fungal sinusitis.pptx

Fungal rhino sinusitis

1. FUNGAL SINUSITIS Presenter : Dr raj pushkar Moderator:-Dr jasmeet kaur

2. INTRODUCTION 400,000 known fungal species of which 400 are human pathogens and 50 of which cause systemic or CNS infection Fungi are normally found everywhere in nature as spores, and most people have fungal colonization in the nasal cavity M o s t c o m mo n r o u te o f F R S : i n h alation o f s p o r es Clinical presentation, imaging features, and treatment differ based on type of fungal sinusitis

3. INVASIVE ACUTE FULMINANT FRS GRANULOMATOUS FRS CHRONIC FRS NON INVASIVE SAPROPHYTIC FUNGAL BALL ALLERGIC FRS

4. N o n I n v asi v e F R S 1. Saprophytic fungal infection Refers to visible fungal colonisation of mucus crust seen in nose and PNS on nasoendoscopy Asymptomatic ; foul smelling odour May be precursor to fungal ball if untreated Rx- Endoscopic cleaning of infected crust with or without continued irrigation with saline water Mechanism Dysfunction in : mucociliary transportation from surgery Nasal crust formation Platform for fungal growth opens

5. 2. Fungal ball Dense accumulation of extramucosal fungal hyphae usually within one sinus Most common Sinus: Maxillary Organism: Aspergillus Immunocompetant,middle aged and elderly females with h/o previous dental procedure esp dental fillings

6. Diagnosis Non specific chronic inflammation of the sinus in the absence of eosinophil predominance, granuloma and allergic mucin Microscopy : Accumulation of fungal hyphae without evidence of tissue fungal invasion Radiology : Sinus opacification with areas of hyper attenuation, cheesy or clay like debri within the sinus

7. T r e atme n t Wide opening of involved sinus and complete removal of fungal debri f/b regular surveillance Antifungal medications usually unnecessary Reccurence is rare

8. HISTORY In 1983 : term ‘ Allergic Aspergillus sinusitis ’ was proposed by Katzenstein et al. ( due to histological similarity with ABPA) - described the thick, inspissated mucoid material containing fungal hyphae in both the sinuses and the bronchi as - Allergic mucin 3 . A LL ERGI C F U N GAL R H INO S INU S IT I S

9. Mycology Common organism implicated: Aspergillus Curvularia Alternaria Bipolaris Fusarium

10. Epidemiology Most common among adolescents and young immunocompetent adults : mean age - 21-33 years Higher male : female ratio - 1.5-2.6 : 1 Warm and humid areas Low socioeconomic status Prevalence of FRS amongst CRS patients who undergo Sx - 12-47% : 56-77% have AFRS

11. Pathophysiology Fungi enters nose and sinuses Type 1 and 3 h y pe r sens i t i vi t y response(1>3) Inflammatory reactions Trapped fungi continues immune system stimulation Production of allergic mucin Stasis of secretion Obstruction of sinus ostia Explained by many theories 1. Manning et al - Immunological theory

12. 2. Panikou et al - Eosinophilic theory Eosinophilic chemotaxis in response to extra mucosal fungi - hallmark of inflammatory reaction in AFRs Introduced the term: Eosinophilic fungal rhinosinusitis Eosinophilic mucin

13. 3. Ferguson In 2000 Fungal Sinusitis AF R S Non allergic FRS Aka eosinophilic mucin RS Histology similar to AFRS but without presence of fungi

14. PATHOPHYSIOLOGY OF AFRS

15. D i agnos i s DIAGNOSTIC CRITERIA : BENT AND KUHN DIAGNOSTIC CRITERIA

16. All major criteria necessary to define AFRS while minor criteria are considered supporting features A n e l e v a ted I g E te s ts m a y n o t a l w a ys b e p r e s ent i n a l l A F R S p a t ien t s ST. PAULS SINUS CENTRE CRITERIA

17. Clinical Presentation Often symptoms are subtle and similar to that of chronic sinusitis with nasal polyposis Long standing history gradual nasal obstruction (often neglected for a period of years until complete obstruction Usually U/L thick or crusty semisolid nasal discharge Facial dysmorphia usually proptosis On nasoendoscopy - U/L or B/L nasal polyp Inspissated thick greenish brown peanut butter like mucus

