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Role of Fungi in Allergic Fungal Sinusitis and Chronic Rhinosinusitis hinosinnsitis

      To the Editor: In the recent study by Ponikau et al,
      • Fonikau JU
      • Sherris DA
      • Kern EB
      • et al.
      The diagnosis and incidence of allergic fungal sinusitis.
      the authors describe a new and more efficient method of nasal mucus collection. They subsequently used this method to demonstrate that of 210 patients diagnosed as having chronic rhinosinusitis (CRS), 202 patients (96%) had fungi (representing 40 different genera) in their nasal mucus. They further found that 100% of their control patients (14/14) also had fungi (from 8 different genera) in their mucus.
      A subset of 101 CRS patients was also treated surgically, and nasal samples were subjected to histopathological examination. Fungal elements were found in 82 (81%) of the 101 samples examined. They also found that eosinophil “presence” was detectable in 96% (97/101) of these cases. In contrast, tissue from 4 control patients subjected to histopathological examination contained no evidence for the presence of eosinophils. Based on their findings, the authors conclude that allergic fungal sinusitis (AFS) is significantly underdiagnosed and is in fact present in the majority of patients suffering from CRS. They also suggest that immunoglobulin E (IgE)—mediated type I hypersensitivity is not the dominant pathophysiological factor in AFS. They indicate that such a role is played by eosinophils and suggest that AFS be renamed eosinophilic fungal rhinosinusitis (EFRS).
      For the most part, the article presents some thoughtful, intriguing, and provocative findings. However, it is also somewhat perplexing how the authors arrive at their conclusion that fungi play an important role in the onset of AFS. In part this is due to the fact that their reported findings violate Koch's postulates on causation of disease and that the authors actually demonstrate that the “causative agents,” ie, fungi, are present in both diseased and control patients. Furthermore, the authors did not demonstrate that the same symptoms can be induced in a healthy subject after infection with the pathogen, in this case the fungus. Hence, it is rather difficult to accept, based on the preliminary data presented, the authors' assertion that fungi are important in the etiology of AFS and CRS.
      The authors' finding that 96% of the individual CRS surgical tissue examined revealed the presence of eosinophils appears to be important, since this finding contrasts with the fact that tissue specimens from all 4 control patients contained no eosinophil presence. However, this is not a new finding. Harlin et al
      • Harlin SL
      • Ansel DG
      • Lane SR
      • Myers J
      • Kephart GM
      • Gleich GJ
      A clinical and pathologic study of chronic sinusitis: the role of the eosinophil.
      reported in 1988 on a study of 26 patients suffering from chronic sinusitis that tissue from such patients “was extensively infiltrated with eosinophils.” Indeed, Hansel,
      • Hansel FK
      Clinical and histopathologic studies of the nose and sinuses in allergy.
      back in 1929, was the first to report such infiltration by eosinophils. Furthermore, this contrast in eosinophil infiltration between CRS vs control patients would have been more compelling if the authors had carried out examinations on a clearly defined control population.
      I also noted that a Mayo Clinic news release
      • Mayo Clinic Rochester News
      Mayo Clinic study implicates fungus as cause of chronic sinusitis [news release].
      issued immediately after the article was published stated that “Mayo Clinic researchers say that they have found the cause of most chronic sinus infections–an immune response to fungus.” The release went on to state that the authors of the article say “this discovery opens the door to the first effective treatment for this problem.” The study findings
      • Fonikau JU
      • Sherris DA
      • Kern EB
      • et al.
      The diagnosis and incidence of allergic fungal sinusitis.
      and these claims
      • Mayo Clinic Rochester News
      Mayo Clinic study implicates fungus as cause of chronic sinusitis [news release].
      were criticized in a Washington Post article published in late November 1999.
      • Boodman SG
      Mayo report on sinusitis draws skeptics', some experts challenge fungal basis for many infections.
      Experts in otolaryngology expressed concern that if “100% of controls have fungi, why does it [Mayo findings] mean anything?” Furthermore, the Washington Post article
      • Boodman SG
      Mayo report on sinusitis draws skeptics', some experts challenge fungal basis for many infections.
      raised the issue that patient expectations to be treated successfully for CRS had been elevated unduly.
      It would appear with hindsight that the Mayo findings
      • Fonikau JU
      • Sherris DA
      • Kern EB
      • et al.
      The diagnosis and incidence of allergic fungal sinusitis.
      may have been reported prematurely. This has already resulted in both criticism and skepticism of the work. On reflection this is somewhat unfortunate, since even the critics of the work
      • Boodman SG
      Mayo report on sinusitis draws skeptics', some experts challenge fungal basis for many infections.
      agree that more comprehensive studies should be done to explore the possible role of fungi in AFS and CRS. However, I would hope that all of us continue to strive for candid and objective assessment of work. This is particularly important in regard to those findings that may impact patients' hopes and expectations regarding treatment of a particular illness or disease. We should all err on the side of caution in terms of conclusions we draw and report based on a very preliminary data set.

      REFERENCES

        • Fonikau JU
        • Sherris DA
        • Kern EB
        • et al.
        The diagnosis and incidence of allergic fungal sinusitis.
        Mayo Clin Prac. 1999; 74: 877-884
        • Harlin SL
        • Ansel DG
        • Lane SR
        • Myers J
        • Kephart GM
        • Gleich GJ
        A clinical and pathologic study of chronic sinusitis: the role of the eosinophil.
        J Allergy Clin Immunol. 1988; 81: 867-875
        • Hansel FK
        Clinical and histopathologic studies of the nose and sinuses in allergy.
        J Allergy. 1929; 1: 43-47
        • Mayo Clinic Rochester News
        Mayo Clinic study implicates fungus as cause of chronic sinusitis [news release].
        (Accessed April 7, 2000.)
        • Boodman SG
        Mayo report on sinusitis draws skeptics', some experts challenge fungal basis for many infections.
        Washington Post. November 23, 1999; (Accessed February 17, 2000.): 207

      Linked Article

      • Role of Fungi in Allergic Fungal Sinusitis and Chronic Rhinosinusitis: In Response
        Mayo Clinic ProceedingsVol. 75Issue 5
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          As Dr Naylor states, extramucosal fungi were found in almost all patients with CRS and also in all controls.1 To conclude for this reason that fungi do not cause disease is flawed. We know that the bacteria responsible for most cases of acute sinusitis are always present in normal, healthy hosts. An event (such as an upper respiratory tract infection) occurs that causes swelling and leads to a cascade of events that allow infection by the same bacteria. From an infectious disease point of view, assuming that the mere presence of organisms causes disease, the conclusions we drew from our study can certainly be challenged.
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