aspergillus sinusitis david w. denning wythenshawe hospital university of manchester
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Aspergillus sinusitis
David W. DenningWythenshawe Hospital
University of Manchester
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Cécile Clercx in www.aspergillus.man.ac.uk
Patient 1Patient 1
Presenting features: 3 month history of sneezing and reverse sneezing, left nasal sanguinopurulent discharge,
2 episodes of epistaxis, ulceration of the external left nare,
hyperkeratosis of the planum nasale
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Cécile Clercx in www.aspergillus.man.ac.uk
Nasal endoscopyNasal endoscopy
severe turbinate tissue destruction, presence of multiple fungal plaques in the left nasal cavity and in the left frontal sinus
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Cécile Clercx in www.aspergillus.man.ac.uk
Treatment of canine nasal Treatment of canine nasal aspergillosisaspergillosis
ProductRoute
DoseInterval(hours)
Duration(weeks)
Efficacy(%)
Reference
Thiabendazole
PO* 10 mg / kg 12h 6 to 8 ± 50 Harvey 1984
Ketoconazole PO* 5 mg / kg 12h 6 to 18 ± 50 Sharp 1989Ketoconazole PO* 5 mg / kg 12h 10 ± 60-70 Legendre 1995Fluconazole PO* 2.5 mg / kg 12h 10 ± 60-70 Sharp 1991Enilconazole IN1 10 mg / kg 12h 1 to 2 times ± 80 Sharp 1993
Enilconazole IN2 5 %, 50 - 200 ml
30 - 45 min infusion
1 month interval, 2 to 3 times
100 McCullough 1998
Enilconazole IN2 1% 1 hour infusion1 month interval, 1 to 3 times
up to 80%
Zonderland 2000
Clotrimazole IN1
1%, once, infusion of 1 gm
± 90 Davidson 1997
Clotrimazole IN1 1%, 60 ml/side
1 hour infusion once 80 - 90 Mathews 1998
Clotrimazole IN2 1%, 60 ml/side
1 hour infusion once 80 - 90 Mathews 1998
2% imaverol solution infused during one hour through nonsurgically placed
catheters
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Cécile Clercx in www.aspergillus.man.ac.uk
Nasal endoscopyNasal endoscopy
severe turbinate tissue destruction, presence of multiple fungal plaques in the left nasal cavity and in the left frontal sinus
After treatment:absence of fungal plaques, cystic appearance of the left nasal and frontal sinus mucosa
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Interaction of Aspergillus with the host
A unique microbial-host interaction
Immune dysfunction
Frequency
of a
sperg
illosis
Immune hyperactivity
Frequency
of
asp
erg
illosi
s
Acute invasive sinusitis
Fungus ball of the sinusChronic granulomatous sinusitis
Allergic sinusitis
. www.aspergillus.man.ac.uk
Chronic invasive sinusitis
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Hope et al, Med Mycol 2005:43 (Suppl 1):S207
Acute invasive Aspergillus sinusitis
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www.aspergillus.man.ac.uk
Myelodysplasia with clinical evidence of sinusitis after
chemotherapy – biopsy showed hyphal invasion of
bone
Pre-treatment 6 months later after initial caspofungin then voriconazole
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Management of acute invasive Management of acute invasive Aspergillus sinusitis
Requires both biopsy and preferably culture for Requires both biopsy and preferably culture for diagnosis – differential diagnosis = diagnosis – differential diagnosis =
mucormycosis, mucormycosis, ScedopsporiumScedopsporium//FusariumFusarium infectioninfection
Requires systemic antifungal therapy to Requires systemic antifungal therapy to minimise minimise tissue destruction, including spread tissue destruction, including spread to face, to face, eye, mouth and brain and cureeye, mouth and brain and cure
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Herbrecht et al, New Engl J Med 2002; 347:408-15
Antifungal treatment of acute Antifungal treatment of acute invasive invasive Aspergillus sinusitis
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Girmenia and the Girmenia group
Antifungal treatment of acute Antifungal treatment of acute invasive invasive Aspergillus sinusitis
First line treatment with voriconazole (n=13)
better responses at day 7 of therapy (62% vs 24%), higher CR + PR, better 3-month survival rate (69% versus 38%) fewer severe side effects
compared to
historical group Rx with amphotericin B or itraconazole (n=21),
with or without combined radical surgery.
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Salvage treatment with caspofungin or micafungin in invasive aspergillosis
Maertens et al Clin Infect Dis 2004; 39:1563; Denning et al, J Infect 2006; in press
Favourable response (%) Micafungin
Caspofungin
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Management of acute invasive Management of acute invasive Aspergillus sinusitis
Requires both biopsy and preferably culture for Requires both biopsy and preferably culture for diagnosis – differential diagnosis = diagnosis – differential diagnosis =
mucormycosis, mucormycosis, ScedopsporiumScedopsporium//FusariumFusarium infectioninfection
Requires systemic antifungal therapy to Requires systemic antifungal therapy to minimise minimise tissue destruction, including spread tissue destruction, including spread to face, to face, eye, mouth and brain and cureeye, mouth and brain and cure
? Requires surgical removal – and if so early or ? Requires surgical removal – and if so early or latelate
? Requires granulocytes/other immunotherapy ? Requires granulocytes/other immunotherapy
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Hope et al, Med Mycol 2005:43 (Suppl 1):S207
Chronic invasive Aspergillus sinusitis
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Hope et al, Med Mycol 2005:43 (Suppl 1):S207
Chronic invasiveChronic invasive Aspergillus sinusitis
Chronic Aspergillus granulomatous Chronic Aspergillus granulomatous sinusitis = A. flavus
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ANITHA, NIZAMUDDIN,PUSHPA, REMADEVI. SIHAM 2006
Diabetic with swelling, nasal obstruction and epistaxis
A. terreus cultured
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Aspergillus precipitins
Chakrabarti. Indian J Chest Dis Allied Sci 2000;42:293-304
Probably useful for diagnosis and
monitoring response to
treatment – but limited data
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www.aspergillus.man.ac.uk
Allergic Aspergillus sinusitisAllergic Aspergillus sinusitis
Clinical features = nasal obstruction, recurrent sinus infections, loss of smell and nasal polyps
Aspergillus precipitins +ve in 85% of original series
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Buzina and the Gras group - www.aspergillus.man.ac.uk /laboratory protocols
Surgical handling of specimen Surgical handling of specimen very very importantimportant – mucus versus tissue: – mucus versus tissue:
allergic or chronic invasiveallergic or chronic invasiveAll surgical procedures should be performed without a power microdebrider or the use of suction devices until sample collection is complete.
