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TheMcGovernMedicalSchool
JournalofMedicine
July14,2016
Volume1,Issue1
ManojThangamMD‐EditorInChief
JeremyA.RossMD‐AssociateEditor
Volume by Ahmed A Salahudeen MD
Volume is in reference to intravascular volume resuscitation. The imagery is intentionally dramatic,
fantastical and horrific in its attempt to capture the clinical magic of administering IV fluids-- a very
simple treatment that can save lives. On the other hand, the imagery might invoke the sensation of
drowning. This sinister perspective might make volume overload, a clinical condition in which excessive
intra/extravascular fluids can literally drown the patient from within, a more apt title reference. The
picture isn't always clear in medicine...
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ClinicalImages
5‐7
IncidentalDetectionofaThrombosedCoronaryAneurysmbyCardiac
MagneticResonanceImagingFollowingMyocardialInfarction
GabrielaSanchezPetitto,DanielOcazionez‐Trujillo,JasonAu,andSalmanA.Arain
8‐11 NotAllMegacolonisToxic.
ManojThangam,JeremyA.Ross,andAmitJ.Patel
12‐13 RicketsLeadingtoFemoralBowingandFracture
VikasGupta,JasonM.Podolnick,NicholasIbanez,KimberleyA.Pate,andNathaniel
P.Avila
14‐15 AGrowingPainintheArm
KarlaBermudezandJoanBull
CaseReports
16‐18 ADyingPatientWithNoAdvocate
KalynCollard,IgnacioDeCicco,IoannisLiras,BlaineSmith,andGabrielAisenberg
19‐23 Anti‐NeutrophilCytoplasmicAntibodies(ANCA)positiveserologyina
patientwithUlcerativeColitis.
AnjuMohan
24‐31 CoronaryArteryThrombosisAssociatedwithEnergyDrink
Consumption
RicardoJ.Hernandez,ManojThangam,HVernonAnderson,andJohnP.Higgins
32‐37MycobacteriumFortuitumInfectionoftheScalpafteraSkinGraft.
BlaineSmith,IoannisLiras,IgnacioDeCicco,KalynCollard,andGabrielAisenberg.
38‐44 HyperesoinophilicSyndromeina17‐YearOldFemaleMimickingHeartFailure
DanielleStoneandJamesStone
45‐49Biventricularfailureastheinitialmanifestationofthyrotoxicosisduring
pregnancy. AmitJ.Patel,ChristinaParuthi,andSalmanArain,
50‐54ARareCaseofMacrophageActivatingSyndrome
ChristineAdaezeNwoha,MD;Akkanti,BinduMD
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55‐55MultidermatomalextensionofRamsayHuntshouldraisesuspicionfor
HIV/AIDS.
IgnacioDeCicco,AbhishekMaiti,FiorellaLlanos‐Chea,andRobertoArduino
57‐61ElevatedLipaselevelsinSmallBowelObstruction
FathimaZahraKamilFaiz
62‐67SpontaneousTumorLysisSyndromeinMetastaticBreastCancer
LeAnneNguyen,GabrielAisenberg
68‐73PositionalSTSegmentElevationCausedbyaVentricularPseudoaneurysm
IgnacioDeCicco,AlexVelasquez,CameronMcBride,JasonAu,GabrielAisenberg,
AlexanderPostalian,RaymundoQuintana‐Quezada,FiorellaLlanosChea,Daniel
OcazionezTrujillo,AbhijeetDhoble,andSalmanArain
74‐80CallforawarenessofWestNilevirusinfection
RohanGupta,ManojThangam,andGabrielAisenberg
QualityImprovement
81‐86IncreasingsafetyofNSAIDprescribingtoosteoarthritispatients.
SarahKazzaz,AnjuMohan,ManojThangam,JamiseCrooms,NidalGanim,Jonas
Gunawan,PoojaGidwani,RaynumdoAQuintanaQuezada,MadelynRosenthal,and
YiChunYeh.
OriginalResearch
87‐96IronDeficiencyAnemiaandThrombocytosis:TheSearchForALink.
NathanielP.Avila,EmmaL.Dishner,andGabrielM.Aisenberg
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IncidentalDetectionofaThrombosedCoronaryAneurysmbyCardiacMagnetic
ResonanceImagingFollowingMyocardialInfarction
GabrielaSanchezPetitto,MD,DanielOcazionez‐Trujillo,MD,JasonAu,MD,SalmanA.Arain,
MD.
Fig1.PanelA.CardiacMRI,coronalaxialblackbloodsequencedemonstratingsaccular
aneurysmintheproximalLAD(arrow).Notethelackofintraluminalflowvoidand
circumferentialedemaofthevesselwallindicativeofacutethrombosis.PanelB.Bright
bloodcinesequenceofCardiacMRI,showingathrombusintheapexoftheleftventricle
(arrow).PanelC.DelayedpostcontrastimagingofCardiacMRI,showingtransmural
delayedenhancementfromanteriorwallinfarct(arrow).
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A31‐year‐oldwomanwithhypertensionpresentedtothehospitalwithananterior
wallmyocardialinfarction(MI).Angiographyrevealedocclusionofthemidleftanterior
descendingartery(LAD)thatcouldnotbecrosseddespitemultipleattempts.Thepatient
madeanuneventfulrecovery,andwasdischargedonoptimalmedicaltherapyforthe
coronaryarterydisease(CAD)andnewleftventriculardysfunction.Twoweekslatershe
presentedtoourhospitalwithanon‐STelevationmyocardialinfarction.Repeat
angiographyshowedpersistentLADocclusionwithoutanewcoronarystenosisor
occlusion.Cardiacmagneticresonance(CMR)imagingwasperformedtodetermine
anteriorwallviabilityanditrevealedathrombosedsaccularaneurysmoftheLADatthe
siteoftheocclusionnotseenduringangiography.Thestudyalsodemonstrateddelayed
transmuralenhancementoftheanteriorandseptalwallsegmentsconsistentwithpoor
myocardialviability.Thepatientwasdischargedafteradjustmentofhermedicaltherapy.
Coronaryarteryaneurysms(CAA)arefocalordiffusedilatationswithinthe
coronaryarterythatexceedthediameteroftheadjacentnormalsegmentsbyatleast1.5
times.TheentitywasfirstdescribedbyMorgagniin1761.TheincidenceofCAAvaries
from0.3%to5.3%inthegeneralpopulation1.Thediagnosisisusuallymadebycardiac
computedtomographyangiography(CCTA),MRI,ortraditionalcatheterbasedcoronary
angiography.OurpatienthadathrombosedCAAwithintheLADthatwasnotidentifiedat
thetimeofangiographybutwassubsequentlydetectedincidentallybyCMR.Thelocationof
theaneurysmwasfundamentalforitsdetectionbecauseCMRisbettersuitedtoevaluatethe
proximalcoronaryarterysegmentsinmostcases2.InthiscaseCMRwasusedtodetermine
cardiacfunctionaswellasstressperfusion.Thepatientwasdeterminedtobeunsuitable
forsinglevesselcoronaryarterybypasssurgeryonaccountofthelackofviabilityinthe
anteriorwall.AlthoughCCTAallowshigherspatialresolutionthanMRIforcoronary
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aneurysms,ourpatientbenefitedfromMRIintermsofviabilityevaluationandavoided
unnecessaryexposuretoionizingradiation.
References
1. CohenP,O'GaraP.CoronaryArteryAneurysms:AReviewoftheNaturalHistory,
Pathophysiology,andManagement.CardiologyinReview.2008;16(6):301‐304
2. MavrogeniS,MarkousisG,KolovouG.Contributionofcardiovascularmagnetic
resonanceintheevaluationofcoronaryarteries.WorldJCardiol.2014.26;6(10):
1060–1066.
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NotAllMegacolonisToxic.
ManojThangam,MD,JeremyA.Ross,MD,AmitJ.PatelDO.
Figure1.Patientinsupineposition.
Figure2.Supineabdominalradiographdisplayingdilationoflargeintestine.
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Figure3.Computedtomographyscanoftheabdomen.Distendedlargeintestinein
transverseplane.
Figure4.Computedtomographyscanoftheabdomen.Distendedlargeintestineinsagittal
plane.
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A42‐year‐oldmanpresentedwithfever,abdominaldistension,andalteredmental
status.Hehadsufferedballistictraumatothecervicalspine22‐yearspriorresultingin
quadriplegiaaswellasneurogenicbladderandbowel.Physicalexaminationrevealeda
distended,non‐rigidabdomen(Figure1)withnormalbowelsoundsandhardstoolinthe
rectalvault.Anabdominalradiographwasobtainedshowingdilationofthetransverse
colonmeasuring19.1cm(Figure2).Computedtomographyscansoftheabdomenand
pelvisrevealedcolonicdilationinthetransverseplanemeasuring20.0cm(Figure3)and
sagittalplanemeasuring18.7cm(Figure4).Initialconcernfortoxicmegacolonprompted
thepatient’sadmissiontothemedicalintensivecareunit.Later,thepatientwasfoundto
havepyuriaandgram‐negativebacteremiathatwastreatedwithintravenousantibiotics.
Hisneurogenicbladderwaslikelythepredisposingculpritforurosepsis.
Gastroenterologyandgeneralsurgerywereconsultedtoevaluateforcolonic
decompressionorpartialcolectomyforrecurrentconstipationinourpatient.Conservative
managementwasdeemedthebestoptionsinceconstipationresolvedwithanimproved
bowelregimenandscheduledsalineenemas.Surgicalmanagementwithsubtotal
colectomyinspinalcordinjury(SCI)patientsisusuallyreservedforpatientswithtoxic
megacolon,bowelperforation,constipationrefractorytointensifiedbowelregimens,or
thosewithsacralulcersconcerningforexcrementalcontamination.1,2Megacolonoccursin
upto72%ofpatientswithSCI.1,3Itisoftendifficulttomanageduetoreduced
responsivenesstolaxativesandmanualintervention.1Ageover50years,useof4ormore
laxativedosespermonth,andgreaterthen10yearspostSCIhavebeenshowntobe
independentcorrelatesofmegacolon.3Inmostcases,medicalmanagementispreferredif
adequatesymptomcontrolcanbeachieved.Therapyistargetedtocleansethecolon,
preventimpaction,andminimizestoolvolumeandgasaccumulation.
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References
1. EbertE.GastrointestinalInvolvementinSpinalCordInjury:aClinicalPerspective.J
GastrointestinLiverDis.2012;21(1):75‐82.
2. TapaniMJ,OlaviKH.SurgicalManagementofToxicMegacolon.
Hepatogastroenterology.2014;61(131):638‐641.
3. HarariD,MinakerKL.Review:Megacoloninpatientswithchronicspinalcord
injury.SpinalCord.2000;38:331‐339.
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RicketsLeadingtoFemoralBowingandFracture
VikasGupta,JasonM.Podolnick,NicholasIbanez,KimberleyA.Pate,NathanielP.AvilaMD.
A60‐year‐oldHispanicfemalewithapastmedicalhistoryofRickets,osteoporosisand
hypothyroidismpresentswithunilateralseverehippainafterfallingfromastanding
position.Shewasoutofthecountrywhenshefell,traveledbackhomeviaairplane,and
presentedimmediatelytotheemergencyroom.Bilateralhipradiographs(Figure1)show
leftsidedcompletefemoralneckfracturewithassociatedsofttissueinflammation.The
radiographisalsosignificantforbilateralbowingwiththeleftworsethanright.Thisis
consistentwithsevererickets.Thepatientwasdiagnosedwithricketsasanadultand
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beganonvitamin‐Dsupplementationafterthedeformityhadoccurred.Herosteoporosis
wasseverewithaT‐scoreof‐3.3onDEXAscan.Orthopedicsurgerywasconsultedand
tookthepatienttotheoperatingroomforfemurrepair.However,shewasfoundtobea
poorcandidateforreamingorbroaching,evenwithosteotomy.Thedecisionwasmadein
theoperatingroomtoperformaunilateralGirdlestoneproceduretoprovideherwithpain
reliefandtolimitherriskforfuturecomplications.
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AGrowingPainintheArm
KarlaBermudezMD,JoanBullMD.
A21‐yr‐oldHispanicmalewithnoknownpastmedicalhistoryexceptremote
traumatohisrightelbowoneyearpriorpresentedtotheemergencydepartmentwith
swellingofhisrightarm(Figure1)andpainbeginningthreeweeksprior.Themasswas
biopsiedforconcernofmalignancy.Pathologicalevaluationsuggestedadiagnosisof
biphasicsynovialsarcoma.Thepatientwasreferredtooncologyandsurgeryfortreatment.
Synovialsarcomaisasofttissuetumorthatconsistofepithelialand/orspindlecells.
Thedifferentialdiagnosisincludesmalignantperipheralnervesheathtumors,muscle‐
derivedsarcomas,andbiphasicmesotheliomas.Thereportedincidenceofsynovial
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sarcomasrangesfrom5.6%to10%.Ninetypercentofthesetumorsareassociatedwitha
chromosomaltranslocation,t(X;18)(p11.2;q11.2).The5‐yearand10‐yearsurvivalratesin
patientswithsynovialsarcomaare50%and20%respectively.Treatmentconsistsoflocal
excisionwithwidemargins,followedbyhighdoseradiationtherapy.Adjuvant
chemotherapycanalsoplayarole.
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ADyingPatientWithNoAdvocate
CollardKMS,DeCiccoIAMD,LirasINMS,SmithBDMS,AisenbergGMD.
Storyfromthefrontlines
An86‐year‐oldmanwithhistoryofdementiacametothehospitalwithananterior
shoulderdislocationafterbeingassaultedinhisgrouphome.Hewasbarelyresponsive,
eventonoxiousstimuli,butwasabletoprotecthisairway.Heseemeduninterestedinfood
andwasonlyabletomumbleafewunintelligiblewords.Personnelfromthegrouphome
werecontacted,andreportedthatthepatienthadbeenatasimilarbaselineforthelast
severalmonths.Abouttwelvehourslaterthepatientwasmorealert,responsive,andable
tofeedhimself.Hisabilitytomakecomplexdecisionswasimpaired.Hisvitalsignswere
normal,andhehadnofocalmotordeficit,orimpairedcranialnervefunction.The
remainderoftheexaminationwasnormal.Acomputedtomographyofthebrain,and
routinelaboratorytestswerenormal,whileRPRandHIVserologywerenegative.
Reassuredbypersonnelathisusualhousehold,alumbarpuncturewaswithheld.The
patienthadnofamilyoranestablishedsurrogatedecisionmaker.Thefollowingdaythe
patientreturnedtothegrouphome,withouthavingappointedaguardian,ormodifiedhis
full‐codestatus.Within48hourshehadreturnedinapparentsepticshockwhich
progressedintocardiopulmonaryarrest,requiring20minutesofresuscitation.Tendays
afterthearrest,thepatienthadvisibleischemiaofthreeofhislimbs,elevatedcreatinine,
andwasonlyabletoopenhiseyeswithnointeractionwithhissurroundings.
Teachablemoment
Thispatientwasfirstidentifiedashavingdementia.Provisionsshouldhavebeen
madetoascertainthepatient’swishesandobtainadvanceddirectivesorfindafamily
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memberorfriendtoserveasasurrogatedecisionmakerintheeventthatthepatientcould
nolongermakedecisionsforhimself.However,asblackandwhiteasthatprocessmay
sound,therealityisquitegray.IneightstatesandtheDistrictofColumbia,guardiansmay
notmakedecisionsregardingend‐of‐lifecare(althoughsomestateshaveexceptions),and
thirty‐sevenstateshavenolanguageintheirguardianshippoliciesregardingend‐of‐life
care.1Morespecifically,whentheissueontargetisthedecisiontoapplyorwithhold
advancedcardiaclifesupport(respectivelydescribedasbeingfullcode,or“Do‐Not‐
Resuscitate”orDNR),notuncommonlytheguardianmaynotbewillingtoimplementor
changeeither.Whilesuchdecisionsshouldnotbemadelightly,oftentheprocessis
complicatedbylonglegalbattlesthatonlyservetoprolongcarethatmayinadvertently
causeharmtothepatient.2
WebelievedthataDNRorderwasappropriategivenourpatient’sapparent
advanceddementia,aslaterconfirmedatthegrouphomeinwhichheresided.However,
therewasnoknownguardiannoranyknownfamilyorfriendsforustocontact.Appointing
acourt‐designatedguardianisanarduousprocess,anddoesn’tensureadequateoutcomes.
Torefereeinthistypeofsituations,mosthospitalshaveanethicscommitteethathelp
guidedecisionsbutcanonlyreplacealegitimatesurrogatedecision‐makerinextreme
conditions.Moreover,timelinessisanobstacletothisoptionbecauseassemblingthis
usuallymultidisciplinarycommitteeoftentakesalongtime.Additionally,themajorityof
themembersofthesecommitteesarephysicians,whichintroducespotentialconflictsof
interesttocontinueprovidingcareinapay‐for‐servicesystem.Anotherdangeristhatthe
physician,whooftendoesnotknowthepatient,willnotactonthepatient’sbehalf.3
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Inconclusion,themedicalsystemisflawedwhenitcomestoend‐of‐lifecareof
thosewhohavenoadvocate.Currently,wemustmuddlethroughthelegalsystemasbest
aswecanwhileprovidingtreatmentweconsiderfutileorevenharmful.
References
1. CohenAB,WrightMS,CooneyL,FriedT.GuardianshipandEnd‐of‐LifeDecision
Making.JAMAInternMed.2015;175(10):1687‐91.
2. HastingsKB.Hardshipsofend‐of‐lifecarewithcourt‐appointedguardians.AmJ
HospPalliatCare.2014;31(1):57‐60.
3. WeissBD,BermanEA,HoweCL,FlemingRB.Medicaldecision‐makingforolder
adultswithoutfamily.JAmGeriatrSoc.2012;60(11):2144‐50.
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Anti‐NeutrophilCytoplasmicAntibodies(ANCA)positiveserologyinapatientwith
UlcerativeColitis.
AnjuMohan,MD
Introduction
TheANCAAssociatedVasculitides(AAVs)includeGranulomatosiswithPolyangiitis
(GPA),formerlyWegener’sgranulomatosis;MicroscopicPolyangiitis(MPA)and
EosinophilicGranulomatosiswithPolyangiitis(EGPA),formerlyChurg‐Strausssyndrome.
Theseprimarysystemicvasculitidesaremulti‐systemdiseasescharacterizedbyapauci‐
immunenecrotizingvasculitisofsmalltomediumsizedbloodvesselswithanassociated
serologicallydetectableANCAinamajorityofthecases.ANCAsareafamilyof
autoantibodiesdirectedagainstcytoplasmicantigens,mainlylysosomalenzymesin
polymorphonuclearneutrophilleukocytes[West224].InmakingadiagnosisofAAVs,the
utilityofANCAsdependsontheclinicalsettingandontheassayused.Indirect
immunofluorescenceisusedtodetectANCApatterns.Threecommonpatternsare
perinuclear(p‐ANCA),cytoplasmic(c‐ANCA)oratypical(notclearlyp‐ANCAorc‐ANCA).
PositiveimmunofluorescenceshouldbefollowedbyELISAforANCAsspecificallydirected
againstproteinase3(PR3)ormyeloperoxidase(MPO),whichareassociatedwithGPAand
MPA,respectively,ingreaterthan80%ofcases[Lally&Spiera,3].
