Mannheimcv狗狗

Toometal.
ActaVetScand(2016)58:46DOI10.
1186/s13028-016-0228-1CASEREPORTInterstitialpneumoniaandpulmonaryhypertensionassociatedwithsuspectedehrlichiosisinadogMarjoleinLisettedenToom1*,TetydaPaulinaDobak2,ElsMarionBroens3andChiaraValtolina1AbstractBackground:Indogswithcaninemonocyticehrlichiosis(CME),respiratorysignsareuncommonandclinicalandradiographicsignsofinterstitialpneumoniaarepoorlydescribed.
However,inhumanmonocyticehrlichiosis,respira-torysignsarecommonandsignsofinterstitialpneumoniaarewellknown.
Pulmonaryhypertension(PH)isclassifiedbasedontheunderlyingdiseaseanditstreatmentisaimedatreducingtheclinicalsignsand,ifpossible,addressingtheprimarydiseaseprocess.
PHisoftenirreversible,butcanbereversibleifitissecondarytoatreatableunderlyingetiology.
CMEiscurrentlynotgenerallyrecognizedasoneofthepossiblediseasesleadingtointerstitialpneumoniaandsecondaryPHindogs.
OnlyonecaseofPHassociatedwithCMEhasbeenreportedworldwide.
Casepresentation:Aseven-year-old,maleintact,mixedbreeddogwaspresentedwith2weekshistoryoflethargyanddyspnea.
ThedogpreviouslylivedintheCapeVerdeanislands.
Physicalexaminationshowedsignsofright-sidedcongestiveheartfailureandpoorperipheralperfusion.
Thoracicradiographyshowedmoderateright-sidedcardio-megalywithdilationofthemainpulmonaryarteryandamilddiffuseinterstitiallungpatternwithperibronchialcuff-ing.
Echocardiographyshowedseverepulmonaryhypertensionwithanestimatedpressuregradientof136mmHg.
Onarterialbloodgasanalysis,severehypoxemiawasfoundandcompletebloodcountrevealedmoderateregenera-tiveanemiaandseverethrombocytopenia.
Aseveregammahyperglobulinemiawasalsodocumented.
SerologyforEhrlichiacaniswashighlypositive.
Treatmentwithoxygensupplementation,atypedpackedredbloodcelltransfu-sionandmedicaltherapywithdoxycycline,pimobendanandsildenafilwasinitiatedandthedogimprovedclinically.
Approximately2weekslater,therewascompleteresolutionofallclinicalsignsandmarkedimprovementofthePH.
Conclusion:ThisreportillustratesthatCMEmightbeassociatedwithsignificantpulmonarydiseaseandshouldbeconsideredasapossibledifferentialdiagnosisindogspresentingwithdyspneaandsecondarypulmonaryhyperten-sion,especiallyindogsthathavebeeninendemicareas.
ThisisimportantbecauseCMEisatreatablediseaseanditssecondarylungandcardiacmanifestationsmaybecompletelyreversible.
Keywords:Canine,Ehrlichiosis,Pulmonaryhypertension,Reversible,Interstitiallungdisease2016denToometal.
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BackgroundEhrlichiacanisisapleomorphicbacteriumthatinfectscirculatingmonocytesandcancausecaninemono-cyticehrlichiosis(CME).
CMEresultsinvariablenon-specificclinicalmanifestationsandclinicalsignscanbesubclinical,acuteorchronic.
Mostdogspresentwithdepression,lethargy,mildweightloss,anorexia,splenomegaly,andlymphadenopathywithorwithouthemorrhagictendencies[1,2].
Respiratorysignsarespo-radicallyreportedindogsbutareregularlydescribedinhumanpatientsinfectedwithhumanmonocyticehrli-chiosis(HME)[3].
Interstitialpneumoniacanhaveaninfectiousornon-infectiousetiology.
