Autoimmune sensorineural hearing loss …

Douglas J Lanska MD MS MSPH

Neuroimmunology

Updated 05.14.2024
Released 04.26.1996
Expires For CME 05.14.2027

Autoimmune sensorineural hearing loss

Author: Douglas J Lanska MD MS MSPH

See Contributor Disclosures

Autoimmune sensorineural hearing loss

In This Article

Quick Link

Introduction

Overview

Autoimmune hearing loss is a potentially reversible form of hearing loss defined by rapidly progressive sensorineural loss and a characteristic recovery with immunosuppressive therapy. The disorder’s pathogenesis is uncertain, but damage to inner ear structures is thought to occur through an immune-mediated process. In this article, the authors review the current understanding of the disorder. The authors also provide an update on treatments for autoimmune hearing loss.

Key points

	• Autoimmune sensorineural hearing loss is a well-described clinical entity with an incompletely understood pathogenesis.
	• Cogan syndrome is characterized by audiovestibular dysfunction and interstitial keratitis.
	• Treatment focuses on suppressing a likely, though presumed, abnormal immune response to inner-ear antigens.
	• Classically, autoimmune sensorineural hearing loss improves with initiation of immunosuppressive therapy, deteriorates with discontinuation of therapy, and recovers with reinstitution of treatment.

Historical note and terminology

Autoimmune sensorineural hearing loss is a well-described clinical entity with an uncertain pathogenesis. Known also as "immune-mediated sensorineural hearing loss," "autoimmune inner-ear disease," and "steroid-responsive sensorineural hearing loss," this disorder is one of only a few forms of sensorineural hearing loss that can be treated with the expectation of significant improvement in auditory acuity.

A relationship between autoimmune diseases and hearing loss is well recognized, with descriptions of sensorineural hearing loss seen in such systemic autoimmune diseases as systemic lupus erythematosus, polyarteritis nodosa, granulomatous polyangiitis (formerly called Wegener granulomatosis), and rheumatoid arthritis (40). In addition, reports have also described associations with celiac disease (124; 55), primary antiphospholipid syndrome (14; 125), Behcet disease (24; 25), Sweet syndrome (16), ankylosing spondylitis (01), Sjögren's syndrome (88; 90); systemic sclerosis (67), sclero-uveitis in the setting of HLA-B27 positivity (97), Cogan syndrome (79), Susac syndrome (22; 50; 06; 09; 101; 111; 112; 86; 96; 102; 127), sarcoidosis (128), and type 1 autoimmune hepatitis (138). See Table 1 in the “Etiology” section for a complete listing of associated diseases.

Behcet disease and autoimmune sensorineural hearing loss (coronal MRI)

Normal coronal MRI of the head in a 37-year-old man with Behcet disease and autoimmune sensorineural hearing loss. (Source: Faisal M, Barjas H, Alwassiti W, Omer W, Abdulla N. Sensory neural hearing loss in Behcet's disease suc...
Behcet disease and autoimmune sensorineural hearing loss (transverse MRI)

Normal transverse MRI of the head in a 37-year-old man with Behcet disease and autoimmune sensorineural hearing loss. (Source: Faisal M, Barjas H, Alwassiti W, Omer W, Abdulla N. Sensory neural hearing loss in Behcet's disease ...

An immune response directed against the inner ear resulting in sensorineural hearing loss was first described in 1979 (75). McCabe described sensorineural hearing loss in 18 patients with a variable presentation of progressive bilateral asymmetrical sensorineural hearing loss accompanied by vestibular symptoms and a positive serologic response to inner-ear antigens. Treatment with dexamethasone and cyclophosphamide substantially improved hearing. The distinctive clinical course, laboratory findings, and clinical response to immune therapy suggested that this entity is autoimmune-mediated. Subsequent literature described a characteristic clinical presentation to include rapid onset (usually unilateral) and a more slowly progressing form of sensorineural hearing loss (76).

A condition referred to as "steroid-responsive bilateral sensorineural hearing loss" appeared in the literature in the 1980s (54). Several patients diagnosed with idiopathic sensorineural hearing loss showed improvement in audiologic measurements following steroid therapy and subsequent deterioration of auditory sensitivity on discontinuation of treatment. These patients also revealed elevated serum levels of immune complexes that responded to steroid treatment (53). Also described was an immune complex-mediated disorder with features of vasculitis that targeted the inner ear and improved with glucocorticoids (122).

Although diagnostic criteria for autoimmune sensorineural hearing loss have not been established, the hallmark features of progressive sensorineural hearing loss and steroid responsiveness are widely recognized features.

Clinical manifestations

Presentation and course

	• Autoimmune hearing loss is believed to constitute less than 1% of all cases of acute/subacute sensorineural hearing loss.
	• Hearing loss is usually bilateral (greater than 80% of patients).

Autoimmune sensorineural hearing loss characteristically presents as an asymmetrical bilateral progressive sensorineural hearing loss frequently accompanied by vestibular symptoms. The temporal progression can range from acute (developing from several hours to 3 days) to a chronic progressive form (developing more slowly over several months). The typical time frame is between these two extremes, presenting as a rapidly progressive and often fluctuating bilateral sensorineural hearing loss, evolving over weeks to months (11). This usually involves high frequencies and results in a down-sloping audiogram. Less commonly, a low-frequency loss has been reported, particularly in patients with lupus (89; 137). Although it is bilateral in up to 80% of cases, unilateral presentations also occur (48). The presence of other immune diseases is also common, with as many as 30% of patients exhibiting some form of systemic immune-related disease (48). Autoimmune hearing loss can be precipitated by treatment with immune checkpoint inhibitors, which activate the immune system to fight the underlying cancer but then are associated with an increased frequency of autoimmune disorders (95).

In addition to complaints of hearing loss, nearly half of patients with autoimmune sensorineural hearing loss report other audiovestibular symptoms, including aural fullness, tinnitus, lightheadedness, and vertigo (48). Facial nerve palsy is also observed occasionally (75). Although the age of presentation is variable, the mean presentation is in the fifth decade, with females making up one to two thirds of autoimmune sensorineural hearing loss cases. This increased prevalence among middle-aged females seen in some studies is consistent with other autoimmune disorders (48). The incidence of autoimmune sensorineural hearing loss is thought to constitute less than 1% of all cases of hearing impairment with dizziness.

Cogan syndrome is characterized by a mix of audiovestibular symptoms and inflammatory ocular disease, occurring concomitantly or within 6 months of each other. This is usually a relapsing condition (29; 86; 96; 102). There can be multisystem involvement (56). Typical ocular symptoms consist of acute unilateral or bilateral interstitial keratitis but can include optic disc edema and macular degeneration (127).

Optic disc edema in Cogan syndrome

Optical coherence tomography shows optic disc edema in a patient with Cogan syndrome. (Source: Wang Y, Tang S, Shao C, Liu Y. Cogan's syndrome is more than just keratitis: a case-based literature review. BMC Ophthalmol 2023;23[...
Macular degeneration in Cogan syndrome

Optical coherence tomography showing macular degeneration in a patient with Cogan syndrome. (Source: Wang Y, Tang S, Shao C, Liu Y. Cogan's syndrome is more than just keratitis: a case-based literature review. BMC Ophthalmol 20...

Audiovestibular symptoms include Meniere-like attacks of severe vertigo; nausea; ataxia; oscillopsia; tinnitus; and fluctuating, progressive hearing loss (29; 127).

Bilateral profound sensorineural hearing loss in Cogan syndrome

Augiogram shows bilateral profound sensorineural hearing loss in a patient with Cogan syndrome. The right ear audiogram is on the left. (Source: Wang Y, Tang S, Shao C, Liu Y. Cogan's syndrome is more than just keratitis: a cas...

Audiovestibular dysfunction leads to progressive hearing loss and deafness in 60% of patients (44). Cogan syndrome may present with symptoms of IgA vasculitis (formerly called Henoch Schoenlein Purpura) before anterior uveitis and bilateral sensorineural hearing loss develop (96).

Clinical vignette

Case 1. An otherwise healthy 28-year-old black man presented with a complaint of hearing loss in his right ear for several weeks’ duration. He had mild disequilibrium but no vertigo or tinnitus. Physical examination was normal. Audiometric analysis revealed an asymmetric, moderate-to-severe sensorineural hearing loss in his right ear with a speech discrimination score of 72%. Blood studies, including a syphilis assay, were normal, and MRI with gadolinium revealed no retrocochlear pathology. The patient was given a prescription for methylprednisolone but did not comply with the medication and was lost to follow-up. He returned 18 months later with complaints of worsening hearing in his left ear and intermittent disequilibrium. Audiogram revealed persistence of his previous right-sided sensorineural hearing loss and interval development of moderate (40 dB) left-sided sensorineural hearing loss with a speech discrimination score of 80%. Electrocochleography and electronystagmography were normal. He was started immediately on a 4-week course of prednisone 60 mg/day. Follow-up audiogram at 4 weeks showed improvement in his pure tone thresholds and speech discrimination. Twelve-week follow-up revealed a residual mild loss in the left ear. The patient has been off immunosuppressive therapy for 6 months with no further change in his hearing and no vestibular symptoms.

Case 2: Susac syndrome with livedo reticularis and autoimmune sensorineural hearing loss (111). A 45-year-old, previously healthy man presented with subacute hearing loss, blurry vision, headaches, intermittent confusion, and a truncal rash. He was afebrile and had a normal mental status examination. With prescription lenses, visual acuity was 20/20 in both eyes, but peripheral vision was impaired in both eyes. Fundoscopic examination revealed bilateral retinal flame hemorrhages and cotton wool spots. A diffuse, nontender, and blanchable rash was present on the abdomen and flank.

Lower back rash in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss

Violaceous net-like rash in an asymmetric pattern on the lower back in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss. (Source: Srichawla BS. Susac syndrome with livedo reti...
Left flank rash in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss

Violaceous net-like rash in an asymmetric pattern on the left flank in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss. (Source: Srichawla BS. Susac syndrome with livedo reti...

Blood studies were unrevealing, including a comprehensive metabolic panel, complete blood count, and PCR test for SARS-CoV-2 RNA. Inflammatory markers and serum autoimmune antibody panel, including C-reactive protein, erythrocyte sedimentation rate, antinuclear antibody, antineutrophil cytoplasmic antibody, rheumatoid factor, and cyclic citrullinated peptide, were also negative.

MRI of the brain without and with contrast showed significant hyperintensities in the white matter throughout the rostrum, genu, and body of the corpus callosum.

