Behcet disease as a cause of hearing loss: A prospective, placebo-controlled study of 29 patients

March 24, 2013
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Abstract

We conducted a prospective, placebo-controlled study to determine the incidence and severity of inner ear involvement and hearing loss in patients with Behçet disease. Our study population was made up of 29 patients with Behçet disease and 28 healthy controls. Audiometric pure-tone thresholds and transient evoked otoacoustic emission (TEOAE) levels were determined in both groups. The main outcome measures were pure-tone audiometry (PTA) levels and TEOAE levels in the two groups. PTA detected a sensorineural hearing loss in 10 of the 29 patients (34.5%). The difference in audiometric findings between the two groups was statistically significant at 1, 2, 4, and 8 kHz (p ≤ 0.0498). A comparison of TEOAE levels revealed that the difference in sound-to-noise ratio between the two groups was not significant at 1, 1.5, 2, and 3 kHz, but it was significant in 4 kHz (p = 0.02), and the difference in reproducibility between the two groups was significant at 2 and 4 kHz (p ≤ 0.03). We conclude that all patients with Behçet disease should be screened for hearing impairment and subsequently treated if an impairment is discovered.

Introduction

Behçet disease is a multisystem vascular inflammatory disease of unknown origin. This entity was first described by Dr. Hulusi Behçet in 1937 as a clinical triad of aphthous ulceration, genital ulceration, and iridocyclitis.1 The presentation of disease is not limited to these three signs. It is a disorder that may involve many areas, including the central nervous system (CNS), gastrointestinal tract, lungs, skin, veins, and arteries.

The International Study Group for Behçet's Disease has recommended that recurrent oral ulceration be a prerequisite for a definitive diagnosis, together with two of the following: genital ulcers, skin lesions, eye lesions, and skin hypersensitivity reaction (pathergy test).2 The presence of other signs-such as arthritis or involvement of the CNS or the gastrointestinal or vascular system-represents minor criteria that may support the diagnosis.2

Hearing loss is also common in Behçet disease. In this study, we aimed to compare the incidence of hearing loss, the degree of hearing loss, and the nature of inner ear involvement in Behçet disease patients and healthy controls.


Patients and methods

We reviewed the cases of 1,000 patients with Behçet disease to identify those who met the inclusion criteria for our study. We identified 29 such patients-18 men and 11 women, aged 22 to 51 years (mean: 37.8). We also recruited a control group of 28 individuals without Behçet disease-14 men and 14 women, aged 20 to 48 years (mean: 31.8). There were no significant differences between the two groups in terms of sex and age (table 1). There is no Institutional Review Board at our hospital, but we did obtain proper informed consent from all participants in keeping with the mandate of the Declaration of Helsinki.

Table 1. Distribution of sex and age in the two groups

Demographic variable

Behçet patients (n = 29)

Controls (n = 28)

Sex, n (%)

 

 

 Men

18 (62.1)

14 (50.0)

 Women

11 (37.9)

14 (50.0)

Age, yr

 

 

 Range

22 to 51

20 to 48

 Mean ± SD

37.8 ± 8.9

31.8 ± 6.2

 

All patients fulfilled the International Study Group's diagnostic criteria for Behçet disease.2 Patients with a history of recurrent otitis, cranial trauma, ototoxic drug use, any condition related to inner ear damage, and any otologic or neurologic disease unrelated to Behçet disease were excluded from the study. All patients and controls underwent an ENT examination, and those who had an acute or chronic ear infection or a perforated tympanic membrane were excluded.

The duration of disease in the Behçet group ranged from 2 to 21 years (mean: 8.9 ± 4.1). All of the study patients had oral ulcers, and most had current or previous genital ulcers and a positive pathergy test (table 2). Eye involvement at some time during the course of the disease and skin lesions were seen in a minority of patients.

Table 2. Clinical findings in the Behçet group

Finding

n (%)

Oral ulcers

29 (100)

Genital ulcers

27 (93.1)

Positive pathergy test

27 (93.1)

Eye involvement

7 (24.1)

Skin lesions

4 (13.8)

 

Patients and controls underwent pure-tone audiometry (PTA) at 0.25, 0.5, 1, 2, 4, and 8 kHz (AC 40 clinical audiometer; Interacoustics; Assens, Denmark) and measurement of transient evoked otoacoustic emissions (TEOAEs) at 1, 1.5, 2, 3, and 4 kHz (Otodynamics; Hatfield, U.K.).

Statistical analysis was performed with the Statistical Package for the Social Sciences software (v. 10.0; SPSS; Chicago). Baseline clinical characteristics are expressed as means with a standard deviation. The Mann-Whitney U test was used to evaluate the differences between the Behçet patients and the controls. A p value of <0.05 was considered to be statistically significant.


Results

PTA detected a sensorineural hearing loss at bone conduction levels (≥25 dB) in 10 Behçet patients (34.5%). The difference in audiometric findings between the Behçet patients and the controls was statistically significant at 1, 2, 4, and 8 kHz (p ≤ 0.0498) (table 3).

Table 3. Audiometric test results in the two groups

Frequency (kHz)

Behçet patients, dB mean ± SD

Control group, dB mean ± SD

p Value

0.25

16.39 ± 4.72

14.86 ± 3,88

0.19

0.5

14.46 ± 4.98

13.11 ± 3.19

0.23

1

14.04 ± 6.19

11.32 ± 3.42

0.0498

2

14.75 ± 6.55

11.01 ± 3.42

0.01

4

16.39 ± 7.86

12.71 ± 4.85

0.04

8

20.64 ± 7.53

15.57 ± 6.65

0.01

 

Analysis of TEOAE test results revealed that the difference in sound-to-noise ratio between the two groups was not significant at 1, 1.5, 2, and 3 kHz, but it was significant at 4 kHz (p = 0.02), and the difference in reproducibility between the two groups was significant at 2 and 4 kHz (p ≤ 0.03) (table 4).

