ARTICLE
Auteur(s) : Chang Kee Hong1, Mu Hyoung
Lee2, Ki Heon Jeong2, Chang Il
Cha1, Seung Geun
Yeo1
1Department of Otorhinolaryngology, College
of Medicine, KyungHee University, #1 Hoegi-dong,
dongdaemun-gu, Seoul 130-702, Korea
2Department of Dermatology, College
of Medicine, KyungHee University, Seoul, Korea
accepté le 12 Septembre 2008
Vitiligo is a relatively common disease caused by the loss of
functional melanocytes, with a worldwide prevalence of about
0.3-1%. Although vitiligo may be inherited or acquired, the exact
causes of the condition have not been determined, although stress,
infection, mutation, neural factors, melatonin receptor
dysfunction, and impaired melanocyte migration and/or proliferation
have all been suggested. The accumulation of toxic intermediate
melanin synthesis products [1], the breakdown of free radical
defenses [2], and the buildup of excessive quantities of hydrogen
peroxide [3], have been found to lead to the self-destruction of
pigment cells.
Embryonically, human melanocytes develop from the neural crest,
later becoming distributed in the epidermis, hair bulbs of the
skin, the uveal tract, the retinal pigment epithelium, the inner
ear, and the leptomeninges, which are collectively regarded as
melanocyte organs. Thus, mechanisms causing the loss of skin
melanocytes can also affect other melanocyte organs [4].
Although the loss or reduction of melanocytes in the inner ear
may have a critical effect on hearing, most vitiligo patients are
asymptomatic for audiological abnormalities. There have been few
studies of hearing loss in vitiligo patients, with most conducted
in Western populations [5-11]. Melanocyte distributions and
melanocyte-associated diseases differ, however, in various racial
groups. To date, there have been no studies of hearing loss in
Asian patients with vitiligo, and no analysis of any relationship
between hearing loss and severity of vitiligo. We therefore
assessed differences in hearing parameters between Korean vitiligo
patients and normal Koreans.
Subjects and methods
Subjects
Patients diagnosed with vitiligo in the Department of Dermatology,
KyungHee University Medical Center, between January 2007 and
December 2007, were recruited. We performed hearing tests on
all vitiligo patients referred by the dermatology department. We
excluded patients with definitive ear diseases (e.g., tympanic
perforation or chronic otitis media), familial hearing loss,
chronic noise exposure, head trauma, or metabolic, neurological,
vascular or autoimmune disease and those aged over 50 years.
Sensory loss and tinnitus were not exclusion criteria in vitiligo
patients.
Vitiligo patients were divided into those with active or stable
disease according to their VIDA (vitiligo disease activity) scores
(table 1). We subdivided vitiligo
patients into those with segmental and non-segmental vitiligo, and
analyzed each subgroup separately. The control group included sex-
and age-matched normal individuals, with no history of otitis media
or inner ear diseases, no exposure to excessive noise, and with
normal tympanic membranes on otoscopic examination and normal peak
amplitudes with – 100 to + 50 daPa tympanic peak pressures in
impedance audiometry.
All subjects provided written informed consent and the study
protocol was approved by the Institutional Review Board of Kyung
Hee University Medical Center.
Table 1 Vitiligo Disease Activity (VIDA) Score on a
6-point Scale*
|
Disease activity**
|
VIDA score
|
|
Active, in the past 6 weeks
|
+ 4
|
|
Active, in the past 3 months
|
+ 3
|
|
Active, in the past 6 months
|
+ 2
|
|
Active, in the past 1 year
|
+ 1
|
|
Stable for at least 1 year
|
0
|
|
Stable for at least 1 year and spontaneous repigmenting
|
– 1
|
*Consists of scoring of the patient’s own opinion of the
present disease activity within the times indicated in the first
column.
**Active refers to expansion of existing lesions or
appearance of new lesions; stable, condition when symptoms are not
present.
