Introduction
The potential efficacy of antifungal agents (e.g. Mycostatin (nystatin), Bristol-Myers Squibb Pharmaceuticals, Swords, Ireland) for the treatment of Ménière's disease was first noticed in 1983, following anecdotes of patients with the disease whose hearing loss and vertigo improved after commencing oral antifungal therapy for unrelated disorders. A preliminary study presented by the House Ear Clinic found that following oral administration of nystatin, 14 out of 21 patients with Ménière's disease reported subjective improvement in hearing, and 13 out of 16 also reported subjective improvement in balance problems.Reference Nelson1 To date, however, there have been no data published on this effect.
A possible explanation for this effect may be related to the role antifungal agents play in reducing the systemic inflammatory response induced by the gastrointestinal yeast load, an effect that has been implicated in Ménière's diseaseReference Wilson2, Reference McMillan3 as well as in other conditions.Reference Dimitrova, Danova and Ivanovska4
Mycostatin is a polyene antimycotic agent derived from Streptomyces noursei that binds to ergosterol, a major component of the fungal cell membrane. It increases cell membrane permeability by forming pores within the membrane, leading to potassium leakage and eventual cell death. Oral Mycostatin has minimal systemic absorption, making it safe to administer, yet effective in the gastrointestinal tract.
Oral Mycostatin has been used as second-line medical treatment for intractable Ménière's disease at our institution since the early 1990s. In order to study the role of oral Mycostatin in reducing the severity of acute attacks in intractable Ménière's disease, particularly symptoms of hearing loss, vertigo, aural fullness and tinnitus, a preliminary descriptive case series study was conducted. In addition, the results will provide information on which to base a future randomised controlled trial.
Materials and methods
A retrospective review of patient data was undertaken at a tertiary neurotology specialist referral centre. All patients with intractable Ménière's disease who had started oral Mycostatin treatment over the period 2010–2012 were included.
The criteria for the diagnosis of Ménière's disease were strictly applied; patients included in the study had definite disease as defined by the guidelines of the American Academy of Otolaryngology – Head and Neck Surgery (AAOHNS).5 All patients had also suffered recurrent attacks of Ménière's disease for at least three years before presenting to the clinic, and had previously not responded to standard first-line non-medical and medical treatments, including dietary sodium restriction, betahistine and diuretics. All patients wanted to try another oral alternative before resorting to other more invasive measures such as intratympanic steroid injections, or chemical or surgical ablation. Patients included in the study were prescribed oral Mycostatin (100 000 units/ml) at 1 ml four times a day, for six months. Patient demographics, treatment duration and clinical improvement measures were evaluated according to AAOHNS guidelines.5
Results
Over the study period, 256 patients presented to the specialist clinic with vertiginous disorders. Of these, 26 consecutive patients had intractable Ménière's disease, 7 of whom had bilateral disease.
Following treatment with oral Mycostatin, 8 of these 26 patients reported improvement in vertiginous symptoms at 6 months’ follow up, and 7 of the 26 patients had an improvement in aural fullness. In addition, three patients noted improvement in tinnitus and another three reported improvement in subjective hearing loss. Interestingly, half of the patients who experienced symptomatic improvement, especially in vertigo and aural fullness, did not wish to stop their course of oral Mycostatin at six months, and continued to take it. At two years’ follow up, three out of the seven patients who continued taking the drug long term had remained completely asymptomatic throughout treatment.
The side-effects of oral Mycostatin were minor and uncommon, consisting mainly of mild gastrointestinal irritation and hyperglycaemia.
Discussion
The use of oral Mycostatin to alleviate symptoms of intractable Ménière's disease showed promising results in this preliminary case series. Although the overall spontaneous remission rate of the disease has been reported to range from 21 per cent to 80 per cent,Reference Torok6, Reference Silverstein, Smouha and Jones7 these rates are unlikely to be extrapolated to patients who are extremely resistant to treatment or have had chronic, longstanding symptoms, whose natural resolution rate is far lower. The aetiology of Ménière's disease remains unknown, but there is evidence to suggest that fungal sensitivity may play a role.
Given the lack of a control group for this series, more robust studies of this treatment are certainly required. These data suggest, however, that Mycostatin may offer a safe and useful alternative for the management of Ménière's disease in patients with chronic, longstanding and unremitting symptoms who have not responded to previous first-line treatment options.
