This document provides information on fungal rhinosinusitis, including its classification and types. It discusses invasive fungal rhinosinusitis, which includes rapidly invasive and chronic invasive types. It also discusses non-invasive fungal rhinosinusitis, which includes saprophytic colonization, fungal ball, and allergic fungal rhinosinusitis. Signs and symptoms, endoscopic findings, microbiology, antifungal drugs, and treatment approaches are described for different fungal infections of the sinus. Allergic fungal rhinosinusitis is discussed in detail, covering its pathophysiology, clinical features, diagnostic criteria, imaging, therapy including surgery, steroids, and immunotherapy.
4. • Fungal manisfestations depends on the immunologic status
of the patient
• Acute invasive occurs in immunocompromised individuals
• Chronic invasive occurs in mildly immunocompromised
patients who appear immunocompetent
• Saprophytic fungal crusts may preceed fungal balls and
occur in immunocompetent individuals
• Allergic fungal rhinosinusitis can occur in ptaients with an
allergy to the fungus
13. AmphotericinB
• continues to be the drug of choice
• intravenous (IV) doses of 0.25 mg/kg/day up to a maximum of 1.5
mg/kg/every other day.
• Nephrotoxicity is the major dose-limiting toxicity
• can be reduced with sodium loading.
• Fever, chills, nausea, and hypotension frequently accompany the first
few doses.
• These toxicities can be reduced or eliminated with the use of
liposomal amphotericin B.
14. Voriconazole
• Available in oral as well as intravenous formulations
• Approved for
invasive aspergillosis
Fusarium sp.
Scedosporium apiospermum(asexual form of peudallescheria boydii)
Dose:-
I/V – Loading dose- 6mg/kg every 12hrs for 1 day
maintainence dose – 4mg/kg every 12 hrs
oral- loading dose wt<40kg- 200mg BD for 2 doses
wt>40 kg- 400mg BD for 2 doses
maintainence dose wt<40kg- 100mg BD
wt>40kg- 200mg BD
15. Adverse effects of Voriconazole:-
Elevation of liver enzymes
Skin Rash
Abnormal Vision
Photosensitivity Reaction
18. • occurs when ubiquitous fungal spores land and germinate on
mucous crusts, which fail to clear the sinonasal cavity
• commonly seen after sinonasal surgery
• Detected grossly on examination.
• Common fungal agent: Aspergillus species
Saprophyticcolonization
19. Clinicalpresentation:
• immunocompetent
• asymptomatic
• an odor in nose
• crusts of debris on nose blowing
• Nasal endoscope: a tuft of fungal material is seen growing on nasal
crusts
Treatment:
Debridement the involved region
20. Fungal Ball
.
• Paranasal sinus fungal balls are common
and grow in the moist cavities of the
paranasal sinuses of a host who usually
has a normal immunologic status.
• Immunocompromised patients can also develop fungus
balls and may come to medical attention more often with
Aspergillus species and nondilated sinus ostia.
• Systemic steroid therapy or surgical abrasion can predispose
a previously contained fungal growth to become invasive.
21. • Nonspecific chronic sinusitis symptoms:
• Nasal obstruction
• Facial pressure
• Postnasal drainage
A variety of fungal species cause fungus balls and include A. flavus, A. fumigatus, and
Alternaria and Mucor species
22. Diagnosis
• A solitory maxillary/ sphenoid sinus
• May also in frontal & ethmoid sinuses
• May involve contiguous sinuses
In asymptomatic patients often detect only after imaging for other
conditions
23. • Fungus ball is grossly a darkened, often crumbly mass, occasionally with visible sporulation.
• The characteristic gross appearance has a positive predictive value of 100% for histologic appearance of
a fungus ball and has a very high negative predictive value as well
• Thus mycologic and histologic studies are essential to confirm the diagnosis.
• Nongrowth on fungal culture can occur in over 30% of specimens, even though hyphae are present on
histopathology.
• Bacterial co-colonization with a wide variety of organisms such as coagulase-negative Staphylococcus,
S. aureus, anaerobes, and pseudomonas species occurs in almost 75% of fungus balls.
24. CT scan findings of metallic or calcified densities within an opacified sinus cavity
have a positive predictive value of around 60% for a fungus ball and a high negative
predictive power.