Methods
Audiometry was performed using a pure-tone audiometer (PTA AC 40;
Interacoustics, Copenhagen, Denmark) in a silent cabin. Pure-tone
thresholds of each ear were determined at frequencies of
125 Hz, 250 Hz, 500 Hz, 1,000 Hz,
2,000 Hz, 4,000 Hz, 6,000 Hz, and 8,000 Hz for
air conduction (TDH 39 headset).
Auditory brainstem responses(ABR) were measured using Medelec
Sapphire Software and two recording channels with a filter bandpass
between 100 and 3,000 Hz. Recording electrodes were attached
to the vertex (Cz, reference), both mastoids, and at a frontal
location midway between the nasion and the vertex (ground). During
testing, all subjects reclined in a dark and quiet room. Monoaural
rarefaction clicks (80-85 dB, 0.1 ms duration) were used as
auditory stimuli. White noise at 30 dB was sent to the
contralateral ear. Sounds were produced by activating earphones
with 0.1 ms pulses at a rate of 8-10/s and at an intensity of
70 dB above sensation level for each click. Analysis time was
100 ms with a system bandpass of 100-200 Hz. The I, III,
and V wave latencies and amplitudes, and the I-III, III-V, and I-V
interpeak latencies, were measured.
Electrocochleography (ECoG) was performed using Nicolet gold
TIPtrode electrodes, with a stimulus sound intensity of 95 dB.
Alternating polarity click stimulation was performed by repeating
sounds for 100 msec (39-3,000 Hz) 1000 times. Action potential
(AP) amplitude was defined as the length from baseline to the
maximally curved point of the top AP and the SP (summating
potential) amplitude was defined as the notch length in the upward
curve of the AP. AP and SP amplitudes and SP/AP ratios were
compared.
Statistical analysis
Pure-tone audiometry, auditory brainstem responses, and ECoG
results were compared between the vitiligo and control groups and
between the active and stable vitiligo groups using Student’s
t-test and Pearson’s correlation coefficient. All statistical
analyses were performed using SPSS software (version 12.0; SPSS
Inc.; Chicago, IL). A p value < 0.05 was the threshold of
significance.
Results
The vitiligo group and the normal control group each consisted of
89 subjects, 35 males and 54 females. As the control group
consisted of sex- and age-matched individuals, the mean ± SD age of
both groups was 25.9 ± 12.1 years (range 6 to 48 years). In the
vitiligo group, the mean ± SD duration of vitiligo was 5.7 ± 6.4
years (range 0.2 to 29.5 years), and the mean ± SD VIDA score was
1.5 ± 1.8. Of these 89 patients, 47 had active disease, with 7, 9,
10, and 21 patients having VIDA scores of 1, 2, 3, and 4,
respectively. The remaining 42 patients in the vitiligo group had
stable disease, with 9 and 34 having VIDA scores of -1 and 0,
respectively. There were 39 patients with segmental vitiligo, 25
men and 14 women, of mean age 29 years; and there were 50 patients
with non-segmental vitiligo, 10 men and 40 women, of mean age 28.9
years (table 2).
Using pure tone audiometry, we found that hearing in the right
ears of the vitiligo group was significantly lower than in the
control group at 125 Hz, 1,000 Hz, 4,000 Hz,
6,000 Hz, and 8,000 Hz (p < 0.05), and that hearing in
the left ears of the vitiligo groups was significantly lower than
in the control group at 1,000 Hz, 2,000 Hz,
4,000 Hz, 6,000 Hz, and 8,000 Hz (p < 0.05) (figure 1, table 3).
When we compared pure tone audiometry results in patients with
active and stable disease, we found that, in the active disease
subgroup, hearing in the right ear was significantly reduced at
500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz,
6,000 Hz, and 8,000 Hz and hearing in the left ear was
significantly reduced at 1,000 Hz, 2,000 Hz,
4,000 Hz, 6,000 Hz, and 8,000 Hz (p < 0.05) (figure 2, table 3). The groups with segmental and
non-segmental type vitiligo showed statistically significant
differences at 2,000 Hz and 8,000 Hz in the right ear,
and at 125 Hz, 2,000 Hz, and 8,000 Hz in the left
ear (p < 0.05 each) (figure 3, table 3).
