Is there a “Yeast Connection” for Sinusitis?

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"IS THERE A "YEAST CONNECTION" FOR SINUSITIS"
John Murray, MD, PhD
otohns.net International Advisory Board
Departments of Medicine and Pharmacology

Most physicians who care for patients with sinus disease are probably aware by now through recent wide spread media coverage and questions from their patients that a report from the Mayo Clinic recently suggested that virtually all chronic sinusitis results from fungal infection. In my practice this has raised the same level of interest and hope in many frustrated patients with chronic sinus disease as did the “Yeast Connection” that was popular several years ago. This “connection” suggested that many ills, including chronic fatigue syndrome, had their origins from chronic fungal infections. However, it never reached the reality purported. Many media reports have quoted several of the authors from the Mayo Clinic about the study’s results published in their own journal (Mayo Clinic Proceedings 1999; 74:877-884). The authors propose that the basis for chronic sinus disease is an underlying fungal infection and further state that new treatments designed to eradicate this infection should be available to cure this disease within the near future. However, on reviewing the paper, I have felt it necessary to temper the optimism expressed by the authors, media reports and hopes of many patients.

This research describes the findings of fungus on culture of the sinuses obtained either by nasal irrigation with aspiration or by surgical removal of tissue (over two hundred patients had aspirations performed with about half going on to have surgery). The paper reported that virtually every specimen cultured grew fungus - and not only one fungus but up to eight distinct species, with the average being almost three. Skin and RAST testing only showed a lesser percent of reactions (30-40%) being identified as positive to mold. Based on the far fewer number of patients being identified as having positive allergy tests, the authors claim that the culture of the fungus should be considered the gold standard in terms of the etiology of this disease process. In light of this, they propose a redefinition of the disease of allergic fungal sinusitis to eosinophilic fungal sinusitis suggesting that an immunological reaction involving eosinophils stimulated by the fungus occurs by mechanisms other through IgE. A similar change in nomenclature was presented a number of years ago introducing the term “NARES” - Non Allergic Rhinitis Eosinophilic Syndrome. The cause for this syndrome remains unclear; however, it does represent a condition that proves sensitive to steroid treatment due to the involvement of eosinophils. It is possible that there may be an overlap of the patients characterized by the Mayo Group and their responsiveness to steroids to the NARES patients.

There are several concerns about the conclusions of the study based on the results presented. The large number of fungal species cultured out from most samples of the sinuses raises some concern about the specificity of these being associated with the disease process. This issue of specificity should have been evaluated by reporting whether the patients who had positive results to allergy testing to the panel of molds correlated in any way with the culture results. Additionally although half of the patients underwent surgery (of note, there was no information given as to the selection process for the patients who did go to surgery), no data were presented as to whether the same fungal culture profile was obtained from the nasal aspirate done on the same individual. The fungi that were reported to have been cultured also do not appear to represent those that we commonly consider as being pathogens in fungal infections or sinusitis. No information was presented about the previous treatment of these patients with antibiotics (predisposing to colonization of the sinuses) or if antifungal therapy had been attempted, and what was the benefit if any.

The major concern questioning the conclusions of this study is the fact that 100% of the individuals serving as controls (no evidence of sinusitis or allergies) for the sinus aspirates demonstrated a similar fungal culture profile. The methods advocated by the authors include a much more extensive harvesting of the surgical tissue or nasal/sinus secretions. The additional manipulations as well as the fact that the preparation of materials for culture require incubation at 30° C, raises the concern of possible contamination of the materials used for culture. A sham (i.e. involving no actual tissue or heating the specimen adequately to kill whatever fungus might be present at the beginning of the preparation) would seem essential to minimize the concern of contamination contributing to the results. Additionally, the there was no difference in either general or specific IgE level of the sinusitis and control patients, which is unusual for an ostensible allergic condition.

Of course the ultimate answer about whether fungus is the underlying cause of all chronic fungal sinusitis is the resolution of sinusitis with eradication of the fungi. This was not presented as part of this paper. With the toxicity associated with the currently available antifungal medications, I remain reluctant, in spite of these new data, to treat chronic sinusitis patients with these meditations. However, the recognition that some chronic diseases such as seborrhea are due to an underlying mycotic infection supports the notion that we need to evaluate the possible role these organisms may have in any sort of chronic infections.

In summary, this recent article from the Mayo Clinic raises more questions than it answers about fungal sinusitis. How can you define this illness with cultures if the control population has a rate of positive findings even greater than that of the diseased patients? This study and the widespread interest that it has attracted if anything has importantly served to highlight the need for continued investigations into identifying the underlying cause and treatment for the number one chronic disease in the US.