Keywords
hearing loss - sensorineural - hearing loss - sudden - autoimmune diseases - humans
Introduction
In recent years, several authors have tried to demonstrate the relationship between
sudden sensorineural hearing loss (SNHL) and systemic autoimmune diseases (SAD), seeking
to elucidate a possible immune-mediated etiology involved in cases of sudden hearing
loss.[1]
[2]
[3]
[4]
[5]
Sudden SNHL was first described by De Kleyn et al in 1944, and the most widely used
definition is based on audiological and temporal parameters, which predict fall of
hearing threshold by bone conduction at least 30 dB in three contiguous frequencies
in a period ranging from a few minutes to 72 hours. Its incidence ranges from 5 to
20 individuals per 100,000 people per annum.[6]
[7]
In 70% to 90% of cases of sudden SNHL, the etiology is not identified. Thus, this
percentage of cases is classified as idiopathic sudden SNHL. Theories as to the cause
of injury in such situations point to vascular injury, rupture of membranes, viral
or bacterial infection, and immune mediated injury.[8]
[9]
[10]
[11]
[12]
Immune-mediated SNHL usually manifests as a rapidly progressive sensorineural loss,
bilateral and asymmetrical. Even today, it remains as a challenging disease.[13]
In 1958, Lehnhardt[14] was the first to suggest the possibility of sudden or rapidly progressive hearing
loss to be the result of an autoimmune process against the inner ear. Schiff and Brown[15] in 1974 speculated that, due to the improvement of patients with SSNHL following
the use of adrenocorticotropic hormone, its etiology should be an autoimmune vasculitis.
In 1979, McCabe[16] reported cases of sudden SNHL loss successfully treated by immune suppressive therapy
and introduced the clinical entity: autoimmune hearing loss.
Although the pathophysiology of immune-mediated SNHL remains unknown, the positive
response to immunosuppressive therapy and corticosteroid reinforces the existence
of immune-mediated mechanisms. Given that the damage to the inner ear can occur not
only by reaction antigen - autoantibody, but also by various other mechanisms such
as activation of the complement system, direct action of cytotoxic T cells, among
others, experts believe that the term immune-mediated PANS is more appropriate than
autoimmune hearing loss.[17]
[18]
In 30% of cases, immune-mediated SNHL may be associated with the SAD. This association
is prominent in the following diseases: systemic lupus erythematosus (SLE), antiphospholipid
syndrome, Susac syndrome, polyarteritis nodosa, rheumatoid arthritis (RA), Wegener's
granulomatosis, Sjögren's syndrome, Behcet's syndrome, sarcoidosis, Cogan syndrome,
among others. However, the incidence of involvement of the inner ear in the SAD varies
greatly.[19]
[20]
Immune-mediated SNHL most often affects female patients between their thirties and
fifties. It is estimated to account for less than 1% of hearing loss - a small percentage,
but it is difficult to assess its impact due to the lack of tests that define this
etiology. Cases of sudden SNHL with immune-mediated etiology are even rarer and difficult
to diagnose.[17]
[18]
In most cases, the clinical picture of immune-mediated SNHL is characterized by sensorineural
hearing loss, bilateral, asymmetric and rapidly progressive, often associated with
tinnitus and vestibular symptoms. An important feature is its fast progression: it
can lead to severe bilateral SNHL in a few days or weeks. In rare cases, it presents
as unilateral sudden SNHL and manifests only in the contralateral ear after a variable
number of days up to years.[13]
[17] The diagnosis is eminently based on the clinical picture.
Anamnesis is essential to provide data regarding the existence of associated systemic
diseases and the ENT exam commonly shows no alterations.[18]
Pure tone audiometry does not reveal typical curve pattern and speech discrimination
cannot present proportional to pure tone thresholds.[17] Imaging tests such as magnetic resonance (MR) imaging and positron emission tomography
can demonstrate inflammatory activity in the inner ear, and thus contribute to the
diagnosis.[21]
[22] There are no appropriate laboratory tests for the diagnosis of certainty yet.[18]
[19]
[23]
The positive response to the therapeutic treatment with corticosteroids and audiogram
worsening in medication dose reduction attempts to reinforce the suspicion that etiology.[19] The suspicion of the disease is fundamental for the diagnosis of immune-mediated
SNHL, especially in cases of atypical and/or evolution with systemic comorbidities.
Early treatment is crucial for a better prognosis.[17]
The clinical importance of immune-mediated SNHL largely lies in the fact that it is
one of the few sensorineural hearing losses that may be reversible with early and
adequate treatment.[13]
[17]
The objective of this study is to describe the different audiological and epidemiological
clinical presentations of patients with idiopathic sudden SNHL and associated systemic
autoimmune disease, who were diagnosed with probable immune-mediated SNHL. Another
aim was to estimate the prevalence of systemic autoimmune diseases in patients with
sudden SNHL.
Methods
The project was an observational retrospective cohort study. Our sample consisted
of patients experiencing sudden SNHL, from the SSNHL clinic of a tertiary university
hospital. These patients' medical records were followed from 2000 up to 2012. This
study received approval from the Ethics Committee of the institution, under the registration
number 0632/11.