Indogs,reportedinfectiousagentsleadingtointerstitialpneumoniaareAngiostrongylusOpenAccessActaVeterinariaScandinavica*Correspondence:M.
L.
denToom@uu.
nl1DepartmentofClinicalSciencesofCompanionAnimals,FacultyofVeterinaryMedicine,UtrechtUniversity,Yalelaan108,3508TDUtrecht,TheNetherlandsFulllistofauthorinformationisavailableattheendofthearticlePage2of8Toometal.
ActaVetScand(2016)58:46vasorum,Leishmaniachagasi,Toxoplasmagondii,Pneumocystiscarinii,Babesiacanis,Leptospirasp.
,Mycoplasmasp,caninedistempervirusandadenovi-rus[4–12].
Inpatientswithinterstitialpneumonia,gasexchangeisoftenimpairedduetoventilation-perfusionmismatching,intrapulmonaryshunting,anddecreaseddiffusionacrosstheabnormalinterstitiumwitharterialhypoxiaasaconsequence.
Incontrasttothesystemicvasculaturethatrespondswitharterialvasodilationtobetterperfusehypoxictissue,thepulmonaryvasculatureconstrictsinresponsetohypoxia.
Besidespulmonaryvasoconstriction,hypoxiaalsocausesproliferationofthesmoothmusclecellsinthearterialwall.
Bothphenom-enaleadtoadecreaseinluminalcross-sectionalareaandanincreaseinpulmonaryvascularresistanceindexwithpulmonaryhypertension(PH)asaconsequence.
Pulmonaryhypertensionisclassifiedbasedontheunderlyingdiseaseanditstreatmentisaimedatimprov-ingtheclinicalsignsandaddressingtheprimarydiseaseprocess[13].
AlthoughPHisoftenirreversible,PHisreversibleinsomecasesiftheunderlyingetiologyisdiag-nosedandtreatedaccordingly.
ReversibilityofPHhasforinstancebeendemonstratedindogsaftersuccessfultreatmentforA.
vasorum[14].
Pulmonarychangesconsistentwithinterstitialpneu-moniahavebeenreportedpreviouslyinhumanswithHME[3]andasanatypicalfindingindogswithCME[15–18].
However,CMEisgenerallynotrecognizedasoneofthepossiblediseasesleadingtointerstitialpneu-moniaandsecondaryPHindogs.
OnlyonecaseofPHassociatedwithE.
canisinfectionhasbeenreportedworldwide[19].
Consequently,CMEmightbeunderdiag-nosedasapossiblecauseofinterstitialpneumoniaandsecondaryPH.
Thiscasereportdescribestheclinical,radiographicandechocardiographicpresentationofadogwithinter-stitialpneumoniaandseverePHsuspectedtobeassoci-atedwithE.
canisinfection.
CasepresentationAseven-year-old,intactmale,mixedbreeddogweigh-ing8.
1kgwaspresentedtotheEmergencyServiceoftheDepartmentofClinicalScienceofCompanionAni-malsoftheFacultyofVeterinaryMedicine,UtrechtUniversitywitha2weekshistoryoflethargy,progres-sivedyspneaandcoughing.
ThedogpreviouslylivedintheCapeVerdeanislandsforapproximately3yearsandreturnedtotheNetherlands10monthsbeforepresenta-tion.
Inthepast2years,thedoghadshowedchronicmildexerciseintoleranceandhadafewepisodesofdiarrheathatresolvedwithsymptomatictherapy.
Thedogwasup-todatewithhisvaccinationsandanthel-minthictreatments.
Physicalexaminationshowedgeneralizedweaknessanddecreasementalstate.
Cardiovascularexamina-tionrevealedtachycardia,weakperipheralpulses,palemucousmembranes,prolongedcapillaryrefilltime,jugu-lardistensionsandvenouspulses,andagradethreeoutofsixsystolicmurmurwiththepointofmaximalinten-sityovertherightcardiacapex.
