What is the treatment for autoimmune ear disease?

Treatment of Autoimmune Inner Ear Disease

Systemic corticosteroids are the only validated first-line treatment for autoimmune inner ear disease (AIED), with intratympanic steroids serving as an alternative for patients who cannot tolerate or become refractory to systemic therapy. 1, 2

Diagnosis and Initial Assessment

AIED is defined as rapidly progressive bilateral sensorineural hearing loss developing over weeks to months that responds to corticosteroid administration 1, 3. The diagnosis remains clinical, based on:

• Rapidly progressive bilateral hearing loss over weeks to months (not days or years) 1, 3
• Positive therapeutic response to corticosteroids within 2-4 weeks of treatment initiation 1, 3
• Exclusion of other causes through audiometry, imaging, and serologic testing 1

AIED can present as an isolated otologic disorder or as part of systemic autoimmune diseases including Wegener granulomatosis, systemic lupus erythematosus, polyarteritis nodosa, relapsing polychondritis, or Cogan's syndrome 1, 4. Importantly, 29% of AIED patients test positive for antiphospholipid antibodies, most commonly lupus anticoagulant, followed by anticardiolipin and anti-beta2 glycoprotein 4.

First-Line Treatment: Systemic Corticosteroids

Oral prednisone at 1 mg/kg/day (maximum 60 mg daily) as a single morning dose for 10-14 days, followed by a taper over 7-14 days, is the standard initial treatment. 5, 1, 2

• Treatment must begin immediately upon diagnosis, as the greatest benefit occurs within the first 2 weeks 5
• Hearing improvement can be dramatic, even after 2 months of profound deafness 3
• Approximately 58% of patients experience hearing improvement with prednisone treatment 6
• Monitor for hyperglycemia, especially in at-risk patients 5
• Obtain audiograms before treatment, at completion, and at delayed intervals 5

Alternative equivalent systemic corticosteroid dosing includes methylprednisolone 48 mg/day or dexamethasone 10 mg/day 5.

Second-Line Treatment: Intratympanic Steroids

For patients who cannot tolerate systemic steroids or become refractory to oral therapy, intratympanic dexamethasone (24 mg/mL, 16 mg/mL, or 10 mg/mL) or methylprednisolone (40 mg/mL or 30 mg/mL) serves as an alternative. 5, 2

• Intratympanic steroids are a potential adjuvant or alternative treatment for steroid-intolerant patients 2
• Higher concentrations of intratympanic dexamethasone show better outcomes 5

Treatment Failures and Long-Term Management

What NOT to Use

Methotrexate does not prevent progression of hearing loss in AIED and should not be used. 1, 6

• A randomized, double-blind, placebo-controlled trial of 67 patients demonstrated that methotrexate (15-20 mg/week) was no more effective than placebo in maintaining hearing improvement achieved with prednisone (hazard ratio 1.31,95% CI 0.79-2.17, P=0.30) 6
• 80% of methotrexate-treated patients experienced hearing loss versus 93.5% in the placebo group (P=0.15) 6

Refractory Cases

For patients who cannot be weaned off corticosteroids or whose disease becomes refractory to treatment:

• Cyclophosphamide is restricted to patients willing to endure significant toxicity risks 1
• Biologic therapies (infliximab, etanercept, adalimumab, golimumab, rituximab, anakinra) have been studied in small cohorts with varying results, but lack rigorous evidence 2
• Steroid nonresponders may benefit from biologic therapy, though prospective studies are needed 2
• Azathioprine has been used in selected cases but lacks strong evidence 2

Managing Flare-Ups

Increase steroid dosage or add cytotoxic medications when flare-ups occur. 3

• Some patients will develop progressive hearing loss despite vigorous treatment 3
• Only 25% of AIED patients with antiphospholipid antibodies experience audiometric improvement during disease course 4

Special Considerations

Antiphospholipid Antibody-Positive Patients

Screen for antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta2 glycoprotein) in all AIED patients to enable appropriate therapeutic management. 4

• 29% prevalence of antiphospholipid antibody positivity in AIED 4
• 25% of positive patients have double positivity 4
• Main clinical manifestations include bilateral hearing loss, vestibular symptoms, and tinnitus 4

Systemic Autoimmune Disease

Evaluate for underlying systemic autoimmune diseases including granulomatosis with polyangiitis, Cogan's syndrome, systemic lupus erythematosus, polyarteritis nodosa, and relapsing polychondritis 1, 4.

Common Pitfalls to Avoid

• Delayed treatment initiation—begin corticosteroids immediately upon diagnosis, as efficacy diminishes significantly after 2 weeks 5
• Underdosing corticosteroids—ensure full 1 mg/kg/day dosing is achieved 5
• Using methotrexate as steroid-sparing agent—it has been proven ineffective in randomized controlled trials 6
• Missing antiphospholipid antibody positivity—screen all AIED patients to guide specific management 4
• Divided corticosteroid dosing—give prednisone as single morning dose to minimize HPA axis suppression 5
• Administering toxic medications to preserve hearing at all costs—with cochlear implants available, this is a less desirable option 1

Monitoring and Follow-Up

• Perform audiometric evaluation at 4,8,12,24,36,48, and 52 weeks, or until hearing loss is documented 6
• Laboratory test sensitivity and specificity vary greatly and may be falsely normal when symptoms are not acute or when patients are taking immunosuppressant medication 3
• The diagnosis of AIED remains predicated on positive therapeutic response to corticosteroid administration, not laboratory testing 1