25. Pathology:
• Gross
• Lesions: vary from soft, wet-appearing bundles of debris to firm, gritty &
crumbly balls
• Color: white, yellow, green, tan, brown & black
28. Recurrence is rare
Wide opening of the involved sinus and complete
removal of the fungal debris
• Antifungals are unnecessary
Treatment
29. Allergic Fungal Rhinosinusitis
• First described in 1981 by Millar and colleagues
• In 1983, the term allergic aspergillus sinusitis was proposed by
Katzenstein et al. because of its histologic similarity to ABPA. Tey
described the thick, inspissated mucoid material containing fungal
hyphae in both the sinuses and the bronchi as “allergic mucin”
• Both groups recognized the histologic similarity of AFRS to the
previously described allergic bronchopulmonary aspergillosis ABPA),
and AFRS is considered to be a sinonasal form of ABPA.
30. • Common among adolescents and young adults
• Common in atopic individuals
70%- Allergic rhinitis
90% High serum IgE
50% Asthma
• incidence varies geographically.
• Endemic areas include areas of high humidity in the United States along the Mississippi River
• In patients undergoing endoscopic sinus surgery, 51% were diagnosed with AFRS in Northern
India, 8.6% in Adelaide Australia, and 12% in Saudi Arabia.
• In 1998, the highest reported rate in the United States was in Memphis,Tennessee, where 20% of
surgical endoscopic sinus cases were for AFRS.
• The presence of mold spores is necessary for AFRS to occur, and outdoor mold spore counts vary
widely both geographically and seasonally.
Epidemiology and Geography
31. Pathophysiology
• Remains unclear
• Similar to that of Allergic Bronchopulmonary aspergillosis
• Multiple factors play role in the disease development
32. Pathophysiology
• The development of AFRS requires that an individual genetically predisposed to fungal
allergy be exposed by inhalation of the mold spore
• The spore must elude mucociliary clearance or expulsion by sneezing or coughing for a
time period sufficient to allow germination.
• Occasionally, because of mucociliary transport disruption, dryness, or a large inoculum,
the mold spore may not be cleared.
• Germination increases the antigenicity of the fungus, leading to increased production of
allergic mucin, in which the fungus continues to grow.
• This leads to a “positive feedback loop” in which growth of the antigenic fungus induces
the production of more allergic mucin, which leads to increased growth of antigenic
fungus.
• The sticky allergic mucin resists clearance by normal mucociliary action, and the
inflammatory cytokine milieu promotes the growth of nasal polyps.
• The immunology of AFRS includes increased IgE and IgG response to the specific fungus.
34. Pathophysiology(Controversial)
• Significance of fungal presence and Eosinophilic mucin Rhinosinusitis
EMRS=AFRS in absence of fungal Hyphae
EMRS occurs due to dysregulation of immunologic controls
involving
upper and lower airway eosinophilia whereas AFRS is localised IgE
mediated reaction to germinated fungus
35. AFRS
• Systemic disease
• Increased incidence of IgG1 deficiency
• Older pateints
• Higher associations with asthma
EMRS
• Allergic response to fungi
• Unilateral Bilateral
• Fungal immunotherapy and antifungal agents
• Younger patients
36. Clinical features
• Young Adult
• Immunocompetent
• Atopic individual
• Predominantly unilateral symptoms
Nasal obstruction /congestion
Post nasal discharge
Purulent rhinorrhoea
Headache or facial fullness
Proptosis or telecanthus
h/o multiple sinus surgery
Recurring sinusitis
Vision loss
Nasal polyposis
37. - Within allergic mucin : “onionskin lamination”
/ cluster of necrotic & degranulation of
eosinophil
- Charcot-Leyden crystal.
- Hyphal fragments scattered
- No fungal tissue invasion
Histopathology
40. • The diagnosis is Culture of the allergic mucin reveals a variety of fungal
species.
• Associated fungal pathogens vary geographically.
• In North America, most cases of AFRS are caused by dematiaceous or
pigmentproducing species such as
Bipolaris
Alternaria species,
Exserohilum robatum,
Curvularia lunata.
• In northern India, the majority of AFRS cases are caused by Aspergillus
flavus, and n the Persian Gulf countries, Aspergillus species
predominate.
Fungal culture
41. IgE Levels
• Total IgE levels are elevated in the AFRS
• Used to monitor the clinical activity of allergic
bronchopulmonary aspergillosis
• IgE levels have been proposed as a useful indicator of AFRS
activity.