Inclusion and Exclusion Criteria
The study included all patients with idiopathic sudden SNHL of at least 30 dB in at
least three consecutive frequencies, over a period of 72 hours.
Then, we selected and separately analyzed patients with SAD, which we diagnosed by
clinical criteria and specific rheumatologic laboratory tests for different diseases.
The study excluded patients with sudden SNHL with defined etiologies, such as tumors,
trauma, multiple sclerosis, and otitis.
Medical Records Review
We analyzed the medical records of patients who met the inclusion criteria for clinical
data on: age and date of birth; gender; start date of hearing loss; concomitant symptoms
such as tinnitus, vertigo, ear pain, and ear fullness; presence of comorbidities,
such as hypertension, diabetes, thyroid changes and habits; use of medications; family
history; audiometric parameters; and imaging tests.
The patients' hearing tests were performed with a standard audiometer (MA-41, MAICO,
Eden Prairie, U.S.A.). This included tonal and vocal audiometry, with a threshold
search and speech recognition index. We evaluated the initial and final audiometric
parameters, the latter being obtained at least two months after the initial audiometry,
or earlier in case of complete recovery. Patients also underwent blood testing that
included complete blood count, serum fasting glucose, lipid dosage, renal function
and thyroid function, erythrocyte sedimentation rate and serology for syphilis, AIDS,
borreliosis when deemed necessary. The majority of patients also underwent imaging
(MR brain). Patients suspected of SAD underwent specific serological tests determined
by the rheumatology team, which could specify the suspected immune-mediated disease.
Audiometric Curves' Classification
For the classification of audiometric curves, we considered the following criteria:
the bass frequencies corresponding to 250 and 500 Hz, the average comprising 1 and
2 kHz, and acute, 3 to 8 kHz. Upward curves were those with a decrease greater than
15 dB at worst severe frequency relative to other frequencies; curve “U” with those
reductions greater than 15 dB in the worst average frequency, compared with the worst
low and high frequencies; curve “inverted U” when there is a decrease greater than
15 dB in the worst low and high frequencies compared with the average; downslope when
there is a reduction of 15 dB in the arithmetic average of 4 to 8 kHz with respect
to the arithmetic average of the frequencies 250 and 500 Hz; and finally, flat, when
there is less than 15 dB difference between the averages of 250 and 500 Hz, 1 and
2 kHz and 4 to 8 kHz.
Intensity Degree Classification of Hearing Loss
We categorized the intensity of hearing loss into four degrees.
When the arithmetic means of pure tones (PTA) was below 25 dB, we did not consider
it a hearing loss; between 26 and 40 dB we considered it mild. Moderate hearing loss
was defined between 41 and 70 dB, severe hearing loss between 71 and 90 dB, and profound
above 90 dB.
Arithmetic Means of Pure Tones Obtained
We obtained arithmetic means from initial and final pure tone in all patients using
the following methodology: arithmetic average of pure tone for each patient in accordance
with the group of frequencies affected. When low and middle frequencies were hit,
we obtained the arithmetic mean of the frequencies of 0.25, 0.5, 1 and 2 kHz; medium
and high when the average of the frequencies of 1, 2, 3, 4, 6 and 8 kHz; when only
acute, average 3, 4, 6 and 8 kHz; when severe, acute medium and the average of all
eight frequencies. When the hearing thresholds of deep losses were not detected, was
considered as the maximum response audiometer, in this case, 120 dB.
Hearing Recovery Criteria by Pure Tone Audiometry and Vocal
- Improvement: change for better on classification of the degree of intensity of hearing loss or
improved more than 12% of the IRF.
- Worsening: change for worse on classification of the degree of intensity of hearing loss worsens
or greater than 12% of the IRF.
- Stable: Maintenance intensity degree classification of the hearing loss and change the IRF
less than or equal to 12%.
Results
We evaluated 339 records of all the patients who were diagnosed with sudden SNHL from
the SNHL clinic of our institution, from 2000 up to 2012. We analyzed the results
by separating the sample with only SSNHL without SAD, and SAD associated patients.
Thirteen patients (3.83%), besides the sudden SNHL also had a previous diagnosis confirmed
by serological and rheumatologic criteria specific SAD exam. Nine (69.23%) were women
and four (30.77%) men, eight (61.54%) were Caucasians, and five (38.46%) afro-descendants.
The average age of patients in this sample at the time of sudden SNHL installation
was 44 years of age, with a minimum age of 21 and maximum 68. Regarding SAD, four
(30.77%) patients of SLE; four (30.77%), AR; two (15.38%), scleroderma; one (7.69%),
Sjogren's syndrome; one (7.69%), Cogan's syndrome; one (7.69%), Susac syndrome; one
(7.69%), psoriasis; one (7.69%), vitiligo and one (7.69%), ankylosing spondylitis.
Three (23.07%) patients showed more than one concurrent SAD, that is, one had AR and
scleroderma; another had Sjogren's syndrome and scleroderma and a third, AR and vitiligo
([Table 1]).
