REVISTA
BRASILEIRA
DE
REUMATOLOGIA
www . r e u m a t o l o g i a . c o m . b r
Case
report
Coexisting
systemic
lupus
erythematosus
and
sickle
cell
disease:
Case
report
and
literature
review
Teresa
Cristina
M.V.
Robazzi
a,∗,
Crésio
Alves
b,
Laís
Abreu
b,
Gabriela
Lemos
baPediatricrheumatology,UniversidadeFederaldaBahia,Salvador,BA,Brazil bUniversidadeFederaldaBahia,Salvador,BA,Brazil
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Articlehistory: Received8May2012 Accepted14May2013
Availableonline28November2014
Keywords: Sicklecellanemia Sicklecelldisease
Systemiclupuserythematosus Hemoglobinopathies
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Objective:Toreportacaseofcoexistingsystemiclupuserythematosus(SLE)andsicklecell disease(SCD)withareviewoftheliteratureonthetopic.
Methodology:Casereportandliterature reviewoftheassociation betweenSLE andSCD throughscientificarticlesinhealthsciencesdatabases,suchasLILACS,MEDLINE/Pubmed andScielo,untilMay2012.Descriptorsused:1.Sicklecellanemia;2.Sicklecelldisease;3. Systemiclupuserythematosus;4.Hemoglobinopathies.
Results:TheauthorsdescribeanassociationbetweenSLEandSShemoglobinopathyinan eight-year-oldfemalepatientpresentingarticular,hematologicandneuropsychiatric mani-festationsduringclinicalevolution.Forty-fivecasesofassociationbetweenSLEandSCDare describedinliterature,mostlyadults(62.2%),women(78%)andwiththeSSphenotypein 78%ofthecases,anddiverseclinicalmanifestations.Comparedwithourpatient,articular, hematologicandneuropsychiatricmanifestationswerepresentin76%,36%and27%ofthe cases,respectively.
Conclusion:SLEandSCDarechronicdiseasesthathaveseveralclinicalandlaboratory find-ingsincommon,meaningdifficultdiagnosisanddifficultyinfindingthecorrecttreatment. Althoughtheassociationbetweenthesediseasesisnotcommon,itisdescribedinliterature, soitisimperativethatphysicianswhotreatsuchdiseasesbealerttothispossibility.
©2014ElsevierEditoraLtda.Allrightsreserved.
Coexistência
de
lúpus
eritematoso
sistêmico
e
doenc¸a
falciforme:
relato
de
caso
e
revisão
da
literatura
Palavras-chave: Anemiafalciforme Doenc¸afalciforme
r
e
s
u
m
o
Objetivo:relatarumcasodecoexistênciadelúpuseritematososistêmico(LES)edoenc¸a falciforme(DF)comrevisãodaliteraturasobreotema.
Metodologia:relatodecasoepesquisadaassociac¸ãoentreLESeDFnaliteratura,atravésde artigoscientíficosnasbasesdedadosdeciênciasdasaúde,comoLILACS,MEDLINE/Pubmed
∗ Correspondingauthor.
E-mail:trobazzi@gmail.com(T.C.M.V.Robazzi).
http://dx.doi.org/10.1016/j.rbre.2013.05.004
rev bras reumatol.2015;55(1):68–74
69
Lúpuseritematososistêmico Hemoglobinopatias
eScielo,atémaiode2012.Descritoresutilizados:1.anemiafalciforme;2.doenc¸afalciforme; 3.lúpuseritematososistêmico;4.hemoglobinopatias.
Resultados: osautoresdescrevemaassociac¸ãodeLESehemoglobinopatiaSSempaciente dosexofeminino,oitoanos,apresentandomanifestac¸õesarticulares,hematológicase neu-ropsiquiátricas durante a sua evoluc¸ãoclínica. Na literaturasão descritos45 casos de associac¸ãoentreLESeDF,sendoamaioriaemmulheres(78%)adultas(62,2%),apresentando fenótipoSSem78%doscasosecommanifestac¸õesclínicasvariadas.Comparandocoma nossapaciente,manifestac¸õesarticulares,hematológicaseneuropsiquiátricas,estiveram presentesem76%,36%e27%doscasos,respectivamente.
