Sabtu, 18 April 2009

Fungal Sinusitis

An article published in the Mayo Clinic Proceedings way back in September, 1999 by the Mayo Clinic suggested that fungal sinusitis may be much more common than previously thought.

The disease is now know as EFRS (eosinophilic fungal rhinosinusitis) or EMRS (eosinophilic mucinous rhinosinusitis); possibly only a major point to a physician. Of greater importance to the patient; those fungal infections may very well have been caused by toxigenic molds.
Fungal growth was found in washings from the sinuses in 96% of patients with chronic sinusitis. Normal controls had almost as much growth, the difference being that those patients with chronic sinusitis had eosinophiles which had become activated. As a result of the activation, the eosinophiles released MBP (Major Basic Protein) into the mucus which attacks and kills the fungus but is very irritating to the lining of the sinuses. It is believed that MBP injures the epithelium and allows the bacteria to proliferate. The injury to the epithelium by the fungus and mucus led to the belief that treatment of chronic sinusitis should be directed at the fungus rather than the bacteria.

Unfortunately the discussion above was not included in the original article by the Mayo clinic. As a result, the article was not well received initially. There was also no information about the success of treatment in the original article, and there was very little discussed about mechanisms. As more data has accumulated, there is more evidence that the problem may be as important as the Mayo Clinic suggests and the significance is starting to be accepted.
The findings of the Mayo Clinic were confirmed in papers presented at The American Rhinologic Society. The well respected group from Graz, Austria were able to show positive fungal cultures in 92 % of their patients. Almost as many of the controls also had fungi. Clusters of eosinophiles were found around fungi in 94% of patients. This is important because we believe that this shows that the eosinophiles are involved in attacking and killing the fungi.

Current techniques make it difficult for private practitioners to clearly establish EFRS. For example, it is possible to tell by electron microscopy that the degranulation of the eosinophile is in response to fungus. The granules will form a horseshoe shape after degranulation, which is specific to activation by fungi. There are also special stains (e.g. chitinase) which the Mayo Clinic has developed which hopefully will be available in the future.

At the present time, some patients are being treated with irrigation with topical antifungals such as Amphotericin B. Many patients require other agents such as nasal or systemic steroids, however many patients were able to stop treatment with steroids. Through current research, we have discovered, patients have an adverse reaction when they have been exposed to toxic molds.

Given topically, Amphotericin B causes minimal problems. These can include burning due to the fact that it must be mixed with sterile water. It cannot be mixed with saline, and must be protected from light and refrigerated. It is therefore very inconvenient to use. We anticipate that patients will need to be treated indefinitely, or at least until we understand better why these problems are occurring.

There is currently a compounded Nizoral Nasal Spray for minor fungal sinusitis and colonization of the sinus cavity, eustachian tubes, and throat. Another remedy that is extremely effective is Nystatin oral powder applied directly to the sinus cavity with a clean swab. It can be mixed with saline as well.
Because irrigation must get into the sinuses in order to be effective, it is often necessary for patients to have endoscopic sinus surgery before irrigation can be effective. It may be possible to use the Grossan irrigator to irrigate effectively without surgery. It is also speculated that since as many as 70% of patients with EFRS have a positive allergy skin test for fungi or mold it may be possible to treat them by standard allergy management. Since we cannot allergy test for all of the fungi, it can be a difficult proposition. We are also concerned about whether exposure to fungi in the environment may also contribute to part of the problem. In some cases, it may be necessary to ascertain what mold levels are in the home.
There are numerous other types of fungal sinusitis which are more customary. The other forms of fungal sinusitis are broken down into several categories: Allergic, Fungul balls (images) (Mycetoma), and Invasive.

Patients who have repeated bouts of sinusitis, as well as those who are immunocompromised should be considered to possibly have a fungal sinusitis. CT scan will sometimes show calcification, but MRI is more sensitive in diagnosis. Cultures are best obtained from the sinuses, as nasal cultures are rather unreliable.
Allergic fungal sinusitis (AFS) is commonly caused by Aspergillus, as well as Fusarium, Curvularia, and others. Patients often have what appears is associated asthma. The criteria include CT or MRI confirmation, a dark green or black material the consistency of peanut butter called "allergic mucin" which typically contain a few hyphae, no invasion, and no predisposing systemic disease. Charcot-Leyden crystals, which are breakdown products of eosinophiles are often found. Sometimes, patients are found to be allergic to the fungus, although this is very controversial. This disease is analogous to Allergic Bronchopulmonary Aspergillosis.
Surgery, irrigation and immunotherapy are helpful, but it can be extremely difficult to treat. It occurs much more commonly in the humid areas in the Southern United States.

Fungus balls often involve the maxillary sinus and may present similarly to other causes of sinusitis including a foul smelling breath. In addition to radiological abnormalities, thick pus or a clay-like substance is found in the sinuses. There is no allergic mucin, but dense hyphae are found. There is an inflammatory response in the mucosa. Removal of the fungus ball is often the typical treatment, but this varies, depending on the circumstances.
Invasive sinusitis can progress rapidly as any infection, and typically necessitates surgery, repeatedly on an emergent basis often requiring AmphotericinB as well. There have been some forms of invasive sinusitis which can cause proptosis. There is a form of chronic invasive fungal sinusitis which is associated with visual abnormalities due to bony erosion.
Fungal sinusitis should obviously be treated by someone with extensive experience in treatment of this disease

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