In 1999 a twist was added to the saga of fungal inflammation following a study performed at the Mayo clinic, which hypothesized a broader role for fungi in the pathogenesis of chronic rhinosinusitis. Using an exquisitely sensitive culture technique, 93% of 101 consecutive patients who underwent ESS for chronic rhinosinusitis demonstrated positive fungal cultures in combination with the histologic presence of eosinophilic inflammation. In comparison, 100% of a small control group also produced positive fungal cultures from nasal mucous. Using this combination of histologically identified eosinophilic inflammation and positive fungal cultures as a less stringent set of diagnostic criteria for AFS, it was proposed that virtually all forms of chronic rhinosinusitis are related in some fashion to non-allergic eosinophilic inflammation caused by fungal exposure. Moreover, when the study population was further evaluated, allergy to fungi failed to correlate with their definition of AFS. It was therefore suggested that the term AFS be replaced with EFRS (Eosinophilic Fungal Rhinosinusitis).

At initial glance the differences between the findings of the Mayo clinic and those supported by already published data appear dramatic. The differences may, however, simply represent a difference of perspective. In the case of the large volume of existing peer-reviewed data concerning AFS, authors have identified patients based upon a recognized set of clinical criteria. When this is done, AFS reliably emerges as a distinct clinical entity that differs from chronic rhinosinusitis in terms of its immunologic, clinical and histologic features. In contrast, it logically follows that reliance upon the combination of an extremely sensitive fungal culture technique and the common histologic presence of eosinophilic inflammation as diagnostic criteria will result in the convergence of the majority of chronic inflammatory sinonasal diseases into a single homogeneous group. Given the vast differences in patient selection, now it appears that no comparisons between AFS and EFRS can be made.

Two questions appear to emerge from these recent developments. First, could a separate, previously unrecognized form of non-allergic fungal eosinophilic inflammation exist? A supportive follow-up study by Kita has demonstrated unique Th1 cytokine stimulation when T-cells were cultured in the presence of Alternaria sp. Such data offer a compelling argument supportive of just such a process. At present, however, the concept warrants independent investigation. Secondly, does AFS exist as a distinct disease entity separate from other forms of chronic rhinosinusitis? This question depends upon how we select our patients. If patients are selected based upon clinical, radiographic and histologic manifestations of the disease, then AFS appears to exist as a distinct clinical entity. In actuality, fungi may incite allergic and non-allergic forms of inflammation, ultimately leading to different disease processes. Certainly, more study is warranted.