![Page 1: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/1.jpg)
Autoimmune Inner Ear
Disease (AIED)
Christopher D. Muller, M.D.
Faculty Advisor: Arun Gadre, M.D.
The University of Texas Medical Branch
Department of Otolaryngology-Head and Neck Surgery
Grand Rounds Presentation
December 10, 2003
![Page 2: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/2.jpg)
Definition:
(RPSNHL) (rapidly progressive SNHL) –
30 dB or greater SNHL over at least three contiguous
audiometric frequencies occurring over weeks to months
SSNHL (Sudden SNHL) –
30 dB or greater SNHL over at least three contiguous
audiometric frequencies occurring in <3 days
![Page 3: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/3.jpg)
Theories
Viral
Autoimmune (autoimmune inner ear
disease – AIED)
Vascular
Intracochlear membrane breaks
![Page 4: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/4.jpg)
Introduction - AIED
Relatively new etiologic mechanism for
sudden or rapidly progressive hearing
loss
Inner ear proteins recognized as foreign
or non-self
Primary process
Secondary to trauma or inflammation
![Page 5: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/5.jpg)
Introduction - AIED
Some clinicians doubt the existence of
the disease
Inner ear antigens not yet known
Inability to evaluate histopathology
![Page 6: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/6.jpg)
Introduction - AIED
Important for physicians to understand
the concept of the disease
Treatable cause of SNHL
Treatment must be started early in the
disease course
![Page 7: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/7.jpg)
Introduction - AIED
Devastating to patients
Frustrating for physicians
![Page 8: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/8.jpg)
Take Home Message
AIED
Rapidly progressive (weeks to months)
bilateral SNHL
Responds to immunosuppression
Treat with steroids first
+/- cytotoxic drugs
![Page 9: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/9.jpg)
Introduction - AIED
1979 – McCabe first described AIED
Series of 18 patients
Bilateral, rapidly progressive SNHL
100% had a + Lymphocyte transformation test
(LTT) compared to 0% in controls
Hearing improved with steroids
One temporal bone showed vasculitis
![Page 10: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/10.jpg)
Inner Ear Immunology
Inner ear is not immune privileged
Endolymphatic sac contains
immunocompetent cells (Takahashi, 1988)
Site of antigen processing in the inner ear
Protects other inner ear sites from foreign
or infectious agents
Protects from immunologic damage
![Page 11: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/11.jpg)
Inner Ear Immunology
Cochlea is devoid of immune cells
Antigens or protein injected into the scala
tympanic will reach the endolymphatic sac (Yeo, 1995)
![Page 12: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/12.jpg)
Inner Ear Immunology
Evidence of inner ear autoimmunity
Loss of hearing in animals immunized with
inner ear proteins (Orozco et. al, 1990)
![Page 13: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/13.jpg)
Inner Ear Immunology
Evidence lacking to support
autoimmunity in the inner ear
No antigen found as a single target of
autoimmunity
Candidate antigens proposed
68 kDa protein linked to hsp 70
Type II collagen
Many more
![Page 14: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/14.jpg)
Histopathology
Postmortem examination has shown
osteoneogenesis
Unable to exam T-bone during disease activity
Response to immunosuppression
Animals pretreated with cyclophosphamide
prior to viral insult have reduced hearing loss (Darmstadt et al.)
