pain Coping Inventory,the Arthritis Self-efficacyScale,andtheSleepQualityScalemayidentify 4factorsassociatedwithactivedisease(withthepresenceof aclinicalimpactondailylife)40:
1. Emotional aspects (33.7% variation) regarding anxiety, depression,andsocialelements;
2. Physicalactivity (15% variation),including pain, fatigue, sleepquality,andfunctionalcapacity;
3. Decision-making capacity or the ability to deal with situations(9%variation)involvingactivecopingand expec-tationsaboutthedisease;and
4. Passivecoping(6.3%variation),whichincludesinactivity orexternalhelprequest(B).40
Somatic symptoms, the feeling of waking up tired and other sleep problems, cognitive decline,fatigue, and mood disordersarevariablesstronglycorrelatedwithtenderpoint countandtheWPIinpatientswithFM(B).13
Patients with FMand sleep disorders have significantly highertenderpointcountsthanpatientswithnosleep impair-ment.Thosepatientsalsohavehigherassociationswithother symptoms,suchasfatigueandreducedfunctionandenergy (B).41
Recommendation
Sleepdisordersandchangesincognitionandfatigueshould be consideredin thediagnosis ofFM. Theyshould alsobe consideredintheassessmentofseverityofpatientswithFM.
Canthe2010criteriabeconsideredinthediagnosisof FM?
The2010ACRcriteriaeliminatetenderpointcounts,essential for diagnosis using the 1990ACR criteria, assessing symp-tomsoftenreportedbypatientsintheclinicalevaluationand enablinginclusionofpatientswithoutwidespreadpain,who areexcludedbythe1990ACRcriteria.42
Patients with suspected diagnosis of FM are evaluated usingthefollowingthreemethods:
(1) AssociationoftheScientificMedicalSocietiesinGermany (Arbeitsgemeinschaft der Wissenschaftlichen Medizini-schen Fachgesellschaften – AWMF; widespread chronic paindefinedasaxialpainandpaininthe4extremities and/ordataonsleepdisordersandfatigueand/orthe feel-ingofswellingorstiffnessinthehandsorfeetorfacein theprevious3months,withaZ1/10scoreinanumerical scaleassessedusingaquestionnaire);
(2) Survey(RegionalPainScore–RPSZ8/19andZ6/10Fatigue Scoreonavisualanalogscaleinthepreviousweek);and (3) ACR(ACR1990)–(widespreadchronicpaindefinedbythe
ACRandpressurestiffnessofatleast11/18tenderpoints).
Inconclusion,71%ofpatientsarediagnosedwithFMusing thesethreemethods;theAWMFandthe1990ACRwere con-cordantin86.6%cases,andtheSurveyandthe1990ACRwere concordantin79.5%cases.Patientspositiveinthethree meth-odshadhigherlevelsofdepressionandsomaticsymptoms than patients positiveinthe AWMFand 1990ACR criteria; positivecasesaccordingtoonlyoneofthesecriteriawere iden-tifiedatpercentagesof1.4%,3.1%,and2.0%intheAWMF,the Surveyandthe1990ACRcriteria,respectively(B).29
Inapopulationofpatientswithaprevalenceof68%FM, theuseofthe2010ACRinstrument(withawidespreadpain scorerangingfrom0to19)andthecut-offpointatthescoreof 10todifferentiatepositive(>10)fromnegative(<10)patients enabledthediagnosisofFMat94%sensitivityand91% speci-ficity,leadingtopost-testdiagnosticprobabilitiesof96%for positiveresultsand87%fornegativeresults(B).43
The2010ACRdiagnosticcriteria,combiningchronicpain (WPI>7)andseverityscale(SS>5)orchronicpain(WPI3–6) andseverityscale(SS>9),had88.1%accuracyinthediagnosis ofFM(B).13
ModificationoftheACR2010ACRcriteria,eliminatingthe estimateofsomaticsymptoms,replacingthesumof3specific symptomsreportedbythepatientusingascaleofFM symp-tomsrangingfrom0to3,andaddingtheWPItothemodified severityscale(SSscale),whenadministeredtopatientswith andwithoutFM,usingascore≥13asthecut-offpointfor
posi-tiveandnegativediagnosis,enableda93.0%correctdiagnosis, with96.6%sensitivityand91.8%specificity(B).14
correctdiagnoses.Conversely,the2010ACRcriteriamodified in2011aremoresuitableforresearchbecausetheyare eas-ilyadministered (self-administered) and,therefore, reach a highernumberofpatients.42
Theeaseofuse ofthe 2010ACR criteriaindicates their applicationmainlytoprimarycarebecausethediagnosis cov-ersthemainpatientcomplaintsandassessestheseverityof theclinicalsymptomsandthepatientfollow-up.20
Recommendation
Werecommendusingthe2010ACRcriteriaforthediagnosis offibromyalgia.Themodificationspublishedin2011aremore appropriateforepidemiologicalresearch.