Apartfromtheoccurrenceinprimarysystemicvasculitidesandrapidlyprogressive
glomerulonephritis,p‐ANCAmaybeseeninotherdiseasestates,forexamplerheumatoid
arthritiswithoutsignsofvasculitisandinflammatoryboweldisease[Peenetal.,1].
CasePresentation
A41‐year‐oldAfrican‐Americanwomanwithulcerativecolitisforovertenyears
thatistreatedwithsulfasalazinepresentedtoclinicwithaperivaginalrash.Herlabswere
significantforanemia(hemoglobin10.6)andthrombocytopenia(platelets121).Shehad
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worseningwaterydiarrheaandherperivaginalrashbegantoulcerate.Shesoughtcarein
theemergencydepartmentandwasfoundtohavehemoglobinof4andmacroscopic
hematuria.Subsequentcystoscopyrevealedanecroticbladdermassaswellasnecrotic
vulvarandvaginalwallsonbiopsy.Sheunderwenttransurethralresectionofthebladder
massanddebridementoftheperinealwound.Thebladderbiopsyrevealed
leukocytoclasticvasculitiswithfibrinoidnecrosis,multifocalacuteandorganizedthrombi,
andacuteinflammationofbladderwall.Shewastransferredtoourhospitalforhigherlevel
ofcare.Onexamination,thepatientappearedtobeill.Thegenitalexamrevealed
indurationofentiremonspubis,hyperpigmentation,exposureofsubcutaneoustissue,
signsofchronicinflammationoftheinnerthighswitherythema,sloughing,and
malodorousliquiddischarge.Thevaginawasnarrowedwithnoinguinal
lymphadenopathy.Nasalandoralcavityexamdidnotrevealanycrustingorulcers.Her
eyeandlungexamswerealsonormal.
Laboratorydatarevealedaleukocytosisof13,000cellspermcL,hemoglobinof8
g/dL,creatinineof1mg/dL,positiveANA(1:160titer),positivep‐ANCA(1:40titer),and
positiveMPO.Theevaluationsforc‐ANCA,SSA/B,RNP,anti‐smanddsDNAwerenegative.
Serumelectrophoresisandimmunofixationindicatedchronicinflammationwithpolyclonal
gammopathy.HIVandhepatitispanelswerenegativealongwitherythrocyte
sedimentationrate(ESR)andC‐reactiveprotein(CRP).Bacterial,viralandAFBcultures
fromtheulcersitesfailedtoidentifyanyorganisms.Also,urinecytologywasnegativefor
malignancy.Computedtomography(CT)scansoftheabdomenandpelviswasdidnot
revealanyabnormalities.
Generalsurgery,urology,colorectalsurgeryandgynecologywereconsulted.With
theirassistance,thepatientunderwentextensiveperinealdebridementwithwound
vacuumplacementandnumerousbiopsies.Therepeatbiopsiesshowedacutenecrotizing
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inflammationandareaswithgranulationtissue(seefigure1).Pathologyrevealedno
evidenceofvasculitis.
Broad‐spectrumantibioticsincludingvancomycinandpiperacillin‐tazobactamwere
started.Sulfasalazinewasrestartedafterherpastcolonoscopyreportsshowingulcerative
colitiswereverified.Shewascontinuedonprednisone60mgdailythatwasstartedatthe
outsideinstitution.RheumatologyruledoutMPAbasedontheclinicalpresentationbut
wasconcernedaboutPyodermaGangrenosum(PG).Althoughdermatologywasconsulted,
thepatienthadundergonevastdebridementpriortoconsultationandadefinitive
diagnosiscouldnotbemade.However,thelikelydiagnosiswasbelievedtobepyoderma
gangrenosum.Hence,thediagnosisofInflammatoryBowelDisease(IBD)withPyoderma
Gangrenosumwasmade.Thepatientunderwentadivertingloopsigmoidcolostomy.Post
surgicalintervention,herwoundhealingprogressedgraduallyandasteroidtaperwas
initiated.Afteraprolongedstay,shewasdischargedhomewithhomehealth.
Discussion
PatientswithIBD(60‐80%withulcerativecolitisandupto25%withCrohn’s
disease)arepositiveforp‐ANCA[West234].AlthoughMPOpositivityisrare,itisnot
unprecedented[Peenetal.,57].OurpatientmayhavehadaflareofherIBDconsistingof
worseningdiarrheathatprecededtheonsetofothersymptoms.IBDisalsoknowntobe
associatedwithseveralskinsmanifestationsincludingerythemanodosumandPG.Inour
case,PGwasbelievedtothemostlikelydiagnosis.Nevertheless,shereceivedtreatment
withsystemicsteroidsfortwoweeksfollowedbyataperwhichineffectisthetreatment
forPG.
WhileMPAisassociatedwithp‐ANCA(60%),theserologyisonlysupportiveofthe
diagnosis.Thedefinitivediagnosisismadeonthebasisofacharacteristicclinical
presentationalongwitharenalbiopsyshowingnecrotizingglomerulonephritiswithout
21
immunedeposits[West231].Eventhoughourpatienthadpositiveserologies,itwas
insufficienttomakeadiagnosisofMPA.Moreover,manypatientswithMPApresentwith
acuteonsetofrapidlyprogressiveglomerulonephritis(100%)andupto50%have
pulmonaryinfiltrates.Nonspecificsymptomslikefever(50‐70%),arthralgias(65%)and
purpura(40%)arecommonlyseen[West231,Guillevinetal.,424].Thispatientdidnot
haveanyoftheabovementionedclinicalsymptomsincludingnormalrenalfunction.
Aliteraturereviewrevealedonlyninepreviousreportsofvasculitisinvolvingthe
urinarybladderincludingPAN(6cases),GPA(2cases)andSLE(1case)[Fisheretal.,903]
andisextremelyrare.Thepatient’srepeatbiopsy,however,didnotreportleukocytoclastic
vasculitis.ThehistologyofPGisnon‐specific,butitfacilitatesthediagnosis.Additionally,it
aidsintheexclusionofotherunderlyingdiseases.Inflammatoryinfiltratesconsisting
mainlyofpandermalneutrophilaccumulationcanbeobservedalongwithabscess
formationsandnecrosis.Severalstudieshavedemonstratedthattheunaffected‐appearing
tissuearoundthePGlesionsactuallyhasaperivasculiticnecrotizingpicture,whichcanbe
classifiedasleukocytoclasticvasculitisin40%ofPGpatients[Ehling3077,Crowsonetal.,
101].Thispatientdidhaveabiopsyreadingofleukocytoclasticvasculitiswhichcanbe
explainedbythediagnosisofPG.
Conclusion
Thiscaseisillustrateshowserologycanpointtowardsoneparticulardiagnosis,
MPA,whiletheclinicalpicturepointselsewhere.Italsoreiteratesthefactthatpositive
ANCAsdonotnecessarilyindicatevasculitis.
InthesettingofGPA,MPAorEGPA,P‐ANCAisusuallyduetoanti‐MPOantibodies.
Inotherdisordersp‐ANCApositivityisnotverywellcharacterized.Goodpasture
syndrome,IBD,autoimmuneliverdisease,cysticfibrosisandinfections(HIV,subacute
22
bacterialendocarditisandacuteparvovirusB19)aresomeoftheotherdisorders
associatedwithp‐ANCA[West234].
IBDisknowntocausevariousskinmanifestationsincludingPGwithpositivep‐
ANCAserologies.Nodules,pustules,and/orpapulescombinedwithseverepainmarkPG
withsuddenonset.Theinitialskinulcersdevelopintolargelesionsreachingdiametersof
fivetotencentimeterswithinafewweeks[Ehling3076].Inongoingactivedisease,they
presentasanecrotic,hemorrhagic,suppurativeerosionwithdeep,purple‐red,irregular,
underminedbordersandanerythematoushalo.Inveryaggressive,rapidlyprogressing
forms,thePGlesionscanevenaffectfascia,muscles,andtendons.ThediagnosisofPGis
generallybasedonclinicalsymptomsandhistologicdiagnosis.
Apreviousstudy,whichexamined1132patientswithulcerativecolitis,
interestinglynotedthat20%ofpatientswithPGhadinactivedisease[Mir‐Madjlessi615].
Treatmentincludessystemicsteroidsandsometimespulsedosesteroids.Ifrefractory,
thencytotoxicoptionsincludingcyclosporine,azathioprine,mycophenolatemofetilmaybe
considered.Also,anti‐TNFbiologicsareincreasinglybeingutilized[Ehling3077,Crowson
etal.,103].
References
1. RheumatologySecrets,3rdedition,SterlingG.West,MD.
2. MicroscopicPolyangitis;LoicGuillevinetal.,Arthritis&Rheumatismvol.42,No.3,March
1999.
3. CurrentlandscapeofANCA‐AssociatedVasculitis;LindsayLally,RobertSpira.
4. Anti‐LactoferrinantibodiesandothertypesofANCAinUC,primarysclerosing
cholangitis,andCrohn’sdisease.EPeenetal.GutJournal,1993;34;56‐62
5. TwoCasesofVasculitisoftheUrinaryBladder;AndrewH.Fisher,ArchPatholLabMed‐
vol.122,October1998.
23
CoronaryArteryThrombosisAssociatedwithEnergyDrinkConsumption
RicardoJ.Hernndez,MDa,ManojThangamMDb,H.VernonAnderson,MDc,JohnP.Higgins,
MDMBAMPhild
aDivisionofCardiology,TheUniversityofTexasHealthScienceCenteratHouston
(UTHealth);bDivisionofInternalMedicine,TheUniversityofTexasHealthScienceCenter
atHouston(UTHealth),cInterventionalCardiology,ProfessorofMedicine,TheUniversityof
TexasHealthScienceCenteratHouston(UTHealth);dChiefofCardiology,LyndonB.
JohnsonGeneralHospital,AssociateProfessorofMedicine,TheUniversityofTexasHealth
ScienceCenteratHouston(UTHealth).
Abstract
Energydrinkshavebecomereadilyavailableandarebeingutilizedglobally.
However,thepotentialsideeffectoftheiruseisnotwellunderstood.Mostconsumersuse
thesebeverageswiththegoalofincreasingstamina.However,unintendedramificationsof
energydrinksmayincludeincreasedsympatheticdrive,endothelialdysfunction,and
mitigationofcoronarybloodflow.Afewreportshavebroughttolighttherare
phenomenonofmyocardialinfarctionoccurringsecondarytoenergydrinkconsumption.
Wepresentthiscaseofayounghealthymanwhosufferedamyocardialinfarction
requiringemergentcoronaryinterventiontocontributetothelimitedliteratureavailable
onthistopic.Theincreasingpopularityanduseofenergydrinksnecessitatesfurther
investigationintotheirunintendedcardiacconsequences.
Introduction
Worldwide,consumptionofenergydrinks(EDs)hasbecomeexceedinglypopular
andbeveragesaleshaveevolvedintoamulti‐billiondollarindustry.1Regularconsumption
ofEDshasbeenreportedashighas68%inadolescentsand30%inadults.1Thesafetyof
EDconsumptionisbeingquestionedduetoassociationswithcardiovascularcomplications
24
including:elevatedarterialpressure,QTcintervalprolongation,arrhythmias,coronary
arteryspasm,coronaryarterythrombosis,Takotsubocardiomyopathy,myocardial
infarction,aorticdissection,andsuddencardiacdeath.2‐4Risingheartrate,elevatedsystolic
bloodpressure,endothelialdysfunction,increasedplateletaggregation,andincreased
bloodviscosityareallproposedmechanismsofED’spotentialsideeffects.2,5Thisreport
describesacaseofahealthyyoungmanwithnopastmedicalhistorypresentingwithaST‐
segmentelevationmyocardialinfarction(STEMI)secondarytothrombosisoftheright
coronaryarteryafterconsumingnumerousenergydrinks.
CaseDescription
A28‐year‐oldmanwithnopastmedicalhistoryhadbeendrinkinganaverageof
fourtofiveenergydrinkspereveningforseveralweeks.Afterexercisingatthegym,he
experiencedacuteretrosternalchestpressureandshortnessofbreath.Hecontacted
emergencymedicalservicesandwasbroughttoouremergencycenter.
Onarrival,theelectrocardiogram(ECG)showedsinusrhythmwithhyper‐acuteT
wavesinleadsII,III,aVF,andST‐segmentdepressioninleadsI,aVL,V1,andV2(Figure1A).
Cardiacenzymesrevealedamildlyelevatedcreatininekinaseandnormaltroponinlevels.
Hereceivedaspirin325mg,clopidogrel600mg,atorvastatin80mg,andwasstartedon
intravenousunfractionatedheparintherapy.Atransthoracicechocardiogram
demonstratedbasalinferiorandinferiorseptalhypokinesiswithapreservedleft
ventricularejectionfractionof60%.ArepeatECGshowed3mmST‐segmentelevations
withtombstonemorphologyinleadsII,III,aVFalongwithST‐segmentdepressioninIand
aVL(Figure1B).Thepatientunderwentemergentcoronaryangiography.Theleftcoronary
systemwasnormal.However,acompleteocclusionofthemidrightcoronaryartery(RCA)
wasobservedwithTIMI0flowinthemidanddistalportionsofthevessel(Figure2A).
Aspirationthrombectomywasperformedwithremovalofasubstantialamountof
25
thrombus(Figure3).Residual20‐30%stenosiswasnotedinthemidRCAwiththeaidof
intravascularultrasonography.Postinterventionangiographyshowedgooddistalrunoff
withTIMI3flow(Figure2B).Neitherangioplastynorstentingwereperformedduetothe
qualityofflow,patient’sage,andpaucityofcomorbidities.Thepatientwascontinuedon
dualantiplatelettherapyandmonitoredinthecoronarycareunit.Hiscreatininekinase
levelspeakedat3,940U/L,troponinTat5.27ng/mL,andtroponinIat>40ng/mL.Repeat
echocardiogramwasperformedaftercatheterizationandremainedunchanged.The
remainderofhislabworkincludingurinedrugscreenwasunremarkable.Thepatientdid
notdevelopanyfurtherchestpainthroughoutthehospitalizationandwasdischarged
homeinstableconditionondualantiplatelettherapy.Hehasremainedfreeofchestpain
foroversixmonthsafterdischargeandcontinuestoabstainfromenergydrink
consumption.
Figure1:A:Initialelectrocardiogram(ECG)withpeakedTwavesandconvexST‐segment
elevationinleadsII,III,aVF,aswellasST‐segmentdepressioninleadsIandaVL.B:Repeat
ECGwith3mmST‐segmentelevationwith“tombstone”appearanceinleadsII,III,aVFand
ST‐segmentdepressioninIandaVL.
26
Figure2:A:Coronaryangiographyrevealedcompleteocclusionofthemiddleright
coronaryartery.B:CoronaryangiographyafterthrombectomyrevealedTIMI3flow
distally.
27
Figure3:Postaspirationthrombectomyshowingasubstantialamountofclotremoved.
Discussion
EDsdiffergreatlyfromtraditionalsoftdrinks,coffee,andteainthateveryED
exceedstheofficialFDAcaffeineconcentrationlimitof71mg/12floz.2Casereportshave
establishedrareinstancesofEDsbeinglinkedwithSTEMI.Atleastfourreportsofcoronary
28
arterythrombosistriggeringSTEMIsinthesettingofEDconsumptionhavebeendescribed
intheliterature.6‐8Giventhattheonlyavailableevidencelinkingcoronaryartery
thrombosiswithEDconsumptionisintheformofcasereports,adefinitivecausal
relationshipcannotbeestablished.
Ourpatientinourreportdevelopedchestpainshortlyafterexercising.Onepossible
explanationmaybeacuteendothelialdysfunction.Inhealthysubjectswhoconsume
caffeinepriortoexercise,myocardialbloodflowmaybesignificantlyreduced.9Intwo
studiesusingpositronemissiontomography(PET),exerciseinducedmyocardialblood
flowfollowingcaffeineconsumptionwasfoundtobedecreasedby14%(P<0.05)and22%
(P<0.01).9Furthermore,studiesutilizingbrachialarterydilationasasurrogatefor
coronaryarteryendothelialfunctiondemonstratethatcaffeineconsumptionpriorto
exerciseattenuatedtheexpectedincreaseinbloodflowbyasmuchas53%.10‐13The
underlyingmechanismforthesefindingsmaybecaffeine’sinhibitionofadenosine
mediatedvasodilationtriggeredbyincreasedcardiacworkduringexercise.9
Astudywasconductedon50healthysubjectswithamedianageof22years.The
studygroupconsumed250mLofsugar‐freeenergydrinkandthecontrolgroupconsumed
250mLofcarbonatedwater.Plateletaggregation,endothelialfunction,andmeanarterial
pressureweretestedbeforeandonehourafterconsumptionoftherespectivebeverages.
IntheEDgroup,therewasasignificantincreaseof13%inplateletaggregationby
adenosinediphosphate‐inducedopticalaggregometry.Endothelialfunctionassessedby
peripheralarteryflowmediateddilationwasacutelydecreasedafterEDconsumptionand
meanarterialpressurewassignificantlyincreased.5
TheincreasedprevalenceofEDconsumptioninrecentyears,hasseenarising
incidenceofemergencyroomvisitsandseriouscardiovascularevents.2,4Thereisgrowing
evidencesuggestingthatthesebeveragesarenotinnocuousperformanceenhancersand
29
mayharborsignificantriskstohealthyyoungpeople.2,14Moreresearchinthisfieldisvital
todevelopingabetterunderstandingofthecardiovascularriskassociatedwithED
consumption.
References
1. BredaJJ,WhitingSH,EncarnacaoR,NorbergS,JonesR,ReinapM,JewellJ.Energy
drinkconsumptioninEurope:areviewoftherisks,adversthealheffects,andpolicy
optionstorespond.FrontiersinPublicHealth2014;2:134.
2. HigginsJP,YarlagaddaS,YangB.CardiovasularComplicationsofEnergyDrinks.
Beverages2015;1:104‐26
3. HigginsJP,TuttleTD,HigginsCL.Energybeverages:contentandsafety.MayoClinic
Proceedings2010;85:1033‐41.
4. LippiG,CervellinG,Sanchis‐GomarF.EnergyDrinksandMyocardialIschemia:A
ReviewofCaseReports.CardiovascularToxicology2015.
5. WorthleyMI,PrabhuA,DeSciscioP,SchultzC,SandersP,WilloughbySR.
Detrimentaleffectsofenergydrinkconsumptiononplateletandendothelial
function.TheAmericanJournalofMedicine2010;123:184‐7.
6. BergerAJ,AlfordK.Cardiacarrestinayoungmanfollowingexcessconsumptionof
caffeinated“energydrinks”.TheMedicalJournalofAustralia2009;190:41‐3.
7. BenjoAM,PinedaAM,NascimentoFO,ZamoraC,LamasGA,EscolarE.LeftMain
CoronaryArterlyAcuteThrombosisRelatedtoEnergyDrinkIntake.Circulation
2012;125:1447‐8
8. SolominD,BorronSW,WattsSH.STEMIAssociatedwithOveruseofEnergyDrinks.
Caserreportsinemergencymedicine2015;2015:537689.
