an emergent entity: indolent mucormycosis of the paranasal … · erika celis-aguilar1 alan...

An Emergent Entity: Indolent Mucormycosis ofthe Paranasal Sinuses. A Multicenter StudyErika Celis-Aguilar1 Alan Burgos-Páez1 Nadia Villanueva-Ramos1 José Solórzano-Barrón1

Alma De La Mora-Fernández1 Juan Manjarrez-Velázquez2 Sergio Verdiales-Lugo1

Lucero Escobar-Aispuro1 Perla Becerril3 Ana Valdez-Flores4 Francisco Javier Merino-Ramírez4

Carmen Beatriz Caballero-Rodríguez4

1Department of Otolaryngology, Centro de Investigación y Docenciaen Ciencias de la Salud (CIDOCS) de la Universidad Autónoma deSinaloa, Culiacán, Sinaloa, México

2Department of Otolaryngology, Culiacan General Hospital, Culiacán,Sinaloa, México

3Department of Otolaryngology, General Hospital Regional No. 1“Ignacio García Téllez” del IMSS, Mérida, Yucatán, México

4Department of Pathology, Centro de Investigación y Docencia enCiencias de la Salud (CIDOCS), Universidad Autónoma de Sinaloa,Culiacán, Sinaloa, México

Int Arch Otorhinolaryngol 2019;23:92–100.

Address for correspondence Erika Celis-Aguilar, MD, Blvd. Alfonso G.Calderón No.2193 Poniente, Cons. 603. Desarrollo Urbano Tres Ríos.Zip code 80050. Culiacán, Sinaloa, México(e-mail: [email protected]).

Keywords

► mucormycosis► mucorales► paranasal sinuses► sinusitis► mycoses► chronic

mucormycosis

Abstract Introduction Indolent or chronic mucormycosis is a rare entity that affects bothimmunosuppressed and immunocompetent individuals. Additionally, its clinical evolu-tion is nonspecific and there is no standardized treatment for this condition.Objective To describe the clinical characteristics and management of patients withindolent mucormycosis.Methods In the project of study with chart review in the Interinstitutional secondarycare centers, patients with evidence of indolent mucormycosis, defined as pathologicalconfirmation of nasal/paranasal sinus mucormycosis for more than 1 month, wereincluded. All patients underwent complete laboratory workup, imaging studies,surgical treatment and adequate follow-up. No evidence of disease status was definedwhen patient had subsequent biopsies with no evidence of mucormycosis.Results We included seven patients, three female and four male subjects. The mean agewas 53.14 years. Four patients were immunosuppressed and three immunocompetent.Among the immunosuppressed patients three had diabetes and one had dermatomyositis.The symptomswere nonspecific: facial pain/headache,mucoid discharge and cacosmiawerethe ones most frequently reported. Maxillary sinus involvement was present in all patients.Two immunosuppressed subjects received amphotericin. Posaconazole was the only treat-ment inone immunosuppressedpatient.All immunocompetentpatientshadsingleparanasalsinus disease and received only surgical treatment. All patients are alive and free of disease.Conclusion Indolent mucormycosis is a new and emerging clinical entity in immu-nosuppressed and immunocompetent patients. Single paranasal sinus disease is afrequent presentation and should not be overlooked as a differential diagnosis in thesepatients. Immunocompetent patients should only be treated surgically.

receivedOctober 29, 2017acceptedMay 23, 2018published onlineOctober 24, 2018

DOI https://doi.org/10.1055/s-0038-1667005.ISSN 1809-9777.

Copyright © 2019 by Thieme RevinterPublicações Ltda, Rio de Janeiro, Brazil

Original ResearchTHIEME

92

Introduction

Mucormycosis is commonly a fatal infection caused by fungi ofthe order Mucorales, with Rhizopus being the most commonspecies associatedwith this disease.1Other isolated species areAbsidia, Mucor and Rhizomucor.2,3 Histologically, it presentswith hyphae that are broad-based and non septatedwith rightangles.4,5 Since this is predominantly a fulminant disease, it ispotentially lethal.5 Patients are usually immunosuppressedindividuals, and the clinical hallmark has been vascular inva-sion with tissue necrosis.6 Nonetheless, new cases of indolentmucormycosis are being reported, occurring among immuno-suppressed4,7–9andimmunocompetentpatients.10–15Theclin-ical characteristics are distinguished by its chronic evolution,14

nonspecific symptoms and in some cases absence of frankvascular invasion and necrosis.5 Additionally, single paranasalsinus disease is also a frequent presentation.11 We currentlyaddress this new form of disease with recent evidence. Theobjective of this study is to describe the clinical characteristicsand management of patients with indolent mucormycosis.