Table 1
Demographic data and underlying diseases
|
Case
|
Age in CN
|
Gender
|
Ethnicity
|
Systemic immune-mediated disease
|
Comorbidities in the new case
|
|
1
|
21
|
M
|
CN
|
EA
|
|
|
2
|
68
|
F
|
AD
|
SLE
|
SH
|
|
3
|
37
|
M
|
CN
|
SLE
|
SH/IRC
|
|
4
|
47
|
F
|
AD
|
RA
|
SH
|
|
5
|
26
|
M
|
AD
|
SD Cogan
|
|
|
6
|
48
|
F
|
CN
|
Psoriasis
|
SH/TH
|
|
7
|
25
|
M
|
CN
|
SLE
|
|
|
8
|
53
|
F
|
CN
|
RA + scleroderma
|
|
|
9
|
56
|
F
|
CN
|
RA
|
SH/DM/CP
|
|
10
|
45
|
F
|
AD
|
SLE
|
smoking habit
|
|
11
|
42
|
F
|
CN
|
SD Susac
|
--
|
|
12
|
52
|
F
|
AD
|
Sd Sjogren + Scleroderma
|
SH
|
|
13
|
54
|
F
|
CN
|
RA + vitiligo
|
smoking habit
|
Abbreviations: AD, Afro-descendant; AS, Ankylosing Spondylitis; CN, Caucasian; CRF,
Chronic Renal Failure; DM, diabetes mellitus; F, Female; HT, Hypothyroidism; M, Male;
RA, Rheumatoid Arthritis; Sd, Syndrome; SH, Systemic Hypertension (high blood pressure);
SLE, Systemic Lupus Erythematosus; UA, Unstable Angina.
With regard to comorbidities at the beginning of follow-up, six (46.15%) patients
had systemic hypertension (SH); two (15.38%), smoking; one (7.69%), hypothyroidism;
one (7.69%), coronary artery disease (CA); one (7.69%), chronic renal failure (CRF)
and one (7.69%), diabetes mellitus (DM). Three (23.08%) of these manifested concomitant
comorbidities, which means, one was hypertension SH, diabetes mellitus DM and AI;
another one, hypertension SH and CRF and the third one, hypertension SH and hypothyroidism
([Table 1]).
Besides the sudden SNHL, other audiological symptoms reported by patients were buzzing
in thirteen patients (100%), dizziness in seven patients (53.8%), and ear fullness
in five patients (38.4%).
Otoscopy test of the thirteen patients was normal. Out of the thirteen patients, ten
(76.92%) underwent magnetic resonance imaging. None of them showed cochlear enhancement
on T1-weighted after contrast injection.
With regard to treatment, we administered a full dose (1mg/kg) of systemic corticosteroids
prednisone in all 13 (100%) patients. In addition to the steroids, we also used immunosuppressants
as shown in [Table 2].
Table 2
Medications taken on the treatment
|
Case
|
S. steroids
|
I. steroids
|
Azathioprine
|
Methotrexate
|
Cyclophosph.
|
Chloroquine
|
Infliximab
|
Sufasa Lazine
|
|
1
|
Y
|
Y
|
N
|
Y
|
N
|
N
|
Y
|
N
|
|
2
|
Y
|
N
|
Y
|
N
|
N
|
N
|
N
|
N
|
|
3
|
Y
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
|
4
|
Y
|
N
|
N
|
Y
|
N
|
Y
|
N
|
N
|
|
5
|
Y
|
N
|
N
|
N
|
Y
|
N
|
N
|
N
|
|
6
|
Y
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
|
7
|
Y
|
N
|
N
|
N
|
N
|
Y
|
N
|
N
|
|
8
|
Y
|
N
|
Y
|
Y
|
N
|
N
|
N
|
Y
|
|
9
|
Y
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
|
10
|
Y
|
N
|
N
|
Y
|
N
|
Y
|
N
|
N
|
|
11
|
Y
|
N
|
N
|
N
|
Y
|
N
|
N
|
N
|
|
12
|
Y
|
N
|
N
|
N
|
N
|
N
|
N
|
N
|
|
13
|
Y
|
N
|
N
|
Y
|
N
|
N
|
N
|
N
|
|
Total
|
13
|
1
|
2
|
5
|
2
|
3
|
1
|
1
|
|
Percentage (%)
|
100
|
7.69
|
15.38
|
38.46
|
15.38
|
23.08
|
7.69
|
7.69
|
Abbreviations: Cyclophosph., Cyclophosphamide; I. steroids, Intra-tympanic steroids;
N, No; S. steroids, Systemic steroids; Y, Yes.
The time between the sudden SNHL and the start of treatment averaged 21 days, with
a minimum of 6 and maximum of 60 days. The average of the follow-up of these patients
was 27.6 months, with a minimum of two months and a maximum of 66 months.
In nine (69.23%) patients, the side initially affected was on the right hand side
and in three (23.08%) was on the left. One patient (7.69%), whose underlying disease
was SLE, expressed simultaneous bilateral involvement. In other two (15.38%) patients,
there was contralateral posterior involvement, approximately 15 days after the first
event. One of these patients had underlying disease as Susac syndrome and the other
one, Cogan's syndrome.
