eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Inner Ear

Inner Ear, Autoimmune Disease

Neeraj N Mathur, MBBS, MS, Professor, Department of Ear, Nose and Throat, Lady Hardinge Medical College and Associated Smt SK and Kalawati, Saran Children's Hospital, University of Delhi, India; Professor and Head, Department of Ear, Nose and Throat, BP Koirala Institute of Health Sciences, Nepal

Updated: Oct 16, 2009

Introduction

Background

In 1979, McCabe first described a cohort of patients with idiopathic, rapidly progressive bilateral sensorineural hearing loss (SNHL). These patients' hearing improved after treatment with corticosteroids, thereby suggesting an autoimmune pathogenesis. The hallmark of this clinically diagnosed condition is the presence of a rapidly progressive, often fluctuating, bilateral SNHL over a period of weeks to months. The progression of hearing loss is too rapid to be diagnostic for presbycusis and too slow to conclude a diagnosis of sudden SNHL. Vestibular symptoms, such as true vertigo, generalized imbalance, and ataxia, may be present.

Inner ear.

Pathophysiology

The term autoimmune inner ear disease (AIED) implies a direct attack of the immune system upon an endogenous inner ear antigen. Most of the evidence linking the immune system to cochleovestibular dysfunction is indirect; therefore, immune-mediated inner ear disease may be a preferred term. AIED is a clinical diagnosis based on its distinct clinical course, immune test results, and treatment response. The most important diagnostic finding is improvement in hearing observed with a trial of immunosuppressants.

Specific criteria for idiopathic progressive bilateral sensorineural hearing loss (IPBSNHL) include bilateral SNHL of at least 30 dB at any frequency with progression in at least one ear, defined as a threshold shift that is greater than 15 dB at any frequency or 10 dB at 2 or more consecutive frequencies or a significant change in discrimination score. This definition excludes patients with sudden SNHL occurring in less than 24 hours, which more likely is due to a microvascular or viral etiology.

A certain subset of patients with presumed Ménière disease (idiopathic endolymphatic hydrops) actually may have Ménière syndrome, in which the underlying pathophysiology is immune mediated. Typically, Ménière disease is initially diagnosed in these patients; however, fluctuating hearing loss in the contralateral ear develops later. This change may prompt a workup for AIED. Hughes et al found that approximately one half of their patients with AIED have manifestations of autoimmune Ménière syndrome.¹

Frequency

United States

Because the existence of autoimmune inner ear disease (AIED) has been recognized only since 1979, incidence is difficult to determine. Recent studies in the literature from large referral centers are based on relatively small sample sizes of patients who fit the criteria for diagnosis of AIED. As diagnostic tests for the condition become more specific and more is known about AIED, more patients will be identified who have an autoimmune basis for inner ear symptoms.

Sex

The condition has been suggested to be more common in female patients who may or may not have concomitant systemic autoimmune disease than in male patients.

Age

In most patients, initial onset of symptoms occurs at age 20-50 years. Cases in pediatric patients are uncommon.

Clinical

History

• Hearing loss: The hallmark of immune-mediated inner ear disease is sensorineural hearing loss (SNHL), which usually is bilateral and occurs rapidly over weeks to months.
• Fluctuation: Sensorineural loss can fluctuate and stabilize at a certain level, or it can progress without fluctuation.
• Laterality: Bilateral hearing loss occurs in most patients (79%). Occasionally, only one ear is involved initially, with the contralateral ear developing hearing loss later. In bilateral cases, audiometric thresholds can be symmetric or asymmetric.
• Speech discrimination scores: Discrimination scores often are poor in immune-mediated inner ear disease. Therefore, in cases of unilateral or bilateral-asymmetric disease, include diagnostic imaging and serologic studies in the workup to exclude retrocochlear disease and syphilitic inner ear disease.
• Vestibular symptoms: Approximately 50% of patients complain of vestibular symptoms typical of Ménière disease. Vestibular symptoms can include disequilibrium, ataxia, motion intolerance, positional vertigo, and episodic vertigo.
• Tinnitus and aural fullness: As many as 25-50% of patients also have symptoms of tinnitus and aural fullness, which can fluctuate in severity.
• Systemic autoimmune disease: Coexisting systemic autoimmune disease occurs in 15-30% of patients. Diagnoses include rheumatoid arthritis, ulcerative colitis, systemic lupus erythematosus, and polyarteritis nodosa.

