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Aspergillus sinusitis David W. Denning Wythenshawe Hospital University of Manchester.

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Presentation on theme: "Aspergillus sinusitis David W. Denning Wythenshawe Hospital University of Manchester."— Presentation transcript:

1 Aspergillus sinusitis David W. Denning Wythenshawe Hospital University of Manchester

2 Cécile Clercx in Patient 1 Patient 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

3 Cécile Clercx in Nasal endoscopy severe turbinate tissue destruction, presence of multiple fungal plaques in the left nasal cavity and in the left frontal sinus

4 Cécile Clercx in Treatment of canine nasal aspergillosis Treatment of canine nasal aspergillosis ProductRouteDose Interval (hours) Duration (weeks) Efficacy (%) Reference ThiabendazolePO * 10 mg / kg12h6 to 8± 50Harvey 1984 KetoconazolePO * 5 mg / kg12h6 to 18± 50Sharp 1989 KetoconazolePO * 5 mg / kg12h10± 60-70Legendre 1995 FluconazolePO * 2.5 mg / kg12h10± 60-70Sharp 1991 EnilconazoleIN 1 10 mg / kg12h1 to 2 times± 80Sharp 1993 EnilconazoleIN 2 5 %, ml min infusion 1 month interval, 2 to 3 times 100McCullough 1998 EnilconazoleIN 2 1%1 hour infusion 1 month interval, 1 to 3 times up to 80% Zonderland 2000 ClotrimazoleIN 1 1%, once, infusion of 1 gm ± 90Davidson 1997 ClotrimazoleIN 1 1%, 60 ml/side 1 hour infusiononce Mathews 1998 ClotrimazoleIN 2 1%, 60 ml/side 1 hour infusiononce Mathews % imaverol solution infused during one hour through nonsurgically placed catheters

5 Cécile Clercx in Nasal 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

6 Interaction of Aspergillus with the host A unique microbial-host interaction Immune dysfunction Frequency of aspergillosis Immune hyperactivity Frequency of aspergillosis Acute invasive sinusitis Fungus ball of the sinus Chronic granulomatous sinusitis Allergic sinusitis. Chronic invasive sinusitis

7 Hope et al, Med Mycol 2005:43 (Suppl 1):S207 Acute invasive Aspergillus sinusitis

8 Myelodysplasia with clinical evidence of sinusitis after chemotherapy – biopsy showed hyphal invasion of bone Pre-treatment 6 months later after initial caspofungin then voriconazole

9 Management of acute invasive Management of acute invasive Aspergillus sinusitis Requires both biopsy and preferably culture for diagnosis – differential diagnosis = mucormycosis, Scedopsporium/Fusarium infection Requires systemic antifungal therapy to minimise tissue destruction, including spread to face, eye, mouth and brain and cure

10 Herbrecht et al, New Engl J Med 2002; 347: Antifungal treatment of acute invasive Antifungal treatment of acute invasive Aspergillus sinusitis

11 Girmenia and the Girmenia group Antifungal treatment of acute invasive Antifungal treatment of acute 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.

12 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

13 Management of acute invasive Management of acute invasive Aspergillus sinusitis Requires both biopsy and preferably culture for diagnosis – differential diagnosis = mucormycosis, Scedopsporium/Fusarium infection Requires systemic antifungal therapy to minimise tissue destruction, including spread to face, eye, mouth and brain and cure ? Requires surgical removal – and if so early or late ? Requires granulocytes/other immunotherapy

14 Hope et al, Med Mycol 2005:43 (Suppl 1):S207 Chronic invasive Aspergillus sinusitis

15 Hope et al, Med Mycol 2005:43 (Suppl 1):S207 Chronic invasive Chronic invasive Aspergillus sinusitis Chronic Aspergillus granulomatous Chronic Aspergillus granulomatous sinusitis = A. flavus

16 ANITHA, NIZAMUDDIN,PUSHPA, REMADEVI. SIHAM 2006 Diabetic with swelling, nasal obstruction and epistaxis A. terreus cultured

17 Aspergillus precipitins Chakrabarti. Indian J Chest Dis Allied Sci 2000;42: Probably useful for diagnosis and monitoring response to treatment – but limited data

18 Allergic Aspergillus sinusitis Allergic Aspergillus sinusitis Clinical features = nasal obstruction, recurrent sinus infections, loss of smell and nasal polyps Aspergillus precipitins +ve in 85% of original series

19 Buzina and the Gras group - /laboratory protocols Surgical handling of specimen very important – mucus versus tissue: Surgical handling of specimen very important – mucus versus tissue: allergic or chronic invasive All surgical procedures should be performed without a power microdebrider or the use of suction devices until sample collection is complete.

20 Buzina and the Gras group - /laboratory protocols Surgical handling of specimen very important – mucus versus tissue: Surgical handling of specimen very important – mucus versus tissue: allergic or chronic invasive All 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.

21 Buzina and the Gras group - /laboratory protocols Surgical handling of specimen very important – mucus versus tissue: Surgical handling of specimen very important – mucus versus tissue: allergic or chronic invasive All 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.

22 Buzina and the Gras group - /laboratory protocols Surgical handling of specimen very important – mucus versus tissue: Surgical handling of specimen very important – mucus versus tissue: allergic or chronic invasive All 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.

23 Chronic invasive Aspergillus sinusitis Complications: - orbital apex syndrome - generalised proptosis and blindness - cavernous sinus thrombosis - osteomyelitis of the base of the skull - cerebral aspergillosis

24 Orbital apex syndrome Orbital apex syndrome Clinical features = sudden or subacute loss of vision, with ophthalmoplegia on one eye, typically associated with sphenoid sinusitis

25 Swift & Denning. J Otol Laryngol 1998;112: Base of skull osteomyelitis Base of skull osteomyelitis Clinical features = headache, general ill-health, raised inflammatory markers, sometimes associated sinus features

26 Sphenoid sinusitis leading to local spread to the brain and cerebral aspergillosis Sphenoid sinusitis leading to local spread to the brain and cerebral aspergillosis 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.

27 Hope et al, Med Mycol 2005:43 (Suppl 1):S207 Non-allergic Aspergillus sinusitis

28 Saprophytic Aspergillus sinusitis Saprophytic Aspergillus sinusitis

29 Saprophytic maxillary Aspergillus sinusitis Often follows upper jaw root canal work, with the use of zinc materials, and penetration of the sinus Presents with chronic or recurrent sinusitis Requires removal of fungal ball, and creation of an antrostomy. Surgical biopsy of the mucosa required to distinguish chronic invasive disease from saprophytic. Antifungal therapy not required

30 Conclusions The same spectrum of Aspergillus disease in the lung is found in the sinuses Bony erosion is consistent with all forms The pace/rapidity of the disease is a good guide to the severity Histology of mucosa and mucous key to determining disease classification and management Precipitating antibodies useful in diagnosis Treatment depends on the type of disease

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