Autoimmune Inner Ear Disease (AIED)
Timothy C. Hain,
Last edited: 1/2003. Please read our disclaimer.
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AIED defined How common is it Diagnosis Treatment Education Index
Autoimmune inner ear disease or "AIED" consists of a syndrome of progressive hearing loss and/or dizziness which is caused by antibodies or immune cells which are attacking the inner ear.
The classic picture is reduction of hearing accompanied by tinnitus (ringing, hissing, roaring) which occurs over a few months. Variants are bilateral attacks of hearing loss and tinnitus which resemble Meniere's disease, and attacks of dizziness accompanied by abnormal blood tests for self-antibodies. About 50% of patients with AIED have balance symptoms.
The immune system is complex and there are several ways that it can damage the inner ear. Both allergy and traditional "autoimmune disease" such as Ankylosing spondylitis, Systemic Lupus Erythematosis (SLE), Sjoegren's syndrome (dry eye syndrome), Cogan's disease, ulcerative colitis, Wegener's granulomatosis, rheumatoid arthritis, and scleroderma can cause or be associated with AIED. Another multisystem disease, Bechet's, commonly has audiovestibular problems. Allergy involving the inner ear is traditionally felt to be food related, but there is presently no agreement as to the importance of food allergy.
How common is Autoimmune Inner Ear Disease ?
AIED is rare, probably accounting for less than 1% of all cases of hearing impairment or dizziness. The precise incidence is controversial. About 16% of persons with bilateral Meniere's disease, and 6% of persons with Meniere's disease of any variety may be due to immune dysfunction.
What causes Autoimmune Inner Ear Disease ?
The cause of AIED is generally assumed to be related to either antibodies or immune cells that cause damage to the inner ear. There are several theories as to how these might arise, analogously to other putatative autoimmune disorders:
Bystander damage: In this theory damage to the inner ear causes cytokines to be released which provoke, after a delay, additional immune reactions. This theory might explain the attack/remission cycle of disorders such as Meniere's disease. There is evidence for cytokines in the cochlea including interleukin-1A, TNF-alpha, NFkB P65 and P50, and IkBa (Adams, 2002). Drugs that block TNF such as etanercept seem to be potentially effective in AIED (Rahmen et al, 2001). Other autoimmune disorders such as Crohn's disease also seem to be linked to TNF (
Cross-reactions: In this theory, antibodies or rogue T-cells cause accidental inner ear damage because the ear shares common antigens with a potentially harmful substance, virus or bacteria that the body is fighting off. This is presently the favored theory of AIED. COCH5B2 has recently been reported to be a target antigen in AIED (Boulassel et al, 2001).
Intolerance: The ear, like the eye may be only an partially "immune privileged" locus, meaning that the body may not know about all of the inner ear antigens, and when they are released (perhaps following surgery or an infection), the body may wrongly mount an attack on the "foreign" antigen. In the eye, there is a syndrome called "sympathetic ophthalmia", where following a penetrating injury to one eye, the other eye may go blind. This theory is not presently in favor for the ear. Nevertheless, the author of this page has seen several patients who develop ear disease in a delayed fashion in the opposite ear treated for an acoustic neuroma.
Genetic factors: There is evidence that genetically controlled aspects of the immune system may increase or otherwise be associated with increased susceptibility to common hearing disorders such as Menieres disease. Bernstein and associates reported that 44% of patients with Menieres, otosclerosis and striatal presbyacusis had one particular extended MHC haplotype (Dqw2-Dr3-c4Bsf-C4A0-G11: 15-Bf:0.4-C2a-HSP70:7.5-TNF), compared to only 7% of controls. Sudden hearing loss in Koreans that does not recover is also associated with HLA-DRB1*04, DQA1 03 and 05 (Yeo et al, 1999; Yeo et al, 2001). The author has also found an association (in the US) with certain types of HLA-types and variants of vertigo in caucasians (unpublished). On the other hand, a recent study by Lopez-Escamez and others performed in Spain found no difference in HLA antigens between 54 patients with definate MD and 534 normal controls (Lopez Escamez et al, 2002). The genetic background of HLA studies is important and it is possible that one group might find HLA differences which are not found in another.