Physical

Findings from physical examination of the ear usually are normal in patients with immune-mediated inner ear disease. Occasionally, associated systemic autoimmune diseases can affect the external ear skin or middle ear mucosa.

Causes

• Association with type I immune reaction involving immunoglobulin E (IgE)–mediated response
  • Solimon postulated that histamine-induced vasodilation of endolymphatic sac vasculature may result in endolymphatic hydrops because of impaired fluid transport.
  • A large percentage of patients treated with immunotherapy for inhalant allergies demonstrated improvement in vertigo and other symptoms of Ménière disease, which suggests an association between IgE-mediated disease and inner ear dysfunction.
• Production of autoantibodies to inner ear antigen
  • Yoo et al reported that rodents injected with type II collagen developed new-onset SNHL and pathologic cochlear changes that appear to be immune mediated.²
  • Harris and Sharp used Western-blot analysis to identify a 68-kd antibody present in the serum of 35% of their patients with idiopathic progressive SNHL. This antibody targeted a bovine inner ear antigen, suggesting an autoimmune basis for hearing loss.³
• Production of immune complexes
  • In a series of 30 patients with Ménière disease, 96% had elevated levels of circulating immune complexes compared with 20% of control subjects.
  • Patients with systemic lupus erythematosus have evidence of circulating immune complexes and multiple autoantibodies. Reports exist of SNHL associated with systemic lupus erythematosus. Likewise, reports of patients with Wegener granulomatosis cite SNHL in association with vasculitis of the cochlear and endolymphatic sac arteries.

Differential Diagnoses

Inner Ear, Meniere Disease, Medical Treatment
Inner Ear, Perilymphatic Fistula
Inner Ear, Sudden Hearing Loss

Other Problems to Be Considered

Ménière disease
Syphilis
Sudden sensorineural hearing loss
Acoustic neuroma
Other neoplasms

Systemic immunologic disorders with otologic symptoms
Cogan syndrome
Polyarteritis nodosa
Rheumatoid arthritis
Systemic lupus erythematosus
Wegener granulomatosis
Sarcoidosis

Workup

Laboratory Studies

• Antigen-nonspecific tests are useful in routine screening for evidence of systemic immunologic dysfunction, yet specifically are not known to correlate with a diagnosis of immune-mediated inner ear disease. Antigen-nonspecific tests are as follows:
• Levels of circulating immune complexes
• Complement levels (C3, C4)
• Antinuclear antibody levels
• Rheumatoid factor
• Acute phase reactants - Erythrocyte sedimentation rate, C-reactive protein

A study by Dayal et al (2008) discovered that patients with autoimmune ear disease having no systemic autoimmune illness often show high levels of antinuclear antibodies (with a speckled pattern) and also sometimes have high levels of rheumatoid factor. The positive yield of other detailed tests was low.⁴

