By Marcello Cherchi, MD PhD
For patients
Autoimmune inner ear disease (AIED) refers to a condition in which the body’s immune system mistakenly attacks the inner ear. Sometimes this occurs in patients who have other autoimmune diseases, but often it appears to occur spontaneously. It manifests with bilateral hearing loss that progresses quite rapidly (over weeks to months), and can be accompanied by other ear symptoms (aural fullness, tinnitus) and sometimes vertigo.
One of the features of this disease is that the hearing loss often improves (though may not normalize) when a person is treated with steroids. This feature, sometimes called “steroid-responsive hearing loss,” is one of the cardinal features of the diagnosis.
If a patient’s hearing improves with steroids, then they may consider longer-term treatment (sometimes called “maintenance therapy”) with an immunomodulatory agent (such as adalimumab or etanercept), as such medications tend to be better tolerated than steroids.
For clinicians
Overview
Autoimmune inner ear disease (AIED) is an immune-mediated attack on the labyrinth, though the precise underlying autoimmune mechanism is unknown. AIED is rare, though appears more common in patients with other autoimmune diseases. It usually presents with bilateral sensorineural hearing loss that is rapidly progressive (typically over weeks or months); rare unilateral cases have been reported. Vestibular symptoms are inconsistently present. There is no proven biomarker of AIED; the diagnosis is based on a compatible clinical history, and on the finding of steroid-responsive hearing loss. Vestibular function testing may show bilateral vestibular weakness, and MRI may show enhancement of the labyrinth. If oral steroids are ineffective, some otolaryngologists may consider transtympanic steroid injections. If AIED is confirmed by steroid-responsive hearing loss, long-term management with an immunomodulatory agent (such as a TNF-alpha blocker) is considered.
Introduction
One of the earliest descriptions of AIED was in a case report by Dr. Brian F. McCabe (McCabe 1979). There was initial skepticism about AIED as a distinct clinical entity (Barna and Hughes 1997; Das, Bakshi, Seepana 2019).
Epidemiology
AIED is rare. Its incidence has been difficult to determine (Ruckenstein 2004), though estimates of 5 cases per 100,000 seems plausible (Das, Bakshi et al. 2019). AIED occurs mostly in adults, but has been reported in children (Oz, Gluth et al. 2019).
AIED seems to occur more commonly in patients with other autoimmune diseases (Ralli, D’Aguanno et al. 2018) such as Hashimoto’s thyroiditis (Fayyaz and Upreti 2018), diffuse systemic sclerosis (Feld, Shupak et al. 2015), ulcerative colitis (Kariya, Fukushima et al. 2008) and other inflammatory bowel disease (Fousekis, Saridi et al. 2018) and several vasculitides (Rahne, Plontke et al. 2020).
Clinical presentation
AIED usually presents with bilateral sensorineural hearing loss that is rapidly progressive (typically over weeks to months). It often causes other aural symptoms (such as fullness and tinnitus). Vestibular symptoms are sometimes also present (Bovo et al. 2010; Matsuoka and Harris 2013; Rahman et al. 2001; Russo et al. 2018), with studies estimating that anywhere from 22% (Dayal et al. 2008) to 50% of patients (Bovo et al. 2006) complain of oscillopsia, disequilibrium, etc.
When AIED occurs in the context of malignancy (Greene, Keefe et al. 2015, Zibelman, Pollak et al. 2016), it may be more correct to view the phenomenon as paraneoplastic rather than idiopathic. As with other paraneoplastic syndromes, the logical treatment is that of the underlying cancer.
Rare cases of unilateral AIED have been reported, though often these involve unusual circumstances such as concomitant malignancy (Rajapakse, O’Leary et al. 2020).
Mechanism of disease
Although the histopathological findings in AIED have been described (Schuknecht 1991), the exact immunological mechanism has remained elusive (Barna and Hughes 1988, Ruckenstein and Harrison 1991, Yoo, Du et al. 2002, Ianuale, Cadoni et al. 2013, Baruah 2014, Goodall and Siddiq 2015, Pathak, Stern et al. 2015, Eisner, Vambutas et al. 2017, Pathak and Vambutas 2020, Miwa and Okano 2022).
Diagnosis
The diagnosis can be suspected from the clinical history of rapidly progressive, bilateral (symmetrical or asymmetrical) hearing loss. Suspicion is bolstered if audiometry shows the hearing loss to be sensorineural. The diagnosis becomes much more likely if the hearing loss responds (improves) to a course of oral steroids, and if no more compelling alternative diagnosis is discovered.
There is not yet any widely accepted biomarker of AIED (Ciorba, Corazzi et al. 2018, Shamriz, Tal et al. 2018). There was some initial enthusiasm that HSP2 (heat shock protein 2) was a candidate biomarker, but this was subsequently shown to have poor sensitivity and specificity (Matsuoka and Harris 2013).
Vestibular function is often not assessed in AIED patients. However, in patients with vestibular symptoms, formal otovestibular testing may show bilateral vestibular weakness (Yukawa, Hagiwara et al. 2010).
In some cases of AIED, MRI may show contrast enhancement of the labyrinth (Lobo, Tunon et al. 2018).
Early diagnosis of AIED is desirable (Agrup and Luxon 2006). Although the disease tends to progress despite best efforts, early treatment may afford a patient more time with serviceable hearing.
Treatment
Systemic corticosteroids (usually orally administered) are generally regarded as first-line therapy (Breslin, Varadarajan et al. 2020). Patients should respond to this (otherwise the diagnosis becomes questionable), but if the response is suboptimal, then some practitioners may attempt transtympanic steroid injections (Hoffmann and Silverstein 2003, Light and Silverstein 2004, Swan, Mescher et al. 2008, Breslin, Varadarajan et al. 2020).
Steroids, whether systemic or transtympanic, are usually not a long-term solution due to the adverse effects of chronic use. Consequently, patients are often transitioned to immunomodulatory agents. Multiple such agents have been studied, including TNF-alpha blockers (etanercept, adalimumab, infliximab, golimumab), CD20 binders (rituximab) and IL‑1 receptor blockers (anakinra, canakinumab), though the studies supporting their efficacy are weak (Brant, Eliades et al. 2015, Balouch, Meehan et al. 2022). In practice, we usually see patients treated with etanercept or adalimumab.
The use of plasmapheresis in the management of AIED has also been studied (Luetje 1989), but never gained significant traction in clinical practice.
Prognosis
Prognosis of AIED is poor. Treatment may decelerate the pace of hearing loss, but generally systems eventually progress despite vigorous therapy.
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