rev bras reumatol.2014;54(6):437–440
REVISTA
BRASILEIRA
DE
REUMATOLOGIA
ww w . r e u m a t o l o g i a . c o m . b r
Original
article
The
relationship
between
hemoglobin
level
and
disease
activity
in
patients
with
rheumatoid
arthritis
Smyrnova
Ganna
DepartmentofInternalMedicine,M.GorkyDonetskNationalMedicalUniversity,Donetsk,Ukraine
a
r
t
i
c
l
e
i
n
f
o
Articlehistory:
Received12November2013 Accepted8June2014
Availableonline23October2014
Keywords:
Rheumatoidarthritis Anemia
Diseaseactivity
a
b
s
t
r
a
c
t
Objectives: Thisstudyaimstoinvestigatetherelationshipofhemoglobinlevelwithdisease activityinpatientswithrheumatoidarthritis(RA).
Patientsandmethods:Thehemoglobinlevel,the66/68jointcount,theDiseaseActivityScore 28joints(DAS28),theHealthAssessmentQuestionnaire(HAQ),theVisualAnalogScales (VAS),theModifiedSharpScore(MSS),andthediseasedurationin89patientswithRAwere usedtoanalyzethepossiblerelationship.TheWorldHealthOrganization(WHO)criteriafor anemiausesahemoglobinthresholdof<120g/Lforwomenand<130g/Lformen.Pregnant orbreastfeedingpatients,patientswithahistoryofotherinflammatoryornoinflammatory arthritis,malignancies,chronicinfectiousandinflammatorydiseasesandotherdiseasesin thestageofdecompensationwereexcludedfromthestudy.
Results:Anemiawasobservedin64%ofthepatients(1stgroup);theothergroup(2ndgroup)
hadnormallevelsofhemoglobin.Therewasastatisticallysignificantnegativecorrelation betweenhemoglobinlevelandswollenandtenderjoints’count,DAS28,HAQscore,VAS, MSS,anddiseaseduration(p<0.001).DAS28,HAQscore,VAS,MSS,swollenandtenderjoints’ countanddiseasedurationweresignificantly(p<0.001)higherin1stversus2ndgroup.
Conclusion: Inconclusion,wedeterminedthatlowhemoglobinlevelwassignificantlyrelated todisabilityandimpairment,diseaseactivity,articulardamage,painanddiseasedurationin RApatientsinourstudy.Webelievethatbykeepingdiseaseactivityundercontrol,therefore preventingarticulardamage,thedisabilityinRApatientscanbelessenedorpossiblyeven eliminated.
©2014ElsevierEditoraLtda.Allrightsreserved.
Relac¸ão
entre
o
nível
de
hemoglobina
e
a
atividade
da
doenc¸a
em
pacientes
com
artrite
reumatoide
Palavras-chave: Artritereumatoide
r
e
s
u
m
o
Objetivos:Esteestudotemcomoobjetivoinvestigararelac¸ãoentreoníveldehemoglobina eaatividadedadoenc¸aempacientescomartritereumatoide(AR).
