SUCCESSFUL TREATMENT OF IMMUNE INNER EAR SYMPTOMS WITH NYSTATIN:
PRELIMINARY FINDINGS
 
Ralph A. Nelson, M.D.
House Ear Clinic and House Ear Institute
Los Angeles, California
 
 
 

Correspondence and Reprint Requests:
 Ralph A. Nelson, M.D.
 House Ear Clinic
 2100 H. Third St.
 Los Angeles, Cal 90057
 (213) 483-9930 FAX:
 (213) 484-5900
 
 
 

Presented at the American Neurotology Society meeting, April 17,
1993, Los Angeles, California.


SUCCESSFUL TREATMENT OF IMMUNE INNER EAR SYMPTOMS WITH NYSTATIN:
PRELIMINARY FINDINGS
Ralph A. Nelson, M.D.

Abstract

Immune-related inner ear disease is usually a progressive condition which can result in total deafness. Although treatable, aggressive therapy is often avoided because of the dangers of the available treatment modalities. Nystatin, a nontoxic fungicidal drug, may provide an alternative treatment approach.

Twenty-three patients with autoimmune or Meniere's inner ear symptoms were placed on a trial with powdered Nystatin. Subjectively, 14 of the 21 patients with hearing loss (66.7%) felt that their hearing was better. Of the 16 patients with balance problems, 13 (81%) were verb subjectively better, while one was rated as worse. Only 3 patients (13.0%) stopped treatment because they felt it was not helpful and another 2 (1.7%) because of side-effects. Of those with objective audiometric data, 23.S% showed a 10 dB or greater improvement in pure-tone average threshold, while 45.5% showed a 15% or better improvement in speech discrimination score.
 
Nystatin USP may be effective in stabilizing or improving the hearing in some patients with autoimmune-type sensorineural hearing loss. Given the relative risks of other treatment modalities, a risk-free agent such as Nystatin USP should be considered as a drug of first choice In appropriate cases of
progressive or fluctuating sensorineural hearing loss.

SUCCESSFUL TREATMENT OF IMMUNE INTER EAR SYMPTOMS WITH NYSTATIN:
PRELIMINARY FINDINGS

Ralph A. Nelson, M.D.

Serendipity has often contributed to advances in medicine. Examples Include the use of digitalis, the discovery of penicillin, and the more recent application of niacin In the towering of cholesterol. The use of the common anti-yeast agent Nystatin for treatment of inner ear problems may represent one more such occurrence.

The successful control of fluctuant and progressive sensorineural hearing loss due to autoimmune disease has required the use of methods and drugs which are both potent and dangerous. The side effects at steroids, the dangers of cytotoxic agents, the cost of plasmaphoresis and the potential complications associated with all of these have been squarely stacked against adequate control of symptoms. For an otologist, there are few feelings worse than
against deafness. Finding a more benign agent to treat autoimmune hearing loss is highly desirable, and serendipity may have led us to one.

About two years ago, a patient being actively treated at the House Ear Clinic for autoimmune hearing loss simultaneously began treatment for allergies in a neighboring city. She was an athletically-gifted college-bound 18-year-old with a binaural fluctuating progressive hearing loss. She had been using a special diet, vasodilators, diuretics, and steroids. However, her hearing loss was not being well-contained. While seeing an allergist, she was placed on regimen of Nystatin without altering her other therapy) because of a family history of mold allergies and there was an immediate improvement in her hearing and general well-being {Creighton, personal communication, 1991).  Eventually, her other medications were discontinued and the only treatment consisted of the Nystatin and dietary control. Because of this success, we began a trial of Nystatin with other patients who had similar symptoms. This report presents the preliminary group results and several case studies.

Methods

Subjects

A retrospective review showed that from April, 1991 through November, 1992, a total of 23 patients were placed on powdered Nystatin for symptoms generally reported in autoimmune inner ear disease. Such symptoms included rapidly progressive binaural hearing losses, fluctuating hearing losses, and dizziness. Table 1 summarizes patient characteristics. The majority of these patients were diagnosed with autoimmune disease (43.5%), while many had Meniere's syndrome (39.1%). Hearing loss was the chief complaint in 69.6% and was reported by 91.3%. Nearly 70% reported vertigo or dizziness. Most, but not all, had had a previous trial with a variety of other routines, but their symptoms were not well-controlled. Later patients were placed on Nystatin as an initial medication of choice because of its lack of significant side effects. Therefore, the duration of symptoms prior to treatment with Nystatin ranged from less then a month to more than 25 years, with an average of just over five years.

Procedures

Nystatin was taken as an oral dose of 1/8th teaspoon of powder in several ounces of water four times daily.2 This was continued for at least a month to determine it there was either objective or subjective improvement of symptoms. Two patients also used vasodilators along with the Nystatin. In addition, 7 patients (30.4%) used steroids during the period of treatment with Nystatin.

Based on availability at chart notes, patients were rated for subjective outcome of hearing and balance, respectively, as 'Better', 'Same', or 'Worse'. When objective audiometric results could be obtained, pure-tone average (PTA) and speech discrimination score (SDS) were recorded for the pretreatment and
posttreatment intervals. An improvement in hearing was considered to be an improvement in either ear of 10 dB or more in threshold or 15% in discrimination when pretreatment hearing was compared to the last available posttreatment test results.

