SOURCE: Dept. of Otolaryngology, UTMB, Grand Rounds
DATE: FEBRUARY 7, 1996
RESIDENT PHYSICIAN: Ramtin Kassir M.D.
FACULTY: Brian Driscoll M.D.
SERIES EDITOR: Francis B. Quinn, Jr., M.D.
to Grand Rounds Index|
"This material was prepared by resident physicians in partial fulfillment of
educational requirements established for the Postgraduate Training Program of
the UTMB Department of Otolaryngology/Head and Neck Surgery and was not intended
for clinical use in its present form. It was prepared for the purpose of stimulating
group discussion in a conference setting. No warranties, either express or implied,
are made with respect to its accuracy, completeness, or timeliness. The material
does not necessarily reflect the current or past opinions of members of the UTMB
faculty and should not be used for purposes of diagnosis or treatment without
consulting appropriate literature sources and informed professional opinion."
1981- Millar et al. recognize histologic resemblance between chronic
fungal sinusitis and allergic bronchopulmonary aspergillosis
1983- Katzenstein et al. - resemblance between ABPA (allergic
bronchopulmonary aspergillosis) and seven cases of chronic sinusitis
associated with fungal hyphae (allergic Aspergillus sinusitis)
1988- Sher and Schwartz report the first case of concurrent ABPA and AFS
1991- Allphin et al. and Manning et al. - fungi of the Dematiaceae family,
not Aspergillus species, were the primary etiologic agent in AFS
1994- Kinsella et al - double density sign
1995- Rassekh et al - Skull base allergic fungal sinus disease
1. acute fulminant - pt immunocompromised, usually caused by Mucormycosis
Aspergillus, life threatening
2. chronic indolent - immunocompetent host, disease escapes confines of
sinus cavities and invades tissue. Rx includes surgery and antifungals
1.mycetoma - proliferation of fungal elements, no immune response, simple
2. AFS - intense immune reaction to fungal antigen, requires surgical
debridement and steroid therapy
Approximately 7% of chronic sinusitis cases requiring surgery are caused
by AFS. As the entity is gaining recognition, reports of its incidence
are increasing. Most series of AFS reports are from medical centers in
the southern United States. A warm humid climate may enhance fungal
growth and amplify disease prevalence.
Most common etiologic agent in ABPA is Aspergillus. In AFS, fungi in the
Dematiaceae (black) family (Curvularia, Bipolaris, Alternaria,
Exserohilum) are responsible in the majority of cases.
1. Atopic host
2. mechanical obstruction (deviated septum, mucosal hypertrophy, polyps,
3. Exposure to ubiquitous fungus
Mucus- allergic mucin very tenacious, thick, and pasty and resembles
peanut butter. Color ranges from light green to dark brown.
Histology- layers of mucus mixed with sheets of eosinophils Can see
Charcot Leyden crystals (necrotic eosinophils) on high power
Fungal hyphae can be seen on H&E stain but best seen on methanamine silver
stains If allergic mucin with hyphal element is seen, the diagnosis of AFS
can be made. However, fungal elements in AFS are relatively scarce and do
not dominate the histologic specimen as in mycetoma. The surgical
specimen must be analyzed promptly as the scant fungal elements
deteriorate in vitro. The morphology of various fungi is similar on
tissue examination, therefore fungal cultures must be obtained. The
absence of fungal invasion in to removed mucosa and bone is necessary to
rule out invasive fungal sinusitis.
ABPA - elevated levels of IgE and IgG to the specific fungal agent. AFS
is the counterpart of ABPA manifested in the sinuses, so it is also
thought to represent Gell and Coombs type I and type III responses.
Type I immunity - emphasized by Manning et al. who demonstrated elevated
levels of total IgE and Bipolaris specific IgE in nine consecutive patients.
Type III - IgG antibodies (in addition to IgE antibodies) to the specific
fungus in the serum can be demonstrated. There is no cytotoxic event
associated with these IgG antibodies (as in type II), therefore it is
thought to be a type III, non IgE mediated, noncytotoxic,
antibody-dependent immune response. Complement mediated immune response
has not been demonstrated in AFS.
The role of hypersensitivity vs. true infection in the pathogenesis of AFS
is still controversial. Clinical, histologic and serologic support for
allergic causes include the incidence of AFS in young immunocompetent
atopic patients, allergic mucin and lack of invasion on histology,
serologic and skin test evidence of IgE mediated fungal hypersensitivity,
and the presence of IgG and precipitating antibodies to fungal antigens.
