Fungal sinusitis

1. FUNGAL
RHINOSINUSITIS

2. (presence or absence of fungal hyphae in tissue)
Fungal
rhinosinusitis
invasive non invasive

3. non-invasive fungal
rhinosinusitis
• Saprophytic fungal
infection
• Fungal ball
• Allergic Fungal
Sinusitis
invasive fungal
sinusitis
• Acute(fulminant)
invasive FRS
• Chronic invasive
FRS
• Chronic
granulomatous
invasive FRS

4. SAPROPHYTIC FUNGAL INFECTION
• Visible fungal colonization
• Asymptomatic / foul smelling odour.
• Mechanism- mucociliary dysfunction after surgery
• Saprophytic fungal infection fungal balls.
• Treatment- Endoscopic cleaning of the infected crust with or without
continued self-irrigation .

5. FUNGAL BALL
• Dense accumulation of extramucosal fungal hyphae.
• M.C -maxillary sinus
• M.C organism -Aspergillus.
• Immunocompetent with history of previous dental procedure.
Clinically
• Symptoms due to mass effect and sinus obstruction
• Presents similar to rhinosinusitis
• Congestion, facial pain, headache, rhinorrhoea.

6. The diagnosis of fungal ball is based on:
• Cheesy or clay-like debris within the sinus.
• Radiological finding- sinus opacification with areas of
hyperattenuation.
• Accumulation of fungal hyphae without tissue fungal invasion.
• Non-specific chronic inflammation of the sinus.
• Absence of eosinophil predominance, granuloma or allergic mucin.

8. Management-
wide opening of sinus and fungal debris clearance.
Oral or topical antifungals are not necessary
Antifungal therapy
• if high risk for invasive disease
• Severely immunocompromised
• Recurrence of disease

9. ALLERGIC FUNGAL RHINOSINUSITIS (AFRS)
• AFRS is a non-invasive fungal sinusitis - allergic and immunologic
response to the presence of extramucosal fungal hyphae in the
sinuses.
• Pathogen- Aspergillus, Bipolaris, Curvularis and Alternaria.
• Young immunocompetent adults.
• Pathophysiology- fungal-specific IgE antibodies and lgG antibodies.
• Atopic host exposed to fungi antigenic stimulation of cell
and Coombs type 1 and type III hypersensitivity.

10. Bent and Kuhn Diagnostic Criteria for AFRS
• All 5 major criteria were necessary to define AFRS while the minor
criteria were considered supporting features
Major criteria
• Evidence of type IgE-
mediated hypersensitivity
• Nasal polyposis
• Characteristic CT findings
[hyperattenuation]
• Eosinophilic mucus
• Positive fungal smear
Minor criteria
• Asthma
• Unilateral predominance
• Radiographic bone
erosion
• Fungal culture
• Charcot-Leyden crystals
• Serum eosinophilia

11. • St Paul's Sinus Centre Diagnostic Criteria for AFRS
• Major criteria
• Immunocompetent patient
• Presence of nasal polyposis
• Characteristic CT findings
• Presence of allergic mucin
• Positive fungal cultures or the presence of fungal hyphae on fungal staining

12. • Clinical presentation
• young patient with uni- or bi-lateral nasal
polyposis with thick, sticky yellow/green
mucus
• Symptoms:
• Nasal obstruction (gradual)
• Rhinorrhea
• Facial pressure/pain
• Sneezing, watery/itchy eyes
• Periorbital edema
• On nasoendoscopy- inspissated thick yellow or
brown peanut-butter like mucus.

13. Investigation
• Immunologic test –
-Elevated IgE level
-An in-vivo (skin prick) or in- vitro (RAST) test - demonstrate fungal
specific IgE
Characteristic findings of AFRS on CT and MRI scans
• CT features
• Heterogenous signal intensities within the paranasal sinuses filled with allergic mucin
('double density sign)
• Expansion of the paranasal sinuses/nasal cavity
• Unilateral or asymmetric disease load
• Bony erosion
• MRI features
• T1 and T2 weighted images- central areas of hypointensity with peripheral
enhancement.

15. • HISTOLOGY
• Most reliable marker - allergic mucin.
• Eosinophilic mucin with necrotic eosinophils, inflammatory cells, Charcot-
Leyden crystals and fungal hyphae.
• Grocott's or Gomori's methamine silver (GMS) stain
• Fungal culture-provides supportive evidence.

16. Management
combination of surgery and post-operative medical regimen.
• Surgical Treatment - first line treatment.
• Endoscopic sinus surgery - gold standard
• The goals of surgery
• To clear fungal mucin and debris to reduce the antigen load.
• To improve ventilation
• To preserve mucosa
• To create a wide sinus opening - detect early recurrence.
• To provide access -removal of fungal mucin and application of topical medication.

