Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause...
Transcript of Fungal rhinosinusitis: classification, diagnosis & treatment · Rhinosinusitis– fungus as a cause...
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
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
While the debate continues, let ussee situation in India
While the debate continues, let ussee situation in India
Fungal rhinosinusitis in India
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
Prevalence study in north Indian villages
• 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
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
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
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)
Areas of bland necrosis
Acute invasive FRS
Invasion of blood vessels
Fungal hyphae
Granulomatous Invasive
Granulomas with few fungal hyphaechronic inflammatory infiltrate
Chronic invasivemixed inflammatorycells with plenty ofhyphae
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
Fungal ball
Usually unilateral Involves the maxillary sinusWell defined, high attenuation mass Occasional flocculent Ca Reactive sclerosis of sinus wall No invasion
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)
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
AFRS – CT view (Dutre et al. J Allergy Clin Immununol 2013; 132: 487)
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
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)
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
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
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
Enhanced cytokine response to fungi
Shin et al.J Allergy Clin Immunol2004; 114: 1369
Enhanced immune response to fungi
Shin et al.J Allergy Clin Immunol 2004; 114: 1369
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
A=mucin+hyphae+hypersensitivity, B=mucin+hypae, C=mucin
Kale P, et al. Med Mycol 2015, Feb 27 (Epub)
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)
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
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)
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
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)
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
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
Allergic fungal rhinosinusitis? invasive
•In 2007, 6 of 105 AFRScases –Mixed reaction(our experience)
•In 2004, 6 (21%) casesof mixed reaction(New Delhi experience)
• 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
Chakrabarti A, et al. Laryngoscope 2009; 119: 1809-18
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
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
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)
• 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
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
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
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
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)
?Fungus allergy
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!