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Fungal RhinosinusitisNiyada Teerasuwanajug
• Cumming otolaryngology head and neck surgery 5th edition
• Bailey otolaryngology head and neck surgery 4th edition
• The Otolaryngologic Clinics of North America 2000• SIPAC 2003
Incidence
• Rare • NoninvasiveNoninvasive fungal rhinosinusitis is more common.
• 4-7% of Sx cases for chronic inflammatory sinonasal dis. are AFSAFS.
• A review by Ferreiro et al. 1984-1994 3.7% of Sx cases for inflammatory sinus dis. were fungal ball.fungal ball.
• CIFSCIFS: very rare in the United States only case reports & a few small series.– More common in region; Sudan & India. More common in region; Sudan & India.
SIPAC 2003SIPAC 2003
Incidence
• Incidence rates of AIFS AIFS for leukemia, CA, or bone marrow transplant = 1-2%
• The incidence of fungal sinus disease seems to be seems to be increasing.increasing.
SIPAC 2003SIPAC 2003
1. practitioner awareness.
2. Technical advanced >> mycology, serology , histopathology and radiology.
3. Growth of immunocompromised population.
4. Inappropriate use of anti-bacterial ATBs.
5. incidence of atopic dis. in the United States.
Factor Contribute to Increase IncidenceFactor Contribute to Increase Incidence
Increased Susceptibility to Invasive Fungal InfectionsIncreased Susceptibility to Invasive Fungal Infections
Disease of the sinuses: Dx & Mx. 2001: 180
Classification of Fungal Rhinosinusitis
• Noninvasive / ExtramucosalNoninvasive / Extramucosal– Saprophytic colonization / Superficial sinonasal mycosisSaprophytic colonization / Superficial sinonasal mycosis– Fungal ballFungal ball– Allergic fungal rhinosinusitis (AFS)Allergic fungal rhinosinusitis (AFS)
• Invasive Invasive – Chronic invasive (indolent) fungal rhinosinusitis (CIFS)Chronic invasive (indolent) fungal rhinosinusitis (CIFS)– Acute invasive (fulminant) fungal rhinosinusitisAcute invasive (fulminant) fungal rhinosinusitis (AIFS)(AIFS)
Disease of the sinuses: Dx & Mx. 2001: 179
Am J Surg Pathol Volume Am J Surg Pathol Volume 3030, Number , Number 66, June , June 20062006
Hypersensitivity Hypersensitivity Host response to fungusHost response to fungus Immunocompromised Immunocompromised
AFRSAFRS Fungus Fungus BallBall
ChronicChronicInvasive Invasive
Acute Acute invasiveinvasive
Non- Non- Invasive Invasive
Invasive Invasive
Fungal sinus dis. manifestations: by Fungal sinus dis. manifestations: by host’s immune responsehost’s immune response & & tissue invasiontissue invasion. .
SIPAC 2003SIPAC 2003
Host Host DefenseDefense
Fungal Fungal FormForm
Immunocompromised Immunocompromised
InvasiveInvasive
Immunocompetent Immunocompetent
Fungus ball Saprophytic GranulomatousFungus ball Saprophytic Granulomatous
AtopicAtopic
AFRSAFRS
The Otolaryngologic Clinics of North America 2000The Otolaryngologic Clinics of North America 2000
Fungal manifestion : Fungal manifestion : by patient’s immunologic statusby patient’s immunologic status
Signs Signs && Symptoms Seen with Fungal Infections Symptoms Seen with Fungal Infections
Disease of the sinuses: Dx & Mx. 2001: 180
Endoscopic Findings Present DuringEndoscopic Findings Present DuringFungal InfectionFungal Infection
Disease of the sinuses: Dx & Mx. 2001: 180
Endoscopic Findings Present DuringEndoscopic Findings Present DuringFungal InfectionFungal Infection
MicrobiologyMicrobiology
Fungal form:
1. Mould• Multicellular colonies• Hyphae• Cause most fungal rhinosinusitis
2. Yeast • Unicellular• Most reproduction by asexual budding
• However, some species >> dimorphic depending upon environmental conditions.