IsthermographyindicatedforthediagnosisofFM?
ThediagnosisofFMsyndromeisbasedonclinical character-istics.Thermographyisnotincludedinthe1990,2010,or2011 diagnosticcriteriaorinthe2016review.12,13,25
Fewcontrolledstudiesontheuseofthermographyinthe FMsyndrome,forbothdiagnosisandassessmentofthe effi-cacyofatreatment,havebeenpublished.
The number of “hotspots” found using this imaging methodisconsideredbysomeasakeyinstrumentinthe diag-nosisofvariousdiseases,includingFMsyndrome.Inastudy, thenumber foundwas higherinpatients withFMthan in healthyindividuals,therebyconcludingthatmorethanseven “hotspots”could predictsensitivityin11ormoreofthe18 specificanatomicalpainsites,termedtenderpoints.44
Basedon the “hotspot” count, 74.2% of 252 individuals (161 FM, 71 with widespread pain and <11 tender points, and20healthycontrols)werecorrectlydiagnosedinanother researchstudy.Althoughtheintra-evaluatorrepeatabilityof the“hotspot”countwasacceptable,itsinter-evaluator repro-ducibilitywasweak.45
InanAustrianstudy,thermographic investigationofFM showed adiagnostic accuracyofonly 60% ofthe so-called “hotspots”fortenderpoints.46
Conversely,astudyconductedinItalyfoundnodifferences inheatdistributionpatternsin156patientswithFMcompared withpatients withosteoarthritis ofthespine. Theauthors concludedthatthermographycouldnotbeadiagnostic instru-mentforFMsyndrome.47
Astudy aimed atassessing the neurogenicresponse to pressurestimuliappliedtothedorsalareasof16patientswith FMandto16healthycontrolssuggestedalower thermograph-icallymeasuredskintemperatureatrestinpatientswithFM. Theauthorsproposedthatsuchafindingwouldresultfrom increasedadrenergicsympatheticactivityatrest.No signif-icant differences were foundbetweenthe groups afterthe stimuli.48
Astudyusedstimulationwithcoldwaterandsubsequent thermographic evaluationto examinepotential differences betweentheautonomicnervoussystemsofpatientswithFM andhealthycontrols.Nosignificantdifferenceswere identi-fiedbetweenthegroups.49
A study involving 23 women with FM and 15 healthy controlsobservedthat patientswithFM showedlower tol-erancetocoldwaterthanparticipantsinthecontrolgroup.
Conversely,thetemperature recoverypatternswere similar inbothgroups.50
Insummary,thestudies revealednopattern of thermo-graphicchangesinFMsyndrome.Therearenoconsistentdata evaluatingtheuseofthermographyinpatientswithFM,and thefewpublishedstudiesfailtosupporttheuseof thermo-graphyasadiagnosticmethodforFM.
Recommendation
Thereisnoscientificevidencetorecommendusing thermo-graphyforthediagnosisofFM.