DOIoforiginalarticle:http://dx.doi.org/10.1016/j.rbr.2014.06.002. E-mail:a.smyrnova@mail.ru
http://dx.doi.org/10.1016/j.rbre.2014.06.003
438
rev bras reumatol.2014;54(6):437–440Anemia
Atividadedadoenc¸a
Pacientesemétodos: Avaliou-seapossívelrelac¸ãoexistenteentreoníveldehemoglobina,a contagemde66/68articulac¸ões,oEscoredeAtividadedaDoenc¸a–28articulac¸ões(DAS28),o QuestionáriodeAvaliac¸ãodeSaúde(HAQ),aescalavisualanalógica(EVA),oEscoredeSharp modificado(MSS)eadurac¸ãodadoenc¸ade89pacientescomAR.Oscritériosparaanemiada Organizac¸ãoMundialdeSaúde(OMS)consideramumlimitedehemoglobina<120g/Lpara asmulherese<130g/Lparaoshomens.Pacientesgrávidasouamamentando,pacientes comhistóriadeoutraartriteinflamatóriaounãoinflamatória,neoplasias,doenc¸ascrônicas infecciosaseinflamatóriaseoutrasdoenc¸asdescompensadasforamexcluídasdoestudo. Resultados: Aanemiafoi observadaem64%dos pacientes(1◦grupo);ooutrogrupo(2◦ grupo)apresentouníveisnormaisdehemoglobina.Houveumacorrelac¸ãonegativa estatis-ticamentesignificativaentreoníveldehemoglobinaeacontagemdearticulac¸õesinchadas esensíveis,DAS28,HAQ,EVA,MSSedurac¸ãodadoenc¸a(p<0,001).ODAS28,escoreHAQ, EVA,MSS,contagemdearticulac¸õesinchadasesensíveisedurac¸ãodadoenc¸aforam signi-ficativamentemaiores(p<0,001)noprimeirogrupoemcomparac¸ãocomosegundo. Conclusão:Determinou-sequeobaixoníveldehemoglobinaestásignificativamente correla-cionadocomadeficiênciaeincapacidade,atividadedadoenc¸a,lesãoarticular,doredurac¸ão dadoenc¸aempacientescomAR.Acredita-seque,mantendoaatividadedadoenc¸asob controle,evitandodanosarticularesserápossíveldiminuirou,possivelmente,atémesmo eliminaraincapacidadeempacientescomAR.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Rheumatoidarthritis(RA)isachronicsystemicinflammatory disordercharacterizedbyinflammationinthe synoviumof joints,malaise,morning stiffness and fatigue.1,2 Itis
asso-ciatedwithprogressivejointdestructionand,dependingon the severity, may be accompanied by systemic manifesta-tion including effects on the blood.3 In particular, anemic
syndrome is avery common manifestation ofrheumatoid inflammationthat couldincrease RAactivity and decrease patient’squalityoflife.4Unfortunately,anemiaisnot
consid-eredamajorprobleminrheumatoidarthritisRAbythevast majorityofphysicians.Thisstatementisbasedonthefactthat studiesonanemiainRAaresparse,withfewsystemicreviews, andno extensiveliteratureonits prevalenceandeffecton variousclinicalandfunctionaloutcomes,includingmorbidity, mortality,andqualityoflife.Someresultssuggestthatanemia isassociatedwithanegativeimpactonbothRAsymptomsand qualityoflife.Thusthequestionneedstoberaisedofwhy solittleresearchonanemia-relatedoutcomeshasbeen con-ducted.Thisgapintheliteratureisstrangebecauseanemiais acommoncomorbidityinpatientswithRA.Additional large-scalestudiesonprevalenceandanemia-relatedoutcomesare neededtosupporttheimportanceofanemiascreeningand treatmentinRA.
Thus,theaimofourstudywastoinvestigatethe relation-shipbetweenhemoglobinlevelanddiseaseactivityinpatients withrheumatoidarthritis(RA)byusingthe66/68jointcount, theDAS28,theHAQ,theVAS,theMSS,anddurationofdisease.
Patients
and
methods
Thestudywascomprisedof89Ukrainianpatients(females; mean age 51.7±10.3 years) who were diagnosed with RA
according to the American College ofRheumatology (ACR) classification criteria,5 and written informed consent was
obtained from all of the participants. The patients were assigned to one of two groups on the basis of their hemoglobinconcentration.Thefirstgroupwascomposedof 57femalepatientswhofulfilledthecriteriaforanemia.The World HealthOrganization(WHO)criteriaforanemiausea hemoglobinthresholdof<120g/Lforwomen,and<130g/L formen.Thesecond groupwasmadeupof32non-anemic femalepatients.The66/68jointcount,theDAS28joints,the HAQ,the VAS,theMSSand diseasedurationofeachgroup were usedtoanalyze thepossiblerelationship.Pregnant or breastfeedingpatients,patientswithahistoryofother inflam-matoryornon-inflammatoryarthritis,malignancies,chronic infectiousandinflammatorydiseasesandotherdiseasesin thestageofdecompensationwereexcludedfromthestudy. ThelocalethicscommitteeoftheNationalMedicalUniversity inDonetsk,Ukraine,gavetheirapproval.
BloodsampleswerecollectedusingtheSarstedttube sys-tem (Sarstedt Inc.,Nümbrecht, Germany).Theblood count was thenmeasured electronicallybytheABXMicros ES60 hemotologyanalyzer(HoribaABXSAS,Montpelier,France).