These data are thus conflicted. If there is indeed an association with HLA, at least in certain populations, it would suggest that more of Menieres disease and other progressive syndromes may be caused by immune dysfunction than is presently generally thought. It is important to remember that HLA-typing is relevant when considered in the context of the patient's genetic background. In other words, studies of Korean subjects for example, such as reported by Yeo, may not cross-apply to persons of non-Korean ethnicity.
How is the diagnosis of Autoimmune Inner Ear Disease made?
The diagnosis is based on history, findings on physical examination, blood tests, and the results of hearing and vestibular tests. As auditory neuropathy can present with a progressive bilateral sensorineural hearing loss, ABR testing should be done in persons with enough hearing for the test to be practical. Otoacoustic emmission tests should be done in those in whom ABR testing cannot be done.
While specific tests for autoimmunity to the inner ear would be desirable, at this writing there are none that are both commercially available and proven to be useful.
Immunoflourescence of supporting cells of guinea pig organ of Corti has also been shown to correlate with disease and steroid responsiveness. According to Gray and others, immunoflourescence is more sensitive and specific (86%, 41%) than is Western Blot (59%, 29%) (Gray and others, ARO abstracts, 1999, #246). The specificity of both tests to us seems unacceptably low.
The lymphocyte transformation assay, like the anti-cochlear antibody test, is presently of uncertain value.
It has recently been reported that antibodies to sulfoglucuronosyl glycolipids are common in autoimmune inner ear disease. (Yamawaki M, 1998). It remains to be seen if this finding will be confirmed and whether a commercial assay will be developed.
At this writing (1/2003), it is not generally felt that anti-cochlear antibody (also called anti-HSP70) blood tests are specific enough to be very useful. We hope that this changes in the future. Accordingly, diagnosis is generally based on evidence from broader tests of autoimmunity, or a positive response to steroids.
As there are no specific tests for AIED, a common approach is to look for other evidence for autoimmune involvement.
Blood tests for autoimmune disorders include:
Blood tests for conditions that resemble autoimmune disorders include:
How is Autoimmune Inner Ear Disease Treated ?
There are several protocols for treatment. In cases with a classic rapidly progressive bilateral hearing impairment, a trial of steroids (Prednisone or Decadron) for 4 weeks may be tried. In persons with response to steroids, in most cases a chemotherapy type of medication such as Cytoxan or Methotrexate will be used over the long term (Sismanis et al , 1994; Sismanis et al, 1997). It has also recently been reported that plasmapheresis may be beneficial (Luetje and Berliner, 1997).
Etanercept (Enbrel) is also emerging as a promising agent for treatment of AIED (Rahmen et al, 2001; Wang et al, 2003). Enbrel is an anti-TNF (tumor necrosis factor) drug. TNF is an inflammatory cytokine (see above). Enbrel is given as an injection twice/week. Unfortunately, at this writing (5/2002), etanercept is presently unavailable due to manufacturing difficulties. A related agent, (infliximab) Remicade, was not found useful for AIED, but this study was based on only a handful of cases(Pyykko et al, 2002). There are newer agents that are in the drug pipeline that will need to be tested for their efficacy. The most interesting is Humira, which is another anti-TNF drug, which was recently approved by the FDA (12/2002). Wang et al recently reported that etanercept given acutely in sterile experimental labyrinthitis resulted in much better hearing results in an animal model.
In animals, attempts have been made to treat variants of AIED with oral collagen (Kim et al, 2001)
Autoimmune inner ear disease is rare, making it difficult to study. One can speculate that there might be effective treatments that simply have not been discovered. For example, there are numerous potential treatments that have not been tried in a formal way. Gamma globulin infusions, given monthly, are useful in numerous autoimmune disorders. This treatment is very expensive, which limits its use. Immune modulating drugs such as are used for treatment of MS (beta-interferon, alpha-inteferon, copaxone) have not been tried in AIED, to this author's knowledge. Other medications that have coincidental suppression of immune responses, such as minocycline, or other anti-TNF drugs, might be tried.