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Buzina and the Gras group - www.aspergillus.man.ac.uk /laboratory protocols
Surgical handling of specimen Surgical handling of specimen very very importantimportant – mucus versus tissue: – mucus versus tissue:
allergic or chronic invasiveallergic or chronic invasiveAll surgical procedures should be performed without a power microdebrider or the use of suction devices until sample collection is complete.
Mucus should be manually removed, together with inflamed tissue, and placed on a saline-moistened sheet of sterile used x-ray film (approx. 10 x 10 cm) to prevent absorption of the mucus. It should not be placed on a surgical towel or gauze.
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Buzina and the Gras group - www.aspergillus.man.ac.uk /laboratory protocols
Surgical handling of specimen Surgical handling of specimen very very importantimportant – mucus versus tissue: – mucus versus tissue:
allergic or chronic invasiveallergic or chronic invasiveAll surgical procedures should be performed without a power microdebrider or the use of suction devices until sample collection is complete.
Mucus should be manually removed, together with inflamed tissue, and placed on a saline-moistened sheet of sterile used x-ray film (approx. 10 x 10 cm) to prevent absorption of the mucus. It should not be placed on a surgical towel or gauze.
Each specimen is then fixed in 10% formalin and embedded in paraffin. Multiple serial sections of different specimens from each patient should be stained with H & E and with GMS.
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Buzina and the Gras group - www.aspergillus.man.ac.uk /laboratory protocols
Surgical handling of specimen Surgical handling of specimen very very importantimportant – mucus versus tissue: – mucus versus tissue:
allergic or chronic invasiveallergic or chronic invasiveAll surgical procedures should be performed without a power microdebrider or the use of suction devices until sample collection is complete.
Mucus should be manually removed, together with inflamed tissue, and placed on a saline-moistened sheet of sterile used x-ray film (approx. 10 x 10 cm) to prevent absorption of the mucus. It should not be placed on a surgical towel or gauze.
Each specimen is then fixed in 10% formalin and embedded in paraffin. Multiple serial sections of different specimens from each patient should be stained with H & E and with GMS.
The pathologists should pay special attention to the mucin, focusing on fungal elements and eosinophils.
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Chronic invasive Aspergillus sinusitis
Complications:- orbital apex syndrome- generalised proptosis and blindness- cavernous sinus thrombosis- osteomyelitis of the base of the
skull- cerebral aspergillosis
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www.aspergillus.man.ac.uk
Orbital apex syndromeOrbital apex syndrome
Clinical features = sudden or subacute loss of vision, with ophthalmoplegia on one eye, typically associated with sphenoid sinusitis
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Swift & Denning. J Otol Laryngol 1998;112:92-97.
Base of skull osteomyelitisBase of skull osteomyelitis
Clinical features = headache, general ill-health, raised inflammatory markers, sometimes associated sinus features
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Sphenoid sinusitis leading to local Sphenoid sinusitis leading to local spread to the brain and cerebral spread to the brain and cerebral
aspergillosisaspergillosis
Sphenoid sinusitis causes a band-like headache over the vertex of the skull, and major deterioration in headache. Nasal symptoms often absent, but loss of smell common.
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Hope et al, Med Mycol 2005:43 (Suppl 1):S207
Non-allergic Aspergillus sinusitis
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www.aspergillus.man.ac.uk
Saprophytic Aspergillus sinusitisSaprophytic Aspergillus sinusitis
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Saprophytic maxillary Aspergillus sinusitis
Often follows upper jaw root canal work, with the Often follows upper jaw root canal work, with the use of zinc materials, and penetration of the use of zinc materials, and penetration of the sinussinus
Presents with ‘chronic’ or ‘recurrent’ sinusitisPresents with ‘chronic’ or ‘recurrent’ sinusitis
Requires removal of fungal ball, and creation of Requires removal of fungal ball, and creation of an antrostomy. Surgical biopsy of the mucosa an antrostomy. Surgical biopsy of the mucosa required to distinguish chronic invasive disease required to distinguish chronic invasive disease from saprophytic. Antifungal therapy not from saprophytic. Antifungal therapy not requiredrequired
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ConclusionsThe same spectrum of Aspergillus disease in the The same spectrum of Aspergillus disease in the lung is found in the sinuseslung is found in the sinuses
Bony erosion is consistent with all formsBony erosion is consistent with all forms
The pace/rapidity of the disease is a good guide The pace/rapidity of the disease is a good guide to the severityto the severity
Histology of mucosa and mucous key to Histology of mucosa and mucous key to determining disease classification and determining disease classification and managementmanagement
Precipitating antibodies useful in diagnosisPrecipitating antibodies useful in diagnosis
Treatment depends on the type of diseaseTreatment depends on the type of disease
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