Multisystemic fusariosis with fulminant evolution,

AnBrasDermatol.2020;95(5):645---648

Anais

Brasileiros

de

Dermatologia

IMAGES

IN

DERMATOLOGY

Multisystemic

fusariosis

with

fulminant

evolution

夽,夽夽

Nelson

Turra

_,

_Agustina

_Acosta

_,

_Andrea

_Incoronato

_,

Pilar

Beltramo

a_{DepartmentofDermatology,Dr.ManuelQuintelaClinicalHospital,Montevideo,Uruguay} b_{DepartmentofPediatricDermatology,PereiraRossellHospital,Montevideo,Uruguay} c_{DepartmentofHemato-oncology,PereiraRossellHospital,Montevideo,Uruguay} d_{DepartmentofPathology,PereiraRossellHospital,Montevideo,Uruguay}

Received15August2019;accepted5March2020 Availableonline12July2020

KEYWORDS Bacterialinfections andmycoses; Bonemarrow transplantation; Centralnervous systemfungal infections; Fusariosis; Fusarium

Abstract Thisreportpresentsthecaseofa13-year-oldfemalepatientwithhistoryofacute myeloid leukemia, who,after abone marrow transplant, began to vomit andexperienced rapidlyprogressivedeteriorationofconsciousness,inadditiontodisseminated erythematous-violaceousmacules,andsomeblisterswithhemorrhagiccontentinside.Skinbiopsyevidenced intravascularfilamentousstructures.AbloodcultureconfirmedthepresenceofFusarium oxys-porum.Intravenoustreatmentwithvoriconazolewasinitiated.Thepatientevolvedunfavorably withmultiplenecroticskinlesions,ischemicbrainlesions,anddeath.

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

Introduction

Fusarium spp. arefungi universally found in soil, air, and

plants; they mainly affect immunocompromised patients

夽 _{Howtocitethisarticle:TurraN,AcostaA,IncoronatoA,} Bel-tramoP.Multisystemicfusariosiswithfulminantevolution.AnBras Dermatol.2020;95:645---8.

夽夽_{StudyconductedatthePereiraRossellHospital,Montevideo,} Uruguay.

∗_{Correspondingauthor.}

E-mail:nelsonturra85@gmail.com(N.Turra).

and may cause localized, focally invasive, or

dissemi-nateddisease.1,2_{Immunosuppressedpatientsandcarriersof}

hematologicmalignanciesareverysusceptibletothe

devel-opmentof invasive forms, showing high mortality.2---4 _This

reportdescribesthecase of apatientwithacutemyeloid

leukemia,whopresented withinvasivefusariosiswith

ful-minantevolutionafterabonemarrowtransplant.

Case

report

13-year-oldadolescent,female,whopresentedthreeyears

agowithacutemyeloblasticleukemia,achievingcomplete

remissionofherdisease.Shepresentedherfirst

hematologi-https://doi.org/10.1016/j.abd.2020.03.007

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

646 TurraNetal.

calrelapsethreemonthsago,thenachievedanewcomplete

remission,and underthese conditionsan allogeneic bone

marrow transplant (BMT) was planned. Myelosuppressive

conditioningwasperformedwithbusulfanandfludarabine,

administeredtogetherwithan infectious prophylaxis with

acyclovir,trimethoprim-sulfamethoxazole,andfluconazole.

Afterfivedaysofthetransplant,administrationof

granu-locytecolony-stimulating factor was initiated (Neupogen®

300␮g/kg/day).

After aweek of BMT,the patientbegan to experience

headache and vomiting, showing central facial paralysis

andrapidlyprogressivedeteriorationofconsciousness,until

reachingascoreof7according totheGlasgowScale;this

motivated her admission to the Intensive Care Unit. The

antibiotic treatment was adjusted to a broad spectrum

scheme with meropenem 60mg/kg/day and vancomycin

40mg/kg/day. At that time, an interconsultation with a

dermatologist wasperformed, due to thesudden

appear-ance of multiple disseminated skin lesions. On physical

examination,shepresenteddisseminateddermatosisonthe

trunk, lower, and upper limbs, characterized by rounded

erythematous-violaceousmacules,infiltratedonpalpation,

andsomeblisterswithhemorrhagiccontentinside(Fig.1).

Laboratory tests showed hemoglobin of 9.4mg/dL; 2,800

mm3 _{leukocytes (60% neutrophils); 53,000mm}3 _platelets,

withnormalliverandkidneyfunction.Bloodcultureswere

negative.Also,polymerasechainreactionwasnegativefor

cytomegalovirus,varicellazostervirus,andherpessimplex

virustypes1and2.

The skin biopsy was processed for staining with

hematoxylin-eosin, PAS, and Grocott-Gomori; evidencing

intraepidermal acantholysis, vessels with fibrinoid

necro-sisof thewall, andocclusive thrombosis.The biopsy also

foundsuperficialperivascular inflammatoryinfiltrate

com-posed of lymphocytes, neutrophils, and leukocytoclasia,

highlightingthepresenceofintravascularfilamentous

struc-tures,correspondingtoseptate hyphae andconidiospores

(Figs.2---4).Asubsequentbloodcultureconfirmedthe pres-enceof Fusarium oxysporum, and treatment was started

withintravenous voriconazole4mg/kg/dose,twice a day.