Whenshouldwerequestpolysomnographyforthe
diagnosisofFM?
Sleepdisorders are amongthemainmanifestationsofFM. However,theroleofthesechangesintheirpathophysiology isstillcontroversial.
MorkandNilsenshowedthatsleepproblemsamongyoung womenwereassociatedwiththeriskfordevelopingFM.The riskincreasedproportionallytotheintensityofthesleep prob-lemsandwiththeincreaseofthepatientagegroup(B).51
SleepdisordersoccurinFMregardlessoftheassessment instrument.Thesymptomsvary,butthemostfrequent com-plaintsarepoorqualitysleep,insufficientsleep,andlightand fragmentedsleep(withahighnumberofawakenings). How-ever, current evidencedoesnotpermitconfirmation ofthe importanceofsleepforthepathogenesisandmaintenance ofFMsymptoms,accordingtoDiaz-Pietra(B).52
Inpolysomnographicassessments,bothpatientswithFM andpatientswithprimaryinsomniashoweddecreasedtotal sleep times and increased latency to persistent sleep and timesofawakeningsafterstartingsleepingwhencompared withnormalpeople.PatientswithFMhadahighernumberof shortwaves,lowerlatencytopersistentsleep,andahigher frequencyofnight awakeningsthan patients withprimary insomnia.Theauthorsconcludedthatthosechangessuggest thatpatientswithFMhaveahigherinabilitytomaintain con-tinuoussleepthancasesofprimaryinsomnia(B).53
The cyclical alternating pattern (CAP) is a neuro-physiological marker of sleep instability observed in elec-trophysiological studies in both normal and pathological conditions.Itexpressesaconditionofinstabilityatthelevel ofvigilanceandleadstobrainfatigueinsleeppreservation andregulation.TheCAPindex(totalCAPtime/non-rapideye movement(REM)sleeptime)isincreasedinFMandis corre-lated withtheseverityofclinicalsymptoms(tenderpoints) andwiththedecreaseinsleepefficiency,withanincreased ratio ofnon-REMsleep andtwiceasmany awakeningsper hourofsleep(B).54
Recommendation
Wedonotrecommendusingpolysomnographyforthe diag-nosisofFM.
IsthediagnosisofFMadiagnosisofexclusion?
women,andthe lackofobjectiveimagingdataand labora-torytestsaresomeofthecharacteristicsthatmaygenerate diagnosticconfusionbecausethesesymptomsarepresentin ahighnumberofotherdiseases(D).55,56
InpatientswithdiagnosticsuspicionofFM,Sheyferetal. showedthat therheumatologist confirmstheclinical diag-nosisin71% cases.Non-specificarthralgia andrheumatoid arthritiswerethemaindifferentialdiagnoses inthis study. When assessedbya family physician,agreement withthe diagnosisoftherheumatologistwas87%(B).55
The1990ACR Diagnostic Criteriashowed high sensitiv-ityandspecificitywhenwidespreadchronicpainandtender pointcountswerepresent.FMshouldbeconsidereda clini-calsyndromewithspecificcharacteristicswithoutrequiring excludingotherconditionsthatmightbepartofits differen-tialdiagnosisaccordingtotheauthorsofthatstudy.FMshould notbeclassifiedintoprimaryorsecondarytypesbutinstead intoisolatedorassociatedFM(B).12
Inthestudyreportingthe2010preliminarycriteriaforthe diagnosisofFM,thecompositionofthecriteriaused2indices: theWPI(0–19)andtheSSscale(0–12).Inthisstudy,theauthors recommendedexcludingotherdiseasesthatmaybeconfused withFM(B).13
Similarly, Goldenberg DL listed clinical situations that should be part of the differential diagnosis of FM and thatmay beruledoutthrough laboratoryorimagingtests, citing rheumatoid arthritis, systemic lupuserythematosus, polymyalgiarheumatica,myopathies,ankylosingspondylitis, hypothyroidism,andperipheralneuropathies(D).57
Thepresenceofcommonsymptomsassociatedwiththe functional nature ofvarious conditionsled Yunus MBinto groupingthemintoso-calledcentralsensitivitysyndromes, whichincludechronicfatiguesyndrome,irritablebowel syn-drome,migraine,andtemporomandibularjointdysfunctions, inadditiontoFM(B).58
Arecentreviewofthe2010/2011criteriaproposedthe valid-ity ofthe FM diagnosis independent from other diagnoses (B).25
Recommendation
FM should not be considered a diagnosis of exclusion, althoughwesuggestalwaysconsideringdifferentialdiagnoses withothersyndromesordiseaseswithsimilarsymptoms,as recommendedbythe2010ACRcriteria.
