Rev. Bras. Hematol. Hemoter. vol.37 número4

revbrashematolhemoter.2015;37(4):263–265

w w w . r b h h . o r g

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Complete

blood

count

alterations

in

disseminated

histoplasmosis

Luciano

Werle

Lunardi

,

Ralf

Wagner

,

Cíntia

Cichowski

dos

Santos

,

Adriane

Turconi

Severo

_,

_Jorge

_Alberto

_Santiago

_Ferreira

a_{HospitalCristoRedentor,PortoAlegre,RS,Brazil}

b_{HospitalNossaSenhoradaConceic¸ão,PortoAlegre,RS,Brazil}

a

r

t

i

c

l

e

i

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f

o

Articlehistory:

Received24February2014

Accepted26November2014

Availableonline14April2015

Introduction

Classicalhistoplasmosis isa cosmopolitanfungal infection

causedbyHistoplasmacapsulatumvarietycapsulatum.1_H.

capsu-latumisadimorphicfungusfoundinnatureinitsfilamentous

form,consistingofbranchedhyphae,whichproduce

tuber-culatemacroconidia,theinfectiveformofthefungus.When

cultivated at37◦_{C and inthe tissues ofinfectedpeople, it}

presentsasbuddingyeastcells.1

Histoplasmosis is a systemic mycosis that may affect

previously healthy individuals. This disease may also be

adisseminated opportunisticmycosisin patientsreceiving

immunosuppressive drugs, those with hematologic

malig-nancies,andinacquiredimmunodeficiencysyndrome(AIDS)

patients.1

In immunocompromised patients, disseminated

histo-plasmosis usually affects the lymphatic tissues, liver,

spleen, kidneys, meninges, and heart. H. capsulatum

∗ _{Correspondingauthorat:Servic¸odeControledeInfecc¸ãoHospitalar,HospitalCristoRedentor,GrupoHospitalarConceic¸ão,Rua}

Domin-gosRubbo,20,91040-000PortoAlegre,RS,Brazil.

E-mailaddress:lwlunardi@gmail.com(L.W.Lunardi).

has been found in its intracellular form in peripheral

blood smears, in the bone marrow, and in lymph node

aspirates.2

Theclinicalsigns ofdisseminated diseaseincludefever,

night sweats, fatigue, weight loss, nausea, vomiting, and

dyspnea.3 _{Cutaneous and mucosal lesions may also be}

detected.Severecasesmaymanifestassepsis,withmultiple

organ dysfunction(includingrespiratory,hepatic,and renal

failure)orconcomitantmeningitis.Mortalitymayreach100%

inAIDSpatientswithoutspecifictreatment.4

Laboratoryabnormalitiesmayalsobepresent;

pancytope-nia due to bone marrow involvement is highly prevalent.

Elevatedtransaminase,lactatedehydrogenase(LDH),and

fer-ritinarecommonfindings.5

The definite diagnosis is established with the isolation

ofH.capsulatumincultureorbydirectdetectionoffungiin

clinicalsamples.Culturesofrespiratorysamples,blood,and

other materials, such asbone marrow, are still considered

thegoldstandardfordiagnosis.However,theseculturesmay

takefourtosixweekstogrowandtheirsensitivitydepends

onthediseaseload.5

http://dx.doi.org/10.1016/j.bjhh.2015.03.006

1516-8484/©2015Associac¸ãoBrasileiradeHematologia,HemoterapiaeTerapiaCelular.PublishedbyElsevierEditoraLtda.Allrights

264

Case

report

A 47-year-old female patient, resident ofPorto Alegre, RS,

Brazil,presentedtotheemergencydepartmentofatertiary

hospitalwithcomplaintsofdysuria,vomiting,rightlowerback

pain,andalteredlevelofconsciousnessoveroneweek.

Afamilymemberreportedthatthepatienthadabdominal

pain,urinarydisorders,fever,andlossofappetite.Thepatient

hadbeenintheemergencydepartmentthepreviousweekand

wastreatedwithantibiotics(nitrofurantoin)forurinarytract

infection.

Hergeneralconditionwasfair,andalthoughshehad

dif-ficultytospeak,shewasabletoanswerquestionsandfollow

instructions.Shewasdehydrated.

Hervitalsignswere:bloodpressure:122/97mmHg;axillary

temperature:35◦_{C;heartrate:90beatsperminute;respiratory}

rate:24breathsperminute;andoxygensaturation:92%.