There was a positive correlation between pure tone audiometry
results and VIDA scores for hearing in the right ear at 500 Hz
(p = 0.231), 4,000 Hz (p = 0,264), 6,000 Hz (p = 0.408),
and 8000Hz (p = 0.404) and hearing in the left ear at 500 Hz
(p = 0.229), 1,000 Hz (p = 0.240), 2,000 Hz (p = 0.271),
6,000 Hz (p = 0.370), and 8,000 Hz (p = 0.454).
Auditory brain stem responses in right ears showed that, in the
vitiligo group, wave I latency was significantly decreased, and
wave III latency and interpeak latencies I-III and I-V were
significantly increased (p < 0.05), compared with the control
group. For left ears, auditory brain stem responses in the vitiligo
group showed a significant decrease in wave I latency and
significant increases in wave III latency and interpeak latencies
I-III and III-V compared with the control group (p < 0.05).
When we compared auditory brainstem responses in the active and
stable disease subgroups, we found that, in right ears, the former
cases showed significant decreases in wave I and wave III latencies
and significant increases in third amplitude and interpeak
latencies I-III and I-V (p < 0.05). For left ears, the active
disease subgroup showed a significant decrease in wave I latency
and significant increases in interpeak latencies I-III and I-V (p
< 0.05) compared with the stable disease group. In right ears,
wave I latency was significantly higher in the segmental type,
whereas interpeak latencies I-III and interpeak latencies I-V were
significantly higher in the non-segmental type. In left ears, III
latencies, V latencies, interpeak latencies I-III, interpeak
latencies III-V, and interpeak latencies I-V were significantly
higher in the non-segmental type (tables
4,5).
We found that wave I (p = – 0.600) and wave III latencies
(p = – 0.292) of right ears and wave I latency (p = – 0.499)
of left ears showed significant negative correlations with VIDA
scores and that third amplitude (p = 0.248) and interpeak latencies
I-V (p = 0.224) of right ears and interpeak latencies I-III (p =
0.253) and I-V (p = 0.212) of left ears showed significant positive
correlations with VIDA scores.
Using electrocochleography, we found that SP amplitude and SP/AP
ratios of right ears were significantly higher in the vitiligo
group compared with the control group (p<0.05), but there were
no significant differences in left ears. When we compared the
active and stable disease subgroups and compared segmental type and
non-segmental types, we found no significant differences in right
ears, but SP amplitude, AP amplitude and SP/AP ratios of left ears
were significantly higher in the active disease subgroup (p <
0.05) (tables 6,7). There was no
significant correlation between any electrocochleography parameter
and VIDA score.
Of 89 patients, 24 had sensorineural hypoacusis, 15 on the same
side, 9 on the other side, and 4 on both sides (considered the same
side). However, the vitiligo side was not related to ear side.
