2. Autoimmune Inner Ear Disease Robert H. Stroud, M.D. Jeffery T. Vrabec, M.D. 12 January 2000

3. Background n Lenhardt 1958 n McCabe 1979 n Harris 1990

4. Immune Function of Inner Ear n blood-labyrinthine barrier n maintenance of homeostasis n little lymphatic drainage n immunoglobulins 1/1000th of serum n immune responsiveness

5. Endolymphatic Sac n Resident lymphocytes n immunoglobulin production n systemic lymphocyte entry –spiral modiolar vein –intercellular adhesion molecule

6. Type I Hypersensitivity n IgE n mast cells n histamine n vasodilation n ? Hydrops  Meniere’s n inhalant allergy

7. Type II Hypersensitivity n Antibodies n complement activation n anti-68kDa protein antibody n SLE, Goodpasture’s

8. Type III Hypersensitivity n Immune complex n Ig deposition n tissue injury n Wegener’s, ?Meniere’s

9. Type IV Hypersensitivity n T-cell mediated n direct lysis n lymphokine production n lymphocyte transformation test n Cogan’s syndrome

10. Clinical Picture n Middle-aged women n progressive SNHL, weeks to months n dizziness, aural fullness n bilateral 79% n  no vestibular symptoms n systemic autoimmune disease in 29%

11. Diagnosis n Clinical n LTT - 93% specific, 50-80% sensitive n Western blot for anti-68kDa protein (hsp70) –95% specific –insensitive –predictor of steroid response

12. Diagnosis n ESR n CRP n C1q binding assay n anti-cardiolipin n ANCA n syphilis testing n Lyme titers n CBC n chemistries n thyroid functions n imaging

13. Polyarteritis Nodosa n Vasculitis of small and medium-sized arteries n renal and visceral n ischemia  osteoneogenesis  fibrosis n hearing loss rare

14. Cogan’s Syndrome n Interstitial keratitis n vertigo, tinnitus, SNHL n positive LTT to corneal antigen

15. Vogt-Koyanagi-Harada (VKH) Syndrome n SNHL, vestibular signs, uveitis n periorbital hair loss, depigmentation n aseptic meningitis n ?autoimmunity to melanocytes

16. Wegener’s Granulomatosis n Necrotizing granulomata n vasculitis n respiratory tract and kidneys n serous OM n cANCA 90% specific

17. Behçet’s Disease

18. Relapsing Polychondritis n Recurrent inflammation of ear, nose, trachea, larynx n autoantibodies to cartilage II & IX n NSAIDs, steroids, dapsone

19. Systemic Lupus Erythematosus n Anti-nuclear, anti- DNA antibodies n numerous systemic manifestations n COM with vasculitis, SNHL, dysequilibrium

20. Rheumatoid Arthritis n Small joints of hands and feet n vasculitis, muscle atrophy, subcutaneous nodules, splenomegaly n IgM 19S and 7S, IgG 7S 75% n 44% bilateral SNHL

21. Meniere’s Disease n Fluctuating SNHL, episodic vertigo, aural fullness n ? Autoimmune etiology –97% with CICs (Derebery) –response to immunotherapy –32% with anti-68kDa antibody

22. Treatment n Steroids n Cyclophosphamide n Plasmapheresis n Methotrexate –dihydrofolate reductase inhibitor

23. Complications of therapy

24. Case Study n 45 year old female n right sided hearing loss and aural fullness, dysequilibrium progressive over 2 months time n physical normal except Weber AS, Rinne positive AU

25. Case Study, continued n CBC, chemistries, TFTs, RPR, ESR normal n MRI acoustic protocol normal n low salt diet, Dyazide

26. Case Study, continued n At follow-up, AD hearing worse n Prednisone 30 mg BID n anti-68kDa protein positive

27. Case Study, continued nHnHearing improved nsnsteroids tapered nonone relapse, again with improvement on steroids

28. Conclusion n Elusive etiology, diagnosis and treatment n potentially treatable cause of progressive SNHL n need less toxic therapy