18. CLINICAL FINDINGS WITH HIGH INDEX OF SUSPICION Nasal polyposis if u/l Young age Classical radiological finding – double density sign in CT Thick sticky yellowish brown or green mucus Proptosis in a case of nasal polyposis Signs of allergic rhinitis but not responding to antihistamines , intranasal steroids

19. Investigations 1. I mm u n olo g i c a l t e s t Total serum IgE : usually elevated; often ranging between 50->1000IU/ml, averaging 550 IU/ml Antigen specific IgE- for both fungal and other inhalants by in vitro ( Rapid Ag test) or in vivo (skin prick test)

20. 2. Histology-Pathology Hallmark of AFRS - Presence of allergic mucin Gross : Thick tenacious, viscous, yellow to brown to dark green- ‘Peanut butter’ or ‘axle grease’

21. Histology : Eosinophilic mucin with Necrotic degranulated eosinophils Charcot Leiden crystals Inflammatory cells Fungal hyphae (often found only with GMS stain)

22. 3. Fungal Culture : Supporting evidence 4. Imaging CT NCCT is the imaging of choice Opacification of the nasal cavity and one or more paranasal sinuses The sinuses are typically opacified by centrally (often serpiginous ) hyperdense material with a peripheral rim of hypodense mucosa. Erosion of bone (skull base and orbit) is seen in 20 - 60% of cases MRI Hypointensity on T1WI and T2WI is the most common finding. Indications of MRI : When diagnosis is uncertain When there is rare intracranial or intraorbital complication

23. CT

24. MR I

25. Management

26. Surgical management Surgery is the fist line of treatment Meticulous and complete ESS is the gold standard F E SS w i t h I G S i s p r e f e rr ed Aim : Complete removal of allergic mucin, polyp and fungal debris to decrease the antigenic load

27. Surgery helps in Re-establishing ventilation Removes antigenic stimulation for AFRS Provides access for surveillance, clinical debridement and application of topical medication Meticulous irrigation may be employed to flush out all debri after sinuses have been opened by widening their ostia Principle of mucosal preservation should be followed

28. Endoscopic staging of mucosal disease post surgery

29. MEDICAL MANAG E MENT Systemic medications 1. Corticosteroids : Useful in perioperative period of patients with AFRS Pre operative period : helps to reduce intra-op bleeding and size of polyp Post operative period : Minimum 6 month of normal mucosa while on steroid in order to slowly discontinue . Prevents recurrence Use should be limited to perioperative period and acute exacerbations ( to suppress growth of recurrent polyp)

30. 2. Antifungals For patients with recalcitrant AFRS Used as steroid sparing medications Oral Itraconazole 200-400mg daily Elevated liver enzymes , CCF, nausea, rash, headache, malaise, fatigue and edema

31. Topical medications 1. Corticosteroids Used as standard Rx for patients with AFRS Most effective in postoperative period Benefit: Ability to achieve highest drug concentration in target area without undesirable systemic side effects Standard topical nasal steroids are Mometasone furoate Fluticasone propionate Fluticasone furoate Budesonide Flumisolide

32. Non standard Topical nasal steroids Budesonide : As drops; atomised sprays or through low volume saline rinses Intranasal dexamethasone ophthalmic drops (0.01%) Prednisolone ophthalmic drop (1%) Ciprofloxacin/dexamethasone otic drops Adv : Can deliver higher volume and/or high concentration of steroids to sino nasal cavity Disadv : Systemic side effects and suppression of HPA axis

33. Mucosal atomisation device (MAD) helps to deliver low volume high concentration steroid into frontal recess and sinuses Position : Head hanging posture (Mygind position) to target frontal recess areas Should stay in this position for 4 – 5 min

34. 2. Antifungals Topical antifungals have been deemed ineffective Some studies show recurrence rate as : Fluconazole nasal spray < Oral itraconazole + topical fluconazole < Fluconazole nasal irrigation < oral itraconazole

