AFRS: Current Approaches to Postoperative Management Bradley F. Marple, MD Professor Dept. of...

AFRS: Current AFRS: Current Approaches to Approaches to Postoperative Postoperative ManagementManagement

Bradley F. Marple, MDBradley F. Marple, MD

ProfessorProfessor

Dept. of OtolaryngologyDept. of OtolaryngologyUniv. of Texas Southwestern at DallasUniv. of Texas Southwestern at Dallas

Potential Role for Potential Role for Fungus in CRSFungus in CRS

Allergic Fungal RhinosinusitisAllergic Fungal Rhinosinusitis

SaprophyteSaprophyte EFRSEFRS

•Fungus•Fungal allergy•Invasive Fungus

•Fulminant•Indolent•Granulomatous

•Non-invasive fungus•Mycetoma•Saprophytic growth•AFRS•EFRS

•Fungus•Fungal allergy•Invasive Fungus

•Fulminant•Indolent•Granulomatous

•Non-invasive fungus•Mycetoma•Saprophytic growth•AFRS•EFRS

Marple, Laryngoscope 2001;111:1006-19.Marple, Laryngoscope 2001;111:1006-19.

Clinical Observations Concerning AFRS

Clinical Observations Concerning AFRS

Radiographic Radiographic Characteristics:Characteristics:Bone ErosionBone Erosion

Radiographic Radiographic Characteristics:Characteristics:Bone ErosionBone Erosion

CTCT11

Allergic mucin mucoceleAllergic mucin mucocele Associated obstructive Associated obstructive

sinusitissinusitis Heterogeneous Heterogeneous

appearanceappearance33

CaCa Chelated Fe, MnChelated Fe, Mn

MukherjiMukherji11

Reviewed 45 AFRS CTsReviewed 45 AFRS CTs Bone erosion - 20%Bone erosion - 20%

Nussenbaum, MarpleNussenbaum, Marple22

Reviewed 142 AFRS CTsReviewed 142 AFRS CTs Bone erosion - 20%Bone erosion - 20% Histology - 0/142 Histology - 0/142

demonstrated invasiondemonstrated invasion11Radiology Radiology 1998; 207:417-221998; 207:417-2222OtoOto HNSHNS 2001;124:150-54 2001;124:150-5433Zinreich et al. Radiology 1988; 169:439-44.

Clinical Presentation: Clinical Presentation: MucinMucin

Mucin is the hallmark of the diseaseMucin is the hallmark of the disease

Allergic MucinAllergic Mucin Gross findings - Gross findings -

indistinguishable indistinguishable from ABPAfrom ABPA Thick viscosityThick viscosity Tan, black, greenTan, black, green

HistologyHistology Non-invasive fungusNon-invasive fungus

GrocottGrocott GiemsaGiemsa PASPAS

EosiniphilsEosiniphils Charcot-Leyden CrxCharcot-Leyden Crx

Diagnostic CriteriaDiagnostic Criteria

CodyCody AllphinAllphin Lowry, SchaeferLowry, Schaefer deShazo, SwaindeShazo, Swain

Bent and KuhnBent and Kuhn PolyposisPolyposis CT findingsCT findings Eosinophilic mucus; Eosinophilic mucus;

no fungal invasionno fungal invasion Gell & Coombs type I Gell & Coombs type I

hypersensitivity hypersensitivity JACI, Oto-HNS 2004JACI, Oto-HNS 2004

Eosinophilic mucinEosinophilic mucin Histo – non invasive Histo – non invasive

fungusfungus Fungal specific IgEFungal specific IgE

Bent, Kuhn, Oto-HNS 1994;111:580-88Meltzer, Hamilos, Hadley, Lanza, Marple, et. al. JACI 2004;114:S155-S212.Bent, Kuhn, Oto-HNS 1994;111:580-88Meltzer, Hamilos, Hadley, Lanza, Marple, et. al. JACI 2004;114:S155-S212.