SIPAC 2003SIPAC 2003
MicrobiologyMicrobiology
Common fungi in fungal rhinosinusitisCommon fungi in fungal rhinosinusitis
CategoryCategory Disease Disease Genera Genera
Zygomycetes (Mucoraceae) Acute invasive Absidia Cunninghamella Mucor Rhizomucor Rhizopus
Hyaline moulds Fungas ball Aspergillus Acute invasive Fusarium Chronic invasive Pseudallescheria
Dematiacious moulds Allergic fungal Alternaria Bipolaris Cladosporium Curoularia Exserohilum
SIPAC 2003SIPAC 2003
Microscopic examinationMicroscopic examination
• 10% , 20% KOH – Light microscopy
– limit in thick specimen
• KOH – calcufluor white stain – Fluorescence microscope
• Gram stain : not common use• H & E (hematoxylin and eosin)• GMS (Gomori methenamine silver)• PAS (periodic acid schiff)
Microscopic examinationMicroscopic examination
GMS and PAS superior to H&E GMS and PAS superior to H&E
• Culture identification – Media : Sabouraud’ s agar (glucose + beef
extract; PH 5 )
• Serology – specific IgE and IgG detected by serum
radioimmunoassay
Noninvasive Fungal RhinosinusitisNoninvasive Fungal Rhinosinusitis
Noninvasive Fungal Rhinosinusitis
• Saprophytic colonization • Fungal ball • Allergic fungal rhinosinusitis
Saprophytic ColonizationSaprophytic Colonization
• Extramucosal sinonasal fungi promote inflammation • Presence of fungal spores on mucous crustsfungal spores on mucous crusts within nose &
paranasal sinus• Detected grossly on examination. • Perhaps one could consider this an early form of a fungus
ball.• Common fungal agent: Aspergillus species
Disease of the sinuses: Dx & Mx. 2001: 180-182
Saprophytic ColonizationSaprophytic Colonization
Clinical presentation:
• immunocompetent• asymptomatic • an odor in nose • crusts of debris on nose blowing • nasal endoscope: a tuft of fungal material is seen growing
on nasal crusts, much like mold growing on old bread
Disease of the sinuses: Dx & Mx. 2001: 180-182
Saprophytic ColonizationSaprophytic Colonization
• Patient undergone previous endoscopic sinus surgery:– disrupt mucocilary transport pathway– dry nasal passageways / have some mucus stasis
• Fungal crusts may appear in areas of high airflow - anterior edge of turbinates , but can also appear in surgical widened sinus cavities.
• Imaging : not seen on imaging
Disease of the sinuses: Dx & Mx. 2001: 180-182
Saprophytic ColonizationSaprophytic Colonization
Treatment:
• Debridement the involved region endoscopic cleaning.
Disease of the sinuses: Dx & Mx. 2001: 180-182
Saprophytic ColonizationSaprophytic Colonization
Treatment:
• Saline irrigation if it accumulate. • Minimizing overuse of drying agents: antihistamine,
topical nasal steriod.• Rx underlying bacterial infection. • Antifungal agent: not used.
Disease of the sinuses: Dx & Mx. 2001: 180-182
Fungal BallFungal Ball
Fungal Ball
Terms:– Mycetoma – Sinus mycetoma– Aspergilloma– Simple sinus aspergillosis
A true mycetoma:
a suppurative & granulomatous subcutaneous fungal infection with draining sinus tracts.
refer to an invasive fungal infection of the feet.
SIPAC 2003SIPAC 2003
Epidemiology:
• The average age reported in an american 29 cases = 64 yr (28-86 yr).
• A review by deShazo et al. >> similar age range, the youngest = 18 yr.
• Common in older• No pediatric.
• Female predominant
Fungal Ball
Fungus ball of paranasal sinus: The Otolaryngologic Clinics of North America 2000Fungus ball of paranasal sinus: The Otolaryngologic Clinics of North America 2000
Often found unexpectedly during Rx of chronic
bacterial sinusitis
Hx : • May be present for months to yearsmonths to years. • Nonspecific chronic sinusitis symptoms:
– Nasal obstruction– Facial pressure– Postnasal drainage
• **Hx of symptoms refractory to common medical Rx: – ATBs– Antihistamines– Nasal steroids
Fungal Ball
SIPAC 2003
Fungal Ball
Diagnosis• No evidence of immunocompromise + No incidence
of atopy• *** A solitory maxillary/ sphenoid sinus• May also in frontal & ethmoid sinuses• May involve contiguous sinuses
In asymptomatic patients often detect only after
imaging for other conditions
SIPAC 2003
Fungal BallPE:• A single sinus• 40% of patients: purulent d/c from
involved sinus• 10% of patients: polyps
SIPAC 2003
F. Pagella et al.: Paranasal sinus fungus ball: Dx & Mx. 2007 50 4Mycoses ( ), ,51456
Fungal Ball
• Hx• PE• Imaging• Histopathologic exam.• Culture
Fungal Ball
- HHyperattenuatingyperattenuating material filling the material filling the RRtt. . mm axillary sin axillary sinusus with with central calcific areas central calcific areas of increased attenuation (lon of increased attenuation (lon
g arrow). g arrow).