Mabry and Manning recently showed not only elevated total IgE levels in
patients with AFS but also a significant degree of allergen-specific IgE
for other inhalants such as grasses, weeds, trees, and dust mite. This
also supports the idea that AFS is a true allergic rather than infectious
The CT and MRI findings in AFS is important for distinguishing fungal
sinusitis from bacterial sinusitis and sinus neoplasms. Serpiginous areas
of increased attenuation on noncontrast CT, particularly on bone windows
are characteristic of AFS. These hyperdense and heterogenous densities in
an opacified sinus are also referred to as the “double density” sign and
most likely represent higher levels of magnesium, manganese, and iron in
fungal mucin. T1-weighted MRIs of fungal sinusitis demonstrate isointense
or slightly hypointense regions surrounded by mucosal inflammation; T2
images often have a signal void and are black. This is in contrast to
MRIs of neoplasms and bacterial infections which are hyperintense. AFS
tends to affect multiple sinuses with a unilateral predominance. It is a
slow growing and chronic entity, and bone erosion is not uncommon. This
occurs in the same manner as mucoceles and polyps. Evidence of bony
erosion on radiography should not be interpreted as invasion without
histologic evidence of invasion..
Clinical Presentation and Diagnosis
AFS occurs in adolescents and young adults who often have asthma that is
exacerbated by their sinusitis. There is no male or female predominance.
All patients are immunocompetent and have a strong history of atopy. All
have nasal polyps and chronic sinusitis; many have had multiple sinus
surgeries. There is no increased aspirin sensitivity despite the
association with asthma and nasal polyps. Patients typically present to
the otolaryngologist with acute worsening of their chronic sinusitis with
nasal obstruction, headache, proptosis, and at times intracranial erosion.
Diagnostic criteria have been suggested by Bent and Kuhn and include
(1) type I hypersensitivity confirmed by history, skin tests, or serology;
(2) eosinophilic mucus without fungal invasion of sinus tissue;
(3) positive fungal stains of sinus contents removed during surgery.
The current therapy for AFS involves surgical extirpation of all allergic
mucin if possible with aeration of diseased sinuses. Endoscopic surgical
decompression with adjunctive steroids are considered initially. Most
patients will experience rapid relief of nasal congestion, drainage,
headache and other associated symptoms; however, this is transitory as the
polyps and associated AFS symptomatology almost always recurs. The
hallmark of this disease is multiple sinonasal surgeries (including
external approaches and frontal sinus obliteration) with recurrence of
symptoms. These recurrences may be treated with adjunctive steroids and
office debridement. Other patients may require repeat radiographic
studies and repeat operative debridement. Total and fungal-specific IgE
levels are useful laboratory studies and can be used to follow the course
of the disease.
Steroids Systemic steroids are the mainstay of therapy in ABPA flairs and
have been used successfully in recurrent cases of AFS. However, steroids
have multiple side effects and their use is controversial. Since surgical
drainage and ventilation is possible in the sinuses but not in the lungs,
some authors reserve systemic steroids for difficult or refractory cases
of AFS. Others believe that systemic low dose steroids should be used
indefinitely. Topical intranasal steroid sprays and saline irrigations
have minimal side effects and are used routinely in the postoperative
management of AFS. However, the duration and effectiveness of steroid
sprays in AFS has not been proven scientifically.
The use of topical and systemic antifungal agents is controversial. No
indication exists for the use of toxic antifungal agents (amphotericin B,
Fluconazole) to treat noninvasive fungal sinusitis. Both amphotericin B
and Fluconazole are ineffective against the Dematiaceous fungi and
Aspergillus species. Since AFS is thought to be an allergic disease caused
by an extrinsic fungal antigen rather than a true infection, systemic
antifungals should be ineffective. Itraconazole, a relatively benign and
oral antifungal agent, has had some usefulness in treatment of ABPA and
may be of adjunctive use in management of AFS associated with Aspergillus.
However, the efficacy of itraconazole against dematiaceous has not been
Immunotherapy based on mold desensitization with serial end point
titration would theoretically blunt the type I immune response. However,
antigen injections, while blunting type I hypersensitivity, increase IgG
levels as blocking antibodies are made.This increase in IgG could
theoretically potentiate the pathologic type III response. However, the
role of the type III response in AFS is debated. Immunotherapy for other
inhalants is recommended to reduce the antigenic load presented to the
AFS is a newly recognized noninvasive disease that accounts for
approximately 7% of all chronic sinusitis requiring surgical intervention.
The vast majority of causative fungal agents belong to the Dematiaceae
family. AFS should be suspected in any atopic patient with refractory
nasal polyposis and characteristic radiographic signs. Thick, tenacious,
allergic mucin encountered at surgery can be confirmed histologically and
hyphae can be demonstrated on special fungal stains or confirmed by a
positive fungal culture. Current therapy includes conservative but
complete removal of all allergic mucin, which usually can be accomplished
endoscopically. Although the use of steroids is controversial, adjunctive
systemic steroids are used short term and topical nasal steroids long
term. Recurrence of AFS with associated symptomatology is common,
necessitating close clinical, endoscopic, and radiographic follow-up.
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