Methods

PatientsThe patients were recruited from November 2012 to Novem-ber 2016. This study was a multicenter clinical chart reviewconducted in secondary care centers. Indolent mucormycosiswas defined as pathological evidence of nasal/paranasal sinusmucormycosis for longer than 1 month. The inclusion criteriawere patients with indolent mucormycosis who had patholo-gical confirmation, complete imaging studies and underwentsurgical/medical treatment with adequate follow-up.

This is an interinstitutional study approved by the ethicalcommittees of the hospitals involved and led by Centro deInvestigación y Docencia en Ciencias de la Salud (CIDOCS) dela Universidad Autónoma de Sinaloa, Sinaloa, Mexico. Asigned informed consent was obtained from all patients.

Evaluation and Surgical TechniqueAll patients were evaluated by the otolaryngology and theinfectiology departments. All patients underwent imaging,laboratoryworkup and surgical treatment. The patientswereoperated on by certified interinstitutional otolaryngologists.

The surgical procedures consisted in external maxillaryapproach (modified Caldwell-Luc procedure), endoscopicethmoidectomy and antrostomy. The endoscopic procedureconsisted in the removal of the uncinated process, ethmoidbulla; the resection of anterior and posterior ethmoid cellswas done depending on the extension of disease. The iden-tification of the natural maxillary ostiumwas performed andenlarged with a backbite and a 45° Blakesley forceps.

All surgical specimens were evaluated by two certifiedpathologists.

Statistical AnalysisThe data were gathered by clinical chart review. The statis-tical analysis was performed using the Statistical Package forthe Social Sciences (SPSS) 18.0 (SPSS Inc., Chicago, IL, USA).

The statistical analysis included descriptive statistics (meanand standard deviation).

Results

Demographic DataWe included seven patients, three female and four malesubjects. The mean age was 53.14 years. Four patientswere immunosuppressed and three were immunocompe-tent. Maxillary sinus involvement was present in all patients.

Amongthe immunosuppressedpatients, threehaddiabetesand one had dermatomyositis. The symptoms were nonspe-cific. Facial pain, mucoid discharge and cacosmia were thesymptoms most frequently reported. (See ►Table 1).

The duration of symptoms ranged from 1 to 28 months.Two patients had asymptomatic mucormycosis, found inci-dentally on computed tomography (CT) scan (cases 3 and 5).

Immunosuppressed CasesCase 1 was a 38-year-old female patient who presentedinitially with fulminant mucormycosis disease. Middle turbi-nate resection, modified Caldwell-Luc procedure and endo-scopicethmoidectomywereurgentlyperformed.Necrosiswasseen intraoperatively in themiddle turbinate. In spite ofocularinvolvement (proptosis, pupillary dilation and restriction ofocular movements), we decided on ocular preservation andhospitalization for a period of 1 month, with strict metaboliccontrol, and administration of up to 3g of amphotericin. At theend of the month, she was asymptomatic, and ocular involve-ment was stable. Nonetheless, the magnetic resonance ima-ging (MRI) and CT scan showed progressive orbital apexpathology. An intraconal biopsy was performed, with finalpathology result of mucormycosis. She underwent orbitalexenterationwith confirmation of orbital disease. Subsequentbiopsies of maxillary and ethmoid sinus were negative. Thiscase was included because it shows a patient with persistentdisease that developed chronic symptoms. Once amphotericinwas prescribed for 1 month, the patient had no diseaseprogression and no additional symptoms. The disease wasconfined to the orbital fat. The fulminant course was arrestedand led to an indolent one. See ►Fig. 1.