Conclusões: LESeDFsãodoenc¸ascrônicasqueapresentamdiversosachadosclínicose laboratoriaisemcomum,implicandoemdificuldadesdiagnósticasenacorretaconduc¸ão terapêuticadessasdoenc¸as.Aassociac¸ãoentreessasenfermidadesnãoécomum,masestá descritanaliteratura,porissoéimportantequemédicosquecuidamdessasenfermidades estejamatentosparatalpossibilidade.
©2014ElsevierEditoraLtda.Todososdireitosreservados.
Introduction
Systemiclupuserythematosus(SLE)isamultisystem autoim-mune disease with an incidence of 1.9 to 5.6 per 100,000 inhabitants,1 while sickle cell disease (SCD) is one of
the most common hereditary diseases, affecting mainly black individuals.2 SCD is characterized by a mutation
in the hemoglobin beta chain with formation of abnor-mal hemoglobin (HbS), responsible for microcirculation obstruction, ischemia, tissue necrosis and systemic organ dysfunction.2
ThecoexistenceofSCDandSLEisrarelydescribedin lit-erature,eveninpredominantly blackpopulations, inwhich the prevalenceof bothconditions is higher.3 Wilson et al.
werethefirsttoreportthisassociation.4Perhapsthedefective
activationofthealternative complement pathwayinsickle cellpatientsand theincreasedriskofinfections causedby encapsulated bacteria predisposethis group todevelop an autoimmunedisease.5
Theclinical features ofSCD and SLEmay show similar manifestations,suchasthepresenceoffever,anemia, artic-ular,renal,neurologicalandcardiopulmonaryinvolvements and,consequently,diagnosticdifficulties.Sicklecellpatients showingatypicalsymptomsorrefractoryresponseto conven-tionaltreatmentshouldbeinvestigatedforthepossibilityof coexistenceofdiseases.6
Inviewoftheuncommonoccurrenceofthisassociation, theauthorsdescribeanearlychildhoodcaseandreviewthe previouslyreportedcasesuntilMay2012.
Methodology
Casereportandliteraturereviewoftheassociationbetween SLE and SCD through scientific articles in health sciences databases, such as LILACS, MEDLINE/Pubmed and Scielo until May 2012. Descriptors used: 1. Sickle cell anemia; 2. Sickle cell disease; 3. Systemic lupus erythematosus; 4. Hemoglobinopathies.
Case
report
Female patientdiagnosed withSShemoglobinopathysince birth,showingrecurring, mildpainful vaso-occlusivecrises responsive to traditional hydration and analgesia. Shehas neverreceived bloodtransfusions.Atthe ageofnine, pain symptoms intensified, mainly characterized by repeated crises ofacute and asymmetric polyarthritis ofthe knees, wrists, elbows and ankles, initially attributed to SCD. The clinical pictureevolvedwiththe developmentof photosen-sitivity, astheniaandintermittentfever,withanepisodeof generalizedtonic-clonicseizureassociatedwithtransientleft hemiparesis. Laboratory tests: hemoglobin, 7.9g/dL; hema-tocrit, 25%;WBC, 12.000/mm3; platelet count, 374.000mm3
(160-400.000); hemoglobin electrophoresis HbS 98.7% and HbA21.26%;positiveantinuclearantibody(ANA)1:320
(homo-geneouspattern);positiveanti-dsDNAantibody;erythrocyte sedimentationrate,68mm(<20);C-reactiveprotein,71units (<6);rheumatoidfactor,anti-Sm,anti-SSA,anti-SSB,wereall negativeaswereviralserology.SerumC3,C4andCH50levels
werenormalaswererenalandliverfunctions.Cranial mag-neticresonanceimagingrevealedanareaofhypoperfusionin therighttemporallobe.Thestudyofthecerebrospinalfluid wasnormal.Thepatienthadasiblingwithsicklecellanemia who died atthe age of two from acute myocardial infarc-tion,andhastwomaternalauntsdiagnosedwithcutaneous lupus. Shewas diagnosedwith SLEaccordingto American CollegeofRheumatology(ACR)criteria,7 andthe possibility
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Table1–Coexistingsystemiclupuserythematosusandsicklecelldisease–literaturereview.