- TT he circumferential he circumferential thickening of the osseous walls thickening of the osseous walls of sinus of sinus
(short arrows) (short arrows)..
Unenhanced CT scan
Fungal Ball
• The typical hyperattenuating hyperattenuating fungus ball withfungus ball with calcific calcific foci in foci in Lt.Lt. maxillary sinus maxillary sinus (long arrow).
• The sclerotic thickening of the osseous wallsthickening of the osseous walls of sinus (short arrows) from chronic sinus inflammation.
Axial unenhanced CT scan
Fungal Ball
Fungal Ball
Pathology:
• Gross – Lesions: vary from soft, wet-appearing bundles of
debris to firm, gritty & crumbly balls – Color: white, yellow, green, tan, brown & black
Fungal Ball
Granville et al: Fungal sinusitis, HUMANPATHOLOGYVolume35,No.4(April2004)
Fungal Culture
• Usually –ve• In Klossek's review (109 patients), only 31% of
cases had positive cultures.
All of these : Aspergillus fumigatus
• Usual pathogen: Aspergillus species• But Pseudallescheria, Alternaria sp, and other
species have been reported.
SIPAC 2003
Fungal BallPathogenesis
• Unknown
• Persistence of fungal spores within nasal cavity into maxillary/ other sinus. When fungal spore is not cleared. (in warm dark recesses of a sinus) germination & growth.
• Saprophytic colonization obstruct sinus ostium& lead to episodes of acute sinusitis and result in a fungal ball.
Fungal Ball
F. Pagella et al.: Paranasal sinus fungus ball: Dx & Mx. 2007 50 4Mycoses , ,51456
Fungal Ball
Treatment • The gold removal of the hyphal mass +
re-establishment of drainage from involved sinus.
• Antifungal Rx : unnecessary
Fungal Ball
Postoperative care
• Saline irrigation & endoscopic debridementsSaline irrigation & endoscopic debridements are indicated until complete healing.
• No further Rx is required & widely aerated sinus should quickly return to normal.
Recurrence rare
Fungal Ball
Treatment :
Should an asymptomatic patient undergo surgery for
an opacified sinus without evidence of bony erosion?
• This is controversial, and following the patient for symptoms & repeated imaging to assess for progression is also a reasonable path.
Fungus ball of paranasal sinus: The Otolaryngologic Clinics of North America 2000Fungus ball of paranasal sinus: The Otolaryngologic Clinics of North America 2000
Allergic Fungal Rhinosinusitis
Epidemiology
• The most common form of fungal rhinosinusitis
• Age: – mostly in young adults– Average age at Dx >> 23-26 yr.– Range 7-62 yr.
• Sex:– Male:Female >> 6:1
SIPAC 2003
Allergic Fungal Rhinosinusitis
Epidemiology
• AR:– 63% of AFS patients give Hx of AR allergy testing
70-90% show evidence of atopy.
• Asthma:– About 50% of patients have asthma. (33-54%)
• Geography:– More common in the warm humid climates of the southern
United States and along the Mississippi River.
SIPAC 2003
Allergic Fungal Rhinosinusitis
Clinical features: Hx
• Onset: difficult to pintpoint.• Symptoms progress slowly (mo./yr. prior to Dx.)
• Typically presented with prolonged Hx of rhinosinusitis sym.:– Nasal congestion & obstruction– Anosmia– Postnasal drainage
SIPAC 2003
Allergic Fungal Rhinosinusitis
Clinical features: Hx
• Despite prolong medical Rx (repeated courses of ATB) fail to improved.