35. 3. Immunotherapy To reduce the production of allergen specific IgE and to increase the production of IgG4 blocking antibodies Most of the studies showed improvement in clinical outcomes with no major systemic reactions or worsening of disease Disadv : works only in conjunction with surgery or other modalities of treatment May not be successful in the presence of fungal antigen load not addressed by surgery – may worsen the disease

36. Adjunctive treatment Manuka Honey Manuka ( Leptospermum scoparium) honey from New Zealand is the most therapeutically potent honey Principal active agent : Methylgloxal E f f e ct i v e i n e ra d ic a ti n g M S SA, M R SA a n d P A b i ofilms Concentration – 0.9 – 1.8 mg/ml ; diluted as 15g in 1L MOA : High glucose content of honey provide energy for phagocytes Acidic pH directly kill the organisms By production of inhibin

37. Future Treatment Strategy Anti Immunoglobulin (IgE) therapy Biologic agents are upcoming group of adjunctive therapies in managent of AFRS O n l y o n e a ge n t h a s b e en s t u died i n u s e o f A F R S – O M A LI Z U M B Specific action at the receptor level – reduce systemic side effects Slows down and may even reverse the inflammatory process

38. Invasive FRS 1. Acute (fulminant) Invasive FRS Life threatening - most lethal form of fungal sinusitis - Mortality 50-80% Rapid hyphal invasion of sinus: Time course<4 weeks Causative organism : Aspergillus and Mucorales (Rhizopus, Rhizomucor, mucor) Immunocompromised patients are more susceptible Uncontrolled DM AIDS Iatrogenic immunosuppression Organ transplantation Hematological Malignancy

39. Clinical features Immunocompromised patients - Pyrexia of unknown origin for 48 hrs despite of broad spectrum IV antibiotics Fever, cough, headache, crusting of nasal mucosa and epistaxis Pain, tenderness and pressure in the sinus area Anaestesia of face or nose – early sign Painless necrotic nasal septal ulcer - eschar

40. Intraorbital, intracranial and maxillofacial extension is common Proptosis Visual disturbances Hypertelorism Headache Mental status changes Seizures Neurological deficits Coma Maxillofacial soft tissue swelling Angioinvasion and haematogenous dissemination common

41. D iagno s i s DNE : Alteration In mucosal appearance such as discoloration, granulation and ulceration- most consistent physical finding crusting, whitish discoloration or black discoloration with eschar formation Granulation or ulceration of nasal mucosa : MT > Septum > Palate and IT Histological feature : - Mycotic infiltration of blood vessels, Vasculitis with thrombosis , tissue infarction, hemorrhage and a/c neutrophilic infiltrate

42. CT Scan- IOC Focal bony erosion Lack of expansion of sinuses Limited sinus disease- more disease outside sinus Mucosal thickening: hypoattenuating Nasal septal ulceration Fat stranding outside the sinus perimeter intraorbital fat periantral fat nasolacrimal duct lacrimal sac masticator space pterygopalatine fossa

43. MRI Better for evaluating intracranial and intraorbital extension Evaluate for inflammatory change in orbital fat and extraocular muscles Obliteration of periantral fat is a subtle sign of extension Leptomeningeal enhancement progressing to cerebritis and abscess

44. Treatment T h e rapy o f i n va s i v e F R S r e q ui r es Reversal of the underlying predisposing condition- most important Appropriate systemic antifungal Surgical debridement It slows prognosis of disease Reduces fungal load Provides specimen for culture

45. Mx include endoscopic debridement, often on multiple successive occasion, combined with both systemic and topical antifungal therapies based on the sensitivity of fungus isolated Before definite organism identified- empirical Rx- Broad-spectrum antifungal IV Amphotericin B is given Once specific organism identified- Triazole

46. A N T I F UNG A L A G E N TS AMPHOTERICIN B From Streptomyces nodosus Poorly absorbed orally –IV route MOA – binds to ergosterole in the cell membrane of fungus increases the permeability of cell membrane cell contents leak out death of cell

