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News -> March, 2000 News
AFRS has been appreciated for almost 20 years based on its histopathologic
findings of eosinophilic mucin with scattered fungal hyphae. The
pathophysiologic basis for AFRS is an IgE mediated hypersensitivity to the
fungus present in the mucin. The atopic individual responds to the antigenic
inhaled spores by secreting mucin, in which the spore germinates and the
hyphal elements grow. This causes increased antigenic stimulation followed by
increased pro-duction of allergic mucin and nasal polyps. Special fungal
stains are often required to see the hyphae. Fungal cultures may be falsely
positive and may fail to grow even in AFRS. The most common fungi associated
with this entity are Bipolaris species, Curvularia, Alternaria, and
Aspergillus species. The disease is the same regardless of the fungal
pathogen. AFRS can lead to erosion of the bony walls of the orbit and the
skull base. In children, presumably with their more malleable bony
structure, proptosis is common. Invasion by the fungus has not been
convincingly shown in any cases of AFRS.
AFRS is unilateral in almost half
of all cases and occurs more commonly in children and young adults, although
it may occur at any age and occurs almost equally in males and females.
Polyps are usually present and frequently the patient can intermittently
expel the characteristic rubbery, greenish mucin. Histopathologic
examination of these plugs frequently reveals hyphae present in allergic mucin, and thus solidifies the diagnosis of AFRS. Computed tomographic imaging
frequently discloses heterogeneity of the soft tissue densities, with the
allergic mucin appearing as a denser mass surrounded by the mucosal hypertrophy and polypoid changes of the nose and sinuses. On Magnetic Resonance Imaging
the proteineous character of the allergic mucin may lead to a signal void on T2 weighted images. Although this is suggestive of AFRS, it is not diagnostic,
since any dense proteineous material in the sinuses may cause a similar image.
The treatment of AFRS is grounded first on diagnosis. Frequently the sinus
surgery that leads to diagnosis is curative, by removing large amounts of the
fungal infested mucin. The microdebriders have greatly aided extirpation of
this tenacious mucin. They must be used with caution adjacent to bony
dehiscences. Persistence or reinfestation is common, occurring in over half of all cases. Systemic corticosteroids, which down regulate the entire
inflammatory cascade, are an important adjunct in alleviating symptoms and
prolonging disease free intervals. Nevertheless, systemic steroids are
associated with significant side effects, including osteoporosis, glaucoma,
cataracts, glucose intolerance, exacerbation of peptic ulcer disease,
hypertension, hypothalamic-pituitary axis suppression, personality changes and growth suppression in children.
The role of topical nasal steroids (NSS)
in AFRS is not well studied, nevertheless most practitioners prescribe them
because of their low incidence of adverse side effects and the theoretically
efficacy of a potent topical steroid in inflammatory disease.
AFRS occurs because of an allergy to the fungus present in the mucous, and
thus it is not much of an extension to assume that NSS's would be effective in AFRS, since NSS's have been shown to be effective for symptomatic relief of
allergic rhinitis.
Antifungal therapy has been advocated in cases of AFRS but no controlled
studies have been performed. Several years ago, a study of the pulmonary
form of the disease, allergic broncho-pulmonary aspergillosis (ABPA) showed
that children with cystic fibrosis and ABPA required less prednisone and had
a fall in total IgE with oral Itraconazole therapy. Anecdotally, the author
has had one patient intolerant of oral steroids, whose AFRS resolved with
a six-week course of Itraconazole. The usual dosage recommended by
Manrin Rains, MD (Tennessee) and Rueben Setliff, MD (South Dakota) is
Itraconazole 100 mg, 4 tablets orally per day for two to four weeks, and
tapered to 200 mg a day for an additional two to four weeks, and finally
to 100 mg a day for an additional month. Itraconazole requires acidity for
optimal absorption, and thus cannot be taken with antacids. Rare hepatic
toxicity has been reported. A course of Itraconazole at a dosage of 400 mg a
day for one month is more than $700. Before long courses of Itraconazole can
be widely advocated controlled trials must be performed.
Over the last five
years, Mabry and colleagues in Dallas Texas have published several studies of
the response of patients to immunotherapy (IT) following surgical removal of
the allergic fungal mucin. IT was initially initiated with fungal antigens
and later other inhalants were added. They demonstrated no adverse reaction
from fungal IT and subsequently in a case-controlled study showed that IT
decreases the rate of recurrence compared to patients electing to forgo IT.
After 3 to 5 years, Mabry and colleagues stopped IT and the studied patients
had no recurrence of disease in a follow up of less than 18 months. Bipolaris
is one of the most common causes of AFRS. Unfortunately, there is no
commercially available Bipolaris antigen. Most patients are allergic to many
molds. Antigenically Helminthosporium is closest to Bipolaris, and many
investigators substitute it for Bipolaris.
The current state of treatment for
AFRS lies first in its diagnosis. The cornerstone of diagnosis is presence of
the characteristic histopathology, which shows eosinophilic mucin with hyphae
present. The treatment consists of conservative surgical exenteration, often
with endoscopic techniques using the microdebrider. Perioperative steroids
are frequently administered to reduce the inflammatory stimulation of surgery
and tapered over one to several weeks. Postoperative IT, containing any fungal antigens to which the patient is allergic or which grow from the mucin, is
instituted within 4 to 8 weeks postoperatively. A preliminary short-term study suggests that after 3 to 5 years, IT may be stopped without risk of recurrence of AFRS. Validation of these promising findings awaits a multicenter-
randomized trial.
Berrylin J. Ferguson, M.D., Board of Directors,
ARS University of Pittsburgh, Pittsburgh, Pennsylvania
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