Skip to main content Skip to journal navigation menu Skip to site footer
contact@ukscip.com
Review

Autoimmune Inner Ear Disease at the Otology–Rheumatology Interface: Mechanisms, Diagnosis and Treatment

Xiao Yu ORCID ,  Fei Li ORCID ,  Xing Wang ORCID ,  Yibin Chen ORCID ,  Hongfei Lou ORCID ,  Minrui Liang ORCID ,  Huawei Li ORCID ,  Wenyan Li ORCID
    Received: 24 September 2026; Revised: 13 October 2026; Accepted: 29 October 2026; Published: 3 November 2026

    Abstract

    Autoimmune inner ear disease (AIED) encompasses immune-mediated sensorineural hearing loss occurring either in isolation or in association with systemic autoimmune, vasculitic or autoinflammatory disorders. Its diagnosis remains difficult because progressive or fluctuating hearing loss is not specific to immune-mediated cochlear injury, and no disease-specific biomarker has been validated. This review examines AIED from the combined perspectives of otology and rheumatology, focusing on systemic disease associations, pathogenic mechanisms, diagnostic limitations and therapeutic evidence. Experimental studies implicate blood–labyrinth barrier disruption, inflammatory cell recruitment, adaptive immune responses and microvascular injury, although direct confirmation of these mechanisms in primary human AIED remains limited. Clinically, serial audiometry, exclusion of alternative causes and targeted assessment for systemic inflammatory disease remain central to evaluation. Corticosteroids are commonly used as initial treatment, but therapeutic responsiveness does not establish the diagnosis. Evidence supporting conventional immunosuppressants and biologic agents remains insufficient for routine application in primary AIED. We distinguish findings obtained directly from patients with suspected AIED from evidence derived from related systemic disorders and experimental models, and identify the methodological priorities needed to improve diagnostic classification and treatment evaluation.

    Keywords

    References

    1. 1.Karayay, B.; Olze, H.; Szczepek, A.J. Mammalian Inner Ear-Resident Immune Cells-A Scoping Review. Cells 2024, 13, 1528.
    2. 2.Keithley, E.M. Inner ear immunity. Hear. Res. 2022, 419, 108518.
    3. 3.Ruckenstein, M.J. Autoimmune inner ear disease. Curr. Opin. Otolaryngol. Head Neck Surg. 2004, 12, 426–430.
    4. 4.Das, S.; Bakshi, S.S.; Seepana, R. Demystifying autoimmune inner ear disease. Eur. Arch. Otorhinolaryngol. 2019, 276, 3267–3274.
    5. 5.Norton, E.W.; Cogan, D.G. Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms; a long-term follow-up. AMA Arch. Ophthalmol. 1959, 61, 695–697.
    6. 6.Lehnhardt, E. Sudden hearing disorders occurring simultaneously or successively on both sides. Z. Laryngol. Rhinol. Otol. 1958, 37, 1–16.
    7. 7.McCabe, B.F. Autoimmune sensorineural hearing loss. Ann. Otol. Rhinol. Laryngol. 1979, 88, 585–589.
    8. 8.Ciorba, A.; Corazzi, V.; Bianchini, C.; et al. Autoimmune inner ear disease (AIED): A diagnostic challenge. Int. J. Immunopathol. Pharmacol. 2018, 32.
    9. 9.Vambutas, A.; Pathak, S. AAO: Autoimmune and Autoinflammatory (Disease) in Otology: What is New in Immune-Mediated Hearing Loss. Laryngoscope Investig. Otolaryngol. 2016, 1, 110–115.
    10. 10.Mijovic, T.; Zeitouni, A.; Colmegna, I. Autoimmune sensorineural hearing loss: the otology-rheumatology interface. Rheumatology (Oxford) 2013, 52, 780–789.
    11. 11.Creber, N.; Bance, M. Primary and secondary autoimmune disorders and hearing loss. Curr. Opin. Otolaryngol. Head Neck Surg. 2025, 33, 286–292.
    12. 12.Psillas, G.; Dimas, G.G.; Savopoulos, C.; et al. Autoimmune Hearing Loss: A Diagnostic Challenge. J. Clin. Med. 2022, 11, 4601.
    13. 13.Matsuoka, A.J.; Harris, J.P. Autoimmune inner ear disease: a retrospective review of forty-seven patients. Audiol. Neurootol. 2013, 18, 228–239.
    14. 14.Lobo, D.R.; García-Berrocal, J.R.; Ramírez-Camacho, R. New prospects in the diagnosis and treatment of immune-mediated inner ear disease. World J. Methodol. 2014, 4, 91–98.
    15. 15.Oz, R.S.; Gluth, M.; Tesher, M.S. Pediatric Autoimmune Inner Ear Disease: A Rare, But Treatable Condition. Pediatr. Ann. 2019, 48, e391–e394.
    16. 16.Varuni, P.; Mahabaleshwar, M.; Neethu, P.; et al. From silence to sound – a case of autoimmune ear disease. Ro. J. Rheumatol. 2024, 33, 59–62.
    17. 17.Arunthanachaikul, T.; Osothsinlp, S.; Nivatwongs, S.; et al. Prevalence and Intriguing Clinical Profiles of Autoimmune Inner Ear Diseases in Sudden Sensorineural Hearing Loss. Otol. Neurotol. 2025, 46, 215–220.
    18. 18.Psillas, G.; Dimas, G.G.; Daniilidis, M.; et al. Audiological Patterns in Patients with Autoimmune Hearing Loss. Audiol. Neurootol. 2022, 27, 336–346.
    19. 19.Hu, B.H.; Zhang, C.; Frye, M.D. Immune cells and non-immune cells with immune function in mammalian cochleae. Hear. Res. 2018, 362, 14–24.
    20. 20.Goodall, A.F.; Siddiq, M.A. Current understanding of the pathogenesis of autoimmune inner ear disease: a review. Clin. Otolaryngol. 2015, 40, 412–419.
