Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause...

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Fungal rhinosinusitis: classification, diagnosis & treatment Arunaloke Chakrabarti Professor & Head Center for Advanced Research in Medical Mycology & WHO Collaborating Center Department of Medical Microbiology Department of Medical Microbiology Postgraduate Institute of Medical Education & Research Chandigarh – 160012, India

Transcript of Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause...

Page 1: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Fungal rhinosinusitis:classification, diagnosis & treatment

Arunaloke ChakrabartiProfessor & Head

Center for Advanced Research in Medical Mycology& WHO Collaborating Center

Department of Medical MicrobiologyPostgraduate Institute of Medical Education & Research

Chandigarh – 160012, India

Arunaloke ChakrabartiProfessor & Head

Center for Advanced Research in Medical Mycology& WHO Collaborating Center

Department of Medical MicrobiologyPostgraduate Institute of Medical Education & Research

Chandigarh – 160012, India

Page 2: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Rhinosinusitis – fungus as a cause

• Rhinosinusitis – inflammation of nose & sinuses

• Course – may be acute or chronic

• CRS affects 12.5% population some time in their life

• Fungus as etiology – Provocative statements

• Rhinosinusitis – inflammation of nose & sinuses

• Course – may be acute or chronic

• CRS affects 12.5% population some time in their life

• Fungus as etiology – Provocative statements

o ‘A small portion of CRS is due to fungi’ - Marple

o ‘All CRS cases are due to fungi’ – Ponikau

oThen, 1.4 billion people suffer from FRS

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While the debate continues, let ussee situation in India

While the debate continues, let ussee situation in India

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Fungal rhinosinusitis in India

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Prevalence study in north Indian villages

• Symptoms & signs >12 weeks, at least 1 major & 1 minor• Major: facial pain/pressure, facial congestion/fullness, nasal

obstruction/blockage, nasal discharge/purulence/post-nasal drip• Minor: headache, fever, fatigue, dental pain, cough, ear pain/pressure

Chakrabarti A, et al. Mycoses 2015, March 10 (Epub)

Chandigarh

DelhiWe also did environmental survey for Aspergillus conidia

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Prevalence study in north Indian villages

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• Point prevalenceo 1.4% young adult suffer from CRS

• Prevalence of FRS –

o 0.11% of population

o 8.1% of all cases of CRS

• Point prevalenceo 1.4% young adult suffer from CRS

• Prevalence of FRS –

o 0.11% of population

o 8.1% of all cases of CRS

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Fungal conidia in air in north Indian villages

95.15138.14

213.9

73.8

102.16

30.36

130.2

192

0

50

100

150

200

250

post monsoon winter summer monsoon

Total Spore Count

9

32.3

10.786.2

13.2

4.71

16.8212.32

0

10

20

30

40

post monsoon winter summer monsoon

Aspergillus Count

Punjab Haryanapost monsoon winter summer monsoon

Punjab Haryana

6.9

28.76

6.683.16.5 3.89

10.666.9

0

5

10

15

20

25

30

35

Post monsoon winter Summer Monsoon

A.flavus count

Punjab Haryana

• 44.2% acquired the

infection in winter

months

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73 FRS cases, how we diagnosed?AFRS EFRS Fungal

ballCIGFRS CIFRS Total

No. of cases 41 11 7 13 1 73

Mycological investigationSmear positive 36 7 5 6 0 54

Culture positive 30 6 0 6 0 42

Aspergillus flavus 29 6 0 6 0 41Aspergillus flavus 29 6 0 6 0 41

Alternaria alternata 1 0 0 0 0 1

HistopathologyEosinophilic mucin 41 11 0 0 0 52C L Crystal 32 7 0 0 0 39Invasion 0 0 0 13 1 14Granuloma 0 0 0 13 0 13Fungus 35 6 7 13 1 62

AFRS = Allergic fungal rhinosinusitis; EMRS = Eosinophilic mucin rhinosinusitis;GFRS = Granulomatous fungal rhinosinusitis; CIFRS = Chronic invasive fungal rhinosinusitis

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Categorization of fungal rhinosinusitis (FRS)

Based on histopathology, clinical findings, laboratoryinvestigations

• Invasive• Acute invasive (necrotizing/fulminant)

