1. 19th INTERNATIONAL SYMPOSIUM ON RECENT ADVANCES IN OTITIS MEDIA
Characteristic findings of the tympanic membrane in otitis media with ANCA-associated vasculitis (OMAAV) patients in relation to relapse
Yuka Morita, Kuniyuki Takahashi, Shuji Izumi, Yamato Kubota, Shinsuke Ohshima, Arata Horii
Department of Otolaryngology Head and Neck Surgery
Niigata University Graduate School of Medical and Dental Sciences
June 4-8, 2017 Gold Coast, Australia

2. ANCA-associated vasculitis (AAV)
GPA
：Granulomatosis with polyangitiis
Otologic symptoms
MPA
：Microscopic polyangiitis
EGPA
AAV consists of 3 groups: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA; formerly Wegener’s granulomatosis), and eosinophilic granulomatosis polyangiitis (EGPA; formerly Churg-Strauss syndrome).
Recently, the occurrence of otologic symptoms such as otitis media and hearing loss frequently have been reported in patients with AAV.
：Eosinophilic granulomatousis
with polyangiitis

3. ANCA-associated vasculitis (AAV)
GPA
：Granulomatosis with polyangitiis
MPA
Otitis media with AAV
:OMAAV
：Microscopic polyangiitis
EGPA
AAV consists of 3 groups: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA; formerly Wegener’s granulomatosis), and eosinophilic granulomatosis polyangiitis (EGPA; formerly Churg-Strauss syndrome).
Recently, the occurrence of otologic symptoms such as otitis media and hearing loss frequently have been reported in patients with AAV.
：Eosinophilic granulomatousis
with polyangiitis

4. ANCA-associated vasculitis (AAV)
GPA
：Granulomatosis with polyangitiis
MPA
Otitis media with AAV
:OMAAV
：Microscopic polyangiitis
EGPA
AAV consists of 3 groups: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA; formerly Wegener’s granulomatosis), and eosinophilic granulomatosis polyangiitis (EGPA; formerly Churg-Strauss syndrome).
Recently, the occurrence of otologic symptoms such as otitis media and hearing loss frequently have been reported in patients with AAV.
：Eosinophilic granulomatousis
with polyangiitis

5. Diagnostic criteria of OMAAV
Japan otological society
A clinical diagnosis of OMAAV was done, if the following three criteria (A, B, C) were fulfilled.
A) Experience of suffering from intractable otitis media with effusion or granulation,
which was resistant to antibiotics and insertion of tympanic ventilation tube,
accompanied by progressive hearing loss over less than 2 months.
B) At least one of the following four findings:
1)positivity for serum MPO- or PR3-ANCA
2)histopathology consistent with AAV
3)diagnosis of AAV (GPA, MPA, EGPA) by the presence of other involvements prior
　　 to occurrence of ear symptoms
4)at least one sign/symptoms of AAV-related involvements other than ear (eye,
nose, pharynx/ larynx, lung, kidney, facial palsy, hypertrophic pachymeningitis,
and the others).
C) Exclusion of the other intractable otitis media such as bacterial otitis media,
cholesterol granuloma, cholesteatoma, malignant osteomyelitis, tuberculosis,
neoplasms and eosinophilic otitis media, as well as exclusion of the other
auto-immune and vasculitis diseases other than AAV such as Cogan‘s disease
and PN, etc.
There are no tympanic membrane findings in this criteria.
This slide shows Diagnostic criteria of OMAAV that we propose.
Using the criteria, we can diagnose AAV without lung or renal dysfunction.
Harabuchi et al. Modern Rheumatol 2016

6. 69 M MPO-ANCA (+) / lung dysfunction
before treatment
posterior wall swelling
vascular dilatation of　pars tensa
thickening of pars tensa

7. 69 M MPO-ANCA (+) / lung dysfunction
before treatment
2 weeks
6 weeks
10weeks
Tympanic membrane findings may reflect the disease activity of OMAAV.
posterior wall swelling
vascular dilatation of　pars tensa
thickening of pars tensa

8. Objectives What are the characteristic findings of
tympanic membrane(TM) in OMAAV ?
Are TM findings useful for early detection of relapse?
We would like to explore the possibility to detect the relapse
by changes of TM findings in OMAAV.
Our question is
What is the clinical feature in the OMAAV patients with facial nerve palsy and/or hypertrophic pachymeningitis?
Furthermore,
What is the clinical feature in the OMAAV patients with relapse?
Because AAV including OMAAV is easy to relapse.
By investigating of them, we would like to explore the clues of early diagnosis and early detection of relapse.

9. unilateral / bilateral
Material & Methods
Among 33 OMAAV patients who were treated in our hospital, 17 patients whose TM findings could be retrieved by photographs were enrolled into the study.
age
41~81 (median 70)
male/ female
5 / 12
affected side
unilateral / bilateral
3 / 14
(Total 31 ears)
Otoscopic findings were retrospectively examined.