White matter lesions in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss (MRI) (1)

Sagittal T2-weighted MRI revealing multiple small-to-large white matter lesions ("snowballs") within the rostrum, genu, and body of the corpus callosum in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmun...
White matter lesions in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss (MRI) (2)

Sagittal T2-weighted MRI revealing multiple small-to-large white matter lesions ("snowballs") within the rostrum, genu, and body of the corpus callosum in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmun...
White matter lesions in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss (MRI) (3)

Sagittal T2-weighted MRI revealing multiple small-to-large white matter lesions ("snowballs") within the rostrum, genu, and body of the corpus callosum in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmun...
Linear lesion in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss (MRI) (4)

Sagittal T2-weighted MRI revealing linear ("spoke") lesion seen within the genu of the corpus callosum in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss. (Source: Srichawla ...

Cerebral angiography revealed no large vessel occlusion.

The patient underwent an audiogram, which revealed moderate unilateral biphasic sensorineural hearing loss in the right ear. The audiogram revealed moderate sensorineural hearing loss at 500 Hz, rising to within normal limits at 750 to 2000 Hz. Moderate sensorineural hearing loss was also recorded at 4000 to 8000 Hz in the right ear.

Unilateral biphasic sensorineural hearing loss in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss (audiogram)

Audiogram revealing unilateral biphasic sensorineural hearing loss in the right ear in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss. (Source: Srichawla BS. Susac syndrome ...

CSF studies were significant for elevated protein (273 mg/dL; normal range 15-45 mg/dL), albumin (207 mg/dL; normal range 0-35 mg/dL), immunoglobulin G (31.4 mg/dL; normal range 0-6 mg/dL), and IgG synthesis rate (47.0 mg/d; reference range < 8.0). A comprehensive autoimmune and infectious panel of the CSF was unremarkable.

A punch biopsy of the left flank revealed mild perivascular lymphocytic infiltrate, vascular congestion, and focal vascular ectasia consistent with livedo reticularis.

Ectatic and congested vessels in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss

Ectatic and congested vessels in the superficial dermis with mild perivascular lymphocytic infiltrate in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss. (Source: Srichawla B...
Congested vessel and perivascular lymphocytic infiltrate in man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss

Congested vessel (packed with red blood cells) and perivascular lymphocytic infiltrate without thrombi in a 45-year-old man with Susac syndrome, livedo reticularis, and autoimmune sensorineural hearing loss. (Source: Srichawla ...

Susac syndrome was diagnosed, and proposed pathogenic mechanisms of Susac syndrome were reviewed; pathophysiological mechanisms of livedo racemosa and livedo reticularis were contrasted.

Proposed pathogenic mechanisms of Susac syndrome

Legend: TOX - thymocyte selection-associated high mobility group box; TCR - T cell receptor; CD8 - cluster of differentiate 8; TNF-α - tumor necrosis factor-alpha. (Source: Srichawla BS. Susac syndrome with livedo reticularis: ...
Pathophysiological mechanisms of livedo racemosa

Dugs associated with livedo reticularis include amantadine, quinidine, and catecholaminergic agents. (Source: Srichawla BS. Susac syndrome with livedo reticularis: pathogenesis and literature review. Cureus 2022;14[7]:e27352. C...
Pathophysiological mechanisms of livedo reticularis

(Source: Srichawla BS. Susac syndrome with livedo reticularis: pathogenesis and literature review. Cureus 2022;14[7]:e27352. Creative Commons Attribution 4.0 International [CC BY 4.0] license, creativecommons.org/licenses/by/4....

Intravenous methylprednisolone (1 g daily for 5 days) and rituximab infusion were started, but rituximab was discontinued due to persistent tachycardia and the development of atrial fibrillation with a rapid ventricular response. Subsequently, cyclophosphamide (1 g) was administered with mesna (ie, a detoxifying agent used to prevent hemorrhagic cystitis). He was discharged on a tapering dose of oral prednisone. At a 2-week follow-up appointment, he received another infusion of cyclophosphamide. His rash resolved, he had no further episodes of encephalopathy, and hearing and peripheral vision both improved.

Case 3: autoimmune sensorineural hearing loss and type 1 autoimmune hepatitis (138). A 60-year-old man was initially hospitalized for low-grade fever, slightly raised erythematous lesions, and asymmetric ankle swelling. C-reactive protein (156 mg/L; reference range < 6 mg/L), erythrocyte sedimentation rate (69 mm/h; reference range 0-30 mm/h), and liver enzymes were elevated.

Liver function trends in man with autoimmune hepatitis and sensorineural hearing loss

Trends of liver function tests (IU/L) in a 60-year-old man with autoimmune hepatitis and autoimmune sensorineural hearing loss. (Source: Zarachi A, Pelechas E, Tsikou A, et al. Immune-mediated inner ear disease associated with ...

Tests for hepatitis (A, B, and C), rheumatoid factor, anti-cyclic citrullinated peptide antibody, iron, ferritin, ceruloplasmin, and angiotensin-converting enzyme were normal. A chest x-ray did not reveal hilar adenopathy or pulmonary infiltrates. Symptoms abated substantially with empiric cefuroxime for a presumptive diagnosis of possible erysipelas.

Two weeks later, he was readmitted for recurrent fever, weight loss, and low back pain. No source of sepsis was found. Laboratory testing showed normochromic, normocytic anemia, leukocytosis, and elevated ESR, CRP, and liver enzymes. Repeat blood cultures, urine culture, microbial serology, and echocardiography were all negative. Because MRI was contraindicated (due to a metallic foreign body after surgery), three-phase scintigraphy and CT scan were done and showed possible sacroiliitis in the left sacroiliac joint (attributed to his congenital right hip dislocation and associated pelvic dysplasia but nevertheless treated as possible septic arthritis). CT of the chest and abdomen revealed mild fibrous elements in the upper lobes of the lungs, but no bile duct stenosis was evident, and the liver was homogenous without focal lesions. A Mantoux test was negative. Fever persisted for more than a week, and liver enzymes and acute-phase reactants remained elevated, so the initial antibiotic treatment was discontinued, and piperacillin-tazobactam and linezolid were started. Two weeks later, the symptoms gradually improved, and the patient was discharged home on a regimen of oral ciprofloxacin and clindamycin, but ESR and liver enzymes remained elevated. Blood tests were positive for antinuclear antibodies (1:160) with a speckled pattern. Anti-double-stranded DNA, anti-Sm, anti-Ro/SSA, anti-La/SSB, anti-RNP, anti-ribosomal P, and antiphospholipid antibodies were all negative. Repeat CT showed no abnormal findings in the left sacroiliac joint.

Four months later, he developed sudden hearing loss and tinnitus with aural fullness in the left ear. Oral corticosteroids were empirically administered for 5 days, but because the symptoms persisted, the patient was readmitted. Neurologic examination and otoscopic findings were normal. Weber test lateralized to the right, consistent with left sensorineural hearing loss. An audiogram showed normal hearing thresholds on the right and profound sensorineural hearing loss on the left.

Profound left ear hearing loss in man with autoimmune hepatitis and sensorineural hearing loss (audiogram)

Initial audiogram, consistent with profound hearing loss of the left ear (90-100 dB), in a 60-year-old man with autoimmune hepatitis and autoimmune sensorineural hearing loss. (Source: Zarachi A, Pelechas E, Tsikou A, et al. Im...

Intravenous methylprednisolone (250 mg daily for 4 days and a gradual taper thereafter) was begun to treat the profound left sensorineural hearing loss. A liver biopsy was performed because of the considerable and persistent elevation of transaminases and enzymes associated with cholestasis. Smooth muscle antibodies (1:40) and perinuclear antineutrophil cytoplasmic antibodies (1:80) were elevated, but antimitochondrial antibodies were negative. Symptoms stabilized, and the patient was discharged home.

Three days later, he was again readmitted because of new hearing loss and tinnitus in the right ear as well as difficulty understanding conversations amid background noise. A repeat audiogram revealed moderate right sensorineural hearing loss.

Right ear hearing loss in man with autoimmune hepatitis and sensorineural hearing loss (audiogram)

Second audiogram in a 60-year-old man with autoimmune hepatitis and autoimmune sensorineural hearing loss. This is consistent with sensorineural hearing loss in the right ear with mild low-frequency loss precipitously sloping t...

Brainstem auditory evoked responses showed findings consistent with asymmetric, bilateral sensorineural hearing loss. CRP and liver tests remained elevated. Brain CT was normal, and high-resolution CT of the temporal bones revealed no lytic findings or erosions. Because of his devastating bilateral sensorineural hearing loss, he received three intratympanic dexamethasone injections in both ears. The liver biopsy revealed lymphocytic inflammatory infiltration of the portal tract and mild findings of non-alcoholic fatty liver disease without hepatic fibrosis or histopathological demonstration of granuloma.

Liver biopsy in man with autoimmune hepatitis and autoimmune sensorineural hearing loss (1)

Pathological examination of liver biopsy in a 60-year-old man with autoimmune hepatitis and autoimmune sensorineural hearing loss (H&E x100). The picture shows a few lymphocytes in a portal tract and steatosis but not fibro...
Liver biopsy in man with autoimmune hepatitis and autoimmune sensorineural hearing loss (2)

Pathological examination of liver biopsy in a 60-year-old man with autoimmune hepatitis and autoimmune sensorineural hearing loss (Masson trichromex100). (Source: Zarachi A, Pelechas E, Tsikou A, et al. Immune-mediated inner ea...

Various other autoantibody tests were obtained, but these were unrevealing except for p-ANCA (1:80 with positive titers > 1:20) and SMA directed against filamentous actin (1:160 with positive titer > 1:40).

As shown on a third audiogram approximately 2 months after the initiation of oral treatment, hearing acuity improved in the right ear by approximately 20 dB after three intratympanic dexamethasone injections followed by a course of intravenous methylprednisolone (500 mg/d x 3 days).

Audiogram after oral immunosuppressive treatment in man with autoimmune hepatitis and sensorineural hearing loss

Third audiogram obtained approximately 2 months after the initiation of oral immunosuppressive treatment in a 60-year-old man with autoimmune hepatitis and autoimmune sensorineural hearing loss. hearing acuity improved in the r...

Oral prednisolone with azathioprine was subsequently started.

Biological basis

Etiology and pathogenesis

Table 1. Diseases Associated with Autoimmune Sensorineural Hearing Loss

Autoimmune:
	Polyarteritis nodosa Granulomatosis with polyangiitis (formerly Wegener granulomatosis) Behcet disease Cogan syndrome Sweet syndrome (acute febrile neutrophilic dermatosis) Churg-Strauss syndrome Sarcoidosis Ankylosing spondylitis Systemic lupus erythematosus Sjogren syndrome Systemic sclerosis Mixed connective tissue disease (MCTD) Rheumatoid arthritis Relapsing polychondritis Crohn disease HLA-B27 sclero-uveitis Primary antiphospholipid syndrome Meniere disease (possible in some cases) Celiac disease Vogt-Koyanagi-Harada syndrome Susac syndrome
Autoinflammatory:
	CAPS (cyropyrin-associated periodic syndrome) Muckle-Wells disease NOMID/CINCA Familial cold autoinflammatory syndrome (FCAS) Monarch-1 H syndrome, also referred to as SLC29A3
Note: NOMID = neonatal onset multisystem inflammatory disease; CINCA = chronic infantile neurologic, cutaneous, and articular syndrome

Although the exact etiology of autoimmune sensorineural hearing loss is unknown, a proposed pathogenic mechanism of autoimmune sensorineural hearing loss involves inflammation and an immune-mediated attack of specific inner ear structures, leading to an excessive Th1 immune response (ie, involving the Th1 subset of T helper cells and producing Th1-type cytokines) with resultant vascular changes and tissue damage in the cochlea (32). Controversy exists as to whether the inner ear is targeted directly through a cell-mediated immune response or whether the damage results from a humoral immune complex destruction of key inner-ear structures. Viral, vascular (ie, microthrombosis), immunologic (eg, immune-complex deposition), and electrochemical (eg, through disruption of neurosignaling) mechanisms have all received consideration (33; 32).

