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Autoimmune Disease of the Inner Ear Treatment & Management

  • Author: Neeraj N Mathur, MBBS, MS; Chief Editor: Arlen D Meyers, MD, MBA  more...
 
Updated: Mar 04, 2016
 

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.[14]

  • 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. [15]
  • 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. [16] 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). [17] 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. [18] 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. [19] 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.
  • A study by Pathak et al suggested that the antioxidant N-acetylcysteine (NAC) may be effective against AIED. The investigators found that peripheral blood mononuclear cells (PBMCs) in patients with AIED had higher baseline TNF-α and myeloperoxidase levels than did those of healthy controls. NAC, however, was found to discourage the lipopolysaccharide-mediated release of TNF- α from PBMCs while only minimally affecting the TNF-α pathway’s downstream targets. [20]
  • In 1989, Luetje studied the use of plasmapheresis in patients with autoimmune inner ear disease. [21] 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.
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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. [22] 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. [23] 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.[24]

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.[25]

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.[26]

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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).

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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.

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Contributor Information and Disclosures
Author

Neeraj N Mathur, MBBS, MS Director-Professor, Department of ENT and Head Neck Surgery, Vardhman Mahavir Medical College and Associated Safdarjang Hospital; Professor, Delhi University and Indraprastha University, India

Neeraj N Mathur, MBBS, MS is a member of the following medical societies: Royal Society of Medicine, Indian Medical Association, Association of Otolaryngologists of India, Cochlear Implant Group of India, National Academy of Medical Sciences (India), Neuro-Otological and Equilibriometric Society of India

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Peter S Roland, MD Professor, Department of Neurological Surgery, Professor and Chairman, Department of Otolaryngology-Head and Neck Surgery, Director, Clinical Center for Auditory, Vestibular, and Facial Nerve Disorders, Chief of Pediatric Otology, University of Texas Southwestern Medical Center; Chief of Pediatric Otology, Children’s Medical Center of Dallas; President of Medical Staff, Parkland Memorial Hospital; Adjunct Professor of Communicative Disorders, School of Behavioral and Brain Sciences, Chief of Medical Service, Callier Center for 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 Auditory Society, The Triological Society, North American Skull Base Society, Society of University Otolaryngologists-Head and Neck Surgeons, American Neurotology Society, American Academy of Otolaryngic Allergy, American Academy of Otolaryngology-Head and Neck Surgery, American Otological Society

Disclosure: Received honoraria from Alcon Labs for consulting; Received honoraria from Advanced Bionics for board membership; Received honoraria from Cochlear Corp for board membership; Received travel grants from Med El Corp for consulting.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, 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, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Additional Contributors

Robert A Battista, MD, FACS Assistant Professor of Otolaryngology, Northwestern University, The Feinberg School of Medicine; 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, Illinois State Medical Society, American Neurotology Society, American College of Surgeons

Disclosure: Nothing to disclose.

Acknowledgements

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

References
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