We observed bilateral cases in three (23.08%) out of 13 patients, which means that
16 ears showed symptoms of sudden SNHL in patients with SAD. We analyze below these
16 ears.
The initial graduation of hearing loss (found upon admission to our service) presented
as follows: seven (43.75%) ears had profound hearing loss; four (25%), severe hearing
loss; three (18.75%) had moderate hearing loss; and two (12.50%), mild hearing loss
([Table 3]). The affected RTS 16 ears performed as follows: ten (62.50%) with RTS greater than
90 dB; one (6.25%) with RTS between 71–90 dB; two (12.50%) with RTS between 26–40 dB;
one (6.25%) with RTS between 41–70 dB; and two (12.50%), up to 25 dB ([Table 3]). The SRI for monosyllabic words of affected ears presented the following distribution:
SRI zero in ten (62.50%); SRI equal to 45% in one (6.25%); SRI equal to 75% in one
(6.25%); SRI equal to 92% in 3 (18.75%); and SRI equal to 96% in one (6.25%) ([Table 3]).
Table 3
Initial audiometric characteristics from 16 affected ears at the time of admission
to our service
|
Case
|
Affected Side
|
Degree of Initial Loss
|
Initial Audio Curve
|
Initial SRI (dB)
|
Initial SRI Monosyllable (%)
|
|
1
|
R
|
moderate
|
downward
|
up to 25
|
92
|
|
2*
|
L
|
deep
|
NA
|
> 90
|
0
|
|
2*
|
R
|
deep
|
downward
|
> 90
|
0
|
|
3
|
L
|
severe
|
flat
|
> 90
|
0
|
|
4
|
L
|
deep
|
U
|
> 90
|
0
|
|
5*
|
R
|
severe
|
downward
|
> 90
|
76
|
|
5*
|
L
|
moderate
|
flat
|
26 to 40
|
44
|
|
6
|
R
|
deep
|
flat
|
> 90
|
0
|
|
7
|
R
|
severe
|
U
|
> 90
|
0
|
|
8
|
R
|
light
|
downward
|
26 to 40
|
96
|
|
9
|
R
|
deep
|
NA
|
> 90
|
0
|
Abbreviations: L, Left; R, Right; SRI, speech recognition index.
* Bilateral cases.
Regarding the initial type of audiometric curve of the 16 affected ears, five (31.25%)
had a flat curve; four (25.00%), downslope; three (18.75%), U-type curve, and in four
(25.00%) we could not classify the type of curve because the loss was too profound
([Table 3]).
At the end of follow-up, the degree of hearing loss of the affected ears presented
as follows: seven (43.75%) ears with profound loss, two (12.25%) with severe loss,
four (25.00%) with moderate loss, two (12.25%) with mild hearing loss, and one (6.25%)
showed no hearing loss ([Table 4]).
Table 4
Audiometric characteristics from 16 affected ears at the end of follow-up
|
Case
|
Affected Side
|
Degree Final Loss
|
Final RST (dB)
|
SRI Final Monosyllable (%)
|
|
1
|
R
|
severe
|
41 to 70
|
75
|
|
2*
|
L
|
deep
|
> 90
|
0
|
|
2*
|
R
|
deep
|
> 90
|
12
|
|
3
|
L
|
moderate
|
41 to 70
|
56
|
|
4
|
L
|
deep
|
> 90
|
0
|
|
5*
|
R
|
deep
|
> 90
|
0
|
|
5*
|
L
|
deep
|
> 90
|
0
|
|
6
|
R
|
severe
|
71 to 90
|
60
|
|
7
|
R
|
moderate
|
41 to 70
|
76
|
|
8
|
R
|
light
|
26 to 40
|
96
|
|
9
|
R
|
moderate
|
41 to 70
|
0
|
|
10
|
R
|
no loss
|
up to 25
|
100
|
|
11*
|
R
|
deep
|
> 90
|
0
|
|
11*
|
L
|
moderate
|
41 to 70
|
95
|
|
12
|
L
|
deep
|
> 90
|
0
|
|
13
|
R
|
light
|
up to 25
|
100
|
Abbreviations: L, Left; R, Right; RTS, reception threshold speech; SRI, speech recognition
index.
* bilateral cases.
The RTS at the end of follow-up of affected ears presented as follows: RTS greater
than 90 dB in seven (43.75%), RTS between 71–90 dB in one (6.25%), RTS between 41–70 dB
five (31.25%), RTS between 26 and 40 dB in one (6.25%), and RTS below 25 dB in two
(12.25%) ([Table 4]). In four (25.00%) ears of different patients, there was an improvement greater
than 40% of the SRI after treatment. In both ears (12.50%) of patients with Cogan's
syndrome, the worsening index was higher than 40%.
Regarding responsiveness to corticosteroids, seven ears (43.75%) showed at least a
partial or temporary response to this treatment. This response was observed by improving
audiometric thresholds. In these seven ears, the time between the beginning of medication
and hearing improvement ranged from 5 to 60 days, with an average of 21.6 days. In
five of these ears (31% of the sample), the answer remained sustained until the last
monitoring conducted with these patients. In two ears of different cases initially
responsive to corticosteroid treatment, the improvement held for about eight months;
after this period, however, there was a further worsening, despite the adequate treatment
([Table 5]). We found normal hearing thresholds in only one ear of a case (7.69%) with unilateral
involvement.