10. The points of tympanic membrane findings
① vascular dilatation of pars tensa
② thickening of pars tensa
③ posterior wall swelling ③ ② ①

11. posterior wall swelling
Results
TM findings of 31 OMAAV ears
(%)
vascular dilatation
of pars tensa
thickening of
pars tensa
posterior wall swelling
These findings are not usually seen in the patients with OME.

12. Case　Presentation

13. Case 1: 68 F Chief complaint: Bil. hearing loss
History of present illness:
The patient initially visited the hospital with complaint of bilateral hearing loss for two months. She was diagnosed as having OME. Hearing loss gradually progressed along with worsening of bone conduction hearing thresholds.

14. Case 1: 68 F Fluid collection was seen in both tympanic cavity.
vascular dilatation
Fluid collection was seen in both tympanic cavity.
Vascular dilatation of pars tensa appeared
in the left ear.
CRP 1.4 mg/dl　MPO-ANCA 62.2 U/ml
She was diagnosed as OMAAV
and 40mg of prednisolone (PSL) started.

15. Case 1: 68 F At the first visit vascular dilatation CRP 1.4 mg/dl
MPO-ANCA 62.2 U/ml
8 months after treatment（PSL10mg, AZP25mg）
CRP 0.62 mg/dl　
MPO-ANCA 1.9 U/ml

16. Case 1: 68 F right hearing loss worsening of TM findings
At 18 months after the initial treatment,
vascular dilatation and thickening of pars tensa appeared
in the right ear.
right hearing loss
worsening of TM findings
no other organ failure
Relapse of OMAAV
CRP 0.97 mg/dl　
MPO-ANCA 3.2 U/ml
PSL was increased to 30 mg

17. Progress of hearing loss
Case 1: 68 F
Relapse
(18 months after the initial treatment)
1 month later
Progress of hearing loss
No other organ failure
PSL30mg
PSL increased to 45mg +
IVCY　4 courses
CRP 0.97 mg/dl　
MPO-ANCA 3.2 U/ml
CRP 0.81 mg/dl　
MPO-ANCA 1.1 U/ml

18. Case 1: 68 F Relapse (18 months after the initial treatment)
1 month later
5 month later
CRP 0.97 mg/dl　
MPO-ANCA 3.2 U/ml
CRP 0.81 mg/dl　
MPO-ANCA 1.1 U/ml
CRP 0.50 mg/dl
MPO-ANCA <1.0 U/ml

19. Summary of Case 1
✔　Otologic symptoms were the only manifestation of OMAAV
throughout the clinical course.
✔　Changes in TM findings were associated with
hearing impairment and increase in ANCA titer.

20. Case 2: 68 F Chief complaint: Rt. hearing loss
History of present illness:
The patient was treated for right sudden hearing loss with vertigo, which showed no improvement. One year later, she was referred to our hospital for intractable otitis media and posterior wall swelling of the same side.

21. Case 2: 68 F severe posterior wall swelling intractable otitis media
profound hearing loss
serum ANCA: negative
no other organ failure
CRP 0.60 mg/dl　MPO, PR3-ANCA <1.0 U/ml
Follow up

22. thickening of pars tensa and vascular dilatation
Case 2: 68 F
At the first visit
6 month later
thickening of pars tensa and vascular dilatation
CRP 0.64 mg/dl

23. Case 2: 68 F At the first visit 6 month later 7 month later
worsening of
TM findings
CRP 0.64 mg/dl
CRP 0.57 mg/dl　MPO-ANCA 2.8 U/ml

24. Case 2: 68 F At the first visit 6 month later 7 month later
MRI CE-T1 (coronal)
hypertrophic pachymeningitis
CRP 0.64 mg/dl
CRP 0.57 mg/dl　MPO-ANCA 2.8 U/ml
At last, she could be diagnosed as OMAAV.
CRP 0.64 mg/dl　MPO-ANCA 4.2 U/ml

25. Case 2: 68 F At the first visit 6 months 7 months 35 months
PSL10mg,AZP50mg
CRP 0.04 mg/dl 　
MPO-ANCA <1.0 U/ml

26. Summary of Case 2
✔　Worsening of TM findings were preceded by ANCA changes.
✔　Hypertrophic pachymeningitis and positive ANCA were noticed
as the final events.

27. The indicator of disease activity
Discussions
The indicator of disease activity
In OMAAV
without other organ failure・・・・
serum ANCA titer / CRP
very slight rise of ANCA titer
difficult to judge the disease activity
associated organ disorder or worsening
Ear disorder can be diagnosed only by otolaryngologist.
TM findings are sensitive to the disease condition of OMAAV.
These two cases showed hearing loss and the rise of ANCA titer along with the worsening of the TM findings.

28. ＞ ＞ For early detection of relapse of OMAAV TM findings hearing loss
serum ANCA titer/CRP ＞ ＞
The changes in TM findings may reflect disease activity.
We should be careful to focus not only hearing examination but also TM findings.

29. Conclusions
Vascular dilatation, thickening of pars tensa and posterior wall swelling are the characteristic otoscopic findings in OMAAV.
 TM findings may be more useful for early detection of relapse than laboratory data.