Disseminated fusariosis in a patient with bone marrow aplasia,

Anais

Brasileiros

de

Dermatologia

CASE

REPORT

Disseminated

fusariosis

in

a

patient

with

bone

marrow

aplasia

夽,夽夽

Danielle

Ferreira

Chagas

,

Lucia

Martins

Diniz

,

Elton

Almeida

Lucas

,

Paulo

Sergio

Emerich

Nogueira

DermatologyService,HospitalUniversitárioCassianoAntonioMoraes,UniversidadeFederaldoEspíritoSanto,Vitória,ES,Brazil Received8October2019;accepted15December2019

Availableonline4July2020

KEYWORDS

Fusariosis;

Immunosuppression; Mycoses;

Neutropenia

Abstract Fusariosisis asuperficial orsystemic infection,which occurs mainlyin

immuno-compromisedhosts,especiallyinpatientswithhematologicalneoplasia;70%---75%ofthecases presentcutaneousmanifestations.Thedisseminatedformisrareanddifficulttodiagnose;even withspecifictreatment,theevolutionisusually fatal.Currently, itisconsideredan emerg-ingdisease;insome centers,itisthesecondmostcommoncauseofinvasivemycosis,after aspergillosis.The authors describeacaseofafemalepatient withidiopathicbonemarrow aplasiaanddisseminatedfusariosis,who initiallyappearedtobenefitfromvoriconazoleand amphotericin B;however,duetopersistentneutropenia, herclinicalconditiondeteriorated withfatalevolution.

©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

Introduction

Fusariosis is an opportunistic, cosmopolitan disease caused by filamentous, hyaline fungi of the Fusarium

genus, widely distributed in nature as soil and plant

夽 _{Howtocitethisarticle:ChagasDF,DinizLM,LucasEA,Nogueira}

PSE.Disseminatedfusariosisinapatientwithbonemarrowaplasia. AnBrasDermatol.2020;95:609---14.

夽夽_{StudyconductedattheHospitalUniversitárioCassianoAntônio}

Moraes,UniversidadeFederaldoEspíritoSanto,Vitória,ES,Brazil.

∗_{Correspondingauthor.}

E-mail:daaani @hotmail.com(D.F.Chagas).

saprobes.1 _{Itrarely affectsimmunocompetent individuals;}

when it does, the infection usually remains superficial, causing onychomycosis and keratitis, related to direct inoculation.2,3

In immunocompromisedpatients, especiallythose with hematologicalcancer,inparticularacutemyeloidleukemia, and after bone marrow transplantation, invasive fun-gal infections are associated with 70% mortality.4 _In

disseminated infections, 80% of patients develop skin lesions,which maybetheonly earlymanifestation ofthe disease.2,5

In its disseminated form, fusariosis is a rare infec-tion, with an incidence of 0.06% to 0.2% in the United States and Europe; in hematological patients,

how-https://doi.org/10.1016/j.abd.2019.12.008

0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).

diagnosedwithpancytopeniaandseverefebrile neutrope-nia(neutrophilsbelow100cells/mm3_{),andbroad-spectrum}

antibiotic therapy (meropenem and vancomycin) was initiated.

In the investigation, a bone marrow biopsy was per-formed;thehistopathologyshowedbonemarrowhypoplasia ofthethreehematopoieticcelllines,withonly5%ofcells. Inaddition, allserologies (includingparvovirus B19)were requested, and all infectious hypotheses were discarded; therefore,thediagnosisofidiopathicbonemarrowaplasia wasreached.

Sabouraud’s medium with chloramphenicol from the skin fragment and subsequent microculture of the colony evi-dencedthegrowthofFusariumspp.(Figs3and4)).Afterthe resultsof thesetests,amphotericinBwasassociatedwith voriconazole, andthepatient initiallybenefited fromthis association.

Thedermatologicalexaminationalsoshowedparonychia in the second and third leftfingers and exuberant livedo reticularis in all lower limbs, extending to the abdomen (Fig.5).

Figure1 (A),Anerythematous-violaceousmaculaontheleftupperlimb.(B),Afteroneweek,thelesionevolvedtoulceration

Figure2 Histopathologicalexaminationofalesionoftheleftupperlimb,showingmultipleseptate,hyaline,andbranchedhyphae withangiolymphaticinvasion.(A,Hematoxylin&eosin,×10;B,Grocott,×40).

Figure3 (A),SkinfragmentcultureinSabouraud’smediumwithchloramphenicol:whitepowderyfilamentouscolony;(B),

Figure5 (A),Paronychiainthesecondandthirdleftfingers;(B),Exuberantlivedoreticularisaffectingtheentirelowerlimb.

Theimageexaminationofthesinusesrevealedextensive shadowingofthemaxillary,frontal,sphenoid,andethmoid sinuses,whichwasattributedtoinvasivesinusitis(Fig.6). The otorhinolaryngology team performed a biopsy of the sinusesand a directexamination of the nasalcavity. Sur-gicaltreatment throughdebridementwasnotpossibledue to persistent thrombocytopenia and lesion angioinvasion. Histopathologyanddirectexaminationweresimilartothe findingsoftheskinlesion.Shealsohadextensivebilateral diffusepulmonary infiltrateconsistentwithinvasive pneu-monia.