Table 5
Responsiveness to treatment, support of the response and comparison between the initial
and final audiometric characteristics of 16 affected ears
|
Case
|
Affected Side
|
Response to steroids
|
Time after starting medication (days)
|
Sustained response or later worsens (months)
|
Degree of initial loss
|
Degree of final loss
|
SRI-initial monosyllable (%)
|
SRI-final monosyllable (%)
|
|
1
|
R
|
Y
|
24
|
9 (subsequent worsening)
|
moderate
|
severe
|
92
|
75
|
|
2*
|
L
|
N
|
not occurred
|
|
deep
|
deep
|
0
|
0
|
|
2*
|
R
|
N
|
not occurred
|
|
deep
|
deep
|
0
|
12
|
|
3
|
L
|
Y
|
15
|
20 (tracking ended)
|
severe
|
moderate
|
0
|
56
|
|
4
|
L
|
N
|
not occurred
|
|
deep
|
deep
|
0
|
0
|
|
5*
|
R
|
N
|
not occurred
|
|
severe
|
deep
|
75
|
0
|
|
5*
|
L
|
N
|
not occurred
|
|
moderate
|
deep
|
45
|
0
|
|
6
|
R
|
Y
|
60
|
7 (worsening afterwards)
|
deep
|
severe
|
0
|
60
|
|
7
|
R
|
Y
|
5
|
2 (tracking ended)
|
severe
|
moderate
|
0
|
76
|
|
8
|
R
|
N
|
not occurred
|
|
light
|
light
|
96
|
96
|
|
9
|
R
|
Y
|
20
|
9 (tracking ended)
|
deep
|
moderate
|
0
|
0
|
|
10
|
R
|
Y
|
15
|
2 (tracking ended)
|
severe
|
no loss
|
0
|
100
|
|
11*
|
R
|
N
|
not occurred
|
|
deep
|
deep
|
0
|
0
|
|
11*
|
L
|
Y
|
12
|
16 (tracking ended)
|
moderate
|
moderate
|
92
|
95
|
|
12
|
L
|
N
|
not occurred
|
|
deep
|
deep
|
0
|
0
|
|
13
|
R
|
N
|
not occurred
|
|
light
|
light
|
92
|
100
|
Abbreviations: L, Left; N, No; R, Right; SRI, speech recognition index; Y, Yes.
* bilateral cases.
Out of the other nine ears (56.25%), which did not respond to the treatment ([Table 5]), seven (77.77%) remained unchanged with audiometric thresholds during evolution.
Five (71.42%) had profound loss from beginning to end monitoring. Both ears of the
patient with Cogan's syndrome showed rapidly irreversible progressive audiometric
worsening.
At the end of follow-up, according to the hearing improvement criteria adopted, of
the 16 affected ears, five (31.25%) showed improvement, three (18.75%) got worse,
and eight (50.00%) had the final loss similar to the initial loss. Note that, initially,
two more ears (12.5%), in addition to the five aforementioned, showed a temporary
hearing improvement, with deterioration of the parameters evaluated during evolution
([Table 5]).
Discussion
Sudden sensorineural hearing loss is a medical emergency and understanding its possible
etiologies for indication of a more effective treatment is a goal that remains under
pursuit by the medical and scientific communities. The probable cause immune-mediated
is suggested by many specialists; so, due to its possible responsiveness when set
up an appropriate and early treatment, should always be remembered.
It is important to highlight that sudden SNHL is a clinical entity defined by hearing
loss symptom of sudden onset associated with audiological and temporal criteria, while
the immune-mediated SNHL would be a likely etiologic diagnosis.
Of our sample of 339 patients with sudden SNHL, 13 (3.83%) had confirmed SAD. Whereas
this systemic immune-mediated change is a possible cause of hearing loss in such patients,
according to the literature, only 10 to 29% of sudden SNHL have a defined etiology.[12]
[24] Given the difficulty to confirm the diagnosis, and mainly the lack of criteria for
this diagnosis, we chose not to include possible immune-mediated hearing loss, which
are not associated with SAD but confirmed with rheumatologic criteria and laboratory
tests in this analysis. This way, the prevalence of sudden sensorineural hearing loss
with immune-mediated etiology should be even greater.
In this study, the mean age of patients with SAD at the time of SSNHL installation
was 44 years and the same average was found in the sample without SAD. This is in
agreement with the literature, in which several studies show that both sudden SNHL
and immune-mediated SNHL most often affect patients between their thirties and fifties.[17]
[18]
Regarding gender, most patients in our sample were women (69.23%). This was expected,
because, according to Cooper and Stroehla,[25] 80% of patients with SAD are women. In 1988, Hughes et al[19] showed that 65% of patients with immune-mediated hearing loss were female. Sudden
SNHL not associated with the SAD, though, affected both sexes in the same proportion,
which is also supported by the literature.[26] In other words, with regard to the prevalence of gender, our sample meets a typical
feature of immune-mediated SNHL, not of idiopathic sudden sensorineural hearing loss.