17. Medical treatment
SYSTEMIC MEDICATIONS
1.Corticosteroids
-Oral steroids
• Pre operative
• A meta-analysis of 1148 patients showed that pre-operative oral corticosteroids also reduced intra-
operative blood loss and improved surgical field quality.
• Post operative
-reduction in IgE and mucosal disease
limited to short courses in the perioperative period and in acute exacerbations of
AFRS to suppress growth of recurrent polyps.

18. 2.Antifungals
Oral antifungals are considered
• oral itraconazole (200-400 mg daily)
• steroid sparing alternative
• prolonging time to disease recurrence
• risk -elevated liver enzymes, congestive heart failure,
headache, malaise, fatigue and oedema
• study comparing the efficacy of oral itraconazole (200 mg BD for 2 days
followed by 100 mg BD for 26 days) in the pre and postoperative period
showed better disease control and lesser chances of recurrence with pre-
operative administration.

19. TOPICAL MEDICATION
• 1.Topical corticosteroid is the standard treatment
• Highest drug concentration in sinonasal mucosa.
• Mucosal atomization devices (MAD) –low volume high concentration steroid .
• Mygind or Regan position - target the frontal recess areas.
• Budesonide rinses (2 ml of 0.5 mg/ml Pulmicort Respules in every 60ml of
normal saline) in the immediate postoperative period.
• After 3 weeks postoperatively, the budesonide is delivered through a MAD (1
ml in each nostril).

20. • A randomised control trial comparing 1 mg nasal budesonide nebulization against topical nasal
sprays (n=15) found that patients using budesonide had no recurrence of disease compared to
26.67% of patients who had recurrence of disease in the second group over a mean follow-up
period of 18.5 months.
• 2 studies that have studied the safety of budesonide in the nasal cavity. One reported the effects of
short-term use of Budesonide (up to 2 months) and found no implications of regular use of
budesonide. The other studied the effects of long-term use of budesonide (>6 months) and found a
3% incidence of asymptomatic adrenal suppression in these patients.

21. 2.Topical antifungals – ineffective
Two meta-analysis studies eventually showed that there was no benefit with the use of intranasal
amphotericin B either in the form of a rinse or nasal spray.

22. Advanced Therapies
Biologic Agents
• Omalizumab, an anti-IgE monoclonal antibody - It
binds to Fc receptor and thereby blocks the IgE mediated
inflammatory pathway.
• it downregulates the Fc receptors on Mast cells,
dendritic cells and basophils
• retrospective chart review by Javer et al which included
seven patients with refractory AFRS & asthma, who
were studied over a 2 year period. These patients had
received an average of 287mg of Omalizumab & showed
a 31% improvement in their SNOT 22 scores and 61%
improvement in the endoscopic grading.

23. Antimicrobial Photodynamic Therapy
(aPDT)
• Non-antibiotic broad-spectrum
antimicrobial - eradicate 99.99% of
organisms.
• Report of aPDT being used in rabbits after
inoculation of Aspergillus fumigatus in their
maxillary sinuses. Compared to control
rabbits, the SinuwaveTM antimicrobial
photodynamic therapy was able to kill
99.99% of recoverable fungus.
Intranasal Betadine Rinses
Broad spectrum antimicrobial
Javer et al reported a study involving patients
with recalcitrant sinusitis being treated with
0.08% povidone iodine rinses and assessed pre
and post-treatment improvement in MLK scores
and SNOT 22 scores. They found a statistically
significant improvement in both parameters.

24. Manuka Honey Rinses
• mechanisms –
• 1. high glucose content of honey is thought to provide energy for the
phagocytes.
• 2. acidic pH- directly kill the organisms.
• 3. produce “inhibin” -hydrogen peroxide.

25. ENDOSCOPIC STAGING OF MUCOSAL DISEASE POST-
SURGERY
• The Philpott-Javer system

26. Invasive fungal sinusitis
• Invasive fungal sinusitis is defined as the presence of fungal hyphae
within the mucosa, submucosa, bone, or blood vessels on
histopathology.
• immunocompromised individuals.

27. Factors predisposing
Metabolic or systemic disorders
Diabetes mellitus
Hematological disorders
Acquired immunodeficiency
syndrome (AIDS)
Iatrogenic immunosuppression
Systemic steroid therapy
Chemotherapy with neutropenia
Prolonged antibiotic therapy
Post-organ or stem cell
transplantation

28. Pathophysiology of invasive fungal sinusitis
Inhaled fungal spores trapped in the paranasal sinuses
impaired macrophages and PMN block replication
undetected fungal proliferation, angioinvasion, necrosis
Progressing fungal invasion, hemorrhage and necrosis
extensive necrosis limits drug delivery and immune response
Dissemination

29. Acute(Fulminant) Invasive FRS
• Life threatening disease- immunocompromised patients
• Rapidly progressing invasive disease
• hyphal invasion of sinus tissue in time course of less than 4 weeks.
• Mucor species or Aspergillus
• In diabetes (80%)-Zygomycetes such as Rhizopus sp, Rhizomucor sp,
Absidia sp., and Mucor sp.
• In immunocompromised with neutropenia(80%)-Aspergillus species
such as A.fumigatus,A.flavus.