Steroids and cytotoxic agents are not specific
to immunity
![Page 15: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/15.jpg)
History
Time course
Associated symptoms Vertigo/dizziness
Aural fullness
Tinnitus
Ototoxic drug use
Symptoms of URTIs
H/O head trauma, straining, sneezing, nose blowing, intense noise exposure
H/O flying or SCUBA diving
![Page 16: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/16.jpg)
History
PMH:
Autoimmune disorders
Vascular disease
Malignancies
Neurologic conditions
Hypercoagulable states
Sickle cell disease (African Americans)
PSH: stapedectomy or other otologic
surgeries
![Page 17: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/17.jpg)
Physical Exam
Complete H&N exam
Ears: r/o effusions, cholesteatoma, cerumen impaction
Weber/Rinne
Neurologic exam – cerebellar findings Tandem gait
Romberg
Nose to finger, heel to shin
Vestibular – Dix-Hallpike test
![Page 18: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/18.jpg)
Diagnosis
AIED – classified as a cause of SSNHL More commonly RPSNHL
Bilateral and asymmetric
50% with vestibular symptoms Ataxia or light-headedness
Episodes are multiple times daily
Vestibular testing reveals bilateral reduced responses
Slight predominance in middle-aged females
< 30% have systemic autoimmune disease
![Page 19: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/19.jpg)
Diagnostic Testing
Audiogram – diagnostic and prognostic Pure tone
Speech discrimination
Tympanometry
Stapedial reflex
![Page 20: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/20.jpg)
Diagnostic Testing
Laboratory testing CBC
ESR, CRP
Chemistry
Cholesterol/triglycerides
T3/T4, TSH
RPR, VDRL
HIV
Lyme titer
Antigen-specific cellular immune tests
Lymphocyte transformation test (LTT)
Western blot
![Page 21: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/21.jpg)
Diagnostic Testing
MRI:
Rule out cerebellopontine angle tumors
Multiple sclerosis
ischemic changes
10%-19% of patients with acoustic tumors
present with SHL
23% may recover hearing
1% of patients with asymmetric SNHL have
acoustic tumors
![Page 22: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/22.jpg)
Diagnosis
No test to definitively diagnose AIED
Dx currently based on
sudden or RPSNHL,
Responsiveness to immunosuppressive therapy,
+/- positive LTT or Western blot
![Page 23: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/23.jpg)
Diagnosis
Hughes (1996) –
Lymphocyte transformation test
Sensitivity – 50-80%
Specificity – 93%
Positive predictive value 56-73%
Western blot
Sensitivity – 88%
Specificity – 80%
Positive predictive value – 92%
![Page 24: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/24.jpg)
Diagnosis
Currently antigen-specific cellular immune tests are not used routinely by most clinicians
Availability
Does not change management
Low sensitivity
Experimental
![Page 25: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/25.jpg)
AIED
Ideal test for AIED Marker specific for AIED
1990 – Harris and Colleagues Used Western blot to discover anti 68kDa
autoantibody in sera of patients with Idiopathic sudden or RPSNHL
22%-89% will have +test
![Page 26: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/26.jpg)
Moscicki (1990)
Run test during disease activity
94% specificity
Correlating results with responsiveness to therapy
and disease activity
![Page 27: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/27.jpg)
AIED
Further studies
Billings and Harris
Linkage of 68KD protein to heat shock protein 70 (hsp
70)
Theories
1) Cross reactivity
2) Over expression leads to autoimmunity
Gong and Yan (2002) – increase expression of hsp 70 in
guinea pigs immunized with CIEAgs
![Page 28: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/28.jpg)
Trune et al.(1998)
Could not induce hearing loss with hsp 70
in guinea pigs
Harris
Could not induce hearing loss in
immunized mice with hsp 70
![Page 29: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/29.jpg)
Multiple other candidate antigens have
been proposed
Type II Collagen (Yoo et al., 1982)
Beta tubulin (Connolly et al., 1997)
30 kDa protein
c Raf
![Page 30: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/30.jpg)
Autoimmune SNHL
Cogan’s syndrome
Wegener’s granulomatosis
Polyarteritis nodosa
Temporal arteritis
Buerger’s disease (Thromboangitis
Obliterans)
Systemic Lupus Erythomatosis
![Page 31: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/31.jpg)
Autoimmune SHL
Cogan’s syndrome
First described by Cogan in 1940
Autoimmune disease of the cornea and inner ear
Age of onset 22-29 years
Presentation – interstitial keratitis and Meniere’s
like episodes of vertigo with BRPSNHL
Associated systemic diseases
Takayasu’s like or medium-sized vessel vasculitis
Aortitis – 10%
![Page 32: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/32.jpg)
Cogan’s Syndrome
![Page 33: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/33.jpg)
Autoimmune SHL
Cogan’s Syndrome
Hearing fluctuates with disease exacerbations and