Case twowasdiagnosedwithdiabetesduringherhospitaliza-tion. Initialnasalendoscopyrevealedonlymiddlemeatusedema.Surgical findingswere compatiblewith fungus ball and necrosisof maxillary mucosa. Pathology study of the mucosa revealedmucormycosis. Two subsequent biopsies were performed, andthe last biopsy showed no evidence of disease. See ►Fig. 2.

Case three was asymptomatic. The patient had diabetesand renal failure and, since he was a candidate for a kidneytransplant, a paranasal sinus CT scan was performed. Sinusoccupation required mandatory surgery, which later led tothe diagnosis of mucormycosis. Subsequent biopsies werenegative. ►Fig. 3 shows histopathological confirmation.

Case four had dermatomyositis. Patient complained of nasalobstruction, facial fullness, chronic rhinorrhea with posteriordischarge and cough. Paranasal sinus CT scan was performedwith leftmaxillarysinusoccupation.See►Table 1 foradditionalsymptoms and treatment. See►Fig. 4 for preoperative CTscan.

International Archives of Otorhinolaryngology Vol. 23 No. 1/2019

An Emergent Entity Celis-Aguilar et al. 93

ImmunocompetentAmong the immunocompetent cases (5, 6, and 7), one patienthad cocaine addiction, interrupted 5 years earlier and 2patients had previous septoplasties.

Patient number 5 had right nasal polyp as the only causeof nasal symptoms. Mucormycosis was contralateral and

asymptomatic. See ►Figs. 5, 6 and 7. See ►Table 1 forcomplete description of symptoms and treatments.

TreatmentAll patients underwent surgical treatment, which consistedmainly in an external maxillary approach and endoscopic

Table 1 Demographics and clinical characteristics of the study population

Patientnumber

Sex Age Immunocompetentstatus

Anatomiclocalization

Duration ofsymptoms(mo)

Clinical features Treatment Follow-up

1 F 38 Immunosuppressed Rhino-orbitalLeft maxillaryLeft ethmoidLeft orbit

1 Maxillary pain,proptosis, pupildilation, restriction ofocular movements.Acute facial pain

Antrostromy,Cadwell Luc,ethmoidectomy,orbital exenteration,liposomalamphotericineBwith a total accumulativedose of 3 g,posaconazole 45 days

4 yearsfollow upNED

2 F 61 Immunosuppressed Left maxillarysinus

6 Headache, facial pain,purulent rhinorrhea,halitosis, cacosmia.

Caldwell Luc,endoscopic antrostomy,amphotericin B 750 mg

2.5 yearsfollow up,NED

3 M 54 Immunosuppressed Right maxillarysinus

NA Asymptomatic Caldwell LucPosaconazole

2 yearsfollow up,NED

4 F 46 Immunosuppressed Left maxillarysinus

28 Nasal obstruction,facial fullness, chronicrhinorrhea withposterior dischargeand cough.

Caldwell Luc 2 months

5 M 77 Immunocompetent Left maxillarysinus

NA Contralateral nasalmassRight Nasalobstruction, Left sideasymptomatic.

Resection ofcontralateral massLeft Caldwell Luc andendoscopic antrostomy

1 yearfollow up,NED

6 M 54 Immunocompetent Right maxillarysinus

8 Headache, cacosmia Caldwell Luc and endo-scopicantrostomy (CaldwellLuc a year after,no recurrence)

1.6 years,asymptomatic,NED

7 M 42 Immunocompetent Left maxillarysinus

24 Mucoid discharge,nasal obstruction,headache.

Caldwell Luc,endoscopic antrostomy

1 yearfollow up,NED

Abbreviations: F, female; M, male; mo, months; NA, none available; NED, no evidence of disease.

Fig. 1 Case 1. Chronic orbital mucormycosis. (A-D) Computed tomography scan shows intraorbital density, predominantly on the apex region.(E). Periodic acid-Schiff (PAS) stain showing mucormycosis with 90-degrees non-septated hyphae.