ShouldweevaluatemooddisordersinpatientswithFM? How?
Therole ofpsychiatricdisorders inFMisstillcontroversial intheliterature.Althoughseveralstudieshaveshownthat therewerehighfrequenciesofpsychiatricdiagnoses, espe-ciallydepressionandanxiety,otherauthorshavedisputedthis statement(B).37,59
Psychological variables, including depression and anxi-ety,wereassociatedwiththeperceptionofincreaseddisease severityandworsenedfunctionalcapacity(B).60
Theseverityofpsychiatricsymptomsshouldbea poten-tialprognosticfactorforFMtobeconsideredintherapeutic interventions(B).61
Thepossibilityofestablishingsubgroupsofpatientsbased onthepresenceofpsychologicalchangeshasbeendiscussed in theliterature. Thestudy byGiesecke et al.showed that patients with FM may be classified based on psychosocial domains(depression/anxiety),cognitivedomains(pain catas-trophizing/control),andneurobiologicaldomains(pain)using instruments such as the Center for Epidemiologic Studies DepressionScale[fordepression],theState-TraitPersonality Inventory (for anxiety-related symptoms), the Visual ana-log scale (VAS), dolorimetry and pressure-pain applied at suprathresholdvalues,andtheCoping Strategies Question-naire(CSQ)[inattention,feelingofpain,coping,prayerorhope, andpaincatastrophizing](B).62Thefirstsubgroupofpatients
wascharacterizedbymoderateindicesofmoodchanges, mod-eratelevelsofpaincatastrophizing,andcontrolandlowlevels ofpain.Asecondsubgroupshowedhighvaluesinthemood disorderevaluations,thehighestvaluesinthepain catastro-phizingscale,andthelowestvaluesofpaincontrolwithhigh levelsofpain.Thethirdsubgrouphadnormalmoodindices, verylowlevelsofpaincatastrophizing,andthehighestlevel ofpaincontrol,despitethehighlevelsofpain(B).62
Theliteratureindicatesthattheevaluationofpsychiatric comorbiditiesorpsychologicalvariablesinpatientswithFM maybeconductedusingseveralspecificinstrumentsor com-ponentsofgenericinstruments,includingthefollowingcited instruments andcomponents:theStructuredClinical Inter-viewforDSM-III-R(SCID)foraxialcomponents;theBDI,the BeckAnxietyInventory(BAI);theSF-36,theNEOPersonality Inventory-Revised(NEOPI-R);theBarskyAmplificationScale; andtheWhitelyIndexofHypochondriasis(B).63,64
Inpatientswithchronicpain,depressionandanxietyhave beenmeasuredusingvariousvalidatedinstruments, includ-ingtheCentersforEpidemiologicalStudiesDepressionScale (CES-D),theProfileforMoodStates(POMS),andtheBDI. How-ever,theiradministrationinoutpatientprimarycaresettings becomesimpracticalduetothetimerequiredtofillthemout. Otherinstruments,suchasthePatientHealthQuestionnaire –9(PHQ-9),aremoreappropriateforprimarycarephysicians inidentifyingandmeasuringdepression(B).65,66
Recommendation
Wesuggestthesystematicmeasurementofmooddisorders usingvalidatedinstrumentssuitabletothehealthcarelevelin whichtheyareadministeredbecausetheyarehighly impor-tantwhenassessingtheseverityofpatientswithFM.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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s
1.WolfeF,RossK,AndersonJ,RusselIJ,HebertL.The
prevalenceandcharacteristicsoffibromyalgiainthegeneral population.ArthritisRheum.1995;38:19–28.
