Fungal Theory Debated in Amphotericin B Controversy

Affecting more than 30 million Americans, chronic rhinosinusitis (CRS) has been a frustrating disease with no long-lasting results from traditional steroidal and antibiotic treatment, or from surgery. With both clinicians and patients desperate for a solution, it is not surprising that hope-and controversy-has arisen over a potential new therapy.

The use of the antifungal agent amphotericin B to treat noninvasive fungi in CRS has become one of otolaryngology’s hot-button issues. Even though the National Institutes of Health (NIH) announced in a 2004 press release that people with chronic sinus inflammation have an exaggerated immune response to common airborne fungi, many in the medical community are hesitant to embrace an antifungal, one-size-fits-all treatment for all CRS patients.

The concept is that airborne fungi gather in the nose and sinuses and are attacked by eosinophils, which produce secondary mucosal inflammation in susceptible individuals. The debate regards the link between these fungi and CRS. Most specialists regard allergic fungal sinusitis (AFS) as a subset of chronic rhinosinusitis (CRS), which has been defined as any inflammatory disease of the nose and paranasal sinuses that lasts longer than three months. Traditionally, the opinion was that AFS consists of fungus within the sinuses and allergy to that fungus. However, studies in recent years suggest that conventional allergy does not matter-that the immune response to fungi may be mediated through a lymphocyte-dependent mechanism independent of an immunoglobulin E (IgE)-mediated allergy.

The issue of whether fungi causes all CRS gained national attention nearly a decade ago when researchers at the Mayo Clinic announced that fungi were present in nearly all CRS patients, as well as in healthy individuals. After publication of their first data in Mayo Clinic Proceedings (1999;74:877-84), the team demonstrated in follow-up studies that intranasal antifungal treatment (specifically with amphotericin B) improved the objective computed tomography (CT) findings such as inflammatory mucosal thickening, nasal endoscopy stages, and CRS symptoms. After several noncontrolled studies were published, the team further demonstrated positive results with a randomized, double-blind, placebo-controlled trial of 30 CRS patients (J Allergy Clin Immunol 2005;115:125-31).

Studies by researchers in Switzerland and Italy have supported the Mayo findings. Ricchetti et al. (J Laryngol Otol 2002;116:261-3) stated that hyper-reactivity to fungal organisms should be one of the mechanisms underlying the development of nasal polyposis. Additionally, the researchers stated that amphotericin B seems to induce the disappearance of nasal polyps in about 40% of patients.

In 2006, Italian researchers (Corradini et al., J Investig Allergol Clin Immunol 2006;16(3):188-93) said their study indicated that long-term topical treatment with lysine acetylsalicylate and amphotericin B may be clinically effective in the treatment of patients with nasal polyposis associated with fungal infection.