An Emergent Entity Celis-Aguilar et al.94

antrostomy. Regarding medical treatment, one immunosup-pressed subject received only amphotericin, and case onereceived both amphotericin and posaconazole. On the otherhand, posaconazole was the only treatment in one immu-nosuppressed patient. (See ►Table 1)

All immunocompetent patients had unilateral maxillarysinus involvement and received only surgical treatment,with resolution of the disease. The surgical findings in thesepatients were similar: black and abundant debris in themaxillary sinus. Two immunocompetent patients had signsof necrosis in the maxillary mucosa. Interestingly, only caseone had evident necrosis at nasal endoscopy.

Discussion

Mucormycosis refers to any fungal infectionbymembersof theorder mucorales, which is in the class zygomycetes. Mostpathogenic species are members of the family mucoraceae.1,8

It is currently known thatmucormycosis affectsmainly immu-nosuppressed individuals,16 especially uncontrolled diabeticpatientswithacidosis. Deferoxamine therapyand traumahavealso been described as risk factors.1,8,13,17 Furthermore,immunocompetent individuals arealsopronetothisdisease.18

Unfortunately, the previous literature has mainly describedthe fulminant course of this disease.

Chronic or indolent mucormycosis of the paranasalsinuses was described initially in 1964.19 Although thedisease is not universally known, over 30 cases have beendescribed in the literature.15,20 Interestingly, indolentmucormycosis can affect immunocompetent and immuno-suppressed individuals. Although, immunocompetent casesare associated with a less severe disease.7

On the other hand, chronic invasive fungal sinusitis hasgenerally been associated with the aspergillus species,10

reinforcing the concept that mucormycosis develops onlyinto an acute fulminant course. It is the objective of thispaper to describe the chronic presentation of mucormycosisand to show our experience in the treatment of both immu-nocompetent and immunosuppressed patients.

The definition of chronic mucormycosis has been con-troversial, since some authors acknowledge a period of onlyweeks,9,21,22while others consider it necessary the presenceof mucormycosis for at least 1 month.4 All the patients

Fig. 2 Case 2. (A and B) Computed tomography scan shows left maxillary sinus with heterogeneous density and osteitis. (C) Hematoxylin eosinstain (100x) and (D) Periodic acid-Schaff stain (400x) demonstrate respiratory epithelium with thick hyphae; at higher magnification,non-septated hyphae with right angles are confirmed (red arrow).

Fig. 3 Case 3. Pathology specimen shows edematous mucosa withlymphocyte and plasmatic cells infiltration. Abundant irregularhyphae were observed, with 15 to 30µm, broad with thin wall,non septated, with irregular ramifications filling blood vessels.

Fig. 4 Case 4. Computed tomography scan showing osteitis of maxillarywalls and occupation with heterogeneous density of left maxillary sinus.



included in our study had at least 1 month of suggestivemucormycosis infection.

Also, chronic mucormycosis has been associated withinternal carotid artery occlusion,9 although none of ourpatients developed this complication. One common clinical

feature we could find in most of our patients was thepresence of facial pain or headache. This could be a hallmarksymptom when faced with a patient with chronic paranasalsinus disease with evident CT scan sinus occupation. Someauthors5,23,24 also describe this pain frequently in their

Fig. 6 Case 6. (A) Computed tomography scan with total right maxillary sinus heterogeneous occupation. (B) Periodic acid-Schiff stain (400x)shows numerous thick hyphae semi-septated (yellow arrow) with 90-degrees angulation (red arrow) (C) Hematoxylin eosin stain (100x) showsabundant pauci-septated hyphae with right angles and necrosis. (D) Grocott Gomori stain (100X) shows abundant hyphae compatible withzygomycetes.

Fig. 5 Case 5. (A) Computed tomography scan demonstrates left maxillary sinus occupation. (B) Periodic acid-Schaff stain (100x): necrotictissue with mixed inflammatory cells and hyphae with diverse diameters non septated, with some showing 90-degrees angulation, compatiblewith mucor (red arrow). (C, D, E, F) Grocott Gomori stain (40x, 100x, 400x): abundant non-septated hyphae with 90-degree angulation; this stainwas highly positive on hyphae walls.