    21. 21.Mahshid, S.S.; Higazi, A.M.; Ogier, J.M.; et al. Extracellular Biomarkers of Inner Ear Disease and Their Potential for Point-of-Care Diagnostics. Adv. Sci. (Weinh) 2022, 9, e2104033.
    22. 22.St Peter, M.; Warnecke, A.; Staecker, H. A Window of Opportunity: Perilymph Sampling from the Round Window Membrane Can Advance Inner Ear Diagnostics and Therapeutics. J. Clin. Med. 2022, 11, 316.
    23. 23.Zhuang, P.; Phung, S.; Warnecke, A.; et al. Isolation of sensory hair cell specific exosomes in human perilymph. Neurosci. Lett. 2021, 764, 136282.
    24. 24.Chiot, A.; Felgner, M.J.; Brownell, D.; et al. Single-cell, spatial, and fate-mapping analyses uncover niche dependent diversity of cochlear myeloid cells. bioRxiv 2024. DOI: https://doi.org/10.1101/2024.10.30.621184
    25. 25.Miwa, T.; Okano, T. Role of Inner Ear Macrophages and Autoimmune/Autoinflammatory Mechanisms in the Pathophysiology of Inner Ear Disease. Front. Neurol. 2022, 13, 861992.
    26. 26.van der Valk, W.H.; Steinhart, M.R.; Zhang, J.; et al. Building inner ears: recent advances and future challenges for in vitro organoid systems. Cell Death Differ. 2021, 28, 24–34.
    27. 27.Shah, S.; Chidarala, S.; Jeong, S.; et al. Secondary autoimmune immune ear disease (AIED): a systematic review and meta-analysis on vestibular manifestations of systemic autoimmune and inflammatory disorders. Clin. Rheumatol. 2023, 42, 2747–2759.
    28. 28.Mancini, P.; Atturo, F.; Di Mario, A.; et al. Hearing loss in autoimmune disorders: Prevalence and therapeutic options. Autoimmun. Rev. 2018, 17, 644–652.
    29. 29.Oghalai, J.S.; Ramirez, A.L.; Hegarty, J.L.; et al. Chronic pachymeningitis presenting as asymmetric sensorineural hearing loss. Otol. Neurotol. 2004, 25, 616–621.
    30. 30.Muelleman, T.; Kavookjian, H.; Lin, J.; et al. Hypertrophic Pachymeningitis of the Internal Auditory Canal: A Rare Case of Unilateral Sudden Sensorineural Hearing Loss. Ann. Otol. Rhinol. Laryngol. 2018, 127, 649–652.
    31. 31.Mahmoud, A.; Dubey, D.; Goonetilleke, A.; et al. Paraneoplastic KLHL11 encephalitis presenting with progressive tinnitus, hearing loss and ataxia. Pract. Neurol. 2025, 25, 443–447.
    32. 32.Dubey, D.; Wilson, M.R.; Clarkson, B.; et al. Expanded Clinical Phenotype, Oncological Associations, and Immunopathologic Insights of Paraneoplastic Kelch-like Protein-11 Encephalitis. JAMA Neurol. 2020, 77, 1420–1429.
    33. 33.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, 349–360.
    34. 34.Hizli, S.; Karabulut, H.; Ozdemir, O.; et al. Sensorineural hearing loss in pediatric celiac patients. Int. J. Pediatr. Otorhinolaryngol. 2011, 75, 65–68.
    35. 35.De Luca, P.; Scarpa, A.; Ralli, M.; et al. Immune-Mediated Association Between Celiac Disease and Sensorineural Hearing Loss: A Systematic Narrative Review. Turk. J. Gastroenterol. 2022, 33, 273–279.
    36. 36.Yazıcı, A.; Yıldırım, A.E.; Konduk, B.T. Does celiac disease cause autoimmune sensorineural hearing loss? Turk. J. Gastroenterol. 2019, 30, 776–781.
    37. 37.Arduc, A.; Isık, S.; Allusoglu, S.; et al. Evaluation of hearing functions in patients with euthyroid Hashimoto's thyroiditis. Endocrine 2015, 50, 708–714.
    38. 38.Topaloğlu, Ö.; Şahin, B. Hearing Impairment and Audiological Alterations in Euthyroid Hashimoto's Thyroiditis. ORL J. Otorhinolaryngol. Relat. Spec. 2022, 84, 238–246.
    39. 39.Mirmosayyeb, O.; Naderi, M.; Raeisi, S.; et al. Hearing loss among patients with multiple sclerosis (PwMS): A systematic review and meta-analysis. Mult. Scler. Relat. Disord. 2022, 62, 103754.
    40. 40.Kim, I.; Kim, H. Management of Sudden Sensorineural Hearing Loss in Multiple Sclerosis: A Comprehensive Case Report of a Patient with Bilateral Loss and Literature Review. Life 2024, 14, 83.
    41. 41.Ma, S.-H.; Ang, M.-D.; Chang, Y.-T.; et al. Association between vitiligo and hearing loss. J. Am. Acad. Dermatol. 2021, 85, 1465–1472.
    42. 42.Li, C.-L.; Ma, S.-H.; Wu, C.-Y.; et al. Association between sensorineural hearing loss and vitiligo: a nationwide population-based cohort study. J. Eur. Acad. Dermatol. Venereol. 2022, 36, 1097–1103.
    43. 43.Lien, K.-H.; Ger, T.-Y.; Chi, C.-C. Association of vitiligo with high-frequency sensorineural hearing loss: a systematic review and meta-analysis. J. Eur. Acad. Dermatol. Venereol. 2022, 36, 373–379.
    44. 44.Lavezzo, M.M.; Sakata, V.M.; Morita, C.; et al. Vogt-Koyanagi-Harada disease: review of a rare autoimmune disease targeting antigens of melanocytes. Orphanet J. Rare Dis. 2016, 11, 29.