3. WhiteKP,SpeechleyM,HarthM,OstbyeT.Co-existenceof chronicfatiguesyndromewithfibromyalgiasyndromeinthe generalpopulation:acontrolledstudy.ScandJRheumatol. 2000;29:44–51.
4. HaqSA,DarmawanJ,IslamMN,UddinMZ,DasBB,RahmanF, etal.Prevalenceofrheumaticdiseasesandassociated outcomesinruralandurbancommunitiesinBangladesh:a COPCORDstudy.JRheumatol.2005;32:348–53.
5. BannwarthB,BlotmanF,Roué-LeLayK,CaubèreJP,AndréE, TaïebC.Fibromyalgiasyndromeinthegeneralpopulationof France:aprevalencestudy.JointBoneSpine.2009;76:184–7.
6. GameroRuizF,GabrielSánchezR,CarbonellAbelloJ,Tornero MolinaJ,Sanchez-MagroI.PaininSpanishrheumatology outpatientoffices:EPIDORepidemiologicalstudy.RevClin Esp.2005;205:157–63.
7. SennaER,DeBarrosAL,SilvaEO,CostaIF,PereiraLV,Ciconelli RM,etal.PrevalenceofrheumaticdiseasesinBrazil:astudy usingtheCOPCORDapproach.JRheumatol.2005;31: 594–7.
8. PereiraAM,ValimV,ZandonadeE,CiconelliR.Prevalenceof musculoskeletalmanifestationintheadultBrazilian population:astudyusingCOPCORDquestionnaires.ClinExp Rheumatol.2009;27:42–6.
9. RuhmanW.Theearliestbookonrheumatism.BrJ Rheumatol.1940;2:140–62.
10.HenchPK.Nonarticularrheumatism,22ndrheumatism review:reviewoftheAmericanandEnglishliteratureforthe years1973and1974.ArthritisRheum.1976;19Suppl:1081–9.
11.YunusM,MaisA,CalabroJ,MillerK,FeigenbaumS.Primary fibromyalgia(fibrositis)clinicalstudyof50patientswith matchedcontrols.SeminArthritisRheum.1981;11:151–71.
12.WolfeF,SmytheHA,YunusMB,BennettRM,BombardierC, GoldenbergDL,etal.TheAmericanCollegeofRheumatology 1990CriteriafortheClassificationofFibromyalgia.Reportof theMulticenterCriteriaCommittee.ArthritisRheum. 1990;33:160–72.
13.WolfeF,ClauwDJ,FitzcharlesMA,GoldenbergDL,KatzRS, MeaseP,etal.TheAmericanCollegeofRheumatology preliminarydiagnosticcriteriaforfibromyalgiaand measurementofsymptomseverity.ArthritisCareRes (Hoboken).2010;62:600–10.
14.WolfeF,ClauwDJ,FitzcharlesMA,GoldenbergDL,HäuserW, KatzRS,etal.Fibromyalgiacriteriaandseverityscalesfor clinicalandepidemiologicalstudies:amodificationofthe ACRPreliminaryDiagnosticCriteriaforFibromyalgia.J Rheumatol.2011;38:1113–22.
15.BernardoWM,NobreMR,JateneFB.Evidence-basedclinical practice.PartII—Searchingevidencedatabases.RevAssoc MedBras(Portuguese).2004;50:104–8.
16.WellsG,SheaB,O’ConnellD,RobertsonJ,PetersonJ,WelchV, etal.TheNewcastle-OttawaScale(NOS)forassessingthe qualityofnonrandomisedstudiesinmeta-analyses.Available at:http://www.ohri.ca/programs/clinicalepidemiology/ oxford.asp.
