2. Main forms of fungi:
1. Yeasts: Unicellular organism.
2. Molds: Multicellular organism
Grow by branching into structures termed
Hyphae.
3. Spores:
Reproductive structures that can be produced in
presence of unfavorable conditions.
Once exposed to a favorable environment, they
begin to grow.
3. Laboratory diagnosis of Fungal
infections:
1. Direct Examination under Microscope (H/P):
Gomori Methenamine Silver (GMS) stain is the
best stain used to detect fungi by turning its color into black
or dark brown.
Fungal elements are recognized for a unique ability to
absorb silver.
2. Fungal Culture:
They are best used as supportive evidence.
Allows the identification of the specific etiologic agent.
Results are not available for days or weeks.
Examples of fungal media is Sabouraud dextrose agar.
7. 1. Saprophytic Fungal Infestation:
Occurs over sinonasal mucosa crusts in
otherwise immunocompetent
patients.
- Clinical Picture:
o Commonly found during
postoperative endoscopic
examinations+ bad odor.
- Diagnosis:
o Made by nasal endoscopy.
- Treatment:
o Weekly endoscopic removal of the
crusting with daily sinonasal rinses
until the disease process resolves.
o Antifungal medications are not
needed.
8. 2. Sinus Fungal Ball:
Sequestration (inhalation) of fungal elements in
immunocompetent patients.
Mycetoma is incorrect term in referring to
paranasal fungus balls, because mycetoma refers
to a fistulous fungal skin infection.
Most common sinus involved is Maxillary sinus
(80%) followed by sphenoid sinus (20%).
Mostly by Aspergillus fumigatus.
9. Risk factors:
1. Prior endodontic
treatment of maxillary
teeth.
2. Female predominance.
3. Bacterial infection:
Augment fungal growth
via purulent secretions
that provide valuable
nutrient supplies to the
fungi.
10. Clinical Picture:
1. Results of mass effect by the fungal ball and
sinus obstruction: Unilateral proptosis, facial
hypesthesia
2. Mimic chronic rhinosinusitis.
11.
12. Diagnosis:
1. Non-contrasted CT Sinuses:
o Gold standard imaging study.
I. Metalic sign: Due to increased heavy metal
content.
II. Bony sclerosis and thickening can be seen.
III. Fungal ball is not enhanced in contrasted
study.
o Helpful in differentiating fungal ball from
malignant processes associated with sinus
opacification and bone erosion.
13. 2. MRI Sinuses:
o HYPO-intense in T1 and
T2.
3. Biopsy with Fungal
Culture:
o Most common
Aspergillus Fumigatus.
o Microscopic
Appearance of
Aspergillus:
Septated hyphae with
acute angle branching at
45⁰.
14. Treatment:
1. Surgery:
1. Complete endoscopic surgical removal.
2. External approaches in only challenging cases.
2. Medical:
o Antifungal medications:
Not needed in immunocompete patients.
Indications start Antifungal medications:
1. High risk patient for invasive disease
(immunocompromised).
2. Continued recurrence of disease.
Topical antifungals should be instituted first followed by
the least toxic medications if they are required.
15. 3. Eosinophilic Mucin Rhinosinusitis
(EMRS):
- Includes:
1. Allergic Fungal Rhinosinusitis (AFRS).
2. Eosinophilic Fungal Rhinosinusitis (EFRS).
3. Eosinophilic Mucin Rhinosinusitis (EMRS).
- All have similar clinical picture and treatment
strategies.
- All have associated Eosinophilic mucin present.
16.
17. 3.I Allergic Fungal Rhinosinusitis
(AFRS):
Pathophysiology:
o IgE mediated hypersensitivity response to
fungal protein (Aspergillus).
o Production of sticky allergic mucin resists
clearance by normal mucociliary action and
promotes growth of nasal polyps.
18. Clinical Picture:
1. Young immunocompetent patient.
2. Positive history of asthma or atopy (40%).
3. Unilateral or asymmetric symptoms of
chronic rhinosinusitis with allergic
component: Nasal obstruction – itching –
polyposis ..etc
4. +ve history of reccurent surgeries.
20. Major Criteria (Diagnostic):
1. Type I hypersensitivity:
Positive RAST and ELISA test.
Elevated total serum IgE level (> 1000 IU/mL).
2. Nasal polyposis.
3. Characteristic CT findings: non-contrsted
a) Unilateral or asymmetric involvement (80%)
b) Metalic sign due to heavy metals (iron and
manganese) and calcium salts.
c) Remodeling and thinning of sinuses bony walls.
d) Bony erosion in advance disease due to
pressure, but not due to fungal invasion.