    45. 45.O'Keefe, G.A.D.; Rao, N.A. Vogt-Koyanagi-Harada disease. Surv. Ophthalmol. 2017, 62, 1–25.
    46. 46.Casella, G.; Corbetta, D.; Zolezzi, M.; et al. Symptomatic sensorineural hearing loss in patients with ulcerative colitis. Tech. Coloproctol. 2015, 19, 729–731.
    47. 47.Pisani, A.; Petito, V.; Paciello, F.; et al. Intestinal inflammation and microbiota modulation impact cochlear function: emerging insights in gut-ear axis. Cell Commun. Signal. 2025, 23, 357.
    48. 48.Reddy, N.; Shenoy, V.S.; Parvathareddy, N.; et al. Is routine hearing screening necessary in patients with inflammatory bowel disease - a prospective study. Eur. Arch. Otorhinolaryngol. 2025, 282, 2939–2946.
    49. 49.Hamed, S.A.; Elattar, A.M.; Hamed, E.A. Irreversible cochlear damage in myasthenia gravis -- otoacoustic emission analysis. Acta Neurol. Scand. 2006, 113, 46–54.
    50. 50.Chaitidis, N.; Theocharis, P.; Festas, C.; et al. Association of rheumatoid arthritis with hearing loss: a systematic review and meta-analysis. Rheumatol. Int. 2020, 40, 1771–1779.
    51. 51.Khoza-Shangase, K.; Riva, R. Hearing Function in Adults with Rheumatoid Arthritis: A Scoping Review for Preventive Audiology Planning. Indian J. Otolaryngol. Head Neck Surg. 2022, 74, 3965–3976.
    52. 52.Paraschou, V.; Partalidou, S.; Siolos, P.; et al. Prevalence of hearing loss in patients with Sjögren syndrome: a systematic review and meta-analysis. Rheumatol. Int. 2023, 43, 233–244.
    53. 53.Ralli, M.; D'Aguanno, V.; Di Stadio, A.; et al. Audiovestibular Symptoms in Systemic Autoimmune Diseases. J. Immunol. Res. 2018, 2018, 5798103.
    54. 54.Yang, T.-H.; Xirasagar, S.; Cheng, Y.-F.; et al. Increased prevalence of hearing loss, tinnitus and sudden deafness among patients with Sjögren's syndrome. RMD Open 2024, 10, e003308.
    55. 55.Okawa, Y.; Ihara, K. Sensorineural Hearing Loss in Sjögren's Syndrome. Int. J. Mol. Sci. 2022, 23, 11181.
    56. 56.Di Stadio, A.; Ralli, M. Systemic Lupus Erythematosus and hearing disorders: Literature review and meta-analysis of clinical and temporal bone findings. J. Int. Med. Res. 2017, 45, 1470–1480.
    57. 57.Bullington, M.; Davies, G.; MacDonald, C.B. Reversible Sensorineural Hearing Loss Resulting from Hypertrophic Pachymeningitis in Systemic Lupus Erythematosus: A Case Report. OTO Open 2019, 3.
    58. 58.Zhao, Z.; Li, A.; Zhu, Y.; et al. Blood-labyrinth barrier damage mediated by granzymes from cytotoxic lymphocytes results in hearing loss in systemic lupus erythematosus. Proc. Natl. Acad. Sci. U.S.A. 2025, 122, e2423240122.
    59. 59.Sieśkiewicz, M.; Rębacz, D.; Sieśkiewicz, A. Hearing impairment in systemic sclerosis patients-what do we really know? Front. Med. 2024, 11, 1322170.
    60. 60.Mazeda, C.; Silva, S.P.; Romão, J.; et al. Audiovestibular Involvement in Patients With Systemic Sclerosis. J. Clin. Rheumatol. 2024, 30, 276–282.
    61. 61.Yan, F.; Reddy, P.D.; Nguyen, S.A.; et al. Hearing Loss in Patients With Ankylosing Spondylitis: A Systematic Review and Metaanalysis. J. Rheumatol. 2021, 48, 40–47.
    62. 62.Kahveci, O.K.; Demirdal, U.S.; Duran, A.; et al. Hearing and cochlear function of patients with ankylosing spondylitis. Clin. Rheumatol. 2012, 31, 1103–1108.
    63. 63.Doğan, E.; Közen, M.A.; Mungan Durankaya, S.; et al. Evaluation of middle ear and hearing status of ankylosing spondylitis patients with wideband tympanometry and pure tone audiometry tests. Eur. Arch. Otorhinolaryngol. 2023, 280, 2273–2281.
    64. 64.Hoshino, K.; Fujiwara, K.; Morita, S.; et al. Evaluation of Semicircular Canal Function in Relapsing Polychondritis Patients With Dizziness and Sensorineural Hearing Loss Using Video Head Impulse Test. Otol. Neurotol. 2024, 45, 1045–1050.
    65. 65.Levy, R.; Gérard, L.; Kuemmerle-Deschner, J.; et al. Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry. Ann. Rheum. Dis. 2015, 74, 2043–2049.
    66. 66.Ahmadi, N.; Brewer, C.C.; Zalewski, C.; et al. Cryopyrin-associated periodic syndromes: otolaryngologic and audiologic manifestations. Otolaryngol. Head Neck Surg. 2011, 145, 295–302.
    67. 67.Fayand, A.; Cescato, M.; Le Corre, L.; et al. Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype. J. Allergy Clin. Immunol. 2023, 152, 1303–1311.
    68. 68.Dietrich, T.; Renaud, A.; Danic, G.; et al. Cochleovestibular nerve involvement in sarcoidosis: a case series and a literature review. QJM 2025, 118, 837–842.
    69. 69.Barreras, P.; Stern, B.J. Clinical features and diagnosis of neurosarcoidosis - review article. J. Neuroimmunol. 2022, 368, 577871.
    70. 70.Mouadeb, D.A.; Ruckenstein, M.J. Antiphospholipid inner ear syndrome. Laryngoscope 2005, 115, 879–883.
