Autoimmune Inner Ear Disease (AIED)

Definition and epidemiology

Autoimmune inner ear disease (AIED) is a condition attributed to an immune response directed at the inner ear, causing bilateral sensorineural hearing loss that progresses over weeks to months. McCabe introduced the concept in 1979, describing a group of patients with progressive bilateral sensorineural loss that responded to corticosteroids and cyclophosphamide (McCabe, 1979). The term “immune-mediated inner ear disease” is also used.

Two forms are recognised. In primary AIED the immune response affects the inner ear alone. Secondary AIED is part of a systemic autoimmune disease; in 15-30% of cases a condition such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome or granulomatosis with polyangiitis (formerly Wegener’s granulomatosis) is present (Ciorba et al., 2018). Cogan syndrome, which combines interstitial keratitis with audiovestibular symptoms, is the classic example of this group (D’Aguanno et al., 2018). The reported frequency of hearing loss across systemic autoimmune diseases varies widely from one disease to another (Mancini et al., 2018).

AIED is rare. Its annual incidence is reported as fewer than 5 per 100,000 and its prevalence as about 15 per 100,000, and it accounts for less than 1% of all sensorineural hearing loss. It is more common in women and usually begins between the third and sixth decades of life (Ciorba et al., 2018). Because there are no established diagnostic criteria, some cases are probably never diagnosed.

Symptoms and signs

The main complaint is hearing loss that becomes obvious over a few weeks or months. It is usually bilateral but need not be symmetrical: early on it often starts in one ear, the other ear follows, and thresholds may fluctuate. Progression is reported to occur mostly over 3-90 days (Ciorba et al., 2018). This is slower than sudden sensorineural hearing loss, which develops within three days, but far faster than losses such as presbycusis that evolve over years.

About half of patients have vestibular symptoms such as imbalance, motion intolerance, ataxia, or positional or episodic vertigo, and 25-50% report tinnitus and aural fullness (Ciorba et al., 2018). When fluctuating hearing, tinnitus and vertigo occur together the picture can resemble Ménière’s disease; a rapid, bilateral course should raise the possibility of an autoimmune process.

In secondary AIED the features of the systemic disease point the way: joint pain, rash, dry mouth and eyes, nasal and sinus symptoms, renal involvement, or a red, light-sensitive eye. In typical Cogan syndrome the ocular and audiovestibular symptoms begin less than two years apart, and about half of patients progress to bilateral profound hearing loss during follow-up (D’Aguanno et al., 2018). In about a third of patients with granulomatosis with polyangiitis, Eustachian tube or middle ear involvement adds a conductive component to the sensorineural loss (Ciorba et al., 2018).

Causes and risk factors

The mechanism is not fully understood. The proposed model is an uncontrolled immune attack on inner ear antigens involving both T-cell responses and autoantibody production. Damage is thought to arise through immune complex deposition, cytotoxic antibodies, vasculitis and microthrombosis. Reported tissue findings include cochlear vasculitis, atrophy of the organ of Corti, endolymphatic hydrops and spiral ganglion degeneration (Ciorba et al., 2018).

The inner ear was long regarded as shielded from the immune system by the blood-labyrinth barrier. Current thinking places the endolymphatic sac at the centre of the immune response, with inflammatory cytokines such as interleukin-1β and TNF-α allowing leucocytes and immunoglobulins to reach the inner ear (Ciorba et al., 2018). Raised interleukin-1β in steroid-resistant patients has prompted research into treatments that block this pathway (Vambutas et al., 2014). Antibodies against inner ear proteins such as cochlin have also been studied, but their diagnostic value remains uncertain.

Risk factors include female sex and a history of systemic autoimmune disease. In the secondary form, inner ear involvement may wax and wane with the activity of the underlying disease, so rheumatological and audiological follow-up should run in parallel.

Audiological and clinical assessment

AIED is a diagnosis of exclusion: there is no pathognomonic test and no established set of diagnostic criteria (Ciorba et al., 2018). Audiological assessment aims to document the type of loss, its rate of progression and the difference between the ears, and to show change objectively over time. The expected findings are:

• Pure tone audiometry: bilateral, often asymmetric sensorineural loss with no air-bone gap. In about 80% of cases the loss is 30 dB or more. Repeated testing at short intervals shows progression and fluctuation; a 15 dB change at one frequency or a 10 dB change at two adjacent frequencies can be taken as significant (Ciorba et al., 2018).
• Speech audiometry: word recognition is as useful as the pure tone average for tracking treatment response; a score poorer than expected from the thresholds calls for investigation of retrocochlear causes.
• Tympanometry and acoustic reflexes: the tympanogram is usually normal; reflex thresholds rise with the degree of loss or reflexes are absent. In granulomatosis with polyangiitis, middle ear involvement can produce a flat tympanogram and an air-bone gap.
• OAE and ABR: otoacoustic emissions (OAE) are reduced or absent when the cochlea is involved. The auditory brainstem response (ABR) helps when a retrocochlear lesion is suspected in asymmetric loss, but exclusion relies on MRI.
• Vestibular tests: in patients with vestibular symptoms, caloric testing, the video head impulse test (vHIT) and vestibular evoked myogenic potentials (VEMP) show labyrinthine involvement and side differences. Bilateral involvement can progress to bilateral vestibulopathy.