9. HigginsJP,BabuKM.Caffeinereducesmyocardialbloodflowduringexercise.The
AmericalJournalofMedicine2013;126:7330e1‐8.
30
10. DeanfieldJE,JalcoxJP,RabelinkTJ.Endothelialfunctionanddysfunction:testingand
clinicalrelevance.Circularion2007;115:1285‐95.
11. HigginsJP.Endothelialfunctionacutelyworseafterdrinkingenergybeverage.
InternationalJournalofCardiology2013;168:e47‐9.
12. HigginsJP,OrtizBL.EnergyDrinkIngredientsandTheirEffectonEndothelial
Function‐AReview.InternationalJournalofClinicalCardiology2014;1:1‐6.
13. HigginsJP,YangB.OrtizB,etal.ConsumptionOfEnergyBeverageIsAssociated
WithAnAttenuationOfArterialEndothelialFlow‐MediatedDilation.Arteriosler
ThrombVascBiol2014;34:A519.
14. Sanchis‐GomarF,Pareja‐GaleanoH,CervellinG,LippiG,EarnestCP.EnergyDrink
OverconsumptioninAdolescents:implicationsforArrythmiasandOther
CardiovascularEvents.TheCanadianJournalofCardiology2015.
31
Mycobacteriumfortuituminfectionofthescalpafteraskingraft.
SmithBDMS,LirasINMS,DeCiccoIAMD,CollardKMS,AisenbergGMD.
Abstract
Mycobacteriumfortuitum(MF)isanon‐tuberculousmycobacteriumfoundinthesoiland
waterofmostregionsoftheworld,andhasbeenreportedtocausediseaseinboth
immunocompetentandimmunocompromisedhosts.Wepresenta52‐year‐oldmanwho
developedascalpabscessunderafreeflapforcraniumcoverageafteramotorvehicle
accident.CultureofmaterialdrainedfromtheabscessgrewMF.
Introduction
Mycobacteriumfortuitum(MF)isanon‐tuberculousmycobacteriumcharacterized
byitsrapidgrowthinculturemedia.1Thisbacteriumcanbefoundinthesoilandwaterof
mostregionsoftheworld,andhasbeenreportedtocausediseaseinboth
immunocompetentandimmunocompromisedhosts.2Disseminatedinfectionismore
commonamongthelatter,whereassofttissue,especiallypost‐surgicalwoundinfections,
donotcorrelatewithimmunestatus.1,3
Wepresenta52‐year‐oldmanwhoreceivedafreeflapwithsplit‐thicknessskin
graftforcraniumcoverageafteramotorvehicleaccident,andsubsequentlydevelopeda
scalpabscess.CultureofmaterialdrainedfromtheabscessgrewMF.Toourknowledge,
thisisthefirstcaseofMFinfectioncausingaflap‐relatedscalpabscessreportedinthe
literature.
CaseReport
A52‐year‐oldAfricanAmericanmanwithahistoryofhypothyroidism,
schizophreniaandhypertensionpresentedtoLyndonBJohnsonHospitalwithatwo‐
monthhistoryofscalppainandtwodaysofpurulentdischargefromascalpwound.The
patientwasinvolvedinamotorvehicleaccidentthreemonthsprior,atwhichtimehe
32
sustainedascalpinjurythatresultedinasignificantareaofexposedcranium.Sincethis
time,thepatienthasundergonemultipleirrigationanddebridementsaswellasa
latissimusdorsifreetissuetransferwithsplit‐thicknessskingraftinordertoachieve
adequatetissuecoverageofthearea.Thenightbeforepresentationthepatient
experiencedswellingandpainintheareaofhisflap,andnoticedbloodyandpurulent
dischargefromthewound.
Onpresentation,thepatientwasoverallhealthyappearing,histemperaturewas
36.8°C,bloodpressure145/100mmHg,pulse82beatsperminute,respiratoryrate18
breathsperminute,andoxygensaturation98%onroomair.Onexam,thepatient’sscalp
flapappearedviablewithnoapparentsignsoftissuenecrosis.Anabscesswasappreciated
atthesuperior‐mostportionoftheflap,withpurulentmaterialnotedtobeexpressedfrom
underthefreeflap.Theflapandscalpwerenon‐erythematous.Theremainderofthe
examinationwasnormal.
Hislaboratoryresultsshowedawhitebloodcellcountof8.3K/mL(68.1%
neutrophils,19.2%lymphocytes),hemoglobinof12.8g/dLwithameancorpuscular
volumeof82fL,andaplateletcountof332K/μL.Hisserumelectrolyteswerenormal,
bloodureanitrogenof17mg/dLandcreatinineof1.0mg/dL.Computedtomography(CT)
oftheheadrevealedmultiplerim‐enhancinglesionsassociatedwiththerightfrontalscalp
flap,thelargestofwhichmeasured3.8cmindiameter.TheCTdidnotdemonstrateany
underlyingirregularityoftheskull.
Empiricaltherapywithvancomycinwasstarted.Thepatientunderwentirrigation
anddebridementthedayafteradmission,whichhetoleratedwell,withnocomplications.
Culturesfromthescalpabscesseswerecollectedduringthesurgery.TheinitialGramstain
reportednoorganisms.However,tendaysafterdischargefromthehospital,thewound
cultureisolatedMF(table1).
33
TABLE1AntimicrobialsucesptibilitytestingofMycobacteriumFortuitum
Antibiotic(s)InterpretationMIC
(mg/ml)
Amikacin
Susceptible Clarithromycin
Imipenem
Resistant
Linezolid
Susceptible 6
Moxifloxacin Susceptible 0.012
Trimethoprim/Sulfamethoxazole 3
Intermediate 3
32
Susceptible 0.094
Discussion
Thereportedincidenceofnon‐tuberculousmycobacterial(NTM)cutaneous
infectionscontinuestorise,andpenetratingwoundsorthepresenceofforeignbodies
appeartobepredisposingconditions.4MFhasbeenassociatedwithabroadvarietyof
exposures,suchasacupuncture,lacerations,body‐scrubbinginpublicbaths,
chemotherapy,andorgantransplants.5,6Outbreakshavebeenreportedinnailsalonsand
withtheuseofelectromyograms,ventriculo‐peritonealshunts,andsteroidinjections.7‐11
Theseinfectionshavebeendescribedbothinimmunocompetentand
immunocompromisedpatients.2,12‐14
Tothebestofourknowledge,wearereportingthefirstcaseintheliteratureofMF
causingaskingraft‐relatedscalpabscess.ThoughMFiswidelydistributedinthe
environment,itisunclearhowtheorganismreachedthispatient’sscalp.Wehypothesize
thatthismightbealateinfectionrelatedtohispriorsurgicalgraft.
IntypicalcasesofskinandsofttissueMFinfections,thelesionsdevelopafteran
inoculationperiodof4to6weeksandcanpresentaspainfulnodules,abscesses,ulcers,
drainingsinustracts,orcellulitis.15Histologically,olderlesionshaveapoorinfiltrate,
whereasacutelesionsdisplaysuppurativegranulomaswithoutcaseation,localtissue
destruction,andamixedinfiltrate.16
34
Antimicrobialsensitivityusuallyguidesthetherapy,andusingacombinationof
antibioticsisrecommended.Forlimitedskinandsofttissueinfections,suchasinourcase,
oraltherapywithtwoagentsisrecommended.Thedurationoftreatmentshouldbefora
minimumoffourmonths.Thepreferredregimensincludeclarithromycinorazithromycin
combinedwithciprofloxacin,levofloxacin,doxycycline,minocycline,ortrimethoprim‐
sulfamethoxazole.Forsevereordisseminateddisease,initialparenteraltreatmentis
recommendedwithtwotothreeeffectiveantibiotics,followedbyoraltreatmentfor6to12
months.1,17Ourpatientstartedempiricantibiotictherapywithvancomycinandcefepime
andunderwentdebridementwithJackson‐Prattdrainplacement.Aftertheprocedure,he
wasdischargedontrimethoprim‐sulfamethoxazole.WhenthewoundculturegrewMF,the
regimenwaschangedtodoxycyclineandciprofloxacin.Currentlythepatienthasreceived
twooffourmonthsofantibiotictreatmentandisprogressingfavorably.
Inconclusion,wedescribeacaseofskin‐graftrelatedscalpabscesscausedbyMF
treatedwithdualantibiotictreatmentandextensivesurgicaldebridement.Aswithother
infectionscausedbyuncommonpathogens,thiscaseshowstheimportanceofthe
microbiologicalanalysisofmaterialdrainedfromskinabscesses.
References
1. UslanDZ,KowalskiTJ,WengenackNL,VirkA,WilsonJW.Skinandsofttissue
infectionsduetorapidlygrowingmycobacteria:comparisonofclinicalfeatures,
treatment,andsusceptibility.ArchivesofDermatology.2006;142(10):1287‐92.
2. IngramCW,TannerDC,DurackDT,KernodleGW,CoreyGR.Disseminatedinfection
withrapidlygrowingmycobacteria.ClinicalInfectiousDiseases.1993;16(4):463‐71.
3. SmithMB,SchnadigVJ,BoyarsMC,WoodsGL.Clinicalandpathologicfeaturesof
Mycobacteriumfortuituminfections.Americanjournalofclinicalpathology.
2001;116(2):225‐32.
35
4. Gonzalez‐SantiagoTM,DrageLA.Nontuberculousmycobacteria:skinandsofttissue
infections.DermatolClin.2015;33(3):563–77.
5. LeeWJ,KangSM,SungH,WonCH,Chang,SE.,LeeMW,KimMN,ChoiJHandMoon
KC.Non‐tuberculousmycobacterialinfectionsoftheskin:Aretrospectivestudyof
29cases.TheJournalofDermatology,2010;37:965–972.
6. MurilloJ,TorresJ,BofillL,Rios‐FabraA,IrausquinE,IstúrizR,GuzmánM,CastroJ,
RubinoL,CordidoM.Skinandwoundinfectionbyrapidlygrowingmycobacteria:an
unexpectedcomplicationofliposuctionandliposculpture.Archivesofdermatology.
2000;136(11):1347‐52.
7. WinthropKL,AlbridgeK,SouthD,AlbrechtP,AbramsM,SamuelMC,LeonardW,
WagnerJ,VugiaDJ.TheClinicalManagementandOutcomeofNailSalon—Acquired
MycobacteriumfortuitumskinInfection.Clinicalinfectiousdiseases.2004;38(1):38‐
44.
8. NolanCM,HashisakiPA,DundasDF.Anoutbreakofsoft‐tissueinfectionsdueto
Mycobacteriumfortuitumassociatedwithelectromyography.JournalofInfectious
Diseases.1991;163(5):1150‐3.
9. CadenaG,WiedemanJ,BogganJE.Ventriculoperitonealshuntinfectionwith
Mycobacteriumfortuitum:arareoffendingorganism:Casereport.Journalof
Neurosurgery:Pediatrics.2014;14(6):704‐7.
10. PaiR,ParampalliU,HettiarachchiG,AhmedI.Mycobacteriumfortuitumskin
infectionasacomplicationofanabolicsteroids:ararecasereport.TheAnnalsof
TheRoyalCollegeofSurgeonsofEngland.2013;95(1):e12‐3.
11. KumarS,JosephNM,EasowJM,UmadeviS.Multifocalkeloidsassociatedwith
Mycobacteriumfortuitumfollowingintralesionalsteroidtherapy.Journalof
laboratoryphysicians.2011;3(2):127.
36
12. SungkanuparphS,SathapatayavongsB,PracharktamR.Infectionswithrapidly
growingmycobacteria:reportof20cases.Internationaljournalofinfectious
diseases.2003;7(3):198‐205.
13. RedbordKP,ShearerDA,GlosterH,etal.Atypicalmycobacteriumfurunculosis
occurringafterpedicures.JAmAcadDermatol2006;54(3):520–4.
14. Dodiuk‐GadR,DyachenkoP,ZivM,Shani‐AdirA,OrenY,MendeloviciS,ShaferJ,
ChazanB,RazR,KenessY,RozenmanD.Nontuberculousmycobacterialinfectionsof
theskin:aretrospectivestudyof25cases.JournaloftheAmericanAcademyof
Dermatology.2007;57(3):413‐20.
15. FowlerJ,MahlenSD.Localizedcutaneousinfectionsinimmunocompetent
individualsduetorapidlygrowingmycobacteria.ArchivesofPathologyand
LaboratoryMedicine.2014;138(8):1106‐9.
16. HutchesonAC,LangPG.Atypicalmycobacterialinfectionsfollowingcutaneous
surgery.DermatolSurg2007;33(1):109–13.
17. BhambriS,BhambriA,DelRossoJQ.Atypicalmycobacterialcutaneousinfections.
Dermatologicclinics.2009Jan;27(1):63‐73.
37
HyperesoinophilicSyndromeina17‐YearOldFemaleMimickingHeartFailure
DanielleStone,MD,JamesStoneMD
Abstract
Hypereosinophilicsyndrome(HES)isadiseasedefinedaspersistenteosinophilia
(bloodeosinophilcount>1500/μL),foratleastsixmonthsandorgandamage.Myocardial
infiltrationisthemostseriouscomplicationandisamajorcauseofmorbidityand
mortalityinHES.Eosinophilicmyocarditis(EM)isarareformofmyocarditiswithlimited
understandingoftheunderlyingetiology.Hypersensitivitytoadrugorsubstancehasbeen
identifiedinvariouscases,butthemajorityofEMareidiopathic.Thespectrumofclinical
presentationvariesgreatlyamongpatientsdiagnosedwithHES.Thefollowingcasereport
describesthepresenceofHESina17year‐oldwomanpresentingwithsymptoms
mimickingheartfailure.Althoughendomyocardialbiopsy(EMB)isthegoldstandardto
diagnoseEM,cardiacmagneticresonance(CMR)imagingwasusedtoestablishthe
diagnosisasprioruppergastrointestinalbiopsiesconfirmedthepresenceofHES.Withthe
earlyinductionofcorticosteroids,hereosinophiliaresolvedandherclinicaloutcome
improveddramatically.
Introduction
Earlyonseteosinophilicmyocarditis(EM)presentingwithnecrosisfollowsa
rapidlydeterioratingcourse.Thus,itisvitaltoobtainanearlydiagnosisandinitiate
treatmentwithcorticosteroids,whichhasbeenshowntohaveanimprovedoverall
outcome.Inthefollowingcase,wediscussthediagnosisandtreatmentmodalitiesofEMby
promptlyidentifyingendomyocardialeosinophilicinfiltrationtopreventtheincreased
morbidityandmortalityassociatedwithnecrotizingEM.
38
Casepresentation
Onadmission,a17‐yearoldfemalewithknownMVPanda3‐yearmedicalhistoryof
hypereosinophilicsyndrome(HES)presentedwithmid‐sternalchestpainalongher
sternotomyincisionsiteandshortnessofbreathwithminimalexertionfortwoweeks.She
alsocomplainedofparesthesiasinherfingertipsandtoes.
Approximately6monthsprecedingthisadmission,thepatienthadbeenadmitted
toourhospitalforasix‐dayhistoryofshortnessofbreathandsub‐sternalchestdiscomfort.
Itwasdiscoveredthatshehadundergonearecentmechanicalmitralvalvereplacement
onlyafewmonthsprioratanOSH.Herpost‐operativecoursewascomplicatedby
thrombosesonhernewvalveandknownresidualposteriorleafletdysfunction.She
subsequentlyreceivedcatheterdirectedtPAinfusionatthattime.Afterfurther
investigation,itwasfoundonTTEthathermechanicalmitralvalvewasseverelystenotic
andleafletswereimmobile,andthussheunderwentasecondmechanicalvalve
replacementatourhospital.Apost‐operativeTTEshowedanormalfunctioning
mechanicalmitralvalveprosthesispriortodischarge.
Duringthisadmission,thepatientwasagainhospitalizedforchestpainand
worseningshortnessofbreath.Herchestpainwasmid‐sternalalongthesternotomy
incisionsite.Shedescribedthepainassevere,sharpandstabbinginnature,without
radiation,andexacerbatedbypalpatingthesite.Shealsopresentedwithparesthesiasin
herfingertipsandtoes.Hervitalswereunremarkable.EKGshowednoSTsegment
changesandcardiacenzymeswereonlyslightlyelevated(TroponinI0.70;CK‐MB2.6).
Herinitialeosinophilcountwas10,100μL.Transthoracicechocardiography(TTE)showed
anEF40‐45%withmildglobalhypokinesisandakineticmidanteroseptal,midinferoseptal
andapicalseptalwallsegments.Chestcomputedtomography(CT)imagingshoweda
39
markedlyenlargedesophaguswithathickenedwallandnodisruptionofsternalwires
fromthesternotomy.
Whileinpatient,thepatientcontinuedtohavechestdiscomfortandshortnessof
breathalongwithlimbparesthesias.Shewasgivenmorphinetocontrolherpain,and
steroidsweregivenoncealltestinghadbeencompletedastoachieveaccurateresults.
Hematology,gastroenterologyandrheumatologywereconsultedtoworkupthecauseof
HESinthispatient.Peripheralsmearandbonemarrowbiopsyshowedmarked
eosinophilia.Cytogenetictestingandautoimmuneworkupwerenegative.EGDwith
biopsyshowedchronicactivegastritis,eosinophilicesophagitisandsub‐mucosal
eosinophiliaintheduodenalbulbandsecondportionoftheduodenum.
CardiacMRIdemonstratedapicalandmidsegmentscompatiblewithareasof
endomyocardialfibrosisconsistentwithHESalongwithmildglobalhypokinesiswithEFof
52%.
Inadditiontoinductionofsteroids,thepatientwasstartedonabeta‐blocker,ACEi,
anddiuretics.Hereosinophilcountreturnedtonormalandhershortnessofbreathand
paresthesiasresolvedaswell.
Discussion
Hypereosinophilicsyndrome(HES)isararedisorderofunregulatedeosinophilia,
whichifuntreated,mayleadtosystemictissueinfiltrationandinflammation.Thecausesof
eosinophiliaaredescribedintheCHINAmneumonic(connectivetissuediseases,
helminthicinfection,idiopathic,neoplasia,allergy).Anelevatedeosinophilcount
(>1500/μL)withoutasecondarycauseandevidenceoforganinvolvementarediagnostic
ofHES.ThemostcommonorgansaffectedbyHESincludetheskin,lungs,gastrointestinal
tract,andheart.Wheneosinophilicinfiltrationcausesdiffusemyocardialinflammation
eosinophilicmyocarditis(EM)results.Inthiscase,thepatient’sHESaffectedherGItract,
40
skinandheart.Withconfirmativebiopsiesshowingeosinophilicinfiltrationinvolvingthe
stomach,esophagusandduodenuminthesettingofprofoundperipheraleosinophilia
(10,100/μL),wesuspectedEMfollowingCMRimaging.Weusedhigh‐dosecorticosteroids
andheartfailuremedicationstoreversethecardiacinjuryandtoimprovetheclinical
outcome.
Accordingtopreviousreports[1‐2],cardiacinvolvementoccursin54–82%ofcases,
and,theprognosisisdeterminedbytheextentofthemyocardialfibrosisandrelated
complications.Thefive‐yearmortalityofEMis30%.
