Autoimmune Inner Ear Disease (AIED) refers to hearing loss or vestibular dysfunction caused by an immune-mediated process in the inner ear. It can be primary, restricted to the inner ear, or secondary to other autoimmune diseases. The cause is thought to be an immune response triggered by antigens in the inner ear. Common symptoms include progressive bilateral hearing loss over weeks to months. Treatment involves corticosteroids, with intratympanic injections as an alternative. Other immunosuppressants may be used if steroids are not effective. Systemic autoimmune diseases like Cogan syndrome, Granulomatosis with polyangiitis, and Systemic Lupus Erythematosus can also cause

1. Autoimmune Inner Ear
Disease(AIED)
Dr. JINU V IYPE
3RD YEAR PG
DEPARTMENT OF ENT

2. References:
• Cummings otorhinolaryngology 6th edition
• Ballenger's otorhinolaryngology – 16th edition
• Diseases of ear 6th edition – Harold ludman
• Scott brown 8th edition

3. • Historically the inner ear has been regarded
as an immunoprivileged site,
separated by the blood labyrinthine
barrier.
• Immunoglobulins (predominantly IgG)
are found in the perilymph at a fraction of
their serum concentrations.

4. • Endolymphatic sac
is thought to be the
likely site for
immune processing
due to the presence
of lymphocytes in the
perisaccular tissues.

5. Definition:
• The term autoimmune inner ear disease (AIED) refers to a
group of diseases in which hearing loss or vestibular
dysfunction results from an immune-mediated process.
Primary Secondary
pathology restricted multi-systemic autoimmune diseases
to the cochlea and inner ear
vestibular organs Cogan syndrome, Wegener
granulomatosis , SLE

6. • AIED was first described by McCabe1 in 1979 as
B/L SNHL that progressed over weeks to months
and was responsive to immunosuppressive agents/
steroids.
• Rare disorder in both its primary and secondary
forms-
<1% of hearing impairment or dizziness.
• Female
• Ages of 20 and 50 years.

7. There are several theories that
propose- cause of AIED
• In1980s -the inner ear
was capable of
mounting a locally
mediated immune
response via
endolymphatic sac
appears to be critical to
the formation of this
immune response

8. Cells that mediate this
response appear to
gain access to the
perilymphatic space
(scala tympani) via the
spiral modiolar vein.
The inflammatory
cascade that results
can cause decreased
function secondary to
loss of sensory cells,
fibrosis, and
eventually
osteoneogenesis
within the cochlea.

9. • Vasculitis within the labyrinthine
vasculature, including the stria
vascularis, is a likely mechanism of
pathogenesis, particularly in cases of
systemic vasculitides.
• A cochlear neuritis could, theoretically,
result in pathology that responds to
immunosuppressive treatment.

10. • Harris et al used bovine inner-ear extract as
antigen in Western blot assays and detected
antibody to a 68 kDa antigen in 35% of
patients with progressive SNHL.
• Inner ear-specific highly inducible heat shock
protein 70 (hsp70).
– hsp70 antibodies are elevated in autoimmune
SNHL
– presence of antibodies to hsp70 found in AIED

11. • Damage to the inner ear results in the release of
cytokines which trigger immune reactions.
– TNF-alpha, IL-1A, NFkB and IkBa have all been
found in the cochlea.
• Activation of cochlear nuclear factor kappa B
(NFКB)
• The inner ear may share common antigens with
potentially harmful substances and T-cells and
antibodies may damage the inner ear when trying
to fight these antigens.
• COCH5B2 has been proposed as a target antigen.

12. • Most recent study found the incidence of anti
type II collagen antibodies to be very low and
disputed it as a cause of AIED.

13. CLINICAL PRESENTATION
• The clinical hallmark of AIED is bilateral SNHL
that progresses over weeks to months.
• Aural fullness
• Tinnitus
• Vestibular symptoms = ataxia
imbalance
positional or episodic vertigo
motion intolerance

14. • Patients with primary AIED will rarely have
significant findings on clinical examination.
• In cases of secondary AIED, systemic
manifestations of the underlying autoimmune
disease
middle ear effusion (WG)
cough (WG);
skin lesions,
chondritis,
chronic sinusitis
visual loss (Cogan or Susac syndrome).