Table 2 Characteristics of vitiligo patients
|
Stable disease
|
Active disease
|
Segmental type
|
Non-segmental type
|
|
Mean age (years)
|
27.2
|
30.5
|
29
|
28.9
|
|
Male/female
|
14/28
|
21/26
|
25/14
|
10/40
|
|
Mean duration (years)
|
6.69
|
4.93
|
5.78
|
5.72
|
|
Family history
|
10
|
25
|
7
|
28
|
|
Extend of lesion (bilaterality)
|
|
|
|
|
|
Face
|
21(3)
|
22(3)
|
19(2)
|
24(4)
|
|
Neck
|
6
|
13(2)
|
7
|
12(2)
|
|
Hand
|
7(2)
|
9(1)
|
11(1)
|
5(2)
|
|
Back
|
2
|
0
|
1
|
1
|
|
Leg
|
3
|
4
|
1
|
6
|
|
Whole body
|
1
|
1
|
0
|
2
|
Table 3 Mean and standard deviations of pure tone
threshold (dB HL)
|
Ear/Hz
|
Patients with vitiligo, Mean ± SD
|
Nomal subjects, Mean ± SD
|
|
Stable disease
|
Active disesase
|
Segmental type
|
Non-segmental type
|
Total
|
|
Rt 125
|
8.69 ± 3.83
|
9.25 ± 3.75
|
9.74 ± 3.61
|
8.40 ± 3.83
|
8.98 ± 3.78*
|
7.80 ± 3.68
|
|
Lt 125
|
8.09 ± 4.80
|
8.19 ± 4.71
|
9.35 ± 4.61
|
7.20 ± 4.64†
|
8.14 ± 4.73
|
7.86 ± 3.52
|
|
Rt 250
|
6.66 ± 5.14
|
7.55 ± 4.76
|
7.69 ± 4.97
|
6.70 ± 4.90
|
7.13 ± 4.93
|
6.51 ± 5.35
|
|
Lt 250
|
6.54 ± 5.11
|
6.70 ± 4.45
|
7.43 ± 4.56
|
6.00 ± 4.84
|
6.62 ± 4.75
|
7.35 ± 5.06
|
|
Rt 500
|
7.97 ± 4.69
|
10.42 ± 4.64**
|
8.97 ± 4.75
|
9.50 ± 4.87
|
9.26 ± 4.80
|
8.03 ± 4.10
|
|
Lt 500
|
7.26 ± 4.30
|
9.14 ± 4.81
|
8.20 ± 4.51
|
8.30 ± 4.80
|
8.25 ± 4.65
|
8.82 ± 4.64
|
|
Rt 1000
|
9.88 ± 4.20
|
11.80 ± 4.93**
|
10.25 ± 3.61
|
11.40 ± 5.34
|
10.89 ± 4.68*
|
7.69 ± 4.71
|
|
Lt 1000
|
9.16 ± 4.67
|
11.91 ± 5.66**
|
9.48 ± 4.55
|
11.50 ± 5.82
|
10.61 ± 5.37*
|
7.58 ± 4.46
|
|
Rt 2000
|
6.54 ± 4.61
|
9.25 ± 6.33**
|
6.41 ± 4.99
|
9.20 ± 6.00†
|
7.97 ± 5.72
|
6.62 ± 3.97
|
|
Lt 2000
|
7.14 ± 5.64
|
10.85 ± 5.83**
|
7.56 ± 4.84
|
10.30 ± 6.57†
|
9.10 ± 6.00*
|
7.19 ± 4.70
|
|
Rt 4000
|
8.45 ± 6.85
|
13.61 ± 6.89**
|
10.38 ± 7.72
|
11.80 ± 6.98
|
11.17 ± 7.30*
|
6.08 ± 4.71
|
|
Lt 4000
|
10.35 ± 8.79
|
16.17 ± 8.98**
|
12.82 ± 10.24
|
13.90 ± 8.58
|
13.42 ± 9.31*
|
6.79 ± 5.28
|
|
Rt 6000
|
9.40 ± 7.42
|
18.93 ± 13.22**
|
12.30 ± 9.92
|
16.10 ± 12.98
|
14.43 ± 11.83*
|
7.13 ± 5.05
|
|
Lt 6000
|
10.59 ± 7.00
|
20.74 ± 11.93**
|
15.25 ± 11.69
|
16.50 ± 10.70
|
15.95 ± 11.10*
|
7.58 ± 6.03
|
|
Rt 8000
|
12.73 ± 7.25
|
22.97 ± 15.06**
|
14.48 ± 8.01
|
21.00 ± 15.35†
|
18.14 ± 13.02*
|
6.74 ± 5.44
|
|
Lt 8000
|
11.78 ± 9.22
|
26.59 ± 18.09**
|
15.51 ± 12.01
|
22.80 ± 18.49†
|
19.60 ± 16.31*
|
7.80 ± 6.48
|
*Statistically significant difference between vitiligo
patients and normal subjects (p < 0.05).
**Statistically significant difference between active
disease and stable disease in vitiligo patients (p < 0.05).
†Statistically significant difference between
segmental type and non-segmental type in vitiligo patients (p <
0.05).