Immunology and molecular biology advances have helped identify serum antibodies directed against several inner-ear antigens in many patients with the disorder. Similarly, experimental models show immune-mediated damage to key inner-ear structures such as the stria vascularis. The possibility that injury to inner-ear structures results from a localized immune response directed against the inner ear or from systemic immune responses with limited target organs remains controversial.

Once thought to be an immunologically privileged site, the inner ear is much more responsive to immune stimulation than the brain and acts as an afferent limb of the immune pathway (38). Both humoral and cell-mediated responses are established for inner-ear tissues and fluids and help to protect these vital structures from infection (42). However, this immune response and resultant inflammation can result in serious injury to the delicate cochlea and vestibular tissues. Researchers propose that with the early inflammatory process, inner-ear tissue up-regulates expression of adhesion molecules, such as ICAM-1, thus, permitting the movement of inflammatory cells into the labyrinth (114).

However, direct evidence of immune-mediated damage to inner-ear structures is not easily demonstrated. The first successful induction of autoimmune sensorineural hearing loss and vestibular disease in rats was accomplished by immunizing the rats with type II collagen, an extracellular matrix protein found throughout the inner ear. Histological analysis of inner ears from these animals demonstrated significantly greater perivascular inflammation and immune complex deposition compared with control animals. Similar experiments with a guinea pig model produced injury to the stria vascularis, organ of Corti, and spiral ganglion cells (132).

Subsequent clinical studies used type II collagen as the antigen for lymphocyte transformation tests and found positive responses in half of the patients (34 of 68) with progressive sensorineural hearing loss compared to only 6% (4 of 68) in controls (07). Additional work using Western blot assays found anti-type II collagen antibodies in 12 of 21 patients with various forms of inner-ear disease. Anti-type IX collagen (specific for the labyrinthine membrane and tectorial membrane) was detected in 13 of 21 blots (52). Animal models have been developed utilizing type II (133) and type IX collagen (15) as well as the myelin P0 protein (71) and tubulin (134). Other authors suggested that at least one other, and perhaps several other, antigens are targets for the immune response (42). Investigators previously reported on a 68-kDa antigen, which was thought to represent heat shock protein 70 (HSP70), identified in the serum of patients with progressive hearing loss suspected to be immune-related (10). However, the identity of this antigen has been called into question in several subsequent studies (131; 83). Mice carrying the Kresge Hearing Research Institute-3 (KHRI-3) antibody developed hearing loss (84); the responsible inner-ear antigen was found to be human choline transporter-like protein 2 (CTL2). Choline plays a central role in the biosynthesis of acetylcholine, an inner-ear neurotransmitter, and is a major component of cell membranes in the form of phosphatidylcholine. Current theories suggest that the CTL2 complex is essential for hair cell survival. In conclusion, there is mounting evidence that the target antigen of the 68-kDa antibody is not HSP70 but is likely CTL2.

Another debate concerns whether the ear is directly affected by specific antibodies against sensory structures or indirectly injured by elevated levels of immune complexes from a systemic disease process. The systemic disease explanation maintains that there is exposure of normally sequestered inner-ear antigens that drive an immune response. The inner ear has its own immune system, comprised of immunocompetent cells and antibody trafficking (37). Once the inner ear has become activated, new cells either form or enter from the systemic circulation, penetrating the blood-labyrinthine barrier. In both humans and animals, macrophages, B cells, and T cells can enter the peri-saccular space (37; 03). Blood vessels of the spiral modiolar vein, adjacent to the scala tympani, serve as the initial site of lymphocyte entry into the inner ear. As early as 6 hours after stimulation, immune cells begin to accumulate around the blood vessels within the spiral modiolar vein and then begin to enter the scala tympani (39). Control of this process is not well understood. Ablation of the endolymphatic sac reduces immune responses in the cochlea (Tomiyama and 38). This process leads to the production of IL-2. IL-2 is normally absent from the perilymph in the resting state, but post-stimulation levels peak approximately 18 hours after stimulation and then decline over a subsequent 5-day period, well in accordance with entry of helper T cells and macrophages. Furthermore, mediators such as ICAM-1 reach their maximum level on the epithelium of the spiral modiolar vein and collecting venules by day 2 and gradually diminish. IgG, IgA, and IgM immunoglobulins have been demonstrated in both human and animal perilymph, but their origin remains to be elucidated (130). Several studies have also demonstrated the presence of IgG immune complex deposits within strial capillaries and extracapillary spaces. These findings accompany marked intercellular edema and capillary basement membrane thickening (59; 78; 129; 85; 64). The studies suggest that immune-mediated injury of stria vascularis may represent a primary injury.

Beyond the cellular mediators of inflammation, attention has been focused on the cytokines involved in this process. Besides elevation of IL-2, multiple studies have reported elevated levels of TNF-alpha in animal models. On binding to its receptor, TNF-alpha triggers expression of cell adhesion molecules on vascular endothelial cells, facilitation of leukocyte and monocyte extravasation, and recruitment to the site of inflammation. In the KLH model of autoimmune inner-ear disease, TNF-alpha is the first cytokine expressed by inner-ear-infiltrating cells following systemic KLH-antigen immunization and infusion into the cochlea (105). Etanercept, a TNF-alpha antagonist, reduced cell infiltration and cochlear fibrosis compared to controls (92). Similar results were obtained with intraperitoneal etanercept injection in the same model (126). Finally, cells within the endolymphatic sac are required for developing an adaptive immune response and are a source of TNF-alpha, needed for amplification of the immune response in the KLH model (106). Apparently, continuous antigen exposure can lead to a chronic inflammatory cascade that results in damage to the sensitive structure of the inner ear. Interleukin-1 is an important cytokine in the immune system activating multiple cell types and is elevated in corticosteroid-resistant patients. Treatment with interleukin-1 inhibitors can improve hearing loss in these patients. Interestingly, although the interleukin-1 decay receptor is induced in corticosteroid-responsive patients, suggesting a decrease in interleukin-1 signaling, treatment with interleukin-1 blockade in those patients produced only a modest change in hearing, suggesting that separate disease processes are involved (118).

An association of autoimmune sensorineural hearing loss with antiphospholipid antibodies (ie, anti-cardiolipin and anti-beta-2-glycoprotein-1) has also been suggested, but this has not been validated in larger cohorts (82; 63). These antibodies are seen in the setting of SLE, myriad autoimmune states, and in isolation. They are associated with a hypercoagulable state. Their exact relationship to sensorineural autoimmune hearing loss is unclear. Antinuclear antibody has also been found at a higher rate in patients with sudden deafness as compared to the healthy population (63; 68) as well as in those with other forms of autoimmune inner ear disease (100). IgE levels were elevated in patients with acute-onset low-tone sensorineural hearing loss, were associated with increased allergic response, and predicted relapse as well as progression to Meniere disease (66). Human leukocyte antigen phenotyping has not been extensively evaluated, but available studies have produced variable results without a strong association identified (93).

Autoimmune mice treated with prednisolone or aldosterone were protected from strial damage (117).

Epidemiology

Autoimmune sensorineural hearing loss is a rare clinical disorder. The estimated yearly incidence is less than five cases per 100,000, and its prevalence is 15 out of 100,000. Some authors report that this condition accounts for less than 1% of all cases of hearing loss, even though the diagnosis of autoimmune sensorineural hearing loss might be overlooked without a specific diagnostic test (11). An approximate 2-to-1 female predominance is reported. Although age at presentation varies from childhood to old age, in most patients, symptoms occur in the third to sixth decades, with a peak incidence in the fifth decade (80). An association with other autoimmune disorders is reported in 30% of presenting patients (48; 20). The prevalence of hearing loss in various autoimmune diseases was reviewed nicely in one study (69). The risk of sudden sensorineural hearing loss was examined in a Korean population with established autoimmune diseases, and the results showed 1.1% of an autoimmune disease group experienced sensorineural hearing loss compared to 0.7% of a matched control group (51). Hearing loss prevalence was significantly higher in patients with antiphospholipid syndrome, multiple sclerosis, rheumatoid arthritis, Sjogren syndrome, and Behcet disease.

In a systematic review and metaanalysis of sensorineural hearing loss in autoimmune diseases, 18 articles were included, involving collectively 27,859 cases affected by autoimmune diseases: the pooled prevalence of sensorineural hearing loss was 21% in systemic lupus erythematosus, 16% in rheumatoid arthritis, and 39% in vitiligo cases (62).

In a cross-sectional study involving nonsegmental vitiligo (112 cases and 23 controls) evaluated through audiometry and serological assay of the anti-Hsp70 antibody, bilateral sensorineural hearing loss was significantly more common in cases than controls (25.0% vs. 4.3%) (70). Six cases (5.4%) had bilateral sensorineural hearing loss of unexplained etiology and anti-Hsp70 antibody positivity, fulfilling diagnostic criteria for immune-mediated inner ear disease, whereas no controls met diagnostic criteria for immune-mediated inner ear disease. Serum anti-Hsp70 antibodies were significantly higher in cases with immune-mediated inner ear disease (median 220.9 vs. 85.1 ng/ml).

Differential diagnosis

Confusing conditions

Autoimmune sensorineural hearing loss is a unique clinical entity with a characteristic history and a response to immunotherapy. Other forms of sensorineural hearing loss may share features with autoimmune sensorineural hearing loss but can usually be differentiated by history or clinical response.

In patients with hearing loss, history taking is a very important step in trying to determine the etiology: it is important to establish the length of time over which the hearing loss has developed, associated symptoms (tinnitus, vertigo, pain, ear discharge), and predisposing factors (eg, noise exposure, chemotherapy, antibiotic treatments, prior ear surgery, trauma, meningitis, or family history of hearing loss) (80). A complete review of systems should be performed in all patients because up to 30% of patients have or will develop a systemic autoimmune disease.

Among the other forms of sensorineural hearing loss that may be confused with autoimmune sensorineural hearing loss are sudden deafness, Meniere disease, cochlear otosclerosis, syphilitic deafness, Cogan syndrome, noise-induced hearing loss, ototoxic hearing loss, and acoustic tumors.