• Chronic invasive

• Granulomatous

• Non-invasive• Fungal ball (sinus mycetoma)

• Eosinophil related FRS including AFRS

• ? Sino-bronchial allergic (SAM)

Based on histopathology, clinical findings, laboratoryinvestigations

• Invasive• Acute invasive (necrotizing/fulminant)

• Chronic invasive

• Granulomatous

• Non-invasive• Fungal ball (sinus mycetoma)

• Eosinophil related FRS including AFRS

• ? Sino-bronchial allergic (SAM)

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Areas of bland necrosis

Acute invasive FRS

Invasion of blood vessels

Fungal hyphae

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Granulomatous Invasive

Granulomas with few fungal hyphaechronic inflammatory infiltrate

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Chronic invasivemixed inflammatorycells with plenty ofhyphae

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Difference - granulomatous & chronic invasive

Characters Granulomatous Chronicinvasive

Host immunocompetent diabetes mellitus

Location India, Sudan no specific areaPresentation proptosis orbital-apex syndromePathology granuloma with necrosis of mucosa,

giant cell, few fungi submucosaplenty of hyphae

Mucosal invasion yes yes

Fungi A. flavus A. fumigatusdeShazo et al., Arch Otolaryngol Head Neck Sur1997; 123: 1181-8

Characters Granulomatous Chronicinvasive

Host immunocompetent diabetes mellitus

Location India, Sudan no specific areaPresentation proptosis orbital-apex syndromePathology granuloma with necrosis of mucosa,

giant cell, few fungi submucosaplenty of hyphae

Mucosal invasion yes yes

Fungi A. flavus A. fumigatusdeShazo et al., Arch Otolaryngol Head Neck Sur1997; 123: 1181-8

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Fungal ball

Usually unilateral Involves the maxillary sinusWell defined, high attenuation mass Occasional flocculent Ca Reactive sclerosis of sinus wall No invasion

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Eosinophil related FRS(the controversial area)

• Allergic Fungal Rhinosinusitis (AFRS)

• Eosinophilic Fungal Rhinosinusitis (EFRS)

• Eosinophilic Mucin Rhinosinusitis (EMRS)

• Allergic Fungal Rhinosinusitis (AFRS)

• Eosinophilic Fungal Rhinosinusitis (EFRS)

• Eosinophilic Mucin Rhinosinusitis (EMRS)

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Allergic fungal rhinosinusitis•Type I hypersensitivity•Nasal polyposis•Characteristic CT findings•Allergic mucin without mucosal invasion•Positive fungal culture of sinus content

Bent & Kuhn, Otolaryngol Head Neck Surg, 1994; 111: 580-8

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AFRS – CT view (Dutre et al. J Allergy Clin Immununol 2013; 132: 487)

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Eosinophilic Fungal Rhinosinusitis (EFRS)

The term coined by Ponikau et al. Mayo Clin Proc 1999; 74: 877-84; Braun

et al. Laryngoscope 2003; 113: 264-9; Ponikau et al., J Allerg Clin Immunol 2005; 116: 362-9

• with sensitive techniques (nasal lavage, PCR) fungi could be

detected in >95% of CRS

• fungi in nasal mucus, which contained eosinophils & eosinophil

degraded product – Eosinophilic mucin

• only 42% had type I hypersensitivity & 30% had specific IgE

• However, fungi can be detected in the nose of 100% healthy

volunteers

The term coined by Ponikau et al. Mayo Clin Proc 1999; 74: 877-84; Braun

et al. Laryngoscope 2003; 113: 264-9; Ponikau et al., J Allerg Clin Immunol 2005; 116: 362-9

• with sensitive techniques (nasal lavage, PCR) fungi could be

detected in >95% of CRS

• fungi in nasal mucus, which contained eosinophils & eosinophil

degraded product – Eosinophilic mucin

• only 42% had type I hypersensitivity & 30% had specific IgE

• However, fungi can be detected in the nose of 100% healthy

volunteers

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Eosinophilic Fungal Rhinosinusitis (EFRS)• Subsequently Ponikau et al., J Allerg Clin Immunol 2003; 112: 877-82