The66/68jointcountincludesthemetacarpophalangeal, proximalinterphalangealanddistalinterphalangealjointsof the hands,the metatarsal phalangeal and distal interpha-langealjointsofthefeetandtheshoulder,elbow,wrist,hip, knee,ankle,tarsus,andtemporomandibular,sternoclavicular andacromioclavicularjoints.
Disease activity was determined with the DAS 28 and calculated using the following equation: DAS 28=0.56×√(tender 28 joint count)+0.28×√(swollen 28 joint count)+0.70×ln(erythrocyte sedimentation rate (ESR), mm/hr)+0.014×general health.6 General health is
subjectglobalassessmentusinga100mmVAS.
Thelevel ofdisabilitywas investigatedusingthe HAQ,7
rev bras reumatol.2014;54(6):437–440
439
Table1–ComparisonoftheRAactivityofthetwogroups.
Parameters P-values 1stGroup
(57patients)
2ndGroup (32patients)
DurationofRA,years 0.004 11.62±3.54 7.63±3.48
Swollenjoint 0.002 28.67±9.01 16.53±8.27
Tenderjoint 0.001 31.42±10.07 18.52±11.28
DAS28 0.001 5.2±1.3 2.8±1.1
HAQ 0.02 1.4±0.6 1.98±0.55
VAS(painassessment),mm 0.004 68.11±12.34 37.17±9.48
VAS(globalassessmentofdiseaseactivity),mm 0.004 71.21±15.42 44.56±11.41
MMS 0.001 235.37±24.82 137.54±19.61
andgrooming,arising,eating,walking,hygiene,reach,grip, and commondailyactivities. Responsesineach functional areaarescoredfrom0(withoutanydifficulty)to3(unableto do).Thehighestscorerecordedforanyquestioninacategory isthescoreforthatcategory,unlessaids,devices,orhelpfrom anotherpersonisrequired.Dependenceonaidsordevicesor helpfrom othersresultsinaminimumcategoryscoreof2. TheHAQscoreiscalculatedasthesumofthecategoryscores dividedbythenumberofcategoriesscored,givingapossible rangeofscoresfrom0to3.
Patientswereaskedtoassesstheiraveragepainduringthe pastweekonaVAS(0to100mm).Thescalerangesfrom0(no pain)to100(severepain).Patientswerealsoaskedtoassess theirdiseaseprogressiononaVAS(0to100mm).Theymarked onaVAStheiroverallassessmentofhowtheirRAhasaffected them,ratinghowtheyaremanagingfrom0(verywell)to100 (verypoorly).TheVASscoresweremeasuredinmillimeters.8
TheMSSwasusedinourstudytoevaluatestructural artic-ulardamageviaplainX-raystakenofbothhandsandfeet.9
Theerosionscorepereachjointofthehandsrangesfrom0 to5,and,pereachjointofthefeet,rangesfrom0to10.The maximumtotalerosionscorefortwohandsis160,thehighest narrowingscoreis120,andthemaximumMSSscoreis280. Themaximumtotalerosionscoreforfeetis120,thehighest narrowingscoreis48,andthemaximumMSSscoreis168.The maximumtotalscoreforonepatientis448.
Statisticalanalyses were performedusing the MEDSTAT version 4.0 for Windows software program (The MEDSTAT Group,Inc.,AnnArbor,MI).TheShapiro-Wilknormalitytest wasemployedto assesswhether or notthe datawas nor-mally distributed and descriptive data was presented as mean±standard deviation (SD) because the data was dis-tributednormally.Correlationsbetweenhemoglobinleveland swollenandtenderjointcount,theDAS28,HAQscore,VAS, MSS,anddiseasedurationwereinvestigatedwithSpearman’s rankcorrelationtest.AP-valueoflessthan0.05was consid-eredtobestatisticallysignificant.
Results
Anemiawasobservedin57(64%)ofthepatients(1stgroup).
