Allergic Fungal Sinusitis

Introduction Over the past 2 decades, allergic fungal sinusitis (AFS) has become increasingly defined. Historically mistaken for a paranasal sinus tumor, allergic fungal sinusitis (AFS) now is believed to be an allergic reaction to aerosolized environmental fungi, usually of the dematiaceous species, in an immunocompetent host. This is in contrast to invasive fungal infections that affect immunocompromised hosts, such as patients with diabetes mellitus and patients with AIDS. Most patients with allergic fungal sinusitis (AFS) have a history of allergic rhinitis, and the exact timing of allergic fungal sinusitis (AFS) development can be difficult to discern. Thick fungal debris and mucin, as shown below, are developed in the sinus cavities and must be surgically removed so that the inciting allergen is no longer present. Recurrence is not uncommon once the disease is removed. Anti-inflammatory medical therapy and immunotherapy are being employed to help prevent recurrence.

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Left middle meatus with suctioning of thick allergic mucin from the ethmoid bulla in the center of the picture; the end of the suction is in the inferior portion of the picture.

History of the Procedure

Several decades ago, fungal disease in the nose and paranasal sinuses represented an invasive deadly disease. Management consisted of extensive surgical debridement followed by therapy with systemic and topical antifungal agents. Early on, Aspergillus, a fungus known to cause invasive disease in the sinuses, was the only fungus recovered from the paranasal sinuses in patients with allergic fungal sinusitis (AFS) because of the limitation of culture techniques and the lack of knowledge that dematiaceous fungi caused disease in the paranasal sinuses. Therefore, the disease was treated aggressively.

In 1976, Safirstein noted that the combination of polyposis, crust formation, and sinus cultures yielding Aspergillus was similar to the constellation of findings observed in allergic bronchopulmonary aspergillosis (ABPA), a benign allergic process.¹ Safirstein's description was duplicated and expanded on by reports of allergic aspergillosis of the paranasal sinuses and allergic Aspergillus sinusitis. In the late 1980s, the disease was more widely accepted as a benign fungal process and often confused with a paranasal sinus tumor on imaging studies because allergic fungal sinusitis (AFS) creates expansion of affected sinus cavities.


In 1989, Robson et al introduced the term allergic fungal sinusitis following reports that this condition could be caused by a number of different fungi, not only Aspergillus.² Although the disease is becoming more recognized, confusion remains regarding diagnosis and treatment.

Problem

No consensus exists among rhinologists concerning diagnostic criteria for allergic fungal sinusitis (AFS). Several authors have made observations.

• In 1991, Allphin and colleagues described certain features that they felt differentiated allergic fungal sinusitis (AFS) from other forms of fungal sinusitis, including radiographic presence of multiple opacified paranasal sinuses, characteristic histologic findings of allergic mucin, and laboratory evidence of allergy.
• In 1993, Loury and Schaefer proposed multiple diagnostic criteria, including eosinophilia, immediate skin reactivity or serum immunoglobulin G (IgG) antibodies to fungal antigen, elevated total immunoglobulin E (IgE) level, nasal mucosal edema or polyposis, histopathologic findings of allergic mucin containing noninvasive fungal hyphae, and characteristic CT or MRI findings.³
• In 1994, in reporting the Mayo Clinic experience, Cody et al simplified the diagnostic criteria to include only characteristic allergic mucin and either noninvasive fungal hyphae within the collected mucin or positive fungal cultures.⁴
• In 1994, Bent and Kuhn described what probably are the most widely accepted criteria for diagnosis. On the basis of the analysis of 15 cases, 5 common characteristics were observed, including Gell and Coombs type I (IgE-mediated) hypersensitivity to fungi, nasal polyposis, characteristic radiographic findings, eosinophilic mucin without fungal invasion into sinus tissue, and positive fungal stain of sinus contents removed at the time of surgery.⁵
• In 1997, deShazo proposed a similar set of 5 criteria, including radiographic evidence of sinusitis, presence of allergic mucin (identified grossly or histopathologically), positive fungal stain or culture from the sinus at the time of surgery, absence of contributory factors (eg, diabetes mellitus, immunodeficiencies), and absence of fungal invasion.⁶

A positive fungal culture does not confirm the diagnosis of allergic fungal sinusitis (AFS), nor does a negative culture exclude it. For example, fungi may proliferate as saprophytic growth in diseased sinuses. Furthermore, mycology laboratories vary in capability, and specimen handling significantly influences the rate of positive fungal cultures in a clinical setting. Allergic mucin remains the most reliable indicator of allergic fungal sinusitis (AFS). Because nasal polyposis and fungal disease in the sinuses are not unique to (AFS), other mycotic diseases in the differential diagnosis must be defined and include the following:

• Invasive fungal sinusitis: This condition typically is encountered in patients who are immunocompromised or have diabetes mellitus and is characterized by angioinvasive fungal penetration of tissue. Hypesthesia, local pain, and intranasal necrosis (in an immunocompromised person) strongly suggest invasive fungal sinusitis and help to differentiate this disease from allergic fungal sinusitis (AFS).
• Saprophytic fungal growth: This growth may be found in one or more paranasal sinus cavities of patients who have chronic suppurative rhinosinusitis. Similar growth may occur within nasal debris of patients who have undergone aggressive sinonasal surgery or those who have rhinitis sicca. Although fungal cultures may be positive, the absence of gross and histiologic findings of allergic mucin and the lack of clinical manifestations of invasive fungal sinusitis suggest saprophytic fungal growth.
• Mycetoma, aspergilloma, or fungus ball of the sinuses: This clinical entity differs from allergic fungal sinusitis (AFS) in presentation. Rather than involving multiple sinuses, a fungus ball typically involves a single sinus, most often the maxillary antrum or sphenoid. Patients affected by this condition are not necessarily allergic and generally do not exhibit nasal polyps. On histologic examination, the material removed from the sinuses demonstrates only fungal hyphae without eosinophils. Surgery in such patients generally is curative.
• Eosinophilic mucin sinusitis: Pansinusitis, polyposis, and mucin that is clinically indistinguishable from that of allergic fungal sinusitis (AFS) are characteristic. However, examination of mucin reveals no fungal hyphae. Allergy is not as constant a feature in this condition as it is in allergic fungal sinusitis (AFS), but asthma is observed more frequently. Ferguson has suggested that this condition may represent a variant of the Samter triad.

Frequency

Approximately 5-10% of patients affected by chronic rhinosinusitis actually carry a diagnosis of allergic fungal sinusitis (AFS). Atopy is characteristic of the disease; approximately two thirds of patients report a history of allergic rhinitis, and 90% of patients demonstrate elevated specific IgE to one or more fungal antigens. Approximately 50% of patients in a series by Manning et al had asthma. No linkage to aspirin sensitivity has been established.

Incidence of allergic fungal sinusitis (AFS) appears to be impacted by geographic factors. Review of world literature reveals that most sites reporting cases of allergic fungal sinusitis (AFS) are located in temperate regions of relatively high humidity. However, incidence of allergic fungal sinusitis (AFS) varied remarkably based on the location of reporting sites. Allergic fungal sinusitis (AFS) in the United States was encountered most commonly within the Mississippi basin, the Southeast, and the Southwest. The reason for this geographic difference remains unexplained.

Allergic fungal sinusitis (AFS) is most common among adolescents and young adults; the mean age at diagnosis is 21.9 years. The male-to-female (M/F) ratio of allergic fungal sinusitis (AFS) differs slightly between published reports but is believed to be equal when all ages are evaluated together. A literature review of 98 cases in the 1980s and early 1990s from 29 published journal articles reported an equal M/F incidence. A review by the author and colleagues of 151 patients at the University of Texas (UT) at Southwestern also revealed an equal M/F ratio, with ages ranging from 5-75 years.⁷

However, the M/F ratio may be age dependent and different in children and adults. In the review of patients at UT Southwestern, in children, males dominated (M/F ratio 2.1:1; average age, 13 y), and in adults, females dominated (M/F ratio 1:1.4; average age, 36 y). When evaluating the average ages and sex ratios of other studies, series with younger average ages are more likely to have a male predominance. The average ages in the male-dominated series were 25 and 27 years, while the average age in the female-dominated series was 33 years. The only other pediatric series consisted of 10 patients and had an M/F ratio of 1.5:1, with a mean age of 13.6 years. Interestingly, when 2 series of patients from a single institution were reviewed over time, an early study had an M/F ratio of 1.5:1, with an age range of 13-51 years (average age, 27.5 y), and a later review had an M/F ratio of 1:1.4, with an age range of 13-69 years (no average age given).

Etiology

Most rhinologists believe that allergic fungal sinusitis (AFS) is an allergic reaction to fungi, in which fungal debris, allergic mucin, and nasal polyposes are formed in the nasal cavity and paranasal sinuses. The causative fungi in allergic fungal sinusitis (AFS) are usually dematiaceous fungi, consisting of the genera Bipolaris, Curvularia, Exserohilum, Alternaria, Drechslera, Helminthosporium, and Fusarium, with a small component of allergic fungal sinusitis (AFS) caused by Aspergillus. In a 1996 review of English literature performed by Manning, 263 cases of allergic fungal sinusitis (AFS) were identified, of which 168 cases yielded positive fungal cultures. Of these 168 positive cultures, 87% were from the dematiaceous genera, while only 13% yielded Aspergillus.

The largest reported single institutional experience to date is at the UT Southwestern Medical Center in Dallas, Texas. The fungi recovered from the paranasal sinuses in that evaluation by the author and colleagues revealed that Bipolaris, followed by Curvularia, is the most common pathogen present, seen with similar incidence in adults and children, see Table 1 below. Most large reviews agree, indicating that Bipolaris and Curvularia species are the most common fungi recovered.

When geographic location is specifically reviewed, the further west and inland the series, the more likely that Bipolaris species dominated the fungi recovered. When the series was performed in the Southeast, Curvularia species were more likely to be recovered. Interestingly, in the UT Southwestern experience, Aspergillus was recovered in 13% of adults but in no children. A report from India found only Aspergillus species identified in all 11 patients with allergic fungal sinusitis (AFS) in whom fungus was recovered.