InfiltrationofeosinophilsintothemyocardiumcausesEMviareleaseoftoxic
eosinophilicgranuleproteinssuchasECPandmajorbasicprotein(MBP),whichcauses
dysfunctionofmyocytemitochondrialeadingtomyocardiallesionsandnecrosis[3].
Myocarditispresentsinmanydifferentwaysfromasymptomaticcasestolife‐
threateningconditionssuchascardiogenicshockorsuddencardiacdeathduetomalignant
ventriculararrhythmias.CommonmanifestationsofEMmaybeintheformofchestpain,
dyspnea,fatigue,palpitations,and/orsyncope.PriortotheonsetofEM,approximately
two‐thirdsofpatientshavesymptomsofthecommoncoldandone‐thirdofcasessuffer
fromallergicdiseasessuchasbronchialasthma,rhinitis,orurticaria[4].
DiagnosisofEMcanbedonebyCMRimaging[5]priortoendomyocardialbiopsy
(EMB)tovisualizetheextentofmyocardialinvolvement.EMBisthegoldstandardfor
diagnosingEM.EMBfindingsarecharacterizedbydiffusemyocardialnecrosisassociated
withextensiveeosinophilicinfiltrationofthemyocardialinterstitium,focalmyocyte
dissolution,perivascularinfiltrationandmyocardialinterstitialfibrosis[6].However,EMB
cannotbeperformedinallpatientssuspectedofhavingEMbecauseitmaybetooinvasive.
HESmayormaynotbeassociatedwithmutationsinthetyrosinekinasereceptor
gene,butsuchinvolvementisimportanttoidentify,becausetreatmentwithimatinibis
41
effectiveinsuchcases.IfHESisnotassociatedwithsuchmutation,treatmentwithhigh‐
dosemethylprednisoneisthestandardofcare.Wedidnotuseimatinibinthispatientas
nomutationinthetyrosinekinasereceptorgeneexisted.
ThetherapyofchoiceafteradiagnosisofEMconsistsofstandardheartfailure
medicationandearlytreatmentwithhighdosesofcortisone[7].Theearlyinitiationof
steroidtherapycanachievesubstantialimprovementsinclinicaloutcomes,prognosisand
long‐termsurvival.CorticosteroidtherapyinHEShasbeensuccessfullydocumentedin
publishedcasereportswithinducedcompleteorpartialresponsesat1monthin85%of
patientsfollowingmonotherapy;mostpatientsremainedonmaintenancedoseswitha
medianof10mgprednisoneequivalentdailydosefor2monthsto20years[7,8,9].
OurpatientlikelyhadasubtypeofEMknownasidiopathichypereosinophilic
syndrome(HES).Thissyndromeischaracterizedbyabsoluteeosinophilcountgreaterthan
1.5×105/Llastingformorethansixmonthsintheabsenceofanyknowncauseof
hypereosinophiliaandwithevidenceofmulti‐organinvolvementdirectlyattributableto
theeosinophiliaorotherwiseunexplainedintheclinicalsetting[4,10,11].
Conclusion
Insummary,myocarditispresentsinavarietyofwaysandEMshouldbeconsidered
incaseswithpersistenteosinophilia.Inthiscase,theresultsofrelevantlaboratory
analysesandCMRimagingledtothediagnosisofasubtypeofEMknownasidiopathicHES.
Earlydiagnosisandinitiationofsteroidtreatmentachievedanormaleosinophilcountand
markedimprovementofthepatient’sprognosis.Inaddition,optimizationofheartfailure
therapydemonstratedtoimprovehemodynamicsandsymptoms.
References
1. ChusidMJ,DaleDC,WestBC,WolffSM.Thehypereosinophilicsyndrome:analysisof
fourteencaseswithreviewoftheliterature.Medicine(Baltimore).1975;54(1):1–27.
42
2. KlionAD,BochnerBS,GleichGJ,NutmanTB,RothenbergME,SimonHU,etal.
Approachestothetreatmentofhypereosinophilicsyndromes:aworkshopsummary
report.JAllergyClinImmunol.2006;117(6):1292–302.
3. ArimaM,KanohT.Eosinophilicmyocarditisassociatedwithdensedepositsof
eosinophilcationicprotein(ECP)inendomyocardiumwithhighserumECP.Heart.
1999;81(6):669–71.
4. S.Kawano,J.Kato,N.Kawanoetal.,“Clinicalfeaturesandoutcomesofeosinophilic
myocarditispatientstreatedwithprednisoloneatasingleinstitutionovera27‐year
period,”InternalMedicine,vol.50,no.9,pp.975–981,2011.
5. DeblK,DjavidaniB,BuchnerS,PoschenriederF,HeinickeN,FeuerbachS,etal.
TimecourseofeosinophilicmyocarditisvisualizedbyCMR.JCardiovascMagn
Reson.2008;10:21.
6. HerzogCA,SnoverDC,StaleyNA.Acutenecrotisingeosinophilicmyocarditis.Br
HeartJ.1984;52(3):343–8.
7. AliA,StraatmanL,AllardM,IgnaszewskiA.Eosinophilicmyocarditis:caseseries
andreviewofliterature.CanJCardiolVol.2006;6(14):1233–1237.doi:
10.1016/S0828‐282X(06)70965‐5.
8. OgboguPU,BochnerBS,ButterfieldJH,GleichGJ,Huss‐MarpJ,KahnJE,Leiferman
KM,NutmanTB,PfabF,RingJ,RothenbergME,RoufosseF,SajousMH,SheikhJ,
SimonD,SimonHU,SteinML,WardlawA,WellerPF,KlionAD.Hypereosinophilic
syndrome:amulticenter,retrospectiveanalysisofclinicalcharacteristicsand
responsetotherapy.JAllergyClinImmunol.2009;6(6):1319–25E3.doi:
10.1016/j.jaci.2009.09.022.
43
9. RoehrlMH,AlexanderMP,HammondSB,RuzinovaM,WangJY,O’HaraCJ.
Eosinophilicmyocarditisinhypereosinophilicsyndrome.AmJ
Hematol.2011;6(7):607–608.doi:10.1002/ajh.21943.
10. HerzogCA,SnoverDC,StaleyNA.Acutenecrotizingeosinophilicmyocarditis.Br
HeartJ.1984;6:343–348.doi:10.1136/hrt.52.3.343.
11. KlionAD,NoelP,AkinC,LawMA,GillilandDG,CoolsJ,MetcalfeDD,NutmanTB.
Elevatedserumtryptaselevelsidentifyasubsetofpatientswitha
myeloproliferativevariantofidiopathichypereosinophilicsyndromeassociated
withtissuefibrosis,poorprognosis,andimatinib
responsiveness.Blood.2003;6(12):4660.
44
Biventricularfailureastheinitialmanifestationofthyrotoxicosisduringpregnancy.
AmitJ.Patel,DO,ChristinaParuthi,MD,SalmanArain,MD
Abstract
Changesincardiovascularphysiologyduringpregnancyincludesystemic
vasodilation,increasedplasmavolume,andincreasedcardiacoutput.Thesechangescreate
anincreaseinpreloadanddecreaseinafterloadresultinginahyperdynamicstate.Similar
changesarefoundinhyperthyroidism.Cardiacreserveistestedwhenthehyperdynamic
statesofpregnancyandhyperthyroidismarecombined,butmosthealthypatientsareable
tocompensate.Itusuallytakesathirdeventtopushthesepatientsintoclinicalheart
failure.Wepresentacaseofapatientwhowasnotabletocompensateandpresentswith
biventricularheartfailuresecondarytoGravesdiseaseduringpregnancy.
Introduction
Thecardiovascularsystemundergoesmanyphysiologicalchangesduring
pregnancytoaccommodatetheincreasingdemandsofthemotherandgrowingfetus.
Increasedlevelsofestrogenandprogesteroneleadtosystemicvasodilationanddecreased
systemicvascularresistance.ThereisalsosignificantactivationoftheRenin‐Angiotensin‐
AldosteroneSystem(RAAS)resultinginincreasedplasmavolume.Intotal,thesechanges
leadtoincreasedcardiacpreloadanddecreasedcardiacafterloadresultingina
hyperdynamicstatecharacterizedbyincreasedcardiacoutput.1Somestudieshave
reportedtheincreaseincardiacoutputcanbeupto80‐85%higherthanthepre‐pregnancy
state.13Healthymothersareusuallyabletoadapttothesehemodynamicchangeswith
littletonosymptomatology.However,anotherinsultthatintroducessimilarhemodynamic
changescanoverwhelmcardiacreserveandleadtoheartfailure.Wepresentacasein
whichthisscenariooccurs.
45
CaseDescription
Ourpatientisa31‐year‐oldgravida5para1femaleat22weeksgestationthat
presentedtoanoutsidefacilitywithcomplaintsofgradualandprogressivedyspneaon
exertionoverthelastmonth.Evaluationattheoutsidefacilityincludedachestradiograph,
electrocardiogram,andtransthoracicechocardiogramthatweresignificantforsinus
tachycardia,biatrialenlargement,bibasilarpulmonarycongestion,andarightventricular
systolicpressure(RVSP)of30mmHg.Shewasstartedonintravenousdiuretics,beta‐
blockers,andtransferredtoourhospitalforhigherlevelofcare.Physicalexamupon
arrivalatourfacilitywasnotablefor2+pittinglowerextremityedema,exophthalmos,
tachycardia,andbibasilarralesonpulmonaryauscultation.Rightheartcatheterization
showedelevatedwedgepressureof28mmHg.Thyroidstudiesweresignificantforthyroid
stimulatinghormone(TSH)<0.005μU/mL,freeT4(FT4)6.23ng/dL,anti‐thyroid
peroxidaselevel(anti‐TPO)>1300IU/mL,andthyroidstimulatingimmunoglobulin(TSI)
of447%suggestingheartfailurefromthyrotoxicosis.Shewasstartedonpropylthiouracil,
propranolol,anddiureticswithgoodresponseanddischargedhome.Shestoppedtaking
heranti‐thyroidmedicationafter2weeksforanunclearreason,andreturnedtothe
hospitalafter3weekswithpre‐termlaboranddecompensatedheartfailure.Duringthis
admissionshehadanemergentcesareansectionat26weeksgestationduetofetal
distress.Sheresumedtreatmentforhyperthyroidismpostpartumwithresolutionofheart
failurewhileherbabywasobservedintheneonatalintensivecareunit.
Discussion
Hyperthyroidismhasaprevalenceof1.3%intheUnitedStateswithwomenaffected
morethanmen.ThemostcommonformofhyperthyroidismisGravesdisease,whichisan
autoimmunedisorderwhereautoantibodiesstimulatetheTSH‐receptoronthyroid
46
follicularcellscausingupregulationofthyroidhormone.7TheannualincidenceofGraves
diseaseisaround20‐30casesper100,00individuals.8
Thyroidhormoneplaysacrucialroleintheregulationofcardiovascularfunction.
Excessthyroidhormonecausesanincreasedrestingheartrate,strokevolume,blood
volume,cardiacoutput,anddecreasedsystemicvascularresistancethroughdirectand
indirecteffects.10Thesechangesleadtomanyofthecardiovascularmanifestationsof
Gravesdisease,includingtachycardia,widenedpulsepressure,anddyspnea.Othersigns
andsymptomsofGravesdiseaseincludeproptosis,eye‐lidlag,andgoiter.Heartfailuredue
tohyperthyroidismonlyoccurredin5.6per100,000individualsinastudybySiuetal.
InastudybySheffieldetal.,Gravesdiseaseaffected1outof1700deliveriesovera
28‐yearperiod.ThemanifestationsofGravesdiseasetendtoregressduringpregnancydue
totherelativeimmunosuppressedstatecausedbypregnancy.6Whenpresent,uncontrolled
Gravesdiseasecanleadtomiscarriage,pre‐termdelivery,pregnancy‐induced
hypertension,low‐birthweight,pre‐eclampsia,andmaternalheartfailure.Asdescribed
above,pregnancyandhyperthyroidismleadtoanincreaseincardiacpreloadanda
decreaseincardiacafterload.Healthymothersareabletocompensateforthe
hemodynamicchangesofpregnancyanddonotpresentwithheartfailure.The
hyperdnynamicstateisstretchedevenfurtherwhenpregnancyiscombinedwithovert
hyperthyroidism,howeverthemajorityofthesepatientsarestillabletocompensate.A
thirdhyperdyanamicevent,suchashemorrhage,sepsis,orpre‐eclampsia/eclampsia,is
requiredtocauseheartfailureinamajorityofpatients.4
Thephenomenonofpregnancy,hyperthyroidism,andathirdhyperdynamicevent
hasbeendemonstratedinmultiplecasereports.Sheffieldetal.described13patientswho
presentedwithheartfailuresecondarytothyrotoxicosisinthesettingofpregnancy.Eleven
ofthe13patientshadanobstetriccomplicationthataddedathirdinsulttotheircardiac
47
reserve.The2patientswhodidnothaveanobstetricrelatedcomplicationweredescribed
ashavingmildanemia,whichwasalsotrueinourcase.Adropinserumhemoglobinisto
beexpectedduringpregnancyhowever,withanadirnear10.5g/dL.9Ourpatient’s
hemoglobinatthetimeofadmissionwas9.8g/dL,whichisunlikelytointroducea
significantstressortothecardiovascularsystem.
Conclusion
Heartfailureduetohyperthyroidismduringpregnancyisarelativelyrareevent
thattypicallyrequiresathirdhyperdynamicinsulttohaveanyclinicalsignificance.Asour
casedemonstrates,athirdeventisnotalwaysnecessary.Cliniciansshouldhavealow
thresholdtoevaluatethyroidfunctioninapregnantpatientpresentingwithheartfailure.
Earlyrecognitionandtreatmentcanpreventseverematernalandfetalmorbidityand
mortality.
References
1. SabahKM,ChowdhuryAW,IslamMS,etal.Graves'diseasepresentingasbi‐
ventricularheartfailurewithseverepulmonaryhypertensionandpre‐eclampsiain
pregnancy‐‐acasereportandreviewoftheliterature.BMCResNotes.2014;7:814.
2. YangMJ,ChengMH.Pregnancycomplicatedwithpulmonaryedemadueto
hyperthyroidism.JChinMedAssoc.2005;68(7):336‐8.
3. KaleliogluIH,HasR,CigerliE,etal.Heartfailurecausedbythyrotoxicosisin
pregnancy‐‐casereport.ClinExpObstetGynecol.2007;34(2):117‐9
4. SheffieldJS,CunninghamFG.Thyrotoxicosisandheartfailurethatcomplicate
pregnancy.AmJObstetGynecol.2004;190(1):211‐7.
5. SiuCW,YeungCY,LauCP,KungAW,TseHF.Incidence,clinicalcharacteristicsand
outcomeofcongestiveheartfailureastheinitialpresentationinpatientswith
primaryhyperthyroidism.Heart.2007;93(4):483‐7.
48
6. Stagnaro‐greenA,PearceE.Thyroiddisordersinpregnancy.NatRevEndocrinol.
2012;8(11):650‐8.
7. DeleoS,LeeSY,BravermanLE.Hyperthyroidism.Lancet.2016;
8. BurchHB,CooperDS.ManagementofGravesDisease:AReview.JAMA.
2015;314(23):2544‐54.
9. HorowitzKM,IngardiaCJ,BorgidaAF.Anemiainpregnancy.ClinLabMed.
2013;33(2):281‐91.
10. Vargas‐uricoecheaH,Bonelo‐perdomoA,Sierra‐torresCH.Effectsofthyroid
hormonesontheheart.ClinInvestigArterioscler.2014;26(6):296‐309.
11. GraisIM,SowersJR.Thyroidandtheheart.AmJMed.2014;127(8):691‐8.
12. SanghaviM,RutherfordJD.Cardiovascularphysiologyofpregnancy.Circulation.
2014;130(12):1003‐8.
13. DucasRA,ElliottJE,MelnykSF,etal.Cardiovascularmagneticresonancein
pregnancy:insightsfromthecardiachemodynamicimagingandremodelingin
pregnancy(CHIRP)study.JCardiovascMagnReson.2014;16:1.
49
ARareCaseofMacrophageActivatingSyndrome
ChristineAdaezeNwoha,MD;Akkanti,BinduMD
UniversityofTexasHealthScienceCenteratHouston
Introduction
MacrophageActivatingSyndrome(MAS)isarareandpossiblyfatalsystemic
inflammatorydisorderthatresultswhenmacrophageactivationleadsto
hemophagocytosiscausingadepressionofcelllines,liverdysfunctionandcoagulopathy.
Becauseofthehighmortalityprofileearlydiagnosisiskey.Thenon‐specificityof
symptomsareassociatedwithabroaddifferentialofdiseaseprocesses.Howeverwitha
closerreview,literaturesearch,andpathologyfollow‐up,wediagnosedthepatient
correctlyandinitiatedlife‐savingtreatment.
Casepresentation
A21‐year‐oldfemalewithnoknownpastmedicalhistoryotherthandental
extractionoffourwisdomteethonemonthpriorpresentedtoanoutsidehospitalwith
complaintsoffever,fatigue,nightsweatsandanunintentionalweightlossof20pounds.
Patientismarriedwithtwochildrenandcurrentlyinparttimeschool.Sheliveswithher
husbandandschoolagedchildren.Shehadnohistoryofsickcontactsorrecenttravel.She
deniedtobaccoandillicitdruguse,butreportedoccasionalalcoholuse.Shewas
unemployedandhadnofamilyhistoryofautoimmunediseaseorillness.
Patientreportedgoingtoanoutsideclinicaweekpriortoadmissionwhereshewas
prescribedantibiotics.Shecompletedhercoursewithnoalleviationofhersymptoms.On
admissiontooutsidehospital,patientwasfoundtobehypotensive,febrileand
pancytopenic(hemoglobin=5.7g/dL,WBC=3.6K/uL,platelet=9K/uL,reticcount=
0.8%).Shewasalsonotedtohaverenalfailure.Shewasadmittedtotheintensivecareunit
forwork‐upandstartedonbroadspectrumantibiotics.Thepatientcontinuedto
50
decompensaterequiringintubationandinitiationofvasopressorsupport.Shewas
transferredforhigherlevelofcare.Onarrivaltoourfacility,shewasnotedtobe
tachycardicatarateto160‐190beatsperminutewithameanarterialpressureof55‐60
mmHg.Shewasrequiringnorepinephrineat50mcg/min.Vasopressinandneosynephrine
wereeventuallyaddedtoweannorepinephrinedownto30mcg/minsinceshewas
requiringaveryhighdose.Thepatientsubsequentlyarrestedwithpulselesselectrical
activityrequiringchestcompressions.Returnofspontaneouscirculationwasachieved
after5minutesofchestcompressionswithadministrationofepinephrineonce.Atthat
time,thepatientwasinastateofseverelacticacidosisof11.5mmol/LwithapHof6.9and
SVO2of90%.Shewasgiven2ampulesofsodiumbicarbonateandcontinuousrenal
replacementtherapy(CRRT)wasinitiated.Herheartrateremainedat180beatsper
minutewithanarrowQRScomplexpatternpresumedtobeSVT.Echocardiogramwas
orderedandrevealedbiventricularheartfailure.Thepatientwastransitionedto
epinephrine,vasopressinanddobutamineinthesettingofheartfailure.Achestx‐raywas
orderedandshoweddiffusebilateralalveolaropacitiesconsistentwithARDSordiffuse
alveolarhemorrhage.Brainnatiureticpeptideandcardiacenzymesweremarkedly
elevated.Patientalsohadtransaminitisandanelevatedcreatininekinaseenzymelevel.
