Epidemiology and Medical Mycology of Fungal Rhinosinusitis

Fungal rhinosinusitis (FRS) refers to a spectrum of disease ranging from benign colonization of the nose and sinuses by pathogenic fungi to acute invasive and fatal inflammation extending to the orbit and brain. FRS is classified into two categories: invasive and noninvasive. Invasive FRS may again be subcategorized into acute invasive (fulminant) FRS, granulomatous invasive FRS, and chronic invasive FRS; while noninvasive FRS is subcategorized into localized fungal colonization, sinus fungal ball and eosinophil related FRS (including allergic fungal rhinosinusitis, eosinophilic fungal rhinosinusitis). This classification is not without controversies, and intermediate and semi-invasive forms may also exist in particular patients. Acute invasive FRS is an increasingly common disease worldwide among the immunocompromised patients and caused most frequently by Rhizopus oryzae, and Aspergillus spp. Granulomatous invasive FRS has mostly been reported from Sudan, India, and Pakistan and is characterized by noncaseating granuloma formation, vascular proliferation, vasculitis, perivascular fibrosis, sparse hyphae in tissue, and isolation of A. flavus from sinus contents. Chronic invasive FRS is an emerging entity occurring commonly in diabetics and patients on corticosteroid therapy, and is characterized by dense accumulation of hyphae, occasional presence of vascular invasion, sparse inflammatory reaction, involvement of local structures, and isolation of A. fumigatus. While localized fungal colonization describes the most benign of all fungal sinusitis in the superficial nasal crusts, sinus fungal ball is a dense mycetoma like aggregate of fungal hyphae in diseased sinuses. Common in southern Europe, especially France, majority of them are sterile on culture while 30-50% may yield Aspergillus spp. The definitions and pathogenesis of the group of syndromes in eosinophil related FRS (AFRS, EFRS) are contentious and a matter of intense research among otolaryngologists, pathologists, immunologists and microbiologists. While dematiaceous fungi are the foremost initiators of these syndromes in the west, Aspergillus flavus is the predominant pathogen in India and the Middle-East.