2018 Section 5 - Rhinology and Allergic Disorders

Curr Allergy Asthma Rep (2015) 15: 75

insufficient to suggest a beneficial effect in AFRS of either topical intranasal antifungal agents or systemic therapies such as itraconazole. It is rational to employ long-term antifungal agents in ABPA as a way to reduce fungal antigenic exposure in the lungs due to trapped hyphae in airway mucin. While AFRS and ABPA share many clinicopathologic similarities, anatomic differences between the paranasal sinuses and lungs may predicate different treatment strategies. The fungal anti- genic burden in allergic fungal sinusitis can be alleviated by sinus surgery, office debridement, and saline irrigations. These mechanical methods to remove the fungal stimulus for inflam- mation may make an antifungal treatment approach irrelevant.

There has been one randomized controlled trial evaluating a systemic antifungal therapy (terbinafine) for patients with CRS. Fifty-three adult patients with CRS were randomized to receive 625 mg of terbinafine daily for 6 weeks or placebo. There was no statistically significant difference recorded on any of the measured outcomes including Lund-Mackay CT score, patient and physician evaluation of therapeutic re- sponse, as well as Rhinosinusitis Disability Index scores [ 21 ]. Several studies have evaluated the effect of amphotericin B sprays and irrigations with different dosing schedules and treat- ment durations. These studies have uniformly failed to show a clinically significant benefit of topical intranasal amphotericin B for CRS either with or without nasal polyps. Weschta et al. ran- domized 78 patients with CRS with nasal polyposis (CRSwNP) to receive topical amphotericin B topical nasal spray (200 μ L of 3 mg/mL for 8 weeks) or isotonic saline placebo spray. There was no significant difference between treatment and placebo arms using the Lund-Mackay CT score, and in fact, the placebo group had better rhinoconjunctivitis quality of life scores [ 22 • ]. A subsequent analysis failed to show any effect of antifungal treatment on fungal recovery rates or markers of inflammation (ECP, tryptase) in sinus lavage samples in these patients [ 23 ]. Ponikau et al. randomized 30 patients with CRS to receive 20 mL of amphotericin B (250 μ g/mL) or placebo via bulb syringe for 6 months. Antifungal treatment did not impact markers of inflammation or fungal burden in the sinuses, nor was there any improvement in sinus symptoms as assessed by the sinonasal outcomes test-20 score [ 24 ]. Ebbens et al. randomized 116 adult patients with CRS to receive 25 mL amphotericin B solution (100 μ g/mL) intranasal irrigation twice daily for 3 months with a control arm performing saline irrigations. Amphotericin B treatment failed to reduce clinical signs and symptoms in patients with CRS [ 25 • ]. Liang et al. randomized 70 CRS patients without nasal polyps to receive nasal irrigation with amphotericin (5 mg/mL) or pla- cebo for a total study time of 4 weeks. Neither symptoms nor nasal endoscopy scores improved with antifungal treatment [ 26 ]. Finally, Gerlinger et al. recruited 33 adult patients with CRSNP, all of whom had undergone prior polypectomy. Patients were randomized to receive amphotericin B nasal spray (100 μ L, 2 puffs BID 5 mg/mL) or saline placebo spray. The study was continued over 1 year. Again there were no significant benefits of amphotericin treatment [ 27 ].

Compliance with Ethical Standards

Conflict of Interest Drs. Ryan and Clark have no conflicts of interest.

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1. •• Ponikau JU, Sherris DA, Kern EB, et al. The diagnosis and inci- dence of allergic fungal sinusitis. Mayo Clin Proc. 1999;74(9):877 – 84. This report coined the term ‘ eosinophilic fungal sinusitis ’ , suggested that most CRS was due to a hypersensitivity to fungal antigens, and launched the current debate regarding fungi in chronic sinus disease . 2. Buzina W, Braun H, Freudenschuss K, et al. Fungal biodiversity-as found in nasal mucus. Med Mycol. 2003;41:149 – 61. 3. Safirstein B. Allergic bronchopulmonary aspergillosis with obstruc- tion of the upper respiratory tract. Chest. 1976;70:788 – 90. 4. •• Katzenstein AL, Sale SR, Greenberger PA. Allergic aspergillus si- nusitis: a newly recognized form of sinusitis. J Allergy Clin Immunol. 1983;72:89 – 93. This is the first case series of AFRS cases. Based upon clinical history and histopathologic findings the authors proposed a pathophysiologic mechanism for the disease as well as a treatment paradigm that persists to this day . 5. Manning SC, Holman M. Further evidence for allergic pathophys- iology in allergic fungal sinusitis. Laryngoscope. 1998;108(10): 1485 – 96. 6. Allphin AL, Strauss M, Addul-Karin FW, et al. Allergic fungal sinusitis: problems in diagnosis and treatment. Laryngoscope. 1991;101:815 – 82. 7. Cody DT, Neel HB, Ferreiro JA, et al. Allergic fungal sinusitis: the Mayo Clinic experience. Laryngoscope. 1994;104:1074 – 9. 8. • Ferguson BJ. Eosinophilic mucin rhinosinusitis: a distinct clin- icopathologic entity. Laryngoscope. 2000;110:799 – 813. This study demonstrated important clinical difference between AFRS as classically defined and other forms of ‘ eosinophil- ic mucin rhinosinusitis ’ such as in aspirin exacerbated re- spiratory disease .

Conclusion

Because of a large body of evidence, antifungal therapy has not been widely adopted in the treatment of CRS with or without nasal polyps. It remains to be determined whether antifungal treatment might be effective in certain subpopula- tions with chronic sinusitis, such as allergic fungal rhinosinusitis. However, the clinical evidence to date is

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