21. 4. Presence of eosinophilic mucin containing non-
invasive fungal hyphae:
Confirm the diagnosis.
Most reliable indicator of AFRS (Pathognemonic).
o Thick, tenacious and highly viscous, Tan to brown or
dark green in appearance.
Charcot-Leyden crystals (Products of eosinophilic
breakdown of cells).
5. Positive fungal stain of sinus contents:
o Gomori Methenamine Silver (GMS) stain.
o No evidence of necrosis, giant cells, granulomas, or
invasion into surrounding structures.
22. NB:
• Sinuses walls thickening in fungal ball.
• Thinning in AFRS. (Allargic).
• Fungal infection has pseudo-pnemutization.
23.
24.
25. Treatment of AFRS:
o Surgery:
- Cornerstone of treatment.
-debridement of involved sinuses.
- Goals of surgery:
1. Removal of all allergic mucin.
2. Provide permanent drainage and ventilation of
effected sinuses.
3. Provide post-operative access to diseased areas.
26. o Medical:
1. Topical treatment (steroid and saline
irrigation):
• Mainstay of medical management.
2. Systemic steroids:
Pre-op steroids reduce bleeding.
Post-op steroids decrease rate of recurrence.
• Long term spray.
3. Immunotherapy:
Decrease recurrence.
• NB:
No need for anti-fungal.
27. Invasive Fungal Rhinosinusitis:
- Defined by fungal elements invading host sinonasal
tissue.
- Diagnosed by histopathologic evidence of fungi
invading nasal tissue with hyphal forms within sinus:
1. mucosa
2. Submucosa
3. blood vessel
4. bone.
So, specimens sent for:
1. histopathology: for invasion assessment.
2. Mycology: to confirm fungal disease.
28. NB:
- A time course of 4 weeks separates acute from chronic
disease.
- Acute invasive and chronic invasive fungal rhinosinusitis
typically occur in patients with some degree of immuno-
compromised.
- Granulomatous invasive fungal rhinosinusitis is limited to
apparently immuno-competent (normal immunity)
patients.
• Any immuno-compromised patient with fever and one
other sinonasal symptom should undergo evaluation for
fungal sinusitis.
29. 4. Acute Fulminant Invasive Fungal
Rhinosinusitis:
• - Almost always seen in immuno-compromised
patients.
• Most common fungi:
o Aspergillus (Most Common)
o Mucormycosis (Most Fulminant)
1. Mucor
2. Rhizopus
3. Absidia
30. Pathophysiology:
o Inhaled Fungus: Grows and begins to invade neural and
vascular structures.
o Leads to thrombosis of vessels with resultant mucosal
necrosis and loss of sensation.
o Acidotic environment of tissue ischemia and necrosis
provide an ideal medium for fungal growth.
o Extends beyond the sinus via:
1. bony destruction.
2. Peri-neural.
3. Peri-vascular spread.
o 50% mortality with CNS or cavernous sinus involvement.
31. Clinical Picture:
• Symptoms are similar to acute bacterial rhino-
sinusitis.
• Fever is the most frequent finding (90%).
• Patient with history of immuno-compromised.
Symptoms of Extra-sinus extension:
• Orbit – CNS .. Etc.
34. Diagnosis:
1. High index of suspicion:
fever + one sino-nasal symptom in immuno-
compromised patient.
2. Nasal Endoscopy:
Changes in appearance and anesthesia of sino-
nasal mucosa are the most consistent findings.
o Pale mucosa in early stage.
o Black necrotic mucosa in late stage.
35. 3. Biopsy and Culture:
Biopsy should be obtained whenever one suspects fungal
disease.
Should be taken from:
1. Diseased mucosa (pale, insensate, ulcerative, black).
2. Middle turbinate and nasal septum in normal
appearance mucosa (Most common sites of involvement).
• Fungal culture is the gold standard for identifying the
responsible fungi.
• Difficult to get positive culture result, especially with
Mucormycosis.
36. 4. CT Sinuses:
Imaging studies are supportive, but not diagnostic of acute invasive
fungal rhinosinusitis.
Findings:
Bone erosion with extra-sinus extension.
38. Management:
1. Prevention from environment.
2. Medical (Correction of underlying condition -
Systemic antifungal - topical anti-fungal –
HBO).
3. Surgery.
39. 1. Prevention:
1. Decreasing environmental exposure to fungi.
2. Prophylactic Antifungal drugs:
A. Amphotericin B.
B. Posaconazole.
• Used in immuno-compromized who exposed
to additional immuno-suppression.
