Autoimmune Inner Ear Disease

Autoimmune inner ear disease (AIED) is a rare disorder in which immune mediated attack on the cochlea and vestibular apparatus causes rapidly progressive, bilateral, asymmetric sensorineural hearing loss. Loss develops over weeks to months (less than 3 months), sometimes with vestibular dysfunction.

It accounts for under 1 percent of cases of sensorineural hearing loss. The peak age is 20 to 50 years, with a female predominance (about 2:1). About 15 to 30 percent of cases have a systemic autoimmune disease.

It can be primary (organ specific) or secondary to a systemic autoimmune disease:

• Cogan syndrome (interstitial keratitis with vestibulo auditory symptoms).
• Granulomatosis with polyangiitis, polyarteritis nodosa, giant cell arteritis.
• Systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, antiphospholipid syndrome.
• Relapsing polychondritis, Behçet disease, ulcerative colitis, sarcoidosis, ankylosing spondylitis.

Pathogenesis includes antibodies against inner ear antigens (heat shock protein 70, cochlin, beta tectorin, and others), T-cell mediated inflammation, and immune complex vasculitis of the labyrinthine artery. Response to corticosteroids is a characteristic feature.

• Rapidly progressive (over weeks to a few months) sensorineural hearing loss, initially unilateral, becoming bilateral in most (asymmetrical), with fluctuation of hearing, tinnitus and aural fullness.
• Vestibular symptoms in about 50 percent: episodic vertigo, imbalance, oscillopsia, ataxia, and positional symptoms (Dandy syndrome with bilateral vestibular loss).
• Systemic features of an underlying disease: fever, arthralgia, rash, red eye or eye pain (scleritis, interstitial keratitis in Cogan syndrome), oral ulcers, nasal crusting, sinusitis, cough, haematuria, or neuropathy.
• Otoscopy normal.
• Hearing loss fluctuates and may recover with steroids, but progression and relapse on steroid withdrawal occur.

• Clinical diagnosis based on the pattern of progressive bilateral sensorineural loss and response to steroids; there is no definitive test.
• Audiometry: bilateral asymmetric sensorineural loss (a drop of at least 15 to 30 decibels at one frequency or 10 dB at two or more adjacent frequencies, over 3 months), with decreasing speech discrimination; monitor serially, every 2 to 4 weeks.
• Vestibular tests: caloric, video head impulse test, and rotary chair.
• Blood tests: erythrocyte sedimentation rate, C-reactive protein, full blood count, antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibodies (anti-proteinase 3, anti-myeloperoxidase), anti-double-stranded DNA, complement, antiphospholipid antibodies, anti-Ro/La, syphilis serology, Lyme serology, angiotensin converting enzyme, and thyroid function. The anti-HSP70 (anti-68 kDa) western blot has been used, but with limited sensitivity and specificity.
• MRI of the internal auditory canals and brain with gadolinium to exclude retrocochlear lesions and show labyrinthine enhancement, with CT temporal bone if needed.
• Urinalysis for glomerulonephritis; chest imaging if sarcoidosis or granulomatosis with polyangiitis are suspected; eye examination (slit lamp) for keratitis.
• Exclude infection, Ménière disease, ototoxicity, genetic causes, and neoplasm.

• First line: start high dose oral corticosteroid promptly. Give prednisolone 1 mg/kg daily (typically 60 mg daily, maximum 80 mg) for 4 weeks. Assess response by audiometry at 4 weeks.
• Responders show improvement of at least 10 decibels in the pure tone average or 12 percent in word recognition, found in about 60 percent. Taper the dose slowly over 6 to 12 weeks (for example 5 to 10 mg reduction every 1 to 2 weeks) to the lowest effective dose.
• Those who relapse on tapering need maintenance or a steroid sparing agent. Taper non-responders off quickly.
• Prophylaxis with high dose steroids: calcium 1,000 to 1,200 mg and vitamin D 800 units daily, proton pump inhibitor, monitoring of glucose and blood pressure, and bone density testing. Consider Pneumocystis prophylaxis (trimethoprim-sulfamethoxazole 480 mg daily) with prolonged immunosuppression.
• Steroid sparing and second line therapy applies to steroid responders who relapse or are dependent, and to those with systemic disease. Options:
  • Methotrexate 7.5 to 25 mg weekly (with folic acid 5 mg weekly).
  • Azathioprine 2 to 2.5 mg/kg daily.
  • Cyclophosphamide 1 to 2 mg/kg daily or intravenous pulse 500 to 750 mg/m2 monthly (for vasculitis and severe disease).
  • Mycophenolate mofetil 1 g twice daily.
  • Rituximab 1,000 mg on days 1 and 15 (or 375 mg/m2 weekly for 4 weeks).
  • Tumour necrosis factor inhibitors (etanercept and adalimumab), with variable and mixed results.
  • Anakinra 100 mg daily (interleukin-1 blocker).
• Methotrexate in trials has not shown benefit as a maintenance after steroids, but is used.
• Intratympanic steroids (dexamethasone 10 mg/mL or methylprednisolone 40 mg/mL) are a rescue or adjunct for local therapy (3 to 4 injections over 2 weeks) to limit systemic steroid dose.
• Treat secondary causes: Cogan syndrome (high dose steroids with immunosuppression for systemic vasculitis), granulomatosis with polyangiitis (rituximab, cyclophosphamide), and others per the underlying disease.
• Rehabilitation: hearing aids early, with the aim of preserving audibility. Cochlear implantation for profound bilateral hearing loss, with good outcomes, ideally early before ossification. Vestibular rehabilitation, assistive listening devices and speech therapy.
• Monitoring: audiometry every 1 to 3 months, then every 6 months. Monitor for relapse, drug toxicity (blood counts and liver tests with methotrexate and azathioprine), and development of systemic disease (follow for years).
• Prognosis: heterogeneous. About 60 percent of patients respond to steroids initially, and relapse is common with dose reduction. Progression to bilateral profound deafness occurs in some.