FUNGAL SINUSITIS TREATMENT:
to spend a lot of time with any patient who develops fungal sinusitis.
Despite the availability of medical and surgical treatments, the recurrence
rate is extremely high, and patients require years of follow-up. "When
I take on a fungal sinusitis patient, I expect to be married to that patient
for the rest of my professional life," said Frederick Kuhn, MD, director
of the Georgia Nasal & Sinus Institute in Savannah.
At the 1999 Annual Meeting of the American College of Allergy, Asthma & Immunology, Dr. Kuhn and three other experts provided an overview of fungal sinusitis. Their presentations covered classification, mycology, and treatment, with a focus on one of the most common forms of the disease--allergic fungal sinusitis (AFS).
"It is estimated that 5% to 10% of all patients with chronic sinusitis requiring surgery have AFS," noted Mark Schubert, MD, PhD, who is in private practice at the Allergy Asthma Clinic in Phoenix, Arizona. "But AFS has often gone unrecognized and is generally underdiagnosed. Also, incidence varies by region; the highest incidence of AFS is currently in the southern and southwestern states."
Fungal sinusitis can be invasive or noninvasive, said Richard D. deShazo, MD, director of the Division of Allergy and Immunology at the University of Mississippi Medical Center in Jackson. In noninvasive disease, fungi appear only in mucus from the sinuses. When the disease is invasive, fungi may penetrate the sinus mucosa, submucosa, blood vessels, and/or bone.
Noninvasive fungal sinusitis
is most common in patients with allergic rhinitis, asthma, chronic sinusitis,
and nasal polyps. These patients, many of whom have undergone multiple
sinus surgeries before diagnosis, may have AFS or sinus mycetoma. Diagnosis
hinges on histopathologic visualization of fungal elements. For instance,
allergic mucin--an eosinophilic, fungi-containing, peanut butter-like
substance--develops in the sinuses of patients with AFS. Although other
forms of fungal sinusitis can have a thick or gravel-like exudate, only
AFS manifests the characteristic allergic mucin.
Sinus mycetoma may occur in any paranasal sinus and, unlike AFS, is often unilateral. Sinus mycetoma patients may present with symptoms of chronic sinusitis. "Some intermittently blow gravel-like material from their noses," added Dr. deShazo.
Invasive fungal sinusitis, which primarily affects immunocompromised patients, exists in three forms: granulomatous invasive fungal sinusitis, chronic invasive fungal sinusitis, and acute fulminate invasive fungal sinusitis. Granulomatous invasive fungal sinusitis occurs almost exclusively in North Africa; it may produce pressure necrosis of the sinus wall, orbital proptosis, or even brain erosion.
Chronic invasive fungal sinusitis is characterized by a low-grade, mixed cellular infiltrate; nasal polyposis; and thick, purulent mucus. Decreased vision, impaired ocular mobility, and proptosis may develop if the infection reaches the orbital apex.
Acute fulminate invasive fungal sinusitis is caused by rapid spread of fungi from the nasal mucosa and sinuses into the orbit, vessels, and brain parenchyma. "Prognosis is poor," said Dr. deShazo, "although with aggressive and early treatment, up to 50% of patients may survive."
ALL FUNGI ARE PATHOGENIC
Patients are increasingly becoming "living Petri dishes," said Michael G. Rinaldi, PhD, a clinical mycologist. The increasing prevalence of immunocompromised patients--the result of human immunodeficiency virus infection and of treatments that impair the immune system--has meant a growing incidence of mycotic infections, including fungal sinus infections. The list of fungi that can infect the sinuses is long.
"Basically, there are no longer any nonpathogenic fungi," indicated Dr. Rinaldi, director of the Fungus Testing Laboratory and a professor of pathology, medicine, and microbiology at the University of Texas Health Science Center at San Antonio. "These days, given the right immunocompromised person, virtually any fungus can cause human disease."
The unique case of a 26-year-old man with end-stage human immunodeficiency virus infection and a low CD4 T-cell count provides an illustration. The patient, Dr. Rinaldi recounted, unknowingly inhaled spores from the wild mushrooms he had gathered and prepared for a meal. Several weeks later, the patient presented, complaining of itchiness and a fissure in the roof of his mouth.
His physician discovered the
head of a mushroom literally growing inside the patient's head. The mushroom
protruded down through the fissure from the sinus cavity. Culture confirmed
it was the same type of fungus--Schizophyllum commune--that the
patient had prepared for the meal.
and A flavus are much more common causes of fungal sinus infection,
and they may be lethal. Under the microscope, A fumigatus has a
smoky, gray-green appearance, said Dr. Rinaldi. In contrast, A flavus
is lime green in color. In addition to Aspergillus sp, Bipolaris
spicifera and Curvularia lunata often cause AFS.
