7 Fungal Diseases of the Paranasal Sinuses

Fungal involvement in sinus disease has a wide variety of manifestations. It has been implicated in sinus disease, from acute infection to chronic disease and invasive disease. There have been debates on direct pathogenic role of fungus versus host response to the fungus. Whether fungus has any role in sinus disease—that it may simply be ubiquitous and seen as a colonizing organism—has been debated for several disease subsets. This chapter will explore different areas of fungus involvement in sinus disease. There have been several methods of classification based on the pathology and epidemiology,1–3 but the disease can be divided into the following categories: noninvasive fungal rhinosinusitis (allergic fungal rhinosinusitis [AFRS] and mycetoma) and invasive fungal rhinosinusitis (acute invasive, chronic invasive, and granulomatous).

Noninvasive Fungal Rhinosinusitis

Allergic Fungal Rhinosinusitis

AFRS is the most common form of fungal rhinosinusitis. It is characterized by dark, thick, inspissated mucus filling the paranasal sinuses. This allergic or eosinophilic mucin is thick and very tenacious, which can be difficult to extract from the sinuses. On microscopic examination, it has onion-skin layers of necrotic and degranulating eosinophils in the background, few fungal hyphae, and small hexagonal lysophospholipase crystals (also known as Charcot-Leyden crystals).^4–6 The most common organisms isolated are dematiaceous fungi such as bipolaris and curvularia.^7,8

The disease classically manifests as unilateral disease. Patients exhibit slow, progressive nasal congestion, postnasal drainage, nasal obstruction, and anosmia. The thick, mucinous debris is commonly found in the nasal discharge. If the fungal element of this disease is not recognized, a patient may have disease refractory to conventional treatments and even have multiple surgeries in an effort to clear the disease process. Patients may have proptosis or telecanthus at presentation.^9–12 Diagnostic computed tomography (CT) scans may suggest the diagnosis by demonstrating opacification of multiple sinuses with areas of central hyperattenuation from mucin, mucoceles, and remodeling of the paranasal sinuses including lamina papyracea. Magnetic resonance imaging (MRI) may also demonstrate similar sinus findings on T1 and T2 imaging, particularly elevated peripheral signal from mucosal inflammation and central signal attenuation from mucin.

Patients are typically young, atopic, and immunocompetent.^8,10 The pathogenesis of the disease has been assumed to be fungal hypersensitivity culminating in Gell and Coombs types 1 and 3 reactions to fungal allergens, similar to Aspergillus bronchopulmonary disease.¹³ Given the association with allergy and with elevated immunoglobulin (Ig) G and IgE levels to fungal antigens, this appears to be a valid hypothesis for one part of the pathogenic mechanism.^9,13–15 Although other investigators have suggested different diagnostic criteria, Bent and Kuhn¹⁶ published criteria that have remained the most reliable in establishing the diagnosis. Their criteria include establishing the following: type 1 hypersensitivity by history, skin tests, or in vitro testing; characteristic CT scan findings as illustrated above; demonstration of nasal polyposis; confirming eosinophilic mucus; finding positive fungal stains in specimens from sinus surgery; and the absence of fungal invasion into sinus tissue. It is believed that the key to successful long-term management of this disease will hinge on developing more effective classification and disease characterization, given the overlap with other forms of chronic rhinosinusitis.

AFRS is treated through a combination of medical and surgical methods. Surgery is employed to open and evacuate the paranasal sinuses, particularly if there is evidence of extensive remodeling and risk of orbital or intracranial complication. Extensive resection of mucosa is not necessary, but re-establishing drainage pathways is essential. Different medical treatments have been used, each with varying success and each carries merit in their use. Immunotherapy, leukotriene inhibitors, systemic steroids, topical nasal steroids, macrolides, and antifungals may be used in management.^10,17–20 Amphotericin B lavage has been advocated in the treatment of rhinosinusitis, targeting fungal etiology, but the data are inconclusive in showing an acceptable risk:benefit ratio.²¹ However, this and other antifungal irrigations may fail because of the inability to properly penetrate the mucinous sinus debris. Despite this inability interventions are chosen, AFRS still has a high risk of recurrence.²² Successful treatment results in a reversal of any sinus and orbit remodeling (i.e., proptosis and volume reduction), as well as resolution of mucin production.

The production of mucin with the presence of fungus is a diagnostic hallmark and helps guide treatment. However, there are variations of the disease that do not have fungal elements identified in the mucin, yet they respond to AFRS treatments. Ferguson²³ proposed eosinophilic mucin rhinosinusitis (EMRS) to describe this variant. Subsequently, Ponikau et al24 reported that fungi was ubiquitous in sinus disease and could be identified using more sensitive testing in chronic rhinosinusitis patients. They postulated that the chronic rhinosinusitis disease may be a cell-mediated hypersensitive response to fungi. These and other reports point to conflicting evidence in the literature; some of the findings have been replicated by other observers, whereas others have not. Additional studies have supported the hypothesis that IgE- and IgG-dependent mechanisms lead to a fungal antigen hypersensitivity response in patients with AFRS and EMRS.^25,26 These incompletely understood mechanisms are presumptively responsible for the production of eosinophilic mucin seen in AFRS and EMRS. Regardless, the exact relationship of fungus in rhinosinusitis continues to be an area of debate (and is further discussed in another chapter), but in AFRS the diagnostic and treatment findings directed toward fungus appear to have utility as well as suggestion of underlying mechanisms. The differences seen in diagnostic and clinical performance of patients likely represent variability in disease pathogenesis as well as the need to identify other key factors to better tailor diagnosis and treatment algorithms.

Mycetoma

This is a form of noninvasive rhinosinusitis that is most often caused by Aspergillus species.²⁷ It has been well characterized as a separate entity given the noninvasive nature of the disease. It has been described classically in the immunocompetent patients. Other reports indicate that they can occur in immunocompromised patients and may also involve Mucorales order organisms.²⁸ It should be noted that in an immunocompromised patient in particular, diagnosis of mycetoma versus invasive fungal rhinosinusitis should be very carefully considered, as the treatments and the overall prognosis are significantly different.

The presentation of mycetoma should be suspected under certain conditions. There is typically a paucity of sinus involvement, and a singular sinus can be involved. The sinuses typically involved are the maxillary (most common) and sphenoid sinuses. The mycetoma grows in the sinus, exerting mass effect. CT is especially useful in supporting the diagnosis, whereas MRI may be useful in some patients where soft tissue delineation may be needed. The classic appearance on CT shows intrasinus inspissation with hyperattenuated areas suggestive of calcification (Fig. 7.1). Sinus remodeling and hyperostosis can be seen as well. On MRI, one sees low signal intensity on T1- and T2-weighted imaging, which can sometimes make diagnosis difficult if used as the sole modality. In general, CT is more useful in supporting the diagnosis.

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