17.WhitingP,RutjesAW,DinnesJ,ReitsmaJ,BossuytPM, KleijnenJ.Developmentandvalidationofmethodsfor assessingthequalityofdiagnosticaccuracystudies.Health TechnolAssess.2004;8:1–234.
18.HowickJ,ChalmersI,GlasziouP,GreenhalghT,HeneghanC, LiberatiA,etal.Explanationofthe2011OxfordCentrefor Evidence-BasedMedicine(OCEBM)LevelsofEvidence (BackgroundDocument).OxfordCentreforEvidence-Based Medicine.Availableat:
http://www.cebm.net/index.aspx?o=5653.
19.WolfeF,HäuserW.Fibromyalgiadiagnosisanddiagnostic criteria.AnnMed.2011;43:495–502.
20.MoyanoS,KilsteinJ,MiguelC.Newdiagnosticcriteriafor fibromyalgia:heretostay.ReumatolClin.2015;11:210–4.
21.KatzRS,WolfeF,MichaudK.Fibromyalgiadiagnosis:a comparisonofclinical,survey,andAmericanCollegeof Rheumatologycriteria.ArthritisRheum.2006;54:169–76.
22.ClauwDJ,CroffordLJ.Chronicwidespreadpainand
fibromyalgia:whatweknow,andwhatweneedtoknow.Best PractResClinRheumatol.2003;17:685–701.
23.WolfeF,WalittB,HauserW.Whatisfibromyalgia,howisit diagnosedandwhatdoesitreallymean.ArthritisCareRes. 2014;66:969–71.
24.CösterL,KendallS,GerdleB,HenrikssonC,HenrikssonKG, BengtssonA.Chronicwidespreadmusculoskeletalpain–a comparisonofthosewhomeetcriteriaforfibromyalgiaand thosewhodonot.EurJPain.2008;12:600–10.
25.WolfeF,ClauwDJ,FitzcharlesMA,GoldenbergDL,HäuserW, KatzRL,etal.2016Revisionstothe2010/2011fibromyalgia diagnosticcriteria.SeminArthritisRheum.2016;46:319–29.
26.WolfeF.Therelationbetweentenderpointsandfibromyalgia symptomvariables:evidencethatfibromyalgiaisnota discretedisorderintheclinic.AnnRheumDis. 1997;56:268–71.
27.HardenRN,RevivoG,SongS,NampiaparampilD,GoldenG, KirincicM,etal.Acriticalanalysisofthetenderpointsin fibromyalgia.PainMed.2007;8:147–56.
28.EggermontLH,ShmerlingRH,LeveilleSG.Tenderpointcount, pain,andmobilityintheolderpopulation:themobilize Bostonstudy.JPain.2010;11:62–70.
29.HäuserW,HayoS,BiewerW,GesmannM,Kühn-BeckerH, PetzkeF,etal.Diagnosisoffibromyalgiasyndrome-A comparisonofAssociationoftheMedicalScientificSocieties inGermany,survey,andAmericanCollegeofRheumatology criteria.ClinJPain.2010;26:505–11.
30.PetzkeF,GracelyRH,ParkKM,AmbroseK,ClauwDJ.Whatdo tenderpointsmeasure?Influenceofdistresson4measures oftenderness.JRheumatol.2003;30:567–74.
31.TastekinN,UzuncaK,SutN,BirtaneM,MercimekOB. Discriminativevalueoftenderpointsinfibromyalgia syndrome.PainMed.2010;11:466–71.
32.GeHY,WangY,Danneskiold-SamsøeB,Graven-NielsenT, Arendt-NielsenL.Thepredeterminedsitesofexaminationfor tenderpointsinfibromyalgiasyndromearefrequently associatedwithmyofascialtriggerpoints.JPain. 2010;11:644–51.
33.SalliA,YilmazH,UgurluH.Therelationshipbetweentender pointcountanddiseaseseverityinpatientswithprimary fibromyalgia.RheumatolInt.2012;32:105–7.