Identifying some of these organisms is difficult because they closely resemble numerous other types of fungi, including some molds that may be equally deadly. Physicians should therefore always use a good microbiologist to identify the infecting organism when fungal sinusitis is suspected, Dr. Rinaldi recommended, not only because it is good medicine, but because such identification may help determine the most appropriate therapeutic approach.
variety of surgical procedures exist for the treatment of fungal sinusitis.
The presence of acute fulminant invasive fungal sinusitis constitutes
a surgical emergency. "It requires immediate, radical resection of
tissue and application of systemic antifungal agents," emphasized
Dr. Kuhn. Without such intervention, the patient has a poor chance of
The previous treatment for chronic sinusitis was open sinus surgery, such as frontal sinus obliteration or external frontoethmoidectomy. A major disadvantage of open surgery, however, is that it typically involves removal of large amounts of bone and healthy sinus tissue.
The newer intranasal
sinus procedures, such as functional endoscopic sinus surgery, are usually
far less damaging. "The purpose of functional endoscopic sinus surgery
is to remove the obstruction at the outflow tract of the sinuses while
preserving all possible mucous membranes and all possible normal structures,"
according to Dr. Kuhn.
Regardless of the procedure, recurrent disease is common--usually, as a result of incomplete surgery that leaves obstructions likely to impair mucocilliary clearance. For example, the recurrence rate of chronic sinusitis is 55% when a poorly resected uncinate process obstructs the maxillary sinus ostium; it jumps to 80% when residual infraorbital ethmoid cells produce such an obstruction.
Postoperative disease recurrence is also highly likely with allergic fungal sinusitis. In a study of 24 patients with the disease, eight of the nine who underwent surgery had a recurrence; the ninth patient experienced a recurrence after the study was completed. "So the key take-home message," said Dr. Kuhn, is that "every patient who is operated on and gets no medical treatment afterward will suffer a recurrence. You just have to wait long enough."
The two longest periods between surgery and recurrence were 29 and 34 months, suggesting that fungal sinusitis patients require very long-term follow-up. In practical terms, the extreme likelihood of recurrence means "that I need to follow these patients for at least five years," Dr. Kuhn concluded. He recommended monthly follow-up for all patients during the first year after surgery, then bimonthly follow-up during subsequent years for those who are doing well.
Further study is required to determine the optimal pharmacotherapy for fungal sinusitis. However, starting long-term oral corticosteroid therapy immediately after surgery appears to reduce recurrences and disease severity, at least with AFS, said Dr. Schubert.
By way of evidence, he described a retrospective study of 67 AFS patients who received standard postoperative treatments (eg, anti-inflammatory nasal sprays, antihistamines, decongestants, and allergen immunotherapy) or standard treatment plus oral corticosteroids.
The corticosteroid group received prednisone; 0.5 mg/kg/d was given for two weeks after surgery, followed by 0.5 mg/kg every other day for about three weeks. The dosage was gradually tapered to between 5 and 7.5 mg every other day by three months, and then 5 mg every other day was given for the remainder of treatment (typically, about a year). If repeat surgery was necessary, this protocol was restarted from the beginning.
At two months' follow-up, most patients in the corticosteroid group had mild or no AFS, whereas patients in the standard treatment group typically had moderate or severe disease, Dr. Schubert said. The results were even better at one year.
The rate of repeat surgery for recurrent disease at 200 days' follow-up also reflected the advantage of corticosteroid use: It was less than 20% in the prednisone group versus about 50% in the standard treatment group. Oral corticosteroids provided significant benefit, stressed Dr. Schubert, even when patients did not complete the entire treatment course.
Serial measurement of total serum immunoglobulin E (IgE) levels has prognostic value, the study also showed. Patients with fungal sinusitis typically exhibit high-titer total and fungal-specific serum IgE levels. "If that level increased 10% or more, the chance of needing recurrent sinus surgery was roughly 50%," Dr. Schubert reported. Furthermore, the total serum IgE level corresponded with the severity of AFS, rising when the disease worsened and falling when it improved.
Dr. Schubert also emphasized the importance of using a "steroid burst" (a temporary increase in the prednisone dose, followed by a rapid taper to its normal level) whenever a patient with AFS has an intercurrent acute upper respiratory tract infection. "Absent that maneuver," he said, "patients with acute upper respiratory tract infections have an increased tendency to relapse."
Systemic antifungal drugs have not been found beneficial, possibly because AFS is noninvasive, Dr. Schubert suggested. It is unknown whether the disease responds to topical antifungals, which are problematic anyway because of the difficulty of applying them to sinus tissue.
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