In addition to autoimmune sensorineural hearing loss, the differential diagnosis of rapidly progressive hearing loss includes the following: intracranial etiologies (eg, meningioma, lymphoma, metastatic deposit, cavernous angioma, meningitis, superficial siderosis), paraneoplastic syndromes (eg, small cell lung carcinoma, thymoma), autoimmune syndromes, infective disorders (eg, syphilis, human immunodeficiency virus), and medication-induced causes (61).

Sudden deafness or sudden sensorineural hearing loss differs from autoimmune hearing loss in that it characteristically develops over a matter of hours (within 72 hours or less), occurs unilaterally, and is often accompanied by tinnitus.

Autoimmune sensorineural hearing loss typically is somewhat insidious in onset, progressing over weeks to months, but more rapid than the development of presbycusis. The course is typically fluctuating and affects bilateral hearing, although the audiometric threshold may be asymmetric. From 25% to 50% of patients also have tinnitus and aural fullness. Facial palsy, as well as destruction of the tympanic membrane, middle ear, and mastoid may occur, but physical examination is usually normal.

Vasculitic processes tend to present as having a small conductive component due to otitis media, with serous otitis media being the most common type (136). Vestibular symptoms, such as imbalance, ataxia, motion intolerance, and positional or episodic vertigo, may be present in up to 50% patients. These patients can have an antecedent viral infection, but often the etiology cannot be determined (87). Despite a different disease time course, evidence supports an immunologic basis for sudden deafness in at least some cases (08).

Meniere disease is characterized by sudden, fluctuating hearing loss, episodic vertigo, tinnitus, and aural fullness; it is usually unilateral, especially early in the course. Meniere disease usually responds to dietary adjustments and diuretics and often will have characteristic findings on electrocochleography. Despite these distinctions, some authors have suggested that some patients with severe Meniere disease, particularly those not responding to conventional therapy, may have an autoimmune etiology (132).

Hearing loss from cochlear otosclerosis typically has a positive family history, flat audiogram, and slow progression over years. It can be differentiated from the more rapidly progressing autoimmune sensorineural hearing loss, as this type usually lacks a hereditary component and improves with glucocorticoids.

Syphilitic deafness is distinguished by significant vertigo and hearing loss that progresses over months to years, with a positive CSF fluorescent treponema absorption antibody (FTA-ABS) assay.

Cogan syndrome is a distinct systemic disorder characterized by audiovestibular dysfunction in the form of acute sensorineural hearing loss and vestibular imbalance or ataxia combined with nonsyphilitic interstitial keratitis (77; 23). The cause is likely a postinfectious immune response, and glucocorticoids are of benefit if initiated promptly (77).

Susac syndrome is a vasculopathic condition that may affect vision (secondary to retinal artery occlusion), the brain, and hearing (22; 50; 06; 09; 101; 111; 112). The auditory component of this triad may precede the other two manifestations (22). Autoimmune-mediated occlusions of the microvasculature in the brain, retina, and inner ear lead to CNS dysfunction, hearing deficits, and branch retinal artery occlusion (50).

Muckle-Wells syndrome is an autoinflammatory disease, part of the spectrum of a rare hereditary inflammatory disorder: cryopyrin-associated periodic syndrome (CAPS). In Muckle-Wells syndrome, sensorineural hearing loss starts in adolescence, and high-frequency sensorineural hearing loss is universal. Associated clinical features are skin rashes, fever, conjunctivitis, arthralgias, abdominal pain, and amyloidosis (58).

NOMID/CINCA is a dramatic autoinflammatory condition manifesting with fever, meningitis, severe joint damage, sensorineural hearing loss, vision loss, uveitis, papilledema, and sensorineural hearing loss that starts in infancy or young childhood (31).

Noise-induced sensorineural hearing loss should readily be distinguished from autoimmune sensorineural hearing loss by antecedent noise exposure.

Toxic sensorineural hearing loss can present as progressive or sudden sensorineural hearing loss. These cases are recognized by a prior history of exposure to known ototoxic agents, including aminoglycosides and chemotherapeutic agents.

Acoustic tumors present with asymmetric sensorineural hearing loss over months to years and have diagnostic radiographic findings absent in autoimmune hearing loss.

Sensorineural hearing loss may be the presenting symptom of paraneoplastic syndrome (34). The hearing loss is usually followed by involvement of different areas of the nervous system. Paraneoplastic sensorineural hearing loss has been described in patients with Hu antibodies, small cell lung cancer (99), sensory neuronopathy, kelch-like protein 11 (KLHL11) antibodies, brainstem encephalitis, and testicular seminomas (36). The cause of the hearing loss is unclear, but in patients with Hu antibodies and sensory neuronopathy, the reason is the loss of cochlear neurons (99).

Other differential diagnoses of autoimmune hearing loss include enlarged vestibular aqueduct syndrome, and Charcot-Marie-Tooth disease (17).

Diagnostic workup

	• No single diagnostic examination or laboratory study can definitively confirm the diagnosis of autoimmune sensorineural hearing loss.
	• MRI studies are indicated to rule out structural lesions.
	• Extensive blood testing is not indicated unless other features suggesting an autoimmune disorder are present.

Autoimmune hearing loss is usually diagnosed by history and physical examination to include neuro-otologic evaluation and audiometry. Improved hearing thresholds after immunosuppressive treatment are a confirmatory feature of the diagnosis. No single diagnostic examination or laboratory study can definitively identify this disorder, nor is a “response” to immunotherapy a definitive diagnostic test.

In obtaining a history, emphasis must be placed on the temporal aspects of the hearing loss and any possible antecedent event, such as viral illness, trauma, or aminoglycoside use. Autoimmune disease can also result in conductive hearing loss and visual loss.

Careful evaluation for vision changes is important as several autoimmune disorders associated with autoimmune sensorineural hearing loss also commonly involve the eye, including Susac syndrome, Cogan syndrome, HLA-B27 sclero-uveitis, and Vogt-Koyanagi-Harada syndrome.

Retinal edema in patient with Susac syndrome (retinography)

Retinography showing retinal edema in the upper temporal zone (dashed line) with arterial occlusions (arrows) in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of...
Retinal nonperfusion with segmental occlusions in patient with Susac syndrome

Fluorescein angiography showing an area of retinal nonperfusion in the superior temporal zone (dashed line) with segmental occlusions in an arterial vessel (arrow) in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzca...
Upper vessel inflammation in a patient with Susac syndrome (angiography)

Fluorescein angiography (late phase) showing upper vessel hyperfluorescence reflecting inflammation (arrows) in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of ...

At a minimum, evaluation should include an assessment of pupillary reactions (including swinging light test for an afferent pupillary defect), visual acuity, visual fields, and fundoscopy.

Careful evaluation for signs and symptoms of a systemic autoimmune disorder that may predispose to immune-mediated hearing loss is important. In 15% to 30% of cases, patients with autoimmune hearing loss have or will develop a systemic autoimmune disease (80).

Differentiation between autoimmune hearing loss and sudden hearing loss is important. Generally, autoimmune hearing loss develops over weeks to months and involves both ears. Sudden hearing loss is usually unilateral and develops within 72 hours.

Ruling out the diagnosis of Cogan syndrome is important, not only because hearing is often lost and vision can be lost, but also because 10% of cases are complicated by aortic insufficiency, which can be life-threatening (28). Firm diagnostic criteria have not been established, and there are no tests that prove or disprove the diagnosis. Diagnosis is made on clinical grounds following the exclusion of other conditions with similar presentations.

If the hearing loss is acute and bilateral, psychiatric, neurologic, and hematologic causes should be considered. Reported etiologies of acute hearing loss have included psychogenic (typically presenting with inconsistencies and variabilities on testing and a discrepancy between pure tone audiometry and auditory brainstem response) (05) and hearing loss related to tumor spread, particularly due to diffuse metastatic leptomeningeal carcinomatosis (57). Sudden hearing loss may also follow shortly after neurosurgical procedures such as intracranial surgery and lumbar punctures; such episodes are typically limited and resolve spontaneously. Neurologic causes can include diffuse encephalitis or paraneoplastic syndromes. Sudden hearing loss may also be a manifestation of vascular insufficiency to the brain – either in the form of acute vertebrobasilar insufficiency due to blood flow occlusion (107) or secondary to decreased cardiac output, as has been described with mitral stenosis (35). A subset of patients who experience an episode of sudden sensorineural hearing loss have 1.64 times greater risk of stroke than controls over a 5-year period (65). Given these findings, consideration for a thorough cardiac and neurologic workup should be made as well as close follow-up for patients judged most at risk.

Following a thorough history and physical examination, including otoscopy and tuning fork tests, pure tone audiometry and word recognition testing is required to determine the type and degree of hearing loss. Autoimmune sensorineural hearing loss is most often bilateral and asymmetrical (76). The audiogram further serves as a baseline study to document any progression of hearing loss or response to treatment. Electronystagmography can also evaluate vestibular function (48).

Neuroimaging with gadolinium-enhanced MRI should be obtained if the cause of hearing loss is not identified with otoscopy and audiometry (102).

Imunomodulatory treatment effects on florid labyrinthitis

MR images in STIR sequences showing (top) florid labyrinthitis before treatment and (bottom) absence of labyrinthitis after 4 months of immunomodulatory treatment. (Source: Rücklová K, von Kalle T, Koitschev A, et al. Paediatri...
Bilateral hyperintense lesions with preferential involvement of corpus callosum in Susac syndrome (MRI)

Axial FLAIR image of the brain showing bilateral hyperintense lesions with preferential involvement of the corpus callosum in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: d...
Bilateral acute small infarcts in a patient with Susac syndrome (DWI)

Axial diffusion-weighted brain MRI sequence displaying bilateral acute small infarcts in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of a single-centre case se...
Susac syndrome (MRI)

Axial T1-weighted MRI with contrast enhancement in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of a single-centre case series. J Clin Med 2022;11[21]:6549. Cre...
Snowball lesions in corpus callosum of patient with Susac syndrome (1)

Sagittal FLAIR sequence image showing several characteristic “snowball” lesions in the corpus callosum in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of a sing...
Snowball lesions in corpus callosum of patient with Susac syndrome (2)

Sagittal image on 3D-MPRAGE showing several characteristic “snowball” lesions in the corpus callosum in a patient with Susac syndrome. (Source: Beça S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of a single...

If the patient cannot undergo MRI, alternatives include CT, auditory brainstem response evaluation, or both, although these are less sensitive than MRI for detection of retrocochlear abnormalities (98). High-resolution, gadolinium-enhanced, T1-weighted MRI studies have shown enhancement of the vestibule, semicircular canals, vestibular nerve, and cochlea in patients with Cogan syndrome and acute disease, whereas patients with chronic deficits but no acute disease have narrowing or occlusion of semicircular canals on images obtained by the 3-dimensional constructive interference in steady-state technique (13; 26). PET may be a useful technique for assessing disease activity in patients with autoimmune inner ear disease (74). Cerebral angiographic findings of vasculitis, including alternating segments of stenosis and ectasia in intracranial arteries as well as a small aneurysm at the vertebrobasilar junction, have been described (02). Autoimmune hearing loss should be suspected when no clear etiology is noted on imaging studies and symptoms are progressing too slowly to be sudden sensorineural hearing loss and too fast to be presbycusis (80).