patients.6 In our study, only one patient had orbital apexsyndrome. This patient had middle turbinate necrosis, evi-dent at nasal endoscopy. Necrosis was seen in most of ourpatients during modified Caldwell-Luc procedure in max-illary mucosa, but no evidence of necrosis was seen onrhinoscopy or nasal endoscopy. This defies the currentknowledge that necrosis is usually seen at the physicalexploration of these patients. In our study, maxillary sinusdisease was the most common paranasal sinus involved,pointing to a more limited disease. Curiously, other authorshave described a more aggressive course with orbital apexsyndrome, cavernous sinus thrombosis4,21,22 and brainabscess.25 Although, on immunocompetent patients, thedisease has been more localized.5,10,26 Other authors havecorroborated single paranasal sinus disease on immunocom-petent patients.7,11,12,15,16 See ►Table 2 and 3 for a briefreview of the literature.

The CT scan in some of these cases may not have thetypical erosion of sinus wall. Mignogna et al and Ketenci et aldid not find erosion in the CT scans of their patients, onlysinus occupation. Erosion could not be considered a hallmarksign in chronic mucormycosis cases.

Among the immunosuppressed patients, case one beganwith a fulminantmucormycosis disease, only to progress to anindolent orbital course. During the patient’s hospitalization,efforts for orbital preservation led to continued observation inan otherwise stable patient; nonetheless, orbital apex diseaseprogressionwas seen on subsequent CTscans, with additionalmucormycosispathological confirmationultimately leading toorbital exenteration. It is possible that treatment with ampho-tericin B lead in fact to an indolent course in case number 1.only amphotericine treatment on iniatilly invasive mucormy-cosis cases with no surgery could lead to an indolent course.

Careful imaging follow-up is necessary, especially in cases oforbital disease. Also, a chronic orbital case treated with acourse of antifungals could erroneously lead a surgeon to dono further surgery, which, in fact, happened in this case,making it necessary first, an orbital biopsy and later, withthis being positive, an exenteration. Mutilation of a patient(exenteration) is a difficult decision. This article recommendsimmediate orbital exenteration in case of progressive orbitaldisease, only evident on CT scan.

Since this is an infrequent disease, no randomized controltrials are possible, and only case series are reported in theliterature.15 Therefore, there is controversy on the besttreatment available for this pathology. Some authors advo-cate a surgical and amphotericin B treatment,4,7,27,28 whileothers support only the surgical or medical treatment, suchas monotherapy.11,12 These patients, as many authors pointout, have different comorbidities that contraindicate eitherthe use of amphotericin or surgical treatment. Several casereports showed us that monotherapy is a viable treatmentwith good results.19,22 Additionally, many authors describe apersistent disease with a very slow progression that has noimpact on the quality of life of the patient.5,10,27,28

We agree with Tyson et al,5 Seung et al7 Jung H, et al11 andKetenci et al27 that an only surgical treatment in immuno-competent patients is possible. Interestingly, there has been arise in the reported cases of acute and chronic mucormyco-sis.1,2 This could mean an increased interest in publishingthese cases, more awareness of this disease with promptdiagnosis and treatment, or a real increment ofmucormycosiscases due to more diabetic or immunosuppressed patients. Apossible explanation to indolent mucormycosis in Mexico isthe tropicalweather andhigh temperatureof thisgeographicalarea, which could increase the risk of fungal infection. Other

Fig. 7 Case 7. (A) Computed tomography scan with left total maxillary sinus occupation. (B) Periodic acid-Schiff (PAS) stain (400x) showingspores and scant hyphae compatible with mucormycosis. (C) Hematoxylin eosin stain (400 x) showing inflammatory cells, spores and hyphaecompatible with mucor. Figure D and E show non-septated hyphae on PAS stain (100x).



Table

2Current

literatureon

indo

lent

muc

ormycos

isim

mun

osu

ppressed

patien

ts

Publication

Year

NSe

xAge

DX

Max

Ethm

Sph

OAS

Oth

erTime

(mo)

Clin

ical

features

Surg

sinus

EXAmph

oB

Follo

w-up

Ferstenfeld

25

(197

7)2

F M61 36

DM

DM

Y YY Y

N NN N

Y N1 0.5

Case1:

Feve

r,Pa

in,n

asalco

nge

stion,

exop

htha

lmos

,op

hthalmop

legia,

loss

ofvision

Case2:

Left

temporal

head

ache

andmaxillaryache

.Sw

ellin

gof

theleftside

offace,p

rotrusionleftof

the

left

eye.