Ferritinwasnotedtobe5,568mcg/L.Attheoutsidehospitalitwasfoundtobeover
18,000mcg/L.Autoimmunework‐upwasinitiatedandrevealedanANAtiterof1:640with
speckledpattern.HIV,EBV,CMVwerenegative,manyotherinfectiousprocesseswere
ruledout.Preliminarybloodcultureswerenegative,althoughoutsidebloodcultures
reportedgrowinggramnegativerods.SpeciationrevealedtheorganismtobeNeiserria
Sicca.Patientwascontinuedonbroadspectrumantibiotics.Plasmaexchangewasoffered
asalastresortforgram‐negativesepsisinthesettingofmulti‐organfailure.Thepatient
remainedinaveryguardedcondition.Therewasuncertaintyastowhatprecipitatedthis
51
rapiddeclineandmultiorganfailureinapreviouslyhealthywomansuspectedofhavingan
autoimmunedisease.
Investigation
Bonemarrowaspirationperformedonadmissionrevealedapreliminaryresultof
hemophagocytosis(HLH).PatientwaspresumedtohaveHLHbymeeting5/8ofcriteria.
AccordingtotheHLH2004Diagnosticcriteria,diagnosiscanbeestablishedifpatientmeet
morethanfiveoftheeightcriteriaincluding:fever,splenomegally,cytopeniainmorethan
2celllineages,hypertrigliceridemiaandhypofibrinogenemia(triglyceridesgreaterthan
265mg/dLorfibrinogenlesthan1.5g/L),hemophagocytosis,loworabsentNK‐cell
activity,ferritingreaterthan500mcg/L,and/orthepresenceofsolubleCD25greaterthan
2400U/mL(6).Itwasthoughttobelikelysecondarytoautoimmunediseasegivenpositive
anti‐nuclearantibodyandanti‐doublestrandedDNA.However,Itwashardtoconfirmthe
diagnosisinthisacutesetting.
Treatment
High‐dosedexamethasonetherapywaschosenovereptoposidegiventhepatient’s
recentliverfailureandsevereinfection.Thepatientwastreatedwithhigh‐dose
solumederolwithnoadditionalimmunosuppressiveagents.Shecontinuedtoimprove
basedontheparametersofferritin,LDHandbloodlines.Thepatientwaseventually
weanedoffventilationandcirculatorysupportandtransferredtostep‐downunitfor
physicalrehabandrecovery.
Finaloutcome
Finalbonemarrowanalysisrevealedahypo‐cellularbonemarrowreplacedwith
sheetsofmacrophagesandevidenceofhemophagocytosisconsistentwithmacrophage
activationsyndrome.Thepatientwascontinuedonmaintenanceprednisonetherapyand
wasreferredtohematologicspecialtyclinicforcontinuedfollow‐up.
52
Discussion
MacrophageActivationSyndromeisarareformofHLH.Itisafatalsystemic
inflammatorydiseaseresultingfromuncontrolledproliferationofTcellandexcessive
activationofmacrophages(1,2).Itisthoughtthatadeficiencyofperforin,aprotein
expressedonlymphocytesandmacrophages,leadstopersistentlymphocyteactivation.It
alsocausesexcessiveproductionofinterferongammaandGMSFleadingtoactivationof
macrophages(1).Perforinisaproteinthatthecytolityiccellutilizestoinduceapoptosisof
targetcellsincludingtumorcellsandthoseinfectedbyviruses.Withtheinabilitytokill
targetcells,thereisuncontrolledproliferationofTcellsandmacrophagesleadingto
decreasednaturalkillercellsandcytotoxiccellfunction(7).Sustainedmacrophage
activationcausesthereleaseofTNF‐alpha,IL1,IL6associatedwiththeclinicalsymptoms
andtissuesdamageassociatedwithMAS(1,5).Ithasalsobeenhypothesizedthatthelack
ofNKcellsandcytotoxicT‐cellsneededtoterminateanimmuneresponseleadsto
sustainedmacrophageactivity,whichmayplayaroleinsecondaryHLH(3).Accumulation
ofintracellularferritinneededforthematurationofmacrophagescanbeseenasamarker
ofhistiocyteproliferationandactivephagocytosisbymacrophages.MAS,onthespectrum
ofHLH,presentsacutelywithnon‐remittinghighfever,lymphadenopathy,
hepatosplenomegally,pancytopenia,liverdysfunction,hypertriglyceridemiaand
hyperferritinemia.Itisalsopossibletonotelowerythrocytesedimentationrate(ESR),
decreasedfibrinogenlevels,andcoagulopathy(1,4).Numerouswelldifferentiated
macrophagesactivelyphagocytosinghaematopoeticelementsonexaminationofthebone
marrowisthepathognomonicfeatureinMAS(4).ItisimportanttorecognizeMASearly
becausetreatmentisessential.Thehyperinflammatoryresponsecanbefatalifleft
untreated(2).Highdosecorticosteroidsarethecornerstoneoftherapyandshouldbe
initiatedearly.Steroidsthatcrossthebloodbrainbarriershouldbepreferred.Eveninthe
53
settingofahighlyfebrilepancytopenicpatientwithsuspectedinfection,
immunosuppresionisrequiredtocontrolthehyperinflammationsyndromeandavoid
multiorganfailure(2,4).CyclosporinA,plasmaexchange,IVIgandcyclophosphamidehave
alsobeenproposedastherapiesbutnosupportingstudieshaveprovenefficacy.Once
treatmentisinitiatedferritinlevelshavebeenproventobeareliableparameterfor
responsetotherapy(1).
References
1. RavielliAngelo,Macrophageactivationsyndrome.Rheumatology200214:548‐552
2. GrittaEJanka,HemophagocyticSyndromesBloodReviewsSept2007Vol
21(5):245‐253
3. AlexiaAGromMD,JoyceVillaneuvaBS,SusanLeeBS,EllenAGoldmuntzMD,
MurrayHPassoMD,AlexandraFilipovixMDNaturalKillerCelldysfunctionin
patientwithsystemic‐onsetjuvenilerheumatoidarthritisandmacrophage
activationsyndrome.TheJournalofPediatrics.March2003.Vol142(3)292‐296
4. S.Sawhney,PWoo,KJMurray.Macrohpageactivationsyndrome:apotentallyfatal
complicationofrheumaticdisordersArchivesofDiseaseinChildhood2001:85:421‐
426
5. JIHenter,GElinder,OSoder,MHansson,BAndersson,UAndersson.
Hepercytokinemiainfamilialhemophagocytosis.Blood.December1,1991.Vol
78(11)
6. Weitzman,S.ApproachtoHemophagocyticSyndromes.ASHEducationBook.
December,102011.Voll2011(1):178‐183
7. Schulert,GS,Grom,A.MacrophageActivationSyndromeandCytokinedirected
therapies.BestPractResClinRheumatol.Apr2014:28(2):277‐292
54
MultidermatomalextensionofRamsayHuntshouldraisesuspicionforHIV/AIDS.
DeCiccoIAMD,MaitiAMD,Llanos‐CheaFMD,ArduinoRMD.
DepartmentofInternalMedicine,TheUniversityofTexasHealthScienceCenteratHouston
Introduction
HerpesZosteriscommonlyassociatedwithHIVinfectedpatients.Itisfrequently
thefirstmanifestationofHIV.Thus,apatientwhopresentswithherpeszosterinfection
shouldalwaysbetestedforHIVinfection.
Casedescription
Apreviouslyhealthy32‐yearoldhomosexualmaninitiallypresentedtohisprimary
carephysicianwithconcernforaburnonhisneckafterusingheatingpadsforneck
discomfort.Subsequently,hedevelopedpainandrasharoundtheipsilateralearwith
completeparalysisoftheleftsideoftheface.Anextensiverash(Figure1)withlower
motorneuronpalsyoftheleftfacialnervewasnotedatpresentationintheemergency
room.
Thepatientwasinitiallytreatedwithbroadspectrumantibioticsalongwith
ofloxacinanddexamethasoneeardropsfortheearcanalinflammation.Awickwasplaced
topreventstenosis.Polymerasechainreactionandculturesfromunroofedvesicleswere
positiveforherpeszoster.ThepatientwasfoundtobepositiveforHIV‐1withaCD4count
of283/µL,andviralloadof16,900copies/mL.Patientshowedimprovementwith
intravenousacyclovirandhighdoseoralprednisone.Atoneyearfollow‐uphehadmild
residualfacialnervepalsy,butwasabletoclosehiseyes.HisCD4countrecoveredto
normallevelswithHAART.
Discussion
RamsayHuntsyndrome(RHS)isaperipheralfacialnervepalsyalongwith
erythematousvesicularrashovertheearcausedbyVZVreactivationinthegeniculate
55
ganglionofthefacialnerve.1Decreasedcellmediatedimmunityhasbeenimplicatedin
RamsayHuntsyndrome.2Theimmunocompromisedstatusinourpatientlikely
contributedtothemultidermatomalpresentation.Althoughacyclovirhasbeenshownto
reduceincidenceofherpeszosterinHIVinfectedpatients,routineprophylaxisisnot
recommended.3ItiscriticallyimportanttoconsiderHIV/AIDSinapatientpresentingwith
RHSofherpeszosterextendingovermultipledermatomes.Earlyinitiationofantiviral
therapyiscrucialtohaveoptimallongtermoutcomesandreducethechancesof
complications.Steroidsmaybeconsideredonanindividualbasis.
Conclusion
TestingpatientsforHIVshouldbepartoftheinitialmanagementofherpeszoster
infections.EarlydetectionandtreatmentofHIVcanbringfavorableoutcomeswithlong
termsurvivalandbetterqualityoflife.Itisimportantthatphysicianscanrecognizeskin
infectionsthatarecommonlyassociatedwithHIV.
References
1.
SweeneyCJ,GildenDH.RamsayHuntsyndrome.JNeurolNeurosurgPsychiatry
2001;71(2):149–54.
2.
HaginomoriS‐I,IchiharaT,MoriA,etal.Varicella‐zostervirus–specificcell‐
mediatedimmunityinRamsayHuntsyndrome.TheLaryngoscope2015;n/a–n/a.
3.
BarnabasRV,BaetenJM,LingappaJR,etal.AcyclovirProphylaxisReducesthe
IncidenceofHerpesZosterAmongHIV‐InfectedIndividuals:ResultsofaRandomized
ClinicalTrial.JInfectDis2015;jiv318.
56
ElevatedLipaselevelsinSmallBowelObstruction
FathimaZahraKamilFaiz,MD
Abstract
Thisisacaseofa69yearoldmanwithpriorabdominalsurgerieswhopresented
withnausea,vomitingandabdominalpain.Laboratoryvaluesshowedanelevatedlipaseand
liverfunctiontests,suggestiveofacutebiliarypancreatitis.Whenfurtherhistoryrevealed
thathehadnothadabowelmovementinaweek,therewashighsuspicionforsmallbowel
obstruction. A stat CT scan of his abdomen and pelvis showed high grade small bowel
obstructionandacontainedperforatedsigmoidabscess.ThepatientwastakentotheOR
emergently and confirmed to have small bowel obstruction with an incarcerated ventral
hernia.Thiscasedemonstratedtheassociationbetweenelevatedpancreaticenzymesand
smallbowelobstruction.Thiscorrelationhasbeenpreviouslydescribedinbariatricsurgery
casereportsbutnotinpatientswithothersurgeriesasinthiscase.Smallbowelobstruction
canbefatalifnotrecognizedearlyanditisbeneficialtoobtainabdominalimagingtorule
outobstructioninpatientswhohaveanelevatedlipase.
Introduction
Smallbowelobstruction(SBO)occurswhenthereisaninterruptioninthepassageof
intestinalcontentsthroughthegutlumen.Ifthisdiagnosisismissed,SBOcanleadtogut
necrosisandsepsis.Consequently,themortalityofanuntreatedSBOiscloseto80%1.While
somepatientscanpresentwithtypicalsymptomsofbiliousvomiting,abdominalpainand
obstipation,othersmayhaveamorenonspecificpresentation.Herewepresentthecaseofa
patient initially admitted with a picture of acute pancreatitis but was found to have
complicatedsmallbowelobstruction
57
CaseDiscussion
A 69‐year‐old man with known incisional and hiatal hernias presented to the
emergencyroomwitha10‐dayhistoryofabdominaldiscomfort,nauseaandvomiting.Initial
labsshowedaLipase>1000andASTandALTtwicetheupperlimitofnormal.Thepatient
wasadmittedtothemedicinefloorwithadiagnosisofacutepancreatitis.Onphysicalexam,
patienthaddecreasedbowelsoundsandalargenon‐reducibleventralherniawithnofocal
tenderness.Basedonfurtherhistoryfromthefamily,itwasdiscoveredthatthepatienthad
nothadabowelmovementforthepastsevendays.Giventhecombinationofemesisand
constipationwithaherniaandhistoryofabdominalsurgeries,therewasconcernforsmall
bowel obstruction. A CT scan of his abdomen and pelvis showed high grade small bowel
obstructionandacontainedperforatedsigmoidabscess(SeeFigure1andFigure2).Ofnote,
hispancreasappearednormal.
The patient was taken to the OR emergently and confirmed to have small bowel
obstruction with an incarcerated ventral hernia that contained about four feet of bowel.
Additionally, he was found to have a perforated sigmoid mass associated with a pelvic
abscess. Given that the mass appeared malignant, the patient underwent recto‐sigmoid
resection with a colostomy and Hartman pouch procedure. The patient did well post‐
operativelyandwasdischargedwithcloseoncologyfollowup.Pathologyshowedinvasive
adenocarcinomaofthecolon
58
Figure1:CTAbdomenshowingmarkedlydilatedloopsofbowelnotedincoronalview.
Figure2:CTAbdomenshowingincarceratedhernialeadingtosmallbowelobstruction,
notedinsagittalview.
59
Discussion
AccordingtotheACG,acutepancreatitiscanbediagnosediftheymeettwooutofthethree
followingcriteria2:

Abdominalpain,nausea,vomiting

Serumlipase/amylasethricetheupperlimitofnormal

Typicalfindingsonabdominalimaging
However,abdominalimagingshouldonlybeconsideredifthereissignificantdoubtabout
thediagnosisorifthepatientfailstorespondtotreatment2.Inthiscase,theonlyobjective
findingwasanelevatedlipaseandseemedtoconfoundtheactualdiagnosisofSBO.
The surgical literature has several case reports3,4,5 where patients with a gastric
bypassorRoux‐enYgastrojejunostomy(RYGB)presentedwithabdominalpainandelevated
pancreatic enzymes and were admitted as pancreatitis but failed to improve. Subsequent
imagingwouldalwaysshowcomplexSBO.A2015retrospectivestudy4of99casesofSBOin
RYGBpatientsconcludedthattherewasanassociationbetweenSBOandelevatedpancreatic
enzymes. A 2009 case report5 of a similar clinical presentation concluded that any RYGB
patientwithabdominalpainandelevatedlipaseshouldhaveanabdominalCT.
Themechanismofhowsmallbowelobstructionleadstoanelevatedlipaseisthought
tobefromincreasedintraluminalbackpressurecausedbytheobstruction.Thisleadstoa
reflux of intestinal content into pancreatic ducts that subsequently activates pancreatic
zymogens. This concept is referred to as reflux pancreatitis and was noted in bariatric
surgeryliteratureandismostlyassociatedwithSBO.However,therefluxpancreatitiswas
nevernecroticorlife‐threatening.Similarly,liverenzymesaresimultaneouslyelevatedby
thesamemechanism,andthepatientisoftenfalselydiagnosedwithgallstonepancreatitis.
In conclusion, when evaluating any patient with a history of abdominal surgeries, who
60
presentswithabdominalcomplaintsandelevatedpancreaticandliverenzymes,abdominal
imagingshouldbeconsideredtoruleoutSBO.Additionally,smallbowelobstructionmustbe
includedinthedifferentialdiagnosisofelevatedpancreaticenzymes.
References
1. Miller G, Boman J, Shrier I, Gordon PH. Etiology of small bowel obstruction.Am J
Surg.2000;180:33–36
2. Tenner S et al. Management of Acute Pancreatitis. Am J Gastroenterol2013;
108:1400–1415
3. Vettoretto,Nereoetal.LaparoscopyinAfferentLoopObstructionPresentingasAcute
Pancreatitis.JSLS :JournaloftheSocietyofLaparoendoscopicSurgeons10.2(2006):
270–274
4. SpectorDetal.Roux‐en‐Ygastricbypass:hyperamylasemiaisassociatedwithsmall
bowelobstruction.SurgeryforObesityandRelatedDiseases.2015Jan‐Feb;11(1):38‐
4
5. Brooks S et al. Markedly elevatedlipaseas a clue to diagnosis ofsmall
bowelobstructionaftergastricbypass.AmJEmergMed.2009Nov;27(9)1167.e5‐
1167.e7
61
SpontaneousTumorLysisSyndromeinMetastaticBreastCancer
LeAnneNguyen,GabrielAisenberg
DepartmentofInternalMedicine,McGovernMedicalSchool,Houston,TX,USA
Abstract
Acutetumorlysissyndrome(ATLS)isanoncologicemergencycausedbyrapidlysis
ofmalignantcells.Spontaneoustumorlysissyndrome(STLS),intheabsenceofcytotoxic
therapy,frequentlyoccursinhematologicmalignancies.Rarely,STLSoccursinsolidnon‐
hematologicmalignancies.WereportacaseofSTLSinapatientwithmetastaticbreast
cancer.
Introduction
ATLSrepresentsanoncologicemergencyandleftuntreatedcanbefatal.ATLSmost
frequentlyoccursinhematologicmalignanciesafterinitiationofcytotoxictherapybutcan
occurspontaneouslyinhematologicmalignancieswithlargeburdenofdiseaseandhigh
proliferativerate.CasesofSTLSarewellknownanddocumentedinlymphomaand
leukemia.OnlyfewcasereportsdescribeSTLSinsolidnon‐hematologictumors1‐6.We
presentthesecondknowncaseofSTLSinapatientwithmetastaticbreastcancer1.
CasePresentation
A29‐year‐oldAfricanAmericanwomanpresentedtothehospitalwitharapidly
enlargingleftbreastmassanddyspnea.Lessthanonemonthpriortoadmission,shewas
diagnosedwithStageIVinvasiveductalcarcinomaoftheleftbreast(estrogenreceptor
weaklypositive,progesteronereceptornegative,HER2negative).Proliferativerateofthe
tumorasmeasuredbythecellularmarkerKi67was95%.CTimagingpriortoadmission
showedamassivenecroticmassinvolvingtheentireleftbreastmeasuring10.8cmx8.4cm
x11.1cm;severalbilateralpulmonarynodules;diaphragmaticpleuralmetastaticimplants;
62
moderateloculatedleftpleuraleffusion;andinnumerablenecroticlivermetastasiswith
replacementoftheentirelefthepaticlobe(Figure1aand1b).
