1. Fungal Sinusitis: A Call for a Better Understanding
Hail M. Al-Abdely, MD
Consultant, Infectious Diseases

2. What does it mean? Inflammation of the sinuses due to a fungus.
Direct effect of the fungus or indirect.

3. What are the clinical forms?
Allergic
Fungal ball
Invasive
Acute
Chronic
- Invasive
- Granulomatous
DeShazo. Arch Otolaryngo Head Nech Surg 1997; 123:1181

4. FEATURES OF NONINVASIVE AND INVASIVE FUNGAL SINUSITIS
SYNDROME
COMMON CAUSES
GEOGRAPHIC
DISTRIBUTION
HOST
ASSOCIATED
CONDITIONS
Allergic fungal sinusitis
Aspergillus Spp., Dematiaceous
Humid areas
Immune-competent
Atopy, nasal polyps
Sinus
Mycetoma
(fungus ball)
Aspergillus Spp., Dematiaceous
Humid areas
Immune-competent
Chronic sinusitis
Acute invasive
fungal sinusitis
Mucorales, Aspergillus Spp
Non-specific
Diabetes, immune-suppressed
Diabetes, cancer, iron chelating
Chronic
invasive fungal sinusitis
Aspergillus fumigatus
Non-specific
Immune-suppressed
Diabetes
Granulomatous
invasive
fungal sinusitis
Aspergillus flavus
Tropical & subtropical
Immune-competent
None
De Shazo: NEJM 337:

5. Allergic Fungal Sinusitis (AFS)

6. Allergic Fungal Sinusitis (AFS)
Most common form of fungal sinusitis
A recently recognized
1976: First described in patients with Allergic broncho-pulmonary aspergillosis (Safirstein. Chest 70: 788)
1983: Few Cases with the histologic triad of necrotic eosinophils, charcot-Leyden crystals and non-invasive fungal hyphae and was named Allergic Aspergillus sinusitis (Katzenstein. J Allergy Clin Immunol 72:89)
1998: English-literature review revealed 263 cases. (Maning. Laryngoscope 108: 1485)

7. AFS: How common?
Chronic rhinosinusitis is the most common chronic disease in the US affecting 37 million (14.13% of population). Vital Health Stat 1995, 10:89
Incidence of AFS in chronic rhinosinusitis is 7%. (Cody DT. Laryngoscope.1996; 4:169)
In a recent prospective cohort from the US, fungi were isolated from 94% of patients with chronic rhinosinusitis. (Ponikau JU. Mayo Clin Proc.1999; 74:877)
In a recent study from Austria, fungi were isolated from 91.3% from patients with chronic rhinosinusitis. 75.5% of patients had fungal elements on histopathology. (Braun H. Laryngoscope.2003; 113:264)

8. The Mayo Clinic Cohort (Ponikau JU. Mayo Clin Proc.1999; 74:877)
Fungal Culture
(Ponikau JU. Mayo Clin Proc.1999; 74:877)

9. (Ponikau JU. Mayo Clin Proc.1999; 74:877)

11. Pathogenesis of AFS

12. Eosinophilic mediators
Local Factors
-Mucostasis
-Anatomic anomaly
Enviromental
-Fungal exposure
Genetic
-Atopy
-Unknown +
Exposure
Fungal proliferation
Antigen exposure
Allergic
Mucin
Inflammatory trigger
IgE mediated
T-cell & other
Edema
Obstruction
Stasis
Reduced
ventilation
Inflammation
Eosinophilic mediators
(MBP, ECP & others)
Marple: Laryngoscope 111:

13. Which fungus causes AFS?
Aspergillus species.
Phaeohyphomycosis:
Bipolaris, Exerohilum, Dreschlera.
Alternaria.
Curvularia
Exophiala.
Others (rare)
Fusarium, Scedosporium (Pseudallescheria).