Table 4. TEOAE test results in the two groups

Frequency (kHz)

Behçet patients mean ± SD

Control group mean ± SD

p Value

* SNR = sound-to-noise ratio.

SNR*

 

 

 

 at 1 kHz

10.448 ± 7.303

12.536 ± 4.351

0.51

 at 1.5 kHz

17.207 ± 15.730

16.857 ± 6.943

0.29

 at 2 kHz

15.724 ± 13.022

15.680 ± 5.136

0.31

 at 3 kHz

15.034 ± 17.517

13.357 ± 3.391

0.46

 at 4 kHz

9.793 ± 16.019

12.536 ± 2.252

0.02

Reproducibility

 

 

 

 at 1 kHz

76.793 ± 36.086

92.250 ± 8.347

0.45

 at 1.5 kHz

86.034 ± 24.744

95.107 ± 5.459

0.09

 at 2 kHz

84.931 ± 25.503

94.929 ± 6.912

0.03

 at 3 kHz

80.034 ± 25.098

94.286 ± 5.091

0.05

 at 4 kHz

69.862 ± 28.763

94.001 ± 1.971

0.001


 

Discussion

Hearing loss in Behçet disease has been researched for many years. For example, Boulassel et al reported on the relationship between this autoimmune disease and hearing loss in 2001.3 A number of studies have concerned inner ear involvement in autoimmune diseases such as Wegener granulomatosis, polyarteritis nodosa, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome, among others.4-6 One common finding in all these studies is that hearing impairment exists in autoimmune diseases, usually at high frequencies.4

The cochlea, saccule, and posterior canal are supplied by the common cochlear artery, while the utricle and anterior and horizontal canals are supplied by the anterior vestibular artery. Outer hair cell function is affected by immunologically mediated inflammation of the common cochlear artery. The common cochlear artery serves as the blood supply to the cochlea, and otoacoustic emissions are sensitive to the measurement of cochlear function.7

Inner ear involvement in Behçet disease was first reported by Alajouanine et al in 1961.8 Since then, several studies of autoimmune involvement of the inner ear have been published,5,6 and the reported rates of hearing loss among patients with Behçet disease have ranged from 15 to 80%.4,7-13 However, some of these previous studies did not include a control group, and many did not include monitoring inner ear involvement via measurements of otoacoustic emissions.4,9-11,14-16

In our study, 34.5% of the Behçet disease patients had a sensorineural hearing loss (≥25 dB hearing level in at least two frequencies), particularly at the higher frequencies. The mean hearing levels were lower in the Behçet group than in the controls at all frequencies, but only the differences at 1 kHz and higher were statistically significant. Similarly, the differences in TEOAE results were significant at the higher frequencies. Our findings demonstrate that Behçet disease is associated with inner ear involvement, especially at the higher frequencies. A similar finding was reported by Kulahli et al.10

It is interesting that none of the Behçet disease patients in our study expressed any complaints about their hearing. This could be attributable to their having only a mild or moderate impairment (none had a severe or profound loss) that had not caused any communication problems in daily life.

In other studies, Soylu et al,4 Gemignani et al,15 and Brama and Fainaru16 failed to find any correlation among age, inner ear involvement, and the duration of the disease. In our study, we did not find any statistically significant relationship between the duration of disease and inner ear involvement.

Many studies have been conducted in an attempt to determine the precise anatomic location responsible for hearing impairment in Behçet disease. The overall results of such studies have demonstrated cochlear (64% of cases), vestibular (28%), retrocochlear (4%), and external and middle ear (4%) disease involvement.4,10,17 In our study, sound-to-noise ratios and reproducibility parameters indicated cochlear disease involvement. None of our patients had retrocochlear involvement, and because we did not perform vestibular testing, we are not able to speculate as to whether any of them had vestibular involvement.

The treatment of inner ear involvement in Behçet disease is generally symptomatic and individualized. The current practice is to administer combination drug therapy with a steroid, an immunosuppressant (e.g., azathioprine or cyclophosphamide), and an anticoagulant or antiaggregant.

As with other investigations, our study had certain limitations. First, as mentioned, we did not perform vestibular testing. Second, our sample size was relatively small, and thus we cannot rule out the probability that the incidence of sensorineural hearing loss would have been statistically significant at all frequencies if we had investigated a larger number of patients.

In conclusion, this study has shown that hearing impairment and inner ear involvement are not uncommon in patients with Behçet disease. All Behçet patients should be regularly monitored by an otolaryngologist and screened with TEOAE testing if possible in order to facilitate the early diagnosis and treatment of inner ear involvement.

 

References

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From the Department of Otolaryngology, Samsun Medicana Hospital, Diyarbakir, Turkey (Dr. Kemal); and the Department of Otorhinolaryngology (Prof. Anadolu), the Department of Dermatology (Prof. Boyvat), and the Department of Audiology (Mr. Tataragasi), Ibn-i Sina Hospital, University of Ankara Faculty of Medicine, Ankara, Turkey. The study described in this article was conducted at Ibn-i Sina Hospital.
Corresponding author: Ozgur Kemal, MD Yesildere mah. Akça cad. Mimoza evleri c blok No:41 Atakum, Samsun, Turkey. Email: dr.ozgurkemal@yahoo.com
 
Ear Nose Throat J. 2013 March;92(3):112-120