The others (2nd group) had normal levels of hemoglobin
(135.5±10.7 g/l).The patientsfrom the 1st and 2nd groups
werestatisticallysimilarwithregardtoage(p=0.21).The clin-icalparametersofthepatientsareshowninTable1.TheDAS 28,HAQscore,VAS,MSS,swollenandtenderjointcount, dis-easedurationweresignificantly(p<0.001)higherin1stgroup
compared to the 2nd. The results ofa correlation analysis
betweenthehemoglobinlevelandtheclinicalparametersof RAactivityareshowninTable2.Therewerestatistically sig-nificantnegativecorrelationsbetweenthehemoglobinlevel andtheswollenandtenderjoint,DAS28,HAQ,MSS,VAS,and diseaseduration(p<0.001).
Discussion
WefoundthatdurationandactivityofRAweresignificantly (p<0.05)higherinpatientswithanemiacomparedtopatients withnormalhemoglobinlevel.In2009,Furstetal.10reported
thatanemic syndromeinRApatientscould beamarkerof highactivityandseverityofdisease.Similarly,Borahetal.11
reportedthatRAactivity,accordingtotheDAS28andHAQ score,wassignificantlyhigherinpatientswithanemia com-paredtopatientswithnormalhemoglobinlevel(6.85±0.64; 1.41±0.44 and 4.76±1.29; 0.7±0.25, respectively; p<0.05). Resultsofotherstudies haveshownthatpatientswithlow hemoglobinlevelhadhighernumberofaffectedjointsthan patientswithoutanemia.12Similartothecurrentliterature,
wefoundnegativecorrelationbetweenthehemoglobinlevel and the swollen/tender joint,DAS 28,HAQ, MSS,VAS, and diseaseduration.
Thewellestablishedrelationshipbetweeninflammation and anemia was confirmed in different studies by signifi-cantassociationsbetweenlowerhemoglobinconcentrations andhigherDAS28,andbyfasterhemoglobinnormalization after TNF-␣ blockade. Anemia in RA may be caused by a shortenedredbloodcelllifespan,pathologicironhomeostasis
Table2–Theresultsofacorrelationanalysisbetween thehemoglobinlevelandtheclinicalparametersofRA activity.
Laboratorytest Correlation
coefficient(r)
P-values
DurationofRA,years -0.62 p<0.001
Swollenjoint -0.61 p<0.001
Tenderjoint -0.59 p<0.001
DAS28 -0.57 p<0.001
HAQ -0.48 p<0.001
VAS(painassessment),mm -0.52 p<0.001 VAS(globalassessmentof
diseaseactivity),mm
-0.59 p<0.001
440
rev bras reumatol.2014;54(6):437–440inducedbyhepcidin,andbluntedresponsetoerythropoietin. Cytokinesalsohaveadirecttoxiceffectonerythropoietin. Kul-lichetal.13foundthatTNF-␣levelwassignificantlyhigherin RApatientswhohadanemia,thaninthosewithoutit. Simi-larly,Zhuetal.reportedthatpatientssufferingfromRAand anemiahadincreasedTNF-␣levelanddecreasedserum eryth-ropoietinconcentration.Thisallowedtheauthorstosuggest thatTNFinhibitstheproductionoferythropoietin. Interest-ingly, erythropoietin treatment reduced disease activity in RApatientsandtissuedamageincollagen-inducedarthritis models.Hepcidinmaytriggerfunctionalirondeficiencyupon inductionbyTNF-␣,interleukin-6,resultinginreduced intesti-nalironuptakeatthemucosalbarrier,andironretentionin thereticule-endothelialsystemviainternalizationofthesame exclusivecellularironexporterferroportinonbothcelltypes. Corticosteroidsmaycarryanincreasedriskofanemiadueto toxicmucosaldrugeffectsorabiasbyindication.
Insummary,theseresultsindicatethatanemiamayserve aspredictorofworseoutcomeinRApatients.Ourdatasuggest thatanemiaisassociatedindependentlyofcommondisease activityoutcomemeasures.Thisreportmayaddclinical back-groundtorecentdiscoveriesatthenexus ofinflammation, hematopoiesisandironmetabolism,andhighlightsthe clin-icalimplicationsofanemiainRA.DiagnosisofanemiainRA shouldpromptathoroughsearchforsubclinicaldisease activ-ity,afterexclusionofotherfrequentcauses.
Conflicts
of
interest
Theauthordeclaresnoconflictsofinterest.
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