47. Drug formulations 1 . A m p h o t er i ci n B d e o x y c h o l at e ( D O C) Insoluble in water – so complexing it with bile salt deoxycholate Prior to starting the drug patient should be hydrated with 500 ml – 1L of normal saline A test dose should be administered by diluting 1mg of the drug in 50-100 ml of 5% Dextrose given slowly IV over 20 min 2 ways to administer the drug Start with a low dose , titrate gradually till maximum dose is achieved Start with a standard dose and maintain the same till a total cumulative dose is achieved

48. Std Dose : 0.25 – 1 mg/kg/day , in a single dose, diluted in 5% dextrose as slow IV Bottle and Tubing should be protected from light Max daily dose – 1.2mg/kg in adults and 1.5 mg/kg in children

49. 2. L i p i d b a s ed f or m ulatio n s Using lipid carriers Adv – selective delivery into RES and lesser degree to lungs better side effect profile Although dose related efficacy may be less the fact that higherdoses can be used makes them more efficacious LIPOSOMAL AMPHOTERICIN B – 1-5 mg/kg AMPHOTERICIN B LIPID COMPLEX – 5 mg/kg AMPHOTERICIN B CHOLESTEROL SULPHATE COMPLEX – 3 to 5 mg/kg

50. ITRACONAZOLE 100 mg 1-2 po bid with meals Active against many dematiaceous fungi; variably active against Aspergillus species; not active against Zygomycetes Best absorbed in acidic stomach; co-administer with cola or cranberry juice; if used long term, liver function must be monitored POSACONAZOLE Oral suspension of 40 mg/mL; dosage is 400 mg bid, given with fatty foods to enhance absorption Indicated for the treatment of a broad range of invasive fungal infections, including Zygomycetes, Fusarium , and Aspergillus, in patients who have refractory infections or cannot tolerate other antifungal therapies Safety in patients younger than 18 years not assessed; use with caution with other drugs metabolized through the cytochrome-P3A4 system

51. TERBINAFINE 250 mg po qd Variable in vivo anti- fungal activity; utilized chiefly for dermatophytosis Not effective in a randomized controlled trial against noninvasive chronic rhinosinusitis VORICONAZOLE 200 mg bid po 1 hour before or after meals; IV formulation given as loading dose, followed by 4 mg/kg bid Indicated for treatment of a broad range of fungal pathogens Liver function and creatinine must be monitored; unusual adverse effect is visual disturbance

52. 2. Chronic granulomatous invasive fungal sinusitis Primary paranasal granuloma and indolent fungal sinusitis Primarily found in Africa (Sudan) and Southeast Asia, only few case reports in US Immunocompetent Caused by Aspergillus flavus Characterized by non-caseating granulomas in the tissues

53. Chronic indolent course similar to chronic invasive fungal sinusitis Considered by some as same entity as chronic invasive fungal sinusitis Imaging characteristics are similar to those of chronic invasive fungal sinusitis Often resembles a mass/neoplasms Treatment is surgical debridement and systemic antifungals

54. 2. Chronic Invasive FRS Slowly destructive disease Time course >12 weeks Granulomatous variant : Aspergillus flavus Tissue invasion and granulomatous reaction with non caseating granuloma Invasive variant : Aspergillus fumigatus Vascular invasion and disease accumulation of fungal hyphae in sinus

55. Clinical feature Most commonly involved- ethmoid and sphenoid Usually in immunocompetant H/O of chronic RS with symptoms of PNS pain, nasal discharge, epistaxis, nasal polyposis and fever Maxillofacial soft tissue swelling Palatal erosions Proptosis with orbital apex syndrome Diminished vision Headache, seizure, decreased mental status

56. D i a g n o s i s CT CT usually shows homogeneous opacification of the affected sinus(es) Other suggestive features include: Relative lack of expansion of sinuses Mottled lucencies or irregular bone destruction may be seen Bone erosion localized to the area of extrasinus extension Extra sinus component of the disease more prominent than the intrasinus component There may also be sclerotic changes in the bony walls of the affected sinuses representing chronic disease

57. MRI Decreased intensity in T1 and markedly decreased intensity in T2 weighted image

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