    71. 71.Riera, J.L.; Del R. Maliandi, M.; Musuruana, J.L.; et al. Sudden Sensorineural Hearing Loss in Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Clinical Review. Curr. Rheumatol. Rev. 2020, 16, 84–91.
    72. 72.Marrodan, M.; Fiol, M.P.; Correale, J. Susac syndrome: challenges in the diagnosis and treatment. Brain 2022, 145, 858–871.
    73. 73.Jarius, S.; Kleffner, I.; Dörr, J.M.; et al. Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study. J. Neuroinflammation 2014, 11, 46.
    74. 74.Triplett, J.D.; Qiu, J.; O'Brien, B.; et al. Diagnosis, differential diagnosis and misdiagnosis of Susac syndrome. Eur. J. Neurol. 2022, 29, 1771–1781.
    75. 75.Greco, A.; Gallo, A.; Fusconi, M.; et al. Cogan's syndrome: an autoimmune inner ear disease. Autoimmun. Rev. 2012, 12, 396–400.
    76. 76.Schuknecht, H.F.; Nadol, J.B. Temporal bone pathology in a case of Cogan's syndrome. Laryngoscope 1994, 104, 1135–1142.
    77. 77.Belfeki, N.; Ghriss, N.; Kammoun, S.; et al. Cogan's syndrome. A comprehensive review. Eur. J. Intern. Med. 2025, 138, 35–43.
    78. 78.Karadağ, A.; Karadağ, M.; Bora, A.; et al. Evaluation of hearing loss and tinnitus in Behcet's disease. Eur. Arch. Otorhinolaryngol. 2019, 276, 2691–2696.
    79. 79.Gomes, I.; Girão, A.; Gomes, J.; et al. Neurological impact of eosinophilic granulomatosis with polyangiitis. Acta Neurol. Belg. 2022, 122, 123–128.
    80. 80.Ashman, P.E.; Chen, T.; Barinsky, G.L.; et al. Otologic Manifestations of Eosinophilic Granulomatosis With Polyangiitis: A Systematic Review. Otol. Neurotol. 2021, 42, e380–e387.
    81. 81.Amor-Dorado, J.C.; Llorca, J.; Garcia-Porrua, C.; et al. Audiovestibular manifestations in giant cell arteritis: a prospective study. Medicine (Baltimore) 2003, 82, 13–26.
    82. 82.McDonald, T.J.; DeRemee, R.A. Wegener's granulomatosis. Laryngoscope 1983, 93, 220–231.
    83. 83.Berrettini, S.; Ferri, C.; La Civita, L.; et al. Inner ear involvement in mixed cryoglobulinaemia patients. Br. J. Rheumatol. 1995, 34, 370–374.
    84. 84.Rowe-Jones, J.M.; Macallan, D.C.; Sorooshian, M. Polyarteritis nodosa presenting as bilateral sudden onset cochleo-vestibular failure in a young woman. J. Laryngol. Otol. 1990, 104, 562–564.
    85. 85.Kimyon, U.; Gözen, E.D.; Karaman, E.; et al. Hearing loss in Takayasu's arteritis. Clin. Exp. Rheumatol. 2024, 42, 872–878.
    86. 86.Kökoğlu, E.O.; Kökoğlu, K.; Şenel, A.S.; et al. An Investigation Into Hearing Functions in Patients With Takayasu Arteritis. J. Clin. Pract. Res. 2024, 46, 185–190.
    87. 87.Chen, H.; Wang, F.; Yang, Y.; et al. Characteristics of Hearing Loss in Patients with Systemic Lupus Erythematosus. J. Clin. Med. 2022, 11, 7527.
    88. 88.Ulusoy, B.; Limon, M.; Yılmaz, S.; et al. Effects of primary Sjögren's syndrome on hearing and vestibular systems. J. Laryngol. Otol. 2022, 136, 1254–1258.
    89. 89.Paira, S.O. Sudden sensorineural hearing loss in patients with systemic lupus erythematosus or lupus-like syndrome and antiphospholipid antibodies. J. Rheumatol. 1998, 25, 2476–2477.
    90. 90.Chawki, S.; Aouizerate, J.; Trad, S.; et al. Bilateral sudden sensorineural hearing loss as a presenting feature of systemic lupus erythematosus: Case report and brief review of other published cases. Medicine (Baltimore) 2016, 95, e4345.
    91. 91.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, 589–592.
    92. 92.González, J.L.T.; Torres, J.R.; Ríos, Y.H.; et al. Extended high-frequency audiometry as early detection of hearing loss in primary Sjögren syndrome. Clin. Rheumatol. 2017, 36, 2237–2241.
    93. 93.Turan, K.; Yayla, M.E.; Arslan, M.; et al. Audiological involvement in patients with systemic sclerosis. Mod. Rheumatol. 2022, 32, 1094–1101.
    94. 94.D'Aguanno, V.; Ralli, M.; de Vincentiis, M.; et al. Optimal management of Cogan's syndrome: a multidisciplinary approach. J. Multidiscip. Healthc. 2018, 11, 1–11.
    95. 95.Kamakura, T.; Lee, D.J.; Herrmann, B.S.; et al. Histopathology of the Human Inner Ear in the Cogan Syndrome with Cochlear Implantation. Audiol. Neurootol. 2017, 22, 116–123.
    96. 96.Jung, D.H.; Nadol, J.B.; Folkerth, R.D.; et al. Histopathology of the Inner Ear in a Case With Recent Onset of Cogan's Syndrome: Evidence for Vasculitis. Ann. Otol. Rhinol. Laryngol. 2016, 125, 20–24.
    97. 97.Jenkins, H.A.; Pollak, A.M.; Fisch, U. Polyarteritis nodosa as a cause of sudden deafness. A human temporal bone study. Am. J. Otolaryngol. 1981, 2, 99–107.
    98. 98.Babin, R.W.; Liu, C.; Aschenbrener, C. Histopathology of neurosensory deafness in sarcoidosis. Ann. Otol. Rhinol. Laryngol. 1984, 93, 389–393.