Table 4 Comparison of ABR parameters between vitiligo
patients and normal subjects for right-ear stimulation
|
|
L I (msec)
|
L III (msec)
|
L V (msec)
|
A I (μV)
|
A III (μV)
|
A V (μV)
|
LI-III (msec)
|
LIII-V (msec)
|
LI-V (msec)
|
|
Normal subjects
|
|
1.56 ± 0.17
|
3.70 ± 0.17
|
5.60 ± 0.23
|
0.28 ± 0.12
|
0.28 ± 0.14
|
0.26 ± 0.13
|
2.13 ± 0.15
|
1.90 ± 0.14
|
4.04 ± 0.21
|
|
Vitiligo patients
|
Stable disease
|
1.60 ± 0.07
|
3.84 ± 0.18
|
5.68 ± 0.22
|
0.25 ± 0.13
|
0.24 ± 0.11
|
0.27 ± 0.12
|
2.23 ± 0.15
|
1.83 ± 0.14
|
4.07 ± 0.20
|
|
Active disease
|
1.43 ± 0.07**
|
3.73 ± 0.16**
|
5.62 ± 0.21
|
0.29 ± 0.16
|
0.30 ± 0.17**
|
0.28 ± 0.12
|
2.30 ± 0.11**
|
1.89 ± 0.12
|
4.19 ± 0.17**
|
|
Segmental type
|
1.55 ± 0.13
|
3.77 ± 0.18
|
5.61 ± 0.23
|
0.31 ± 0.15
|
0.24 ± 0.12
|
0.25 ± 0.13
|
2.21 ± 0.14
|
1.83 ± 0.14
|
4.05 ± 0.20
|
|
Non-segmental type
|
1.48 ± 0.08†
|
3.79 ± 0.18
|
5.68 ± 0.20
|
0.25 ± 0.14
|
0.30 ± 0.16
|
0.29 ± 0.11
|
2.31 ± 0.12†
|
1.89 ± 0.13
|
4.20 ± 0.17†
|
|
total
|
1.51 ± 0.11*
|
3.78 ± 0.18*
|
5.65 ± 0.22
|
0.27 ± 0.15
|
0.27 ± 0.15
|
0.27 ± 0.12
|
2.26 ± 0.14*
|
1.86 ± 0.13
|
4.13 ± 0.20*
|
*Statistically significant difference between vitiligo
patients and normal subjects (p < 0.05).
**Statistically significant difference between active
disease and stable disease in vitiligo patients (p < 0.05).
†Statistically significant difference between
segmental type and non-segmental type in vitiligo patients (p <
0.05).
Table 5 Comparison of ABR parameters between vitiligo
patients and normal subjects for left-ear stimulation
|
|
L I (msec)
|
L III (msec)
|
L V (msec)
|
A I (μV)
|
A III (μV)
|
A V (μV)
|
LI-III (msec)
|
LIII-V (msec)
|
LI-V (msec)
|
|
Normal subjects
|
|
1.56 ± 0.17
|
3.71 ± 0.17
|
5.62 ± 0.21
|
0.30 ± 0.12
|
0.26 ± 0.14
|
0.29 ± 0.13
|
2.15 ± 0.11
|
1.89 ± 0.15
|
4.05 ± 0.18
|
|
Vitiligo patients
|
Stable disease
|
1.57 ± 0.10
|
3.81 ± 0.19
|
5.66 ± 0.20
|
0.28 ± 0.15
|
0.26 ± 0.16
|
0.31 ± 0.14
|
2.13 ± 0.49
|
1.76 ± 0.40
|
3.89 ± 0.88
|
|
Active disease
|
1.42 ± 0.08**
|
3.77 ± 0.16
|
5.63 ± 0.21
|
0.30 ± 0.13
|
0.27 ± 0.11
|
0.26 ± 0.11
|
2.34 ± 0.10**
|
1.86 ± 0.10
|
4.20 ± 0.16**
|
|
Segmental type
|
1.52 ± 0.12
|
3.74 ± 0.19
|
5.58 ± 0.20
|
0.32 ± 0.14
|
0.26 ± 0.14
|
0.31 ± 0.14
|
2.10 ± 0.50
|
1.74 ± 0.41
|
3.85 ± 0.90
|
|
Non-segmental type
|
1.48 ± 0.11
|
3.83 ± 0.16†
|
5.70 ± 0.19†
|
0.27 ± 0.14
|
0.27 ± 0.13
|
0.26 ± 0.12
|
2.34 ± 0.09†
|
1.87 ± 0.12†
|
4.22 ± 0.16†
|
|
total
|
1.49 ± 0.11*
|
3.79 ± 0.17*
|
5.65 ± 0.20
|
0.29 ± 0.14
|
0.27 ± 0.14
|
0.28 ± 0.13
|
2.24 ± 0.36*
|
1.81 ± 0.29*
|
4.06 ± 0.63
|
*Statistically significant difference between vitiligo
patients and normal subjects (p < 0.05).
