Autoimmune Inner Ear Disease

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.

Epidemiology

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

Pathophysiology

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

Autoimmune sensorineural hearing loss
- Rapidly progressive sensorineural hearing loss
  - Most often bilateral loss; usually asymmetrical
- Fluctuating hearing loss – disease severity usually unrelated to degree of hearing loss
- May be accompanied by ataxia, dizziness
Other autoimmune disorders present in 15-30% of cases
- Systemic lupus erythematosus (SLE)
- Antiphospholipid syndrome
- Behçet disease
- Rheumatoid arthritis
- Cogan syndrome
- Sjögren syndrome
- Wegener granulomatosis
- Hashimoto thyroiditis

Treatment

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

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
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
- Antinuclear antibodies (ANA), rheumatoid factor, antineutrophil cytoplasmic antibodies (ANCA)
- Thyroid – consider thyroid stimulating hormone (TSH)
- T. pallidum – fluorescent treponemal antibody (FTA)
- Borrelia burgdorferi – Lyme serology
- Diabetes mellitus – hemoglobin A1c
- HIV – Western blot
- Erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) – helpful if elevated; often normal
Specific hearing loss autoimmune testing
- HSP70 testing helpful if positive; however, negative result does not rule out hearing loss due to an autoimmune disease process
  - 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

Vasculitis
- Cochlear vasculitis
- Cogan syndrome
Infectious disease
- Lyme disease hearing loss
- Syphilitic hearing loss
- Viral – HIV
Ménière disease
Nonsyndromic hearing loss
Idiopathic sensorineural hearing loss
Systemic disease
- Diabetes mellitus
- SLE

Tests generally appear in the order most useful for common clinical situations

Test name: Sedimentation Rate, Westergren (ESR)

ARUP #: 0040325

Methodology: Westergren

Use:

Assess degree of inflammation

Test name: C-Reactive Protein

ARUP #: 0050180

Methodology: Quantitative Immunoturbidimetric

Use:

Assess degree of inflammation

Test name: Anti-Neutrophil Cytoplasmic Antibody with Reflex to Titer & MPO/PR-3 Antibodies

ARUP #: 2002068

Methodology: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multi-Analyte Fluorescent Detection

Use:

Rule out systemic vasculitis

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

Test name: Anti-Nuclear Antibody (ANA), IgG by ELISA with Reflexes to ANA by IFA and to dsDNA, RNP, Smith, SSA, and SSB Antibodies

ARUP #: 0050317

Methodology: Qualitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Multi-Analyte Fluorescent Detection

Use:

Rule out autoimmune connective tissue disease

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

Test name: Rheumatoid Factor, IgM, IgG, & IgA by EIA

ARUP #: 0051298

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Use:

Rule out rheumatoid arthritis

Test name: Heat Shock Protein 70 (68 kDa), IgG by Western blot

ARUP #: 0097338

Methodology: Qualitative Western Blot

Use:

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

Limitations:

False positives from other systemic autoimmune diseases

Test name: Treponema pallidum Antibody (FTA-ABS), Serum, IgG by IFA with Reflex to Treponema pallidum Antibody by TP-PA

ARUP #: 0050477

Methodology: Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Particle Agglutination

Use:

Confirm reactive screening nontreponemal test in suspected syphilis

Limitations:

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

Test name: Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot (Early Disease)

ARUP #: 0050267

Methodology: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Use:

Screen for Lyme disease <8 weeks after onset of disease

Limitations:

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

Diagnosis depends on clinical features combined with available laboratory tests

Test name: Hemoglobin A₁C

ARUP #: 0070426

Methodology: Quantitative High Performance Liquid Chromatography/Boronate Affinity

Use:

Monitor DM

Hemoglobin A1c values greater than or equal to 6.5% are diagnostic

Diagnosis should be confirmed with a repeated test

Limitations:

Unstable hemoglobins or hemolytic anemia may yield falsely low results

Iron deficiency anemia may yield falsely high results

Test name: Human Immunodeficiency Virus Types 1 and 2 (HIV-1, HIV-2) Antibodies with Reflex to Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Confirmation by Western Blot

ARUP #: 2005377

Methodology: Qualitative Chemiluminescent Immunoassay/Qualitative Western Blot

Use:

Screen for presence of HIV infection

Screen for antibodies against HIV-1 and HIV-2

Additional Tests Available

Test name: Thyroid Stimulating Hormone

ARUP #: 0070145

Methodology: Quantitative Electrochemiluminescent Immunoassay

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