Reference Age/Sex HbType Articular involvement
Serositis Renal involvement
Neuropsychiatric involvement
Malar rash
Oralulcer Photosensitivity Discoid lupus
Hematological alterations
ANA
Currentreport 8/F SS + - - + - - - - + +
21 28/F SS + - + - + - + - + +
55/F SS - - + - - - + +
22 8/M SS + - - + + + - + - +
5 63/F SS + - - - - - + + - +
21/M SS + + + - - - + +
16/F SS + + - - - - + - - +
14 35/F AS - - + - - - - - - +
15 30/F SS + + + - - - - - - +
40/M SS + - - - + - +
32/F SC - - - + +
35/F SS + - + - - - +
27/F SS + - - - +
25/F SS + - + - - - +
26/M SC + - - - +
28/F SS + - + - - - +
32/F SS + - - - +
27/F SS + - - - +
40/F SS + - - - + - +
38/F SS + - - - +
17/F SC + - - - + +
16 28/F SC + - + - - + - - - +
23/M SS + + - + + - - - - +
16/F SS + - - + - - - + - +
24/F SS - + + + - - - +
17 17/M SS + + + - + - - + - +
14/F SS + + - + + - - + + +
11/F S + + - + + - - - + +
7/F SS + - + - - - - + - +
9/M SS - + - + - - - +
31 18/F SS - - + + - - - - - +
9 29/M S0- + + - - - - - - + +
33 10/F SS + + - - - - - - + +
19 15/M SS + + + - + - - - + +
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T able 1 – ( Continued ) Refer ence Ag e/Se x Hb TypeArticular inv
olv
ement
Ser
ositis
Renal inv
olv ement Neur opsyc hiatric in v olv ement Malar rash Or alulcer Photosensiti vity Discoid lupus Hematolo g ical alter ations AN A 15/F SS + + -+ + 12 11/F SC -+ + -+ + 3 14/M SS -+ -+ 8/F SS -+ -+ + 20 23/F SC -+ -+ 11 50/F SS + + + -+ 16/F SS + + + -+ 23 27/F SS -+ + + + -+ + 13 24/F SS + -+ -+ -+ 10 10/F SS + + + + + + -+ + 4/F SS + -+ F, female; M, male; Hb , hemo globin; SS , homozygous sic kle cell disease; S  , beta-thalassemia sic kle cell disease; SC, Sic kle-Hemo globin C Disease; AN A, antin uclear antibodies; + , pr esent; -, a bsent.
Discussion
EpidemiologyofSLEandSCD
ThecoexistenceofSCDandSLEisrarelydescribedinthe lit-erature,probablyduetothesmallnumberofcases.Because oftheoverlappingofsymptomsofbothdiseases,particularly thoserelatedtotheCNS,establishingadifferentialdiagnosis betweenthediseasesisunquestionablydifficult.UntilApril 2012, 45 patients with SCD and SLEhad been reported in the MEDLINE database (Table 1). Thirty-five (78%)of these patientswerefemale,while10(22%)weremale.Themajority ofpatientsareadults(62.2%),withameanageof23 years-old atdiagnosis (variation:4to63).Thisresemblesthe age groupofSLEpatientsproposedbyManzi,inwhichthe dis-easedevelopedduringtheagesof15to45.8SLEdevelopedin
patientsaged≤16inonly37.7%ofthecasesdescribed.Among patientswithSCDandSLE,33(78%)hadtheSSphenotype.Due to thecoexistence ofsevere complications,life expectancy oftheseindividuals canpotentiallybereduced when com-paredtothatofindividualswhoarediagnosedwithoneofthe diseases.9Treatmenthasalsobecomeagreatchallenge,since
therearenocontrolledand randomizedtrials(thataddress theimpactofSCD)ofimmunosuppressivedrugsoftenusedin SLE.