Figure1a.CTchestshowingalarge,necrotic,leftbreastmass.
Figure1b.CTabdomenshowingmultiplenecroticlivermetastases.
63
Thepatientwasadmittedforinductionofpalliativechemotherapywithdoxorubicin
andcyclophosphamide.Onphysicalexam,shewasnormotensivebuttachycardic.The
entireleftbreastwasfirmwithalarge,fungatinglesionsuperiortotheareolawithsero‐
sanguinousdischarge.Therewasapalpable4cmleftaxillarynode.Breathsoundswere
decreasedattheleftlungbase.Theliverwaspalpableseveralfingerbreadthsbelowthe
rightcostalmargin.
Laboratoryfindingsonadmission(Table1)revealedrenalinsufficiency,elevated
potassium,elevateduricacid,andelevatedLDH.ThiswasconcerningforSTLS,so
chemotherapywasdelayed.Shewasstartedonintravenousnormalsalineandreceived
onedoseofrasburicase.Dailytherapywithallopurinolwasalsostarted.Herlaboratory
dataimprovedaftertreatment(Table1),andshethenreceiveddoxorubicinand
cyclophosphamide.Unfortunately,herclinicalcoursewascomplicatedbyarapidly
accumulatingpleuraleffusion,whichledtohypoxiaandcardiacarrestresultinginher
deathonhospitaladmissiondaysix.
Table 1. Metabolic abnormalities throughout course of hospitalization. Hospital Admission Day Uric Potassium acid (mmol/L) (mg/dL) Phosphorous Calcium (mg/dL) BUN (mg/dL) (mg/dL) Creatinine LDH (mg/dL) (U/L)
1 6.1 10.7 4.7 8 50 1.5 5317
2 3.9 1.4 2.8 7.4 32 1.2 3980
3 4.1 0.9 2.4 7 34 1.1 3958
5 4.6 2. 8 3.3 7.1 45 1.2 6883
6 5.5 3.4 5.5 7.9 49 1.6 6857
64
Discussion
ATLSistheresultofrapidtumornecrosiswiththereleaseofcellularcontentsinto
thebloodstreamleadingtometabolicderangementssuchashyperuricemia,hyperkalemia,
hyperphosphatemia,andhypocalcemia.Hyperuricemiaincreasestheriskofuricacid
crystallizationinrenaltubulesandcanleadtorenalfailure.Thereleaseofpotassium
increasestheriskofhyperkalemia—themostdreadedcomplicationofwhichiscardiac
arrhythmiasanddeath.Thereleaseofphosphatecanresultinhyperphosphatemia.
Phosphateprecipitationwithcalciumcanworsenpre‐existingrenalfailureandresultin
hypocalcemia.
ATLSmostfrequentlyoccursaftercytotoxictherapyinhematologicmalignancies,
however,itcanoccurspontaneouslyandiswelldescribedinliterature.STLSisrarely
describedinsolidnon‐hematologicmalignancies.Uponliteraturesearch,wefoundthe
followingcasereportsofSTLSinsolidnon‐hematologictumorsasshowninTable2.There
isonlyonepublishedcasereportofSTLSinmetastaticbreastcancer1.
Table 2. Published case reports of STLS in solid non‐hematologic tumors Germcelltumors
Colon cancer Pheochromocytoma Hepatocellular carcinoma Lung adenocarcinoma Squamous cell carcinoma of lung Gastric adenocarcinoma Metastatic adenocarcinoma of unknown primary Prostate cancer Squamous cell carcinoma of maxillary sinus RiskfactorsforATLSincluderapidlyproliferatingorchemosensitivemalignancies,
pre‐existingrenalinsufficiency,elevateduricacidatbaseline,andextensivetumorburden
65
asquantifiedbybulkydisease>10cm,elevatedLDHgreaterthantwotimestheupperlimit
ofnormal,orelevatedwhitebloodcellcountabove25,000/μl7.
Inthiscasereport,webelievethatourpatientshowedevidenceofSTLS.Priorto
receivinganychemotherapy,shepresentedwithrenalinsufficiency,hyperkalemia,and
hyperuricemia.Shehadmultipleriskfactorsincludingextensivetumorburdenwith
massivenecrosisseenonCTimaging,highlyproliferativetumor,andelevatedLDH.We
excludedothercausesofAKIsuchasparenchymalkidneydiseaseandpost‐renal
obstructionbyCTimaging.Additionally,withtheadministrationoffluidsandrasburicase,
herrenalfunctionimprovedandlaboratorydatanormalized.Herdeathwasattributedto
rapidlyaccumulatingpleuraleffusionresultinginhypoxiaandcardiacarrest.
STLScanbelifethreatening,thereforeawarenessandearlyrecognitionis
important.Although,solidnon‐hematologictumorsareclassifiedasloworintermediate
riskofTLSbasedonexpertguidelines7,itisimportanttomaintainanelevatedindexof
suspicioninpatientswithriskfactorsandweighthebenefitofprophylaxis.
References
1.N.T.SklarinandM.Markham.“Spontaneousrecurrenttumorlysissyndromeinbreast
cancer.”AmericanJournalofClinicalOncology18.1(1995):71‐73.
2.D.R.CrittendenandG.L.Ackerman.“Hyperuricemicacuterenalfailureindisseminated
carcinoma.”ArchivesofInternalMedicine137.1(1977):97‐99.
3.J.Feld,H.Mehta,andR.L.Burkes.“Acutespontaneoustumorlysissyndromein
adenocarcinomaofthelung:acasereport.”AmericanJournalofClinicalOncology23.5
(2000):491‐493.
4.E.Vaisban,A.Braester,O.Mosenzon,M.Kolin,andY.Horn.“Spontaneoustumorlysis
syndromeinsolidtumors:reallyararecondition?”AmericanJournaloftheMedicalSciences
325.1(2003):38‐40.
66
5.I.S.Woo,J.S.Kim,M.J.Parketal.“Spontaneousacutetumorlysissyndromewith
advancedgastriccancer.”JournalofKoreanMedicalScience16.1(2011):115‐118.
6.N.Saini,K.P.Lee,S.Jhaetal.“Hyperuricemicrenalfailureinnonhematologicsolid
tumors:acasereportandreviewoftheliterature.”CaseReportsinMedicine2012(2012),
ArticleID314056,5pages.doi:10.1155/2012/314056.
7.B.Coiffier,A.Altman,C.H.Pui,A.Younes,M.S.Cairo.“Guidelinesforthemanagementof
pediatricandadulttumorlysissyndrome:anevidence‐basedreview.”JournalofClinical
Oncology26.16(2008):2767‐2778.
67
PositionalSTSegmentElevationCausedbyaVentricularPseudoaneurysm
DeCiccoIAMD,VelasquezAHMD,McBrideCLMD,AuJMD,AisenbergGMMD,PostalianA
MD,Quintana‐QuezadaRAMD,LlanosCheaFMD,OcazionezTrujilloDMD,DhobleAMD,
ArainSMD,TheUniversityofTexasatHoustonHealthScienceCenter
Introduction
Ventricularpseudo‐aneurysms(VPAs)areararebutseverecomplicationof
myocardialinfarction(MI),firstdescribedbyWilliamHarveyin1649[1].Therelationship
betweencoronaryarterydisease(CAD)andcardiacrupturewasestablishedbyJoseph
Hodgronin1850whenhenotedthatscartissueoriginatingwithininfarctedmyocardium
wassusceptibletorupture[2,3].Whenbloodpassingfromtheventriclethroughtheareaof
ruptureissurroundedbyadjacentstructuressuchaspericardiumorfibroustissue,aVPA
isformed[4].VPAscanalsoformasacomplicationofcardiacsurgery,tumorinvasionor
trauma[5].
Wereportthecaseofapatientwithaventricularwallrupturethatwascontained
withinthepericardium,presumablyduetofibrosisformedasaconsequenceofprior
coronaryarterybypassgrafting(CABG).Thepatientwasalsonotedtohaveintermittent
positionalSTsegmentelevationonelectrocardiogram(ECG),possiblycausedby
intermittentcoronaryarterycompressionbytheVPA.
CasePresentation
An84‐year‐oldwomanpresentedtoourhospitalcomplainingofpressure‐likechest
painthatradiatedtoherbackandleftmandible.ShehadahistoryofCADtreatedwith
CABG18yearsearlier.Approximately2monthspriortopresentation,sheunderwent
percutaneouscoronaryinterventionwithstentplacementtotherightcoronaryartery,the
coronaryangiogramwasdoneduetorecurrentanginapectorisandarecentabnormal
treadmillstresstest.Onphysicalexamination,shewasdiaphoreticandappeared
68
uncomfortable.Auscultationrevealeda3/6systolicmurmurbestheardoverlyingtheleft
sternalborder.Bilaterallowerextremity1+pittingedemawaspresent.SerialECGs
revealedintermittentSTelevationinleadsIandaVL.Interestingly,theSTelevation
occurredwhilethepatientwasseatedorstandingandresolvedwhenshewassupine.
Theseepisodeswerealsoassociatedwithhypotension.Pertinentlaboratoryexamination
findingsincludedatroponinIof9.48ng/mlandtroponinTof1.160ng/ml.Thepatient
underwentemergentcoronaryangiographybutnoculpritlesionwasidentified.Duringthe
procedure,shedevelopedcardiogenicshockrequiringintra‐aorticballoonpumpinsertion
andvasopressortherapy.Onceshewastransferredtothecoronarycareunit,a
transthoracicechocardiogramwasdoneandrevealedalargeecholucentmassanteriorto
therightventriclewhichcompressedtherightventricularoutflowtract.Subsequently,a
computedtomography(CT)ofthechestwithintravenousiodinatedcontrastwasobtained
tobettercharacterizethemass.Itshowedafocaldefectintheanteriorwalloftheleft
ventriclewithlinearextravasationofcontrastandacontainedhematomawithinthe
pericardium.Inanticipationofpossiblesurgicalintervention,acardiacmagneticresonance
image(MRI)wasdone,whichshowedapericardialhematomaof3.2cmx6.1cmx5.5cm
(Figure1),secondarytoleftventricularrupture.Uponfurtherreviewoftheimaging,left
ventricularwallthinningandhypokinesisoftheanteroseptalsegmentswerenoted,
presumedtobesecondarytoachronicinfarctoftheleftanteriordescendingartery
territory.Rightheartcatheterizationandleftvenctriculographywereperformed,
confirmingfreewallrupturewithacontainedpseudo‐aneurysm(Figure2).After
discussingthecasewiththepatient´sfamily,adecisionwasmadetopursueconservative
management.Thepatientrecoveredsuccessfullyandremainedhemodynamicallystable
afterdiscontinuationofmechanicalandpharmacologicsupport.
69
Figure1.MRIshowingventricularpseudoaneurysm.PanelAshowingthepseudoaneurysm
inthesagittalplane.PanelBshowingthepseudoaneurysminthecoronalplane.
A
B
Figure2.ExtravasationofcontrastthroughtheLeftVentricularwall(Arrow).
70
Discussion
Priorliteraturesuggeststhatapproximately55%ofVPAsaresecondarytoMI,33%
relatedtocardiacsurgery,18%totraumaand5%toinfection.Only20%ofthesecases
presentwithSTsegmentelevation[5],whichmaycomplicatethediagnosticprocess.The
mortalityofventricularrupturewithoutemergentsurgicalrepairhasbeenreportedtobe
ashighas90%[6].
Echocardiogramisawidelyavailableandsensitivediagnostictoolwhichcanidentify
pericardialeffusion,themostcommonfindinginpatientswithleftventricularwallrupture
[7,8].CT,MRIandventriculographyareotherusefultoolstodiagnoseVPAsandmeasure
leftventricularvolumes[9,10].Intheacutesetting,itisimperativetodiagnoseVPAs
promptlyduetotheextremelyhighmortalitythatcanresultwhennointerventiontakes
place[2].
OurpatientpresentedwithSTelevationandelevatedcardiacenzymes.Coronary
angiographydidnotrevealcoronaryarteryocclusion.Aftercarefulreviewofthe
echocardiogram,andconsideringthepatientwashavingSTelevationonECGthatwas
reproduciblyrelatedtoposture,wehypothesizethattherewasintermittentexternal
compressionoftheleftanteriordescendingartery(LAD).Whenthepatientwassittingor
standing,thepseudoaneurysmcompressedtheLADresultinginanginalsymptomsandST
segmentelevationinleadsIandaVL.Thiscoronaryarterycompressionwasnotobserved
intheCTorMRIowingtothefactthepatientwassupineduringimageacquisition.
Regardingthecauseoftheventricularrupture,wepostulatethatwireperforationmay
haveoccurredduringtheleftventriculogramdone2monthspriortopresentation.
However,webelieveourpatient’spseudoaneurysmdevelopedasaconsequenceofa
subclinicaltransmuralmyocardialinfarctionthatoccurredsometimebetweenthelast
percutaneouscoronaryinterventionandthispresentation.IftheVPAhadbeena
71
consequenceofthepriorventriculogram,itwouldhaveformedmuchearlier.Wealso
hypothesizethatthepatientsurvivedwithoutsurgicalinterventionbecausetheVPA
occurredinthesettingofapoorly‐compliantscarredpericardiumasaconsequenceof
priorsternotomyduringherCABG,resultinginasmalltomoderatehematomathat
preventedfurtherbloodloss.
References
1‐HarveyW.DeCirculatioSanguinis.Exercit3.CitadoporMorgagniGBIn:Theseatsand
causesofdiseases.Trad.BenjaminAlexander.London:Letter27;1769.p.830.
2‐ReardonMJ,CarrCL,DiamondA,etal.Ischemicleftventricularfreewallrupture:
prediction,diagnosisandtreatment.AnnThoracSurg.1997Nov;64(5):1509‐13.
3‐BoniniRC,VerazainVQ,MustafaRM,etal.Ruptureoftherightventricularfreewallafter
myocardialinfarction.RevBrasCirCardiovasc.2012Jan‐Mar;27(1):155‐9.
4‐SunkaraB,BriasoulisA,AlfonsoL,etal.Leftventricularpseudoaneurysmasafatal
complicationofpurulentpericarditis.HeartLung.2015Sep‐Oct;44(5):448‐50.
5‐Garcia‐GuimaraesM,Velasco‐Garcia‐de‐SierraC,Estevez‐Cid,etal.Currentroleof
cardiacimagingtoguidecorrectionofagiantleftventricularpseudoaneurysm.IntJ
Cardiol.2015Nov;198:152‐3.
6‐HondaS,AsaumiY,YamaneT,etal.Trendsintheclinicalandpathological
characteristicsofcardiacruptureinpatientswithacutemyocardialinfarctionover35
years.JAmHeartAssoc.2014Oct;3(5):e000984.
7‐PetrouE,VartelaV,KostopoulouA,etal.Leftventricularpseudoaneurysmformation:
Twocasesandreviewoftheliterature.WorldJClinCases.2014Oct;2(10):581‐6.
8‐SutherlandFW,GuellFJ,PathiVL,etal.Postinfarctionventricularfreewallrupture:
strategiesfordiagnosisandtreatment.AnnThoracSurg.1996Apr;61(4):1281‐5.
72
9‐HeatlieGJ,R.MohiaddinR.Leftventricularaneurysm:comprehensiveassessmentof
morphology,structureandthrombususingcardiovascularmagneticresonance.ClinRadiol.
2005Jun;60(6):687‐92.
10‐BuckT,HunoldP,WentzKU,etal.Tomographicthree‐dimensionalechocardiographic
determinationofchambersizeandsystolicfunctioninpatientswithleftventricular
aneurysm:comparisontomagneticresonanceimaging,cineventriculography,andtwo‐
dimensionalechocardiography.Circulation.1997Dec;96(12):4286‐97.
73
CallforawarenessofWestNilevirusinfection.
RohanGupta,DO;ManojThangam,MD;GabrielAisenberg,MD
TheUniversityofTexasatHoustonInternalMedicineResidencyProgram,Houston,TX,
USA
Abstract
Background:WestNilevirusisendemicintheUnitedStatesofAmericacausingWestNile
feverandWestNileNeuroinvasivedisease(WNND)includingmeningitis,encephalitisor
acuteasymmetricflaccidparalysisduringthemonthsofJulyandSeptember.Basedonthe
initialnonspecificsymptomsitcanbedifficulttodistinguishWestNileNeuroinvasive
diseasefrombacterialmeningitis.
Methods:Wepresentashortcaseseriesof3caseswhichpresentedattheLyndonB
JohnsonandMemorialHermanHospitalandwerediagnosedwithWestNileinfection.
Patient’smedicalrecordswerereviewedtoobtainhospitalcourse,laboratoryandimaging
data.
Results:Threepatientspresentedto2differenthospitalsinHouston,TexasfromJulyto
Septemberin2014withfeverandconfusion.Meningitiswassuspectedasinitialdiagnosis
inthesepatients.CSFstain/culture,HSVPCR,VDRL,Enterovirusandbloodcultureswere
negative.All3patientsreceivedempiricbroadspectrumantibioticsincludingVancomycin,
Ceftriaxone,andAmpicillinforpresumedbacterialmeningitis.InallcasesCSFserologies
subsequentlywerepositiveforWestNilevirus.
Conclusion:AntibioticsdonotplayanyroleinmanagementofWNNDandshouldonlybe
administeredwithsuspectedbacterialmeningitis(eg,positiveGramstain,WBC
>1000/microL,glucose<40mg/dL).Patientwithviralmeningitisneedsupportivecareand
reassurance.Adverseeventsareonlyseeninpatientswhoareimmunosuppressedwith
neurologicaldeficits.
74
Introduction
WestNilevirusisamemberofJapaneseencephalitisviralantigencomplex.Itwas
discoveredinNewYorkCityin1999andsincethenithasbecomeendemicinUSAand
CanadaespeciallyinthemonthsofJulytoSeptember.Mostinfectionsarecausedby
transmissionofvirusaftermosquitobitesbutcanalsobetransmittedviabloodproduct
transfusionsandorgantransplants.
About20%patientswithWNVinfectionsdevelopafeverwithothersymptomssuchas
headache,bodyaches,jointpains,vomiting,diarrhea,orrash.Mostpeoplewiththistypeof
WestNilevirusdiseaserecovercompletely,butfatigueandweaknesscanlastforweeksor
months.Lessthan1%ofpeoplewhoareinfectedwithWNNDsyndromewithaserious
neurologicillnesssuchasencephalitisormeningitis,andacuteflaccidparalysis(CDC).
ClinicalpresentationofWNNDisdifferentfrombacterialcerebrospinalfluidinfectionsbut
sometimesitcanbechallengingtodistinguishbetweenthem.Wepresentashortcase
seriesofpatientswithWestNileinfectionwhichweremistreatedasbacterialmeningitis.
TheprimaryobjectiveofthisstudyistoincreaseawarenessofWestNileinfectionamongst
primarycarephysiciansespeciallyinpatientspresentingwithfeverandconfusioninthe
monthsofJunetoSeptember.