15. Criteria for Diagnosis of AFS
No consensus but several proposals that share:
Presence of allergic mucin on histopathology
Presence of non-invasive hyphae on histopathology +/- fungal culture
Fungal Ig-E mediated hypersensitivity
Nasal polyposis
High-signal intensity opacification of sinuses on CT scan
? Associated atopy (65%) with asthma (50%)
Marple: Laryngoscope 111:

16. CT and MRI scans in AFS
The sinus filled with high signal intensity soft tissue
Bone erosions (20% of cases) and extension to surrounding structures can happen BUT due to pressure and not invasion (Nussenbaum B,Otolaryngol Head Neck Surg 001;124:150–154)
Remodeling is common
MRI: hypointense central T1 signal, central T2 signal and the presence of increased peripheral T1/T2 enhancement .

18. Treatment Goals for AFS
Clear current episode
Reduce number of recurrences. Very common (90% of cases)
Improve quality of life
It’s NOT easy
Patient education about the nature of the disease

19. Eosinophilic mediators
Therapeutic Strategies for Allergic Fungal Sinusitis
Surgery
Irrigation
Antifungals
Exposure
Fungal proliferation
Antigen exposure
Inflammatory trigger
IgE mediated
T-cell & other
Edema
Obstruction
Stasis
Reduced
ventilation
Allergic
Mucin
Steroids
Immunotherapy
Inflammation
Eosinophilic mediators
(MBP, ECP & others)

20. Management of AFS Clear current episode Prevent recurrence Surgery
Steroids
Desensitization to fungal antigens
Antifungal therapy
Combination of the above

21. Steroids Topical Systemic Indicated post-operative
Efficacy is not well established But has the advantage of lower complications
Systemic
success of this strategy in the treatment of ABPA.
Few studies indicated efficacy in reducing recurrences (Schubert MS, J Allergy Clin Immunol 1998;102:395–402.
Use is limited by serious long-term complications

22. Immunotherapy Few and small studies
Indicate reduction in recurrences up to 50% (Laryngoscope Nov;108:1623)
Problems:
No adequate data
Long and tedious process 3-5 years.
Disease can worsen

23. Antifungal Therapy Prior to Azoles
short courses of Amphotericin B were tried mainly because of the concern of invasive disease
no success in reducing recurrences
Recent data indicate significant success of azoles in ABPA
Combining itraconazole with systemic steroids.

24. Steroids + itraconazole
Retrospective study
139 patients
Average F/U 31.4 months
Strategy:
Endoscopic surgery
Itraconazole orally, continuous
Topical steroids
Short courses of low-dose systemic steroids
Outcome: recurrence of disease in 50% BUT the need for surgery was 21%)
Rains BM. Am J Rhinol (1):1-8.

25. Topical antifungal
Ampho B tried as a nasal lavage for 4 weeks reduced nasal polyps by 39%
J Laryngol Otol. 2002, 116(4):261-3.

26. Prognosis of AFS
Mortality is rare even with extensive disease and extension to surrounding structures.
Morbidity is high due to recurrent surgeries and nasal blockage
Visual loss is rare
Marple. Otolaryngol Head Neck Surg 2002;127:361-6.

27. Acute Invasive Sinusitis

28. Acute Invasive Sinusitis
Relatively uncommon
Life-threatening
Typically in diabetics and the immunocompromised
Caused by
Mucorales of Zygomycetes (Rizopus, mucor).
Aspergillus species.
Fusarium.
Scedosporium (Pseudallescheria boydii).
Phaeohyphomycosis.

32. Mucormycosis
Mucormycosis is unusual fungal infection caused by fungi of the order Mucorales from the class Zygomycetes of the phylum Zygomycota.
Rizopus spp. are responsible for about 90% of reported cases.
Identified predisposing factors include uncontrolled diabetes with ketoacidosis, cancer, immunosuppressive conditions and dialysis patients on deferoxamine therapy
It affects primarily the sinuses with local destruction extending to the orbit and the brain. The lung is the second most common organ.
The overall mortality rate is approximately 50% to 70%

33. Rizopus Spp.
Absidia Spp.
Cunninghamella Spp.
Rizomucor Spp.

35. A retrospective chart review was conducted from 1985 to 2001.
Mucormycosis (Zygomycosis) at King Faisal Specialist Hospital and Research Centre
A retrospective chart review was conducted from 1985 to 2001.
Source for cases identification was medical Records
Cases were reviewed for
demographic data
risk factors
clinical features
relevant laboratory and radiological studies
fungal cultures and histopathology
Management, complications and outcome