Thedogwasalsoseverelydyspneicanddemonstratedharshlungsoundsonauscul-tation.
Theabdomenwasdistendedandpositiveundula-tionwasdetected.
Thesefindingswereconsistentwithpulmonarydisease,right-sidedheartfailureandpoorperipheralperfusion.
Completebloodcount(CBC)showedamoderatemicrocytic,hypochromicanemia,moderateleukocyto-siswithamarkedleftshiftandaseverethrombocyto-penia.
Biochemistryshowedseverehyperproteinemia,hyperglobulinemiaandamildhypoalbuminemia.
Serumproteinelectrophoresisshowedapolyclonalpeakinthegammaglobulinregion.
Arterialbloodgasanalysisshowedaseverehypoxemiawithhypocapnia.
Urinaly-sisshowedmildhemoglobinuria,glucosuriaandpro-teinuria.
Bloodsamplesweresubmittedforserologicalandmolecularbiologicaltesting.
Immunofluorescenceantibodytest(IFAT)forE.
canis(MegaFLUOEhrlichiacanis,MegaCorDiagnostikGmbH,Hrbranz,Aus-tria)waspositive(IgGtiter>2560),butpolymerasechainreaction(PCR)amplificationforEhrlichiagenus(real-timePCR,LightCycler2.
0,RocheDiagnosticsGmBH,Mannheim,Germany,primersusedasdescribedprevi-ously[20])wasnegative.
SerologyforLeishmaniasp.
(Dog-DAT,Leishmaniaspecificantibodydetectionkit,KoninklijkInstituutvoordeTropen,Amsterdam,theNetherlands)andB.
canis.
(MegaFLUOBabesiscanis,MegaCorDiagnostikGmbH,Hrbranz,Austria)andantigensnaptestsforA.
vasorum(AngioDetectTest,IDEXXLaboratories)andDirofilariaimmitis(SNAPHeartwormRTTest,IDEXXLaboratories)werealsoneg-ative.
LaboratoryresultsaresummarizedinTable1.
Onthoracicradiographs,amilddiffuseincreaseinpulmonaryopacitywithaninterstitiallungpatternandmildperibronchialcuffingwasseen,whichwasmostaccentuatedinthecaudodorsallunglobes.
Thinpleuralfissurelineswerenotedbetweenalllunglobes.
Thecar-diacsilhouetteshowedsignsofright-sidedcardiomegaly(vertebralheartscore(VHS):11.
0,referenceinterval75mmHg)[13],(Fig.
3).
ToaddresstheseverehypoxemiaandPHthedogwasplacedinanoxygencagewithaninspiredconcentra-tionofoxygenbetween40and50%.
Theclinicalsignsofthedogdidnotimprovemarkedlywiththeextraoxygensupplementation.
Becauseanemiacouldhavecontributedtothecardiovascularsignsandthepoortis-sueoxygenation,atypedpackedredbloodcelltransfu-sionwasadministered.
Basedonthetravelhistory,theabnormalitieswithintheCBCandbiochemicalanalysisandthepositiveserologyforE.
canis,aninfectionwithCMEwassuspected.
Treatmentwithdoxycycline(5mg/kg,orallytwicedaily)(Doxoral,ASTFarma,Oudewa-ter,theNetherlands),pimobendan(0.
3mg/kg,orallytwicedaily)(CardisureFlavour,EurovetAnimalHealthBV,Bladel,theNetherlands)andsildenafil(1.
5mg/kg,orallytwicedaily)(Viagra,Pfizer,NewYork,USA)wasinitiated.
Thehematocritincreasedfrom20to36%afterthebloodtransfusionandthedog'sclinicalconditionimprovedremarkably.
However,thedogremainedmod-eratelydyspneicandseverelyhypoxic(PaO2:46.
5mmHg,referenceinterval:85.
0–103.
3mmHg).