15. DIFFERENTIAL DIAGNOSIS
1. SSNHL
AIED SSNHL
Hearing loss
progresses over weeks
to months
Sudden and not
progressively
occur with unilateral
hearing loss,
eventually both ears
are involved
uniformly unilateral

16. LABORATORY TESTING
• The lymphocyte migration inhibition assay
• lymphocyte transformation test
-are of historic interest.
• Anti–HSP(heat shock protein )-70
• Serum tumor necrosis factor (TNF) levels.
an elevated TNF in a patient who comes in with
hearing loss strongly supports a diagnosis of an
immune-related hearing loss
low sensitivity precludes its use as a screening test.
Additionally, the level of TNF was not found to correlate
with treatment response with corticosteroids.

17. • complete blood count with differential
• erythrocyte sedimentation rate
• C-reactive protein
• rheumatoid factor
• antinuclear antibodies
• antineutrophil cytoplasmic antibodies(ANCA)
• anti–double-stranded DNA antibodies,
• anti-SSA/B antibodies,
• antiphospholipid antibodies,
• complement levels,
• thyroid-stimulating hormone and free thyroxine
levels.

18. • Otosyphilis must be ruled out with a test for
tertiary syphilis
–fluorescent treponemal antibody absorption
test
–micro-hemagglutination assay.

19. TREATMENT OF PRIMARY
AUTOIMMUNE INNER EAR
DISEASE
• Corticosteroids (prednisone or dexamethasone)
remain the standard of care for patients with
primary AIED.
• for adults consists of a therapeutic trial of
prednisone 1 mg/kg/day for 4 weeks and
must be started as soon as possible, because
irreversible damage can occur within 3 months
of onset.

20. • Patients who do respond are tapered slowly over
4 weeks to a maintenance dose of 10 to 20
mg/day.
• Relapse of symptoms-
restarted with high-dose steroids for 4
weeks.
• Side effect:
– Hyperglycemia, hypertension, Gastritis, weight gain,
pancreatitis, osteroporosis, opportunistic infection

21. INTRATYMPANIC CORTICOSTEROIDS
• Gaining popularity as a treatment for SSNHL.
Advantage
• Reduction in systemic corticosteroid side effects.
• IT steroids very rarely cause changes in serum glucose levels in
patients with diabetes.

22. • Given to patients with cataracts, myasthenia gravis
and glaucoma.
• The most frequently administered IT steroids are
DEXAMETHASONE- 10–24 mg/mL
SOLUMEDROL (methyl prednisolone sodium
succinate)- 30–40 mg/mL
Higher concentrations
may have better outcomes.

23. Use of facilitator
• Improved transport across the round window
membrane-histamine and hyaluronic acid.

24. Frequency and injection technique
• via a spinal needle on a syringe, through a
grommet or myringotomy,
• via a MicroWick or microcatheter
• hydrogel applications
• nanoparticles.
• Transtympanic needle or grommets are the
most frequently used

25. METHOTREXATE
• use methotrexate as a first-line prednisone-
sparing treatment.
• oral dose 7.5 to 20 mg weekly with folic acid

26. • Patients with severe hearing losses
• positive 68 kD Western blots
• Non responsiveness to prednisone or MTX
therapy
should be given to a trial of cyclophosphamide

27. CYCLOPHOSPHAMIDE
• Low-dose cyclophosphamide with low-dose
prednisolone as a test treatment for AIED for
3 weeks
• Cyclophosphamide was discontinued first
• steroids were tapered as long as hearing was
maintained.

28. Side effects
– Infection
– Myelosuppression
– Hemorrhagic cystitis
– Infertility
– Malignancy.
oral doses of 1 to 2 mg per day taken each
morning with liberal amounts of fluid

29. ETANERCEPT
• An antibody to TNF,
an important
inflammatory mediator
throughout the body
found at high levels in
the spiral ligament
fibrocytes when they
are stimulated by
inflammatory cytokines.

30. • Etanercept has proven to
be both safe and
relatively effective for
patients with
rheumatoid arthritis,
and several small,
studies have
demonstrated return of
hearing and a positive
safety profile in AIED
patients.
• Animal studies have
supported its use as
well, with reduced
cochlear inflammation
and improved hearing
reported.

31. OTHER TREATMENTS
• Mycophenolate mofetil - inhibits both T- and
B-cell synthesis, is well tolerated, and has a
favorable toxicity profile.
• Systemic administration of medications-
blood-cochlea barrier limits the amount of a
drug that can be delivered to the inner ear
doses that are systemically toxic may be
required to achieve therapeutic
concentrations at the site of interest.