ProbableetiologyforcoexistenceofSCDandSLE
TheinfectiouscomplicationsofSCDpatientshavea multifac-torialetiology:splenicatrophy,reducedphagocyticcapacity, defectiveopsonization,reducedproductionofantibodiesand alternativecomplementpathwaycomponents.Someauthors haveproposedthat thedeficiencyoffactors ofthe alterna-tive pathway complement and recurring infections caused by encapsulated bacteria could be the link between the immune complex disease and hemoglobinS.10–12 However,
therehadbeennoreductionofalternativecomplement path-waycomponentsinthisreportorinothersdescribedinthe literature.6,13
Articularmanifestations
Articular disease were present in 35 patients (76%) with SLE and SCD, corresponding to the most common manifestation.5,6,9–11,13–22 The difficulty in diagnosing the
coexistenceofthesetwodiseasesisduetothefactbothhave articular manifestations. Hence, SCD patients’ joint com-plaintsareinterpretedasvaso-occlusivecrises,delayingthe diagnosisofSLE.6,17Inthisstudy,thepatientpresentedwith
aclinicalpictureofanasymmetric,additive,non-deforming polyarthritisunresponsivetoanalgesia and withprolonged evolution. Such characteristics diverge from standard SCD arthritis, whichis usuallyshort-term, monoarticular,acute and recurrent.16 Thus, general practitioners, pediatricians,
Hematologicalmanifestations
Hematologicaldisorders arecommoninbothSCDand SLE.
Table1showspatientswithanemia,leukopeniaor thrombo-cytopenia.Inthisreview,16patients(36%)metatleastone ofthesecriteria.3,5,6,9,10,12,15,17–19,21–24However,hematological
laboratoryevaluationisnotveryspecificand,separately,it doesnotcontributetotheclinicalsuspicionofcoexistenceof bothdiseases.
Inmostcases,SLEanemiaisinitiallynormocyticand nor-mochromicand,ifpersistent,evolvesintomicrocytosisand hypochromia.1 Hemolytic anemia is only found in 13% of
thecases.25Ontheotherhand,thedecreasedhemoglobinin
SCDismoreimportant,reachinglevelsthatrange from6g to9g/dL,25particularlyincasesofsicklecellanemia(HbSS).
Therefore,patients sufferingfrombothdiseases mayshow moresevereanemiaduetotheoverlappingof pathophysio-logicaldisorders.
Leukopenia is identified in20% to 40% ofcases of iso-lateSLE,1includinggranulocytopeniaandlymphopenia.These
findingsare caused by autoantibodies and by the systemic involvement ofthe disease. In SCD, predominantly leuko-cytosis and thrombocytosisare observeddue tofunctional aspleniaaroundtheageoffive.16
Neuropsychiatricmanifestations
Cerebralinfarction,intracranial hemorrhage, cognitive dys-functionandseizuresareneuropsychiatricdisorderscommon tobothSLEandSCD.Theprevalenceofneurologicaldisorders inSLEpatientsisestimatedtobe50%,withlargevariation amongstudies,26whileinSCDitoccursin25%ofpatients.27,28
InSLE,hemorrhage,thrombosisassociatedwith antiphospho-lipidantibodies,hypertensionand thrombocytopeniarelate tocerebrovascularaccident,29whileinSCDtheformationof
aneurysmsand the accumulationofdrepanocytes inbrain vesselspromoteincreasedadhesion,intimalhyperplasiaand limitedendoluminalflow.30 InTable1,onecansee that12
patients(27%)withSLEand SCDhad neuropsychiatric dis-orders,includingseizures,psychosis,cognitivedisordersand cerebrovascularaccident,andonlytwopatientsdidnothave the SS phenotype.10–12,14,16,17,22,23,31 Presumably, individuals
withbothdiseases,particularly ofSSphenotype, are more likelytodevelopcerebrovasculardisease.However,identifying itsetiologyisimperativeforaneffectivetreatment.Additional testsarecriticalforthisdifferentiation.TranscranialDoppler ultrasonographyisavaluabletoolforassessingcerebralblood flowdynamic.30Thepresenceofantiphospholipidantibodies
