Clin Rheumatol

DOI 10.1007/s10067-017-3651-4

ORIGINAL ARTICLE

Prevalence of hearing impairment in patients with rheumatoid

arthritis, granulomatosis with polyangiitis (GPA, Wegener’s
granulomatosis), or systemic lupus erythematosus
Torsten Rahne 1 & Franziska Clauß 1,2 & Stefan K. Plontke 1 & Gernot Keyßer 2

Received: 27 November 2016 / Revised: 12 April 2017 / Accepted: 18 April 2017

# International League of Associations for Rheumatology (ILAR) 2017

Abstract Hearing loss in patients with autoimmune diseases,
such as systemic lupus erythematosus (SLE), granulomatosis
with polyangiitis (GPA, Wegener’s granulomatosis), or rheuma-
toid arthritis (RA), is controversial. Many studies lack measure-
ments of bone-conduction thresholds to sufficiently differentiate
between sensorineural hearing loss and conductive hearing loss.
In addition, many studies lack control groups or comparisons to
an age-related normal hearing threshold. This study investigates
hearing performance with an extended audiological battery using
psychoacoustic and objective measures. A total of 22 adults with
RA, 16 with GPA, 20 with SLE, and two age- and gender-
matched control groups (n = 34 for GPA and RA and n = 42
for SLE) were included. Pure-tone hearing thresholds, speech
perception in quiet and noise, tympanometry, and high-
resolution otoacoustic emissions were assessed. GPA patients
exhibited impaired pure-tone hearing compared to the control
group, whereas SLE and RA patients did not. In GPA patients,
a larger air-bone gap indicated conductive hearing loss. In addi-
tion, speech perception was reduced exclusively in GPA patients.
A significant correlation was found between hearing loss and
both the cumulative steroid dose and number of organ manifes-
tations in GPA and SLE patients. Our data indicate that GPA and
SLE patients are at moderate-to-high risk of conductive hearing
loss. In contrast, RA patients are at low risk of disease-associated
hearing loss.
Keywords Conductive hearing loss . Distortion products of
otoacoustic emissions (DPOAEs) . Granulomatosis with
polyangiitis . Pure-tone threshold . Rheumatoid arthritis .
Sensorineural hearing loss . Speech perception . Systemic
lupus erythematosus

Key messages
• We found neither conductive hearing loss nor mixed hearing loss in RA
patients. Introduction
• We found a high conductive hearing loss and mixed hearing loss
prevalence in the GPA group. Inflammatory rheumatic diseases are systemic in nature and
• The prevalence of sensorineural hearing loss was higher in SLE patients
account most prominently for autoimmune diseases, such as
than in the control group.
systemic lupus erythematosus (SLE) and granulomatosis with
Torsten Rahne and Franziska Clauß contributed equally to the p o l y a n g i i t i s ( G PA , We g e n e r ’s g r a n u l o m a t o s i s ) .
manuscript.
Autoantibodies and other autoimmune phenomena, such as
vasculitis and granuloma formation, may lead to a widespread
* Torsten Rahne
Torsten.rahne@uk-halle.de inflammatory reaction that damages a variety of tissues. In
addition, rheumatoid arthritis (RA) may affect many structures
in addition to the joints. Though damage to vital organs is
1
Department of Otorhinolaryngology, Head and Neck Surgery, increasingly well understood, such as nephritis in SLE and
University Hospital Halle (Saale), Martin Luther University
Halle-Wittenberg, Ernst-Grube-Str. 40, 06120 Halle
GPA, some manifestations are subtle and difficult to discern
(Saale), Germany from mechanisms attributable to degeneration and aging or
2
Clinic for Internal Medicine II, Department of Internal Medicine,
the adverse effects of immunosuppressive therapy. In patients
University Hospital Halle (Saale), Martin Luther University with systemic rheumatic diseases, their sense of hearing may
Halle-Wittenberg, Halle, Germany be impaired by all three mechanisms mentioned above.