    99. 99.Birk-Bachar, M.; Cohen, H.; Sofrin-Drucker, E.; et al. Discovery of a Novel Missense Variant in NLRP3 Causing Atypical Cryopyrin-Associated Periodic Syndromes With Hearing Loss as the Primary Presentation, Responsive to Anti-Interleukin-1 Therapy. Arthritis Rheumatol. 2024, 76, 444–454.
    100. 100.Murillo-Cuesta, S.; Seoane, E.; Cervantes, B.; et al. NLRP3 inflammasome and hearing loss: from mechanisms to therapies. J. Neuroinflammation 2025, 22, 225.
    101. 101.Ma, J.-H.; Lee, E.; Yoon, S.-H.; et al. Therapeutic effect of NLRP3 inhibition on hearing loss induced by systemic inflammation in a CAPS-associated mouse model. EBioMedicine 2022, 82, 104184.
    102. 102.Toledano-Pinedo, M.; Marco-Contelles, J.; Dobrydnev, A.V. NLRP3 Inflammasome Role and NLRP3 Inhibitors in Sensorineural Hearing Loss. Biomolecules 2026, 16, 186.
    103. 103.Oziębło, D.; Leja, M.L.; Jeznach, A.; et al. Hearing Loss as the Main Clinical Presentation in NLRP3-Associated Autoinflammatory Disease. Front. Immunol. 2022, 13, 904632.
    104. 104.Xia, X.; Wei, X.; Wang, L.; et al. Inflammatory bowel disease and hearing loss: A study of Mendelian randomization. Medicine (Baltimore) 2025, 104, e44863.
    105. 105.Gür, E.; Binkhamis, G.; Kluk, K. Effects of multiple sclerosis on the audio-vestibular system: a systematic review. BMJ Open 2022, 12, e060540.
    106. 106.Rance, G.; Zanin, J.; Merlo, D.; et al. Binaural hearing, neurological disability and brain imaging in Multiple Sclerosis. Mult. Scler. Relat. Disord. 2026, 107, 106982.
    107. 107.Liu, T.; He, R.; Tian, Y.; et al. Cochlear immunology and its therapeutic revolution. Front. Immunol. 2025, 16, 1666224.
    108. 108.De Backer, E.; Verdoodt, D.; Ponsaerts, P.; et al. Cochlear T cells and their role in health and disease: A systematic review. Autoimmun. Rev. 2025, 24, 103814.
    109. 109.Li, X.; Wang, H.; Wang, J.; et al. Inner ear immunity and audio-vestibular dysfunction. Sens. Neurosci. 2025, 1, e7.
    110. 110.Cosentino, A.; Agafonova, A.; Modafferi, S.; et al. Blood-Labyrinth Barrier in Health and Diseases: Effect of Hormetic Nutrients. Antioxid. Redox Signal. 2024, 40, 542–563.
    111. 111.Nyberg, S.; Abbott, N.J.; Shi, X.; et al. Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier. Sci. Transl. Med. 2019, 11, eaao0935.
    112. 112.Yi, Z.; Wang, X.; Yin, G.; et al. The Blood-Labyrinth Barrier: Non-Invasive Delivery Strategies for Inner Ear Drug Delivery. Pharmaceutics 2025, 17, 482.
    113. 113.Trune, D.R. Cochlear immunoglobulin in the C3H/lpr mouse model for autoimmune hearing loss. Otolaryngol. Head Neck Surg. 1997, 117, 504–508.
    114. 114.Iwai, H.; Inaba, M.; Tomoda, K.; et al. T cells infiltrating from the systemic circulation proliferate in the endolymphatic sac. Ann. Otol. Rhinol. Laryngol. 1999, 108, 1146–1150.
    115. 115.Sekulic, M.; Giaglis, S.; Chatelain, N.; et al. Neutrophil Extracellular Traps Affect Human Inner Ear Vascular Permeability. Int. J. Mol. Sci. 2024, 25, 9766.
    116. 116.Sekulic-Jablanovic, M.; Paproth, J.; Sgambato, C.; et al. Lack of NHE6 and Inhibition of NKCC1 Associated With Increased Permeability in Blood Labyrinth Barrier-Derived Endothelial Cell Layer. Front. Cell. Neurosci. 2022, 16, 862119.
    117. 117.Liu, Y.-C.; Xu, K. Macrophage-related immune responses in inner ear: a potential therapeutic target for sensorineural hearing loss. Front. Neurosci. 2024, 17, 1339134.
    118. 118.Ito, T.; Kurata, N.; Fukunaga, Y. Tissue-Resident Macrophages in the Stria Vascularis. Front. Neurol. 2022, 13, 818395.
    119. 119.Hough, K.; Verschuur, C.A.; Cunningham, C.; et al. Macrophages in the cochlea; an immunological link between risk factors and progressive hearing loss. Glia 2022, 70, 219–238.
    120. 120.Okano, T.; Nakagawa, T.; Kita, T.; et al. Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea. J. Neurosci. Res. 2008, 86, 1758–1767.
    121. 121.Noble, K.; Brown, L.; Elvis, P.; et al. Cochlear Immune Response in Presbyacusis: a Focus on Dysregulation of Macrophage Activity. J. Assoc. Res. Otolaryngol. 2022, 23, 1–16.
    122. 122.Pathak, S.; Goldofsky, E.; Vivas, E.X.; et al. IL-1β is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. J. Immunol. 2011, 186, 1870–1879.
    123. 123.Pathak, S.; Vambutas, A. Autoimmune inner ear disease patient-associated 28-kDa proinflammatory IL-1β fragment results from caspase-7-mediated cleavage in vitro. JCI Insight 2020, 5.
    124. 124.Wang, M.; Zhang, P.; Li, Q.; et al. Investigating the Process of Autoimmune Inner Ear Disease: Unveiling the Intricacies of Pathogenesis and Therapeutic Strategies. Int. J. Med. Sci. 2025, 22, 179–187.