• Antigen specific tests are as follows:
• Migration inhibition assay: The patient's lymphocytes are placed in a capillary tube with serum containing inner ear antigens present on one end. If the patient's lymphocytes previously have been sensitized to the inner ear antigen, migration inhibition factor is released and impedes dispersion of lymphocytes from the tube. This assay is a gross test of immune reactivity.
• Lymphocyte transformation test (LTT): The LTT measures the response of the patient's sensitized lymphocytes to known inner ear antigens. The patient's lymphocytes are exposed to serum containing inner ear antigens. A proliferative response occurs and is compared to that of known negative control lymphocytes. Measurement is made by recording the incorporation of tritiated thymidine into new DNA as cell synthesis occurs. Sensitivity of the LTT is reported to be 50-80% when symptoms are active in an immunocompetent patient.
• Western blot analysis for antibodies to inner ear antigen
• Harris and Sharp used bovine inner ear extract as antigen in Western blot assays and detected antibody to a 68-kd inner ear antigen in 19 of 54 patients (35%) with progressive SNHL. Recent update includes a cohort of 279 patients with rapidly progressive SNHL, of whom 90 (32%) had positive results of Western blot analysis for the 68-kd antibody.
• Animals with experimentally induced SNHL possessed autoantibodies to the identical component of the inner ear antigenic isotope to which patients' sera reacted.
• Moscicki et al confirmed the finding of circulating antibodies against a 68-kd protein, which was found in 42 of 72 patients (58%) with IPBSNHL.⁵ Patients with positive test results for the antibody were more likely than those with negative results to have hearing loss that responded to steroid treatment (75% vs 18%). This study is the first to show a correlation between Western blot 68-kd positivity and steroid responsiveness.
• Rauch subsequently identified the 68-kd protein as heat shock protein 70 (HSP 70).⁶ Heat shock proteins are constitutively produced by host and pathogens and usually are up-regulated in response to infection or other stresses.
• Antibodies to HSP 70 were detected in 47% of 30 patients with Ménière disease, thus identifying a subset of patients with Ménière disease with an immune basis for their symptoms.
• The LTT and Western blot immunoassay must be performed in specialized immunology laboratories, often on a send-out basis.
• Control populations vary from persons with normal hearing to those with systemic autoimmune diseases. The 68-kd positivity in these control populations averages 5%. This specificity of approximately 95% appears fairly high but is rather insensitive when used in the general population.
• Gong et al found that 2 subcomponents of crude inner ear antigen (the 31 kD protein and the 60 kD protein) may induce autoimmune inner ear disease independently in the guinea pig cochlea.⁷ The 31 kD protein may correspond to the 30 kD protein identified by Cao et al as myelin protein zero (P0), which is derived from the acoustic nerve and spiral ganglion.⁸ The 31 kD protein may be of use in the future for early diagnosis of autoimmune inner ear disease (AIED).

Histologic Findings

Histopathologic human temporal bone studies of patients with immune-mediated inner ear disease rarely are reported in the literature. Further studies may help elucidate the pathophysiology involved in this condition.

Treatment

Medical Care

The natural history of untreated immune-mediated inner ear disease is unknown; much of the current therapy is based on empiric clinical data gathered during the past 20 years. A key feature of immune-mediated inner ear disease is a positive response to immunosuppressive therapy (ie, corticosteroids) in the form of improved hearing.

