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Antifungals

Four different types of antimicrobial therapies, with and without surgery, are now employed for fungi-induced disease of the sinuses. Invasive fungal sinusitis is a life threatening infection, and appears more frequently in chronically ill patients, such as insulin-dependent diabetics. 

Treatment consists of intravenous antifungal medications, such as amphotericin B and surgical debridment of infected tissue (Gillespie,1998). In contrast, allergic fungal sinusitis (AFS) is a non-life threatening, often indolent, non-invasive colonization of the nose and sinuses, which occurs in healthy individuals. 

Treatment is directed towards surgical removal of the fungus and inflammatory polyps with restoration of drainage of involved sinuses, and oral steroids to reduce the inflammatory response of the mucous membrane to the fungi (Manning, 1993). Oral antifungals, or lavage of the sinuses with such agents, may be empirically useful but relatively few reports support such therapy. At a minimum, daily lavage of the nose with normal saline is helpful.

Intra-operative photograph of allergic fungal sinusitis debris within sphenoid sinus.

Intra-operative photograph of the maxillary sinus in another patient with AFS. The edematous or swollen mucous membrane (mm) is typical of the inflammatory response to the fungus (fungus)

Axial CT scan of patient with allergic fungal sinusitis. The image has been electronically manipulated on the right to better show the contrast between the fungi and mucus membrane. The areas of increased density (appearing more white) within the maxillary sinuses are sequestered fungi. As the fungus proliferates within the sinuses the protein content of the mucous produced in response to the fungus increases. This inflammatory reaction leads to pockets of increased density typical of AFS.

Most recently, the presence of an inflammatory response (as evidenced by an intense eosinophilic infiltration into the nose and sinus mucus membrane) to fungi, which normally colonize the nose and sinuses leading to chronic sinusitis (or chronic rhinosinusitis [CRS]) has been postulated by the Mayo Clinic (Ponikau, 2002, 2003). 

In theory, diminution of this allergic response should lead to cessation of infected mucous drainage and/or other inflammatory reactions to the fungi. Recommended treatment now consists of a three-month or greater trial of amphotericin B nasal lavage twice daily or voriconazole nose spray once a day. 

This therapy is often supplemented by nasal lavage with Wilson's solution (gentamycin in saline) twice daily, followed by the application of one of the above antifungal agents. If after three months the patient is positively responding to the protocol, antifungal treatment is continued indefinitely to diminish re-colonization of the nose with fungi. Wilson's solution is selectively discontinued after six months. 

Role of fungi in chronic rhinosinusitis (Ponikau, 2002, 2003). Fungi (1) elicit an inflammatory response by lymphocytes (2). The lymphocytes then trigger the release of major basic protein (MBP, 4) by eosinophils (3). The MBP is normally synthesized to destroy foreign agents, such as viruses or parasites. In this case, the MBP causes ulcer in the mucous membrane (5) of the nose and sinuses, giving rise to bacterial sinusitis (6)

The fourth form of fungus sinusitis is mycetoma (myceto = fungus + oma = mass; fungus ball). This is a non-life threatening sequestration or fungus ball, that forms within most typically the maxillary sinus. Treatment is primarily surgical, and consists of removing the fungus ball from the involved sinus. We recommend chronic saline irrigation of the nose after surgery to reduce the likelihood of re-colonization of the sinus with fungus. 

References

Gillespie MB, O'Malley BW Jr, Francis HW. An approach to fulminant invasive fungal rhinosinusitis in the immunocompromised host.Arch Otolaryngol Head Neck Surg. 1998;124:520-6.

Malani PN, Kauffman CA. Invasive and Allergic Fungal Sinusitis. Curr Infect Dis Rep. 2002;4:225-232

Manning SC, Mabry RL, Schaefer SD.Evidence of IgE-mediated hypersensitivity in allergic fungal sinusitis. Laryngoscope. 1993;103:717-21.

Ponikau JU, Sherris DA, , Kita H, Kern EB. Intranasal antifungal treatment in 51 patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2002;110:862-866. 

Ponikau JU, Sherris DA, Kephart GM, Kern EB, Gaffey TA, Tarara JE, Kita H..Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis: is the histopathology similar to asthma? J Allergy Clin Immunol. 2003;112:877-82.

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