Regarding ethnicity, in our sample, 61.54% were Caucasian and 38.46% were afro-descendant.
The predominance of white skin color is noteworthy; however, we did not find this
correlation in the literature.
The immune-mediated SNHL can be associated with SAD in 30% of cases. However, the
incidence of involvement of the inner ear in the SAD is very variable.[19]
[20] Installing this hearing loss can present abruptly, featuring a sudden SNHL, and
the progression can be fast and with bilateral involvement.
The pathophysiology of immune-mediated character that may be involved in inner ear
dysfunction include: immediate hypersensitivity, with production of IgE immunoglobulins
against cochlear antigens; immune complex deposits in the stria vascularis and spiral
ligament; direct action of cytotoxic T cells in the cochlea; and delayed hypersensitivity
with immune reactivity mediated collagen type II. These mechanisms can act in a complementary
way and often do so simultaneously.[27]
Although some authors report that hearing loss can manifest as the first symptom of
SAD,[28] this was not the case in our sample. All patients had already had other systemic
symptoms related to autoimmune disease prior to the installation of sudden SNHL.
In our sample, 30.77% had SLE, the same prevalence as that of patients with RA.
Several authors have demonstrated the relationship between SLE and sudden SNHL. Researchers
have also speculated on the existence of a strong relationship between the presence
of anticardiolipin antibodies, often found in patients with SLE, and sudden SNHL.[2]
[27]
[29] In such cases, the authors argue that the formation of microthrombus in cochlear
vessels could be the etiology of sudden SNHL.
In a retrospective cohort population study in patients with SLE in the population
of Taiwan, Lin et al[5] reinforce the relationship between SLE and sudden SNHL by showing that patients
affected by this immune-mediated disease have an incidence rate of sudden SNHL up
to 4.27 times higher than the general population.
The literature related to RA with hearing loss[30] demonstrates involvement of the inner ear in 60% of cases. Moreover, although we
believe in this association, we found no studies that indicate a relationship of this
disease with sudden SNHL.
In our study, 15.38% of patients had scleroderma. Hearing loss and other audiological
symptoms such as tinnitus, have been reported in up to 40% of patients with systemic
sclerosis.[31] Deroee et al[4] described the case of a 65 year-old patient who developed sudden SNHL as the first
manifestation of scleroderma. The two patients with scleroderma shown in our study
showed sudden SNHL years after diagnosis of the disease.
One of the patients included in this study had Sjogren's syndrome. The literature
shows the presence of hearing loss in up to 25% of patients with the syndrome.[32] Nonetheless, we have not found in our review any article that would correlate this
syndrome with sudden SNHL. Thus, our report renders it a breakthrough.
Yet another patient included in this study has presented with Cogan's syndrome. Several
authors associate this syndrome with sudden SNHL.[33]
[34]
[35]
Another patient included in our sample had Susac syndrome. The literature review shows
that many authors correlate this devastating syndrome with sudden SNHL.[36]
[37]
[38]
[39]
One of the patients included in our case series was diagnosed with psoriasis. We found
little evidence in the literature showing a possible link between this disease and
sudden SNHL.[40]
The vitiligo patient described in our results also had RA. Several authors have described
increased prevalence of SNHL, as well as other hearing disorders in patients with
vitiligo.[41] However, we have not found any article that directly relates vitiligo with sudden
sensorineural hearing loss.
One of our patients had ankylosing spondylitis (AS). In our review, we found evidence
of an increased prevalence of sensorineural hearing loss in patients with AS, but
not specifically its relationship with sudden SNHL.[42]
Eight patients (61.53%) expressed other systemic comorbidities aside from SAD, at
the time when they had sudden SNHL: hypertension, diabetes mellitus, CRF, HT, UA,
and smoking. It is not sure that these comorbidities may be risk factors for sudden
SNHL.[43]
Regarding associated symptoms, all (100%) patients in our study had tinnitus; 54%,
dizziness, and 38%, ear fullness concomitant with sudden sensorineural hearing loss.
These percentages are identical to those found in the literature concerning the sudden
SNHL idiopathic.[44] As for immune-mediated hearing loss, 83% expressed tinnitus; 60% dizziness, and
50% ear fullness.[45]
[46] In other words, we found a higher incidence of tinnitus in our study when compared
with literature findings.
The otoscopy of 13 patients did not show significant alterations. This matches findings
in the literature, noting the normality of these patients' tests.[17]
In our study, we chose not to emphasize the analysis of autoantibodies, as the diagnosis
of several autoimmune diseases evaluated would require several specific laboratory
tests whose results would vary at different stages of evolution for each patient.
The diagnosis for each of the above diseases relies on their own rheumatologic clinical
criteria. Regarding the search for specific autoantibodies of the inner ear for the
diagnosis of immune-mediated SNHL, although once considered a promising method, recent
studies show a low sensitivity of these tests. Among these, the most researched is
the Anti-Heat Shock Protein 70 antibody (Hsp 70), which also has not demonstrated
efficiency in diagnosing such illness.[23]
Out of the 13 patients, ten (76.92%) underwent magnetic resonance imaging. Cochlear
showed no enhancement in any of the ears on the T1-weighted after contrast injection.