CaseSeries
Case1
A63yearoldmanwithnopastmedicalhistorypresentedwithconfusionand
subjectivefever.Fifteendayspriortoadmission,heexperiencedworseningfatigue,nausea,
andbilateralfrontalheadaches.Hedeniedanyphotophobia,phonophobia,cough,urinary
symptoms,sorethroat,orpain.Duetoa103.2°Ffever,leukocytosisof12k/uL,and
disorientation,heunderwentalumbarpuncture.Cerebralspinalfluid(CSF)analysis
demonstratedopeningpressureof16cmH2O,glucose66mg/dL,protein41.6mg/dL,7
75
WBC/uLwith60%neutrophils,28%lymphocytesand12%monocytes.Thepatientwas
startedonVancomycin,Ceftriaxone,andAmpicillinforpresumedbacterialmeningitis.CSF
stain/culture,HSVPCRandVDRLwerenegative.CXRshowednoacuteabnormalities.
Bloodculturesdidnotgrowanyorganisms.Theprimaryteamdecidedtoholdantibiotic
treatmentonadmissiontothemedicalfloorandmonitorthepatientcarefully.Thepatient
clinicallyimprovedwhileremainingafebrile.Hewasdischargedafter3daysof
observation.FivedayspostdischargeCSFserologieswerepositiveforwestnilevirus.
PatientwasdiagnosedwithWestNileviralmeningoencephalitis.
Case2
A42yearoldmanwithhistoryofmigrainespresentedwithsevereheadache,
myalgias,fatigueandfeversince5dayspriortoadmission.Attheonsetofsymptomshe
wenttoalocalclinicandwasprescribedamoxicillin.Hetookitfor5dosesbuthis
symptomsdidnotimproveandhedecidedtocometotheemergencydepartment(ED)for
furtherevaluation.Thepatientwasafebrileonarrival.Hedeniedanyhistoryofrecent
travelorsickcontacts.Onphysicalexam,thepatientwasalertandorientedtimesthree.
InitialCBCandCMPwerenormal.IntheED,lumbarpuncturewasperformedwhich
showed70WBC(63%neutrophil,30%lymphocytes),77glucose,and57protein.Hewas
empiricallystartedonacyclovir,ceftriaxone,andvancomycinformeningitis.Acyclovirwas
discontinuedbytheprimaryteamduetoalowsuspicionofHerpesinfectionhowever
otherantibioticsweregivenintravenouslyfor7days.Hissymptomscontinuedtoimprove
overthenext7days.Atthetimeofdischarge,hehadnofever,headaches,ormeningeal
signsandwasbacktohisusualstateofhealth.Finalbloodculture,CSFbacteria
stain/cultureandHSVPCRandenterovirusPCRcamebacknegative.Twodaysafter
dischargeCSFserologiescamebackpositiveforWestNileVirus.Thepatientwasdiagnosed
withWestNilemeningitis.
76
Case3
A56yearoldmanwithpastmedicalhistoryofhypertension,dyslipidemia,and
coronaryarterydiseasepresentedafterbeingfoundunresponsive.Onexam,hewasfebrile
withatemperatureof104°Fandnon‐responsivetoverbalstimuli.Hewasparalyzedon
hisrightarmandbilaterallowerextremities.Additionally,hisleftarmhaddecreased
musclestrength.Laboratorystudieswerenotablefor17.7k/uLleukocytosis.CSFanalysis
revealed13RBC/uL,28WBC/uLwith45%neutrophilsand41%lymphocytes,70mg/dL
glucose,and76mg/dLprotein.Gramstain,culture,andsyphilistestingofCSFwere
negative.ViralstudiesofCSFwerenotordered.Thepatientwasstartedonvancomycin,
cefepime,ampicillin,andacyclovirforpresumedbacterialmeningitis.Hishospitalcourse
wascomplicatedbysepsisduetohospitalacquiredAcinetobacterpneumoniaand
bacteremiawithchronicrespiratoryfailure,kidneyinjuryrequiringrenalreplacement
therapy,sacraldecubitousulcersandrightglutealabscesscomplicatedwithosteomyelitis.
Duetoworseningofthepatient’sclinicalconditionwithlittleimprovementinmental
status,repeatlumbarpuncturewasperformed.Serologyforwestnileviruswaspositive
28daysafterinitialpresentation.Thepatientwaseventuallystabilizedafterbeingtreated
forpneumonia,bacteremia,andosteomyelitis.Patientwasinitiatedonhemodialysisandis
awaitingplacementforalongtermacutecarefacility.
Discussion
WestNileneuroinvasivediseaseisanendemicdiseaseinUnitedStateswithover
16000casesreportedsince1999.Clinicalpresentationisdifferentfrombacterial
cerebrospinalfluidinfectionsbutsometimescanbechallengingtodistinguishbetween
them.Mostpeople(70‐80%)whobecomeinfectedwithWestNilevirusdonotdevelopany
symptoms.CasesaremorefrequentlyseeninthemonthsofJulytoSeptemberwithan
incubationperiodof2weeks.Inacutepresentationspatientstendtohaveabruptonsetof
77
lowgradefever,fatigue,headacheswithvaryingseveritiesofmentalstatuschanges
rangingfrommildheadachestoseverecoma.Onestudyhasshownthatclinicaloutcome
dependsatage,genderandspecificneurologicaldeficitsatonset[2].
ThediagnosisismadebydetectionofIgMantibodyinserumorCSFusingenzymelinked
immunosorbentassayorinsomecaseswithdetectionofviralRNAbynucleicacid
amplificationtestssuchaspolymerasechainreaction(PCR).ACanadianstudywith276
symptomaticcasesofWestNilevirusshowedtheyieldofthediagnostictestingwaslow.Of
191weretestedbybothserologyandPCR,86(45.0%),111(58.1%),and180(94.2%)
weredetectedbyPCR,serology,andcombinedPCRandserology,respectively[3].CSF
studiescanshowpictureofearlybacterialinfectionwithnormalorlowglucose,elevated
proteinandmoderatepleocytosis(<500cells/microliter)withlymphocyticpredominance.
IncaseofWNNDCSFWBCcountsareusuallyaroundorlessthan230cells/mm3asseenin
all3ofourcases.However,neutrophilicpredominanceashighas50%ofcellcountcanbe
seeninthesecasesatthetimeofearlypresentationin35‐40%ofpatients[4].Inallthe
threecasespresentedinthisseriestherewasneutrophilpredominancewhichmightbethe
reasonthepatientsweretreatedwithantibioticsforsuspectedbacterialmeningitis.
DuetolowyieldoftheCSFandserumtestingrepeatlumbarshouldbeperformedifthereis
highsuspicionorlackofclinicalimprovementinthepatientafter10days.Thiswasevident
inthecase3ofourseries.Onimaging,whichisseldomrequiredfordiagnosis,CTscanof
thebrainisoftennormalacutelyandMRIbrainshowsdiffusionweightedorT2weighted
imagingintheregionsofbasalganglia,thalami,caudatenuclei,brainstem,andspinalcord
[5].Inthecaseseriespresentedabovethediagnosiswasmadewithoutimaging.Itis
importanttoobtainagoodtravelandexposurehistoryinallthepatientstoexcludeother
viralillnesslikedengue,herpessimplex,varicellazoster,StLouisencephalitisand
78
enterovirus.Bacterialmeningitisandtickborneillnessessuchaslymediseaseandrocky
mountainspottedfeverarealsoincludedinthedifferentialdiagnosis.
ThereisnoproventreatmentforWNND.Supportivecareincludingintravenousfluids,pain
medicationsandnursingcarearemainstayfortreatment.Antibioticsdonotplayanyrole
inmanagementofWNNDandshouldonlybeadministeredwithsuspectedbacterial
meningitis(eg,positiveGramstain,WBCcount>1000/microL,glucoseconcentration<40
mg/dL[2.2mmol/L]).RoleofInterferon,RibavarinandIVIGareunclearandthereisno
evidencebyrandomizedcontroltrial.Inourcasespatientsweremistriagedonadmission
andgivenunnecessaryantibioticsforaclinicalpictureofbacterialmeningitis.While
treatingthesepatientsoneshouldknowthatseriousadverseoutcomesareonlyseenin
immunosuppressedpatientswhodevelopWNNDwithseveremuscleweaknessor
deteriorationinthelevelofconsciousness.Thusifbacterialmeningitisisruledoutbased
oninitialCSFtestingthenempirictreatmentwithbroadspectrumantibioticsshouldbe
avoided.
Conclusion
Despiteaverydifferentclinicalpresentationphysiciansoftentreatviralencephalitis
withmultiplebroadspectrumantibiotics.SeveralvirusesincludingWestNilevirus,St.
Louisencephalitisvirus,Easternequineencephalitisvirus,Californiaencephalitisvirus,
andWesternequineencephalitisvirusmaypresentwithsimilarsymptoms.Theuseof
unnecessaryantibioticsoftenleadstoincreasedcost,anxietyandpossibletoxiceffects.All
oftheabovementionedpatientsneededsupportivecareandreassuranceatpresentation
ratherthanpromptantimicrobials.ItisimportanttorecognizethatWestNilevirus
presentsinadifferentwaythanbacterialmeningitis.Obtainingathoroughhistory,
assessmentofexposures,timeofpresentation(JulytoSeptember)andCSFWBCcountare
importantfactorswhichcanbeusedtodistinguishthecasesfrombacterialmeningitis.
79
References
1. CentersforDiseaseControlandPreventionWestNilevirus.
http://www.cdc.gov/ncidod/dvbid/westnile/surv&control.htm.AccessedJuly15,
2006.
2. Hart,Jetal.WestNilevirusneuroinvasivedisease:neurologicalmanifestationsand
prospectivelongitudinaloutcomes.BMCInfectiousDiseases2014,14:248
3. TilleyPA,FoxJD,JayaramanGC,PreiksaitisJK.Nucleicacidtestingforwestnile
virusRNAinplasmaenhancesrapiddiagnosisofacuteinfectioninsymptomatic
patients.JInfectDis2006;193:1361.
4. TylerKL1,PapeJ,GoodyRJ,CorkillM,Kleinschmidt‐DeMastersBK.CSFfindingsin
250patientswithserologicallyconfirmedWestNilevirusmeningitisand
encephalitis.Neurology.2006Feb14;66(3):361‐5.Epub2005Dec28.
5. AliM,SafrielY,SohiJ,etal.WestNilevirusinfection:MRimagingfindingsinthe
nervoussystem.AJNRAmJNeuroradiol2005;26:289.
6. O'LearyDR,MarfinAA,MontgomerySP,etal.TheepidemicofWestNilevirusinthe
UnitedStates,2002.VectorBorneZoonoticDis2004;4:61.
80
IncreasingSafetyofNSAIDPrescribingtoOsteoarthritisPatients.
SarahKazzazMD,AnjuMohanMD,ManojThangamMD,JamiseCroomsMD,NidalGanim
MD,JonasGunawanMD,PoojaGidwaniMD,RaynumdoAQuintanaQuezadaMD,Madelyn
RosenthalMD,YiChunYehMD.
Abstract
Osteoarthritisiscommonlyencounteredintheprimarycaresetting.Nonsteroidal
anti‐inflammatorydrugs(NSAIDS)arefrequentlyusedforpaincontrolbutpatientsare
usuallyunawareoftheadverseeffectsofthesemedications.Thestudyteamconducteda
retrospectiveanalysisforabaselinedata,followedbyinterventionphaseaimedtoincrease
counselingforpatientsonNSAIDSaboutthemedicationsideeffectsinprimarycareclinics.
Duringbaselineperiod54%(6/11)patientwithOAweretakingNSAIDs,ofthese17%
(1/6)hadacontraindicationand17%(1/6)receivedcounseling.Duringthepilotperiod,
95%(20/21)patientswithOAwereonNSAIDs.Fromthese,35%(7/20)hada
contraindication,and57%(4/7)ofthosewithcontraindicationreceivedcounseling.
Introduction
Theaverageannualprevalenceofosteoarthritis(OA)intheambulatoryhealthcare
systemintheUnitedStatesisestimatedtobe3.8%,whichamountsto7.7millionpatients
withOA.1,2AccordingtotheAmericancollegeofRheumatologyguidelines,theinitial
pharmacologicforOAincludesNSAIDS,acetaminophen,tramadol,andintraarticular
steroids.1,3
Non‐steroidalanti‐inflammatorydrugs(NSAIDs)arefrequentlyusedduetoeaseof
availabilityover‐the‐counter,perceivedsafetyprofile,andrelativelylowcost.When
properlyprescribed,NSAIDscanprovideaneffectiveandsafetreatmentforOA.However,
theymustbeusedwithcautionastheyareassociatedwithnumerousadverseeffectsand
arecontraindicatedincertainpatientpopulations(SeeTable1).
81
Table1:Potentialadverseeffects.2,3,4
OrganSystem
AdverseEffects
Gastrointestinal(GI)
GIbleed,Dyspepsia,PepticUlcerDisease
Renal
AcuteRenalFailure,UncontrolledHypertension
Cardiovascular
IncreasedRiskofMyocardialInfarction
Hematological
AntiplateletEffects
TheAmericanCollegeofRheumatology(ACR)recommendationsstatethathealthcare
providersshouldnotuseoralNSAIDSinpatientswithcontraindicationstotheseagents
andshouldbeawareofthewarningsandprecautionsassociatedwiththeuseofthese
agents.3RecommendationsforspecificpopulationscanbefoundinTable2.
Table2:Recommendationsforosteoarthritistherapyinspecificpatientpopulations.5
PatientPopulation
RecommendedTherapy
Person’solderthan75yrsofage
TopicalNSAIDsinsteadoforalNSAIDs
GIulcerwithnoGIbleedinover1year
COX‐2selectiveNSAIDorNSAID+PPI
GIulcerwithGIbleedwithin1year
COX‐2selectiveNSAID+PPI
ChronickidneydiseasestageIVorV
StronglysuggestNSAIDavoidance
EnsuringappropriateNSAIDprescribingpracticesisanimportantaspectof
maintainingthehealthofpatientswithOA.Therefore,wedevelopedaquality
improvementinitiativetoevaluatecurrentprescribingtendenciesofNSAIDsforOA
associatedpaininoneofourambulatoryclinics.
82
Objectives
•
TodecreaseinappropriateuseofNSAIDsinOApatientswithrelativecontra‐
indications.
•
ToincreasecounselinganddocumentationregardingNSAIDsthroughtheuseofa
texttemplateinclinicprogressnote.
Methodology
Thisqualityimprovementstudywasundertakenbyinternalmedicineresidents
formtheUniversityofTexasinHoustonworkingin2outpatientclinics.Patientswitha
historyofOAwereidentifiedbyresidentsandfacultyduringambulatoryclinic.
InformationregardingNSAIDuseandthecoexistenceofrelativecontraindicationswas
gatheredbetweenNovember2015toJanuary2016.Wedefinedrelativecontraindications
toincludemyocardialinfarction,percutaneousintervention,coronaryarterybypass
grafting,congestiveheartfailure,peripheralarterydisease,hypertension,historyofupper
GIbleeding,chronickidneydiseasewithaglomerularfiltrationrateoflessthan60forat
least12months,anduseofanticoagulationtherapy.Wealsonotedwhetherpatientswere
takingNSAIDsappropriately:correctdosing,ingestionwithmeals,andnotconcurrentwith
protonpumpinhibitors.Lastly,residentsdeterminedwhetherappropriatecounselingfor
NSAIDusewasprovidedanddocumented.
Wedevelopedanintervention,whichaimedtoincreasecounselingconcerning
contraindicationstoNSAIDuseviatexttemplateintheclinicprogressnote(SeeBox1).
83
Box1:ClinictemplateforcounselingregardingNSAIDuseinOA.
“IcertifythatIhavecounseledthepatientontherisksoftheirNSAIDmedicationusage
basedonthepertinentpositivestatementsregardingthepatient’spastmedicalhistory,as
above.TheseadverserisksincludeprogressionofHTNaswellasincreasedriskofcoronary
arterydisease,MI,developmentandprogressionofCKDaswellasincreasedriskofpeptic
ulcerdiseaseandGIbleeding.”
Inthepostinterventionphase,wereviewedrecordsfromFebruarytoApril2016to
documentcompliancewiththeuseofourtexttemplate.Wenotedifresidentshave
reevaluatedNSAIDuseinpatientsdiagnosedOAandprovidedcounselingconcerning
contraindications.AssessmentofcounselingandreevaluationofNSAIDprescriptionswas
basedondocumentationinpatientcharts.
Results
84
Duringthebaselineperiod(November2015),54%(6/11)ofpatientswithOAseen
weretakingNSAIDs.Atotalof17%(1/6)ofpatientshadacontraindicationtoNSAIDuse
buthadreceivedcounseling.Another17%(1/6)ofpatientshadacontraindicationbuthad
notreceivedcounseling.
Duringtheinterventionphase,95%(20/21)patientswithOAweretakingan
NSAID.Ofthese,35%(7/20)hadacontraindication,and57%ofthosewitha
contraindication(4/7)receivedcounselingwhichwasdocumentedusingourtexttemplate.
Ofnote,allofthepatientsthatreceivedcounselingdecidedtocontinueNSAIDuse.
Discussion
Participationinthisprojectraisedawarenessamongresidentstocounselpatients
regardingNSAIDcontraindications.Duringthepilotstudy,wecounseledmorethanhalfof
patientsusingNSAIDsdespiteanyrelativecontraindication(4/7).However,ourlimited
baselinedatamakesitdifficulttodetermineifourinterventionactuallyincreased
counselinginourclinics.Sinceweonlyhad2patientsinthebaselinegroupwitharelative
contraindicationtoNSAIDs,potentialpre‐interventionandpost‐interventionpercentages
maynotberepresentativeofanyimprovement.Thelimitedstudysizemakesuseful
comparisonsdifficult.
Futureprojectsoughttohavealongerstudyperiodtoimprovepatientsize.
Additionally,ourtemplatewasutilizedinconsistently.Theetiologyforreducedtemplate
utilizationwaslikelytheextratimeandeffortrequiredtouploadandpopulatethe
template.Inthefuture,electronicautomatizationoftemplateloadingandpopulatingmay
helpimprovetemplateuse.
Itisinterestingtonotethatallpatientsinourstudywhoreceivedcounseling
decidedtocontinueNSAIDtherapy.Theseindividualsdesiredtounderstandpotential
85
complicationsassociatedwithNSAIDusebutultimatelydeterminedpaincontroltobe
moreimportant.
References
1. MarchL,SmithE,HoyD,Cross,M,Sanchez‐RieraL,BlythF,BuchbinderR,VosT,
WooflA.“Burdenofdisabilityduetomusculoskeletaldisorders.”BestPractice&
ResearchClinicalRheumatology2014;28(3):353‐366.
2. “Osteoarthritis.”NationalInstituteofArthritisandMusculoskeletalandSkin
Diseases.April2015.RetrievedJuly2016.
3. SacksJJ,LuoY‐H,HelmickCG.Prevalenceofspecifictypesofarthritisandother
rheumaticconditionsintheambulatoryhealthcaresystemintheUnitedStates,
2001–2005.ArthritisCare&Research.2010;62(4):460‐464
4. AmericanCollegeofRheumatology2012RecommendationsfortheUseof
NonpharmacologicandPharmacologicTherapiesinOsteoarthritisoftheHand,Hip,
andKnee
5. HershEV,PintoA,MoorePA.Adversedruginteractionsinvolvingcommon
prescriptionandover‐the‐counteranalgesicagents.ClinTher2007;29Suppl:2477–
97
86
IronDeficiencyAnemiaandThrombocytosis:TheSearchForALink.