Contrast-enhanced MRI of the internal auditory canals and cerebellopontine angles is recommended to exclude retrocochlear causes such as vestibular schwannoma (Ciorba et al., 2018). Laboratory work-up may include a full blood count, ESR, CRP, renal and thyroid function, autoimmune markers such as ANA, ANCA and rheumatoid factor, and serology for syphilis, Lyme disease and HIV. Without systemic features serological tests are of limited value, and the evidence on the diagnostic value of inner ear-specific antibodies such as anti-HSP70 and anti-cochlin is insufficient (Ciorba et al., 2018).

Response to steroids is used as supportive evidence. In a multicentre study, hearing improved in 57.8% of patients given a prednisone challenge (Harris et al., 2003). A commonly used definition of response is an improvement of more than 10 dB in pure tone average and more than 12% in word recognition (Ciorba et al., 2018). Lack of response does not rule out the diagnosis. The differential diagnosis includes Ménière’s disease, enlarged vestibular aqueduct, retrocochlear lesions, infections such as syphilis and Lyme disease, and ototoxicity.

Treatment and audiological rehabilitation

Treatment decisions rest with the ENT physician, together with a rheumatologist when systemic disease is present; medicines are mentioned here only as options, without doses. Systemic corticosteroids are first-line treatment. In responders treatment continues until hearing stabilises and is then tapered slowly, while the side effects of long-term steroid use limit what can be achieved (Brant et al., 2015; Ciorba et al., 2018).

For patients who do not respond to steroids, become steroid-dependent or cannot tolerate side effects, immunosuppressants such as methotrexate, cyclophosphamide and azathioprine, biological agents such as TNF-α inhibitors and rituximab, intratympanic steroids and plasmapheresis have been tried. The evidence for these options comes mostly from small series; a systematic review of 12 prospective studies with 272 patients concluded that clear evidence of an effective treatment from high-quality trials is still lacking (Brant et al., 2015). In a randomised controlled trial, methotrexate was no better than placebo at maintaining the hearing gained with prednisone (Harris et al., 2003). In a small open-label study of the interleukin-1 receptor antagonist anakinra, 7 of 10 evaluable patients responded; this finding needs confirmation in controlled trials (Vambutas et al., 2014).

Audiological rehabilitation is planned alongside medical treatment. When thresholds fluctuate, hearing aids with several programmes that can be reprogrammed easily are helpful; the fitting should be reviewed after every change in thresholds and verified with real ear measurement (REM). When hearing aids no longer give enough benefit in severe to profound loss, a cochlear implant (CI) is an effective option: a systematic review of implantation in primary and secondary AIED reported improved hearing in 114 of 115 patients and suggested that early implantation may be a valid choice (Lee et al., 2021). Because cochlear fibrosis or new bone formation can develop, preoperative MRI is advised (D’Aguanno et al., 2018).

During follow-up, monthly audiograms are suggested while thresholds fluctuate, then about every six months once hearing is stable (Ciorba et al., 2018). Vestibular rehabilitation is added for patients with vestibular involvement, and counselling helps patients cope with uncertainty and prepare for a decision about implantation.

Impact on quality of life and advice

For an adult losing hearing over weeks, one of the hardest parts is uncertainty: it is not possible to know in advance where the loss will stop, whether treatment will work or whether the other ear will be affected. This can lead to anxiety, depressive symptoms and withdrawal from work and social life. The side effects of long-term steroid and immunosuppressive treatment can also affect daily life.

If you notice a new drop in hearing, increasing tinnitus or fullness, tell your team rather than waiting for your next scheduled test. At home and at work, remote microphone systems, captions and speech-to-text apps make communication easier. It helps if people face you and speak clearly at a natural pace. If the loss is progressing, discussing cochlear implantation early reduces the risk of a long period with poor communication. If you are unsteady, using a light at night and clearing obstacles from the floor reduces the risk of falls.

Self-report questionnaires such as hearing handicap scales and the Tinnitus Handicap Inventory complement the audiogram in tracking how treatment affects daily life. It may also help to discuss adjustments with your employer for meetings, telephone calls and noisy environments.