Y YY N

Y YCase1:

Reco

verof

func

tiona

lcap

acity.

Case2:

Afebrile

,righ

tarm

wea

knessan

dseizures.

Finn

2

(198

2)2

F M82 58

RA

DM/

Lymph

oma

N YY N

Y NN N

N NCase1:

Periorbital

edem

a,ne

crotic

crust.

Case2:

Prop

tosis,

purulent

nasald

isch

arge

Y YN N

Y NCase1:

36mon

ths.

Nasal

cavity

remaine

dclea

nCase2:

12mon

ths

Norecu

rren

ceof

infection.

Doo

ley2

2

(199

2)1

M45

DM

NY

YY

N1.5

Orbital

Apex

Synd

rome.

YN

Y48

mon

ths.

Improve

doc

ular

mov

emen

t.

Harril,2

1

(199

6)2

F F46 66

DM

DM

Y NY N

Y YY Y

N NCase1:

8Case2:

1.5

Case1:

Ptos

isOphtha

lmop

legia,

intran

asal

mass

Case2:

Facial

pain,op

htha

lmop

legia

Y YN N

Y YCase1:

NED

,21

Months

Case2:

Diedof

unrelatedcause

Ruop

pi16

(200

1)2

F M62 72

Asthm

aDM

Y YN Y

N YN N

N NCase1:

0.6

Case2:

0.1

Case1:

Facial

pain,pu

rulentdischa

rge,

swellin

gin

therigh

tup

perging

ivaan

dpa

late.

Case2:

Facial

pain,co

njun

ctivitis,prop

tosisan

dch

emos

isof

theco

njunc

tiva

Y YN N

Y YCase1:

38mon

ths

Nofung

alinfectionha

soc

curred

.Case2:

37mon

ths.

Nosign

sof

recu

rren

ce.

Rumbo

ldt1

8

(200

2)1

M16

Leuk

emia

NN

YN

IC3

Feve

r,he

adache

,ch

anges

inthemen

talstatus

NN

Y3mon

ths.Only

biopsy.

Thelesion

continu

edto

grow

,an

dthepa

tien

tde

veloped

aninfarction

intheright

middle

cerebral

artery.

WaizelH

aiat

6

(200

3)1

M55

DM

YY

YY

N3

Left

palpeb

ralp

tosiswithincrea

sedvo

lume,

purulent

anterioran

dpo

steriordischa

rge.

YY

Y12

mon

ths.

Nosign

sof

recu

rren

ce.

Bertin

26

(200

3)1

m61

DM

YY

NN

NFacial

cellu

lite

NN

Y6months.

NED

orrecu

rren

ce.

Marin-

Men

dez4

(200

5)

2M M

70 72DM

DM

Y YY Y

Y YY N

N N1

Case1:

wea

kness,

nasalo

bstruction,

rhinorrhea

,OAS

Case2:

ptosis,

nasalo

bstruction,rhino

rrhe

a,OAS

Y YN Y

N YCase1:

Reco

very

ofey

emov

emen

tCase2:

Cav

erno

ussinu

sthrombo

sis,

dece

ased

.

Odessey2

4

(200

8)1

M64

DM

AR

YN

NN

NSe

veral

days

Frontal

head

ache

,righ

tpe

riorbital

pain,diplopia,

numbne

ssan

drigh

tfacial

wea

kness

YN

YNone

spec

ified

.Despite

improv

emen

tin

facial

symmetry

and

ocular

symptom

s.

Kim

7

(201

3)1

F56

DM

YN

NN

NSe

veral

mon

ths

Seve

rena

salo

bstructionwithfacial

tend

erne

ssY

NY

19mon

ths.

Noev

iden

ceof

infectionor

recu

rren

ce

Texeira3

(201

3)1

F46

DM

NY

NY

N24

Right

side

periorbitalan

dde

ficitof

II,III,IV,V

,VIa

ndVIIcran

ialn

erve

s.Y

YY

9years.Asymptom

atican

dwithou

tev

iden

ceof

diseaserecu

rren

ce.