• Consider aggressive treatment for every patient, assuming no contraindications to steroid therapy are present, including peptic ulcer disease, diabetes mellitus, glaucoma, hypertension, and history of tuberculosis. Short-term bursts of steroids usually are insufficient (except as an aid in diagnosis) and may result in relapse.
• No standardized regimens for corticosteroid therapy exist, yet many recommend a trial of high-dose prednisone (1 mg/kg/d) for 1 month, followed by a slow taper over several weeks to a maintenance dose of 10-20 mg/d or every other day. Occasionally, higher doses are needed to maintain hearing as disease activity waxes and wanes. Patients often learn what maintenance dose is sufficient, below which their hearing deteriorates.
• Not all patients respond to corticosteroid therapy in the same manner. Some show improvement in threshold, discrimination scores, or both. Others with fluctuation and progression before therapy stabilize without actually improving. Still others actually lose hearing despite immunosuppressive therapy.
• In some patients, hearing loss becomes refractory to steroids, or patients develop adverse effects of chronic steroid administration. These patients may be candidates for cytotoxic therapy.
• Overall steroid response rates are approximately 60%, defined as an improvement in threshold of 15 dB at 1 frequency, 10 dB at 2 consecutive frequencies, or a significant improvement in discrimination score.
• Cytotoxic drugs generally are used for steroid-intolerant patients or those who fail to demonstrate a continued response to steroid therapy. However, McCabe recommends cyclophosphamide in addition to steroids as a first-line treatment.⁹
• Cyclophosphamide is a cytotoxic drug with adverse effects, including myelosuppression, hemorrhagic cystitis, infertility, and increased risk of malignancy.
• Other cytotoxic agents are used to treat immune-mediated inner ear disease, including methotrexate and azathioprine (Imuran). Sismanis et al used low-dose methotrexate to treat a small group of patients with autoimmune SNHL.¹⁰ Significant improvement in speech discrimination, but not pure-tone averages, was observed.
• Harris et al performed, from 1998-2001 and across 10 tertiary care centers, a randomized, double-blind, placebo-controlled study of 67 patients with rapidly progressive, bilateral sensorineural hearing loss (SNHL).¹¹ Patients who had a response to a one-month prednisone challenge were randomized to receive either placebo or methotrexate (15-20 mg/wk). The authors found that methotrexate was not able to maintain the hearing improvements obtained by high-dose prednisone over time better than placebo. The authors mention, however, that patients may have benefitted from fewer hearing fluctuations over time, but this was not specifically measured by the study.
• Several recent studies studied etanercept (Enbrel) in the treatment of AIED. Etanercept is a potent tumor necrosis factor (TNF) antagonist often used in the treatment of rheumatoid arthritis. Cohen et al enrolled 20 patients in a 12-week blinded placebo-controlled randomized trial of etanercept (25 mg SC twice weekly) versus placebo.¹² They found that etanercept was no better than placebo for the treatment of AIED. Similarly, Harris et al found no benefit of methotrexate over placebo in a 12-month placebo-controlled randomized trial. Finally, Matteson et al studied 23 steroid-responsive patients who received etanercept, 25 mg twice weekly for 24 weeks in an open-label pilot study.¹³ Although a significant improvement of hearing loss in these patients was not evident, the previously progressive hearing loss in 87% of these patients appeared to stabilize or improve. Of the patients with symptoms of vertigo, 50% noted improvement.
• In 1989, Luetje studied the use of plasmapheresis in patients with autoimmune inner ear disease.¹⁴ Improvement in auditory function occurred in 6 of 8 patients, 3 of whom were able to discontinue immunosuppressive medication.
• Plasmapheresis involves filtering a patient's whole blood, which removes antibody, antigen, and immune complexes and other immune mediators. Albumin and normal saline are used as replacement fluids. The procedure is expensive and is considered an adjunctive therapy until further controlled studies determine its role in the treatment of immune-mediated inner ear disease.

Surgical Care

Immune-mediated inner ear disease usually is bilateral and often responds to medical management. Surgery generally is not appropriate. However, intratympanic therapy performed under local anesthesia recently has been found beneficial for some patients with immune-mediated inner ear disease.

