Disseminated Fusarium infection in autologous stem cell transplant recipient

braz j infectdis.2015;19(1):90–93

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

Case

report

Disseminated

Fusarium

infection

in

autologous

stem

cell

transplant

recipient

Vivian

Iida

Avelino-Silva

_,

_Jessica

_Fernandes

_Ramos

_,

_Fabio

_Eudes

_Leal

_,

Leonardo

Testagrossa

_,

_Yana

_Sarkis

_Novis

a_{DepartmentofInfectiousandParasiticDiseases,UniversityofSaoPauloMedicalSchool,SãoPaulo,SP,Brazil} b_{HospitalSirio-Libanês,SaoPaulo,SP,Brazil}

c_{DivisionofClinicImmunologyandAllergy,MedicalSchool,UniversityofSãoPaulo,SãoPaulo,SP,Brazil} d_{FleuryMedicinaDiagnóstica,SaoPaulo,SP,Brazil}

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Articlehistory:

Received26December2013 Accepted1August2014 Availableonline13October2014

Keywords:

Stemcelltransplant Autologous

Fusarium

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Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromisedpatients, includingbone marrow transplantrecipients. However, autologousbonemarrowtransplantrecipientsarenotexpectedtobeathighrisktodevelop fusariosis.WereportararecaseoflethaldisseminatedFusariuminfectioninanautologous bonemarrowtransplantrecipientduringpre-engraftmentphase.

©2014ElsevierEditoraLtda.Allrightsreserved.

A 53-year-old male patient, diagnosed with a gradeII fol-licular lymphoma, was submitted to an autologous bone marrow transplant (BMT) as therapeutic procedure follow-ingrecurrencetoinitialchemotherapy.Hehadbeentreated with eightcycles of R-CVP (Rituximab, Cyclophosphamide, Vincristineand prednisone), followed bythree cycles of R-ICE (Rituximab, Iphosphamide Carboplatin and Etoposide) and two cycles of R-DA-EPOCH (dose-adjusted etoposide, prednisone,vincristine,cyclophosphamide,doxorubicinplus rituximab).ConditioningregimenwasprescribedwithBEAM (carmustine, etoposide, cytosine arabinoside, melphalan). Prophylacticantimicrobialtreatmentwasprescribedwith flu-conazole 200mg QD. He started with neutropenia in the

∗ _{Correspondingauthorat:FaculdadedeMedicinadaUniversidadedeSãoPaulo,Av.Dr.EnéasdeCarvalhoAguiar,470,CerqueiraCésar,} 05403-000SaoPaulo,SP,Brazil.

E-mailaddress:viviansilva87@gmail.com(V.I.Avelino-Silva).

D+1post-transplant,andpresentedfeverintheD+3 post-transplant, followed by intense myalgia and papular skin lesionwithrapiddissemination.Someofthepapularlesions progressedwithcentralischemiaandnecrosis(Fig.1).Empiric antimicrobialtreatment withmeropenen,vancomycin,and liposomal amphotericin5mg/kgQD was initiated.Baseline totalleukocyte countattheonsetoftheinfectiousepisode was20leucocytes.Askinbiopsyrevealedabundanthyphae structures (Fig. 2). Concomitantly, blood cultures identified

Fusariumsolanithroughmacro-andmicroculture.Thepatient wasimmediatelytransferredtotheintensivecareunit,and voriconazole 400mgIV BIDwas associatedto the antifun-galtherapy.Ophthalmologicevaluationrevealednosignsof

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Fig.1–Skinpapularlesions(A)progressedwithcentralischemiaandnecrosis(B).

endophthalmitis, and radiographicimageswere unremark-able. Laboratory findings were heavy myoglobinuria, with normal creatine phosphokinase, worsened renal function withincreasedbloodlactateandelevationofbothC-reactive proteinandpro-calcitonin. Serum(1-3)-␤-d-glucanwas not assessed.Granulocytewastransfusedintwoconsecutivedays without significant improvement of the clinical condition. Thepatientdevelopedrefractorysepticshockand,inspite of intensive care support, renal replacement therapy, and mechanicalventilation, progressedtounresponsivecardiac arrestfourdaysafterinitialclinicalpresentation.Thepatient hadno previoushistoryoffungal diseases.Noskinornail lesionhadbeenobservedatthoroughdailyphysical examina-tionpriortotheterminalevent.Fungalsusceptibilitytesting performedbyE-testmethodrevealedresistancetofluconazole andsusceptibilitytovoriconazoleandamphotericin. Investi-gationregardingpotentialsourceofinfectionwasconducted, andculturesoftapandshowerbathwaterobtainedfromthe patient’shospitalunitwerenegativeforfungalgrowth.