associatedwiththe increaseofinflammatorymarkersmay suggestlupusetiology,requiringhighdosesofcorticosteroids andadditionalimmunosuppressiveagents.1
Renalmanifestations
BothSCDandSLEcancauseprogressiverenalfailure, particu-larlyjuvenileSLE.Lupusnephritisisreportedin29%to80%of juvenilecases,dependingonthespecialtyoftheresearchers, ifrheumatologistsornephrologists.1ThediagnosisofSLEin
sickle cell individuals could be neglected due to the over-lapping of signals that suggest renal disorder. Proteinuria,
hematuria, hyperfiltration, glomerulopathy, nephrotic syn-drome and chronic renal failure occur in both diseases. However,nephroticsyndromeisparticularlyinterestingsince itoccursmuchmoreofteninSLEthaninSCD.4InTable1,21
patients(47%)developedrenaldiseaseattributedtothe devel-opmentoftheSLE.3,5,6,10,11,13–17,19,21,23Sicklecellnephropathy
hasabroadspectrumofpathologicalpresentations. Glomeru-larhyperfiltration,hemosiderindeposits,papillarynecrosis, corticalinfarction,focalsegmentalglomerulosclerosis, mem-branoproliferativeglomerulonephritiswithorwithout depo-sitionofimmunecomplexes,tubularatrophyandinterstitial fibrosismayoccur.30Duetothewiderenalinvolvement
vari-etyinSCD,renalbiopsybecomesausefuldiagnosticmethod for sickle cell patients with suspected coexistence of SLE. Lupus renal involvement targets glomeruli in most cases, with subendothelial immune deposits and proliferation of mesangialcells.1Thedefinitionofthe etiologyoftherenal
involvementinpatientswithbothSCDandSLEhasdifferent implicationwithregardtomorbidity,mortalityandtreatment options.16
Immunologicmanifestations
BothSCDandSLEshowimportantimmunologic manifesta-tions.Suchinvolvementismentionedinallcasereportsof coexistenceofbothdiseases.TheANAmaybepresentinthe twodiseases,beingpositiveinalmost100%ofSLEpatients.1
Approximately20%ofSCDpatientshavepositiveANAwith titers greater than 1:160;32 however, mechanisms related
to the development of antibodies in such patients remain unknown.16Nonetheless,inthecaseoftheassociationofboth
diseases,morespecificautoantibodies,e.g.anti-dsDNA, anti-SM,anti-SSAandanti-SSB,shouldbeorderedtosupportthe diagnosis.Testingforantiphospholipidantibodiesandlupus anticoagulantarealsosuggested,althoughthesearealsomore commonlyfoundinSLEthaninSDCpatients.23Ourpatient
presentedwithapositiveANAandanti-dsDNA.Anti-Sm, anti-SSA,anti-SSBwerenegativeandC3,C4andCH50werewithin
normallevels.
Serositis
Serositis is a clinical manifestation observed in both SCD (asaconsequenceofvaso-occlusivecrises)andSLEpatients, presentin18patients(42.8%)ofthisreview.3,5,6,9–11,15–19,23The
clinicalsimilaritiesofthesetwodiseasesmaydelaythe diag-nosisofanunderlyingconnectivetissuedisorder;pericarditis insicklecellpatientsisapossibleevidenceofanactive sys-temicautoimmunediseaseand/oraninfectiousprocess.33
Skinmanifestations
Cutaneous involvement is reported in 50% to 80% of SLE patients at diagnosis and in 85% of patients during the courseofthedisease.1Skinmanifestationsmayincludemalar
rash, photosensitivity, vascular skin lesions with nodules and ulceration, palmar/plantar erythema, Raynaud’s phe-nomenon,annularerythema,alopeciaand,lessoften,discoid lupusorlupusprofundus.1Thecharacteristiccutaneous
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mostcommonmanifestationinpatientswithbothSLEand SCDhasnotbeenreportedyet.