Eosinophilic Fungal Rhinosinusitis

Eosinophilic Fungal Rhinosinusitis

Mayo Experience – Mayo Experience – Evolution of a PathogenesisEvolution of a Pathogenesis

Ponikau – Improved ability Ponikau – Improved ability to identify nasal fungusto identify nasal fungus 94/101 clinical diagnosis of 94/101 clinical diagnosis of

AFSAFS 100% controls with 100% controls with

fungusfungus Allergy – no difference Allergy – no difference

from general CRS from general CRS populationpopulation

Proposed term “EFRS”Proposed term “EFRS” Shin, Kita – PBMC + Shin, Kita – PBMC +

AlternariaAlternaria IL-5, IL-13, IF-IL-5, IL-13, IF-

Taylor – Fluorescein-Taylor – Fluorescein-labeled chitin stainlabeled chitin stain

Wei – Chemotaxis of Wei – Chemotaxis of eosinophils in presence of eosinophils in presence of tissue/mucin of CRStissue/mucin of CRS Demonstrates Demonstrates

chemoattractant effectschemoattractant effects Ponikau – Ampho B Ponikau – Ampho B

irrigationirrigation 38/51 symptoms improved38/51 symptoms improved

45 with prior surgery45 with prior surgery 35% endoscopically 35% endoscopically

clearedcleared No control group No control group

Ponikau. Mayo Clin Pro. 1999;74:877-84.Shin. JACI (abstract). Shin SH, Kita H et al . AAAAI NY, March 6, 2002Taylor. Oto-HNS 2002;127:377-383.Wei. Laryngoscope 2003;113:303-306.Ponikau. JACI 2002;110:862-866

Ponikau. Mayo Clin Pro. 1999;74:877-84.Shin. JACI (abstract). Shin SH, Kita H et al . AAAAI NY, March 6, 2002Taylor. Oto-HNS 2002;127:377-383.Wei. Laryngoscope 2003;113:303-306.Ponikau. JACI 2002;110:862-866

Why the Difference?Why the Difference?What are we calling What are we calling

“mucin”?“mucin”?

Chitin

GMS

GMS

EFRS AFRS

GMS

Courtesy of Ponikau

Impact of Clinical Findings Impact of Clinical Findings upon Immunologic Dataupon Immunologic Data

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Total IgE Skin test History

Total

Mayo '99

8787

6767

179179

2020

179179

Marple, presented Maryland CRS meeting 2003

AFRS vs EFRS: Why the AFRS vs EFRS: Why the Difference?Difference?

AFRSAFRS EFRSEFRS

Patient selection Patient selection NarrowNarrow Broad Broad Definition of allergic mucinDefinition of allergic mucin GrossGross MicroscopicMicroscopicIncidence of atopyIncidence of atopy Near 100%Near 100% Same as CRSSame as CRSSpecificity vs sensitivitySpecificity vs sensitivity Too specificToo specific Too sensitiveToo sensitive

Marple, ARS Newsletter 2002;21Marple, ARS Newsletter 2002;21

Fungal Specific Humoral Fungal Specific Humoral ResponseResponse

BackgroundBackground Literature to 2004: Literature to 2004:

Fungal allergy plays central role in Fungal allergy plays central role in pathogenesis of AFRSpathogenesis of AFRS

Fungal specific IgE is a critical marker for Fungal specific IgE is a critical marker for AFRSAFRS

Inconsistent definitions for AFRSInconsistent definitions for AFRS Pant/WormaldPant/Wormald

Sub-classified CRS in an attempt to better Sub-classified CRS in an attempt to better understand the role of humoral responses in understand the role of humoral responses in the pathogenesis of the disease the pathogenesis of the disease

Pant H, Laryngoscope 2005;115:601-606.Pant H, Laryngoscope 2005;115:601-606.


DesignDesign 86 study subjects were enrolled86 study subjects were enrolled

Sub-classified based upon following criteriaSub-classified based upon following criteria Presence of macroscopic eosinophilic mucinPresence of macroscopic eosinophilic mucin Presence of fungal allergyPresence of fungal allergy Histologic presence of fungi in eosinophiloc Histologic presence of fungi in eosinophiloc

mucinmucin Cultures obtained from mucinCultures obtained from mucin Serologic testsSerologic tests

Fungal specific IgEFungal specific IgE Fungal specific IgG, IgM, IgAFungal specific IgG, IgM, IgA

Pant H, Laryngoscope 2005;115:601-606.Pant H, Laryngoscope 2005;115:601-606.


spIgE (spIgE (Alternaria Alternaria alternata alternata and and Aspergillus Aspergillus fumagatusfumagatus) failed to ) failed to differentiatedifferentiate EMCRS from controlsEMCRS from controls Subsets within Subsets within