40. 2. Medical:
• I. Correction of underlying compromised state:
• Most important step in treatment.
• Control DM and treat DKA and underlying
dehydration.
• Restoration of Neutropenia:
• Absolute Neutrophil Count (ANC) ≤1000 is
associated with poor prognosis.
• o WBC transfusion and administration of GCS-F.
41. II Systemic Anti-Fungal therapy:
1. Amphotericin-B Infusion:
• Drug of choice for systemic treatment of
invasive and disseminated fungal infections.
• 1mg/kg/day.
• Used mainly in Mucormycosis.
• Serious side effects:
1. Myelosuppression
2. Ototoxicity
3. Nephrotoxicity (80%)
42. 2. Extended Spectrum Tri-Azoles:
Voriconazole, Itraconazole and Posaconazole.
Used as treatment and prophylaxis of invasive
fungal sinusitis in patients with
immunocompromised state.
Less toxic than Amphotericin B.
Used for Aspergillus pathogens but resistant with
Mucormycosis.
3. Echino-candins:
• Caspofungin, Micafungin, and Anidulafungin.
• Used in combination.
43. III. Topical Amphotericin B Nasal Rinses:
• Used as adjunctive measures.
IV Hyperbaric Oxygen:
• Reduces ischemia and acidosis which are needed
for fungus growth.
• Adjuvant therapeutic option.
• NB:
• Voriconazole is used in any intracranial extension.
44. 4. Surgical:
• Less important step than intact immunity and
appropriate medical therapy (unlike other
fungals).
Goals of surgery:
1. Confirm the diagnosis through tissue biopsy.
2. Debridement of devitalized tissue.
3. Decrease pathogen load.
4. Provide drainage and ventilation of effected
sinuses.
5. Provide post-operative access to diseased areas
for monitoring.
45. Prognosis:
o Factors affecting mortality rate:
1. Time onset of treatment.
2. Absolute Neutrophil Count (ANC):
• ANC < 1000/mm3 is associated with a worse prognosis.
• Recovery from neutropenia is the most predictive
indicator for survival.
3. Intra-cranial involvement:
• Single most predictive indicator for mortality.
4. Type of Fungus:
Mucor infection tends to worse than Aspergillus.
5. Type of immunocompromised state.
46. 5. Chronic Invasive Fungal
Rhinosinusitis:
- Rare condition in which deveolps over time
(months to years).
- Has similar clinical appearance of acute
fulminant invasive fungal sinusitis.
- Occurs mainly in immunocompetent and mild
immunocompromised patients (steroid
treatment, diabetes mellitus, HIV).
47. • Most common fungi:
o Aspergillus Fumigatus (Most common >80%)
o Bipolaris
o Candida
o Mucormycosis
48. Clinical Picture:
o Nonspecific chronic rhinosinusitis (CRS)
symptoms:
Nasal congestion, rhinorrhea, facial pressure,
headaches, polyposis.
o Ocular symptoms are indication of extent and
aggressiveness of the disease.
49. Diagnosis
1. High index of suspicion:
If patient presented with CRS that is unresponsive to antibiotics.
2. Nasal Endoscopy.
3. Biopsy and Culture:
Required for the diagnosis.
Histopathology:
• Identification of submucosal invasion of fungal elements.
Few if any inflammatory cells:
o Major difference between acute and chronic invasive disease.
No Granuloma formation:
o Main difference between chronic invasive and granulomatous invasive
fungal disease.
4. CT & MRI.
50. Treatment:
o Similar to Acute fulminant invasive sinusitis with a combination
of surgical and medical treatments.
1. Anti-Fungal drugs:
• Systemic and topical Amphotericin B should be started until
cultures prove that the offending agent is not a Mucor species.
• If not a Mucor species, Voriconazole, Itraconazole and
Posaconazole is used to limit the side effects.
• Most recommend duration of therapy is 3-6 months.
2. Surgical debridement.
3. Close Follow-up visits.
51. 5. Granulomatous Invasive Fungal
Rhinosinusitis:
• Similar clinical picture, work-up and treatment to
chronic invasive fungal sinusitis.
• Main differences:
1. Caused by Aspergillus Flavus.
2. Almost exclusively found in North Africa and
Southeast Asia.
3. Presence of multinucleated giant cell
granulomas on microscopic examination.
52.
53. Mycology:
1. Fungal ball: A. Fumigatus.
2. Allergic fungal RS: A. Flavus.
3. Acute fulminant: Aspergillus – Mucor.
4. Chronic invasive: A. Fumigatus.
5. Granulomatus invasive: A. Flavus.