**Statistically significant difference between active
disease and stable disease in vitiligo patients (p <
0 .05).
†Statistically significant difference between
segmental type and non-segmental type in vitiligo patients (p <
0.05).
Table 6 Comparison of electrocochleographic parameters
between vitiligo patients and normal subjects for right-ear
stimulation
|
|
SP
|
AP
|
SP/AP
|
|
Normal subjects
|
|
0.11 ± 0.07
|
0.52 ± 0.17
|
0.20 ± 0.07
|
|
Vitiligo patients
|
Stable disease
|
0.14 ± 0.12
|
0.52 ± 0.19
|
0.22 ± 0.09
|
|
Active disease
|
0.17 ± 0.19
|
0.59 ± 0.25
|
0.23 ± 0.10
|
|
Segmental type
|
0.16 ± 0.15
|
0.57 ± 0.24
|
0.24 ± 0.10
|
|
Non-segmental type
|
0.15 ± 0.17
|
0.54 ± 0.21
|
0.22 ± 0.10
|
|
total
|
0.15 ± 0.16*
|
0.55 ± 0.22
|
0.23 ± 0.10*
|
*Statistically significant difference between vitiligo
patients and normal subjects (p < 0.05).
Table 7 Comparison of Electrocochleographic parameters
between vitiligo patients and normal subjects for left-ear
stimulation
|
|
SP
|
AP
|
SP/AP
|
|
Normal subjects
|
|
0.11 ± 0.07
|
0.54 ± 0.18
|
0.20 ± 0.09
|
|
Vitiligo patients
|
Stable disease
|
0.09 ± 0.06
|
0.48 ± 0.16
|
0.19 ± 0.09
|
|
Active disease
|
0.16 ± 0.17*
|
0.58 ± 0.24*
|
0.24 ± 0.10*
|
|
Segmental type
|
0.14 ± 0.13
|
0.53 ± 0.22
|
0.22 ± 0.09
|
|
Non-segmental type
|
0.12 ± 0.12
|
0.53 ± 0.20
|
0.21 ± 0.10
|
|
total
|
0.13 ± 0.13
|
0.53 ± 0.21
|
0.21 ± 0.10
|
*Statistically significant difference between active
disease and stable disease in vitiligo patients (p < 0.05).
Discussion
The stria vascularis produces an endocochlear potential, a
potential difference measured in the endolymph of the scala media
[12, 13]. Endocochlear potential and high K+
concentration in the endolymph are essential for sound transduction
through hair cells. Human stria vascularis consists of three main
cell types: marginal cells, basal cells, and intermediate cells or
melanocytes. Marginal cells are arranged along the luminal surface,
meet with the endolymph in the scala media, and develop from an
epithelial origin; basal cells are located next to the spiral
ligament and in the cochlear walls; and melanocytes, which develop
from the neural crest, are scattered around the stria between the
marginal and basal cell layers [14]. Congenital deficiency of the
intermediate cells increases the threshold of sound pressure
levels, inducing a low endocochlear potential and compound action
potentials [15]. Thus, endocochlear potential is important for hair
cell function and reversible damage to hair cells, and, in the
absence of histological changes such as endolymphatic hydrops, can
increase the SP/AP ratio [16]. Therefore, in contrast to previous
studies, which utilized only pure tone audiometry and auditory
brainstem responses, we also employed electrocochleography to
assess the functioning of the stria vascularis, especially the
SP/AP ratio, an indirect measurement of intermediate cell activity.