34.PamukON,Yes¸ilY,CakirN.Factorsthataffectthenumberof tenderpointsinfibromyalgiaandchronicwidespreadpain patientswhodidnotmeettheACR1990criteriafor fibromyalgia:aretenderpointsareflectionofneuropathic pain.SeminArthritisRheum.2006;36:130–4.
35.BidariA,Ghavidel-ParsaB,GhalehbaghiB.ReliabilityofACR criteriaovertimetodifferentiateclassicfibromyalgiafrom nonspecificwidespreadpainsyndrome:a6-month prospectivecohortstudy.ModRheumatol.2009;19:663–9.
36.AmrisK,WæhrensEE,JespersenA,BliddalH,
Danneskiold-SamsøeB.Observation-basedassessmentof functionalabilityinpatientswithchronicwidespreadpain:a cross-sectionalstudy.Pain.2011;152:2470–6.
37.WalkerEA,KeeganD,GardnerG,SullivanM,KatonWJ, BernsteinD.Psychosocialfactorsinfibromyalgiacompared withrheumatoidarthritis:I.Psychiatricdiagnosesand functionaldisability.PsychosomMed.1997;59:565–71.
38.NicassioPM,MoxhamEG,SchumanCE,GevirtzRN.The contributionofpain,reportedsleepquality,anddepressive symptomstofatigueinfibromyalgia.Pain.2002;100:271–9.
40.VallejoMA,RiveraJ,Esteve-VivesJ,GroupICAF.Development ofaself-reportingtooltoobtainacombinedindexofseverity offibromyalgia(ICAF).HealthQualLifeOutcomes.2010;8:2.
41.StuifbergenAK,PhillipsL,CarterP,MorrisonJ,ToddA. Subjectiveandobjectivesleepdifficultiesinwomenwith fibromyalgiasyndrome.JAmAcadNursePract.
2010;22:548–56.
42.WolfeF,FitzcharlesM,GoldenbergD,HauserW,KatzR,Mease PJ,etal.Acomparisonofphysicianbasedandpatientbased criteriafordiagnosisoffibromyalgia.ArthritisCareRes (Hoboken).2016;68:652–9.
43.UsuiC,HattaK,ArataniS,YagishitaN,NishiokaK,Kanazawa T,etal.TheJapaneseversionofthe2010AmericanCollegeof RheumatologyPreliminaryDiagnosticCriteriafor
FibromyalgiaandtheFibromyalgiaSymptomScale:reliability andvalidity.ModRheumatol.2012;22:40–4.
44.AmmerK.Thermalimaging:adiagnosticaidforfibromyalgia. ThermolInt.2008;18:45–50.
45.AmmerK,EngelbertB.Reproducibilityofthehotspotcount inpatientswithfibromyalgia:anintraandinter-observer comparison.ThermolInt.2009;19:47–51.
46.AmmerK,SchartelmullerT,MelnizkyP.Thermographyin fibromyalgia.BiomedThermol.1995;15:77–80.
47.BiasiG,FioravantiA,FranciA,MarcolongoR.Therole computerizedtelethermographyinthediagnosisof fibromyalgiasyndrome.MinervaMed.1994;85:451–4.
48.HauPP,RogerA,ScuddsRA,HarthM.Anevaluationof mechanicallyinducedneurogenicflarebyinfrared thermographyinfibromyalgia.JMusculoskelPain. 1996;4:3–20.
49.DeSchamphelaereE.Thermographicevaluationandanalysis ofacold-watertest:acomparativestudybetweenpatients withthefibromyalgiasyndromeandhealthycontrols. Dissertationpresentedinthe2ndMasteryearinthe programmeofMasterofMedicineinMedicine.Universiteit Gent.AcademicYear2012–2013.