Thepatientevolvedunfavorablyandwithskinlesionsthat

adopteda centralnecroticappearancewithascaling

col-Figure 1 Invasive fusariosis, early clinical manifestations (left thigh). Dermatosis characterized by the presence of erythematous-violaceousmacules,whichcoexisttogetherwith hemorrhagicblisters,situatedonerythematousandinfiltrated skin.

Figure 2 Fusariosis, histopathology of skin lesions (Hema-toxylin & eosin, ×40). Vessels with fibrinoid wall necrosis and occlusive thrombosis in their lumens, accompanied by a superficial perivascular inflammatory infiltrate composed of lymphocytes, neutrophils, and leukocytoclasia. The yel-lowarrowhighlightsthepresenceofintravascularfilamentous structures,correspondingtoseptatehyphae.

Figure3 Fusariosis,histopathologyofskinlesions(PAS,×40). Septatehyphaeandintravascularconidiophoresareevident.

larette (Fig. 5). Subsequently, she began to suffer from

severe diabetes insipidus (hypernatremia crisis of up to

170 mEq/L). Magnetic resonance of the brain, taken 20

dayspost-transplant,evidencedthepresenceof extensive

ischemiclesionsandcerebraledema,withtonsillar

hernia-tionandbulbo-spinalcompression.Afterthreeweeksofthe

transplant,thepatientdied.

Discussion

Fusariumspp.arefungipresentinthesoilinallpartsofthe

world,includingtropical,desert, andevenarcticregions;

thisis duetotheir highadaptability.Regarding their

inci-dence,theycorrespondstothesecondmostfrequentcause

of invasivemoldinfectioninhemato-oncological patients,

behindAspergillusspp.5_{Theriskfactorsforinvasive}

Multisystemicfusariosiswithfulminantevolution 647

Figure4 Fusariosis,histopathologyofskinlesions (Grocott-Gomori,×40).Septatehyphaeandintravascularconidiophores areevident.

Figure 5 Invasive fusariosis, late clinical manifestations (right arm). Dermatosis characterized by the presence of necroticskinlesionswithscalingcollarette.

induction chemotherapy for leukemia, recent BMT, and

graft vs. host disease.1,6 _{Likewise, the authors highlight}

that the current patient was a carrier of acute myeloid

leukemiaand hadrecentlyreceived aBMT. Itis expected

thatafteraBMT,severeneutropeniawilloccur,inthe

con-textofthemyelosuppressiveconditioningrequiredforthis

procedure.

Invasiveformsoffusariosisshowcutaneousinvolvement

in 63% of cases, and this is characterized by the

pres-ence of subcutaneous nodules, erythematous macules, or

vesicle-pustulesthatmaybecomenecrotic.4,7_Thispathogen

is highly angio-invasive, producing tissue infarctions such

as those evidenced in the brain of the current patient,

whichgenerateintravascularsporulation,favoringagreater

sensitivity of blood cultures in the final stages of the

disease.8 _{Fusarium spp. are resistant tomultiple}

antifun-gals, but are highly susceptible to amphotericin B and

voriconazole.1,9,10_{However,severeneutropeniaisthemost}

importantprognosticfactor,determininglethalityofupto

75%ofcases.6,10

Final

considerations

Invasivefusariosisisextremelyseriousandisassociatedwith

high mortality in immunosuppressed patients. It requires

intensiveantifungaltreatmentandadministrationof

gran-ulocyte colony stimulating factor, since its prognosis is

closely related to the recovery of neutropenia. The role

of the dermatologist as part of a multidisciplinary team

mustbeemphasized,havingahighdiagnosticsuspicionof

this pathology in the case of immunosuppressed patients

withclinicalmanifestationssimilartothosepreviously

elu-cidated.

Financial

support

Nonedeclared.

Authors’

contributions

NelsonTurra:Approvalofthefinalversionofthemanuscript;

draftingandeditingofthemanuscript;participationinstudy

design;participationinthetherapeuticand/or

propaedeu-tic conduct of the studied cases; critical review of the

literature;criticalreviewofthemanuscript.

Agustina Acosta: Approval of the final version of the

manuscript;participationin study design; participationin

thetherapeuticand/or propaedeuticconductofthe

stud-iedcases;criticalreviewoftheliterature;criticalreviewof

themanuscript.

Andrea Incoronato:Approvalof thefinalversion ofthe

manuscript;participationin study design; participationin

thetherapeuticand/orpropaedeuticconductofthestudied

cases;criticalreviewoftheliterature;criticalreviewofthe

manuscript.

Pilar Beltramo: Approval of the final version of the

manuscript;participationin study design; participationin

thetherapeuticand/or propaedeuticconductofthe

stud-iedcases;criticalreviewoftheliterature;criticalreviewof

themanuscript.

Conflicts

of

interest

Nonedeclared.

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