Using six grades of pure tone audiometry, we found that average
hearing thresholds in the control group were 7.12 dB in right ears
and 7.52 dB in left ears. In comparison, thresholds in the vitiligo
group were 9.69 dB in right ears and 10.18 dB in left ears.
The thresholds were 8.21 dB and 8.36 dB, respectively,
for those with stable disease, and 11.02 dB and 11.8 dB,
respectively, for those with active disease. In the segmental type,
right and left thresholds were 8.5 dB and 8.36 dB, respectively,
whereas in the non-segmental type, right and left thresholds were
10.03 dB and 10.03 dB, respectively, all within the normal range.
Although all subjects were within normal hearing ranges, we found
that hearing decreased at high frequencies in the vitiligo group
compared with the control group, and decreased in the active
disease compared with the stable disease subgroups, in agreement
with previous findings [5-11] (table 8).
Decreased hearing at high frequencies may indicate more serious
damage to the stria vascularis, especially to intermediate cells at
the base of the cochlea. In correlations of auditory sensation
areas and optimal frequencies of basement membranes, high
frequencies are recognized at the base of the cochlea, whereas low
frequencies are recognized toward the apex, a finding supported by
our results.
We observed statistically significant differences at 125 Hz
and 1,000 Hz between the right ears of the normal and vitiligo
groups and at 1,000 Hz and 2,000 Hz between the left
ears. Hearing at 500 Hz, 1,000 Hz, and 2,000 Hz
differed significantly between the right ears of the stable and
active disease subgroups and at 1,000 Hz and 2,000 Hz
between the left ears of these subgroups, indicating that hearing
was affected even at low frequencies. Although 2 previous studies
showed ABR abnormalities, they showed different results [7, 9]
(table 9).
We found that wave I latency was significantly reduced and
interpeak latency I-III was significantly increased in the vitiligo
group compared with the control group and in the active disease
compared with the stable disease subgroup. Wave I latency is
related to the interconnections among the cochlear mechanism, the
movement of basilar membranes, and the displacement of hair cells
[17, 18]. The interaction between melanocytes and epithelial cells
in the inner ear plays a critical role in maintaining ion gradients
between the endolymph and perilymph [19]. In addition, inner ear
melanin acts as an intracellular calcium buffer and as a storage
site for essential metal ions that control the activity of various
enzymes and metabolic processes [20]. The decrease in first peak
latency may therefore be because of the smaller number or lower
activity of inner ear melanocytes in vitiligo patients.
Moreover, increased I-III interpeak latency has been correlated
with the pathology of the superior olivary nucleus and the upper
brainstem or inferior colliculus and with disorders of transmission
and synaptic activity of action potential from the auditory nerve
to the cochlear nucleus and from the cochlear nucleus to the
superior olivary nucleus and inferior colliculus [9]. Thus,
vitiligo patients may experience delayed synchronization of action
potentials in the nuclei. Alternatively, I-III peak latency may be
delayed following lower first peak latency with a normal range of
absolute third peak latency.
We found that mean SP/AP ratio was significantly higher in the
right ears of vitiligo compared with control patients, as well as
being significantly higher in left ears of active disease compared
with stable disease patients. Because these levels were within the
normal range, however, it is unclear whether hair had been damaged
irreversibly.
Melanin-containing cells in inner ears are thought to protect
the cochlea from various stresses, especially loud noise [21] and
skin pigment changes have been found to correlate with hearing
loss. For example, albino animals were found to be more susceptible
to noise-induced hearing loss and to show abnormal auditory
brainstem potential [22, 23]. In albino humans, noise-induced
hearing loss showed racial differences, in that whites were more
vulnerable than blacks [24] and abnormal responses were observed in
auditory brainstem potential determinations, with evidence for
superior olivary nucleus involvement [23, 25]. These results, which
were similar to ours, indicate that ototoxic drugs should be
carefully administered to vitiligo patients. Moreover,
noise-induced hearing loss, especially hearing loss in adolescents
caused by MP3 player use, is a serious preventable condition.
