Rev. Bras. Hematol. Hemoter. vol.39 número3

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rev bras hematol hemoter. 2017;39(3):278–280

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

Revista

Brasileira

de

Hematologia

e

Hemoterapia

Brazilian

Journal

of

Hematology

and

Hemotherapy

Case

Report

Erythrovirus

B19

induced

persistent

bicytopenia

in

a

healthy

child

Mili

Jain

∗

_,

_Gurleen

_Oberoi,

_Rashmi

_Kumar,

_Ashutosh

_Kumar

KingGeorge’sMedicalUniversity,Lucknow,India

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Articlehistory:

Received24March2017 Accepted4April2017 Availableonline9May2017

Introduction

Immunethrombocytopenia(ITP),withanincidenceof3–5per 100,000individuals,isdiagnosedbyexclusion.Erythrovirus B19 (EV19) infection has been reported to be associated withITPinfrom13%to50%ofcases.1–3 _Combined _chronic

red cell hypoplasia and thrombocytopenia hasbeen rarely reportedinotherwisehealthyindividuals.Wereportacase ofEV19-inducederythroidhypoplasiaandthrombocytopenia diagnosedonbonemarrowexamination.

Case

report

Anotherwisehealthy4-year-oldmalechildinthemonthof June presented to us with a history of multiple petechiae andpurpura allover hisbody forthreemonthsalong with twoepisodesofmelenaeightdayspreviously.Hehadneither history ofother bleeding manifestationssuchas epistaxis, gum bleeding, hematemesis, hematuria, hemoptysis and hemarthrosis, nor were there reports of fever, rash, jaun-dice,diarrhea,acuteabdomenorarthralgia.Inaddition,no

∗ _{Corresponding}_author_at_:_Department_of_Pathology,_King_George’s_Medical_University,₂₂₆₀₀₃_Lucknow,_India.

E-mails:milijain@kgmcindia.edu,milijain786@gmail.com(M.Jain).

historyofrecentimmunization,drugintake,ortransfusions wasdescribed.Hispasthistoryandfamilyhistorywerenot significant.Onexamination,thepatienthadpallor,petechiae andpurpura alloverhisbody.Nolymphnodeenlargement orhepatosplenomegalywaspresent.Hisprevious investiga-tions from anotherinstitution showedagradual declinein hemoglobinfrom12.8to8.0g/dLoveraperiodofonemonth. Hisplateletcountwaslowovertheentireperiodrangingfrom 30×109/Lto50×109/L.

Onroutinebloodinvestigation,hemoglobinwas6.6g/dL. Generalbloodpicturerevealednormocyticandnormochromic redbloodcellswithnoevidenceofspherocytes,fragmented cells,schistocytes,polychromatophilsorimmaturecells.The whitebloodcellcountwasnormal(6.0×109/L)alongwith rel-ativelymphocytosis(58%).Theplateletcountwasmarkedly reducedto15.0×109cells/L.Hisbleedingtimewasraisedto 14min (by Ivy’s method); however, prothrombin time and thromboplastin time were within the normal ranges. His biochemical investigations were also within normal limits includingserumurea,creatinine,bilirubin,vitaminB12and folic acid. Serological tests for human immunodeficiency virus (HIV), hepatitisBand Cand Epstein BarrVirus(EBV)

http://dx.doi.org/10.1016/j.bjhh.2017.04.002

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revbrashematolhemoter.2017;39(3):278–280

279

Figure1–Bonemarrowaspirate(magnification400×:

Leishmanstain)giantproerythroblastwithintranuclear

inclusionandabundantcytoplasmandnormalgranulocytic

precursors.