• demonstrated toxic major basic protein (MBP) from eosinophil in

mucus of patients with CRS

• the level of MBP was very high (toxic level)

• that could damage nasal epithelium & predisposed bacterial

infection

• Therefore, the question remains whether

• AFRS, a distinct entity, that requires presence of eosinophilic

mucin, hyphae & atopy

• EFRS – a non-allergic fungal eosinophilic inflammation, leads to

secondary bacterial infection (most cases CRS)

• Subsequently Ponikau et al., J Allerg Clin Immunol 2003; 112: 877-82

• demonstrated toxic major basic protein (MBP) from eosinophil in

mucus of patients with CRS

• the level of MBP was very high (toxic level)

• that could damage nasal epithelium & predisposed bacterial

infection

• Therefore, the question remains whether

• AFRS, a distinct entity, that requires presence of eosinophilic

mucin, hyphae & atopy

• EFRS – a non-allergic fungal eosinophilic inflammation, leads to

secondary bacterial infection (most cases CRS)

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Eosinophilic mucin rhinosinusitis (EMRS)

• Proposed by Ferguson, Laryngosocope 2000; 110: 799-813

• Eosinophilic mucin present without fungus

• A systemic disease with dysregulation of immunological

control

• Significantly associated with asthma, incidence of

aspirin sensitivity, incidence of IgG1 deficiency

• Though systemic steroid could be useful, fungal

immunotherapy & antifungal agents would be

ineffective

• Proposed by Ferguson, Laryngosocope 2000; 110: 799-813

• Eosinophilic mucin present without fungus

• A systemic disease with dysregulation of immunological

control

• Significantly associated with asthma, incidence of

aspirin sensitivity, incidence of IgG1 deficiency

• Though systemic steroid could be useful, fungal

immunotherapy & antifungal agents would be

ineffective

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Controversies surrounding AFRS/EFRS/EMRS

• Cautions

• In certain cases of AFRS fungi are sparse & detection

difficult – may lead to diagnose as EMRS

• In a prospective study we found considerable overlap

between AFRS, EFRS & EMRS (Saravanan K, et al. Arch

Otolaryngol Head Neck Surg, 2006; 132: 173-8)

• However, difference of therapy is predicted

• Cautions

• In certain cases of AFRS fungi are sparse & detection

difficult – may lead to diagnose as EMRS

• In a prospective study we found considerable overlap

between AFRS, EFRS & EMRS (Saravanan K, et al. Arch

Otolaryngol Head Neck Surg, 2006; 132: 173-8)

• However, difference of therapy is predicted

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Controversy

• Is it a systemic allergic disease?

• Is it a localized allergic disease?

• Allergy – not at all

• Is it a systemic allergic disease?

• Is it a localized allergic disease?

• Allergy – not at all

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Enhanced cytokine response to fungi

Shin et al.J Allergy Clin Immunol2004; 114: 1369

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Enhanced immune response to fungi

Shin et al.J Allergy Clin Immunol 2004; 114: 1369

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Geographical distribution of fungi in AFRS

6%3%1%A. flavus

OtherAspergillus sp.

0%

13%

0%

90%

OtherAspergillus sp.

Dematiaceousfungi

Other fungi

87%

India study USA study

Page 31: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

A=mucin+hyphae+hypersensitivity, B=mucin+hypae, C=mucin

Kale P, et al. Med Mycol 2015, Feb 27 (Epub)

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A=mucin+hyphae+hypersensitivity, B=mucin+hypae, C=mucin

IL 2, IL4, IL5, IL10, TNF, INF were

significantly elevated in patients with

group A, B, and C as compared to

NECRS and normal subjects (P <.001)

Kale P, et al. Med Mycol 2015, Feb 27 (Epub)

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Comparison between mucin vs. non-mucinchronic FRS