Thefollowingcutaneousmanifestationsaredescribedin
Table1: malar rash(26%), discoid lesions (21%), photosen-sitivity (9.3%) and oral ulcers (6.9%).5,9,10,12,16,17,19–23 These
featuresareuncommoninSCD patientsandmay facilitate thediagnosisofassociationofthetwodiseases.5
Conclusion
Thereisconsensusamongauthorsthatphysiciansmayface diagnosticdifficultieswhentreatingaSCDpatientwho devel-ops SLE. These are different diseases, both with greater prevalenceamongblacksandsharingsimilarclinical manifes-tationsduringthecourseofthedisease,delayingthediagnosis ofasystemicautoimmunediseaseinthesepatients.Another confoundingfactoristhatapproximately20%ofSCDpatients haveapositiveANAathighertiters.32
Duetomicrovascularocclusionandhemolyticanemiaat variablelevels,SCDpatientswillhaveclinicalmanifestations, suchasseverelocalizedordiffusepainthatmaybeassociated withedemaanderythema,aswellaschestpain,pulmonary infiltrates,cardiomegaly,congestiveheartfailure,abdominal painandothervaso-occlusivemanifestations.2
Thelimitednumberofcasespublishedintheliteratureon thecoexistenceofSLEandSCDinthesameindividualdoes notallowstatingifSCDpatientsaremorelikelytodevelop SLE.
According to the findings shown in this review, the presence of certain clinical features in SCD should alert pediatricians, hematologists and rheumatologists to the possibilityofSLEdiagnosis,particularlyarticular manifesta-tionsunresponsivetousualsupportivemeasures,recurrent and refractory neuropsychiatric manifestations (especially if associated to the presence of antiphospholipid antibod-ies), presence of nephrotic proteinuria and, also, presence of leukopenia and/or thrombocytopenia. Renal biopsy and assessmentofthespecificantibodies forSLEcouldbevery usefulinthesecases,justaspositivityforotherclinical man-ifestations,suchasmalarrash,photosensitivity,oralulcers, alopeciaanddiscoidlupus.
Prospectivestudies arerequiredtoclarifywhich mecha-nismsleadSCDindividualstodevelopSLEorifthecoexistence ofthesetwodiseasesisamerecoincidence.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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1. BenselerSM,SilvermanED.Systhemiclupuserythematosus. PediatrClinNAm.2005;52:443–67.
2. LoureiroMM,RozenfeldS,PortugalRD.Acuteclinicalevents inpatientswithsicklecelldisease:epidemiologyand treatment.RevBrasHematol.Hemoter.2008;30:95–100.
3. LubanNL,BoeckxRL,BarrO.SicklecellanemiaandSLE.J Pediatr.1980;96:1120.
4.WilsonFM,CliffordGO,WolfPL.Lupuserythematosus associatedwithsicklecellanemia.ArthritisRheum. 1964;7:443–9.
5.AppenzellerS,FattoriA,SaadST,CostallatLT.Systemiclupus erythematosusinpatientswithsicklecelldisease.Clin Rheumatol.2008;27:359–64.
6.KatsanisE,HsuE,LukeK,McKeeJA.Systemiclupus erythematosusandsicklehemoglinopathies:areportoftwo casesandreviewoftheliterature.AmJHematol.
1987;25:211–4.
7.HochbergMC.UpdatingtheAmericanCollegeof Rheumatologyrevisedcriteriafortheclassificationof systemiclupuserythematosus.ArthritisRheum. 1997;40:1725.
8.ManziS.Lupusupdate:perspectiveandclinicalpearls.Cleve ClinJMed.2009;76:137–42.
9.KaloterakisA,FiliotouA,HaziyannisS.Sickle
cell/◦-thalassemiaandsystemiclupuserythematosus.
Lupus.1999;8:778–81.
10.WilsonWA,NicholsonGD,HughesGR,AminS,AlleyneG, SerjeantGR.Systemiclupuserythematosusandsickle-cell anaemia.BrMedJ.1976;1:813.
11.WilsonWA,DecelauerK,MorganAG.Sicklecellanemia, complement,andsystemiclupuserythematosus.Arthritis Rheum.1979;22:803.