Phys-icalexaminationshowedasoftandpainlessabdomen;lung

auscultationrevealedsomebilaterallungcrackles,andheart

auscultationwasnormal.

Laboratorytests showed the followingresult: urea level

increasedbetweenfirstandsecondmedicalvisit(sevendays

later) from 42 to 160mg/dL and creatinine level increased

from0.97to5.01mg/dL.UrinecultureshowedProteusmirabilis

resistanttonitrofurantoin.Treatmentwithcephalothinwas

initiated.

Theinitialdiagnosiswasacutepyelonephritisandacute

renalfailureduetotheinfectiousprocessanddehydration.

Thepatientwasadmittedtohospital.

Onthe2nddayofhospitalization,therewasclinical

wors-ening, including blood dyscrasia. The patient was placed

on mechanical ventilation, and the use of vasopressor for

septicshockwasinitiated.Shewastransferredtothe

inten-sive care unit (ICU) and the antibiotic was replaced with

piperacillin–tazobactam. Ananti-HIVtestwas requested to

rule out suspected HIV infection because previous tests

showedleukopeniawithlymphopeniaand anemia.Dialysis

wasstarted.

Urealevels increasedto194mg/dL,whilecreatinine

lev-els increased to 6.28mg/dL. A complete blood count did

notshowanysignificantchanges:hemoglobin(Hb)10.7g/dL;

hematocrit(Ht) 30%;totalleukocytes 4.2×109/L; bands 9%;

neutrophils36%;lymphocytes48%;monocytes7%;however,

erythroblasts(1.05×109/L)werealreadydetected.

On the 3rd day of hospitalization, the patient

devel-opedmultipleorgandysfunction,includingcoagulopathy,and

renal,circulatory,andpulmonaryfailure.Onthisday,shehad

petechiaeonherchestandabdomen,aswellasdiffuse

bleed-ingintheoralcavity,withlesionsintheoralmucosa.

Acompletebloodcountshowedsevereanemia:Hb6.5g/dL

andHt18.6%.Thepatientreceivedtwounitsofpackedred

bloodcells.Therewereno significantchangesinthewhite

bloodcount,butstructureswerefoundthatcouldbe

bacte-riaorfungi.Themicrobiologydepartmentinformedthatthe

resultofblood culturewasnegativeforbacteriauptothat

moment,buttherewerechanges,suggestingthepresenceof

yeasts.

Onthe4thdayofhospitalization,thepatienthadanuria,

cyanotic extremities, and refractory shock. The complete

Figure1–Peripheralbloodsmearwithseveralyeastcellsof

Histoplasmacapsulatum.

bloodcountwassignificantlyabnormal:Hb6.9g/dL;Ht20%;

erythroblasts 8.62×109/L; total leukocytes 0.5×109/L;

neu-trophils10%;lymphocytes80%;monocytes10%andplatelets

15.0×109/L.

There were a large number of platelet-like structures,

withsizesthatrangedfrom 2to4␮mthat weresuspected

to beyeasts(Figure1).Other structureswere phagocytized

by monocytes (Figure 2). After analysis of the findings by

the microbiology department, the presence of yeasts was

confirmed. Inaddition, somebuddingyeastcells werealso

detectedafterGramstainingofthebloodculturesample.

Basedonthelaboratoryinformationaboutthegrowthof

yeastsinthebloodculture,micafunginwasinitiatedbythe

ICUmedicalteam.Despitethesemeasures,thepatientdied

onthatday.

Thebloodculturesamplewasfurthercultivatedandthe

presenceofH.capsulatumwasconfirmed.Theanti-HIVtest

resultwaspositive.

Figure2–Peripheralbloodsmearwithseveralyeastcellsof

revbrashematolhemoter.2015;37(4):263–265

265

Discussion

H.capsulatumconsistsofsmall(2–5␮m)ovalstructures,

show-ing an evident clear halo around a central or eccentric

stainedchromatin.Therefore,itmaybeconfusedwithCandida

glabrata,Penicilliummarneffei,Pneumocystis(carinii)jiroveci, Toxo-plasmagondii,Leishmaniadonovani,platelets(measuring1–4␮m

inintracellulardiameter)orstainingartifacts.6,7_Whenthese

structuresaredetectedinblood,theyshouldraiseasuspicion

ofdisseminatedinfection,thusleadingtoaninvestigation.