Fitzgerald and Mark described a series of cases in which 66% of patients with sudden
SNHL with immune-mediated etiology presented highlight the labyrinth after contrast
injection. Although post-administration gadolinium enhancement of the inner ear is
a widespread finding in the literature, we found scarce studies confirming the hypothesis
of immune-mediated SNHL. These were based on a few cases that demonstrate this alteration.[22]
[47] We believe the discrepancy between our findings and the literature could be justified
with examination after the start of corticosteroids therapy and the methodology of
accomplishment and different analysis.
The currently recommended treatment for sudden SNHL is the use of systemic corticosteroids
in full dose, which is the equivalent of 1mg/kg of prednisone, and a gradual reduction
of the dose based on audiometric recovery parameters. Transtympanic infusion of corticosteroids
is indicated in cases of failure or contraindication of systemic therapy or incomplete
improves as a rescue therapy.[48] In cases of immune-mediated SNHL, in addition to systemic corticosteroids and/or
transtympanic, it is possible to use other immunosuppressive medications. These are
recommended for patients who did not respond to corticosteroids or as a way to preserve
the prolonged use of corticosteroids to provide sustainability and maintain hearing
recovery, as well as prevent and slow the deterioration of hearing of these individuals.[17]
[46]
[49]
All cases presented in this study had full dose systemic corticosteroids as initial
treatment for sudden SNHL. Only a particular person (case 1) was treated with a series
of transtympanic injections of corticosteroids and, therefore, proved to be refractory
to the initial systemic therapy.
As all of the patients had SAD, the use of other immune-suppressive medications was
very common, occurring in 77% of cases during follow-up at our clinic. Sometimes we
indicated such medications for the treatment of hearing loss; in most cases, however,
it was aimed to control the systemic disease base.
The most commonly used immunosuppressant in the cases was methotrexate, administered
to 40% of patients. Its efficacy in the treatment of immune-mediated sensorineural
hearing loss has been widely studied. More recently, however, a study demonstrated
that this drug does not have the expected result for the treatment of immune-mediated
sensorineural hearing loss.[49] Garcia-Berrocal et al[50] reported the treatment of five patients with methotrexate for refractory immune-mediated
SNHL. According to the authors, the drug improved vestibular symptoms but was not
successful in achieving hearing improvement. Although we initially believed in the
effectiveness of methotrexate, we have not seen significant improvement to our patients
hearing.
Among other immunosuppressants used in patients followed, the literature still points
to cyclophosphamide as an alternative for patients refractory to corticosteroids or
the ones who have contraindication to use it. However, we must be alert to the possible
ototoxic effects of this drug, which can lead to worsening of hearing.[46] Two patients described in our study used this medication and we did not detect ototoxic
effect during either one's follow-up.
We have not found in our review overwhelming evidence that shows that chloroquine,
azathioprine, or sulfasalazine, also used in the patients described above, are effective
in the treatment of SNHL immune mediated.[49]
One of our patients tried infliximab for a period. We did not notice improvement in
hearing parameters during his use of the medication. Liu et al[51] demonstrated eight cases of patients with immune-mediated SNHL refractory to corticosteroid
treated with infliximab. None of them showed audiometric improvement.
Although controversy remains over the effectiveness of these immunosuppressive drugs
for the hearing improvement, we believe the specific treatment to control SAD can
indeed slow down the progression of the inner ear lesion. Thus, even if there is recovery
of hearing thresholds already committed, it would prevent the progression of the lesion
in the ear as well as contralateral involvement. Moreover, we observed significant
improvement of vestibular symptoms during the use of these drugs. The literature also
describes the improvement of vestibular symptoms with the use of immunosuppressants,
even without achieving hearing improvement.[50]
Patients with sudden SNHL with probable immune-mediated origin, as opposed to those
with idiopathic sudden SNHL without the suspicion, have more severe initial impairment,
higher percentage of bilateral, lower response to treatment, and worse prognosis.
This is likely to occur due to the continued assault on the immune-mediated inner
ear structures, whereas most patients with idiopathic sudden SNHL suffer a single,
acute triggering event, without further worsening of hearing loss. Several authors
have also stated that the responsiveness of immune-mediated SNHL happens in the early
stages, that is, in the first days or weeks.[16]
[19] Therefore, establishing appropriate treatment at the earliest possible time is important
to be able to stop the progression of the lesion and get a better prognosis.[49]
In our study, the time elapsed between the onset of sudden SNHL and the start of treatment
was 21 days on average. We believe that this delay occurred due to other priorities
demanded by SAD, which means some patients do not prioritize the treatment of sudden
sensorineural hearing loss among the systemic manifestations caused by the underlying
disease. Several authors show the correlation between the start of treatment time
and the prognosis for hearing recovery in cases of sudden SNHL and suggest that the
shorter it takes, the better the prognosis.[52]
The mean follow-up time of these patients was 27.6 months, which provided us a longitudinal
observation of their evolution. We realize, therefore, the dynamic and often unpredictable
nature of the illness, even with treatment for the underlying disease. One should
also pay attention to further worsening of hearing loss; it may be a sign of acute
relapse or activity of the disease base.[30]
As for unilateral or bilateral involvement, out of the 13 cases presented, three (23%)
had bilateral involvement, including one occurring simultaneously. Curiously enough,
in these three cases, the installation of hearing loss happened suddenly in both ears.