• Considerable overlap in eosinophil-related FRS

• Exaggerated humoral IgE, cellular eosinophilic & elevated

Th1/Th2 cytokine response to fungi or their extract

• The response is to the commonly isolated fungus A. flavus

in this region rather than A. alternata

• The distinction between AFRS/EFRS/EMRS - arbitrary

• Distinction may be important if therapy varies

• The question of allergy in this group not resolved

• Considerable overlap in eosinophil-related FRS

• Exaggerated humoral IgE, cellular eosinophilic & elevated

Th1/Th2 cytokine response to fungi or their extract

• The response is to the commonly isolated fungus A. flavus

in this region rather than A. alternata

• The distinction between AFRS/EFRS/EMRS - arbitrary

• Distinction may be important if therapy varies

• The question of allergy in this group not resolved

Page 34: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Asthma vs. CRS with nasal polyp• CRS is accompanied by polyp in 9-36% cases

• Eosinophil & related inflammatory products in polypoid

inflammation

• IL4, IL5, IL13 are raised in both asthma & CRS with nasal polyp(Eloy P. et al, Curr Allergy Asthma Rep 2011;11: 146-62; Chen & Kuhn 2009)

• ↑leukocytes, eosinophilia, ↑IgE, ↑sensitivity to mold allergens

in both asthma & CRS with nasal polyp

• Can atopy alone explain pathogenesis of CRS & asthma?

• However, nasal polyp is also seen in 40% patients with non-

allergic asthma (Eloy P. et al, Curr Allergy Asthma Rep 2011;11: 146-62)

• CRS is accompanied by polyp in 9-36% cases

• Eosinophil & related inflammatory products in polypoid

inflammation

• IL4, IL5, IL13 are raised in both asthma & CRS with nasal polyp(Eloy P. et al, Curr Allergy Asthma Rep 2011;11: 146-62; Chen & Kuhn 2009)

• ↑leukocytes, eosinophilia, ↑IgE, ↑sensitivity to mold allergens

in both asthma & CRS with nasal polyp

• Can atopy alone explain pathogenesis of CRS & asthma?

• However, nasal polyp is also seen in 40% patients with non-

allergic asthma (Eloy P. et al, Curr Allergy Asthma Rep 2011;11: 146-62)

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AFRS vs. ABPA

Characters AFRS ABPAAffected population Young, atopic, competent Asthma

Mucus Thick, tenacious, casts Thick, tenacious, plug

HLA association HLADQB1 0301/0302 HLA-DR2 & HLA DR5

Serology

Total & specific IgE Elevated Elevated

Specific IgG (precipitin) Inconsistently present Frequent

Peripheral eosinophilia Inconsistently present Generally >1000/mL

Treatment

Systemic steroid Useful Useful

Systemic antifungal Contradictory evidence Adjunctive

Immunotherapy Low quality of support Not used

Anti-IgE antibody Lack of evidence Low quality of support

Callejas & Douglas Clin Exp Allergy 2013; 43: 835-49

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Sino-bronchial allergic mycosis (SAM syndrome)Shah et al. Clin Exp Allergy 2001; 31: 1896-1908

• 22(23%) of 95 patients with ABPA had radiologicalevidence of sinusitis

• 9 agreed for surgery – 7 confirmed for AAS• Other 13 may have AAS, but refused invasiveprocedure

• 22(23%) of 95 patients with ABPA had radiologicalevidence of sinusitis

• 9 agreed for surgery – 7 confirmed for AAS• Other 13 may have AAS, but refused invasiveprocedure

•Similar cases of SAM were reported from different parts ofthe world, but those were rare•Contemporaneous occurrence of ABPA, AAS, aspergilloma- a case report (Ann Allergy Asthma Immunol 2006; 96: 874-8)

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Stapylococcal entertoxin playing major role?• No doubt that fungi function as allergen in AFRS, raise specific IgE

• If AFRS is akin to ABPA, it would not cause so much total IgE rise

• Aspergillus possibly prepares the ground for impact of S. aureus

superantigens by breaking epithelia barrier & initiating Th2 bias

Dutre T, et al. J Allergy Clin Immunol 2013; 132: 487

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Fungal protease – the missing link?

