Gr Rounds Fungal Sinusitis

8/3/2019 Gr Rounds Fungal Sinusitis

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FungalRhinosinusitisAileen Delos Santos-Garcia, MD

RPT-III


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Fungal sinusitis

Classification:

1. Acute/Fulminant, Invasive(immunocompromised host)

2. Chronic/Indolent, Invasive

3. Fungal Ball

4. Allergic Fungal Sinusitis (AFS)

Bent JP and Kuhn FA. Diagnosis of allergic fungal

sinusitis. Otolaryngol Head Neck Surg. 1994.


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Fungal sinusitis

Classification:

1. Invasive:

}Acute (fulminant)

}Chronic ( granulomatous and non granulomatous )

2. Non-invasive:

} Saprophytic

} Fungus balls ( mycetoma )

}Allergic Fungal Sinusitis ( AFS )

Ferguson BJ. Definitions of fungal rhinosinusitis.Otolaryngol Clin North Am. 2000 Apr;33(2):227-35.


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Fungal sinusitis

Classification:

1. Invasive:

}Acute Fulminant Invasive Fungal Sinusitis (AFIFS)

}Chronic Invasive Fungal Sinusitis (CIFS)

}Granulomatous Invasive Fungal Sinusitis (GIFS

2. Non-invasive:

} Saprophytic Fungal Infestation (SFI)

} Sinus Fungus Ball (SFB)

}Allergic Fungal Sinusitis ( AFS )

Adelson et al. Fungal rhinosinusitis: state-of the-artdiagnosis and treatment. J Otolaryngol. 2005


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Fungal sinusitisClassification:

1. Invasive:

} Acute Fulminant Invasive Fungal Sinusitis (AFIFS)} Chronic Invasive Fungal Sinusitis (CIFS)} Granulomatous Invasive Fungal Sinusitis (GIFS

2. Non-invasive:} Saprophytic Fungal Infestation (SFI)} Sinus Fungus Ball (SFB)}

Eosinophil Mediated Forms} Allergic Fungal Sinusitis ( AFS )} Eosinophilic Fungal Rhino-sinusitis (EFRS)

3. Transitional.

(Stammberger 2008 AAO-HNS)


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Allergic fungal sinusitis

} Frequency:

}

It is estimated that approximately 5-10% ofpatients affected by chronic rhinosinusitis

actually carry a diagnosis of AFS

} The (M/F) ratio of AFS equal.


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Fungi implicated inAFS are known asthe dematiaceous(darkly pigmented)fungi.

}Aspergillus spp,

} Bipolaris

} Curvularia

}Alternaria

PATHOGENIC

ORGANISM


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Pathophysiology(Controversial)

Significance offungal presence and

eosinophilic mucin rhinosinusitis (EMRS)?} EMRS = AFS in the absence of fungal hyphae.

} EMRS occurs because of dysregulation ofimmunologic controls involving upper and

lower airway eosinophilia, whereas AFS is a

localized IgE-mediated reaction to thegerminated fungus.

Ferguson BJ: Eosinophilic mucin rhinosinusitisa distinctiveclinicopathological entity. Laryngoscope 2000


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Pathophysiology(Controversial)} EMRS:} Systemic disease, therefore not unilateral

} Higher association with asthma, ASA sensitivity} Increased incidence of IgG1 deficiency

} Older patients: avg 50s

} AFS:} Allergic response to fungi

} Unilateral or bilateral

} Fungal immunotherapy and antifungal agents} Younger patients: avg 30s

Ferguson BJ: Eosinophilic mucin rhinosinusitisa distinctiveclinicopathological entity. Laryngoscope 2000


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DIAGNOSIS OF AFS

5 MAJOR criteria are:

1. Evidence of type I hypersensitivity (IgEmediated) by history, skin tests or serology.

2. Nasal polyposis.

3. Characteristic CT findings.

4. Eosinophilic mucus.

5. Positive fungal stain.

Bent JP and Kuhn FA: Diagnosis of allergic fungal sinusitis.Otolaryngol Head Neck Surg 1994


