Autoimmune Ear Disease

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Autoimmune Ear Disease Powered By Docstoc
					      Hearing Loss with
     Rheumatic Diseases
Disease Hearing Loss           Correlations
RA      25%-44%             +/-: Activity, RF
                            None: Disease duration,
                            NSAIDs, MTX

SLE 31%-15%                 None: age, disease activity,
                            antibodies, creatinine

GCA 64%      (Subjective)   None: ESR
      (90 % had             (With prednisone Rx: 27% hearing
      Vestibular             & 70% vestibular sx improved )
        Hearing Loss with
       Rheumatic Diseases
Disease Hearing Loss       Correlations
 PSS       20%         None: age, systemic
                       manifestations, antibody profile
         (PT=20)       or drugs

  SS       46%         None: duration, Prior CS, extra-
                       glandular complications
        (PT=30)        9/14 pts + ACLA

  TA    Anecdotal
  RP    ~20%
       Hearing Loss with
      Rheumatic Diseases
Disease    Hearing Loss        Clinical Course

WG        Anecdotal     May improve with
          reports, one  Prednisone/CTX
          series had 8%
          with S-N
PAN       Anecdotal        May improve with prednisone

Cogan’s 97%                Improve with Treatment
Autoimmune Ear Disease
How much Hard Science?
“Twenty-eight of the 132 patients revealed
  symptoms typical for FMS or CFS including
  fatigue, myalgia, arthralgia, depression,
  sicca syndrome and diarrhea. Because of
  the association of antibodies known to be
  present with these diseases and hearing
  loss, the authors recommend questioning
  patients that present with hearing loss for
  symptoms of CFS and FMS.” ?????
                         Current Rheum Reports 2000, 2:171
          Treatment of AIED
    Problems with Published Studies

• Limited studies due to rarity of the clinical disorder
• Length of hearing loss 3 weeks - 5 year
• Poor long term follow-up
• Empirically based in many papers
• Only one randomized, double blind, prospective
  study- Most are open label or anecdotal
• Cogan’s syndrome, Meniere’s and AIED are
  published together in many articles
• Subjective Improvement ≠ Objective Improvement
         Criteria used for

• Primary Outcomes
  • 10 dB Pure Tone Improvement
  • 12% improvement in Speech
• Secondary Outcomes
  • Vestibular symptoms reported but very
    few objective measurements
  • Subjective hearing improvement
 Autoimmune Ear Disease
• First patient described had hearing loss and 7th
  nerve paralysis. After almost total hearing loss the
  patient was started on prednisone and had 2 -2
  week courses of CTX improved
• Published a series of 18 patients (5 had facial
  paralysis & “ vestibular dysfunction also involved”)
• 18 patients with + response (treated 6 mo-2 yr)
• No long term follow-up
• Some cases had middle ear tissue destruction

                                      Ann Otol 1979;88:585-589
 Autoimmune Ear Disease
• Patients: 17 with hearing loss and/or
  vestibular dysfunction who responded to
  one week of high dose prednisone
• Protocol: Prednisone tapered to lowest
  level needed to maintain improvement
  CTX added. After maximal improvement
  tapered off. If flared then CTX restarted x 3
• 100% response
                           Laryngoscope 1994;104:1235-1239
         Treatment with
•  Study 1-12 patients with hearing loss for a
  mean 22 days : Rx with Azathioprine + Pred
   3 -6 month
   • 10/12 improved- How long?
   • Pred vs Aza effect ?
• Study 2 -10 patients (CS, Meniere’s, Hydrops)
  treated with Pred+ Azathioprine6/10
• Study 3 Azathioprine 4/7 Prednisone non-
  responders improved
• Does the azathioprine have a beneficial
             ENT J 2001;80:808-822, J Int Med Res1993;21:192-196,
              Acta Otolaryngol 1997; Suppl 529:83-85
 Autoimmune Ear Disease
       MTX Studies
• Open-label prospective study of 17 patients
  (Cogan’s(3), Meniere’s(9), Idiopathic S-N
  hearing loss(5)) who improved with high dose
  prednisone challenge
• MTX:7.5 mg/week 25mg/week over 8 weeks
• Results after one year
   •   AIED: 3/5 improved, 1/5 stable, 1/5 worse
   •   Meniere’s: 5/7 improved,1/7 stable, 1/7 worse
   •   Cogan’s 3/3 improved
• Although 12/15 objectively improved only 6/17
  subjectively improved !
                               Arth Care and Res 2001;45;146-150
   Autoimmune Ear Disease
         MTX Studies