• Improvements in treatment may be facilitated by local delivery for both SNHL and autoimmune ear disease. Intratympanic administration of corticosteroids results in higher inner ear levels compared with systemic steroid administration. Intratympanic administration avoids the blood-labyrinthine barrier and systemic adverse effects observed with oral or intravenous steroids.
• Parnes et al used intratympanic steroids to treat 37 patients with a variety of inner ear disorders causing SNHL.¹⁵ Patients with immune-mediated hearing loss showed promising results, as did several patients who presented with sudden SNHL.
• Steroids initially are administered through a myringotomy placed over the round window region. A tympanostomy tube is left in place for continued treatments.
• Otoendoscopy of the middle ear may be performed to confirm the location of the round window and identify any mucosal adhesions that may impede drug penetration.
• Silverstein developed a drug delivery system that involves placing a small wick through a tympanostomy tube directly into the round window niche.¹⁶ This allows a patient to self-administer the medication into the ear canal, where the drug is absorbed by the wick and directly transported to the round window membrane.
• The different inner ear drug delivery methods can be summarized as follows:
  • Intratympanic drug delivery
    • Passive intratympanic delivery
    • Biodegradable polymer intratympanic delivery
    • Hydrogel-based intratympanic delivery
    • Nanoparticle delivery
    • Active intratympanic drug delivery
    • Round window microcatheter
    • Silverstein MicroWick
    • Preclinical Alzet osmotic pump
    • Other systems
  • Intracochlear drug delivery
    • Syringe delivery
    • Direct injection
    • Syringe pump delivery
    • Osmotic pump delivery
    • Cochlear prosthesis- based delivery
    • Other delivery devices

As treatment options improve for many inner ear diseases and injuries, methods for delivering precise and controlled doses become vital. Researchers in the field of inner ear drug delivery are constantly in the process of advancing new and existing techniques that support the arrival of better and better therapeutic compounds. Those suffering from hearing related disorders can look forward to improved quality of life as the field progresses.²⁷

However, physicians must realize that a potential impact of glucocorticoids on ion homeostasis functions exists in addition to immune suppression. These functions are quite interlinked with regard to maintenance of the endolymphatic potential in fluids around auditory and vestibular hair cells. Therefore, assuming that all steroid-responsive hearing loss is due to immune processes simply cannot be justified in light of our current understanding of other cellular and molecular processes under the control of glucocorticoids.¹⁷

In a retrospective study of intratympanic dexamethasone for sudden sensorineural hearing loss after failure of systemic therapy, 39% of patients were found to recover 20 dB or 20% SDS (if treated within 6 weeks). This was higher than the figure of 9.1% in their controls.¹⁸

Consultations

Consultation with a rheumatologist or hematologist often is necessary if steroid therapy fails to help the patient and he or she requires treatment with cytotoxic drugs, which requires close hematologic monitoring. Occasionally, patients may require treatment with plasmapheresis (see Medical Care).

Diet

Patients with immune-mediated endolymphatic hydrops usually are placed on a low-sodium diet, similar to the diet recommended for patients with Ménière disease.

Medication

The goals of pharmacotherapy are to prevent complications and reduce morbidity.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Sterapred)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Dosing

Adult

1 mg/kg/d PO for 30 d, then taper as indicated

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Cytotoxic agents

These agents inhibit cell growth and proliferation and are useful in the treatment of autoimmune diseases.

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. An alkylating agent; mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Dosing

Adult

1-2 mg/kg/d PO for 4-6 wk; treat those whose symptoms respond for 6-12 mo

Pediatric

Not established

Interactions

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effects of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leucopenia and neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Can cause myelosuppression; requires weekly hematologic monitoring; hemorrhagic cystitis; infertility

Methotrexate (Folex PFS, Rheumatrex)

Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).
Adjust dose gradually to attain satisfactory response.

Dosing

Adult

7.5-15 mg PO qwk

Pediatric

Not established

Interactions

Oral aminoglycosides may decrease absorption and blood levels; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response to MTX
Coadministration with NSAIDs may be fatal; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels
Probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines

Contraindications

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor CBCs monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or in presence of risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems
Discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly with MTX (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)

Follow-up

Prognosis

• Fifty percent of patients with Autoimmune ear disease have an excellent response to steroids. Those with vestibular symptoms only are in particular responsive to steroids. Those with systemic disease have a lower response rate.⁴
• Patients who demonstrate improvement in hearing in response to immunosuppressive therapy have a better prognosis than those who do not improve. The natural history of untreated immune-mediated inner ear disease is unknown at this time.