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DIAGNOSIS OF AFS

6 associated criteria are

1. asthma. (8/15)2. unilateral predominance. (13/15)

3. radiographic bone erosion. (12/15)

4. fungal culture. (11/15)

5. Charcot-Leyden crystals. (6/15)

6. serum eosinophilia. (6/15)

Bent JP and Kuhn FA: Diagnosis of allergic fungal sinusitis.Otolaryngol Head Neck Surg 1994


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DIAGNOSIS OF AFS

1. nasal polyposis.

2. characteristic CT scan.

3. eosinophilic mucus.

Accepted in most centers


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Allergic (Eosinophillic) mucin

} The hallmark of AFS

} Remains the most reliableindicator of AFS

} Grossly, allergic fungalmucin is thick, tenacious,

and highly viscous.

} Peanut butter-like .


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Allergic (Eosinophillic) mucin

}Endoscopic findings

} Polyps.

} Allergic mucin

} Thick/Green


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Endoscopic mucosal staging

} Endoscopic mucosal staging system wasdeveloped by Kupferberg et al. in 1996

} Stage 0: No mucosal edema or allergic

mucin

} Stage I: Mucosal edema

} Stage II: Polypoid edema

} Stage III: Sinus polyps


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} Mucosal Staging System

Stage 0 Stage I


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} Mucosal Staging System

Stage II Stage III



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Histology} Branching noninvasive

fungal hyphae.

} Eosinophils and

elongated eosinophilicbodies

} Charcot-Leyden

crystals.


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IgE levels

} Total IgE values generally are elevated in

AFS(90%)

} Total IgE level traditionally has been used to

monitor the clinical activity of allergicbronchopulmonary fungal disease.

} IgE levels have been proposed as a useful

indicator of AFS clinical activity.


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Ocular manifestations} 82 patients} Orbital involvement without visual loss was

found in 14.6% of the patients and mostcommonly resulted in} Proptosis (seen in 6.1% of patients)} Telecanthus (seen in 7.3%).} Visual loss from AFS, encountered in 3.7% of

patients, was reversible with immediate

surgical treatment of the underlyingdisease.

Marple BF, Gibbs SR, NewcomerMT,Mabry RL: Allergic fungal sinusitis-inducedvisual loss. Am J Rhinol 1999,


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Imaging- CT

} Expansion, remodeling, or thinning of

involved sinus wall was common (98%) and

was due to the expansile nature of theaccumulating mucin.

} Signal heterogentiy due to accumulation of

heavy metals (eg, iron and manganese)and calcium within inspissated allergic

fungal mucin.

Mukherji SK,Figueroa R, Ginsbergy LE, Zeifer BA,Marple BF, Alley JG, et al.:

Allergic fungal sinusitis: CT findings. Radiology 1998


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Imaging- CT

} Rail tracks

} Very suggestive but notdiagnostic by itself.

Mukherji SK,Figueroa R, Ginsbergy LE, Zeifer BA,Marple BF, Alley JG, et al.:

Allergic fungal sinusitis: CT findings. Radiology 1998


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CRS and fungi

} 54 patients with CRS

} 54 of 54 (100%) specimens stained fungi

using the fluorescein-labeled chitinase.

} 41 of 54 (76%) of the specimens stained withthe Grocott methanamine silver staintechnique demonstrated fungi

Taylor MJ, Ponikau JU. Detection of fungal organisms ineosinophilicmucin using a fluorescein-labeled chitin-

specific binding protein. Otolaryngol Head Neck Surg.2002 Nov;127(5):377-83.


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CRS and fungi

} Fungi in (93%) patients undergoing surgery for

any form of chronic rhinosinusitis.

