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.