Patient Education

• Inform patients with immune-mediated inner ear disease that regular follow-up care with their otolaryngologist is necessary to correlate subjective hearing fluctuations with objective audiometric data. This information helps guide immunosuppressive therapy, which needs to be monitored closely by a rheumatologist or immunologist.
• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Ménière Disease.

Miscellaneous

Medicolegal Pitfalls

• Informed consent about the possible risks of immunosuppressive therapy in the management of immune-mediated inner ear disease is necessary before treatment.
• Perform workup on patients with a history consistent with bilateral Ménière disease to evaluate for an autoimmune etiology before considering surgery for vestibular symptoms. A workup with results that are positive for an autoimmune etiology may lead to a trial of immunosuppressive therapy and, thereby, avoid the potential morbidity associated with surgery.
• Perform workup such as serologic or imaging studies to exclude conditions such as otosyphilis or acoustic neuroma before immunosuppressive therapy is instituted.
• Patient counseling may be helpful regarding the variable and often poor response to medical therapy for AIED. Patients need to know that immune-mediated inner ear disease is not a uniform disease with a simple diagnosis and treatment. The disease often results in long-term disability due to progressive and often permanent hearing loss. The response to aggressive immunosuppressive therapy can also be disappointing because of variable response rates and high risk of side effects.

Multimedia

Media file 1: Inner ear.

References

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2. Yoo TJ, Tomoda K, Stuart JM, Cremer MA, Townes AS, Kang AH. Type II collagen-induced autoimmune sensorineural hearing loss and vestibular dysfunction in rats. Ann Otol Rhinol Laryngol. May-Jun 1983;92(3 Pt 1):267-71. [Medline].

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Keywords

Ménière disease, inner ear, autoimmune disease, idiopathic endolymphatic hydrops, Ménière syndrome, bilateral sensorineural hearing loss, SNHL, autoimmune inner ear disease, AIED, immune-mediated inner ear disease

Contributor Information and Disclosures

Author

Neeraj N Mathur, MBBS, MS, Professor, Department of Ear, Nose and Throat, Lady Hardinge Medical College and Associated Smt SK and Kalawati, Saran Children's Hospital, University of Delhi, India; Professor and Head, Department of Ear, Nose and Throat, BP Koirala Institute of Health Sciences, Nepal
Neeraj N Mathur, MBBS, MS is a member of the following medical societies: Association of Otolaryngologists of India, Cochlear Implant Group of India, Indian Medical Association, National Academy of Medical Sciences, India, Neuro-Otologic and Equlibriometric Society of India, and Royal Society of Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robert A Battista, MD, FACS, Assistant Professor of Otolaryngology, Northwestern University Medical School; Physician, Ear Institute of Chicago, LLC
Robert A Battista, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Neurotology Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Peter S Roland, MD, Professor, Department of Neurological Surgery, Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, Director of Clinical Center for Auditory, Vestibular and Facial Nerve Disorders, Chief of Pediatric Otology, University of Texas Southwestern Medical Center; Adjunct Professor of Communicative Disorders, University of Texas School of Human Development
Peter S Roland, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American Auditory Society, American Laryngological Rhinological and Otological Society, American Neurotology Society, American Otological Society, North American Skull Base Society, and Society of University Otolaryngologists-Head and Neck Surgeons
Disclosure: Alcon labs Honoraria Speaking and teaching; GSK Honoraria Speaking and teaching; Advanced Bionics Honoraria Board membership; Cochlear corp Honoraria Board membership; Med El corp travel grants Consulting

CME Editor

Christopher L Slack, MD, Otolaryngology-Facial Plastic Surgery, Private Practice, Associated Coastal ENT; Medical Director, Treasure Coast Sleep Disorders
Christopher L Slack, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA, Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society
Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation unstricted gift unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Syndicom Ownership interest Consulting; Oxlo  Consulting; Medvoy Ownership interest Management position

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Shelley Jaquish, MD, and William L Meyerhoff, MD, PhD, to the development and writing of this article.

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