Case report: Naproxen-associated sudden sensorineural hearing loss

Military Medicine,  Nov 1998  by McKinnon, Brian J,  Lassen, Lorenz F

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LCDR Brian J. McKinnon, MC USN*

CAPT Lorenz F. Lassen, MC USN*

Naproxen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) whose side effects include tinnitus and transient hearing loss. Sudden sensorineural hearing loss has rarely been reported as a result of NSAID use. This usually occurs in patients taking other ototoxic medications, with poor renal function, or with autoimmune disease. This article reports the case of an otherwise healthy patient who experienced permanent sensorineural hearing loss after a brief course of naproxen and reviews the literature on NSAID-related permanent sensorineural hearing loss.

Introduction

Naproxen is a commonly used nonsteroidal anti-inflammatory drug (NSAID) that is generally considered effective, safe, and well tolerated. It is available both by prescription and as an over-the-counter medication. A propionic acid derivative related to ibuprofen, its anti-inflammatory effects are thought to be from the inhibition of cyclooxygenase and the resultant decrease of prostaglandin synthesis. Naproxen is completely absorbed from the gastrointestinal tract and is 99% bound to the serum. Although temporary ototoxic side effects (tinnitus with occasional transient hearing loss and/or vertigo) have been reported to occur in 1 to 9% of patients,' sensorineural hearing loss from the use of naproxen is rare.2-5

Case Report

An otherwise healthy 35-year-old African-American woman was prescribed naproxen (500 mg by mouth twice a day) for low-back pain. Forty-eight hours after the first naproxen dose, she experienced bilateral hearing loss, tinnitus, otalgia, intolerance to loud noise, and dizziness. She was seen by a primary care physician and referred to an otolaryngologist.

Head and neck examination was normal. Audiometric evaluation showed moderate, bilateral sensorineural hearing loss (Fig. 1). A military reference audiogram, done several years earlier, was normal. Rotational chair vestibular examination was normal, and electronystagmography showed left-sided vestibular nerve weakness. Magnetic resonance imaging of the brain and internal auditory canals was normal. There was a slightly elevated erythrocyte sedimentation rate (23 mm/h) and a weakly positive anti-nuclear antibody test (1:40). Raji cell assay was negative. Other laboratory studies (complete blood count, electrolytes, complement profile, microhemagglutination-treponema pallidum, and thyroid and liver function tests) were normal.

The patient was given a 2-week course of prednisone (60 mg/d) without resolution of her symptoms. Follow-up 6 months later showed no significant improvement in hearing, tinnitus, or noise intolerance. At present, she uses bilateral hearing aides, but these are uncomfortable because of her poor dynamic range and hyperacusis.

Discussion

Although salicylates have been used since the 4th century BC, it was Miller in 1877 who recognized the ototoxic effects of salicylates in high doses.3 Typically, the hearing loss is a temporary 20- to 40-dB threshold shift that is bilateral, symmetric, and sensorineural. Tinnitus usually accompanies hearing loss and is a result of this auditory distortion caused by alterations of cochlear neuron activity. Tinnitus may precede the development of sensorineural hearing loss.3

The mechanisms of naproxen's ototoxic effects have been suggested to be similar to those described for salicylates.35 Ototoxicity appears to be multifactorial.3 Salicylates and NSAIDs have been shown to increase levels of norepinephrine, decrease concentrations of prostaglandins, and increase leukotrienes in the perilymph.6 Decreased blood flow and cochlear hemorrhage (which may be influenced by catecholamines and arachidonic metabolites) have been suggested as occurring in salicylate and NSAID ototoxicity.3-6 Reversible morphologic changes to cochlear outer hair cells have been observed that may result from changes in cellular permeability.3 Physiologic evidence of cochlear outer hair cell injury is strongly supported by diminished otoacoustic emission activity during salicylate toxicity.3

Several reports of permanent sensorineural hearing loss associated with either salicylates or NSAIDs describe individuals who had underlying renal dysfunction, rheumatoid arthritis, polyarteritis nodosa, advanced age, or the use of NSAIDs with other potentially ototoxic medications.2'8 In 1982, Chapman2 reported five patients who developed sensorineural hearing loss while taking naproxen; only two patients completely recovered after stopping the medication. Chapman implicated impaired renal function as a cofactor in one patient with permanent hearing loss. Similar adverse reactions have been reported with piroxicam7 and ketoralac.1

The patient described here had a slightly elevated erythrocyte sedimentation rate and a weakly positive anti-nuclear antibody test. Although there were no other signs or symptoms of autoimmune disease, she could have had a subclinical early autoimmune problem. Kastanioudakis et al. evaluated 45 patients with rheumatoid arthritis and observed a 35.5% incidence of mild symmetric bilateral sensorineural hearing loss.9 There was no correlation of hearing loss with drug therapy (which included NSAIDs, D-penicillamine, plaquenil, and methotrexate), age, sex, disease duration, articular and extra-articular manifestation, or the presence of autoantibodies. Hence, the significance of the minimally abnormal anti-nuclear antibody test and erythrocyte sedimentation rate in an otherwise healthy individual to the development of sudden hearing loss is difficult to interpret.