Thedyspneagraduallyimprovedandthedogseemedcomfortableout-sidetheoxygencageafter6daysoftreatment,althoughtheimprovementofthehypoxemiawasonlyminimal(PaO2:55mmHg,referenceinterval:85–103.
3mmHg,Table1).
Becauseoffinanciallimitationsoftheowner,thedogwasdischargedwiththeabove-mentionedthera-piesatthattime.
Seventeendaysafterinitiationoftreatment,thedogwasadmittedviathecardiologypolyclinicsofthesameuni-versityandre-examined.
Atthattime,therewascompleteresolutionofallclinicalsignsandphysicalexaminationwascompletelyunremarkable.
CBCshowednormalplate-letcountsandleukogram,withonlyaverymildmicrocytichypochromicanemia.
Biochemicalanalysisagainshowedseverehyperproteinemiaandhyperglobulinemia.
TheTable1Summaryofhaematological,biochemical,serologicalandurineandbloodgasanalysisresultsArterialbloodgasanalysiswasperformedwithaninspiredconcentrationofoxygenof21%ValuesinitalicsareoutsidethereferenceintervalMCVmeancorpuscularvolume,MCHCmeancorpuscularhemoglobinconcentration,MCHmeancorpuscularhemoglobin,WBCwhitebloodcellcount,UPCurinaryproteintocreatinineratio,PaO2partialarterialoxygenpressure,PaCO2partialarterialcarbondioxidepressure,BEbaseexcessParameterDay1Day7Day17Day50ReferenceintervalHematocrit(L/L)0.
200.
380.
400.
340.
42–0.
61MCV(fl)57.
759.
959.
963.
5–72.
9MCHC(mmol/L)21.
721.
822.
220.
5–22.
4MCH(fmol)1.
251.
311.
331.
37–1.
57TotalWBC(*109/L)23.
16.
66.
74.
5–14.
6Segmentedneutrophils(*109/L)17.
32.
64.
42.
9–11.
0Bandneutrophils(*109/L)3.
20.
00.
00.
0–0.
3Lymphocytes(*109/L)2.
13.
01.
80.
8–4.
7Monocytes(*109/L)0.
50.
40.
30.
0–0.
9Eosinophils(*109/L)0.
00.
50.
20.
0–1.
6Platelets(*109/L)15251166144–603Urea(mmol/L)4.
17.
03.
0–12.
5Creatinine(mol/L)33747750–129Sodium(mmol/L)145145141141–150Potassium(mmol/L)4.
14.
73.
73.
6–5.
6Totalprotein(g/L)911198955–72Albumin(g/L)16272626–37Gamma-globulins(g/L)5768403–9UPC0.
80.
31:25601:256040areconsideredpositiveforE.
canisexposure[21].
InFig.
3Echocardiographicimagesatpresentationfromleftapical4-chamberview.
acolorDopplermapofseveretricuspidregurgitation.
RArightatrium,RVrightventricle,LAleftatrium,LVleftventricle.
bspectralDopplertraceoftricuspidregurgitation.
Tricuspidsystolicvelocityof5.
8m/s,indi-catingapeaktricuspidpressuregradientofapproximately136mmHg,gradedasseverepulmonaryhypertension(reference75mmHgFig.
4Rightlateral(a)anddorsoventral(b)thoracicradiographs2weeksafterdischarge.
Radiographsdemonstratingresolutionofcardiomegaly(vertebralheartscore:10.
2,referenceinterval2560),whichstrength-enedthesuspicionofanactiveinfection[22].
However,definiteactiveinfectionatthetimeofpres-entationcouldnotbeproven,becausePCRamplifica-tionforEhrlichiagenuswasnegativeandanti-EhrlichialIgGantibodiespersistforseveralmonthstoyearsaftereliminationoftheparasite[23].
AnegativeresultfromaPCRtestcanoccurwhenorganismsincirculationarebelowthelevelofdetection,asmayhappenwheninfec-tionsarechronic.