• The common allergens Der p 1 of mite, Per a 10 of cockroach, &

Cur 11 of C. lunata are proteases (Van Zele T, et al, Allergy 2006; 61: 1280)

• Fungal protease bind PAR on epithelial, airway cell, blood

vessels etc. release of cytokine, chemokine, eicosanoids,

metalloproteinases disruption of epithelial tight junction (Yike I,

Mycopathologia 2011; 171: 299-323)

• Not clear whether genotypic difference in PAR expression can

explain the difference of CRS patients & healthy controls

• Fungal protease in hyphae, not spores; aerosolized particles

must contain hyphal fragment

• The common allergens Der p 1 of mite, Per a 10 of cockroach, &

Cur 11 of C. lunata are proteases (Van Zele T, et al, Allergy 2006; 61: 1280)

• Fungal protease bind PAR on epithelial, airway cell, blood

vessels etc. release of cytokine, chemokine, eicosanoids,

metalloproteinases disruption of epithelial tight junction (Yike I,

Mycopathologia 2011; 171: 299-323)

• Not clear whether genotypic difference in PAR expression can

explain the difference of CRS patients & healthy controls

• Fungal protease in hyphae, not spores; aerosolized particles

must contain hyphal fragment

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Allergic fungal rhinosinusitis? invasive

•In 2007, 6 of 105 AFRScases –Mixed reaction(our experience)

•In 2004, 6 (21%) casesof mixed reaction(New Delhi experience)

Page 41: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

• developed a consortium to work together and to exchange

ideas for resolving problems in the area of fungal sinusitis

• the network has been named as Fungal Sinusitis Network

(FSN) with website http://fungalsinusitisgroup.org/

• the basic aim of our network is to understand the disease

and to develop a management protocol

• developed a consortium to work together and to exchange

ideas for resolving problems in the area of fungal sinusitis

• the network has been named as Fungal Sinusitis Network

(FSN) with website http://fungalsinusitisgroup.org/

• the basic aim of our network is to understand the disease

and to develop a management protocol

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Chakrabarti A, et al. Laryngoscope 2009; 119: 1809-18

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Management of FRS

• Acute invasive – surgery + amphotericin B +reversal of immunosuppression

• Chronic invasive/ - surgery + ampho B/itraconazoleChronic granulomatous

• Localized colonization - ? surgery

• Fungal ball - surgery

• AFRS/EFRS/EMRS - surgery + steroid (local/systemic)

immunotherapy, avoid allergen

• Acute invasive – surgery + amphotericin B +reversal of immunosuppression

• Chronic invasive/ - surgery + ampho B/itraconazoleChronic granulomatous

• Localized colonization - ? surgery

• Fungal ball - surgery

• AFRS/EFRS/EMRS - surgery + steroid (local/systemic)

immunotherapy, avoid allergen

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Chronic granulomatous FRS (amphotericin B vs. itraconazole)

Itraconazole

(16)

Amphotericin B

(10)

P value

Cured 5 2 0.668

Persistent disease 7 4 1.000Persistent disease 7 4 1.000

Relapse 3 1 1.000

Lost for follow up 1 0 1.000

Death 0 3 0.138

•Itraconazole vs. amphotericin B – equally efficacious•Itraconazole has fewer side effect

Page 45: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Our experience in AFRSTopical steroid Nasal spray - 150µg / spray

Oral steroid 0.8mg/kg X 4d 0.5mg/kg X 4d 0.3mg/kg X 1month

Therapy No. of patients Failure/recurrence (%)

p valueFailure/recurrence (%)

Local steroid 26 11 (42)

0.009

Oral steroid 26 2 (8)

0.420

Local + oralsteroid

26 5 (19)

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• Concern – immunotherapy may produce Type III