    125. 125.Gloddek, B.; Gloddek, J.; Arnold, W. Induction of an inner-ear-specific autoreactive T-cell line for the diagnostic evaluation of an autoimmune disease of the inner ear. Ann. N. Y. Acad. Sci. 1997, 830, 266–276.
    126. 126.Yuan, V.G.; Kullar, P.; Xia, A.; et al. NLRP3 inflammasome as a therapeutic target in autoimmune inner ear disease. Front. Audiol. Otol. 2025, 3, 1673518.
    127. 127.Tomiyama, S. Th1: mediator lymphocytes in experimental autoimmune labyrinthitis. Acta Otolaryngol. 2001, 121, 673–678.
    128. 128.Solares, C.A.; Edling, A.E.; Johnson, J.M.; et al. Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides. J. Clin. Invest. 2004, 113, 1210–1217.
    129. 129.Zhou, Y.; Song, F.; Luo, J. The role of CD4+ CD25+ Treg in the mechanism of autoimmune auditory neuropathy in SD rats. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2023, 58, 225–232. (in Chinese)
    130. 130.Zhou, Y.; Yuan, J.; Zhou, B.; et al. The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology 2011, 133, 133–140.
    131. 131.Tebo, A.E.; Szankasi, P.; Hillman, T.A.; et al. Antibody reactivity to heat shock protein 70 and inner ear-specific proteins in patients with idiopathic sensorineural hearing loss. Clin. Exp. Immunol. 2006, 146, 427–432.
    132. 132.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, 214–219.
    133. 133.Bustos-Merlo, A.; Ortiz-Parra, A.; Rosales-Castillo, A.; et al. Autoimmune inner ear disease associated with antiphospholipid antibodies. Clin. Exp. Rheumatol. 2024, 42, 2268–2271.
    134. 134.Lunardi, C.; Bason, C.; Leandri, M.; et al. Autoantibodies to inner ear and endothelial antigens in Cogan's syndrome. Lancet 2002, 360, 915–921.
    135. 135.Kullar, P.; Santa Maria, P. Advances in immune mediated inner ear disease. Front. Audiol. Otol. 2025, 3, 1624303.
    136. 136.Gorthey, S.W.; Pathak, S.; Vambutas, A. The Correlation of Clinical Corticosteroid Responsiveness With Expression of IL-6 in Peripheral Blood Immune Cells (PBMC) in Patients With Autoimmune Inner Ear Disease (AIED). Otol. Neurotol. 2021, 42, 1422–1428.
    137. 137.Yellin, I.; Pathak, S.; Vambutas, A. Effect of betahistine on pro-inflammatory cytokine expression in autoimmune inner ear disease and Meniere's disease patients. Laryngoscope Investig. Otolaryngol. 2024, 9, e70032.
    138. 138.Pathak, S.; Tan, N.; Vambutas, A. A pilot study on the effect of SARS-CoV-2 spike protein on IL-1β-mediated inflammation in peripheral blood immune cells from AIED patients. Mol. Med. 2025, 31, 174.
    139. 139.Rauch, S.D. Clinical management of immune-mediated inner-ear disease. Ann. N. Y. Acad. Sci. 1997, 830, 203–210.
    140. 140.Varga-Balázs, G.; Tamás, T.L.; Nagy, L.; et al. Differential diagnosis of bilateral Ménière's disease and autoimmune inner ear disease. Orv. Hetil. 2024, 165, 1176–1183.
    141. 141.Fernandes, C.P.; Vernier, L.S.; Dallegrave, E.; et al. The Ototoxicity of Chloroquine and Hydroxychloroquine: A Systematic Review. Int. Arch. Otorhinolaryngol. 2022, 26, e167–e177.
    142. 142.Tharwat, S.; Elshawaf, W.; Nassar, M.K. Audiologic evaluation in systemic lupus erythematosus patients and impact of hydroxychloroquine therapy. Egypt. Rheumatol. 2022, 44, 171–174.
    143. 143.Page, J.C.; Gidley, P.W.; Nader, M.-E. Audiovestibular Toxicity Secondary to Immunotherapy: Case Series and Literature Review. J. Immunother. Precis. Oncol. 2022, 5, 2–6.
    144. 144.Bulut Gökten, D.; Ersözlü, T.; Gökten, M.; et al. Audiometric evaluation of bone conduction thresholds reveals subclinical sensorineural hearing loss in patients with ankylosing spondylitis and psoriatic arthritis. Braz. J. Otorhinolaryngol. 2026, 92, 101813.
    145. 145.Elnagdy, O.H.; Elfarrash, S.; Fawzy, I.M.; et al. Early detection of cochlear hearing loss in rheumatoid arthritis patients: a cross-sectional study. Egypt. J. Otolaryngol. 2022, 38, 91.
    146. 146.Hirose, K.; Wener, M.H.; Duckert, L.G. Utility of laboratory testing in autoimmune inner ear disease. Laryngoscope 1999, 109, 1749–1754.
    147. 147.Buniel, M.C.; Geelan-Hansen, K.; Weber, P.C.; et al. Immunosuppressive therapy for autoimmune inner ear disease. Immunotherapy 2009, 1, 425–434.
    148. 148.Harris, J.P.; Weisman, M.H.; Derebery, J.M.; et al. Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate: a randomized controlled trial. JAMA 2003, 290, 1875–1883.
    149. 149.Tebo, A.E.; Jaskowski, T.D.; Keith, L.L.; et al. Comparison of immune assays for the detection of anti-HSP70 antibodies in patients with idiopathic sensorineural hearing loss. Clin. Chim. Acta 2007, 381, 140–144.
    150. 150.Del Poggio, A.; Cangiano, I.; Baldissera, E.; et al. Clinical significance of endolymphatic hydrops on MRI in Cogan's syndrome: a case series of five patients. Eur. Arch. Otorhinolaryngol. 2025, 282, 2753–2760.
