Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Autoimmune Inner Ear Disease The role of immunity in sensorineural hearing loss was first suggested in 1958 by Lenhart. Kikuchi, in 1959, wrote of "sympathetic otitis" whereby surgery on one ear affected hearing in the other. He proposed an autoimmune phenomena as the etiology. In 1961 Beickert, and two years later, Terrayama presented data supporting autoimmunity in experimental guinea pig cochleas. McCabe described 18 patients with bilateral asymmetric hearing loss progressing over weeks to months which responded to steroid therapy. His 1979 paper asserted the importance of a high index of suspicion in these patients since, if diagnosed early, they could be treated and their hearing preserved. Humoral and cell mediated immunity, the lymphocyte-macrophage system, and the complement cascade work in homeostatic harmony to provide immune protection to the host. B cells are produced in the bone marrow and, through antigen stimulation and differentiation into plasma cells, produce specific antibodies. T cells are derived in the thymus and provide regulatory function for B cells, cytotoxic activity, and generate lymphokines. B and T cells also form immunologic memory. Cells of the lymphocyte-macrophage system phagocytose foreign cellular components, process antigen, and produce interferons. The complement cascade amplifies antigen antibody reactions. Chemotactic, anaphylotoxic, opsoninization, and immune adherence functions arise from the complement system. Kinin-like substances are also complement generated. The inner ear is immunologically active. The endolymphatic sac acts as the afferent limb of inner ear immunity since it can concentrate and primarily synthesize antibody. IgG is the most common antibody produced with IgM, IgA, and secretory component being present in lower concentrations. The distal endolymphatic sac is the site of immunologic activity due to extensive perisaccular lymphatics. Antibody production is independent of serum or cerebrospinal fluid levels. Secondary exposure to antigen in the inner ear induces a more intense response than primary exposure to antigen. Autoimmunity occurs with loss of homeostatic control in the immune system. Host tissues become recognized as foreign and induce damaging vasculitis and fibrosis. Veldman described a continuum of autoimmunity. On one end, organ specific responses with organ specific autoantibodies and T cells produce tissue alteration (i.e. Hashimoto's thyroiditis). On the opposite end of the spectrum is non-organ specific diseases with circulating non-specific autoantibodies (i.e. systemic lupus erythematosus). In between is organ specific disease with non-specific autoantibodies (ie primary biliary cirrhosis). Patients with idiopathic autoimmune sensorineural hearing loss present most commonly with bilateral progressive hearing loss. Fifty percent have vestibular signs, and symptomatically progress over weeks to months. Females between the ages of 17 to 42 years represent 65% of the cases reported by Hughes. Twenty percent of Hughes' study later manifested signs of systemic autoimmune disease. McCabe proposed using ESR, ANA, RF, complement levels, and quantitative immunoglobulin levels as a screening panel for autoimmune inner ear disease in high risk patients. Positive values in any of the screening tests would warrant leukocyte inhibition testing. Hughes classified patients as high risk if they had bilateral and progressive sensorineural hearing loss, no response to conventional therapy, concomitant immune disorders, abnormal screening tests or improvement of hearing with steroid therapy. Treatment goals in autoimmune inner ear disease include improving speech thresholds to levels treatable with hearing aids in severely affected patients and recovery of hearing to near normal levels in those with mild to moderate losses. Steroids, cytoxan, and plasmapheresis compose the available therapeutic modalities. Hughes advocates high dose (prednisone 20 mg four times daily for 10 days then 10 mg every other day for 3-6 months) steroids as initial treatment. Patients are tapered slowly and restarted if symptoms recur. As initial therapy, McCabe recommends cytoxan (2mg/kg twice daily) combined with steroids (prednisone 30 mg every other day) for 3 weeks. If speech discrimination scores increase by 20% or pure tone average improves by 15 dB, therapy is continued for 3 months. Cyclophosphamide is tapered first followed by steroids. If symptoms recur both drugs are restarted. Three month cycles are continued until patients can be weaned. No patient required more than 24 months of treatment in McCabe's study. Hughes advises plasmapheresis for those patients unresponsive to steroids and cytoxan after 6 to 8 weeks at the above stated doses. Plasmapheresis theoretically removes unwanted humoral and cellular elements. Treatments are given three times weekly for 2 weeks followed by once weekly for 4 additional weeks. In summary, otolaryngologists need a high index of suspicion for autoimmune etiologies in patients with sensorineural hearing loss. Ophthalmologic, neurologic and rheumatologic consultations are useful in ruling out systemic vasculitic diseases. Steroids and cyclophosphamide remain the cornerstones of treatment in autoimmune inner ear disease, with reservation of plasmapheresis for refractory cases. If caught early, and with aggressive medical management, hearing stabilization and possible improvement are feasible. Case Presentation A 53-year-old white woman was first seen in November 1991 by a private MD, for sore throat, otalgia, scleritis, and