hypersensitivity

• However, limited case reports & retrospective studies

reported improvement of nasal crust & polyp

formation, decrease steroid use & improvement of quality

of life

• Double blind placebo control trial required to increase the

confidence of clinicians

• Concern – immunotherapy may produce Type III

hypersensitivity

• However, limited case reports & retrospective studies

reported improvement of nasal crust & polyp

formation, decrease steroid use & improvement of quality

of life

• Double blind placebo control trial required to increase the

confidence of clinicians

Page 47: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Summary

Features AIFRS CIFRS GFRS Fungalball

AFRS EFRS

Host Immunuo-suppressed

Mild immun-suppressed

Competent Competent Atopy Non-atopic

Demography Any age/sex Adult Young adultvillagers

Middle &elderlyfemale

Urban inUSA,

villagers inAsia

Any personUrban inUSA,

villagers inAsia

Geographicdistribution

Worldwide Worldwide India,Sudan,

Pakistan,Saudi

Worldwide,more

common inFrance

SouthwestUSA, India,

Pakistan

Worldwide

Fungi Mucor morecommon,

thenAspergillus

Aspergillusspecies

A. flavus Aspergillusspecies

Dematiaceoushyphae in USA,A. flavus in

India

Dematiaceoushyphae in USA,A. flavus in

India

Role offungus

Pathogen Pathogen Pathogen Saprobe Allergen Not clear

Page 48: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Summary

Features AIFRS CIFRS GFRS Fungalball

AFRS EFRS

Pathology Acuteinvasion

bloodvessels

Mixedreaction,

plentyhyphae

Granuloma,scantyhyphae

Denseaccumulationof hyphae

Eosinophilicmucin, few

hyphae

Eosinophilicmucin, few

hyphae

Course ofdisease

Acute <4w Chronic>12w

Chronic>12w

Chronic>12w

Chronic>12w

Chronic>12w

Course ofdisease

Chronic>12w

Chronic>12w

Chronic>12w

Chronic>12w

Chronic>12w

Presentation Acute,eschar ,

involvementof eye, brain,

face

Ethmoid,sphenoid

involvement,orbital

extension

One or moresinuses,

orbital apexsyndrome

Nasalobstruction,facial pain,

purulentdischarge

Nasalobstruction,facial pain,hyposmia,

orbital

Nasalobstruction,rhinorrhoea,facial pain

Diagnosis Endoscopicbiopsy, CT

Endoscopicbiopsy, CT

Endoscopicbiopsy, CT

Endoscopicbiopsy, CT

Type I skintest, polyp,eosinophilicmucin, fungi,characteristic

CT

Non-allergiceosinophilicmucin, fungi

Page 49: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

Summary

Features AIFRS CIFRS GFRS Fungalball

AFRS EFRS

Treatment Aggressivesurgery,amph B,control ofimmuno-

suppression

Surgery,systemicantifungal

Surgery,systemicantifungal

Surgery Surgery,oral/ or local

steroid,?immunothe

rapy

Surgery,?steroid,

?antifungaltherapy

Aggressivesurgery,amph B,control ofimmuno-

suppression

Prognosis Highmorality,fungal

emergency

Betterprognosis,recurrencemay occur

Betterprognosis,recurrencemay occur

Cure rategood

Recurrencecommon

Not clear

Page 50: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

ConclusionsThe case for fungus – unproven (more questions than answers)

• Fungus can cause a variety of conditions in the nose & paranasal sinuses,

partly competency of immune system determines severity

• Fungi & eosinophil can be detected in nearly all CRS patients (However,

fungi are also present in healthy controls)

• Many mechanisms may be involved for the fungi to cause disease in those

individuals (more research required!)

• Definite geographical variation exists in fungi causing CRS & allergy

• Antifungal therapy required for invasive varities

• Antifungal therapy appears to be beneficial in selected group of patients

like AFRS (but the effect is not permanent)

• Fungus can cause a variety of conditions in the nose & paranasal sinuses,

partly competency of immune system determines severity

• Fungi & eosinophil can be detected in nearly all CRS patients (However,

fungi are also present in healthy controls)

• Many mechanisms may be involved for the fungi to cause disease in those

individuals (more research required!)

• Definite geographical variation exists in fungi causing CRS & allergy

• Antifungal therapy required for invasive varities

• Antifungal therapy appears to be beneficial in selected group of patients

like AFRS (but the effect is not permanent)

Page 51: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

?Fungus allergy

Page 52: Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause • Rhinosinusitis – inflammation of nose & sinuses • Course – may be acute

John E Bennett , USABerrylin J Ferguson , USAHirohito Kita , USAJens Ponikau, USAWiley Schell , USARonald G. Washburn, USABradley F. Marple, USAJennifer O Foley, USAAnnette W Fothergill , USADonald C. Lanza , USAAnil A Panackal, USA

David Denning, UKR K Gurunathan , UK

Heinz Stammberger, AustriaWalter Buzina , Austria

Sharon CA Chen , Australia

Stephan Vlaminck , Belgium

Saad Jaber Taj-Aldeen, Qatar

Keyvan Pakshir , IranTahereh Shokohi , IranMohammad T. Hedayati , IranSeyedmojtaba Seyedmousavi , Iran