12.WarrierRP,SahneyS,WalkerH.Hemoglobinsicklecell diseaseandsystemiclupuserythematosus.JNatlMedAssoc. 1984;76:1030–1.
13.KarthikeyanG,WallaceSL,BlumL.SLEandsicklecell disease.ArthritisRheum.1978;21:862–3.
14.KanodiaKV,VanikarAV,GoplaniKR,GuptaSB,TrivediHL. Sicklecellnephropathywithdiffuseproliferativelupus nephritis:acasereport.DiagnPathol.2008;3:9.
15.MichelM,HabibiA,GodeauB,BachirD,LaharyA,Galacteros F,etal.Characteristicsandoutcomeofconnectivetissue diseasesinpatientswithsickle-celldisease:Reportof30 Cases.SeminArthritisRheum.2008;38:228–40.
16.KhalidiNA,AjmaniH,VargaJ.Coexistingsystemiclupus erythematosusandsicklecelldisease:adiagnosticand therapeuticchallenge.JClinRheumatol.2005;11:86–92.
17.SaxenaVR,MinaR,MoallemHJ,RaoSP,MillerST.Systemic lupuserythematosusinchildrenwithsicklecelldisease.J PediatrHematolOncol.2003;25:668–71.
18.ShettyAK,BaligaMR,GedaliaA,WarrierRP.Systemiclupus erythematosusandsicklecelldisease.IndianJPediatr. 1998;65:618–21.
19.EissaMM,Lawrence3rdJM,McKenzieL,LittleFM,Mankad VN,YangYM.Systemiclupuserythematosusinachildwith sicklecelldisease.SouthMedJ.1995;88:1176–8.
20.ShawHE,OsherRH,SmithJL.Amaurosisfugaxassociated withSChemoglobinopathyandlupuserythematosus.AmJ Ophthalmol.1979;87:281–5.
21.ChernerM,IsenbergD.Theoverlapofsystemiclupus erythematosusandsicklecelldisease:reportoftwocases andareviewoftheliterature.Lupus.2010;19:
875–83.
22.OqunbiyiAO,GeorgeAO,BrownO,OkaforBO.Diagnosticand treatmentdifficultiesinsystemiclupuserythematosus coexistingwithsicklecelldisease.WestAfrJMed. 2007;26:152–5.
23.WhiteLE,ReevesJD.PolyarthritisandpositiveLEpreparation insicklehemoglobinopathies:areportoftwocases.JPediatr. 1979;95:1003–4.
24.NossentJC,SwaakAJC.Prevalenceandsignificanceof haematologicalabnormalitiesinpatientswithsystemic lupuserythematosus.QJMed.1991;80:605–12.
26.BrunsA,MeyerO.Neuropsychiatricmanifestationsof systemiclupuserythematosus.JointBoneSpine. 2006;73:639–45.
27.AdamsRJ,MckieVC,HsuL,FilesB,VichinskyE,PegelowC. Preventionofafirsstrokebytransfusionsinchildrenwith sicklecellanemiaandabnormalresultsontranscranial dopplerultrasonography.NEnglJMed.1998;339:5–11.
28.PreulMC,CendesF,JustN,MohrG.Intracranialaneurysms andsicklecellanemia:multiplicityandpropensityforthe vertebrobasilarterritory.Neurosurgery.1998;42:971–7.
29.AinialaH,LoukkolaJ,PeltolaJ,KorpelaM,HietaharjuA.The prevalenceofneuropsychiatricsyndromesinsystemiclupus erythematosus.Neurology.2001;57:496–500.
30.LonerganGJ,ClineDB,AbbondanzoSL.Sicklecellanemia. Radiographics.2001;21:971–94.
31.PhamPT,PhamPC,WilkinsonAH,LewSQ.Renal abnormalitiesinsicklecelldisease.KidneyInt.2000;57: 1–8.
32.BaethgeBA,BordelonTR,MillsGM,BowenLM,WolfRE, BairnsfatherL.Antinuclearantibodiesinsicklecelldisease. ActaHaematol.1990;84:186–9.
