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Fungal Rhino-sinusitis
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.
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.
Microscopic appearance:
1. Aspergillus:
Septated hyphae with acute angle branching
at 45⁰.
2. Mucromycosis:
Non-septated hyphae with branching at 90⁰.
Classification of Fungal Rhinosinusitis:
Invasive:
1. Acute Fulminant
Invasive Fungal
Rhinosinusitis.
2. Chronic Invasive
Fungal Rhinosinusitis.
3. Granulomatous
Invasive Fungal
Rhinosinusitis.
Non-Invasive:
1. Saprophytic Fungal
Infestation.
2. Sinus Fungal Ball.
3. Eosinophilic Mucin
Rhinosinusitis:
a. Allergic Fungal
Rhinosinusitis.
b. Non-Allergic Eosinophilic
Fungal Rhinosinusitis.
c. Non-Fungal Eosinophilic
Mucin Rhinosinusitis.
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.
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.
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.
Clinical Picture:
1. Results of mass effect by the fungal ball and
sinus obstruction: Unilateral proptosis, facial
hypesthesia
2. Mimic chronic rhinosinusitis.
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.
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.
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.
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.
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.
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.
Diagnosis:
• Pt must met all 5 Major criteria.
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.
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.
NB:
• Sinuses walls thickening in fungal ball.
• Thinning in AFRS. (Allargic).
• Fungal infection has pseudo-pnemutization.
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.
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.
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.
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.
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
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.
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.
Diagnosis:
1. History ( immuno-compromised).
2. Examination: endoscopy (pale-dark mucosa).
3. Biopsy & culture (gold standard).
4. CT scan (supportive).
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.
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.
4. CT Sinuses:
Imaging studies are supportive, but not diagnostic of acute invasive
fungal rhinosinusitis.
Findings:
Bone erosion with extra-sinus extension.
5. MRI Sinuses: supportive
(pseudo-pneumotization).
Management:
1. Prevention from environment.
2. Medical (Correction of underlying condition -
Systemic antifungal - topical anti-fungal –
HBO).
3. Surgery.
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.
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.
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%)
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.
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.
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.
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.
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).
• Most common fungi:
o Aspergillus Fumigatus (Most common >80%)
o Bipolaris
o Candida
o Mucormycosis
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.
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.
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.
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.
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.

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Fungal Rhinosinusitis Diagnosis and Treatment

  • 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.
  • 4. Microscopic appearance: 1. Aspergillus: Septated hyphae with acute angle branching at 45⁰. 2. Mucromycosis: Non-septated hyphae with branching at 90⁰.
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  • 6. Classification of Fungal Rhinosinusitis: Invasive: 1. Acute Fulminant Invasive Fungal Rhinosinusitis. 2. Chronic Invasive Fungal Rhinosinusitis. 3. Granulomatous Invasive Fungal Rhinosinusitis. Non-Invasive: 1. Saprophytic Fungal Infestation. 2. Sinus Fungal Ball. 3. Eosinophilic Mucin Rhinosinusitis: a. Allergic Fungal Rhinosinusitis. b. Non-Allergic Eosinophilic Fungal Rhinosinusitis. c. Non-Fungal Eosinophilic Mucin Rhinosinusitis.
  • 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.
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  • 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.
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  • 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.
  • 19. Diagnosis: • Pt must met all 5 Major criteria.
  • 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.
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  • 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.
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  • 33. Diagnosis: 1. History ( immuno-compromised). 2. Examination: endoscopy (pale-dark mucosa). 3. Biopsy & culture (gold standard). 4. CT scan (supportive).
  • 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.
  • 37. 5. MRI Sinuses: supportive (pseudo-pneumotization).
  • 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.
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  • 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.