Excessive blood testing is expensive and often of no clinical consequence (46). Nevertheless, it may be reasonable to obtain serum tests that might confirm the suspicion of a systemic autoimmune disease, such as circulating immune complexes, quantitative immunoglobulin levels, antinuclear antibodies, and antibodies to extractable nuclear antigens, rheumatoid factor, complement levels, sedimentation rate, cryoglobulins, ANCA (anti-neutrophil cytoplasmic antibody), and thyroid autoantibodies. Negative serologic and treponemal tests for syphilis are mandatory to rule out congenital and acquired syphilis, which are the conditions most similar to Cogan syndrome. Sarcoidosis is the next most likely diagnosis to be excluded in patients with Cogan syndrome. Pathologic findings of necrotizing vasculitis have been demonstrated by biopsy of the skin, kidney, liver, spleen, gastrointestinal tract, subcutaneous nodules, muscle, myocardium, and coronary arteries (123). Bone marrow and brain biopsy generally have nonspecific findings (123).

Heat shock protein 70 (Hsp-70) antibodies have been examined as a diagnostic test for autoimmune hearing loss, but the evidence supporting this test’s diagnostic utility is weak (49) because it has a sensitivity of only approximately 50% (80). HSP70 antibodies have subsequently been detected in controls at a rate similar to cases (120). Anti-CTL-2 antibodies are found in 50% of patients with autoimmune sensorineural hearing loss; however, antibody testing is not commercially available, and the diagnostic value has yet to be evaluated (80). Of note, in humans with immune-mediated hearing loss, elevated TNF levels have been associated with a greater response to treatment with steroids (120).

Although a positive laboratory test result may suggest an autoimmune process, it is important that these tests not be overinterpreted, and simple positivity should not be viewed as diagnostic of an autoimmune process. Clinical experience suggests more specific immune complex assays are unlikely to aid in the diagnosis of autoimmune sensorineural hearing loss if the erythrocyte sedimentation rate is normal (113). Normal results, however, certainly do not exclude an immune-mediated etiology for hearing loss.

A diagnostic tool that is fairly specific for autoimmune sensorineural hearing loss is the response to treatment. Patients with the disorder have hearing levels that improve with treatment and deteriorate with interruptions in treatment, only to again have hearing improvement with reinstitution of therapy. This response to treatment is the hallmark of autoimmune sensorineural hearing loss and its most consistent diagnostic test.

Management

	• Steroids are considered first-line therapy.
	• The role of intratympanic steroid administration is unclear.
	• There is insufficient evidence that any of the proposed alternative treatments can replace steroids as initial treatment.

A multidisciplinary approach is recommended with otolaryngology, rheumatology, and audiology involvement. Rheumatologic consultation is recommended, especially if the need to resort to immunosuppressive agents beyond corticosteroids is considered.

Classically, autoimmune sensorineural hearing loss improves with initiation of immunotherapy, deteriorates with discontinuation of therapy, and recovers with reinstitution of treatment.

Advances in treatment remain complicated by the lack of reliable and easily available diagnostic testing as well as the lack of an animal model.

Oral glucocorticoids. High-dose glucocorticoids block the immune response or reduce inflammation and are considered first-line therapy. Contraindications to using steroids may include active infection, peptic ulcer disease, uncontrolled diabetes mellitus, glaucoma, or uncontrolled hypertension (87; 42). Dose and duration recommendations for therapy vary. Steroid doses tapered too rapidly can result in deterioration of hearing (54). The current standard of care includes a trial of oral prednisone at an initial dose of 60 mg/kg/day or 1 mg/kg per day for 4 weeks (98). Hearing tests are performed at therapy onset and after 1 month of treatment. Therapy is continued in those patients until monthly audiograms demonstrate stabilization (80). Steroids are tapered over 8 weeks to a maintenance dose of 10 mg for a total treatment time of at least 6 months. Steroid doses tapered too rapidly can result in deterioration of hearing (54). In patients who fail the initial 4-week trial, steroids are tapered over 12 days.

Oral glucocorticoids are also useful for the prevention of hearing loss when used early in the course of Cogan syndrome, before substantial loss has occurred, as well as for treating the vasculitic manifestations of Cogan syndrome; in a series, 22% of patients treated with glucocorticoids died, compared to 67% of untreated patients (123). Immunomodulatory agents have been successfully used in glucocorticoid-unresponsive or -dependent patients to improve hearing, control vasculitis, and reduce relapses (108). Hearing fluctuations that occur late in the course of the disease respond to oral thiazide diuretics (44; 45). Aortic valve replacement can be lifesaving in patients with Cogan syndrome who have symptomatic aortitis and aortic insufficiency. Coronary artery bypass grafting has been used successfully in patients with coronary arteritis (123).

Intratympanic steroid administration. Human studies of intratympanic steroid administration for autoimmune sensorineural hearing loss have been limited to small uncontrolled case series (109; 91; 27; 80), and there has not been a good randomized controlled trial. Overall, it remains to be shown whether oral or intratympanic steroids are more efficacious or whether other distinct advantages exist for intratympanic steroid administration in autoimmune inner ear disease (120).

Immunosuppressive agents. Immunomodulatory agents, such as methotrexate, cyclophosphamide, azathioprine, or mycophenolate mofetil, may be used to supplant the glucocorticoids if the patient has had a positive response, although there are no high-quality studies supporting these agents. A retrospective analysis suggested that there remains a subset of patients with autoimmune hearing loss who are steroid nonresponders but show improvement with other cytotoxic medications (60). Although methotrexate showed promise in preliminary studies, in a randomized, double-blind, placebo-controlled study, it failed to show efficacy in preserving hearing recovery gained through prednisone therapy (43). A prospective open-label study of 17 patients with autoimmune hearing loss (five of whom had idiopathic autoimmune hearing loss) demonstrated audiometric improvement in 65% (11 of 17) at 12 months (73). Other reports have included azathioprine or mycophenolate mofetil as monotherapy, azathioprine combined with prednisone, or azathioprine combined with methotrexate (104; 47), but controlled studies have yet to be conducted. A review of one group’s 10-year experience with various nonbiological steroid-sparing agents in 16 patients with autoimmune hearing loss suggested a beneficial modest response (12). Given the relative paucity of data regarding this situation, use of these agents as first-line therapy cannot be recommended.

Monoclonal antibodies. A systematic review identified 12 studies investigating the impact of biological medications on hearing outcomes, including one randomized control trial, seven prospective cohort studies, and four retrospective cohort studies (04). Seven biological medications (ie, etanercept, infliximab, adalimumab, golimumab, rituximab, anakinra, and canakinumab) were identified for three unique molecular targets: TNF-alpha, CD20, and IL-1. The effects of biological medications in treating sensorineural hearing loss were highly variable without clear efficacy of any of these drugs, likely due in part to the rarity and multiple disease associations of autoimmune sensorineural hearing loss and also to the low quality of available studies (94; 72; 121; 80; 119; 120). Several medications seemed to alleviate symptoms associated with autoimmune sensorineural hearing loss, such as vertigo and tinnitus, but available data were not generally derived from controlled trials. Although biological medications may be promising therapeutics in autoimmune sensorineural hearing loss, the evidence for their utility is inconclusive. Large-scale randomized control trials are required to establish the efficacy of biological medications in treating hearing loss.

A 12-week blinded, placebo-controlled, randomized clinical trial of etanercept performed on 20 patients with autoimmune hearing loss revealed no statistically significant effect versus placebo (18).

Presently, there is insufficient evidence that any of the proposed alternative treatments can replace steroids as initial treatment. More studies are needed to test the value of biological therapies and how to manage steroid-resistant disease (103).

Auditory amplification. In those patients whose hearing loss is stabilized with therapy but does not return to premorbid levels, amplification devices are often employed.

Cochlear implants. When bilateral inner-ear disease leaves patients with severe or profound sensorineural hearing loss, cochlear implants successfully restore functional hearing (30). Although cochlear implant outcomes are generally excellent, the utility of cochlear implants may be adversely affected by intracochlear fibrosis intraoperatively, and the likelihood of implant performance fluctuation is related to ongoing inflammation in the cochlea (30).

Enoxaparin. Enoxaparin, a low-molecular-weight heparin, has shown promise in managing immune-related sensorineural hearing loss. Patients receiving enoxaparin twice daily demonstrated both a subjective and objective reduction in symptoms with no reported side effects (81).

Hyperbaric oxygen therapy. Hyperbaric oxygen therapy increases oxygen supply to ischemic cochlear structures in sensorineural hearing loss. The American Academy of Otolaryngology-Head and Neck Surgery recommends hyperbaric oxygen therapy as an optional therapy to be used within 3 months of sensorineural hearing loss onset. A meta-analysis including three randomized controlled trials and 16 nonrandomized studies, pooling 2401 patients, revealed that compared to medical therapy alone, hyperbaric oxygen therapy combined with medical therapy may be more efficacious for patients treated in a salvage setting, with severe-to-profound (greater than 70 dB HL) sensorineural hearing loss, and treated for a total treatment duration of 1200 minutes (110).

Follow-up. Patients who have successfully been managed and no longer have active symptoms should be followed closely. It is commonly advised to repeat audiometric testing over the course of a year (at 2 months, 6 months, and 12 months after the onset of hearing loss) to document recovery, guide aural rehabilitation (and hearing aid fitting and adjustment), and monitor for signs of relapse in the affected ear or development of hearing loss in the contralateral ear, which would warrant consideration of other diseases, such as Meniere disease.

Outcomes

Prognosis for patients who do not receive therapy is poorly categorized; the anticipated outcome is progressive hearing loss and, ultimately, sensorineural deafness. The prognosis for those patients with autoimmune hearing loss who receive and respond to therapy is usually good, with recovery of most, if not all, premorbid hearing. Patients with systemic manifestations of autoimmune disease at presentation generally have a lower response rate and those with isolated vestibular symptoms are usually responsive to steroids (20). The long-term outcomes in these patients are variable, with some patients requiring continued immunotherapy for several years to prevent relapses whereas others can complete treatment in a period of months (76; 48; 87; 42). The response rates to treatment are difficult to determine and the use of response to treatment as a diagnostic criterion artificially elevates the success of therapy. The consensus opinion is that spontaneous recovery almost always occurs within 2 weeks. Given that steroids have been reported to work best within 1 to 2 weeks of symptom onset with little benefit seen in cases over 4 weeks, there is a sense of urgency in making an appropriate diagnosis and instituting therapy to maximize successful outcomes.