We believe that bilateral involvement occurred in only 23% of cases in our sample
because we established correct treatment early and patients underwent rigorous clinical
monitoring. As the bilateral involvement is often asymmetric, the other ten patients
may subsequently have a contralateral involvement that can be installed both sudden
way of progressively. We did not find in the literature the incidence of bilateral
involvement in cases of immune-mediated SNHL in patients with SAD.
Bilateral involvement is a common feature of the SNHL immune-mediated, even used as
an indicator for diagnostic.[16] However, in our view, bilateral is clearly predominant in undiagnosed patients who
have not received proper treatment. When we think of sudden SNHL as a whole, the literature
describes 1.7% to 3% of bilateral occurrences, being the exception rather than the
rule.[26] Fetterman et al[26] describe patients with simultaneous bilateral sudden SNHL as well as symmetrical
audiometric curves between both sides. The authors state they are more likely to have
positive antinuclear antibodies, indicating an association with immune-mediated etiology.
The patient with bilateral simultaneous sudden SNHL received diagnosis of SLE as the
underlying disease. It was quite distressing for both the patient and his physician
to face bilateral and simultaneous installation.[17] Nevertheless, this was the patient inspired our search for a specific treatment
for hearing loss (60 days). He was in a severe state of depression compounded by hearing
loss.
In 70% of ears, the degree of hearing loss present upon admission to our study was
severe or profound: 43.75% had profound hearing loss while 25% had severe hearing
loss. Penido et al[44] reported that 50% of patients with sudden SNHL analyzed in their clinic had severe
or profound loss. Initially, 63% of ears in our sample presented RTS greater than
90 dB and SRI zero. We ponder that the higher incidence of more severe early hearing
loss in our current sample results from a more aggressive lesion due to the likely
immune-mediated etiology involved. These initial audiometric findings were indication
of a worse prognosis from the beginning.
Our patients did not show a predominant audiometric curve configuration at the time
of admission. We stress that in 25% of affected ears, we could not classify the type
of audiometric curve because the loss was too deep. The literature shows that 43%
of patients with sudden sensorineural hearing loss showed plane curve and the type
of audiometric initial curve is not related to the prognosis of these patients.[44] Some authors present results suggesting the involvement fist of higher frequencies
in immune-mediated SNHL, however, this fact was not observed in our patients.
As for responsiveness to corticosteroids, 44% of affected ears presented a presented
at least a partial or temporary positive response to this treatment, with improvement
of the audiometric thresholds. This data agrees with the literature, whereby several
studies report responsiveness to corticosteroids at a rate ranging from 44% to 70%
in cases of immune-mediated SNHL.[45]
[53]
In our study, 31% of the ears analyzed showed sustained response to the latest monitoring
conducted. However, two ears (12.5%) of different patients sustained a response for
about eight months, after which they had hearing impairment despite treatment. According
to Broughton et al,[45] 70% of patients with immune-mediated SNHL are initially responsive to corticosteroids
and only 14% sustain this response after 34 months of treatment.
Although we have not monitored for as long as this author, we believe that the response
to corticosteroids may be temporary in some cases, a fact that brings us great concern.
Still about the responsiveness to treatment, we found normal hearing thresholds only
in one ear of one case (7.69%) with unilateral involvement, suggesting a poor prognosis
of this disease. Another fact that also strongly indicates a poor prognosis related
to immune-mediated SNHL associated in patients with SAD is that, at the end of follow-up,
only 30% showed sustained improvement, while 20% got worse, and 50% had a final loss
similar to the initial loss. Unfortunately, we know that those who improved could
still worsen and it is unlikely those who suffered worsening will improve satisfactorily.
Moreover, some ears remained stable: 71% showed profound loss from beginning to end
of monitoring. We believe that this occurs because there is a point at which damage
to the inner ear cells becomes irreversible and, therefore, there is no possibility
of improvement with treatment currently available.
The likely immune-mediated etiology of sensorineural hearing loss is still uncertain,
as well as the association with systemic autoimmune diseases, more research is needed
to clarify these possible relationships. In the future, with the new possibilities
of molecular medicine, gene therapy, and the development of treatment with stem cells,
this reality can change and give us the ability to offer a better prognosis for such
patients.
Conclusion
In our sample of patients with sudden sensorineural hearing loss, the prevalence of
systemic autoimmune disease was considerable. This association was more frequent among
white adult women. Most patients had unilateral hearing loss, severe or profound,
associated with concomitant dizziness. All had tinnitus. Most cases did not improve
audiometric thresholds, not even with the treatment.
Our patients with sudden SNHL and SAD have more severe initial impairment, higher
percentage of bilateral, lower response to treatment, and worse prognosis when compared
with patients without this association.