• May multiple sinus procedures without benefit if overlooked the Dx.
SIPAC 2003
Allergic Fungal Rhinosinusitis
Clinical features: PE
• By the time of Dx >> advanced PE findings reflect this.• GA: nasal widening, proptosis• Incidence of proptosis 20% • Reversible blindness from sphenoid involved (several case
reports) • fungal mucocele formation
SIPAC 2003
Allergic Fungal Rhinosinusitis
Clinical features: PE
Intranasal exam.• Polyposis
-predominantly unilateral, maybe bilat. -often massive & visible at nasal vestibule
•** Allergic mucin-mucin: rubbery-difficult to suction out-often visibly nestle within the polyps
SIPAC 2003
Sinus Surgery Endoscopic & Microscopic Approaches, Howard L. Leveine 2005
Allergic Fungal Rhinosinusitis
Laboratory
• May provide evidence of atopy, but not usually required for Dx
• CBC: peripharal eosinophilia (7-15%)• Elevated total IgE level: mean 668 IU/ml (normal= <125 IU/ml)• RAST (radioallergosorbent test for quantifying antigen-specific IgE)(radioallergosorbent test for quantifying antigen-specific IgE) :
+ve to multiple fungi.• Skin test: +ve to multiple fungi.
SIPAC 2003
Sinus Surgery Endoscopic & Microscopic Approaches, Howard L. Leveine 2005
Allergic Fungal Rhinosinusitis
Laboratory• Total IgE fluctuates with disease activity.
• In a review of 67 patients in Arizona, Schubert & Goetz found:– Total serum IgE correlated significantly with severity of disease.Total serum IgE correlated significantly with severity of disease.– Importantly, an increase >=10% in total serum IgE during F/U >> strong Importantly, an increase >=10% in total serum IgE during F/U >> strong
predictor of recurrence & need for Sx.predictor of recurrence & need for Sx.
Schubert MS, Goetz DW. Evaluation & Rx of ARS. J Allergy Clin Immunol. 1998
Allergic Fungal Rhinosinusitis
Pathology
• Gross- The distinctive pathology of AFS >> tenacious
inspissated mucin / “peanut butter-like”
- Thick yellow, brown, or green debris fills the involved sinuses. similar to fungal ball grossly
Allergic Fungal Rhinosinusitis
Histopathology
• Microscope: - Within allergic mucin : “onionskin lamination” / cluster of necrotic & - Within allergic mucin : “onionskin lamination” / cluster of necrotic &
degranulation of eosinophildegranulation of eosinophil
- Charcot-Leyden crystal.- Charcot-Leyden crystal.- Hyphal fragments scatteredHyphal fragments scattered- No fungal tissue invasionNo fungal tissue invasion
Sinus Surgery Endoscopic & Microscopic Approaches, Howard L. Leveine 2005
Allergic Fungal Rhinosinusitis
• Histopathology
Special stains for fungus: GMS >> hyphae
Sinus Surgery Endoscopic & Microscopic Approaches, Howard L. Leveine 2005
• Histopathology
GMS >> scatter hyphae Periodic acid-Schiff, ×520
Allergic Fungal Rhinosinusitis
Fungal culture
• Positive 70-80% of patients diagnosed with AFS.• Dematiaceous fungi : the most common based on C/S
data 84% of the total positive C/S
The most common fungi = Bipolaris species
Allergic Fungal Rhinosinusitis
Fungal culture• Aspergillus species 13% of all fungal C/S
Allergic Fungal Rhinosinusitis
Fungal culture
• Appear to be geographic variability in incidence of AFS & in fungal organism – Dematiaceous fungi : most common in the United states– Aspergillus species : most cases reported in the Middle East.
Allergic Fungal Rhinosinusitis
Staging System
• Kupferberg et al. >> F/U patients: recurrent following surgery.