42. Ocular Manifestations
• Orbital involvement without vision loss(14.6%)
• Proptosis(6.1%)
• Telecanthus(7.3%)
• Vision loss (3.7%)
43. CT
Heterogenous signal intensities within the paranasal sinuses filled
with hyperattenuated allergic mucin (Double density sign)
Expansion of the paranasal sinuses/nasal cavity
Unilateral or asymmetric disease load
Bony erosion
Imaging
44. MRI
• T1-weighted images—central areas of hypointensity with peripheral enhancement
• T2-weighted images—central areas of hypointensity or signal void with peripheral
enhancement
45. Allergic Fungal Rhinosinusitis
Diagnostic Criteria
• Several criteria have been proposed for the Diagnosis
• Kartzenstein 1983
• Manning 1989
• Ence 1990
• Bent 1994
• deShazo 1995
• Kuferupferberg 1996
• Schubert 1998
• Ponikau 1999
• Schubert 2000
• McCann 2002
• Meltzer 2004
46. Bent and Kuhn diagnostic criteria for allergic fungal
rhinosinusitis
1. Evidence of type I IgE-mediated hypersensitivity
2. Nasal polyposis
3. Characteristic CT fndings
4. Eosinophilic mucus
5. Positive fungal smear
1.Asthma
2. Unilateral predominance
3. Radiographic bone erosion
4. Fungal culture
5. Charcot-Leyden crystals
6. Serum eosinophilia
Minor criteria
Major criteria
47. Therapy of Allergic Fungal Rhinosinusitis
• Steroids, systemic or
topical
• Surgery
• Nasal lavage
Immunotherapy
Oral antifungals
Anti–
immunoglobulin E
Topical amphotericin B
Leukotriene modulators
Calcineurin inhibitors
Antibiotics
Definitely Helpful Probably or Possibly Helpful Not Helpful or Unclear
48. Surgery
Goals of Surgical Treatment:-
Eradicate allegic mucin
Prviding permanent drainage
Provinding ventilation Route
• Treatment of AFRS consists of conservative, mucosal-preserving surgical
removal of the nasal polyps and inspissated allergic mucin, which usually can
be accomplished with endoscopic techniques.
• The mucin is tenacious, and microdebriders can facilitate removal;
49. Adjunctive systemic steroids, usually given perioperatively at a prednisone
dose of 60 mg for several days and tapered off over 2 to 4 weeks, can result in
remission.
Preoperative systemic steroids may resolve the eosinophilic component of the
process and lead to a misdiagnosis by the pathologist of a fungus ball.
When steroids are withdrawn, the eosinophilic content for the fungus usually
returns, and a resampling may yield the histopathologic diagnosis of AFRS.
Unfortunately, the predisposition to the allergic response can result in
recurrence.
Once large sinus cavity openings have been created, recurrences often can be
managed in the office with endoscopic debridement, systemic and topical
steroids, and possibly antifungal therapy.
Role of steroids
50. Initially, immunotherapy was considered to be contraindicated in AFRS because of
a theoretic potential to worsen the disease through the formation of immune
complexes.
Mabry and colleagues initially showed that fungals pecific immunotherapy
following endoscopic sinus surgery (ESS) for AFRS did not cause harm and could
lead to improvement within the first several years postoperatively.
A recent study by Greenhaw and colleagues also demonstrated the safety of high-
dose immunotherapy in patients with AFRS
The humanized monoclonal antibody to the Fc portion of IgE, omalizumab, is
currently approved for patients with severe allergic asthma. Usage in patients
with AFRS has not been reported, although the senior author (B.J.F.) has seen a
case that responded within a week of initiating omalizumab
Immunotherapy
51. Antifungals
• Oral antifungals are considered as a treatment option in patients with
recalcitrant chronic fungal sinusitis.
• also used as a steroid-sparing medication, allowing some patients to
be weaned of from long-term oral corticosteroid therapy.
• Oral itraconazole, when used in steroid dependant ABPA patients, was
found to reduce the dosage of steroids required, improve pulmonary
function and exercise tolerance, and decrease IgE levels.
• AFRS is considered similar to ABPA is thought to respond similarly to
antifungals.
55. AFRSinChildren
• Needs special care
• More aggressive
• Bone erosion is severe
• Intraorbital extension is high
• Intrcranial extension is more sggresive
56.
57. RapidlyInvasive Fungal Rhinosinusitis
• Also called fulminant invasive FRS
• Confined to the patient with altered host defenses.
• Course is rapid
• It is the most lethal form of fungal rhinosinusitis.