Media

References

01: Adam M, Erkan AN, Arslan D, Leblebici B, Ozluoglu L, Nafiz Akman M. High-frequency sensorineural hearing loss in patients with ankylosing spondylitis: is it an extrarticuler feature of disease. Rheumatol Int 2008;28(5):413-7. PMID 17899090
02: Albayram MS, Wityk R, Yousem DM, Zinreich SJ. The cerebral angiographic findings in Cogan syndrome. AJNR Am J Neuroradiol 2001;22(4):751-4. PMID 11290493
03: Altermatt HJ, Gebbers JO, Muller C, Arnold W, Laissue JA. Human endolymphatic sac: evidence for a role in inner ear immune defence. ORL J Otorhinolaryngol Relat Spec 1990;52(3):143-8. PMID 1972790
04: Balouch B, Meehan R, Suresh A, et al. Use of biologics for treatment of autoimmune inner ear disease. Am J Otolaryngol 2022;43(5):103576. PMID 35963108
05: Ban JH, Jin SM. A clinical analysis of psychogenic sudden deafness. Otolaryngol Head Neck Surg 2006;134(6):970-4. PMID 16730540
06: Beca S, Elera-Fitzcarrald C, Saiz A, et al. Susac syndrome: description of a single-centre case series. J Clin Med 2022;11(21):6549. PMID 36362776
07: Berger P, Hillman M, Tabak M, Vollrath M. The lymphocyte transformation test with type II collagen as a diagnostic tool of autoimmune sensorineural hearing loss. Laryngoscope 1991;101:895-9. PMID 1865740
08: Berrocal JR, Ramirez-Camacho R. Sudden sensorineural hearing loss: supporting the immunologic theory. Ann Otol Rhinol Laryngol 2002;111(11):989-97. PMID 12450172
09: Bhatia S, Sharma D, Bahl VJ, et al. Susac syndrome: a rare cause of bilateral sensorineural hearing loss from North India: a case report with review of literature. Indian J Otolaryngol Head Neck Surg 2022;74(2):196-204. PMID 35813770
10: Billings PB, Keithley EM, Harris JP. Evidence linking the 68 kilodalton antigen identified in progressive sensorineural hearing loss patient sera with heat shock protein 70. Ann Otol Rhinol Laryngol 1995;104:181-8. PMID 7872600
11: Bovo R, Aimoni C, Martini A. Immune-mediated inner ear disease. Acta Otolaryngol 2006;126(10):1012-21. PMID 16923703
12: Broughton SS, Meyerhoff WE, Cohen SB. Immune-mediated inner-ear disease: 10-year experience. Semin Arthritis Rheum 2004;34(2):544-8. PMID 15505770
13: Bursztejn AC, Lesens O, Hansmann Y, et al. Cogan's syndrome revealed by haemorrhagic glairous diarrhoea. Presse Med 2005;34(4):289-92. PMID 15798548
14: Cavallasca JA, Nasswetter GG, Gutierrez DM, Bercellini EA, Brodsky AL. Sudden sensorineural hearing loss as a manifestation of primary antiphospholipid syndrome. Joint Bone Spine 2007;74(4):403-4. PMID 17587629
15: Cheng KC, Matsuoka H, Lee KM, et al. Proto-oncogene Raf-1 as an autoantigen in Meniere's disease. Ann Otol Rhinol Laryngol 2000;109(12 Pt 1):1093-8. PMID 11130817
16: Cheng S, da Cruz M. Sweet's disease and profound, bilateral, sensorineural hearing loss. J Laryngol Otol 2010;124(1):105-7. PMID 19840424
17: Ciorba A, Corazzi V, Bianchini C, et al. Autoimmune inner ear disease (AIED): a diagnostic challenge. Int J Immunopathol Pharmacol 2018;32:205873841880680. PMID 30376736
18: Cohen S, Shoup A, Weisman MH, Harris J. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol Neurotol 2005;26(5):903-7. PMID 16151336
19: Currie C, Wax JR, Pinette MG, Blackstone J, Cartin A. Cogan’s syndrome complicating pregnancy. J Matern Fetal Neonatal Med 2009;22(10):928-30. PMID 19488953
20: Dayal VS, Ellman M, Sweiss N. Autoimmune inner ear disease: clinical and laboratory findings and treatment outcome. J Otolaryngol Head Neck Surg 2008;37(4):591-6. PMID 19128599
21: Deliveliotou A, Moustakarias T, Argeitis J, Vaggos G, Vitoratos N, Hassiakos D. Successful full-term pregnancy in a woman with Cogan's syndrome: a case report. Clin Rheumatol 2007;26(12):2181-3. PMID 17574494
22: Dorr J, Radbruch H, Bock M, et al. Encephalopathy, visual disturbance and hearing loss-recognizing the symptoms of Susac syndrome. Nat Rev Neurol 2009;5(12):683-8. PMID 19953118
23: Durtette C, Hachulla E, Resche-Rigon M, et al. Cogan syndrome: characteristics, outcome and treatment in a French nationwide retrospective study and literature review. Autoimmun Rev 2017;16(12):1219-23. PMID 29037902
24: Erbek S, Erbek SS, Yilmaz S, Yucel E, Ozluoglu LN. Vestibular evoked myogenic potentials in Behcet's disease. Eur Arch Otorhinolaryngol 2008;265(11):1315-20. PMID 18365227
25: Faisal M, Barjas H, Alwassiti W, Omer W, Abdulla N. Sensory neural hearing loss in Behcet's disease successfully controlled with infliximab: case report and review of literature. Clin Case Rep 2022;10(10):e6457. PMID 36254147
26: Fugate JE, Smith JH, Claassen DO. Bilateral cochlear enhancement in Cogan syndrome. Neurology 2009;73(1):75. PMID 19564589
27: Garcia-Berrocal JR, Ibanez A, Rodriguez A, et al. Alternatives to systemic steroid therapy for refractory immune-mediated inner ear disease: A physiopathologic approach. Eur Arch Otorhinolaryngol 2006;263(11):977-82. PMID 16802138
28: Garcia Berrocal JR, Vargas JA, Vaquero M, Ramón y Cajal S, Ramírez-Camacho RA. Cogan's syndrome: an oculo-audiovestibular disease. Postgrad Med J 1999;75(883):262-4. PMID 10533627
29: Gluth MB, Baratz KH, Matteson EL, Driscoll CL. Cogan syndrome: a retrospective review of 60 patients throughout a half century. Mayo Clin Proc 2006;81(4):483-8. PMID 16610568
30: Goh X, Muzaffar J, Bance M. Cochlear implantation in systemic autoimmune disease. Curr Opin Otolaryngol Head Neck Surg 2022;30(5):291-7. PMID 36004773
31: Goldbach-Mansky R. Current status of understanding the pathogenesis and management of patients with NOMID/CINCA. Curr Rheumatol Rep 2011;13(2):123-31. PMID 21538043
32: Goodall AF, Siddiq MA. Current understanding of the pathogenesis of autoimmune inner ear disease: a review. Clin Otolaryngol 2015;40(5):412-9. PMID 25847404
33: Greco A, Fusconi M, Gallo A, Marinelli C, Macri GF, De Vincentiis M. Sudden sensorineural hearing loss: an autoimmune disease. Autoimmun Rev 2011;10(12):756-61. PMID 21619944
34: Greene JJ, Keefe MW, Harris JP, Matsuoka AJ. Paraneoplastic syndrome: a masquerade of autoimmune inner ear disease. Otol Neurotol 2015;36(1):e3-10. PMID 25427223
35: Gur C, Lalazar G, Raphaeli G, Gilon D, Ben-Chetrit E. Mitral stenosis presenting with acute hearing loss. PLoS Med 2006;3(6):e233. PMID 16768545
36: Hammami MB, Eggers SDZ, Madhavan A, Montalvo MJ, Pittock SJ, Dubey D. Paraneoplastic cochleovestibulopathy: clinical presentations, oncological and serological associations. J Neurol Neurosurg Psychiatry 2021;92(11):1181-5. PMID 34285066
37: Harris JP. Immunology of the inner ear: evidence of local antibody production. Ann Otol Rhinol Laryngol 1984;93(2 Pt 1):157-62. PMID 6712089
38: Harris JP. Experimental autoimmune sensorineural hearing loss. Laryngoscope 1987;97:63-76. PMID 3796177
39: Harris JP, Fukuda S, Keithley EM. Spiral modiolar vein: its importance in inner ear inflammation. Acta Otolaryngol 1990;110(5-6):357-65. PMID 2284910
40: Harris JP, Keithley EM. Inner ear inflammation and round window otosclerosis. Am J Otol 1993;14(2):109-12. PMID 8503480
41: Harris JP, Ryan AF. Immunobiology of the inner ear. Am J Otolaryngol 1984;5(6):418-25. PMID 6400717
42: Harris JP, Ryan AF. Fundamental immune mechanisms of the brain and inner ear. Otolaryngol Head Neck Surg 1995;112(6):639-53. PMID 7777346
43: Harris JP, Weisman MH, Derebery JM, et al. Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA 2003;290(14):1875-83. PMID 14532316
44: Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci AS. Cogan's syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature. Medicine (Baltimore) 1980;59(6):426-41. PMID 6969345
45: Haynes BF, Pikus A, Kaiser-Kupfer MI, Fauci AS. Successful treatment of sudden hearing loss in Cogan's syndrome with corticosteroids. Arthritis Rheum 1981;24(3):501-3. PMID 7213429
46: Heman-Ackah SE, Jabbour N, Huang TC. Asymmetric sudden sensorineural hearing loss: is all this testing necessary. J Otolaryngol Head Neck Surg 2010;39(5):486-90. PMID 20828509
47: Huang KH, Lin HC, Lin CD, Wu PC. Relapsing autoimmune inner ear disease with significant response to methotrexate and azathioprine combination therapy: A case report and mini literature review. Medicine (Baltimore) 2023;102(23):e33889. PMID 37335659
48: Hughes GB, Barna BP, Calabrese LH, Kinney SE, Nalepa NJ. Clinical diagnosis of immune inner-ear disease. Laryngoscope 1988;98:251-3. PMID 3343873
49: Ianuale C, Cadoni G, De Feo E, et al. A systematic review and meta-analysis of the diagnostic accuracy of anti-heat shock protein 70 antibodies for the detection of autoimmune hearing loss. Otol Neurotol 2013;34(2):214-9. PMID 23295728
50: Jarius S, Kleffner I, Dorr J, et al. Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study. J Neuroinflammation 2014;11:46. PMID 24606999
51: Jeong J, Lim H, Lee K, Hong CE, Choi HS. High risk of sudden sensorineural hearing loss in several autoimmune diseases according to a population-based national sample cohort study. Audiol Neurotol 2019;24(5):224-30. PMID 31550708
52: Joliat T, Bernstein J, Cho JS, et al. Antibodies against a 30 kilodalton cochlear protein and type II and IX collagens in the serum of patients with inner ear disease. Ann Otol Rhinol Laryngol 1992;101:1000-6. PMID 1463290
53: Kanzaki J, Inoue Y, Ouchi T. Immunologic findings of serological tests in steroid-responsive sensorineural hearing loss. Acta Otolaryngol Suppl 1994b;514:66-9. PMID 7915487
54: Kanzaki J, Ouchi T. Steroid-responsive bilateral sensorineural hearing loss and immune complexes. Arch Otolaryngol 1981;230:5-9. PMID 7011284
55: Karunaratne D, Karunaratne N. ENT manifestations of celiac disease: a scholarly review. Ear Nose Throat J 2022;101(9):600-5. PMID 33155859
56: Kessel A, Vadasz Z, Toubi E. Cogan syndrome--pathogenesis, clinical variants and treatment approaches. Autoimmun Rev 2014;13(4-5):351-4. PMID 24418297
57: Koda H, Kimura Y, Iino Y, Eishi Y, Murakami Y, Kitamura K. Bilateral sudden deafness caused by diffuse metastatic leptomeningeal carcinomatosis. Otol Neurotol 2008;29(5):727-9. PMID 18451746
58: Kuemmerle-Deschner JB, Koitschev A, Ummenhofer K, et al. Hearing loss in Muckle-Wells syndrome. Arthritis Rheum 2013;65(3):824-31. PMID 23440695
59: Kusakari C, Hozawa K, Koike S, Kyogoku M, Takasaka T. MRL/MP-lpr/lpr mouse as a model of immune-induced sensorineural hearing loss. Ann Otol Rhinol Laryngol Suppl 1992;157:82-6. PMID 1416659
60: Lasak JM, Sataloff RT, Hawkshaw M, Carey TE, Lyons KM, Spiegel JR. Autoimmune inner ear disease: steroid and cytotoxic drug therapy. Ear Nose Throat J 2001;80(11):808-11, 815-6, 818 passim. PMID 11816893
61: Lee CW, Walters H, Steele H, Stafford F. Rapidly progressive hearing loss occurring over weeks: review of differential diagnoses. J Laryngol Otol 2022;136(8):775-82. PMID 34641994
62: Li X, Cao Z, Chen F, Yang D, Zhao F. Sensorineural hearing loss in autoimmune diseases: a systematic review and meta-analysis. J Int Adv Otol 2023;19(4):277-82. PMID 37528591
63: Li X, Chen W, Yi H, et al. The association between the levels of autoimmune related indicators and clinical condition in sudden deafness patients. Ann Palliat Med 2021;10(10):10535-41. PMID 34763500
64: Lin DW, Trune DR. Breakdown of stria vascularis blood-labyrinth barrier in C3H/lpr autoimmune disease mice. Otolaryngol Head Neck Surg 1997;117(5):530-4. PMID 9374179
65: Lin HC, Chao PZ, Lee HC. Sudden sensorineural hearing loss increases the risk of stroke: a 5-year follow-up study. Stroke 2008;39(10):2744-8. PMID 18583554
66: Ma Y, Sun Q, Zhang K, Bai L, Du L. High level of IgE in acute low-tone sensorineural hearing loss: a predictor for recurrence and Meniere disease transformation. Am J Otolaryngol 2021;42(2):102856. PMID 33429184
67: Maciaszczyk K, Waszczykowska E, Pajor A, Bartkowiak-Dziankowska B, Durko T. Hearing organ disorders in patients with systemic sclerosis. Rheumatol Int 2011;31(11):1423-8. PMID 20461385
68: Magen E, Blum I, Waitman DA, Kahan N, Forer B. Autoimmune inner ear disease among patients with selective IgA deficiency. Audiol Neurootol 2021;26(2):127-34. PMID 33311024
69: Mancini P, Atturo F, Di Mario A, et al. Hearing loss in autoimmune disorders: Prevalence and therapeutic options. Autoimmune Reviews 2018;17(7):644-52. PMID 29729446
70: Marchioro HZ, de Castro CCS, Chiesorin AST, Bindi EW, Jiacomini IG, Miot HA. Prevalence of immune-mediated inner ear disease in non-segmental vitiligo: A cross-sectional study. Autoimmun Rev 2023;22(7):103336. PMID 37062442