Allergic Fungal Rhinosinusitis
Imaging• CT:
– Initial study of choice– An important roadmap before Sx
>> • MultipleMultiple opacified sinusessinuses• Predominantly unilateral, possibly bilateral• Expanded sinuses• Bone erosionBone erosion into orbit, cranium, or soft tissue of face.• Focal areas within sinuses: hyperattenuationhyperattenuation = fungal fungal
allergic mucinallergic mucin irregular, speckled, or serpiginous
SIPAC 2003
Allergic Fungal Rhinosinusitis
• Coronal sinus CTCoronal sinus CT • Axial sinus CTAxial sinus CT
Sinus Surgery Endoscopic & Microscopic Approaches, Howard L. Leveine 2005
Allergic Fungal Rhinosinusitis
Imaging• MRI
– Sinus contents >> low T2 & isointense/hypointense T1 signal– Peripheral mucosa & polyps >> hyperintense on both T1 & T2
Allergic Fungal Rhinosinusitis
Imaging
• Bony remodeling / erosionBony remodeling / erosion is common (90%) from atrophy / the release of inflammatory mediators that dissolve bone, not due to fungal invasion
While definitive Dx requires histological verification, the
imaging findings are almost pathognomonicimaging findings are almost pathognomonic & facilitate
pre-op planning.
SIPAC 2003
Allergic Fungal Rhinosinusitis
Diagnostic Criteria
• Several criteria have been proposed for the Dx.– Kartzenstein 1983– Manning 1989– Ence 1990– Bent 1994– deShazo 1995– Kuferupferberg 1996 – Schubert 1998– Ponikau 1999– Schubert 2000– McCann 2002– Meltzer 2004
Singhal D et al. Medical interventions for post-surgical Mx of AFRS: The Cochrane Library 2008Singhal D et al. Medical interventions for post-surgical Mx of AFRS: The Cochrane Library 2008
Allergic Fungal Rhinosinusitis
Diagnostic Criteria
• Presence of allergic mucinPresence of allergic mucin: fundamental criterion for the dis.
Bent & Kuhn diagnostic criteria for allergic fungal rhinosinusitisBent & Kuhn diagnostic criteria for allergic fungal rhinosinusitis
1. Type I hypersensitivity confirmed by Hx, skin test, or serology2. Nasal polyposis3. Characteristic CT scan findings4. +ve fungal strain of sinus contents5. Eosinophilic mucus without fungal invasion into sinus tissue
Bent JP III, Kuhn FA: Dx of AFS. Otolaryngol Head Neck Surg 1994; 111: 580-588.
Pathophysiology & Natural Course
Local Local • MucostasisMucostasis• Anatomic anomalyAnatomic anomaly
Environmental Environmental • Fungal exposureFungal exposure
Genetic Genetic • AtopyAtopy• T-lym susceptibilityT-lym susceptibility
Exposure Exposure Fungal proliferation Fungal proliferation
Antigen exposureAntigen exposure
Anatomic Anatomic factorsfactors
Bacterial Bacterial infectioninfection
Edema Edema ObstructionObstruction StasisStasis DecreasedDecreased ventilationventilation
AllergicAllergicmucinmucin
InflammationInflammationEosophillic inflammationEosophillic inflammation
(MBP, ECP, etc)(MBP, ECP, etc)
Inflammatory triggerInflammatory trigger Gell & Coombs I/IIIGell & Coombs I/III T-cellT-cell OtherOther
The UT Southwestern model of AFS pathogenesis. Local tissue, environ., & immunologic factorsconverge in pathogenesis of this disease. (Laryngoscope 2001; 111: 1006-1019)
Allergic Fungal Rhinosinusitis
Natural Course
• Frequent recurrence
• Reported recurrent rate 10-100%
SIPAC 2003
Allergic Fungal Rhinosinusitis
Treatment :Treatment :
1. Surgical – Required in almost all cases.– Goal: removing fungal mucin + widely marsupialize the
involved sinuses.
– Occasionally, the fungal mucin is so difficult to clear from the maxillary sinus & frontal sinus >> external approach / frontal sinus trephination may be necessary.
Marple BF: AFRS: Current theories & Mx strategies. Laryngscope 2001; 111: 1006-1019
Allergic Fungal Rhinosinusitis
1. Surgical • Dis. may distort normal intranasal landmarks & erode
important bony barriers to orbit/cranium. CT prior SxCT prior Sx.
Sx alone isn’t sufficient Rx for AFS, it is a crucial first step in Mx.
SIPAC 2003
Allergic Fungal Rhinosinusitis
1. Surgical
•Goal : same as primary Sx; allergic mucin, nasal polyps & other sinus obstruction should be removed.
•Complete Sx to removed all fungal mucin is critical to reduce risk of recurrence.