Autoimmune Inner Ear Disease (AIED) Bastaninejad, Shahin, MD Assistant Professor of ORL-HNS, TUMS, AmirAlam Hospital

Case Presentation 45yrs female Right sided hearing loss and aural fullness, dysequilibrium progressive over 2 months Normal Px, except Weber test CBC, chemistries, TFTs, RPR, ESR were normal MRI  Normal

Low salt diet, Thiazide diuretics At follow-up, Left hearing worsed Prednisone 60 mg Daily Serum anti- 68kDa protein positive

On steroids, Hearing improved While steroid taper down, one relapse occured, again with improvement on steroids

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Definition AIEDAIED (McCabe 1979): –Rapidly progressive SNHL (over a course of weeks to months) –Bilateral –Responds to the administration of corticosteroids ImportanceImportance: –AIED is one of the few medically reversible causes of sensorineural hearing loss

Definition Classification: –Primary –Primary AIED  AIED –Secondary –Secondary AIED: SLE Ulcerative Colitis Cogan’s Syndrome Multiple Sclerosis Wegener’s Granulomatosis Various systemic vasculitides Sjogren’s Syndrome Celiac Disease

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Epidemiology & Pathogenesis Primary AIED is a rare disorder True incidence is not clear. More common in middle aged woman Pathogenesis: there is no direct evidence that Primary AIED is autoimmune in etiology … –Although this disorder is likely immune mediated, there is no direct evidence that Primary AIED is autoimmune in etiology … –inflammation –inflammation lead to the fibrosis and osteoneogenesis of the cochlea –Vasculopathy  necrosis associated with vasculitis in the absence of inflammation Secondary AIED

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Clinical Presentation may initially be unilateralThe hearing loss may initially be unilateral, and it may take months for the bilaterality to emerge Fluctuations in hearing may occurFluctuations in hearing may occur, but the overall course is one of a relentless deterioration in auditory function 50% 20%50% have Vestibular symptoms, in 20% of the cases Vertigo is like Meniere’s disease

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Differential Diagnosis Sudden deafnessSudden deafness –It’s mainly unilateral  while AIED is bilateral –It is an emergency  while AIED is not –It develops in less than 72hr  but AIED occurs in weeks to months –In SSNHL treatment window is 2 to 4 weeks, but in a patient with AIED who develop SNHL in 6 to 12mo, we can still achieve significant recovery with corticosteroids

Differential Diagnosis Meniere’s DiseaseMeniere’s Disease –Very difficult to differentiate these two entities during first months of evaluation –The only difference is: more aggressive course of AIED (regarding haring loss) OtosyphilisOtosyphilis Acoustic neuromaAcoustic neuroma MeningitisMeningitis MSMS MalignancyMalignancy (e.g., metastatic disease, lymphoma)

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Laboratory and Paraclinical work up Lab: –CBC/diff –ESR –RF –ANA, Anti-dsDNA, Anti-phospholipid –Anti-SSA/B –C3, C4 complement level –FTA-ABS –HIV but can neither confirm nor rule out the diagnosis –Western blotting for antibody against 68-kD Ag, or Anti-HSP70  positive result may support the diagnosis of AIED, but can neither confirm nor rule out the diagnosis

Laboratory and Paraclinical work up Paraclinics:Paraclinics: –MRI, Brain and Skull base, +/-Gd –ENG –Monthly –Monthly Audiometeric assesment About Anti-HSP70:About Anti-HSP70: –It is positive in 89% of AIED –Further studies have failed to show that this test has sufficient sensitivity and specificity to rule in or rule out the diagnosis of AIED

progressive sensorineural a positive response to the administration of corticosteroidsThe diagnosis of primary AIED is based on clinical evaluation, the demonstration of progressive sensorineural hearing loss on audiometric assessment done at monthly intervals, and most importantly  a positive response to the administration of corticosteroids In summary

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Treatment Corticosteroid therapy –In Adult patients start with 60mg/day for 4weeks (children 1mg/kg/day) nonresponders –Taper down in days in nonresponders responders –In responders (15dB Improvement in one freq. or 10dB at two freq. or significant SDS improvement)…

Treatment …Continue full-dose therapy until monthly audiograms reached a plateau of recovery maintenance doseThen taper it down slowly over 8 weeks to a maintenance dose of 10 to 20mg every other day (total treatment duration more than 6mo)Continue maintenance dose for a variable time (total treatment duration more than 6mo)

Treatment Other therapies:Other therapies: –MTX (?)  Steroid sparing (?) –CTX (Cyclophosphamide)  severe side effects –Etanercept (?)  inhibitor of TNF-alpha –IT Steroid therapy –IT TNF-alpha –Systemic IgG injection –Plasmapheresis –Cochlear implantation

Treatment The only drug of proven utility in the management of AIED is CorticosteroidThe only drug of proven utility in the management of AIED is Corticosteroid

Presentation Outlines Definition Epidemiology & Pathogenesis Clinical Presentation Differential Diagnosis Laboratory and paraclinical work up Treatment Secondary AIED

Cogan’s Syndrome Interstitial keratitis vertigo, tinnitus, SNHL archetypal autoimmune inner ear disease Typical Cogan

Labyrinthine pathology may be coincident with the ocular manifestations or may occur up to 6 months before or after the onset of eye disease

Vogt-Koyanagi-Harada (VKH) Syndrome SNHL, Vestibular signs, Uveitis, … Periorbital hair loss and skin depigmentationPeriorbital hair loss and skin depigmentation Aseptic meningitis It may be autoimmunity to melanocytes

Wegener’s Granulomatosis Necrotizing granulomata Vasculitis Respiratory tract and kidneys involvement Serous OM C-ANCA 90% specific 30-50% ear involvement, usually middle ear, concomitant inner ear involvement  30%  SNHL30-50% ear involvement, usually middle ear, concomitant inner ear involvement  30%  SNHL

Polyarteritis Nodosa Vasculitis of small and medium-sized arteries Renal and visceral involvement Rarely rapidly progressive hearing loss

Behçet’s Disease

Relapsing Polychondritis Recurrent inflammation of ear, nose, trachea, larynx Autoantibodies to cartilage NSAIDs, steroids, dapsone

Systemic Lupus Erythematosus Anti-nuclear, anti- DNA antibodies Numerous systemic manifestations 58%COM with vasculitis, SNHL (58%), dysequilibrium

Rheumatoid Arthritis Small joints of hands and feet Vasculitis, muscle atrophy, subcutaneous nodules, splenomegaly 44% bilateral SNHL