71: Matsuoka H, Cheng KC, Krug MS, Yazawa Y, Yoo TJ. Murine model of autoimmune hearing loss induced by myelin protein P0. Ann Otol Rhinol Laryngol 1999;108(3):255-64. PMID 10086618
72: Matteson EL, Choi HK, Poe DS, et al. Etanercept therapy for immune-mediated cochleovestibular disorders: a multi-center, open-label, pilot study. Arthritis Rheum 2005;53(3):337-42. PMID 15934127
73: Matteson EL, Fabry DA, Facer GW, et al. Open trial of methotrexate as treatment for autoimmune hearing loss. Arthritis Rheum 2001;45(2):146-50. PMID 11324778
74: Mazlumzadeh M, Lowe VJ, Mullan BP, Fabry DA, McDonald TJ, Matteson EL. The utility of positron emission tomography in the evaluation of autoimmune hearing loss. Otol Neurotol 2003;24(2):201-4. PMID 12621332
75: McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol Rhinol Laryngol 1979;88:585-9. PMID 496191
76: McCabe BF. Autoimmune inner ear disease: clinical varieties of presentation. In: Veldman JE, McCabe BF, editors. Otoimmunology. Amsterdam: Kugler, 1987:143-8.
77: McDonald TJ, Vollersten RS, Younge BR. Cogan's syndrome: audiovestibular involvement and prognosis in 18 patients. Laryngoscope 1985;95:650-4. PMID 3873592
78: McMenomey SO, Russell NJ, Morton JI, Trune DR. Stria vascularis ultrastructural pathology in the C3H/lpr autoimmune strain mouse: a potential mechanism for immune-related hearing loss. Otolaryngol Head Neck Surg 1992;106(3):288-95. PMID 1534162
79: Migliori G, Battisti E, Pari M, Vitelli N, Cingolani C. A shifty diagnosis: Cogan's syndrome. A case report and review of the literature. Acta Otorhinolaryngol Ital 2009;29(2):108-13. PMID 20111622
80: Mijovic T, Zeitouni A, Colmegna I. Autoimmune sensorineural hearing loss: the otology-rheumatology interface. Rheumatology (Oxford) 2013;52(5):780-9. PMID 23436581
81: Mora R, Jankowska B, Passali GC, et al. Sodium enoxaparin treatment of sensorineural hearing loss: an immune-mediated response. Int Tinnitus J 2005;11:38-42. PMID 16419687
82: Naarendorp M, Spiera H. Sudden sensorineural hearing loss in patients with systemic lupus erythematosus or lupus-like syndromes and antiphospholipid antibodies. J Rheumatol 1998;25(3):589-92. PMID 19324520
83: Nair TS, Kozma KE, Hoefling NL, et al. Identification and characterization of choline transporter-like protein 2, an inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced hearing loss. J Neurosci 2004;24(7):1772-9. PMID 14973250
84: Nair TS, Prieskorn DM, Miller JM, Mori A, Gray J, Carey TE. In vivo binding and hearing loss after intracochlear infusion of KHRI-3 antibody. Hear Res 1997;107:93-101. PMID 9165350
85: Nariuchi H, Sone M, Tago C, Kurata T, Saito K. Mechanism of hearing disturbance in an autoimmune model mouse NZB/kl. Acta Otolaryngol Suppl 1994;514:127-31. PMID 8073875
86: Nasrollahi T, Borrelli M, Lin HW, Djalilian HR. Cogan syndrome: a case study and review of the literature. Ear Nose Throat J 2023;102(9_suppl):35S-39S. PMID 37551701
87: Nelson RA. Sensorineural hearing loss: medical therapy. In: Gates GA, editor. Current therapy in otolaryngology- head & neck surgery. 5th ed. St. Louis: Mosby, 1994:56-7.
88: Okawa Y, Ihara K. Sensorineural hearing loss in Sjögren's syndrome. Int J Mol Sci 2022;23(19):11181. PMID 36232483
89: Paraschou V, Chaitidis N, Papadopoulou Z, Theocharis P, Siolos P, Festas C. Association of systemic lupus erythematosus with hearing loss: a systemic review and meta-analysis. Rheumatol Int 2021;41(4):681-9. PMID 33533981
90: Paraschou V, Partalidou S, Siolos P, Papadopoulou Z, Chaitidis N. Prevalence of hearing loss in patients with Sjögren syndrome: a systematic review and meta-analysis. Rheumatol Int 2023;43(2):233-24. PMID 36305918
91: Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids: an animal study followed by clinical application. Laryngoscope 1999;109(7 Pt 2):1-17. PMID 10399889
92: Peppel K, Crawford D, Beutler B. A tumor necrosis factor (TNF) receptor-IgG heavy chain chimeric protein as a bivalent antagonist of TNF activity. J Exp Med 1991;174(6):1483-9. PMID 1660525
93: Psillas G, Binos P, Dimas GG, Daniilidis M, Constantinidis J. Human leukocyte antigen (HLA) influence on prognosis of autoimmune hearing loss. Audiol Res 2021;11(1):31-7. PMID 33503870
94: Rahman MU, Poe DS, Choi HK. Etanercept therapy for immune-mediated cochleovestibular disorders: preliminary results in a pilot study. Otol Neurotol 2001;22(5):619-24. PMID 11568668
95: Rajapakse A, O'Leary C, Gundelach R, Deva R, O'Byrne K. Unilateral autoimmune inner ear disease in a patient with lung cancer treated with nivolumab. Oxf Med Case Reports 2020. PMID 32995031
96: Ramani PK, Grigorian F, Lightle H, Joshi SV. Paediatric Cogan syndrome masquerading as IgA vasculitis. Mod Rheumatol Case Rep 2023;8(1):229-36. PMID 37902167
97: Rao V, Gallagher M, Bhat P, Foster CS. Sensorineural hearing loss in a patient with HLA-B27 sclero-uveitis. Br J Ophthalmol 2008;92(3):425. PMID 17537786
98: Rauch SD. Clinical practice. Idiopathic sudden sensorineural hearing loss. N Engl J Med 2008;359(8):833-40. PMID 18716300
99: Renna R, Plantone D, Batocchi AP. Teaching neuroimages: a case of hearing loss in a paraneoplastic syndrome associated with anti-Hu antibody. Neurology 2012;79(15):e134. PMID 23045521
100: Ribeiro R, Serôdio JF, Amaral MC, et al. Sensorineural hearing loss and systemic autoimmune disease: the experience of a systemic immune-mediated diseases unit. Cureus 2021;13(3):e14075. PMID 33903837
101: Roskal-Wałek J, Mackiewicz J, Wypchło Ł, Biskup M, Odrobina D. Susac's syndrome: the crucial role of imaging tests for proper diagnosis. Ann Agric Environ Med 2022;29(2):190-200. PMID 35767750
102: Rucklova K, von Kalle T, Koitschev A, et al. Paediatric Cogan´s syndrome - review of literature, case report and practical approach to diagnosis and management. Pediatr Rheumatol Online J 2023;21(1):54. PMID 37291629
103: Sakano H, Harris JP. Emerging options in immune-mediated hearing loss. Laryngoscope Investig Otolaryngol 2018;4(1):102-8. PMID 30828626
104: Saracaydin A, Katircioglu S, Katircioglu S, Karatay MC. Azathioprine in combination with steroids in the treatment of autoimmune inner-ear disease. J Int Med Res 1993;21(4):192-6. PMID 8112477
105: Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM. Tumor necrosis factor-alpha, an initiator, and etanercept, an inhibitor of cochlear inflammation. Laryngoscope 2002;112(9):1627-34. PMID 12352677
106: Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM. Proinflammatory cytokine expression in the endolymphatic sac during inner ear inflammation. J Assoc Res Otolaryngol 2003;4(2):139-47. PMID 12943369
107: Sauvaget E, Kici S, Petelle B, et al. Vertebrobasilar occlusive disorders presenting as sudden sensorineural hearing loss. Laryngoscope 2004;114(2):327-32. PMID 14755213
108: Shamriz O, Tal Y, Gross M. Autoimmune inner ear disease: immune biomarkers, audiovestibular aspects, and therapeutic modalities of Cogan's syndrome. J Immunol Res 2018;2018:1498640. PMID 29850616
109: Silverstein H, Choo D, Rosenberg SI, Kuhn J, Seidman M, Stein I. Intratympanic steroid treatment of inner ear disease and tinnitus (preliminary report). Ear Nose Throat J 1996;75(8):468-71. PMID 8828271
110: Singh A, Irugu DVK. Sudden sensorineurial hearing loss – a contemporary review of management issues. J Otol 2020;15(2):67-73. PMID 32330269
111: Srichawla BS. Susac syndrome with livedo reticularis: pathogenesis and literature review. Cureus 2022;14(7):e27352. PMID 36046280
112: Suman NS, Poovaiah PP, Rangarajan A, et al. Cervical and ocular vestibular evoked myogenic potential recovery in Susac syndrome: a case report. Am J Audiol 2022;31(4):1059-66. PMID 36356212
113: Suslu N, Yilmaz T, Gursel B. Utility of anti-HSP 70, TNF-alpha, ESR, antinuclear antibody, and antiphospholipid antibodies in the diagnosis and treatment of sudden sensorineural hearing loss. Laryngoscope 2009;119(2):341-6. PMID 19160386
114: Suzuki M, Harris JP. Expression of intercellular adhesion molecule-1 during inner ear inflammation. Ann Otol Rhinol Laryngol 1995;104:69-75. PMID 7530436
115: Tarney CM, Wilson K, Sewell MF. Cogan syndrome in pregnancy. Obstet Gynecol 2014;124(2 Pt 2 Suppl 1):428-31. PMID 25004327
116: Tomiyama S, Harris JP. The role of endolymphatic sac inner ear immunity. Acta Otolaryngol 1987;103(3-4):182-8. PMID 21449640
117: Trune DR, Kempton JB, Kessi M. Aldosterone (mineralocorticoid) equivalent to prednisolone (glucocorticoid) in reversing hearing loss in MRL/MpJ-Fas1pr autoimmune mouse. Laryngoscope 2000;110:1902-6. PMID 11081607
118: Vambutas A, Davia DV. Biologics for immune-mediated sensorineural hearing loss. Otolaryngol Clin North Am 2021;54(4):803-13. PMID 34119332
119: Vambutas A, Lesser M, Mullooly V, et al. Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease. J Clin Invest 2014;124(9):4115-4122. PMID 25133431
120: Vambutas A, Pathak S. AAO: Autoimmune and auto inflammatory (disease) in otology: what is new in immune-mediated hearing loss. Laryngoscope Investig Otolaryngol 2016(15):110-5. PMID 27917401
121: Van Wijk F, Staecker H, Keithley E, Lefebvre PP. Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol Neurootol 2006;11(6):357-65. PMID 16988499
122: Veldman J, Roord JJ, O'Connor AF, Shea JJ. Autoimmunity and inner ear disorders: an immune complex mediated sensorineural hearing loss. Laryngoscope 1984;94:501-7. PMID 6231440
123: Vollertsen RS, McDonald TJ, Younge BR, Banks PM, Stanson AW, Ilstrup DM. Cogan's syndrome: 18 cases and a review of the literature. Mayo Clin Proc 1986;61(5):344-61. PMID 3486332
124: Volta U, Ferri GG, De Giorgio R, et al. Sensorineural hearing loss and celiac disease: a coincidental finding. Can J Gastroenterol 2009;23(8):531-5. PMID 19668795
125: Wang JG, Xie QB, Yang NP, Yin G. Primary antiphospholipid antibody syndrome: a case with bilateral sudden sensorineural hearing loss. Rheumatol Int 2009;29(4):467-8. PMID 18810450
126: Wang X, Truong T, Billings PB, Harris JP, Keithley EM. Blockage of immune-mediated inner ear damage by etanercept. Otol Neurotol 2003;24(1):52-7. PMID 12544029
127: Wang Y, Tang S, Shao C, Liu Y. Cogan's syndrome is more than just keratitis: a case-based literature review. BMC Ophthalmol 2023;23(1):212. PMID 37173630
128: Wong J, Leach L, Chen-Xu M, Truman L. Rare case of sudden onset sensorineural hearing loss in a patient diagnosed with sarcoidosis. BMJ Case Rep 2022;15(7):e248969. PMID 35820728
129: Wong ML, Young JS, Nilaver G, Morton JI, Trune DR. Cochlear IgG in the C3H/lpr autoimmune strain mouse. Hear Res 1992;59:93-100. PMID 1629052
130: Yeo SW, Gottschlich S, Harris JP, Keithley EM. Antigen diffusion from the perilymphatic space of the cochlea. Laryngoscope 1995;105(6):623-8. PMID 7769947
131: Yeom K, Gray J, Nair TS, et al. Antibodies to HSP-70 in normal donors and autoimmune hearing loss patients. Laryngoscope 2003;113(10):1770-6. PMID 14520104
132: Yoo TJ. Etiopathogenesis of Meniere's disease: a hypothesis. Ann Otol Rhinol Laryngol 1984;113:6-12. PMID 6207756
133: Yoo TJ, Shea J Jr, Ge X, et al. Presence of autoantibodies in the sera of Meniere's disease. Ann Otol Rhinol Laryngol 2001;110(5 Pt 1):425-9. PMID 11372925
134: Yoo TJ, Tanaka H, Kwon SS, et al. B-tubulin as an autoantigen for autoimmune inner ear disease. In: Sterkers O, Ferrary E, Daumann R, Sauvage JP, Tran Ba Huy R, editors. Meniere's Disease 1999 – Update. Proceedings of the 4th International Symposium on Meniere's Disease, Paris. The Hague, Netherlands: Kugler Publications, 2000:529-35.
135: Yoo TJ, Tomoda K, Hernandez AD. Type II collagen-induced autoimmune inner ear lesions in guinea pigs. Ann Otol Rhinol Laryngol 1984;93(Suppl 113):3-5. PMID 6435495
136: Yoon TH, Paparella MM, Schachern PA. Systemic vasculitis: a temporal bone histopathologic study. Laryngoscope 1989;99(6 Pt 1):600-9. PMID 2566880
137: Yuen E, Fried J, Nguyen SA, Rizk HG, Ward C, Meyer TA. Hearing loss in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Lupus 2021;30(6):937-45. PMID 33645314
138: Zarachi A, Pelechas E, Tsikou A, et al. Immune-mediated inner ear disease associated with type 1 autoimmune hepatitis: a challenging coexistence. Mediterr J Rheumatol 2022;33(3):349-60. PMID 36531431