    151. 151.Lee, B.; Bae, Y.J.; Choi, B.Y.; et al. Construction of an MRI-based decision tree to differentiate autoimmune and autoinflammatory inner ear disease from chronic otitis media with sensorineural hearing loss. Sci. Rep. 2021, 11, 19171.
    152. 152.Khorrami, M.; Pastras, C.; Haynes, P.A.; et al. The Current State of Proteomics and Metabolomics for Inner Ear Health and Disease. Proteomes 2024, 12, 17.
    153. 153.Mohseni-Dargah, M.; Falahati, Z.; Pastras, C.; et al. Meniere's disease: Pathogenesis, treatments, and emerging approaches for an idiopathic bioenvironmental disorder. Environ. Res. 2023, 238, 116972.
    154. 154.Flook, M.; Escalera-Balsera, A.; Rybakowska, P.; et al. Single-cell immune profiling of Meniere Disease patients. Clin. Immunol. 2023, 252, 109632.
    155. 155.Yuan, V.G.; Xia, A.; Santa Maria, P.L. Immunological mechanisms in Meniere's disease. Front. Immunol. 2025, 16, 1639916.
    156. 156.Sekulic, M.; Kobivasan, S.; Giaglis, S.; et al. Circulating Clues in Ménière's Disease: Elevated Cell-Free DNA and a Pro-Inflammatory Signature in Patients' Blood. Int. J. Mol. Sci. 2026, 27, 1948.
    157. 157.Zhang, D.; Li, X.; Lv, Y.; et al. Lymphatic Vessels in the Inner Ear of Patients With Meniere Disease: A Novel Pathological Finding. OTO Open 2024, 8, e171.
    158. 158.Lopez-Escamez, J.A.; Liu, Y. Epidemiology and genetics of Meniere's disease. Curr. Opin. Neurol. 2024, 37, 88–94.
    159. 159.Meliante, P.G.; Colizza, A.; Turchetta, R.; et al. Meniere’s disease variants and endolymphatic hydrops-related conditions: a systematic review of the literature. Otorhinolaryngology 2022, 72, 130–139.
    160. 160.Kangasniemi, E.; Hietikko, E. The theory of autoimmunity in Meniere's disease is lacking evidence. Auris Nasus Larynx 2018, 45, 399–406.
    161. 161.Caulley, L.; Quimby, A.; Karsh, J.; et al. Autoimmune arthritis in Ménière's disease: A systematic review of the literature. Semin. Arthritis Rheum. 2018, 48, 141–147.
    162. 162.Broughton, S.S.; Meyerhoff, W.E.; Cohen, S.B. Immune-mediated inner ear disease: 10-year experience. Semin. Arthritis Rheum. 2004, 34, 544–548.
    163. 163.García-Berrocal, J.R.; Ibáñez, A.; Rodríguez, A.; et al. Alternatives to systemic steroid therapy for refractory immune-mediated inner ear disease: A physiopathologic approach. Eur. Arch. Otorhinolaryngol. 2006, 263, 977–982.
    164. 164.Bird, P.A.; Begg, E.J.; Zhang, M.; et al. Intratympanic versus intravenous delivery of methylprednisolone to cochlear perilymph. Otol. Neurotol. 2007, 28, 1124–1130.
    165. 165.Breslin, N.K.; Varadarajan, V.V.; Sobel, E.S.; et al. Autoimmune inner ear disease: A systematic review of management. Laryngoscope Investig. Otolaryngol. 2020, 5, 1217–1226.
    166. 166.Stachler, R.J.; Chandrasekhar, S.S.; Archer, S.M.; et al. Clinical practice guideline: sudden hearing loss. Otolaryngol. Head Neck Surg. 2012, 146, S1–S35.
    167. 167.Lambert, P.R.; Carey, J.; Mikulec, A.A.; et al. Intratympanic Sustained-Exposure Dexamethasone Thermosensitive Gel for Symptoms of Ménière's Disease: Randomized Phase 2b Safety and Efficacy Trial. Otol. Neurotol. 2016, 37, 1669–1676.
    168. 168.Plontke, S.K.; Meisner, C.; Agrawal, S.; et al. Intratympanic corticosteroids for sudden sensorineural hearing loss. Cochrane Database Syst. Rev. 2022, 7, CD008080.
    169. 169.Balouch, B.; Meehan, R.; Suresh, A.; et al. Use of biologics for treatment of autoimmune inner ear disease. Am. J. Otolaryngol. 2022, 43, 103576.
    170. 170.Cohen, S.; Shoup, A.; Weisman, M.H.; et al. Etanercept treatment for autoimmune inner ear disease: results of a pilot placebo-controlled study. Otol. Neurotol. 2005, 26, 903–907.
    171. 171.Mata-Castro, N.; Sanz-López, L.; Varillas-Delgado, D.; et al. Intratympanic infliximab is a safe and effective rescue therapy for refractory immune-mediated hearing loss. Eur. Arch. Otorhinolaryngol. 2020, 277, 393–400.
    172. 172.Derebery, M.J.; Fisher, L.M.; Voelker, C.C.J.; et al. An open label study to evaluate the safety and efficacy of intratympanic golimumab therapy in patients with autoimmune inner ear disease. Otol. Neurotol. 2014, 35, 1515–1521.
    173. 173.Van Wijk, F.; Staecker, H.; Keithley, E.; et al. Local perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss. Audiol. Neurootol. 2006, 11, 357–365.
    174. 174.Heywood, R.L.; Hadavi, S.; Donnelly, S.; et al. Infliximab for autoimmune inner ear disease: case report and literature review. J. Laryngol. Otol. 2013, 127, 1145–1147.
    175. 175.Cohen, S.; Roland, P.; Shoup, A.; et al. A pilot study of rituximab in immune-mediated inner ear disease. Audiol. Neurootol. 2010, 16, 214–221.