EMCRSEMCRS Culture results only Culture results only

partially matched partially matched those spIgEthose spIgE

Pant H, Laryngoscope 2005;115:601-606Pant H, Laryngoscope 2005;115:601-606


ResultsResults Alternaria alternataAlternaria alternata

and and Aspergillus Aspergillus fumigatusfumigatus IgG3 IgG3 marked the presence marked the presence of EM (p=0.002, 0.004)of EM (p=0.002, 0.004)

spIgG3 spIgG3 Distinguished EMCRS Distinguished EMCRS

from all other controlsfrom all other controls May signify pathogenic May signify pathogenic

significance of IgG3significance of IgG3

Pant H, Laryngoscope 2005;115:601-606Pant H, Laryngoscope 2005;115:601-606

Alternaria spIgG3

Types of Fungal SinusitisTypes of Fungal Sinusitis

InvasiveInvasive FulminantFulminant IndolentIndolent

GranulomatousGranulomatous Non-Non-

granulomatousgranulomatous

Non-invasiveNon-invasive Fungal Ball Fungal Ball

(Mycetoma)(Mycetoma) Saprophytic growthSaprophytic growth Eosinophilic Fungal Eosinophilic Fungal

InflammationInflammation IgE – dependent IgE – dependent

fungal inflammationfungal inflammation Classic AFRSClassic AFRS

Non IgE-dependent Non IgE-dependent fungal rhinosinusitisfungal rhinosinusitis

Eosinophilic Eosinophilic Fungal Fungal Rhinosinusitis Rhinosinusitis (EFRS)(EFRS)

Meltzer, Hamilos, Hadley, Lanza, Marple, et. al. Rhinosinusitis: Establishing Definitions for Clinical Research and Patient Care JACI 2004;114:155-212.

Meltzer, Hamilos, Hadley, Lanza, Marple, et. al. Rhinosinusitis: Establishing Definitions for Clinical Research and Patient Care JACI 2004;114:155-212.

2006: Role of Fungus and 2006: Role of Fungus and Allergy in AFRSAllergy in AFRS

AFRS is a distinct clinical entity that exists AFRS is a distinct clinical entity that exists as a subset of CRS and is strongly associated as a subset of CRS and is strongly associated withwith FungusFungus AllergyAllergy

The central role of allergy in the The central role of allergy in the pathogenesis of AFS is now in questionpathogenesis of AFS is now in question But IgE-mediated sensitivity remains important But IgE-mediated sensitivity remains important

identifieridentifier It is reasonable to direct therapy based upon It is reasonable to direct therapy based upon

the presence of allergy and fungusthe presence of allergy and fungus Evidence-based data is limitedEvidence-based data is limited

AFRS: TreatmentAFRS: TreatmentFungusFungus

ProliferationProliferationAntigen ExposureAntigen Exposure

Immune ResponseImmune ResponseIgE/non-IgEIgE/non-IgE

Mast Cell DegranulationMast Cell DegranulationMucosal EdemaMucosal Edema

InflammationInflammation

Decreased DrainageDecreased DrainageDecreased VentilationDecreased Ventilation

Stasis (Mucin)Stasis (Mucin)

SurgerySurgery Complete removal of Complete removal of

fungal antigenfungal antigen Tissue sparingTissue sparing

ImmunomodulationImmunomodulation Perioperative steroidsPerioperative steroids ImmunotherapyImmunotherapy

Close follow-upClose follow-up Saline irrigationSaline irrigation Office visitsOffice visits

AFSAFS

SurgerySurgery IrrigationIrrigation

ImmunotherapyImmunotherapySteroidsSteroids

AntifungalsAntifungals

Marple,Mabry, AJR 1998:12;263-268Marple,Mabry, AJR 1998:12;263-268

Treatment PrinciplesTreatment Principles

I. Elimination of Fungal Antigen (Surgery)

II. Control of Recurrence

Immunomodulation Antifungal Rx

IT Steroids Topical Systemic





Marple, Laryngoscope 2001;111:1006-19.Marple, Laryngoscope 2001;111:1006-19.