NathanielP.AvilaMD,EmmaL.DishnerMD,GabrielM.AisenbergMD.
Abstract
Background:Theassociationofirondeficiencyanemia(IDA)andreactive
thrombocytosis(RT)isfrequentlydescribed,butthecausationbetweenIDAandRTisstill
unclear.
Aims:ToidentifyacausativelinkbetweenRTandIDA.
Methods:WeretrospectivelyreviewedthechartsofpatientswithIDAandtabulatedtheir
demographic,clinical,andlaboratorydatabetweenMarch2011andMarch2012.Patients
withRTandwithoutRTwerecompared.
RESULTS:Among194patientswithIDA70hadRT(groupT)and124didnothaveRT
(groupNT).Thrombocytosiswasmorecommoninwomenthaninmen.PatientsingroupT
hadsignificantlyhighertotalleukocyteandlymphocytecountsthanthoseingroupNT,but
thosevalueswerewithinnormalvalues.Inourseriesiron,ferritinortransferrinlevels,
creatinine,hemoglobin,reticulocytes,meancorpuscularvalue,andhemoglobinA1cwere
similarinbothgroups.Therewasnodifferenceintherelativeprevalenceofchronic
inflammatorydisease.
Conclusion:ThelinkbetweenIDAandRTremainselusive.Giventhecomplexityinvolvedin
thedevelopmentofbothIDAandRT,itseemsplausiblethatthemechanismthatlinksone
totheotherwillbediscoveredthroughlaboratory‐basedratherthanclinicaldata.
Keywords:irondeficiencyanemia,thrombocytosis,reactivethrombocytosis,ferritin,
anemia.
87
Introduction
Thrombocytosisisdefinedasanelevatedplateletcountabovetheuppernormal
limitof400,000/ l1.Itcanresultfromaclonalbonemarrowproliferation(definedthenas
primary),orcanbereactive(secondarythrombocytosis)2.Irondeficiencyanemia(IDA)is
frequentlylistedasacauseofreactivethrombocytosis(RT)3,4.Thoughthegoldstandard
fordiagnosisofirondeficiencyanemia(IDA)istheabsenceofironstoresinabonemarrow
examination,theassociatedcostandinvasivenessmakesthetestlessdesirablethan
surrogateexaminations.Amongavailabletests,thelevelsoftransferrinanditsiron
saturationlosesensitivitywhenanemiaismild5,andareoflowspecificityowingtoits
diurnalvariationandlevelchangesininflammatorystates.Onthecontrary,lowlevelsof
ferritinhavenootherexplanationthanirondeficiency6,makingitareliablemarkerofsuch
condition.Previousresearchhasfoundusefulmarkerstodiscriminatebetweenclonal
versusreactivethrombocytosis7‐10,buttheunderlyingmechanismsleadingtoRTinIDA
remainelusive11‐14.Ourstudyaimstofindalinkbetweentheseconditions.
Methods
ThestudywasundertakenatLyndonB.JohnsonHospital(LBJH),atertiarycare
centerinHouston,Texas,afterobtainingInstitutionalReviewBoardapproval;patient
consentrequirementswerewaived.Ourhospitaladmitsabout14,000patientsperyear.
FromMarch2011toMarch2012,wecollectedinformationfromtheelectronic
recordsofpatientsolderthan18yearswithferritinlevelslowerthannormal(10‐291
ng/ml).Wedefinedascurrentepisodetheoneinwhichthepatienthadalowserumferritin
level.
Weusedastandardizedquestionnairetoretrieveinformationfromthemedical
records.Thisincludeddemographicdata(ageandsex),clinicaldata(knownhistoryof
rheumaticdiseaseoractivecancer),andlaboratorydata(serumiron,transferrin,
88
creatinine,hemoglobin,meancorpuscularvolume,plateletcount,serumcreatinine,white
bloodcellcountanditsdifferential,reticulocytecount,sedimentationrate).Thecauseof
IDAwasalsoextractedfromthemedicalrecords:weclassifiedthesedatainbroad
categoriesfirst(example:genitalbleed,uppergastrointestinalbleed),andtheninmore
specificones(example:fibroids,orgastriculcer).
Weinvestigatedthenumberofpreviousepisodesofthrombocytosiswhilethe
patienthadmicrocyticanemia,aswellasthrombocytosispriortotherecordedanemia,and
calculatedthedurationofboththeanemiaandthrombocytosis.
Statistics
CategoricalvariableswereanalyzedusingtheFisherexacttest,anddiscrete
variableswereanalyzedusingtheStudentttestforunpairedsamples.Atwo‐sidedP<0.05
wasconsideredindicativeofstatisticalsignificance.Wecalculatedacorrelationcoefficient
(r)betweenthehighestplateletlevelmeasuredduringtheepisodeinwhichtheferritin
levelwasmeasured,andthatserumferritinlevel.
Results
Onehundredandninetyfourpatientsmetinclusioncriteria.Table1describestheir
baselinecharacteristics(SeeTable1).Theirmedian±standarddeviationagewas45±13
yearsold.Thefemale/maleratiowas4.24/1(157womenand37men).Onehundredand
seventeen(60%)patientswereseenintheED/Hospital,andseventy‐seven(40%)patients
wereseenintheoutpatientclinics.
ThecauseoftheIDAwasunknownorundisclosedforthemajorityofpatients(84,
43%),andwasattributedtogenitalbleedin55(28%)patients,lowergastrointestinal
bleedin25(13%)patients,anduppergastrointestinalbleedin23(12%)patients.Seven
patients(4%)hadmiscellaneouscauses.Overallthemostfrequentspecificcauseinour
89
patientpopulationwasbleedingfibroids(17,9%patients).Nospecificcausewas
associatedstatisticallywithahigherprobabilityofthrombocytosis.
Forty‐eightpatientshadthrombocytosisonthesameday(±2days)oftheferritinresult.
Whencountingfromtheoriginofrecordedmicrocyticanemia,66patientshad
thrombocytosisrecordedin348occasions(5times/patient).Manyofthe194patientshad
microcyticanemiaforanaverageof1073±1147dayspriortothecurrentepisode.
Countingpreviousandcurrentepisodes,wefoundthrombocytosisin78patients.Ofthese,
8wereexcludedsincetheyhadthrombocytosisbeforehavinganemia.Then,weselected
70patientswiththrombocytosis(36%ofpatientswithlowferritin)(GROUPT)and124
patientswithoutthrombocytosis(GROUPNT).
Table 1-Baseline characteristics
(n=194)
Age
Sex (M/F)
Ferritin
Iron
TIBC
Hgb
MCV
Platelets
WBC
ANC
ALC
AMC
AEoC
ABC
Retic count †
Creatinine
Chronic inflam. disease ‡
45±13
37/157
4.7±1.96
25±25
449±104
8.3±2
70.7±10
312,000 ±
135,000
7,110 ± 2,570
5,090 ± 6,610
2,100 ± 2,000
500 ± 200
190 ± 240
56 ± 76
2.1 ± 1
0.9 ± 0.8
30
range 0.5-7.9 ng/ml
g/dl
g/dl
g/dL
fL
per l
per l
per l
per l
per l
per l
per l
per l
mg/dL
ANC= absolute neutrophil count; ALC: absolute lymphocyte count; AMC: absolute
monocyte count; AEoC: absolute eosinophil count; ABC: absolute basophil count.
NOTES:
†: Reticulocyte count: 96 entries
‡: Chronic inflammatory disease: active cancer or rheumatic disease
90
Table2comparesthosewithandwithoutthrombocytosis.Thrombocytosiswas
morecommoninwomenthaninmen(SeeTable2).Thetotalnumberofleukocytesorthe
numberoflymphocyteswassignificantlyhigherintheGROUPT,butinbothcasesthe
valueswherewithinnormalrange.WithintheGROUPTtherewere4patients(6%)who
hadthrombocytopeniaatthemomentofinclusion(2ofthose4hadpancytopenia),
whereaswithintheGROUPNTtherewere20patients(16%)withthrombocytopeniaon
inclusion(10ofthose20hadpancytopenia)(P=0.04).Only4patientsinGROUPThadthe
sedimentationratemeasured(alwayselevated),while11haditmeasuredinGROUPNT
(elevatedin9ofthem).Thesefewpatientsareinsufficienttodrawconclusionsupona
potentialassociation.Iron,transferrinorferritinlevelswerenotdifferentbetweengroups.
Table 2-Comparison of patients with and without thrombocytosis
With thrombocytosis
Without
(n=70)
thrombocytosis
(n=124)
Age
44 ± 12
46 ± 14
Sex (Male)
7 (10%)
30 (24%)
Platelet (median/range)
416,000 (76,000-872,000)
259,000 (16,000396,000)
Ferritin
4.40 ± 2
4.86 ± 1.9
Iron
26 ± 31
24 ± 22
TIBC
451 ± 100
447 ± 106
Transferrin saturation
6 ± 0.07%
5 ± 0.05%
Hgb
8.0 ± 2.2
8.4 ± 2.2
MCV
69 ± 11
71 ± 10
WBC
8,000 ± 2,820
6,600 ± 2.300
ANC
6,100 ± 8,300
4.500 ± 5,400
ALC
2,100 ± 800
2,000 ± 2,400
AMC
520 ± 240
450 ± 230
AEoC
210 ± 250
170 ± 240
ABC
70 ± 10
50 ± 50
Retic count
2.25 ± 1.3
2.06 ± 0.8
Creatinine
1.00 ± 1.2
0.85 ± 0.4
Chronic inflammatory
10 (14%)
20 (16%)
disease
P
0.65
0.02
0.12
0.51
0.80
0.59
0.48
0.20
<0.001
0.10
0.04
0.07
0.21
0.07
0.41
0.19
0.84
ANC= absolute neutrophil count;
ALC: absolute lymphocyte count;
AMC: absolute monocyte count;
AEoC: absolute eosinophil count;
ABC: absolute basophil count
91
Discussion
Inthisretrospectivestudywefoundnosignificantdifferencebetweenpatientswith
andwithoutthrombocytosis,otherthanthefactthatthrombocytosiswasmorecommonin
womenthaninmen.Thedifferenceinthenumberofleukocytes,orlymphocytesis
significant,yetwithinnormalvalues.
Severalelementsparticipateintheregulationofironcycle:transferrinandits
receptorinthebonemarrowredcellprecursors,erythropoietin,ferritin,ferroportin,
hepcidin,C‐reactiveprotein(CRP)andinterleukin6(IL‐6),thelasttwobeingnon‐specific
serummarkersofinflammation15.Interleukin6promotesthehepaticreleaseofhepcidin,
whichpreventsadequatedeliveryofirontothebonemarrowerythroblasts.Several
studieshaveassignedIL‐6aroleinthedevelopmentofthrombocytosismediatedby
synthesisandreleaseofthrombopoietin(TPO)ininflammatory16andpostoperativestates
17.Moreover,astudyshowedtemporalcorrelationbetweenthepeakofIL‐6,CRPandTPO
levelsandapeakinplateletcountinaseriesofpediatricpatientswithproveninfection,
thoughthatstudydidnotexaminetheconcomitantpresenceofIDA18.Findingprooffor
thepresenceofaninflammatorystateisadifficulttaskinabsenceofclinicalmarkersof
inflammation.Laboratorymarkersofinflammationlackbothsensitivityandspecificity.
Furthermore,elevationofsuchmarkersisnotnecessarilyassociatedwithanemia,orwith
thrombocytosis19.WhethertheplateletelevationreflectstheresponsetoIL‐6soluble
receptors,asdescribedinpatientswithessentialthrombocytemia20,orpolymorphismof
theIL‐6gene21ratherthantotheactualIL‐6levelsrequiresfurtherstudy.The
retrospectivenatureofourstudypreventsusfromclearlyassessingthecoexistenceof
inflammatoryconditions;also,sedimentationrate,anon‐specificinflammatorymarkerwas
requestedintheminorityofourpatients.
92
Theroleoferythropoietinonthedevelopmentofthrombocytosisremainsdebatable
11,14.Mortalitywashigheramongpatientsonhemodialysis,whowhilebeingon
erythropoietinwithoutironsupplementation,hadirondepletionleadingtothrombocytosis
22.However,mortalitywasnotobservedmoreoftenamongpatientswhohad
erythropoietintreatmentforreasonsdifferentthanadvancedrenaldisease.
ThemechanismbywhichIDAcausesRThasalsobeenstudiedinanimalmodels23.
Anirondeficiencydietcausedthrombocytosis,withlargerplateletsandincreased
aggregation,notmediatedbyTPOorIL‐6.Meanwhile,olderreviewsdiscardadirectroleof
irondeficiencyuponthedevelopmentofthrombocytosissimplybecausepatientswithIDA
canpresentwithRT,butalsowithnormalorlowplateletlevels24.Twostudiesfoundthat
womenwithlowiron,lowtransferrinsaturationandlowferritinhadmorecommonly
thrombocytosis,butwecouldnotreplicatethesefindings25,26.
Regardingtheresponsetoirontherapy,astudyshowedthatpediatricpatients
treatedwithoralironandwhoseplateletswereinaverageabove400,000/ levolvedwith
decreasingplateletslevel,whereasthosetreatedwithintramuscularironandwhose
baselineplateletlevelswerenormalatbaselineevolvedwithreactivethrombocytosis
withinaweekoftreatment,creatingevenmoreconfusion27.Otherresearchersfounda
moreconsistentdose‐responsecorrectionofRTinIDA28.
Theretrospectivenatureofthisworklimitstheabilitytofindacausallink.A
prospectiveapproachmaymoreaccuratelycapturedataoninflammatoryorinfectious
conditions,rapidityofanemiadevelopment,andtheetiologyofIDA,oncethelatteris
diagnosed.
Inconclusion,thelinkbetweenIDAandRTremainselusive.Someinflammatory
markersaremostly,butnotalwaysincreasedinIDAmakingtheirpathogenicroleless
clear.Giventhecomplexityandmultiplicityofthedeterminantsinvolvedinthe
93
developmentofbothIDAandRT,itseemsplausiblethatthemechanismthatlinksoneto
theotherwillbediscoveredthroughlaboratory‐basedratherthanclinicaldata,provided
thatmostvariablescanbecontrolledinthatsetting.
References
1. DalyME.Determinantsofplateletcountinhumans.Haematologica2011;96:10‐13
2. SchaferAI.Thrombocytosis.NEngJMed2004;350:1211‐9
3. SchaferAI.Thrombocytosisandthrombocythemia.BloodReviews2001;15:159‐1661
4. SchloesserLL,KippMA,WenzelFJ.Thrombocytosisiniron‐deficiencyanemia.JLabClin
Med1963;107‐14
5. SzokeD,PanteghiniM.Diagnosticvalueoftransferrin.ClinChimActa2012;413:1184‐89
6. UrrechagaE,BorqueL,EscaneroJF.Biomarkersofhypochromia:thecontemporary
assessmentofironstatusanderythropoiesis.BioMedResInt2013,articleID603786,8
pages.
7. YadavD,ChandraJ,SharmaS,SinghV.Clinicohematologicalstudyofthrombocytosis.
IndianJofPediatr2010;77:643‐7)
8. CustodiP,BalduiniCL.Whichtestsaremostusefultodistinguishbetweenclonaland
reactivethrombocytosis?AmJMed1996;101:233‐5
9. KarakusS,OzcebeOI,HaznedarogluIC,etal.Circulatingthrombopoietininclonalversus
reactivethrombocytosis.Hematology2002;7:9‐12
10. WangJC,ChenC,NovetzkyAD,LichterSM,AhmedF,FriedbergNM.Bloodthrombopoietin
levelsinclonalthrombocytosisandreactivethrombocytosis.AmJMed1998;104:451‐5
11. VaziriND.ThrombocytosisinEPO‐treateddialysispatientsmaybemediatedbyEPO
ratherthaniron‐deficiency.AmJKidDis2009;53:733‐6
94
12. AkanH,GuvenN,AydogduI,AratM,BeksacM,DalvaK.Thrombopoieticcytokinesin
patientswithirondeficiencyanemiawithorwithoutthrombocytosis.ActaHaematol
2000;103:152‐6
13. DanK.ThrombocytosisinIronDeficiencyAnemia.IntMed2005;44:1025‐6
14. RackeFK.EPOandTPOsequencesdonotexplainthrombocytosisinirondeficiency
anemia.JPediatrHematolOncol2003;25:919
15. HandelmanGJ,LevinNW.Ironandanemiainhumanbiology:areviewofmechanisms.
HeartFailRev2008;13:393‐404
16. KaserA,BrandacherG,SteurerW,etal.Interleukin‐6stimulatesthrombopoiesisthrough
thrombopoietin:roleininflammatorythrombocytosis.Blood2001;98:2720‐25
17. FolmanCC,OomsM,KuenenB,etal.Theroleofthrombopoietininpost‐operative
thrombocytosis.BrJHematol2001;114:126‐133
18. IshiguroA,SuzukiY,MatiM,etal.Elevationofthrombopoietinprecedesthrombocytosis
inacuteinfections.BrJHematol2002;116:612‐8
19. CeresaIF,NorisP,AmbaglioC,PecciA,BalduiniCL.Thrombopoietinisnotuniquely
responsibleforthrombocytosisininflammatorydisorders.Platelets2007;18:579‐82
20. MartaR,GoetteN,LevP,etal.Increasedlevelsofplasmainterleukin‐6solublereceptorin
patientswithessentialthrombocytemia.Haematologica2004;89:657‐663
21. FernandezRealJM,VendrellJ,RichartC,GutierrezC,RicartW.Plateletcountand
Interleukin6genepolymorphisminhealthysubjects.BMCMedGen2001;2:6‐9
22. StrejaE,KovesdyCP,GreenlandS,etal.Erythropoietin,irondepletion,andrelative
thrombocytosis:apossibleexplanationforhemoglobin‐survivalparadoxinhemodialysis.
AmJKidDis2008;52:727‐36
95
23. EvstatievR,BukatyA,JimenezK,etal.Irondeficiencyaltersmegakaryopoiesisand
plateletphenotypeindependentofthrombopoietin.AmJHematol2014;Epubaheadof
print.
24. KarpatkinS,GargSK,FreedmanML.Roleofironasaregulatorofthrombopoiesis.AmJ
Med1974;57:521‐5
25. KadikoyluG,YavasogluI,BolamanZ,SenturkT.Plateletparametersinwomenwithiron
deficiencyanemia.JNatMedAssoc2006;98:398‐402
26. ParkMJ,ParkPW,SeoYH,etal.Therelationshipbetweenironparametersandplatelet
parametersinwomenwithirondeficiencyanemiaandthrombocytosis.Platelets2013;
24:348‐51
27. GrossS,KeeferV,NewmanAJ.Theplateletsiniron‐deficiencyanemia.I.Theresponseto
oralandparenteraliron.Pediatrics1964;34:315‐23
28. Kulnigg‐DabschS,EvstatievR,DejacoC,GascheC.Effectofirontherapyonplateletcounts
inpatientswithinflammatoryboweldisease‐associatedanemia.PLoSONE2012;7,
e34520:1‐6
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