Autoimmune Inner Ear Disease


Indications for Testing

  • Appropriate clinical presentation and exclusion of other causes of hearing loss, including Ménière disease, other autoimmune diseases (with associated hearing loss), otosclerosis, retrocochlear disorders and infectious diseases such as syphilis and Lyme disease

Criteria for Diagnosis

  • Autoimmune inner ear disease (AIED) considered if 3 major or 2 major plus >2 minor criteria fulfilled (Berrocal, 2002)
    • Berrocal criteria for AIED

      Berrocal criteria for AIED

      Major criteria

      • Bilateral
      • Autoimmune systemic disease
      • ANA positive
      • Low number of T cells
      • Recovery of 80% of hearing

      Minor criteria

      • Unilateral
      • Pediatric age
      • Female
      • Anti-68 kDa antibodies
      • Good response to steroid therapy (hearing recovery rate <80%)

Initial Testing

  • Audiology – initial testing for pure tones, speech discrimination, tympanometry, acoustic reflex testing
  • If vestibular symptoms present
    • Vestibular function testing for pursuit, saccade optokinetic nystagmus, positional and spontaneous nystagmus, caloric stimulation and rotation chair stimulation

Laboratory Testing

  • No single laboratory test recommended for evaluation of disorder; consider non-specific antibody screening to rule out autoimmune or infectious disease associated with hearing loss
  • Specific hearing loss autoimmune testing
    • HSP70 testing helpful if positive; however, negative result does not rule out autoimmune hearing loss
      • HSP70 positivity is an indicator of steroid responsiveness of the disease; however, a subset of AIED patients who are HSP70 antibody negative may respond to steroid treatment
    • Cochlin antibody testing helpful if HSP70 is negative

Differential Diagnosis

Clinical Background

Autoimmune inner ear disease (AIED), also called autoimmune sensorineural hearing loss (ASNHL), is characterized by bilateral, rapidly progressive sensorineural hearing loss over a period of weeks to months. Ménière disease (MD), which is a recurrent and spontaneous episodic vertigo associated with hearing loss, fullness in the ear, and tinnitus, may sometimes be confused with AIED. Individuals with MD or variants of MD may have symptoms due to immune dysfunction.


  • Prevalence – rare disease, accounting for <1% of all cases of hearing impairment; true prevalence unknown
  • Age – peak onset in 20s-40s, rare in pediatric ages
  • Sex – M:F ratio unknown due to low prevalence of disease


  • Inner ear cells are delicate and have limited ability for regeneration and repair
  • Disruption of regulating mechanisms may cause substantial damage to inner ear structures, resulting in loss of hearing function
  • Both cell-mediated and antibody responses have been associated with AIED; immune response may cause substantial damage to inner ear structures
  • Possible antibodies involved in AIED
    • Heat shock protein 70 (HSP70) – also known as anti-68kDa antigen
    • Cochlin protein
    • Choline transporter-like protein 2
    • Myelin protein P0
    • Beta-tectorin

Clinical Presentation


  • Corticosteroid therapy – does not reverse hearing loss in all patients
  • If not steroid responsive, cytotoxic drugs may be considered

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
C-Reactive Protein 0050180
Method: Quantitative Immunoturbidimetry

Preferred test for evaluation of inflammation (eg, autoimmune disease)

Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer and MPO/PR-3 Antibodies 2002068
Method: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Rule out systemic vasculitis as etiology of hearing loss

Panel contains ANCA IgG; myeloperoxidase antibody and serine protease 3 antibody

If screen is positive, titer and MPO/PR-3 antibodies testing will be added to aid in antibody determination

Anti-Nuclear Antibodies (ANA), IgG by ELISA with Reflexes to ANA, IgG by IFA and to dsDNA, RNP, Smith, SSA, and SSB Antibodies, IgG 0050317
Method: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multiplex Bead Assay

Rule out autoimmune connective tissue disease as etiology of hearing loss

If ELISA screen is positive, then IFA using HEp-2 substrate will be added; if confirmed by IFA, titer and pattern will be reported and testing for dsDNA antibody and ENA antibodies will be added

Rheumatoid Factors, IgA, IgG, and IgM by ELISA 0051298
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Enzyme-Linked Immunosorbent Assay.

Rule out rheumatoid arthritis as etiology of hearing loss

Heat Shock Protein 70 (68 kDa), IgG by Western Blot  0097338
Method: Qualitative Western Blot

Predict corticosteroid responsiveness in patients with idiopathic, rapidly progressive sensorineural hearing loss

False positives from other systemic autoimmune diseases

Treponema pallidum Antibody, IgG by IFA (FTA-ABS), Serum 0050477
Method: Semi-Quantitative Indirect Fluorescent Antibody

Rule out syphilis as etiology of hearing loss

Confirm reactive screening nontreponemal test in suspected syphilis

FTA tests for syphilis may be false positive in autoimmune disease, leprosy, febrile illnesses, advanced age, Lyme disease and endemic treponematoses

Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG and IgM by Western Blot (Early Disease) 0050267
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Rule out Lyme disease <8 weeks after onset of disease as etiology of hearing loss

No objective tests for Lyme borreliosis are 100% sensitive and 100% specific

Diagnosis depends on clinical features combined with available laboratory tests

Borrelia burgdorferi Total Antibodies, IgG and/or IgM by ELISA with Reflex to IgG by Western Blot (Late Disease) 0050268
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Rule out Lyme disease >4 weeks after onset of disease symptoms as etiology of hearing loss

Hemoglobin A1c 0070426
Method: Quantitative High Performance Liquid Chromatography/Boronate Affinity

Rule out diabetes mellitus as etiology of hearing loss

Unstable hemoglobins or hemolytic anemia may yield falsely low results

Iron deficiency anemia may yield falsely high results

Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies by CIA with Reflex to HIV-1 Antibody Confirmation by Western Blot 2005377
Method: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Screen for presence of HIV infection

Screen for antibodies against HIV-1 and HIV-2

Additional Tests Available
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Sedimentation Rate, Westergren (ESR) 0040325
Method: Visual Identification

Marker of inflammation in autoimmune disease

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Rule out thyroid dysfunction as etiology of hearing loss

Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay

Rule out thyroid dysfunction as etiology of hearing loss