} Of note, the presence of fungi was alsoidentified within 100% of the control subjects

used for comparison

Ponikau et al. The diagnosis and incidence of allergic fungalsinusitis. Mayo Clin Proc 1999.


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AFS- Controversies

} CRS- no sufficient evidence to show

bacterial cause (resistance to antibiotics).

} CRS not explained by IgE mediated

hypersensitivity:

}Only 40-60% have positive allergy tests

} Eosinophil content is independent of IgE levels

}

Symptoms are different from those of pateintsIgE mediated allergies (sneezing, itching)

}Allergic rhinitis occurs as a comorbid disease

Ponikau, et al., J Immunol. 2009 183(10):6708-16. Epub 2009. Recognition of fungal

protease activities induces cellular activation and eosinophil-derived neurotoxin release

in human eosinophils


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AFS- Controversies

} prominent IgE independent and cytokine

driven inflammation has been found.

} IL-5, IL-13 and IFN-gamma are present in

CRS and absent healthy controls.

} IL-5: eosinophil migration

} IL-13 eosinophil aPonikau et al.

} ctivation





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AFS- ControversiesPathophysiology

} Eosinophils attack germinating spores of hyphae

(not the hyphae themselves)

} Eosinophils release major basic protein (MBP)

} Toxic to epithelium (3000x)

} Epithelial damage

} Entry port for bacteria causing recurent-ABRS





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AFS- Controversies

Pathophysiology

} 7 different fungi tested

} Only Alternaria caused activation ofeosinophils

} One protein was responsible.

} No neutrophilic response was observed

} AFS should be replaced by EFRS


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Treatment of AFS

} Requires both medical & surgical treatment.

} Goals:

1) reduce the fungal load in the sinuses.

2) reestablish physiologic mucous clearance,

while preserving normal mucosa.

3)postoperative access to previously diseased

areas to monitor for signs of recurrent AFS, whichcan often be managed in the office setting


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Treatment: Anti-fungal

} The benefit of systemic antifungal agents is

unclear in the literature.

} Amphotericin B, ketoconazole,

itraconazole, and fluconazole have allbeen evaluated.

} Mixed results have been reported; the

drugs are expensive and sometimesdangerous

} Regular evaluation of their LFT.


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x: 32 patients AFRS refractory to treatment.

method: Sporanox X 3months

Results:} Subjectively by RSOM-31} 9(28%) significant improvement.

} 9(28%) moderate improvement.} 14(44%)little or no change.

} Endoscopically} 12 improvement.} 15 no change.

} 5 worse.

Chan et al. Pilot study: itraconazole in the managementof refractory AFRS, 2000



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Liver function test

}6 (19%) had increase in LFTD/C drug.

}1 chemical hepatitis with jaundice.

}All LFT returned to normal.

Chan et al. Pilot study: itraconazole in the managementof refractory AFRS, 2000



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} The role and efficacy of antifungal irrigations is

also unclear.

} Amphotericin B has been advocated strongly

as the answer to maintenance therapy

Treatment: Anti-fungal irrigation

Sherris DA, Ponikau JU et al. Treatment of chronic rhinosinusitis with intranasalamphotericin B: A prospective, randomized, placebo-controlled trial.

J Allergy Clin Immunol. 2005;115:125-31.


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Treatment: Anti-fungal irrigation

Sherris DA, Ponikau JU et al. Treatment of chronic rhinosinusitis with intranasalamphotericin B: A prospective, randomized, placebo-controlled trial.

J Allergy Clin Immunol. 2005;115:125-31.

x: 24 patients completed the 6 months

Method: Instill 20 mL amphotericin B

(250 mug/mL) or placebo to each nostriltwice daily for 6 months

Result:

} Reduction in the percentage of mucosalthickening on CT scans (-8.8%) compared with

placebo (+2.5%; P=

.030)} Endoscopic scores improved in the

amphotericin B group compared with placebo( P = .038).


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Thank you

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Gr Rounds Fungal Sinusitis