However, only a few systematic investigations have compared
the performance and possible impairment of the auditory sys-
tem in patients with different inflammatory rheumatic
diseases.
Hearing loss can be categorized as sensorineural hearing
loss (SNHL) or conductive hearing loss (CHL). SNHL is
mainly attributable to the loss of inner or outer hair cells in
the cochlea and is usually permanent, causing presbycusis.
CHL occurs with increased mechanical resistance anywhere
along the route of the sound wave through the outer ear, tym-
panic membrane, or middle ear.
In patients with RA, the incudostapedial and incudomalleolar
joints can be affected by the same inflammatory and destructive
changes as other joints. Although this process may lead to CHL,
the prevalence and relevance of the latter are controversial. Apart
from damage to the auditory ossicles, damage may occur to inner
ear structures due to vasculitis or neuritis, or the ototoxicity of
antirheumatic drugs. This phenomenon could lead to SNHL.
Autoantibodies against inner ear antigenic epitopes may also
cause SNHL in RA [1]. Reviews by Ememifar et al. [2, 3] refer
to the wide variation in the reported prevalence of different types
of hearing loss in RA patients.
Colletti et al. [4] investigated 30 patients with RA and ob-
served neither CHL nor SNHL. However, the authors described
a modified behavior of the middle ear to static pressure, which
reflects reduced function of the Eustachian tube and promotes
the development of CHL. This is in line with other studies that
did not show a significant difference in SNHL or CHL between
29 [5] or 20 RA patients [6] compared to age-matched control
groups. In contrast, Takatsu et al. [7] found CHL in low fre-
quencies and an increased prevalence of SNHL in 36 RA pa-
tients, though this finding was of low significance. Other au-
thors have described a high prevalence of SNHL in cohorts of
194 [8] and 113 [9] RA patients, or at high frequencies by de la
Vega et al. [10]. However, these studies lacked either a mea-
surement of bone-conduction thresholds or a comparison to a
control group. On the other hand, Ozcan et al. [11] measured an
increased prevalence of SNHL in 37 RA patients compared to
age-matched controls, but the difference was not significant.
Inner ear impairment was assumed [12, 13], but the reduced
otoacoustic emissions in RA patients [6] could also be caused
by CHL. No studies have yet investigated the impact of modern
biologic treatments on hearing capability in RA or the dynamic
process of hearing impairment in RA patients over the course
of the disease.
In patients with GPA, otologic manifestations of the disease
are very common [14–16]. Takagi et al. [17] reported otologic
manifestations in 60% of 25 patients with chronic otitis media,
and Morales-Angulo et al. [18] reported otologic manifesta-
tions in 32% of 70 patients. Due to the involvement of the
middle ear in GPA patients, CHL is more likely than SNHL.
Bakhtavachalam et al. [19] reported CHL in 33% of 36 pa-
tients with GPA using pure-tone audiometry, and Martinez del
Clin Rheumatol
Pero et al. [14] found that 38% of 144 patients with GPA had
CHL as indicated by a negative Rinne’s test. Importantly, the
studies did not include a control group. Yoshida and Lino [20]
summarized a review of case studies showing CHL or mixed
SNHL and CHL (mixed hearing loss, MHL) in GPA patients.
The treatment options for GPA have improved over the last
few years. However, the impact of modern biological therapy
on the auditory system in GPA has not yet been investigated.
In SLE patients, vasculitis and microinfarctions are caused
by the deposition of immune complexes in the microvessels of
the temporal bone. This process is known to induce SNHL
[21]. A loss of spiral ganglion and hair cells, atrophy of the
stria vascularis [22], and an endolymphatic hydrops caused by
perisaccular deposition of immune complexes [23] have been
reported as well. In clinical studies of SLE, the prevalence of
SNHL varied between 8 and 57.5% [24], but no hearing def-
icits were found in a study of 20 SLE patients [25]. Karabulut
et al. [26] evaluated 26 patients with SLE and found low-
frequency hearing loss, referred to as an endolymphatic
hydrops. SNHL has been reported in patients with SLE in
studies with 35 [27], 45 [28], and 89 patients [29].
Interestingly, a higher incidence of sudden SNHL was report-
ed in a study of 3847 patients [30]. However, some of those
studies did not report bone-conduction thresholds or even ex-
cluded patients with CHL. Thus, no sufficient differentiation
of SNHL and CHL is possible in these cases.
The present study includes patients with RA, GPA, and
SLE, as well as an appropriate number of controls. Hearing
was assessed with an extended audiological battery consisting
of psychoacoustic and objective measures, rendering a direct
comparison between the groups and their respective control
groups possible.
Methods
Patients
A total of 58 consecutive adult patients at the outpatient clinic
for Rheumatology University Hospital Halle (Saale) who
were diagnosed with RA, GPA, or SLE and fulfilled the clas-
sification criteria for the respective diagnosis were included in
the analysis. All patients provided written informed consent.
An age-matched control group without a history of known
hearing impairment was recruited by a bulletin with the coop-