Throughout the period of neutropenia, the patient receivedtransfusionsandstimulatingfactorforgranulocytic colonies,but did notpresent anybone morrowresponse. Afterfourweeks,shedevelopedrefractorysepticshockand, despitesupportivemeasures,died54daysafter hospitaliza-tion.

Discussion

Fusariosisisthesecondmostfrequentinvasivefungal infec-tion in patients with hematological neoplasms; Fusarium solaniisthemostcommon,virulent,andresistantspecies,

presenting the highest mortality, confirmed in the case presented.6---8

The infection starts by inhaling conidia or by direct contactwithmaterials contaminated by spores.1,2 _Studies

indicate that disseminated cases are usually acquired by inhalation withsubsequent dissemination to other organs suchasthekidneys,liver,eyes,spleen,andbrain.1,8_Inthe

reportedcase,skinlesionsprecededsinusitisand pneumo-nia, suggesting hematogenous spread of cutaneous focus. The infection is classified as disseminated when two or more organs are involved, as seen in the case reported, in which the patient presented sinusitis and pneumonia, confirmed byimageexamination andthepresence ofskin lesions.4

The most common presentation is persistent fever unresponsivetobroad-spectrumantibiotictherapyina neu-tropenic patient,suchasthepatientstudied.Typicalskin involvementshowspainfulerythematous-violetmaculesor papules, the center of which evolves to necrosis, usu-ally on the extremities; all these findings were observed in the present case. The dermatological examination also showedlivedoreticularisintheentirelowerlimbreaching the abdomen, which probably occurred due to intravas-cular proliferation of the fungus leading toocclusion and

Figure 6 (A), Chest tomography showing a pattern of parenchymalconsolidationwithintermingledairbronchograms, notablyintheposteriorregionofthepulmonaryfields(black arrows).(B,C,andD)CTscanofthesinusesshowingdiffuse veil-ingoftheparanasalsinuses,characterizedbymaterialwithsoft tissuedensityfillingthemaxillary(redarrow),sphenoid(yellow arrow),andfrontalsinuses(bluearrow),andtheethmoidalcells (whitearrow).

necrosis of the microvasculature, although the authors have not found any reports of this phenomenon in the literature.5,8,9

ThediagnosisrequirestheisolationofFusariumspp.5_In

thepresentcase,hyphaewereobservedinthe histopathol-ogy of the skin and sinuses, confirmed by the growth of fungi in the culture of samples collected at these sites. In histopathological examination, fungi characteristically present angiolymphatic invasion by septate, hyaline, and branched hyphae.1 _{Culture identification is important to}

help differentiate fusariosis from other hyalohyphomy-coses. The Fusarium genus is identified in the culture by multiple canoe-shaped hyaline macroconidia.6,7

However, species identification requires molecular methods.7

Invasive and generalized infections respond poorly to antifungal therapy, partly due to drug resistance, but mainly due tothe lack of an effective responsefrom the host,whichledtoourpatient’sunfavorableoutcome,who remained with persistent neutropenia. Therefore, treat-ment is based on systemic antifungals and reversal of immunosuppression.The idealtreatmentshouldbeguided by the antifungal sensitivity test, which is available in only a few centers; therefore, most authors recommend combined therapy for severe cases, with voriconazole and amphotericin B, the scheme used in the present patient.2,8,10

The patient had severe neutropenia related to bone marrow aplasia, and the authors found in the litera-turethreecasesofdisseminatedfusariosisassociatedwith this hematological disease, all of which also had a fatal outcome.

Financial

support

Nonedeclared.

Authors’

contributions

Danielle Ferreira Chagas: Conception and planning of the study; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or thera-peutic conduct of studied cases; critical review of the literature.

LuciaMartinsDiniz:Approvalofthefinalversionofthe manuscript;conceptionandplanningofthestudy;effective participationinresearchorientation;intellectual participa-tioninpropaedeuticand/ortherapeuticconductofstudied cases;criticalreviewoftheliterature;criticalreviewofthe manuscript.

Elton Almeida Lucas: Intellectual participation in propaedeuticand/ortherapeuticconductofstudiedcases. Paulo Sergio Emerich Nogueira: Intellectual participa-tioninpropaedeuticand/ortherapeuticconductofstudied cases.

Conflicts

of

interest

Nonedeclared.

References

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2.MeriglierE,PuyadeM,CateauE,MaillardN.Nodularskinlesions revealingfusariosisinasevereaplasticanemiapatient.Presse Med.2015;44:574---6.

3.McCarthyWM, KatragkouA, IosifidisE,Roilides E, WalshJT. Recentadvancesinthetreatmentofscedosporiosisand fusar-iosis.JFungi(Basel).2018;4,pii-73.

4.GarnicaM,daCunhaMO,PortugalR,MaiolinoA,ColomboAL, Nucci M.Risk factors for invasiveFusariosis inpatients with acutemyeloidleukemiaand inhematopoietic celltransplant recipients.ClinInfectDis.2015;60:875---80.

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