remissions
Majority develop bilateral deafness (67%)
Etiology is unknown
? Microbial etiology
Borrelia burgdorferi
Chlamydia species
![Page 34: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/34.jpg)
Autoimmune SHL
Cogan’s Syndrome
Diagnosis –
Requires both eye and inner ear
manifestations of inflammation
CBC, ESR, RPR, FTAbs
MRI/CT
Therapy – Same as for AIED
![Page 35: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/35.jpg)
Treatment
Controversial
Varied
Lack of double-blind, prospective
clinical trials
Consensus – steroids are effective and
should be used
![Page 36: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/36.jpg)
Treatment
Prednisone 1mg/Kg/day for 4 weeks
Slow taper
Relapse during taper – restart (?higher dose)
Slow taper
If relapse during taper – Cytotoxic agent Methotrexate (7.5-15mg weekly + folic acid)
Cyclophosphamide (100mg po bid)
Monitor electrolytes, LFTs, blood counts, U/A
Rheumatology consultation
![Page 37: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/37.jpg)
Treatment
McCabe favors starting with
cyclophosphamide and prednisone from
the start
![Page 38: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/38.jpg)
Treatment
1996 - Review by Hughes
Recommendations for treatment
Low salt (2g/day diet) and Maxide once daily
Prednisone 1mg/kg/day
Acyclovir 1-2 g orally daily in five divided doses
for 10 days
![Page 39: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/39.jpg)
Treatment Data
Sismanis 1997 – MTX 69.6% with hearing improvement
80% with vestibular improvement
Matteson (2001) – prednisone 72% w/ hearing improvement
Moscicki (1994) – prednisone 75% w/ hearing improvement w/ + Western blot
18% w/ - Western blot
![Page 40: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/40.jpg)
Treatment Data
Harris (2003) 57% improved on prednisone
Found that MTX did not have any affect on maintenance of hearing improvement compared to placebo
Lasak (2001) Prednisone had more effect on PTA
(14.8 vs. 4.5 dB)
Cytotoxic drugs had more effect on speech discrimination
(26.2 vs. 6.9%)
![Page 41: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/41.jpg)
Treatment
Steroids 1980 – Wilson and colleagues
Double-blind studies with oral steroids in patients with SSNHL
Decadron given over 10-12 days
Patients stratified based on audiogram
Results: steroids work in patients with hearing loss between 40 and 90 db
No effect for patients with >90 db
Midfrequency loss – patients excluded from study
1984 - Findings confirmed by Moskowitz
![Page 42: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/42.jpg)
![Page 43: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/43.jpg)
Plasmapheresis
Proposed by Luetje (1989)
1997 – Luetje reported on 21 patients
Several had remarkable improvements in
hearing
If available, reserved by most for
immunosuppressive treatment failures
![Page 44: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/44.jpg)
Some patients will progress to bilateral
profound deafness
Remember cochlear implantation
Excellent candidates
![Page 45: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/45.jpg)
Prognosis
Natural course of AIED is not known
47%-63% w/ SSNHLspontaneously resolve
Combined patients with all audiogram types
Four prognostic variables
Time since onset
Audiogram type
Vertigo
age
![Page 46: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/46.jpg)
Prognosis
1984 – Byl
8 year prospective study of 225 patients with
RPSNHL or SSNHL
Looked at factors for prognosis
Age
Vertigo
Tinnitus
Audiogram pattern
Time elapsed on presentation
ESR level
![Page 47: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/47.jpg)
Prognosis
Age - <15 and >65 years had worse
prognosis
![Page 48: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/48.jpg)
Prognosis
Vertigo – 29% recovery if affected
- 55% if not affected
![Page 49: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/49.jpg)
Prognosis
Audiogram type
![Page 50: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/50.jpg)
Prognosis
56% recovery presenting within 7 days onset
27% presenting 30 days or later
![Page 51: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/51.jpg)
Conclusion
Devastating to patients
Frustrating for physicians to dx and tx
Thorough H&P
Rule out treatable cause
Directed labs, Audiogram MRI
Discuss risks, benefits, and alternatives of treatment with the patient
Treat the disorder aggressively
Rehabilitate those whose hearing does not improve
Follow patients for development of associated diseases and for contralateral ear disease
![Page 52: Autoimmune Inner Ear Disease (AIED) - The University of Texas](https://reader030.vdocuments.net/reader030/viewer/2022021120/62060870cf456418c32f2619/html5/thumbnails/52.jpg)
Future
Improved understanding of immunologic
events in the inner ear
Balance of Th1 and Th2 lymphocytes
Th2 – maintenance of “tolerance”
Understanding the role of Th2 gene
products
May lead to new immunotherapeutic strategies