Sensorineural Hearing Loss and Systemic Autoimmune Disease: The Experience of a Systemic Immune-Mediated Diseases Unit

Abstract

Background Autoimmune inner ear disease (AIED) represents less than 1% of all cases of sensorineural hearing loss (SNHL) but its frequency may be underestimated due to lack of specific clinical and laboratory criteria. AIED can be associated with a systemic autoimmune disease (SAID) in 15%-30% of the cases. The objective of the present study was to characterize the clinical and prognostic factors of a cohort of patients with AIED. Materials and methods The authors conducted a retrospective descriptive analysis of a cohort of patients with AIED referred from the otorhinolaryngology department to a systemic immune-mediated diseases unit between March 2013 and November 2020. A consecutive sample of 39 patients with suspected AIED was referred. SNHL was defined as a fall of the hearing threshold of at least 30 decibels in three consecutive frequencies. Eight patients were excluded for not meeting the audiometric criteria or having confounding factors. The remaining 31 patients were included with a total of 50 affected ears. To classify the intensity of hearing loss, an arithmetic mean of pure tone was calculated. Normal hearing or mild hearing loss at the last pure tone audiometry of the followup were an indicator of good prognosis and were considered the outcome of interest. Results Thirty-two percent of the patients had an associated SAID. There were no differences regarding demographic and clinical characteristics when comparing patients with AIED alone and patients with AIED and a SAID, except for the positivity of antinuclear antibodies (ANA). ANA positivity was superior in patients with the association of AIED and a SAID when compared with patients with AIED alone (90% vs 50%; p=0.037). The SAID was diagnosed after the AIED in 70% of the patients, in which diagnosis of the SAID occurred a median of 4,2 (IQR 0.8-5.1) years after the diagnosis of the AIED. Normal audiometric evaluation or a mild hearing loss was achieved in 31% of the ears at the last audiometric evaluation. A normal audiometry or a mild hearing loss at the time of diagnosis was independently associated with a better outcome (31%, 14%, CI 1.71-273.69; p=0.018). Bilateral hearing loss was independently associated with a worse outcome (54%, 79%, CI 0.01-0.84; p=0.035). The use of systemic corticosteroids (p=0.941), transtympanic corticosteroids (p=0.700) and non-steroid immunomodulator drugs (p=0.986) did not affect prognosis. The presence of a SIAD did not affect the prognosis (p=0.986). Conclusions In this cohort, SAID was present in one-third of the patients with AIED. A good prognosis was achieved in one-third of the patients. A normal audiometry or mild disease at presentation was associated with a good outcome, whilst bilateral involvement was associated with a bad one. Association of a SAID did not seem to influence the hearing-related prognosis. Positivity of ANA antibodies may justify performing a complementary investigation to determine the presence of a SAID.

Decoding the impact of autoinflammatory/autoimmune diseases on inner ear harmony and hearing loss

“…Studies have indicated an association between sudden SNHL and the presence of antibodies against specific inner ear antigens, including heat shock protein 70 (HSP-70), cochlin, β-tectorin, connexin 26, β-actin, choline transporter-like protein 2, and types II and IX collagen [14,15]. Description of the immune system attack on the cochlea in autoimmune and autoinflammatory diseases: inflammation is triggered, leading to irreversible damage as activated lymphocytes migrate, while autoantibodies also contribute to hearing loss and vestibular symptoms.…”

Role of Inner Ear Macrophages and Autoimmune/Autoinflammatory Mechanisms in the Pathophysiology of Inner Ear Disease

“…The inner ear is fully able to mount an immune response following the invasion of outside antigens. Consequently, numerous mechanisms have been proposed to underlie cochlear damage that include antibody–antigen reactions with autoantibody enhancement (type II immune responses), complement machine activation, immune-complicated depletion (type III immune responses), direct damage mediated via cytotoxic T-cells crossing the blood–labyrinth barrier and reaching the endolymphatic sac, vasculitis, micro-thrombosis, and electrochemical reactions (type IV immune responses) ( 10 , 12 , 14 , 20 , 58 ). Antigen recognition by the innate immune cells of the inner ear (neutrophils, Mφs, and dendritic cells) stimulates the release of IL-1β, which in turn triggers a series of adaptive immune responses.…”

“…The recruitment of immunocompetent cells and the promotion of an adaptive immune response occur in the presence of immune mediators, such as IL-1β, IL-2, and TNFα ( 13 , 20 ). Studies have suggested an association between sudden sensorineural hearing loss and the presence of vestibulocochlear antibodies against inner ear antigens, such as heat shock protein 70, cochlin, β-tectorin, and types II and IX collagen ( 12 , 20 , 59 – 61 ).…”

“…Autoimmune inner ear disease (AIED) represents much fewer than 1% of all cases of sudden sensorineural hearing loss ( 10 , 11 ), generally presenting as subacute, swiftly progressing, frequently fluctuating, bilateral, and asymmetrical sensorineural hearing loss ( 9 – 14 ). AIED can be labeled as primary AIED, in which the inner ear is the most affected organ, or secondary AIED (15–30% of cases), which develops in association with a systemic autoimmune disease ( 12 ), such as autoimmune hepatitis ( 15 ), systemic lupus erythematosus (SLE) ( 16 ), multiple sclerosis (MS) ( 17 ), rheumatoid arthritis ( 18 ), inflammatory bowel disease (IBD) ( 19 ), or antiphospholipid syndrome ( 14 , 20 ).…”

Moving forward from hearing loss in vitiligo – Does autoimmune sensorineural hearing loss play a role?

“…rheumatoid arthritis, thyroid disease, lupus, scleroderma and Sj€ ogren's syndrome) and the presence of autoantibodies (anti-Hsp70), and it favourably responds to immunosuppressant drugs. [10][11][12] The estimated prevalence of ASNHL in the population is 0.015%; however, it is probably underdiagnosed due to the stringency of the diagnostic criteria, which include anti-Hsp70 autoantibodies, reduced number of na€ ıve T cells (CD4RA) and a favourable response to immunosuppressive therapy. 7 To date, vitiligo has not yet been explored as a probable autoimmune disorder associated with ASNHL, nor the prevalence of anti-Hsp70 is known among patients with vitiligo.…”