58. •Two clinical populations:-
• Poorly controlled diabetes
Caused by:-
Zygomycetes- Rhizopus, Rhizomucor, Absidia, Mucor
• Immunocompromised with severe neutropenia
includes Chemotherapy patients, organ taransplants, AIDS,
Bone marrow tumors
Aspergillus fumigatus accounts for 80% infections of this group
59. Clinical Features
• Fever
• symptoms related to the nose or paranasal sinus area
orbital swelling,
facial pain or numbness,
nasal congestion
nasal discharge
• Almost half of all patients with invasive FRS may come to medical
attention with orbital findings such as ophthalmoplegia, proptosis,
and visual loss.
60. • Intra-orbital, intracranial and maxiloofacial extension is common
resulting in
Proptosis
Visual disturbances
Headache
Changes in mental status
Seizures
maxillofacial soft tissue swelling
Angioinvsaion and haematogeneous dissemination is common
61. Nasal Endoscopy
• Initial Nasal examination may not reveal anything significant.
• Crusting
• Whitish Discolouration
• Blackish discoloration
• These changes are most commonly found on middle
turbinatefollowed by septum and inferior turbinate.
62.
63.
64.
65.
66.
67. Imaging
NCCT
Severe unilateral nasal cavuty soft tissue thickening
Hypoattenuating mucosal thickening within lumen of
paranasal sinuses with rapid aggressive bone destruction of
sinus walls
Fungi can also spread via vessels beyond the sinuses with
intact bony walls
69. MRI
o Better for evaluating intracranial and intraorbital
extension
o Evaluate for inflammatory change in orbital fta
and extraocular muscles
o Obliteration of periantral fat is subtle sign of
extension
o Leptomeningeal enhancement
72. Prognosis
• Depends on
Early diagnosis
Resolution of the predisposing condition
Survival is positively correlated with the time of diagnosis and initiation
of treatment.
73.
74. CHRONICINVASIVEFRS
Slowly destructive disease.
Patients are usually immunocompetent.
Most common fungi implicated is Aspergillus
Fumigatus.
Other fungi- Mucor, Rhizopus, Aspergiillus, Bipolaris
and Candida
Progression is over months to years with invasioin of
mucosa, submucosa, blood vessels and bony walls.
75. SignsAndSymptoms
Presents with frequent orbital involvement.
The ethmoid and sphenoid sinuses are most commonly involved.
Synptoms include:-
Paranasal sinus pain
Nasal discharge
Epistaxis
Fever
76. • Disease is persistent and recurrent
• Maxillofacial Soft tissue swelling
• Invasion of maxillary floor leads to palatal erosions
• Orbital invasion leads to Orbital Apex Syndrome
• Invasion of adjacent structures such as orbit, cavernous sinus and
anterior cranial fossa may lead to
eoidural abscess
cavernous sinus thrombosis
mycotic aneurysm,etc
77. HISTOLOGY
• Chronic invasive FRS
demonstrates invasion of
fungi into the sinonasal
mucosa with a dense
accumulation of fungal
hyphae, occasional vascular
invasion, and chronic or
sparse infammatory reaction.
78. IMAGING
• NCCT-
• Hyperattenuating soft tissue mass within one or more
paranasal sinuses
• Bone involvement gives mottled appearance with or
without sclerosis
• MRI
Decreased signal on T1, Markedly decreased signal
on T2 weighted images.
81. • It is usually of gradual onset and is seen more
commonly in Sudan, India, Pakistan and Saudi
Arabia.
• Caused by Aspergillus flavus.
• Immunocompetent
GRANULOMATOUS INVASIVE FRS
82. Clinical features
Proptosis with an enlarging mass in the cheek, nose,
paranasal sinus and orbit
IMAGING
Similar features to that of Chronic invasive fungal
rhinosinusitis
83. Histology
• The distinguishing feature from chronic invasive FRS is
histological findings of fungal tissue invasion and a
granulomatous reaction with considerable fibrosis.
• This is evident from the presence of noncaseating
granulomas with foreign body or Langerhans-type giant cells,
occasional vasculitis and sparse hyphae.
84.
85.
86.
87. Treatment
• Complete surgical removal
• Antifungal agents.
• For Aspergillus species, voriconazole is the drug of
choice although itraconazole and pasoconazole are viable
alternatives.
• For non-Aspergillus species, amphotericin B is the
treatment of choice while awaiting the results of susceptibility testing