Goals of SurgeryGoals of Surgery

Complete Complete extirpation of extirpation of mucin mucin Fungi stimulate Fungi stimulate

inflammationinflammation

Permanent Permanent drainage & drainage & ventilationventilation Preserve mucosaPreserve mucosa ““Complete, but Complete, but

conservative”conservative”

Post-operative Post-operative accessaccess SurveillanceSurveillance

IrrigationIrrigation

Marple,Mabry, AJR 1998:12;263-268Marple,Mabry, AJR 1998:12;263-268

Postoperative RecidivismPostoperative Recidivism

Bent - Near 100% recurrence in absence of medical Bent - Near 100% recurrence in absence of medical treatmenttreatment

Kupferberg - 19/24 patients recurred after d/c of Kupferberg - 19/24 patients recurred after d/c of steroidssteroids

Schubert - 67ptsSchubert - 67pts

Steroids for >2 mo. - 35% recurrence @ 1yrSteroids for >2 mo. - 35% recurrence @ 1yr

Steroids for <2 mo. - 55% recurrence @ 1yrSteroids for <2 mo. - 55% recurrence @ 1yr

Marple, Mabry - 42pts Marple, Mabry - 42pts

Immunotherapy - 10% recurrence @ 12 - 37 mo.Immunotherapy - 10% recurrence @ 12 - 37 mo.Allergy Asthma Proc 1996;17:259-68, Allergy Asthma Proc 1996;17:259-68, Oto-HNS 1997;117:35-41, Oto-HNS 1997;117:35-41, J Allergy Clin Immunol1998;102:395-402, J Allergy Clin Immunol1998;102:395-402, Am J Rhinology 2000;14:223-26Am J Rhinology 2000;14:223-26

Immunotherapy for AFS: Immunotherapy for AFS: TheoryTheory

Originally contraindicatedOriginally contraindicated Analogies to ABPAAnalogies to ABPA Theoretically contraindicated in treatment of Theoretically contraindicated in treatment of

ABPA “because of the uncertainties involved”ABPA “because of the uncertainties involved”11

Specific IgG production may elicit immune complex Specific IgG production may elicit immune complex reaction (G&C III)reaction (G&C III)

FergusonFerguson22 - concluded no effect - concluded no effect 7 AFS patients7 AFS patients

2 responded (surgery)2 responded (surgery) 5 no response5 no response

11Middleton & Reed, pp.1395-1414, 1993.Middleton & Reed, pp.1395-1414, 1993.22Ferguson, Abstract AAOA, 1993.Ferguson, Abstract AAOA, 1993.

Could IT be used as a Could IT be used as a part of a comprehensive part of a comprehensive

plan?plan? SurgerySurgery

Remove antigenic Remove antigenic load!load!

Allergic evaluationAllergic evaluation RAST (or skin test)RAST (or skin test)

3 most relevant fungal 3 most relevant fungal antigensantigens

Non-fungal antigensNon-fungal antigens

Skin test (or RAST) Skin test (or RAST) for additional fungifor additional fungi

Allergy treatmentAllergy treatment Treat for all Treat for all

positive reactorspositive reactors Do notDo not treat only treat only

cultured funguscultured fungus Treat non-fungal Treat non-fungal

reactive antigensreactive antigens

Mabry, Marple, Mabry Oto-HNS 1999;121:252-4Mabry, Marple, Mabry Oto-HNS 1999;121:252-4

Treatment of AFS: a comparison Treatment of AFS: a comparison trial of postoperative IT with trial of postoperative IT with

specific fungal antigensspecific fungal antigens11

Cross-sectional Cross-sectional study of 22 AFS study of 22 AFS ptspts 2 groups matched 2 groups matched

for preop severity for preop severity of disease (CT&PE)of disease (CT&PE)

Similar surgerySimilar surgery 11 tx’d with IT11 tx’d with IT 11 no IT11 no IT

11Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998

EvaluationEvaluation Regular exam and Regular exam and

endoscopic staging endoscopic staging (Kupferberg)(Kupferberg)

Chronic Sinusitis Chronic Sinusitis Survey (Glichlick & Survey (Glichlick & Metson)Metson)

Treatment of AFS: a comparison Treatment of AFS: a comparison trial of postoperative IT with trial of postoperative IT with

specific fungal antigensspecific fungal antigens11

Follow-upFollow-up Overall mean f/u Overall mean f/u

33 mos.33 mos. IT group IT group

Mean - 30 mos.Mean - 30 mos. Range - 12-43 mos.Range - 12-43 mos.