• Open label prospective study of patients with
  bilateral Meniere’s (11) or progressive S–N hearing
  loss (10)
• Sx average 5.3 years, 6 had an autoimmune
  disease, responded to prednisone challenge
• MTX 7.5 mg/wk 15 mg/wk for 12.9 months
• Improved Hearing
   • Meniere’s- 7/11
   • Progressive S-N hearing loss- 8/10

                     Otolarygol Head Neck Surg 1997;116:146-152
    Autoimmune Ear Disease
          MTX Studies
• Patient Population: Retrospective clinical trial of 18
  patients with Meniere’s who had failed “standard
  treatment” and improved with one month high
• Mean duration of symptoms: 10 years
• Treatment: MTX 7.5 mg/kg 15 mg/week (16.7
  month av.)
• Improvement:
    • Vertigo-78%
    • Hearing- 28% (stabilized in 39%)
    • Tinnitus- 65%
•   Follow up 6- 12 month intervals

                                         ENT J 2000;79:82-92
Immunosuppressive in
Prednisone Non-responders
or Relapse off Prednisone
Open label study
  • Progressive hearing loss
  • 68 kD inner ear antigen
  • Non-responders to prednisone (21 pts) or
    relapsed off prednisone (6 pts)
• 17/27 improved with the addition of MTX or
• 2/6 control ears also improved!
• How many weaned off prednisone?

                                   ENT J 2001;80:808-822
    Autoimmune Ear Disease
          MTX Studies
•   Randomized, double-blind, placebo
    controlled trial
•   Protocol: Prednisone 60 mg/day for one
    month randomized to receive either MTX
    7.5 mg/week  20 mg/week or placebo
•   Prednisone tapered over 18 weeks
•   1° End Point- Compared to improvement
    obtained after treatment with prednisone
•   2 ° Endpoint – Compared to baseline

                               JAMA 2003;290:1875-1883
 Hearing Loss Relative to
Point of Randomization into
               Both placebo and
                deteriorated equally
                with time

                         JAMA 2003;290:1875-1883
Hearing Loss in Comparison
   with Baseline Values

                  Both placebo and
                   deteriorated to
                   entry level
                  MTX no more
                   effective than

                     JAMA 2003;290:1875-1883
    Autoimmune Ear Disease
• Infliximab- Anecdotal report of one patient
  that improved 15 db
• Adalimumab- no studies

• Anakinra- no studies

• Etanercept- 12 patients (Meniere’s or S-N
  hearing loss) who responded to high dose
  prednisone Rx 25 mg twice a week
Results: 7/12 improved and 4/12 stabilized
                          Acta Otolaryngol 2002;122:684-687,
                          Curr Opin Rheum 2001;13:184-189
Summary of Treatment

• Initial therapy
  • Prednisone 60 mg/day x 4 weeks
     • No improvement taper off steroids
     • Improvement  continue until monthly
       audiograms stabilize taper over 2 months
       to 10-20 mg QOD treat for 6 months
  • Relapse with taper  retreat with
  • Add an immunosuppressive ?
Summary of Treatment

• Recurrence after prednisone taper add
  •   Cytoxan ?
  •   Methotrexate?
  •   Azathioprine?
  •   TNF Inhibitors?