A Serda Kantarcioglu , TurkeyMehmet Macit Ilkit , Turkey

Malcolm Richardson , FinlandElina Toskala , Finland

Maria Anna Viviani , Italy

Catherine Kauffmann-lacroix , France

Jamal M A Jawad , Saudi Arabia

Maya Chandrani Attapattu , Srilanka

Naresh Kumar Panda , IndiaAshim Das, IndiaKusum Joshi, IndiaBishan D Radtora, IndiaR K Vashistha, IndiaRamandeep Singh Virk IndiaRupa Vedantam , IndiaH S Randhawa, IndiaShivaprakash M R , IndiaThungapathra, IndiaParamjeet, IndiaNiranjan Khandelwal, IndiaHemashettar BM, India

Shilpa Chandrashekar, IndiaPradipta Kumar Parida , IndiaAshok Gupta, IndiaRijunita, IndiaSanjay Sachdeva, IndiaManu Jatana, IndiaAbhishek Bhagela, IndiaVarghese K George, IndiaManpreet Dhaliwal, IndiaSandeep Mohindra , IndiaAmanjit Bal , IndiaRupa Mehta , IndiaSatyawati Mohindra, IndiaNiranjan Nayak , IndiaJagdish Chander, IndiaKumud Kumar Handa, IndiaAru Chhabra Handa , IndiaRagini Tilak, IndiaJaimanti Bakshi , IndiaSandeep Bansal, IndiaSurinder K Singhal , IndiaDeepinder Kaur Chhina , IndiaMohnish Grover, IndiaUsha Singh , IndiaRatna Rao , IndiaShesh Rao Nawange , India

Members of ISHAM Working group on Fungal Sinusitis

Thankyou!

John E Bennett , USABerrylin J Ferguson , USAHirohito Kita , USAJens Ponikau, USAWiley Schell , USARonald G. Washburn, USABradley F. Marple, USAJennifer O Foley, USAAnnette W Fothergill , USADonald C. Lanza , USAAnil A Panackal, USA

David Denning, UKR K Gurunathan , UK

Heinz Stammberger, AustriaWalter Buzina , Austria

Sharon CA Chen , Australia

Stephan Vlaminck , Belgium

Saad Jaber Taj-Aldeen, Qatar

Keyvan Pakshir , IranTahereh Shokohi , IranMohammad T. Hedayati , IranSeyedmojtaba Seyedmousavi , Iran

A Serda Kantarcioglu , TurkeyMehmet Macit Ilkit , Turkey

Malcolm Richardson , FinlandElina Toskala , Finland

Maria Anna Viviani , Italy

Catherine Kauffmann-lacroix , France

Jamal M A Jawad , Saudi Arabia

Maya Chandrani Attapattu , Srilanka

Naresh Kumar Panda , IndiaAshim Das, IndiaKusum Joshi, IndiaBishan D Radtora, IndiaR K Vashistha, IndiaRamandeep Singh Virk IndiaRupa Vedantam , IndiaH S Randhawa, IndiaShivaprakash M R , IndiaThungapathra, IndiaParamjeet, IndiaNiranjan Khandelwal, IndiaHemashettar BM, India

Shilpa Chandrashekar, IndiaPradipta Kumar Parida , IndiaAshok Gupta, IndiaRijunita, IndiaSanjay Sachdeva, IndiaManu Jatana, IndiaAbhishek Bhagela, IndiaVarghese K George, IndiaManpreet Dhaliwal, IndiaSandeep Mohindra , IndiaAmanjit Bal , IndiaRupa Mehta , IndiaSatyawati Mohindra, IndiaNiranjan Nayak , IndiaJagdish Chander, IndiaKumud Kumar Handa, IndiaAru Chhabra Handa , IndiaRagini Tilak, IndiaJaimanti Bakshi , IndiaSandeep Bansal, IndiaSurinder K Singhal , IndiaDeepinder Kaur Chhina , IndiaMohnish Grover, IndiaUsha Singh , IndiaRatna Rao , IndiaShesh Rao Nawange , India

Thankyou!