Transcript Fungal sinusitis -pat..>

Fungal Sinusitis: A Call for a
Better Understanding
Hail M. Al-Abdely, MD
Consultant, Infectious
Diseases
What does it mean?
Inflammation of the sinuses due to a
fungus.
Direct effect of the fungus or indirect.
What are the clinical forms?
Allergic
Fungal ball
Invasive
• Acute
• Chronic
- Invasive
- Granulomatous
DeShazo. Arch Otolaryngo Head Nech Surg 1997; 123:1181
FEATURES OF NONINVASIVE AND INVASIVE FUNGAL SINUSITIS
SYNDROME
COMMON
CAUSES
GEOGRAPHIC
DISTRIBUTION
HOST
ASSOCIATED
CONDITIONS
Allergic fungal
sinusitis
Aspergillus
Spp.,
Dematiaceous
Humid areas
Immunecompetent
Atopy, nasal
polyps
Sinus
Mycetoma
(fungus ball)
Acute invasive
fungal sinusitis
Aspergillus
Spp.,
Dematiaceous
Humid areas
Immunecompetent
Chronic
sinusitis
Mucorales,
Aspergillus Spp
Non-specific
Diabetes,
immunesuppressed
Diabetes,
cancer, iron
chelating
Chronic
invasive fungal
sinusitis
Aspergillus
fumigatus
Non-specific
Immunesuppressed
Diabetes
Granulomatous
invasive
fungal sinusitis
Aspergillus
flavus
Tropical &
subtropical
Immunecompetent
None
De Shazo: NEJM 337:257. 1997
Allergic Fungal Sinusitis (AFS)
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 noninvasive 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)
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)
The Mayo Clinic Cohort
Subjects
224
Chronic
Rhinosinusitis
210
Volunteers
14
Fungal Culture
Sinus surgery
101
Fungal elements
81%
Positive culture
100%
Eosinophilic mucin
97%
Fungal Culture
Positive culture
96%
(Ponikau JU. Mayo Clin Proc.1999; 74:877)
(Ponikau JU. Mayo Clin Proc.1999; 74:877)
Pathogenesis of AFS
Local Factors
-Mucostasis
-Anatomic anomaly
+
Enviromental
-Fungal exposure
+
Genetic
-Atopy
-Unknown
Exposure
Fungal proliferation
Antigen exposure
Inflammatory trigger
Edema
Obstruction
Stasis
Reduced
ventilation
Allergic
Mucin
IgE mediated
T-cell & other
Inflammation
Eosinophilic mediators
(MBP, ECP & others)
Marple: Laryngoscope 111:1006. 2001
Which fungus causes AFS?
– Aspergillus species.
– Phaeohyphomycosis:
Bipolaris, Exerohilum, Dreschlera.
Alternaria.
Curvularia
Exophiala.
– Others (rare)
Fusarium, Scedosporium (Pseudallescheria).
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 111:1006. 2001
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
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
Therapeutic Strategies for Allergic Fungal Sinusitis
Surgery
1. Irrigation
2. Antifungals
Exposure
Fungal proliferation
Antigen exposure
Inflammatory trigger
Edema
Obstruction
Stasis
Reduced
ventilation
Allergic
Mucin
IgE mediated
T-cell & other
Inflammation
Eosinophilic mediators
(MBP, ECP & others)
Steroids
Immunotherapy
Management of AFS
Clear current episode
– Surgery
Prevent recurrence
– Steroids
– Desensitization to fungal antigens
– Antifungal therapy
– Combination of the above
Steroids
Topical
– 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
Immunotherapy
Few and small studies
Indicate reduction in recurrences up to
50% (Laryngoscope. 1998 Nov;108:1623)
Problems:
– No adequate data
– Long and tedious process 3-5 years.
– Disease can worsen
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.
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. 2003 17(1):1-8.
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.
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.
Acute Invasive Sinusitis
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.
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%
Rizopus Spp.
Cunninghamella Spp.
Absidia Spp.
Rizomucor Spp.
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
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
Results
22 cases
4 Wrong diagnosis
18 Cases
Distribution of Mucormycosis Cases over the Years
6
5
Cases
4
3
2
1
0
1985-1990
1991-1996
1997-2002
Results
# Cases (%)
Male
13 (72.2)
Female
5 (27.8)
Age (median)
45 (range 4-83)
Clinical
# Cases (%)
Fever
11
Facial pain
7
Proptosis
6
Double vision
4
Headache
4
Blindness
5
Palate necrosis
4
Nasal Blockade
3
Diagnosis of Mucormycosis
60
50
% Cases
40
30
20
10
0
Definite
Probable
Possible
Underlying Conditions in Patients with Mucormycosis
9
8
7
Cases
6
5
4
3
2
1
0
Diabetes
Hematology
Cancer
Chemotherapy
CRF
Steroids
Transplant
Fungal Culture in Patients with Mucormycosis
10
9
8
7
Cases
6
5
All were Rizopus Spp.
4
3
2
1
0
negative
Not done
Positive
Extent of Sinus Disease
# cases
%
Localized lesion to sinus
2
18.2
Involvements of sinus +orbit
1
9.1
Involvements of sinus +orbit + palate
1
9.1
Involvements of sinus +orbit + palate + brain
7
63.6
Site of Infection Related to Underlying Condition
Outcome of Patients with Mucormycosis
Outcome Related to Underlying Condition
Mortality Related to Type of Management
P <0.01
80
70
60
% Cases
50
5
40
13
30
20
10
0
Medical
Med+Surgical
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.
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
Chronic Invasive Fungal
Sinusitis
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
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 65:83. 2001
Alrajhi et al: A J Trop Med Hyg 65:83. 2001
Alrajhi et al: A J Trop Med Hyg 65:83. 2001
Alrajhi et al: A J Trop Med Hyg 65:83. 2001
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
– A. fumigatus
– Aspergillus spp.
15 (65%)
2 (9%)
6 (26%)
Two cases of visual loss
No mortality
Alrajhi et al: A J Trop Med Hyg 65:83. 2001
Management of Chronic Invasive
Sinusitis
Surgery
Prolonged antifungal therapy
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