Whenever the staff of a hematology department finds

yeast-likeorganismsonaperipheralbloodsmear,the

micro-biologydepartmentshouldbeinformedandtestsshouldbe

performedtoidentifytheorganisms.2

Inthecurrentcase,theinitialdiagnosiswasurinary

infec-tion.Suspicionoffungusinfectionwasbasedontheanalysis

ofthebloodtestslide.Thedefinitivediagnosiswasonly

estab-lishedbybloodculture,whichisatime-consumingdiagnostic

test.Stainingofabloodtestslideisasimpleandrapid

diag-nosticmethod.Itssensitivitydependsonthediseaseloadand

itmaybeusedinresource-limitedsettings.7

Disseminated histoplasmosis is often detected in AIDS

patients. Unfortunately,in many individuals,HIV infection

is only diagnosed when there are signs of opportunistic

diseases.2

Earlydiagnosisofinfectionmaybeachievedbydetecting

thepresenceofyeast-likeorganismsinneutrophilsor

mono-cytesfromperipheralblood.Toconfirmthediagnosis,fresh

bloodsamplesshouldbecultured.Otherlaboratoryfindings

consistentwiththisconditionareleukopenia,lymphopenia,

andmonocytopenia.2

Becauseofthe potentially lethal characteristicof

histo-plasmosis,especiallyinAIDSpatients,adefinitivediagnosis

shouldbeestablishedasquicklyaspossible.2_Astheculture

canbea difficultandtime-consuming process,other

labo-ratorytestscould beuseful.SerumLDHlevels higherthan

1000IU/LarefoundinpatientswithAIDSanddisseminated

histoplasmosis.Determinationofserumferritinisalso

use-fulindiagnosis,sincevalueshigherthan10␮g/mLinpatients

withAIDSanddisseminatedhistoplasmosisarehighly

spe-cificmarkersofthiscondition.2

Therefore,ahigh degreeofclinical suspicion,rapidand

sensitivediagnosticmethods,andappropriatespecific

treat-ment are necessary to reduce the mortality rate of AIDS

patients with histoplasmosis.1 _{The presence of persistent}

feverandsevereweightlossshouldraisethesuspicionofHIV

andopportunisticinfections,suchastuberculosisand

histo-plasmosis.

BasedonbloodtestsinsouthernBrazil,although

dissem-inatedhistoplasmosisiscommoninpatientswithAIDS,its

diagnosisisnotoftenestablished.Yeast-likestructuresthat

are phagocytizedbymonocytesare foundinadvanced

dis-easeandtherearefewcasesinoursetting.Therefore,careful

analysisoftheslideiscrucialincasesofsuspicionofan

infec-tioussyndrome,evenwhenadiagnosisofHIV-infectionhas

notbeenestablished.

Unfortunately,inthepresentcase,thedetectionof

abnor-malresultsinthebloodtestandbloodculturesdidnotbring

benefitstothepatientbecauseshediedwithinashortperiod

oftime.Therearecasesintheliteratureshowingthatthis

sus-picionhelpedtobenefitpatientsbecauseofearlydiagnosis

andtreatment.2

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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1.PassoniLFC,RibeiroSR.Histoplasmosedisseminadacomo primeiramanifestac¸ãodeAids:umdiagnósticotardiodemais. RevMédHSE.2003;37(1).

2.ElinRJ,WhitisJ,SnyderJ.Infectiousdiseasediagnosisfroma peripheralbloodsmear.LabMed.2000;31(6):324–8.

3.WheatLJ,Connolly-StringfieldPA,BakerRL,CurfmanMF,Eads ME,IsraelKS,etal.Disseminatedhistoplasmosisinthe acquiredimmunedeficiencysyndrome:clinicalfindings, diagnosisandtreatment,andreviewoftheliterature.Medicine (Baltimore).1990;69(6):361–74.

4.MandellGL,BennettJE,DolinR.Mandell,Douglasand Bennett’sprinciplesandpracticeofinfectiousdiseases.7thed. Philadelphia,PA:ChurchillLivingstone/Elsevier;2010.

5.BaddleyJW.Diagnosesandtreatmentofhistoplasmosisin

HIV-infectedpatients;2013.Availablefrom:

http://www.uptodate.com[10.06.13].

6.BainB.Célulassanguíneas:umguiaprático.3rded.Artmed EditoraSA;2004.