Jung

11

2013

1F

67DM

YN

NN

N36

Foul

odor,po

stna

sald

rip.

YN

N10

mon

ths

Dim

aka8

(201

4)1

M82

DM

YY

YN

N6

Purulent

andod

orou

sna

sald

isch

arge,

epistaxis,

anos

mia

NN

Y42

mon

ths

Still

alivean

drelative

lywell.

Gutierrez-

Delga

do9

(201

6)

1M

47DM

YN

NN

N3

Paresthe

sia,

pain

andsw

ellin

gin

theleft

zygo

matic

bone

YN

Y4months.

NED

orrecu

rren

ce

Abbrev

iation

s:Amph

oB,

ampho

tericinB;

RA,rhe

umatoidarthritis;

DM,d

iabetes

mellitus

;DX,d

iagn

osis;E

thm,e

thmoidsinu

s;EX

,exe

nteration;

F,female;

M,m

ale;

Max,m

axillarysinu

s;MCI,middlece

rebral

infarction

;mo,

mon

ths;

N,no

ne;NED

,no

eviden

ceof

disease;

OAS,

orbitala

pexsynd

rome;

Sph,

sphe

noid

sinu

s;Sinu

ssurg,sinu

ssurgery;

Y,ye

s.



Table

3Current

literatureon

indo

lent

muc

ormycos

is:immun

ological

competen

tpa

tien

ts

Public

ation

Year

nSe

xAge

Prev

DX

Max

Ethm

Sph

OAS

Other

Time(m

o)Clin

ical

Features

Sinu

ssu

rgEX

Amph

oB

Follo

w-up

Tyso

n5

(199

2)1

F26

No

YY

NN

N48

Nasal

obstruction,

muc

oiddischa

rge,

left

facial

pain

andpressu

reY

NY

Sheha

sbe

enfree

ofdiseaseformorethan

36mon

thspo

stop

eratively

Del

Valle28

(199

6)1

M54

No

NN

YN

N0.75

days

before

interven

tion.

Seve

releft

temporal

head

ache

,the

patien

twas

healthyun

tilthisacute

episod

e.

YN

Y12

mon

ths.

Exam

inations

andbiopsies

have

show

nto

befree

ofdisease.

Ketenc

i27

(200

5)1

F63

No

NN

YN

N3

Seve

rehe

adache

YN

N6mon

ths

Biopsyan

dCTscan

show

edno

recu

rren

ce.

Virk1

0

(200

7)1

M40

No

YY

YN

N24

Nasal

obstruction,

proptosis,

diplopia.

YN

YNot

spec

ified

Free

ofdiseaseon

regu

laren

dos

copic

follo

w-up.

Migno

gna

(201

1)15

5M

67RP

CY

NY

NN

0.5–

1Case1:

Chron

icbilateralo

rofacial

pain

andfeve

rN

NY

6mon

ths

M46

No

YN

NN

N0.5–

1Case2:

respiratorydistress,feve

rN

NY

24mon

ths

M47

BPH

YN

NN

N0.5–

1Case3:

acutediplopia,

orbital

pain

NN

Y60

mon

ths

M54

No

YN

NN

N0.5–

1Case4:

rhinorrhea

,facial

pain

NN

Y14

mon

ths

F53

No

YN

NN

Y Erosion

oforbit

.5–1

Case5:

rhinorrhea

,he

adac

he,o

rbital

pain

NN

Y20

mon

ths

Jung

11

(201

3)4

F67

No

YN

NN

N5

Case1:

Foul

odor,p

ostna

sald

rip,n

asal

stuffine

ssY

NN

17mon

ths

M60

No

YN

NN

N4

Case2:

Stuffine

ss,po

stna

sald

rip

YN

N24

mon

ths

F68

No

YN

NN

N4

Case3:

Foul

odor,p

ostna

sald

rip,n

asal

stuffine

ssY

NN

12mon

ths

Therewas

norecu

rren

cein

anypa

tien

t.

Jad1

2

(201

5)1

F34

No

YY

YN

N2

Hea

dach

e,bloc

kageof

left

nasal

cavity,ch

ange

sin

voice.