eration of three general practitioners and personal contacts of
the author FC and JLS. The study was approved by the local
ethics committee.
Clinical assessment
The following disease-related information was obtained: dis-
ease duration, number and extent of organ-specific
Clin Rheumatol
manifestations, previous and current immunosuppressive
medication, and the cumulative steroid dose. The
Birmingham Vasculitis Activity Score (BIVAS), Disease
Activity Score 28 (DAS28), and European Consensus Lupus
Activity Measurement (ECLAM) were calculated for vasculi-
tis, RA, and SLE patients, respectively.
Hearing assessment
In an interview carried out by FC and JLS, the patients were
asked about subjective hearing loss and tinnitus and their his-
tory of conditions that may have contributed to their hearing
impairment: previous head injury, otologic surgery, idiopathic
sudden SNHL, acute acoustic trauma, long-term (chronic)
noise exposure, frequent middle ear infections in childhood,
familial occurrence of hearing loss, diabetes mellitus, and ex-
posure to ototoxic drugs (e.g., aminoglycosides and acetylic
acid).
Otologic and hearing assessment
All multimodal hearing assessments were performed at the
Hearing Centre of the Department of Otorhinolaryngology,
Head and Neck Surgery at the University Hospital Halle
(Saale). Micro-otoscopy of the ears was performed for all
patients by an experienced otologist prior to audiological test-
ing. Subsequently, routine pure-tone audiometry was per-
formed, followed by measurement of tympanic membrane
compliance, acoustic reflexes, and otoacoustic emissions.
Pure-tone audiometry
For each ear, pure-tone audiometry was performed using an
Auritec AT900 clinical audiometer (Hamburg, Germany) in a
sound-attenuated booth (Industrial Acoustics Company,
Niederkrüchten, Germany) with noise levels within the stan-
dardized limits (ISO 8253-1). Audiometric headphones (HDA
200, Sennheiser, Wedemark, Germany) were used to obtain
air conduction (AC) pure-tone thresholds at 0.125, 0.5, 1, 1.5,
2, 3, 4, 6, and 8 kHz according to a standardized protocol (ISO
8253-1) with a step size of 5 dB. Bone conduction (BC) pure-
tone thresholds were obtained for the limited frequency range
of 0.25, 0.5, 1, 1.5, 2, 3, 4, and 6 kHz. Masking narrow-band
noise was presented at the contralateral ear, if applicable. The
average pure-tone threshold (4PTA) was calculated as the
mean of the thresholds at 0.5, 1, 2, and 4 kHz. The air-bone
gap (ABG) was determined as the difference in 4PTA between
AC and BC measurements. The age- and gender-dependent
predicted median of hearing level and 5th and 95th percentiles
were computed according to the algorithm provided by the
ISO 7029 protocol. CHL was defined as ABG >10 dB,
SNHL as 4PTA for AC and BC >15 dB HL, and MHL as
both SNHL and CHL being present.
At the better-hearing ear, the fine structure of the hearing
threshold was determined using a customized MATLAB-
based psychoacoustic setup. Sinusoidal tones generated by
an RME Fireface 400 audio interface (Haimhausen,
Germany) were amplified by a HB7 Headphone Drive
(Tucker Davis, Alachua, FL, USA) and delivered by an
HDA 200-type audiometric headphone. With an adaptive
up-down paradigm, the threshold was determined in the fre-
quency range from 0.5 to 10 kHz with a resolution of 10
frequencies per octave. The mean fine structure amplitude
was calculated as the average of differences between the ac-
tual thresholds and a gliding average over one octave (low-
pass filter).
Speech perception
Speech reception thresholds (SRTs) were determined for mul-
tisyllabic numbers and the word recognition score at 65 dB
sound pressure level (SPL) for monosyllables in quiet (WRS)
in sound field condition using the Freiburger speech test. For
the WRS, the mean correct words of two randomized lists of
20 items were analyzed. Speech perception in noise was mea-
sured using the Oldenburg sentence test. To avoid training
effects, the second of two randomized lists was used to adap-
tively measure the SRT as the signal-to-noise ratio. A constant
noise level of 65 dB SPL was used.
Tympanometry and acoustic reflex
Tympanometry and the ipsilateral and contralateral acoustic
reflex thresholds were recorded using a standard clinical im-
pedance meter (MI 24, MAICO, Berlin, Germany) to assess
middle ear function. Admittances were recorded with a stim-
ulation frequency of 85 dB SPL and a probe frequency of
226 Hz. The compliance of the tympanic membrane was eval-
uated to classify tympanogram types A, AS, AD, B, and C
according to Jerger [31]. Briefly, a type A tympanogram rep-
resents patients with normal compliance of the tympanic
membrane. Type AS tympanograms exhibit reduced mobility
of the tympanogram, possibly due to fixation of the ossicular
chain, and AD types represent hypermobility of the tympanic
membrane. Type B represents restricted mobility, mostly due
to a stiff middle ear system, as seen in otitis media. Type C
tympanograms represent significant negative pressure in the
middle ear cavity, which is mostly caused by reduced ventila-
tion by the Eustachian tubes. For frequencies of 0.5, 1, 2, and
4 kHz, the acoustic reflex was evoked by sine tones presented
ipsilaterally or contralaterally with increasing simulation,
starting with 80 dB HL and increasing in steps of 5 dB. The
number of frequencies for which a reflex was evoked was
analyzed.
 Clin Rheumatol

