Pathogenesis

A variety of host and environmental factors have been held responsible for the development of fungal sinusitis (1). The common pathway in the conversion of the ubiquitous organisms from saprobic to pathogenic state is sinus obstruction with impaired ventilation. Climate appears to be important factor as higher incidence of fungal rhinosinusitis has been reported from areas, which have a warm and dry climate (2, 3, 4, 5, 6, 7). Dusty, arid conditions possibly predispose to rhinitis and recurrent sinusitis that facilitates the growth of saprobic fungi. Aspergillus species at higher concentration was cultured from straw roofs, earthen floors, bedding and grains stored in the houses (8). Summer sandstorms possibly further disseminate the fungal conidia leading to widespread colonization. Prolonged exposure of large inocula of conidia, probably initiates chronic sinonasal infection (6). Contrasting this common belief of high prevalence of fungal sinusitis in hot and dry climate, cases are now reported at increased frequency in hot and humid environment of south India (9, 10).

Regarding host factors, it is well known that fulminant form is common in compromised host especially in patients with bone marrow transplantation, diabetes, malignant disease, burns and trauma, but it is not so common in patients on steroid or recipients of solid organ transplant (1). AIDS, leukemia, lymphoma and head and neck primary malignancies as underlying disease have been stressed by some workers (1, 11). Other forms of fungal sinusitis can occur in individuals without any underlying disease except possibly chronic invasive fungal rhinosinusitis that occur in patients with diabetes mellitus (12).

Studies in rat suggest that a viral infection of the nasal airway enhances susceptibility to Aspergillus rhinosinusitis (13). Fungal mycelium within a sinus can produce sinusitis either by acting as a foreign body producing metabolites or by producing a hypersensitivity reaction. Both immediate and delayed hypersensitivity may be responsible in pathogenesis (5). The possible role of excess dental root filling materials, which contain zinc oxide and paraformaldehyde from endodontically treated upper molar and pre-molar teeth, in inducing and stimulating antral aspergillosis was claimed by Beck-Mannagetta et al, 1983 (14). They showed that soluble zinc promotes the growth of Aspergillus species; the effect diminishes with decreasing concentration
of zinc (15). In a patient, either zinc diffuses from the area of endodontic therapy or it comes from exposure to dust or from antral foreign body that contains zinc.

The pathogenesis of AFRS is not well understood. It has been suggested that fungal elements trapped in the mucous in sinus release antigenic material that stimulates IgE, IgG, IgA production (16, 17). What predisposes the condition is not clear. AFRS may entail a patho-physiologic course similar to ABPA, with some initial insult causing accumulation of secretions and predisposition of fungal hypersensitivity. It is believed to be a T. helper (Th)2-like, lymphocyte initiated, eosinophil-rich inflammatory disease and once initiated, cellular differentiation pathways may lead to the development of an antigen independent permanent phase (18,19). Numerous models that may be responsible for the patho-physiology of this disorder, including putative role of allergens, fungal derived antigen, bacteria, and bacterial derived superantigens are postulated (19). Till the definite proof that T-cells within the sinuses are actively responding to fungal antigens and further demonstration that removal of the fungal antigens ameliorates the disease, the case against the fungus remains circumstantial.

Other factors important for pathogenesis like genetic risk factors relating to fungal rhinosinusitis, or whether the fungi that cause rhino-sinusitis are different from those causing infections in other body sites are not studied yet.

Experimental model of rhinosinusitis had been attempted in rabbits. Initially Chakrabarti et al (20) developed paranasal sinus infection in rabbit by direct inoculation into the sinuses with an inoculum size of 108 conidia per milliliter of A. flavus. Later Dufour et al (21) developed a better model by introduction of fungi into a sinus with a blocked ostium.

References

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