(sim

ilarev

entayear

ago)

NN

N3mon

ths

trea

tmen

twithfluc

onazole.

After

3mon

ths,

theCTscan

was

repea

tedan

dfoun

dto

beno

rmal.

Wolko

w13

(201

7)1

F74

No

YY

YY

N1

Feve

r,ch

ills,

left

facial

pain,a

ndleftpe

riorbitale

rythem

aan

ded

ema.

YN

Y4mon

ths

Lesions

recu

rred

,acco

mpa

nied

byspon

tane

ous

draina

geof

purulent

fluid.

Hem

ashe

ttar

14

(201

1)1

M18

No

NN

NN

Nose

Facial

skin

144

Ulcerativelesion

ontheno

sean

dpa

late

NN

NDeb

ridem

entan

dfluc

onazole.

6mon

thsfollo

w-up.

Thewoun

dhe

aled

butlaterthepa

tien

twas

lost

tofollo

w-up.

Abbrev

iation

s:Amph

oB,

amph

otericin

B;BP

H,b

enignpros

tatichy

pertrophy

;;Ethm

,ethmoidsinu

s;EX

,exenteration;

F,female,

M,m

ale;

Max,m

axillarysinu

s;mo,

mon

ths;N,n

one;

OAS,

orbitalape

xsynd

rome;

Prev

DX,prev

ious

diag

nosis;

RPC

,rhinoph

aryn

geal

canc

er;Sp

h,sphe

noid

sinu

s;Sinu

ssurg,sinu

ssurgery;

Y,ye

s.



authorshavehypothesizedthatchronic sinusitis couldbea riskfactor for this fungal infection.15

In contrast to acute fulminant invasive sinusitis, chronicmucormycosis could have better survival. In a recent sys-tematic review,20 only half of the patients with acute fulmi-nant disease survived, with diabetic patients having betterprognosis than patients with other comorbidities. Chronicmucormycosis, at least in our series, had a 100% survival rate.Other authors support this improvement in survival, espe-cially in immunocompetent patients.5,10,11,24,27

Differential diagnosis of this disease should be kept inmind, such as neoplasms, bacterial sinusitis, granulomatousdisorders, cavernous sinus thrombosis, pseudotumors, etc.9

The limitations of this study are mainly the lack ofmucormycosis cultures. Nonetheless, the characteristicbroad non-septated hyphae with right angle branchingusually suffices for diagnosis. Since this is an emerging entity,we are confident that new studies could confirm our resultsand shed new light on this disease.

The strengths of this study are the high number of patientsincluded, in contrast to what has been previously published,the longer follow-up and the fact that it is amulticenter study.

Finally, indolent mucormycosis is a differential diagnosisin patients with facial pain or headache, mucoid discharge,cacosmia with a paranasal sinus occupation on CT scan inimmunosuppressed and immunocompetent individuals.

Conclusion

Indolent mucormycosis is a new and emerging clinical entityin immunosuppressed and immunocompetent patients. Sin-gle paranasal sinus disease is a frequent presentation andshould not be overlooked as a differential diagnosis in thesepatients. Immunocompetent patients should only be treatedsurgically. More studies are needed to confirm our results.

References1 Ibrahim AS, Kontoyiannis DP. Update on mucormycosis patho-

genesis. Curr Opin Infect Dis 2013;26(06):508–5152 FinnDG, Farmer JC Jr. Chronicmucormycosis. Laryngoscope 1982;

92(7 Pt 1):761–7663 Teixeira CA, Medeiros PB, Leushner P, Almeida F . Rhinocerebral

mucormycosis: literature review apropos of a rare entity. BJMCase Rep 2013. Doi: 10.1136/bcr-2013-008552https://www.ncbi.nlm.nih.gov/pubmed/23389725

4 Marin-Mendez H. Monroy- Aguirre D, Rodríguez- Perales M.Caretta-Barradas Sergio. Síndrome de ápex orbitario causadopor mucormicosis orbito cerebral crónica e indolente: reportede dos casos. An Orl Mex 2005;50:64–68

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an emergent entity: indolent mucormycosis of the paranasal … · erika celis-aguilar1 alan...

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