IthasbeendemonstratedthatdogscanbePCRnegativeonbloodsamples,butPCRpositiveonsplenicaspirates[21].
ItishypothesizedthattheE.
canisaresequesteredinsplenicmacrophagestoavoidimmuneelimination.
Unfortunately,inthepresentcase,theown-ersdeclinedfineneedleaspiratesofthespleenduetothepotentialrisksandstressinvolved,e.
g.
internalbleeding,aggravationofthedyspnea.
Pairedserologysamplescanalsoprovideusefulinformationaboutantibodykinetics,whichmaypointtocurrentstatusofinfection.
Afour-foldincreaseinIgGantibodiesovertimeissuggestedtobeevidenceforanactiveinfection[24].
Antibodytiterswilldecreasegraduallyafterappropriatetreatment,butmaypersistformonthstoyearsevenafterfullclini-calrecovery[23,25].
Inthiscase,theEhrlichiaIgGtiterwasstillveryhigh17daysafterinitiationofdoxycyclinetherapy,probablyduetotheshorttimebetweenstartofthetreatmentandretesting;IFATwasunfortunatelynotrepeatedonday50.
Althoughdoxycyclinetherapygenerallyresultsinfastclinicalimprovementandimprovementofmostlabora-toryabnormalities,persistenceofhyperglobulinemiaisgenerallyobservedforalongerperiod.
Moststudieshaveshownnormalizationofserumproteinelectrophoresisresultsafter3–9monthsoftherapy[1,15].
Thisexplainsthepersistenceofhyperglobulinemiaatthere-examina-tionsofthedogatdays17and50.
Inhumanmedicine,respiratorysignsarecommonlydescribedasaconsequenceofHMEinfection[3]andacuterespiratorydistresssyndrome(ARDS)hasalsobeenreportedasasevere,althoughuncommon,findinginHME[26–28].
BothCMEandHMEanimalmodelsalsorevealedprominentmononuclearcellularinfiltrationintheinteralveolarsepta,endothelialdamageandvasculi-tisinthelungs[16,29].
Thiscouldexplainthepulmonarychangesfoundinthisdogandtheclinicalandradio-graphicimprovementaftertreatmentwithdoxycycline.
However,recently,acuteresolutionofpatchypulmonaryalveolarinfiltrateshasbeendescribedaftersildenafiltherapyindogswithidiopathicPHandPHsecondarytoidiopathiclungfibrosis[30].
Therefore,sildenafiltherapymightalsohavecontributedtotheimprovementoftheradiographicchangesinthiscase.
AnotherexplanationFig.
5Echocardiographicimagesobtained2weeksaftertreatmentfromrightparasternalshortaxisview.
a,b:Two-dimensional(a)andM-mode(b)viewdemonstratingnormalizationofcardiacdimensionsandfunction.
cTwo-dimensionalviewofpulmonaryartery(PA)andaorta(AO).
ThePAisuniformlyminimallydilatedwithaPA/Aoratioof1.
2(referenceinterval:0.
8–1.
15)Page7of8Toometal.
ActaVetScand(2016)58:46fortheradiographicabnormalitiesandtheimprovementondoxycyclinetherapythatcannotbeexcludedisthatthedogsufferedfromabacterialpneumonia.
Furthermore,animportantpossiblefactorthatmighthavecontributedtothehypoxemiaandPHinthisdogispulmonarythromboembolism(PTE)[31].
PTEcanoccurascomplicatingsequelaeinpatientswithPHorcanbetheprimarycauseofPH[32].
Inpeople,itisincreasinglyrecognizedthatpatientswithpulmonaryarterialhypertensionhavedysregulatedcoagulationandantithrombotichomeostasis,whichmaycontributetoaprothromboticstate[33].