Non-IT groupNon-IT group Mean - 35 mos.Mean - 35 mos. Range - 12-50 mos.Range - 12-50 mos.

11Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998

CorticosteroidsCorticosteroids IT groupIT group

Systemic - 0%Systemic - 0%

Non-IT groupNon-IT group Systemic - averaged Systemic - averaged

2 courses per year2 courses per year

Endoscopic Mucosal Endoscopic Mucosal StagingStaging

Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998

0

2

4

6

8

10

Stage 0 Stage 1 Stage II Stage III

ITControl

P<0.02

Chronic Sinusitis SurveyChronic Sinusitis Survey

Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998Folker, Marple, Mabry, Mabry, Laryngoscope 108:1623-27, 1998

71

49

0

10

20

30

40

50

60

70

80

CSS Score

IT Control

p<0.05


I. Elimination of Fungal AntigenElimination of Fungal Antigen (Surgery)(Surgery)

II. Control of RecurrenceII. Control of Recurrence

ImmunomodulationImmunomodulation Antifungal R Antifungal Rxx

IT IT SteroidsSteroids Topical Systemic Topical Systemic

I. Elimination of Fungal AntigenElimination of Fungal Antigen (Surgery)(Surgery)

II. Control of RecurrenceII. Control of Recurrence

ImmunomodulationImmunomodulation Antifungal R Antifungal Rxx

IT IT SteroidsSteroids Topical Systemic Topical Systemic

Corticosteroids: Corticosteroids: RationaleRationale

Concept Concept originates from originates from the treatment of the treatment of ABPAABPA Anti-inflammatoryAnti-inflammatory ImmunomodulationImmunomodulation

Systemic Systemic Used in some form Used in some form

for all patients with for all patients with AFSAFS

Topical Topical Standard therapyStandard therapy No published No published

evidence of effect evidence of effect in AFSin AFS

Effect demonstrated Effect demonstrated in NPin NP

CorticosteroidsCorticosteroids

BentBent11 Universal Universal

recurrence of AFS recurrence of AFS in following in following discontinuation of discontinuation of corticosteroidscorticosteroids

SchubertSchubert22 - 67 pts - 67 pts Corticosteroids < 2moCorticosteroids < 2mo

55% recurrence at 1yr55% recurrence at 1yr Shorter time to Shorter time to

recurrencerecurrence Higher total IgEHigher total IgE

Corticosteroids > 2moCorticosteroids > 2mo 35% recurrence at 1yr35% recurrence at 1yr Longer time to Longer time to

recurrencerecurrence Lower total IgELower total IgE

11Bent, Kuhn, Allergy Asthma Proc 17:259-68, 1996Bent, Kuhn, Allergy Asthma Proc 17:259-68, 199622Schubert, Goetz, J Allergy Clin Immun 103:395-402, 1998Schubert, Goetz, J Allergy Clin Immun 103:395-402, 1998

Systemic Antifungals Systemic Antifungals DenningDenning

Use of itraconazole for ABPAUse of itraconazole for ABPA Decrease in total IgEDecrease in total IgE Decrease in systemic corticosteroid useDecrease in systemic corticosteroid use

FergusonFerguson Limited available dataLimited available data Potential drug related morbidityPotential drug related morbidity Cost of treatmentCost of treatment

Rains Rains Safety of itraconazoleSafety of itraconazole

KennedyKennedy Terbenifine offered no benefit to the treatment Terbenifine offered no benefit to the treatment

of CRSof CRS11Denning, et al, Chest 100:813-19, 1991Denning, et al, Chest 100:813-19, 199122Ferguson, Arch Otolaryngol Head Neck Surg 124:1174-77, 1998Ferguson, Arch Otolaryngol Head Neck Surg 124:1174-77, 1998

May limitMay limitusefulness ofusefulness of

therapytherapy

Systemic AntifungalsSystemic Antifungals Alternate effect of antifungalsAlternate effect of antifungals

Kanda et.alKanda et.al CDCD33/CD/CD2828 cells from atopic derm and cells from atopic derm and

controlscontrols In vitro T-cell helper-1 (TIn vitro T-cell helper-1 (THH1) and T-cell 1) and T-cell

helper-2 (Thelper-2 (THH2) cytokines studied in 2) cytokines studied in response to antimycoticsresponse to antimycotics

ResultsResults Azole derivatives suppressed expression of Azole derivatives suppressed expression of

IL-4 and IL-5 by reducing 3,5 cAMP signal IL-4 and IL-5 by reducing 3,5 cAMP signal

Kanda N. Journal of Investigative Dermatology. 117(6):1635-46, 2001 Dec.