Table 8 Features of the sensorineural hypoacusis in
patients with vitiligo
|
Vitiligo
|
Features of hypoacusis
|
|
Author
|
No. of patients
|
Mean age (years)
|
Sex (M/F)
|
Mean Duration (years)
|
Type
|
Ear Affected (n)
|
Frequency Range (Hz)
|
Hearing Loss (dB)
|
|
Ardic et al. [5]
|
N/A /29
|
30.6
|
14/15
|
7.1
|
Generalized (16)
|
-
|
10,000-16,000
|
>30
|
|
|
|
|
|
Focal (9)
|
|
|
|
|
|
|
|
|
Segmental (4)
|
|
|
|
|
Aydogan et al. [6]
|
8/57 (14%)
|
31.4
|
4/4
|
4.8
|
Generalized
|
Bilateral (6)
|
2,000-8,000
|
30
|
|
|
|
|
|
|
Unilateral (2)
|
4,000-8,000
|
30
|
|
Hong et al.
|
24/89 (26.9%)
|
25.9
|
35/54
|
5.7
|
Segmental (39)
|
Bilateral (8)
|
4,000-8,000
|
> 30
|
|
|
|
|
|
Non-segmental (50)
|
Unilateral (16)
|
|
|
|
Nikiforidis et al. [7]
|
4/50 (8%)
|
N/A
|
N/A
|
5.3
|
N/A
|
Bilateral (4)
|
2,000-8,000
|
30 to > 40
|
|
Orecchia et al. [8]
|
4/50 (8%)
|
25
|
1/3
|
8.2
|
Generalized (3)
|
Bilateral (3)
|
2,000-4,000
|
35-60
|
|
|
|
|
|
Acral (1)
|
Unilateral (1)
|
4,000
|
55
|
|
Ozuer et al. [9]
|
2/50 (4%)
|
43.2
|
N/A
|
8.2
|
Generalized
|
Bilateral (2)
|
4,000-8,000
|
> 30
|
|
Sharma et al. [10]
|
34/180 (18.9%)
|
35.2
|
N/A
|
5
|
Generalized
|
Bilateral (34)
|
2,000-4,000
|
30-40
|
|
Tosti et al. [11]
|
8/50 (16%)
|
36.3
|
5/3
|
7.3
|
Generalized
|
Bilateral (3)
|
2,000-8,000
|
≤ 40-60
|
|
|
|
|
|
|
Unilateral (5)
|
4,000-8,000
|
≤ 40-60
|
Table 9 The results of ABR in patients with vitiligo
|
Authors
|
L I (msec)
|
L III (msec)
|
L V (msec)
|
A I (μV)
|
A III (μV)
|
A V (μV)
|
LI-III (msec)
|
LIII-V (msec)
|
LI-V msec)
|
|
Aydogan et al. [6]
|
N
|
↑
|
↑
|
N
|
N
|
N
|
↑
|
N
|
N
|
|
Hong et al.
|
↓
|
N
|
N
|
N
|
N
|
N
|
↑
|
N
|
↑
|
|
Nikiforidis et al. [7]
|
↓
|
N
|
N
|
N
|
N
|
N
|
↑
|
N
|
N
|
|
Ozuer et al. [9]
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
Conclusion
Korean vitiligo patients have reduced hearing compared with normal
subjects. Among vitiligo patients, hearing was reduced in those
with active disease more than in those with stable disease. The
mechanism of hearing loss in vitiligo may involve the functional
destruction of intermediate cells and/or melanocytes in the stria
vascularis.
Acknowledgments
This study was funded by scholarships for researchers in the
Graduate School of Kyung Hee University, in 2007. Conflict of
interest: none.
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