temporal headaches. ANA, RF, RPR, and VDRL were all negative at that time. Her ESR was mildly elevated to 56. Magnetic resonance imaging of the head and neck was read as normal. She was treated unsuccessfully for occipital nerve impingement with local steroid injection. Systemic steroids relieved all symptoms until attempted taper when the headaches returned. In December 1991 she was admitted to the Neurology service at The Methodist Hospital with a diagnosis of temporal artery headaches. Further past medical history revealed an episode of temporal headache and pleuritic chest pain 6 months prior to her workup in Beaumont. Neurological and ophthalmologic evaluations revealed no specific anomalies. Lumbar puncture and temporal artery biopsy were without pathological change. VDRL was nonreactive. RF, ANA, and HIV testing were all negative. She had improvement of her headaches with systemic steroids. She was readmitted to Hospital in January 1992 with new onset nausea, vomiting, and sudden hearing loss in her left ear. ESR on admission was 37, urinalysis clear, and blood hematologic assessment showed a very mild iron deficiency anemia. C3, C4, RPR, FTA:ABS, SSA, SSB, RF, ANA, and antineutrophil cytoplasmic antibody were all within normal values. ACE inhibitor level was 8.4 (1.8 to 6.2). Serum protein electrophoresis was consistent with an acute phase response to inflammation. Chest x-ray was normal. Repeat MRI was remarkable only for left middle ear inflammation. Gallium scan showed increased uptake in the auricular region. Electronystagmography was consistent with a left peripheral (nerve or end organ) deficit. Lip biopsy was negative for inflammatory changes. Mastoid and middle ear biopsies obtained after complete mastoidectomy showed no pathologic abnormality. She has been managed with long-term steroid therapy with good control of her vestibular symptoms. Bibliography Bauwens LJJM, Veldman JE, Huizing EG. Progress in temporal bone histopathology. III. An improved technique for immunohistochemical investigation of the adult human inner ear. Acta Otolaryngol Suppl 1990;470:34-39. Berlinger NT. Immunobiology. In: Paparella MM, Shumrick DA, Gluckman JL, Meyerhoff WL, editors. Otolaryngology. Volume I. Basic sciences and related principles. 3rd edition. Philadelphia: WB Saunders, 1991:725-737. Harris JP. Autoimmunity of the inner ear. Am J Otol 1989;10:193-195. Harris JP. Immunology of the inner ear: evidence of local antibody production. Ann Otol Rhinol Laryngol 1984;93:157-162. Harris JP. Immunology of the inner ear: response of the inner ear to antigen challenge. Otolaryngol Head Neck Surg 1983;91:18-23. Hughes GB, Barna BP, Kinney SE, Calabrese LH, Nalepa NJ. Clinical diagnosis of immune inner-ear disease. Laryngoscope 1988;98:251-253. Hughes GB, Barna BP, Kinney SE, Calabrese LH, Nalepa NL. Predictive value of laboratory tests in "autoimmune" inner ear disease: preliminary report. Laryngoscope 1986;96:502-505. Hughes GB, Kinney SE, Barna BP, Calabrese LH. Practical versus theoretical management of autoimmune inner ear disease. Laryngoscope 1984;94:758-767. Kanzaki J, O-Uchi T. Circulating immune complexes in steroid-responsive sensorineural hearing loss and the long-term observation. Acta Otolaryngol Suppl 1983;393:77-84. McCabe BF. Autoimmune inner ear disease: therapy. Am J Otol 1989;10:196-197. ]McCabe BF. Autoimmune sensorineural hearing loss. Ann Otol 1979;88:585-589. McCabe BF, McCormick KJ. Tests for autoimmune disease in otology. Am J Otol 1984;5:447-449. Mogi G, Lim DJ, Watanabe N. Immunologic study on the inner ear. Arch Otolaryngol 1982;108:270-275. Mogi G, Maeda S, Watanabe N. The development of mucosal immunity in guinea pig middle ears. Internatl J Pediatr Otorhinolaryngol 1980;1:331-349. Musiek FE, Morgan GJ. The use of central auditory tests in a case of vasculitis. Ear Hear 1981;2:100-102. Plester D, Soliman AM. Autoimmune hearing loss. Am J Otol 1989;10:188-192. Quick CA. Antigenic causes of hearing loss. Otolaryngol Clin North Am 1975;8:385-394. Rask-Andersen H, Stahle J. Immunodefence of the inner ear? Lymphocyte-macrophage interaction in the endolymphatic sac. Acta Otolaryngol 1980;89:283-294. Ryan AF, Cleveland PH, Hartman MT, Catanzaro A. Humoral and cell-mediated immunity in peripheral blood following introduction of antigen into the middle ear. Ann Otol 1982;91:70-75. Stephens SDG, Luxon L, Hinchcliffe R. immunological disorders and auditory lesions. Audiology 1982;21:128-148. Veldman JE, Cochlear and retrocochlear immune-mediated inner ear disorders. Pathogenetic mechanisms and diagnostic tools. Ann Otol Rhinol Laryngol 1986;95:535-540. Veldman JE. The immune system in hearing disorders. Acta Otolaryngol Supple 1988;458:67-75. Veldman JE. Immunology of hearing: experiments of nature. Am J Otol 1989;10:183-187. Veldman JE, Roord JJ, O'Connor AF, Shea JJ. Autoimmunity and inner ear disorders: an immune-complex mediated sensorineural hearing loss. Laryngoscope 1984;94:501-507. Yoo TJ, Stuart JM, Kang AH, Townes AS, Tomoda K, Dixit S. Type Ii collagen autoimmunity in otosclerosis and Meniere's disease. Science 1982;217:1153-1155. Yoo TJ, Tomoda K, Stuart JM, Cremer MA, Townes AS, Kang AH. Type II collagen-induced autoimmune sensorineural hearing loss and vestibular dysfunction in rats. Ann Otol Rhinol Laryngol 1983;92:267-271. Yoo TJ, Tomoda K, Stuart JM, Kang AH, Townes AS. Type II collagen-induced autoimmune otospongiosis. A preliminary report. Ann Otol Rhinol Laryngol 1983;92:103-108. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2006 Baylor College of Medicine
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