Otoacoustic emissions with GPA (6 males, 10 females; age range 40–74 years, mean
60.2 years, SD 9.9 years), and 20 patients with SLE (5 males,
Distortion product otoacoustic emissions (DPOAEs) were re- 15 females; age range 23–66 years, mean 42.3 years, SD
corded using customized MATLAB-driven hardware. Sounds 14.5 years) were included in the analysis. The demographic
were generated by an RME Fireface 400 audio interface data are summarized in Table 1. The control group for the RA
(Haimhausen, Germany) and amplified by an HB7 and GPA groups consisted of 34 volunteers (13 males, 21
Headphone Drive (Tucker Davis, Alachua, FL, USA). For females; age range 40–75 years, mean 54.8 years, SD
three frequency intervals (low 1.2–2.5 kHz, middle 2.4– 11.0 years). The control group for the SLE patients consisted
5.0 kHz, and high 4.9–10.0 kHz), two sine tone sweeps with of 42 volunteers (15 males, 27 females; age range 23–75 years,
a frequency ratio of 1/1.22 were simultaneously presented to
the ear with a resolution of 390/octave. The SPL combination
Table 1 Demographic and clinical data of the patients
was 65 dB/55 dB for the two stimulation tones as suggested
by Boege and Janssen [32]. An ER-10C probe and DPOAE RA GPA SLE
Probe Driver pre-amplifier (both by Etymotic Research Elk
Grove Village, IL, USA) were used for recording. DPOAE Demographic data
amplitudes and noise amplitudes were analyzed. The mean Total number 22 16 20
fine structure of the DPOAE amplitude was calculated as the Mean (SD) age (years) 56.6 (11.1) 60.2 (9.9) 42.3 (14.5)
average of differences between the actual amplitudes and a Sex (male/female) 6/16 6/10 5/15
gliding average over 30 frequencies (low-pass filter). Mean (SD) duration of disease 4.1 (12.3) 6.8 (6.0) 10.4 (5.1)
(years)
Clinical status
Statistical analysis
Mean (SD) DAS28 score 2.8 (1.5) n.a. n.a.
Mean (SD) BIVAS score n.a. 0.9 (1.3) n.a.
Statistical analyses were carried out using SPSS 22 software
Mean (SD) ECLAM n.a. n.a. 1.5 (2.5)
(IBM, Ehningen, Germany). The age distributions were com-
Patients in remissiona 5 (23%) 9 (56%) 12 (60%)
pared by means of analysis of variance (ANOVA) with the
Patients with antiphospholipid n.a. n.a. 7 (35%)
between-subject factors age and gender. Pure-tone thresholds, syndrome
4PTA, and ABG were compared using a repeated measures Patients with nephritis n.a. n.a. 5 (25%)
AVOVA with a subset of the within-subject factors frequency, Patients with pulmonary n.a. 4 (25%) n.a.
AC/BC mode, and side and the between-subject factor dis- involvement
ease. One-way ANOVA with the factor disease was used to Patients with renal involvement n.a. 7 (44%) n.a.
compare SRT and WRS distributions. The mean fine structure Immunological profile
amplitudes of the hearing threshold, DPOAE amplitude, and RF positive 15 (68%) n.a. n.a.
DPOAE SNR were also compared between diseases and con- CCP-AK positive 15 (68%) n.a. n.a.
trol groups using one-way ANOVA. ANCA positive n.a. 15 (94%) n.a.
Greenhouse-Geisser-corrected degrees of freedom were DNS-AK positive n.a. n.a. 15 (75%)
used if Mauchly’s test of sphericity was significant. Immunosuppressive treatment
Bonferroni-corrected planned comparisons were used for post Glucocorticoids 15 (68%) 15 (94%) 14 (70%)
hoc analysis. The distributions of tympanogram types and Methotrexate (MTX) 12 (54%) 4 (25%) 1 (5%)
number of frequencies that generated acoustic reflexes were Biologicals 10 (45%) 3 (19%) 1 (5%)
compared using the Mann-Whitney U test. For all compari- TNF inhibitors 7 (32%) 0 0
sons, α was set to 95%. Leflunomid (LEF) 5 (23%) 3 (19%) 0
Correlations between the disease-related parameters dis- Rituximab (RTX) 3 (14%) 3 (19%) 1 (5%)
ease duration, cumulative steroid dose, and number of Sulfasalazine (SASP) 2 (9%) 0 0
organ-specific manifestations and the PTA, ABG, WRS, and Azathioprine (AZA) 0 6 (38%) 6 (30%)
SRT were calculated by Spearman rank tests. Cyclophosphamide (CYC) 0 2 (13%) 1 (5%)
Mycophenolat-mofetil (MMF) 0 1 (6%) 2 (10%)
Hydroxychloroquine (HCQ) 0 0 11 (55%)
Results
BIVAS Birmingham Vasculitis Activity Score, DAS Disease Activity
Score, ECLAM European Consensus Lupus Activity Measurement,
Patient demographics GPA granulomatosis with polyangiitis, n.a. not applicable, RA rheuma-
toid arthritis, SD standard deviation, SLE systemic lupus erythematosus
A total of 22 patients with RA (6 males, 16 females; age range a
DAS28 score < 2.0 for RA patients, BIVAS score = 0 for GPA patients,
36–74 years, mean 56.6 years, SD 11.1 years), 16 patients and ECLAM = 0 for SLE patients
Clin Rheumatol