Discussion

FusariuminfectionisarareeventfollowingautologousBMT, probably dueto less intenseimmunossupression relatively to allogeneic or cord cell transplant. To our knowledge, only one casereport has described fusariosisin an autol-ogous BMT recipient who survived after administrationof amphotericin B, eye enucleation due to fungal endoph-thalmitis, and neutrophil recovery.1 _{Other 10 reports of} fusariosisinanautologousBMTdescribedfataloutcomes.2,3 Ourpatientdevelopedafatal,disseminated fusariosisafter a very short period of neutropenia. This unexpected out-come propelled immediate investigation of the potential sourceoffungalcontamination.Hospitalenvironmental con-tamination by fungal specimens has been demonstrated inmedicalliterature,eveninhigh-efficiencyparticulateair (HEPA)filtration-equippedunits.4,5 _{Althoughculturesoftap} andshowerbathwaterturnedoutnegativeforfungalgrowth

Fig.2–Skinbiopsyshowingabundantseptatehyphaestructures.(A)200×hematoxylin–eosinstainrevealingbasophilic

yeastandhyphaestructuresinsuperficialdermisandperivascularsites,withminimalinflammatorycomponent.(B)Skin

biopsyin100×Periodicacid-Schiffstain,revealingfungalcellwallsinmagenta.(C)200×Grocott’smethenaminesilver

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in our case, it is likely that environmental sources, either hospital-relatedornot,mightbeaccountedastheinfection source.

A throughoutphysical examination, including skin and nail inspection did not reveal any lesion that could raise suspicionforacutaneousportalofentry, eitherathospital admissionoratthepost-transplantperiod.Astrong associ-ationbetweeninvasiveFusarium infection andasuperficial skinlesion,especiallyonychomycosisorintertrigo,hasbeen demonstratedinrecentstudies.6,7_{Moreover,thepresenceofa}

Fusariumskinlesionatadmissionwasassociatedwiththe sub-sequentdevelopmentofinvasivefusariosisinaprospective cohort.6

Our patient was not under prophylactic therapy with voriconazole, in accordance with his short period of neu-tropenia and lowrisk ofinvasivemold infection. However, anincreasingincidenceofinvasivemoldinfectionshasbeen reportedamongpatientswithhematologicalmalignancies,8,9 including autologous BMT recipients.10 _{In Brazil, cases of} invasivefusariosisaffectingpatientswithhematologic malig-nancies and hematopoietic cell transplant recipients have been reported to increase over the years 2000–2010.7 _The widespreaduse ofmonoclonal antibodies,including Ritux-imab,might potentially increase risk for infections among hematologic patients,11 _{but the association with invasive} moldsneedsfurtherinvestigation.

TreatmentofFusariuminfectionisachallengingissue, par-ticularlyintheimmunocompromisedhost.Lipidformulations ofamphotericinBandvoriconazolearethemostfrequently usedmedicationsforfirst-linemonotherapy.12_Fusarium sus-ceptibilitytovoriconazoleisvariable,13 _{andabreakthrough} infectionhasbeenreportedin16outof44consecutive fusario-siscasesinalargeretrospectivereport.Amongthosepatients diagnosed with fusariosis, 69% were receiving prophylaxis withanextendedspectrumtriazole,eithervoriconazole(8/16; 50%)orposaconazole(3/16;19%).14

Combination therapy with amphotericin formulations, voriconazole,itraconazole,andechinocandinshavebeen pre-viously reported,12,15,16 but more studies are required to exploretherealbenefitofthisapproach.

Granulocyte transfusion is often considered as a sup-portingtherapyforpatientswithprolongedneutropeniaor abnormalleukocytefunctionandsevereinfection.Although itsefficacy isnotwell established,someauthors suggest a beneficialeffect,basedonuncontrolledcasereportsandcase series.17,18

In conclusion, our report illustrates a rare case of a lethal,disseminatedFusariuminfectioninanautologousBMT recipient during pre-engraftment phase. This unexpected manifestationreinforces the need forcareful clinical eval-uation of BMTcandidates, as well as exhaustive vigilance ofenvironmentalcleansingprocedures.Antifungal prophy-laxismustbeselectedaccordingtothecharacteristicsofeach patient,andfurtherstudiesassessingtheuseofantifungal prophylaxiswithactivityagainstmoldsarenecessary.

Conflicts

of

interest

Theauthorshavenoconflictsofinteresttodeclare.

Authorship

VIAS conceivedthe manuscript, participated inthe collec-tion ofclinical data, study designand manuscriptwriting; JFR and FEL participated in the collection of clinical data and manuscriptrevision;LTparticipatedinthe assemblage ofhistopathologydataandmanuscriptwriting;YSN partici-patedinthecollectionofclinicaldataandmanuscriptreview. Allauthorsreadandapprovedthefinalmanuscript.

Acknowledgment

We acknowledgeDr. Mariana Serpa and Dr.Esper Georges Kallásforthemanuscriptrevisionandusefulcontribution.

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