30. Symptoms
• Fever
• Nasal blockage, bloodstained serosanguineous nasal discharge,
crusting of nasal mucosa
• Facial or periorbital swelling, facial pain, numbness and headache.
• Orbital symptoms: chemosis, proptosis, ptosis, blurring of vision, loss
of vision and ophthalmoplegia.
• Loosening of teeth/ discoloration of palate
• Cranial nerve palsies - 2nd, 3rd, 4th, 5th, 6th and 7th nerve palsy.
• CNS symptoms- altered consciousness, delirium, convulsions,
hemiparesis, coma

32. ENT Examination
nasal endoscopy.
• Discoloration of the nasal mucosa and serosanguineous discharge.
• Crusting, tissue ischemia or black discoloration with eschar formation.
• Granulation or ulceration of the nasal mucosa.
Histopathology
• Mycotic infiltration of blood vessels, vasculitis with thrombosis, tissue
infarction, haemorrhage and acute neutrophilic infiltrate.

34. CT scan -initial radiological IOC
• mucosal thickening
• Focal bony erosions, lacks expansion of sinuses and intraorbital and
intracranial extension.
• MRI is superior to CT to evaluate intraorbital and intracranial
extension.

35. MR imaging
features of
ROCM
Sinonasal
involvement

36. Extrasinus
extension

37. Orbital
involvement

38. Intracranial
extension

39. Granulomatous invasive fungal sinusitis
• Invasive fungal > 12 weeks
• Causative agent-Aspergillus flavus.
• immunocompetent individuals.
• CT Scan- multiple sinus involvement
• Histology-fungal tissue invasion and granulomatous reaction with
considerable fibrosis.

41. Chronic Invasive Fungal Sinusitis
• Invasive fungal > 12 weeks
• Causative agent-Aspergillus fumigatus.
• immunocompetent individuals
• M.C- Ethmoid and sphenoid sinus.
• Histology- invasion of fungi with dense accumulation of fungal
hyphae, occasional vascular invasion, and chronic or sparse
inflammatory reaction.

43. Management
• Correction of predisposing factors
• Tapering of immunosuppressive therapy
• Discontinuation of steroid
• Glycaemic control
• G-CSF for neutropenia, discontinuation of chemotherapeutic agents causing
bone marrow suppression.
• Surgical debridement
• Early, aggressive and repeated surgical excision.
• The limits of debridement- intraoperative frozen sections

44. Antifungal for invasive mucormycosis
Drug Dose Properties
LAMB 5-10 mg/kg/day Less nephrotoxicity, Expensive,
Good CNS penetration
Amphotericin B lipid complex
(ABLC)
5-7.5 mg/kg/day Less nephrotoxicity, Expensive
Posaconazole 800 mg/day PO in 4 divided dose Oral administration for salvage
maintenance/ secondary
prophylaxis
Isavuconazole Loading dose: 200 mg 8 hourly for
the 1st 48 hours (total of 6 doses).
Maintenance: 200 mg once daily
Oral and iv administration,
treatment of invasive aspergillosis
and invasive mucormycosis

45. Antifungal for invasive aspergillosis
Drug Dosage Properties
Voriconazole IV: 6 mg/kg Q12 × 24 h,
4 mg/kg Q12 starting Day 2
PO: 200 mg Q12 h
Oral formulation may be used as
step down therapy after initial
stabilisation with IV preparation
LAMB 3-5 mg/kg/day IV IV, No nephrotoxicity, High CNS
Penetration
Posaconazole IV: 300 mg Q12 × 24 h, 300 mg
daily starting Day 2
Delayed-release: 300 mg Q12 ×24
h, 300 mg daily starting Day 2
Oral suspension: 200 mg TID
IV and Oral formulation
Isavuconazole IV: 200 mg Q8 h × 48 h, 200 mg
daily starting Day 3
PO: 200 mg Q8 h for 48 h, 200 mg
daily starting Day 3
IV and Oral formulation
Caspofungin 70 mg daily on Day 1, 50 mg daily
starting Day 2
IV, Low CNS Penetration

48. Triggers that may precipitate mucormycosis in people with COVID-19 in relation to
corticosteroids:
I. Presence of DM with or without DKA
II. Steroid use reduces the phagocytic activity of WBC
III. Endothelial damage, thrombosis, lymphopenia, and reduction in CD4+ and CD8+ T-
cell level
IV. Hyperglycemia reduces iron binding allowing increased free iron.
V. High glucose, low pH, free iron, and ketones in presence of decreased phagocytic
activity of WBC.
• Enhanced expression of glucose-regulator protein 78 (GRP-78) of endothelium- enabling
angio-invasion, hematogenous dissemination and tissue necrosis.

49. BIBLIOGRAPHY
• Scott Brown’s otorhinolaryngology 8th edition
• Invasive-Fungal-Rhinosinusitis-Gauri-Mankekar

50. Thank you