Results

Of the 23 patients who Started treatment with Nystatin, (47.8%) are currently (March 1, 1993) continuing to use it. Three (13.0%) stopped treatment because they felt it was not helpful; 2(8.7%) because of side effects (one nausea, one headache); and 5 (21.7%) because they felt that it was no longer
necessary. In 2 cases, the reason for discontinuation is not known. The mean duration of use of Nystatin Is 6.1 months, with a range from 19 days to 16.5 months.

Subjectively, 14 of the 21 patients with hearing loss (66.7%) felt that their hearing loss was better. For some, this evaluation was based on the feeling that their hearing fluctuated less frequently. Of the 16 patients with balance problems, either vertigo or dizziness, 13 (81.3%) were subjectively better, while one was rated as worse.

Objective audiometric data were available on many of the patients. Four of 17 (23.S%) showed a 10 dB or greater improvement in pure-tone average threshold from pre- to posttreatment in at least one ear, while 5 of 11 (45.5%) showed a 15% or better improvement in speech discrimination score.
Changes in PTA ranged from an increase (poorer hearing) of 14 dB to an improvement of 31 dB. Changes in SDS ranged from a decrement of 16% to an improvement of 84%. Average follow-up time was 4 months, with a range from 1 to 8 months.

Case Reports

Case 1. A 19-year-old young woman had a history of sensorineural hearing loss which was first diagnosed when she was a toddler and which had been extensively evaluated with blood studies and x-rays.  In November, 1987 the hearing in her left ear dropped from a 79 dB PTA and 76% SDS to NR and 0%. She was treated with vasodilators and Prednisone, and, within two weeks, her hearing returned to 83 dB and 80%. She was maintained on vasodilators
and had no further problems until March, 1990 when the right ear dropped from 80 to 90 dB in a predominately low-tone pattern SDS was objectively unaffected, but she subjectively reported some distortion. Treatment with steroids in doses up to 30 mg bid did not help, and the hearing fluctuated widely and frequently during the next year. In April, 1991 the hearing on the right side was down to 114 dB PTA with 4% SDS. Nystatin was added to her steroid therapy, and within a month her hearing improved and stabilized to 84 dB and 88%. She was weaned from the steroids and maintained for the next two years on Nystatin and diet alone.

Case 2. A 60-year-old male with bilateral Meniere's disease diagnosed in 1972 had undergone binaural shunt procedures. When first seen at House Ear Clinic in 1991, his hearing loss was progressing quite rapidly and he was having frequent drop attacks. Of interest was the fact that he had a bad dermatitis.
a sed rate of 50 (normal 0-10mm) and an IgG of 469 (565-1765). He had been placed on steroids in the past after his shunt failures and had some marginal success. Therefore, he was continued on the steroid while instituting powdered Nystatin in October of 1991. In one month his hearing had improved from  71 dB PTA and 72% SDS to 60 dB and 80%. He was experiencing only a mild disequilibrium and had had no further drop attacks. Within 3 months, his hearing wee stabilized at 63 dB and 92% SDS on the right and 58 db and 96% on the left (up from 80% SDS). He had no dizziness at all.

Case 3. This 32-year-oft male was first diagnosed with autoimmune hearing loss In 1988. He had experienced a progressive loss since 1984. Although steroids provided improvement in his hearing, he was never able to drop below 12 to 13 mg per day without incurring additional loss. He had developed some increased weight and moderate acne as well. By July, 1992, hearing in his left ear had fallen to 69 dB PTA with 36% SDS despite the low dose steroid therapy. He was placed on Nystatin because he was becoming concerned with long-term steroid complications.  Within 2 months, his hearing had improved to 54 dB and 96% SDS. At a 6-month follow-up, his SDS maintained on the left and the right side had risen from 88% to 96%. His subjective assessment is that the Nystatin had an obvious positive influence on stabilization of hearing with a marked reduction in fluctuation.

Case 4.  A 63-year-old male with a diagnosis of autoimmune sensorineural hearing loss dating to 1986 had an active and poorly controlled fibrositis and poorly controlled diabetes. He had used vasodilators without success,  but because of his diabetes was reluctant to undertake steroid therapy. Although
also reluctant to try Cytoxin, he eventually did so without success. His hearing was poor with a PTA of 103 dB and 40% SDS on the right and 80 dB and 76% on the left, with wide fluctuations downward. He was placed on Nystatin in August, 1992. When seen one month later, his SDS bad improved to 92% on the left and remained at 40% on the right. At a 4-month follow-up, his hearing on the left was maintaining at 76 dB and 96% discrimination, and his dizziness was markedly improved. Discrimination on the right side, however, had decreased further. He related that this visit was on a particularly bad day. He continues to use Nystatin, feeling that his hearing is more stable and his dizziness is better.