36. Case Definition The diagnosis of mucormycosis was defined as:
Definite: if the histopathology was positive for fungal hyphae typical of mucorales and positive culture
Probable: if histopathology positive for fungal hyphae typical of mucorales or positive culture and compatible clinical and radiological features
Possible: if sampling was not done or was negative on hisopathology and culture but has compatible clinical and radiological features

37. Results

38. Distribution of Mucormycosis Cases over the Years

39. Results # Cases (%) Male 13 (72.2) Female 5 (27.8) Age (median)
45 (range 4-83)

40. Clinical # Cases (%) Fever 11 Facial pain 7 Proptosis 6 Double vision4
Headache
Blindness 5
Palate necrosis
Nasal Blockade 3

41. Diagnosis of Mucormycosis

42. Underlying Conditions in Patients with Mucormycosis

43. Fungal Culture in Patients with Mucormycosis
All were Rizopus Spp.

44. Extent of Sinus Disease
# cases %
Localized lesion to sinus 2
18.2
Involvements of sinus +orbit 1
9.1
Involvements of sinus +orbit + palate
Involvements of sinus +orbit + palate + brain 7
63.6

45. Site of Infection Related to Underlying Condition

46. Outcome of Patients with Mucormycosis

47. Outcome Related to Underlying Condition

48. Mortality Related to Type of Management5 13

49. Conclusion of the study
Mucormycosis is a relatively uncommon but aggressive fungal infection associated with high mortality.
Sinus was the most common site especially in diabetics
All the culture-positive cases were due to Rizopus Spp.
Combined medical and surgical therapy provided the best outcome.

50. Management of Acute Invasive Fungal Sinusitis
Life-threatening condition with the time factor as the main determinant of success
Emergency surgery with radical debridement.
Adjunctive aggressive antifungal therapy
Amphotericin B is the only drug for mucormycosis
Modify risk factors

51. Chronic Invasive Fungal Sinusitis

52. Chronic Invasive Fungal Sinusitis
Poorly described entity
Indolent course with soft-tissue invasion.
Classified into two histological entities (DeShazo. Arch Otolaryngo Head Nech Surg 1997; 123:1181)
Chronic invasive
Invasion of vessels
Immunocompromised and diabetics
Caused mainly by Aspergillus fumigatus
Chronic granulomatous invasive
Immune competent individuals
Non-caseating granulomatous inflammation, no vessel invasion
Reported mainly in Sudan, India and Pakistan
Caused by Aspergillus flavus and dematiaceous fungi

54. CHRONIC INVASIVE ASPERGILLOSIS OF THE PARANASAL SINUSES IN IMMUNOCOMPETENT HOSTS FROM SAUDI ARABIA
Patient selection.
Cases (N 23) involving positive isolates of Aspergillus from paranasal sinus material between1991 and 1997
grew Aspergillus and had histopathology showing fungi breaching mucosal barriers and causing tissue necrosis.
Alrajhi et al: A J Trop Med Hyg 65:

55. Alrajhi et al: A J Trop Med Hyg 65:83. 2001

56. Alrajhi et al: A J Trop Med Hyg 65:83. 2001

57. Alrajhi et al: A J Trop Med Hyg 65:83. 2001

58. Granulomata were found in 6 of 23 patients Fungal organisms:
CHRONIC INVASIVE ASPERGILLOSIS OF THE PARANASAL SINUSES IN IMMUNOCOMPETENT HOSTS FROM SAUDI ARABIA
Granulomata were found in 6 of 23 patients
Fungal organisms:
A. flavus 15 (65%)
A. fumigatus 2 (9%)
Aspergillus spp. 6 (26%)
Two cases of visual loss
No mortality
Alrajhi et al: A J Trop Med Hyg 65:

59. Management of Chronic Invasive Sinusitis
Surgery
Prolonged antifungal therapy

60. Conclusion Fungal sinusitis is a relatively common problem
Understanding the nature of the disease determine the approach to therapy
Surgery is the mainstay treatment for fungal sinusitis
The diagnosis of allergic fungal sinusitis could mean a life-long relationship with the patient.
Antifungal therapy is an absolute indication in acute and chronic invasive fungal sinusitis and a relative indication in allergic fungal sinusitis

61. Thank You