Topical AntifungalsTopical Antifungals Test of fungal hypothesisTest of fungal hypothesis

MethodsMethods Double blind placebo Double blind placebo

controlledcontrolled 24 CRS subjects randomized24 CRS subjects randomized

Ampho B irrigation - 10Ampho B irrigation - 10 Saline control - 14Saline control - 14

ResultsResults CT scoresCT scores SNOT – 20 – no sig changeSNOT – 20 – no sig change Endoscopy (7/10, 5/14)Endoscopy (7/10, 5/14) IL-5 – no sig changeIL-5 – no sig change Eosinophils – no sig changeEosinophils – no sig change Alternaria – no changeAlternaria – no change

Conclusion – Ampho B Conclusion – Ampho B worksworks

Ponikau, et al. JACI 2005;115:125-31.

StratificationStratificationIssuesIssues

AlternariaAlternaria No change over 6 No change over 6

monthsmonths Does this support Does this support

hypothesis?hypothesis? Stratification IssuesStratification Issues

DemographicsDemographics Inflammatory Inflammatory

MediatorsMediators EDNEDN IL-5IL-5

Ponikau, et al. JACI 2005;115:125-31

Topical AntifungalsTopical Antifungals Test of fungal Test of fungal

hypothesishypothesis MethodsMethods

Double blind placebo Double blind placebo controlledcontrolled

74 CRS subjects 74 CRS subjects randomizedrandomized

Ampho B sprayAmpho B spray Saline controlSaline control

ResultsResults 60 completed the study60 completed the study

Conclusion – no effectConclusion – no effect

Controversy in delivery Controversy in delivery

Weshta, et al. JACI 2004;113:1122-28.

Recidivism after Recidivism after treatmenttreatment

Bent - Near 100% recurrence in absence of medical Bent - Near 100% recurrence in absence of medical treatmenttreatment

Kupferberg - 19/24 patients recurred after d/c of Kupferberg - 19/24 patients recurred after d/c of steroidssteroids

Schubert - 67ptsSchubert - 67ptsSteroids for >2 mo. - 35% recurrence @ 1yrSteroids for >2 mo. - 35% recurrence @ 1yrSteroids for <2 mo. - 55% recurrence @ 1yrSteroids for <2 mo. - 55% recurrence @ 1yr

Marple, Mabry - 42pts Marple, Mabry - 42pts Immunotherapy - 10% recurrence @ 12 - 37 mo.Immunotherapy - 10% recurrence @ 12 - 37 mo.

Marple, Newcomer - 17pts followed 4 - 11yrs.Marple, Newcomer - 17pts followed 4 - 11yrs.1/17 with recurrence of AFS1/17 with recurrence of AFSNo decrease in fungal IgENo decrease in fungal IgENo difference in treatment armsNo difference in treatment arms

Allergy Asthma Proc 1996;17:259-68, Allergy Asthma Proc 1996;17:259-68, Oto-HNS 1997;117:35-41, Oto-HNS 1997;117:35-41, J Allergy Clin Immunol1998;102:395-402, J Allergy Clin Immunol1998;102:395-402, Am J Rhinology 2000;14:223-26Am J Rhinology 2000;14:223-26Oto-HNS: 2002 Oto-HNS: 2002 127(5) 361-6127(5) 361-6

Elimination of Fungal Antigen

Control of Recurrence



Elimination of Fungal Antigen

Control of Recurrence



ConclusionConclusion

AFS remains AFS remains intriguingintriguing Subset of CRSSubset of CRS SurgerySurgery

Crucial part of Crucial part of treatmenttreatment

Medical follow-up Medical follow-up appears crucial to appears crucial to long-term successlong-term success

Need for evidence-Need for evidence-based studiesbased studies

AFRS: Current Approaches to Postoperative Management Bradley F. Marple, MD Professor Dept. of...

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