Case 5. This 44-year-old female was referred to us for shunt surgery to quiet her severe right-sided Meniere's symptoms, She had been evaluated  thoroughly elsewhere and had tried a number of Meniere's medical regimens without success. She was placed on steroids in a last ditch trial of medicines and experienced a disappearance of dizziness. Her SDS, however, also dropped. The steroids were tapered over the next two months, but at lower doses, the dizziness returned. The vertigo immediately responded to elevated doses of steroids. This same pattern was repeated on three more occasions at which time in April, 1992 she was placed on Nystatin. One month later her dizziness was totally gone, her hearing was markedly up, and she had been able to reduce her steroids significantly.  She was eventually weaned from the steroids while maintaining her Nystatin. The hearing in her affected right ear improved from 46 dB and 76% pretreatment to 15 dB and 100% posttreatment and has been maintained to this date.

Discussion

Twenty-three patients with symptoms of autoimmune-type inner ear disease were given a trial treatment with Nystatin. Approximately two-thirds subjectively report improvement in hearing, while 81% had subjective improvement in balance problems. Only 13% of the patients stopped treatment because they felt it was not helpful. Objective evidence of improvements in hearing and balance remains to be established.

Nystatin USP is an anti-yeast anti-fungal compound derived from Streptomyces noursei and is a close relative of amphotericin-8 2 It is a polyene antibiotic which increases the permeability of cell membranes in yeast and is considered fungistatic and fungicidal. Taken orally, it will have an effect on the gastrointestinal yeast throughout the entire alimentary tract, but has no significant systemic absorption. Although poorly absorbed, persons with renal insufficiency may develop high plasma concentrations. Nystatin is commonly used to treat oral and anal thrush (moniliasis) in children and is also used in
vaginal candidiasis. The dosage is 500,000 units four times daily. As a powder, this is 1/8 teaspoon in an ounce or two of water; as a tablet, this is one tablet each dose; and as the suspension, this is one teaspoon per dose. It comes in many forms, including oral suspension (mixed in 50% sucrose to deaden
its bitterness), oral tablets, powder, creams or ointments, and vaginal tablets. We chose the powdered form because it is theoretically more effective through the entire GI tract than the tablets which affect the lower GI tract only. The syrup is 50% sucrose, and it would appear to be contraindicated in treatment
of the very yeast that feed on sugars. One patient in the current trial who was reasonably well-controlled on oral powder switched to the suspension for logistical reasons. She typically would become aware of response to the Nystatin within 3 to 4 days whenever starting or stopping the powder, but became worse whenever she substituted the suspension.

There are no known long-term side effects or serious known complications with the drug. A few people have complained of nausea or headache. These symptoms are usually eliminated by reducing the amount of Nystatin taken until better tolerance is achieved.

Several years ago when we first began treating autoimmune hearing loss, it was recognized that many patients developed symptoms after ingesting quantities of sugar (Weisbart R. unpublished data, 1983). It was an observation we were unable to duplicate experimentally, but clinical responses to sugar restriction were well-documented. This is why we continue to encourage dietary control side by side with other accepted methods of treatment.
 
At that time, it was postulated that the potential mechanism of damage was an abnormal glycosylation via gastrointestinal flora (Weisbart, personal communication, 1983). The serendipitous discovery that Nystatin also has positive influence on this disease process provided us with one more piece to a puzzle which increasingly points towards a dietary and yeast causation. Whether this is representative of yeast allergy, glycosylation errors or other toxic phenomena is not yet known.

There is little in the standard medical literature concerning the influence of yeast on hearing and the possible treatment. However, there has been a groundswell of interest, including a national best seller, 3 in yeast, its alleged manifestations and the treatment thereof.  Well-conceived prospective studies are now needed to properly explore the potential of this avenue of thought for application to autoimmune hearing loss.

Conclusions

Observations in 23 patients suggests that Nystatin USP may be effective in stabilizing or improving the hearing in some patients with autoimmune-type sensorineural hearing loss. Given the relative risks of many treatment modalities such as steroids, cytotoxic drugs or plasmaphoresis, a risk-free agent such as
Nystatin USP should be considered as a drug of first choice in cases of fluctuating sensorineural loss, rapidly progressive sensorineural loss, and Meniere's Syndrome symptoms. A trial using 1/8 teaspoon of powdered Nystatin USP in one to two ounces of water orally four times dally for a month is recommended.

Acknowledgments

The author wishes to thank Karen I. Berliner, Ph. D. who performed data analyses and helped in preparation of the manuscript.

References

1. Nelson RA: Sensorineural hearing loss: Medical therapy. In, Gates G (Ed): Current Therapy In Otolaryngology - Head and Neck Surgery, 5th Ed. Philadelphia: Mosby Year Book,  (in press).

2.  Bellman AG, Goodman LS, Gilman A: The Pharmacological Basis  of Therapeutics. 6th Ed. New York: Macmillan Publishing Co, Inc., 1980; pp 1232-1233.

3.  Crook WG : The Yeast Connection. New York: Random House, Inc., 1986.
 
 

[Note: This is a digitally-reproduced copy of the original paper. Every care has been taken to reproduce the original accurately. The only exceptions are that pagination has changed slightly (the original covers 16 pages) and that the Acknowledgments and References appear on one page instead of two.]


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