Unfortunately,wedidnotperformdiagnosticinvestigationssuchasD-dimercon-centration[34],computedtomographypulmonaryangi-ography[35]orthromboelastography(TEG)[36,37]toinvestigateifthedogsufferedfromPTEoraprothrom-boticstate.
However,totheauthor'sknowledge,PTEhasneverbeenassociatedwithCMEinveterinaryliterature.
OnlytwocasesofaorticandportalveinthrombosishavebeendescribedindogswithCME[38,39].
TreatmentofPHisaimedateliminatingorimprovingtheunderlyingdiseaseprocess.
IfthePHisnotcontrolledbyprimarydiseasetherapyorifthePHisidiopathic,treatmentwithpulmonaryarterialdilatorsmaybeimple-mented.
Inveterinarymedicinecurrently,onlyphos-phodiesteraseinhibitorsareused.
Sildenafilisahighlyselectivephosphodiesterasefiveinhibitorthathasbeenusedinveterinarymedicinewithencouragingresults[30,40].
Pimobendan,acalcium-sensitizingagentwithphosphodiesterasethreeinhibitingactionshasalsobeenused,especiallywhenleftheartdiseaseisacontributingcause[41].
Inthepresentcase,adualtherapywithpul-monaryarterialdilatorswasinitiated,becausewehopedthiswouldamelioratetheveryseverePHandclinicalsignsfasterthanamonotherapywithsildenafil.
Althoughrecoveryhasbeendescribedinasimilarcasewithjustamonotherapywithdoxycycline[19],webelievethatthesymptomaticsupportwithpulmonaryvasodilatorswasjustifiedinthisdog.
MildtomoderateimprovementoftricuspidregurgitationgradientbysildenafiltherapyhasbeendescribedinsomedogswithPH[30],butnotinothers[42].
Consequently,wecannotruleoutthattheimprovementoftheechocardiographicchangescouldalsobepartiallyexplainedbytheuseofthevasodilatingdrugs.
Ideally,anotherechocardiogramshouldhavebeenperformedafterdiscontinuationofthevasodilatorther-apy.
However,theimprovementwassodramatic,thatwedonotbelievethatthiscouldbesolelyexplainedbythevasodilatortherapy.
ThiscasereportillustratesthatCMEmightbeasso-ciatedwithsignificantpulmonarydiseaseandthatitshouldbeconsideredasapossibledifferentialdiag-nosisindogspresentingwithdyspneaandsecondarypulmonaryhypertension,especiallyindogsthathavebeeninendemicareas.
ThisisimportantbecauseCMEisatreatablediseaseanditslungandcardiacmanifesta-tionsmaybecompletelyreversible.
Authors'contributionsCVperformedtheinitialclinicalinvestigationsofthedogandwasresponsibleforthecareandtreatmentofthedogduringadmittanceattheIntensiveCareUnit.
EBwasresponsiblefortheserologicalandmolecularbiologicaldiagnostictesting.
MDTalsoperformedclinicalinvestigationsofthedogandperformedandevaluatedtheechocardiogramsofthedogduringhospitaliza-tionandatfollow-up.
TDperformedandevaluatedtheinitialechocardiogramofthedogatpresentationandwasresponsiblefortheinterpretationofthethoracicradiography.
ThemanuscriptwasdraftedbyMDTandfinalizedjointlybyallauthors.
Allauthorsreadandapprovedthefinalmanuscript.
Authordetails1DepartmentofClinicalSciencesofCompanionAnimals,FacultyofVeterinaryMedicine,UtrechtUniversity,Yalelaan108,3508TDUtrecht,TheNetherlands.
2DepartmentofDiagnosticImaging,FacultyofVeterinaryMedicine,UtrechtUniversity,Yalelaan108,3508TDUtrecht,TheNetherlands.
3DepartmentofInfectiousDiseasesandImmunology,FacultyofVeterinaryMedicine,Utre-chtUniversity,POBox80.
165,3508TDUtrecht,TheNetherlands.
CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.
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