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Douglas J Lanska MD MS MSPH

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile

Former Authors

Wayne S Quirk PhD
Timothy D Doerr MD
Rebecca Jacobs RN
Nadera Sweiss MD
Kavitta B Allem MD
Vladimir M Liarski MD
Richard M Keating MD
Megan Lynch DO
Monica Budianu MD
Michael Crone DO
Francesc Graus MD PhD

Patient Profile

Age range of presentation: 6 to 65+ years
Sex preponderance: female>male, >2:1
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Conductive and sensorineural hearing loss: H90
ICD-11: Acquired conductive hearing loss: AB51.0

Acquired mixed conductive and sensorineural hearing loss: AB51.2

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Autoimmune sensorineural hearing loss

Associated Disorders

Ankylosing spondylitis
Behçet disease
Cogan syndrome
Polyarteritis nodosa
Progressive system sclerosis
- Relapsing polychondritis
- Rheumatoid arthritis
- Sjögren syndrome
- Systemic lupus erythematosus
- Takayasu arteritis
- Temporal arteritis
- Vogt-Koyanagi-Harada syndrome
- Wegener granulomatosis
- patients with Hu antibodies
- small cell lung cancer
- sensory neuronopathy
- patients with kelch-like protein 11 (KLHL11) antibodies
- brainstem encephalitis
- testicular seminomas

Differential Diagnosis

other forms of sensorineural hearing loss
sudden deafness
Meniere disease
cochlear otosclerosis
syphilitic deafness
- Cogan syndrome
- Susac syndrome
- noise-induced hearing loss
- ototoxic hearing loss
- acoustic tumors
- psychogenic hearing loss
- cerebrovascular hearing loss
- enlarged vestibular aqueduct syndrome
- endocrine hypertension
- Charcot-Marie-Tooth disease

Also Relevant

Hearing loss in infants and children
Noise-induced hearing loss
Sporadic schwannomas and neurofibromas
Sensorineural hearing loss
Sudden deafness
- Vestibular schwannoma

Clinical Categories

Neuroimmunology

Autoimmune sensorineural hearing loss …

Autoimmune sensorineural hearing loss

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Clinical vignette

Biological basis

Etiology and pathogenesis

Table 1. Diseases Associated with Autoimmune Sensorineural Hearing Loss

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Giant cell arteritis

Chronic inflammatory demyelinating polyradiculoneuropathy

Autoimmune autonomic neuropathy

HTLV-1 associated myelopathy

Myositis and cancer

Paraneoplastic retinopathy

Autoimmune sensorineural hearing loss

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Clinical vignette

Biological basis

Etiology and pathogenesis

Table 1. Diseases Associated with Autoimmune Sensorineural Hearing Loss

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Media

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Giant cell arteritis

Chronic inflammatory demyelinating polyradiculoneuropathy

Autoimmune autonomic neuropathy

HTLV-1 associated myelopathy

Myositis and cancer

Paraneoplastic retinopathy

This is an article preview.
Start a Free Account
to access the full version.