cameout to benegative. Direct antiglobulin test was neg-ative.Reticulocytecountwas <1%.Bone marrowaspiration smears were cellular with absolute reduction in erythroid precursors.Granulocyticprecursorsshowednormal morphol-ogyand maturation.Giant proerythroblastwith prominent intranuclearinclusionsandcytoplasmicprojections(dogear) suggestederythrovirus infection (Figure1). Megakaryocytes wereincreasedinnumberwithnumerousclusterformations. Multilobatedandhypolobated,andgranularand hypogranu-larformswereseen.However,allofthemwerenon-functional (consistentwithITP).Positiveserum immunoglobulin(Ig)M and IgG antibodies against EV19 confirmed our suspicion. Afinal diagnosis oferythrovirus induced red cell hypopla-siaand thrombocytopenia was rendered after detection of erythrovirusDNAbyqualitativerealtimepolymerasechain reaction(RT-PCR)usingprimersforthevirionstructural pro-tein(VP1).Theamplificationproductsweredetectedonthe basis of fluorescent dye labeled probes.4 _The _patient _was

treatedwithintravenousimmunoglobulin(IVIG,1mg/kgbody weight)approvedforuseinerythrovirusinfections.

Discussion

YvonneCossartdiscoveredEV19(previouslycalledparvovirus B19)in1974inLondon.5_Infection_is_most_common_in_late

win-terandearlyspring.Thevirusistransmittedthroughexposure torespiratorydropletsorbloodproductsaswellasthrough vertical transmission from mother to fetus. It is a single strandedDNAviruswithmarkedtropismforerythroidcells viaattachmenttotheglobosidePantigen.Theantigenisalso foundonplatelets,endothelialcells,cardiacmyocytes,and synovium,liver,lung,andkidneytissue.Specificitytoinfect erythroidlineagemaybeattributedtopreferentialexpression ofthePantigeninerythrocytesandhighactivityoftheviral P6promoterinthesecells.6

Theclinicalmanifestationsarestronglyinfluencedbythe immunologicalandhematologicalstatusofthehost.In non-immunocompromised individuals,the infection may range fromasymptomatictomildflu-likeillness.Theotherprimary manifestations include erythema infectiosum, arthropathy

and hydropsfetalis.7 _Viremia_is_usually_detected_5–10_days

afterexposure.Inahealthyindividual,atransientdecreaseof hemoglobinofupto1g/dLmaybeseenwithmarked reticulo-cytopeniaduringthephaseofviremia.Clinicallyinsignificant leucopenia,thrombocytopeniamayalsobeseen.All hemato-logicalparametersusuallynormalizewithintwoweeks.Thus, subclinicalerythroidhypoplasiafollowedbyrashor arthral-giaisthemostcommonclinicalpictureinimmunocompetent hosts.Inimmunocompromisedhosts,theinfectionmay man-ifestwithaplasticcrisis,chronicanemiaorITP.8_In_patients

with hemolytic anemia such as sickle cell anemia, EV19 may cause a transient aplastic crisis with sudden drop in hemoglobin.Althoughthemajorityofpatientsrecoverwithin twoweeks,thereisincreasedriskofcongestiveheartfailure, stroke,andacutesplenicsequestration.9

Ourcasewasanotherwisehealthychildpresentingwith symptomaticthrombocytopeniaandseverenormocytic nor-mochromicanemia.Bonemarrowexaminationrevealedclues forEV19infection(Lanterncells)alongwithmegakaryocytic hyperplasia(consistentwithITP).Thiswasfurtherconfirmed by positive IgM antibodies (indicating immunocompetency andacuteinfection).Ourcaseisuniqueduetopersistenceof erythroid suppressionandimmunemediated thrombocyto-peniainanotherwisehealthychild.Cytokinemediatedtoxic effectsofviralNS-1(centraltype)mayexplainthebi-lineage involvementinthiscase.10,11_The_second_mechanism_may_be

immune-mediateddestruction(peripheraltype).12

SerumIgMantibodytestinghas89%sensitivityand99% specificity.13_An_elevated_level_of_IgM_antibodies_appears_10–12

daysandremainsdetectablefor3–6monthsafteracute infec-tion.IgGantibodiespresumablypersistforlife.Thediagnostic antibodies are detected against VP1 and VP2 antigens. In immunocompromisedhosts,asantibodyproductionis min-imal or absent, viral DNA testing by PCR is necessary for diagnosis. PCR is moresensitive than in situ hybridization assays.

Ourcasehighlightstheimportanceoftheidentificationof morphologicalfeaturesofEV19infection.Thecasealso illus-tratesthevariableclinicalmanifestationofEV19infection.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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