32. • Plasmapheresis has also been shown to
improve hearing in some patients with
AIED.
• Its use as an adjunct for patients who do
not respond to or are intolerant of
immunosuppression

33. SYSTEMIC
AUTOIMMUNE
DISEASES
ASSOCIATED
WITH HEARING
LOSS

34. COGAN SYNDROME
• It is an autoimmune
disease characterized by
nonsyphilitic ocular
keratitis
vestibulocochlear
dysfunction.
• an interval between the
onset of the ocular and
audiovestibular features
of less than 2 years.

35. • The cochleovestibular symptoms include
vertigo and tinnitus
– Vestibular symptoms generally have a sudden
onset and last for days
• Hearing loss sudden, bilateral, fluctuating, and
progressive, and is most often down-sloping

36. • Ocular symptoms result from interstitial
keratitis
– bilateral
– Pain
– scleral redness
– photophobia.
– Visual acuity is decreased secondary to corneal
clouding

37. • Diagnosis is based on clinical examination and
exclusion of other autoimmune diseases.
• Anti-HSP 70 antibodies may be a marker for
the autoimmune nature of the hearing loss.
• ANCA positivie
• Ocular manifestations are treated with topical
steroids
• Hearing improvement with systemic
steroids(~)

38. • Vogt-Koyanagi-Harada syndrome is similar to
Cogan syndrome
– also includes alopecia
– vitiligo
– meningeal findings.
It is thought to be secondary to melanocytic antigens.

39. Granulomatosis with polyangiitis
• Necrotizing granulomatous inflammation
usually involves the upper and lower
respiratory tracts.

40. • Conductive hearing loss caused by middle ear
inflammation, or eustachian tube dysfunction
• pulmonary granulomata
• necrotizing glomerulonephritis
• skin rashes, arthritis, neuropathies,
• CNS, heart and GI involvement can all occur.

41. • In the localized phase of the disease 50% are
ANCA negative
• when generalized disease is present 90% are
positive for PR3 ANCA.
Treatment:
• intensive treatment with high dose steroids,
cyclophosphamide,
• for severe cases with methotrexate
• rituximab in milder cases.

42. Systemic lupus erythematous (SLE)
• Systemic lupus erythematous (SLE) represents
a common autoimmune disease characterized
by excessive production of antinuclear
antibodies that can form immune complexes
in the

44. SUSAC SYNDROME
• Aka retinocochleocerebral vasculopathy, is
thought to be an AIED.
• It is also known as RED-M syndrome :-
– retinopathy,
– Encephalopathy
– deafness
– microangiopathy.

45. • The inner ear pathology results from cochlear end-
arteriole occlusion.
• Hearing loss generally fluctuates and is asymmetric;
it is worse in the low to middle
frequencies, which reflects the predominance of
arteriopathy at the cochlear apex.
• Vestibular symptoms may also be present, and this
indicates involvement of the labyrinth.

46. Treatment
• Immunosuppressive treatment regimens form the
foundation of treatment, and antiplatelet agents serve
as adjuvants.

47. Behçet’s disease
• Behcet’s disease (BD) is a multi-system
vasculitis characterized by recurrent oral and
genital ulceration, skin lesions, audiovestibular
involvement and ocular inflammation.

48. • Diagnostic criteria are based on recurrent oral ulcers
occurring three times in 12 months plus two of the
following:
• scarring recurrent genita ulcers
• ocular involvement (uveitis or retinal vasculitis)
• skin lesions (such as erythema nodosum,
pseudofolliculitis)
• positive pathergy test (skin reaction to needle
insertion).

49. • Audiovestibular involvement is frequent with
sensorineural hearing loss in 23–32% of
patients
• bilateral, affecting high frequencies- due to
vasculitis of vessels supplying the cochlea.
• Recurrent vertigo

50. SUMMARY
• AIED refers to a group of diseases in which hearing
loss or vestibular dysfunction results from an
immune-mediated process.
• It can be Primary & Secondary
• The clinical hallmark of AIED is bilateral,Aural
fullness, Tinnitus and Vestibular symptoms
• Differenciate from SSNHL
• Investigation
• Treatment – systemic steriods/ Intra tympanic
treatment

51. Thank you!!