50.BrusselmansG,CarvalhoHN,DeSchamphelaereE,Devulder J,CrombezG.Skintemperatureduringcoldpressortestin fibromyalgia:anevaluationoftheautonomicnervous system.ActaAnaesthesiolBelg.2015;66:19–27.
51.MorkPJ,NilsenTIL.Sleepproblemsandriskoffibromyalgia: longitudinaldataonanadultfemalepopulationinNorway. ArthritisRheum.2012;64:281–4.
52.Diaz-PiedraC,DiStasiLL,BaldwinCM,Buela-CasalG,Catena A.Sleepdisturbancesofadultwomensufferingfrom fibromyalgia:asystematicreviewofobservationalstudies. SleepMedRev.2015;21:86–99.
53.RothT,Bhadra-BrownP,PitmanVW,RoehrsTA,ResnickEM. Characteristicsofdisturbedsleepinpatientswith
fibromyalgiacomparedwithinsomniaorwithhealthy volunteers.ClinJPain.2016;32:302–7.
54.RizziM,Sarzi-PuttiniP,AtzeniF,CapsoniF,AndreoliA,Pecis M,etal.Cyclicalternatingpattern:anewmarkerofsleep alterationinpatientswithfibromyalgia.JRheumatol. 2004;31:1193–9.
55.ShleyferE,JotkowitzA,KarmonA,NevzorovR,CohenH, BuskilaD.Accuracyofthediagnosisoffibromyalgiabyfamily physicians:isthependulumshifting.JRheumatol.
2009;36:170–3.
56.MenningerH.Otherpainsyndromestobedifferentiatedfrom fibromyalgia.ZRheumatol.1998;57Suppl2:56–60.
57.GoldenbergDL.Diagnosisanddifferentialdiagnosisof fibromyalgia.AmJMed.2009;122Suppl:S14–21.
58.YunusMB.Fibromyalgiaandoverlappingdisorders:the unifyingconceptofcentralsensitivitysyndromes.Semin ArthritisRheum.2007;36:339–56.
59.AhlesTA,KhanSA,YunusMB,SpiegelDA,MasiAT. Psychiatricstatusofpatientswithprimaryfibromyalgia, patientswithrheumatoidarthritisandsubjectswithoutpain: ablindcomparisonofDSM-IIIdiagnoses.AmJPsychiatry. 1991;148:1721–6.
60.HawleyDJ,WolfeF,CatheyMA.Pain,functionaldisability,and psychologicalstatus:a12-monthstudyofseverityin fibromyalgia.JRheumatol.1988;15:1551–6.
61.Soriano-MaldonadoA,AmrisK,OrtegaFB,Segura-JiménezV, Estévez-LópezF,Álvarez-GallardoIC,etal.Associationof differentlevelsofdepressivesymptomswith
symptomatology,overalldiseaseseverity,andqualityoflife inwomenwithfibromyalgia.QualLifeRes.2015;24: 2951–7.
62.GieseckeT,WilliamsDA,HarrisRE,CuppsTR,TianX,Tian TX,etal.Subgroupingoffibromyalgiapatientsonthebasisof pressure-painthresholdsandpsychologicalfactors.Arthritis Rheum.2003;48:2916–22.
63.JensenKB,PetzkeF,CarvilleS,FranssonP,MarcusH,Williams SC,etal.Anxietyanddepressivesymptomsinfibromyalgia arerelatedtopoorperceptionofhealthbutnottopain sensitivityorcerebralprocessingofpain.ArthritisRheum. 2010;62:3488–95.
64.JansenGB,LinderJ,EkholmKS,EkholmJ.Differencesin symptoms,functioning,andqualityoflifebetweenwomen onlong-termsick-leavewithmusculoskeletalpainwithand withoutconcomitantdepression.JMultidiscipHealthc. 2011;4:281–92.
65.PoleshuckEL,BairMJ,KroenkeK,DamushTM,TuW,WuJ, etal.Psychosocialstressandanxietyinmusculoskeletalpain patientswithandwithoutdepression.GenHospPsychiatry. 2009;31:116–22.