    176. 176.Orsoni, J.G.; Laganà, B.; Rubino, P.; et al. Rituximab ameliorated severe hearing loss in Cogan's syndrome: a case report. Orphanet J. Rare Dis. 2010, 5, 18.
    177. 177.Bunker, D.R.; Kerr, L.D. Rituximab Not Effective for Hearing Loss in Cogan's Syndrome. Case Rep. Rheumatol. 2016, 2016, 8352893.
    178. 178.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, 4115–4122.
    179. 179.Vambutas, A.; Mullooly, V.; Weber, S.; et al. Corticosteroid-Resistant and Corticosteroid-Dependent AIED Patients Treated With Anakinra: A Decade of Experience. Otol. Neurotol. 2025, 46, 1059–1069.
    180. 180.Kuemmerle-Deschner, J.B.; Koitschev, A.; Tyrrell, P.N.; et al. Early detection of sensorineural hearing loss in Muckle-Wells-syndrome. Pediatr. Rheumatol. 2015, 13, 43.
    181. 181.Iida, Y.; Wakiguchi, H.; Okazaki, F.; et al. Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene. Clin. Rheumatol. 2018, 38, 943–948.
    182. 182.Chen, Y.; Hu, J.; Wu, D.; et al. Tocilizumab Successfully Treating Refractory Hearing Impairment in a Patient With Cogan Syndrome: A Case Report and Review of the Literature. Ear Nose Throat J. 2026, 105, NP870–NP873.
    183. 183.Anderson, C.; McAllister, K.; Walsh, J. P158 A case of refractory paediatric Cogan’s syndrome treated with tocilizumab. Rheumatology 2022, 61, keac133.157. DOI: https://doi.org/10.1093/rheumatology/keac133.157
    184. 184.Hara, K.; Umeda, M.; Segawa, K.; et al. Atypical Cogan's Syndrome Mimicking Giant Cell Arteritis Successfully Treated with Early Administration of Tocilizumab. Intern. Med. 2022, 61, 1265–1270.
    185. 185.Suckfuell, M.; Lisowska, G.; Domka, W.; et al. Efficacy and safety of AM-111 in the treatment of acute sensorineural hearing loss: a double-blind, randomized, placebo-controlled phase II study. Otol. Neurotol. 2014, 35, 1317–1326.
    186. 186.Staecker, H.; Jokovic, G.; Karpishchenko, S.; et al. Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study. Otol. Neurotol. 2019, 40, 584–594.
    187. 187.Wang, Y.; Tang, S.; Shao, C.; et al. Cogan's syndrome is more than just keratitis: a case-based literature review. BMC Ophthalmol. 2023, 23, 212.
    188. 188.Gordis, T.M.; Shah, S.R.; Ward, C.; et al. Disease-Modifying Antirheumatic Drugs in the Treatment of Autoimmune Inner Ear Disease: A Systematic Review and Meta-Analysis of Auditory and Vestibular Outcomes. Otol. Neurotol. 2023, 44, 2–9.
    189. 189.Yoo, T.J.; Du, X.; Zhou, B. The paracrine effect of mesenchymal human stem cells restored hearing in β-tubulin induced autoimmune sensorineural hearing loss. Hear. Res. 2015, 330, 57–61.
    190. 190.Lee, M.P.; Waldhaus, J. In vitro and in vivo models: What have we learnt about inner ear regeneration and treatment for hearing loss? Mol. Cell. Neurosci. 2022, 120, 103736.
    191. 191.Liu, S.S.; Yang, R. Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities. Front. Neurosci. 2022, 16, 867453.
    192. 192.Luetje, C.M. Theoretical and practical implications for plasmapheresis in autoimmune inner ear disease. Laryngoscope 1989, 99, 1137–1146.
    193. 193.Luetje, C.M.; Berliner, K.I. Plasmapheresis in autoimmune inner ear disease: long-term follow-up. Am. J. Otol. 1997, 18, 572–576.
    194. 194.Sakano, H.; Harris, J.P. Emerging options in immune-mediated hearing loss. Laryngoscope Investig. Otolaryngol. 2018, 4, 102–108.
    195. 195.Goh, X.; Muzaffar, J.; Bance, M. Cochlear implantation in systemic autoimmune disease. Curr. Opin. Otolaryngol. Head Neck Surg. 2022, 30, 291–297.
    196. 196.Atturo, F.; Portanova, G.; Russo, F.Y.; et al. Cochlear implant in immune mediated inner ear diseases: Impedance variations and clinical outcomes. Cochlear Implants Int. 2022, 23, 70–79.
    197. 197.Milon, B.; Shulman, E.D.; So, K.S.; et al. A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma. Cell Rep. 2021, 36, 109758.
    198. 198.Ma, Q.; Wang, Q.; Zhu, Z.; et al. Single-Cell Sequencing Reveals Circadian Sensitivity of Noise-Induced Hearing Loss Mediated by Macrophage-Driven NLRP3 Inflammasome Activation. Neurosci. Bull. 2026, 42, 319–337.
    199. 199.Wu, M.-Y.; Chen, A.-H.; Li, L.-Q.; et al. Single-cell RNA sequencing analysis of mouse cochlea identifies a novel proinflammatory CD74+CD14+ macrophage subset in mice with age-related and noise-induced hearing loss. Hear. Res. 2025, 466, 109376.
    200. 200.Ma, X.; Guo, J.; Tian, M.; et al. Advance and Application of Single-cell Transcriptomics in Auditory Research. Neurosci. Bull. 2024, 40, 963–980.
    201. 201.Liu, Y.; Gong, Q. Deep Learning Models for Predicting Hearing Thresholds Based on Swept-Tone Stimulus-Frequency Otoacoustic Emissions. Ear Hear. 2024, 45, 465–475.
    202. 202.Ogawa, M.; Kisohara, M.; Yamamoto, T.; et al. Utility of unsupervised deep learning using a 3D variational autoencoder in detecting inner ear abnormalities on CT images. Comput. Biol. Med. 2022, 147, 105683.
    ×