AAAAI: Fungi Stake a Claim in Allergic Sinusitis Pathology

SAN DIEGO, Feb. 28 -- Allergic fungal sinusitis deserves a place of its own at the table of nasty chronic rhinosinusitis infections, researchers asserted here.

It may account for up to 10% of chronic rhinosinusitis, said Patricia S. Hutcheson, of Saint Louis University Medical School, at a briefing during the American Academy of Allergy, Asthma, & Immunology meeting here.

"Allergic fungal sinusitis appears to be a separate and distinct form of chronic rhinosinusitis," she said.

Clinically, patients with allergic fungal sinusitis look pretty much the same as those with chronic rhinosinusitis of non-fungal origin, but the serology tells a different story, said Raymond G. Slavin, M.D., director of the division of allergy & immunology, at Saint Louis University, who headed the research team.

The question is, however, what can be done about it?

"With allergic fungal sinusitis, certainly the most successful treatment has been long term prednisone," Dr. Slavin said. "There is great controversy about antifungal treatment of chronic rhinosinusitis, and as a matter of fact there is now an ongoing multicenter double-blind placebo study on intranasal amphotericin B, and there's also one in the offing on oral itraconazole [Sporanox] for chronic rhinosinusitis, following the Mayo Clinic proposition that the vast majority are due to fungi."

In a study of 84 patients with chronic rhinosinusitis and nasal polyps who underwent nasosinus surgery, the authors found that the patients with fungal infection had total immunglobulin E (IgE), specific immunoglobulin G (IgG) anti-Alternaria mold antibody, and specific IgE against seven different fungi were significantly elevated compared with patients with chronic rhinosinusitis. Also IgE appears to play an important role in the pathogenesis of the fungal infections.

The investigators came to their conclusions after recovering exudates from the patients, culturing them and examining them by histology for the presence of eosinophils, Charcot-Leyden crystals (breakdown products of eosinophils), and for fungal elements, such as hyphae.

They also looked for serum total IgE and IgG anti-Alternaria antibodies, and looked for evidence of six additional fungal species including Aspergillus, Bipolaris, Curvularia, Epicoccum, Fusarium and Phoma.

They found that the exudates from 66 patients had high numbers of eosinophils, visible fungal hyphae, or were culture positive, and these patients were designated as have allergic fungal sinustitis. An additional 18 patients were labeled as having standard (non-fungal) chronic rhinosinusitis.

Both the serum total IgE and specific IgG anti-Alternaria were statistically significantly elevated in the allergic fungal compared to the chronic rhinosinusitis group. The total mean IgE was 1,080 IU/ml (range, 28-12,230 IU/ml) for patients with fungal infections, compared with 324 IU/ml (range 8.8-1081 IU/ml) for those without evidence of fungal infection.

The mean specific IgG-anti-Alternaria 40.6 mg/l (range 0-182 mg/l) for those with allergic fungal sinusitis, and 8.2 mg/l (range 2-37.7 mg/l) for those with chronic sinusitis.

Among the 15 patients who were tested for the presence of all seven fungi, immunoblotting tests for IgE anti-fungi showed multiple bands to all fungi in nine of 10 patients with allergic fungal infections, compared with none of five patients with chronic rhinosinusitis. The number of positive bands for each fungus was significantly higher among patients with allergic fungal sinusitis compared with those with chronic rhinosinusitis.

"A significant and distinct immune response was observed in allergic fungal sinusitis subjects that was different from that seen in chronic rhinosinusitis subjects," Hutcheson said. "The antibody responses reflect our view that IgE antibodies do indeed play an important role in the differences seen in allergic fungal sinusitis subjects, and this distinguishes them from chronic rhinosinusitis subjects."

"IgG is also increased in these subjects, probably due to a heightened general inflammatory resposnse," she continued. "Interestingly, the one chronic rhinosinusitis patient in whom IgE reactivity was seen against all seven fungi had twice the specific IgG-anti-Alternatira level of any other chronic rhinosinusitis subject."