mean 49.2 years, SD 15.4 years). The age and gender distri-
butions between the case and control groups were not signif-
icantly different (ANOVA, p > 0.1).
Disease duration was 1 to 42 years (mean 14.1 years, SD
12.3 years) for RA patients, 1 to 18 years (mean 6.8 years, SD
6.0 years) for GPA patients, and 4 to 23 years (mean
10.4 years, SD 5.13 years) for SLE patients.
Cumulative steroid dose was 0 to 5.5 g (mean 1.9 g, SD
1.7 g) in RA patients and 0 to 4.0 g (mean 2.0 g, SD 1.2 g)
in GPA patients. The mean DAS28 was 2.8 (SD 1.5) in RA
patients. The mean BIVAS was 0.87 (SD 1.3) in GPA
patients.
Otoscopic inspection revealed a normal tympanic mem-
brane. In two GPA patients, an atrophic tympanic membrane
scar was found, and two GPA patients had permanent venti-
lation tubes.
Pure-tone audiometry
Table 2 shows the pure-tone thresholds for the diseases and
their respective control groups. For RA and GPA patients, the
effects of side and the side × disease and frequency × disease
interactions on the pure-tone thresholds were not significant.
The audiometric test frequency significantly affected the pure-
tone threshold (F(1.7, 119.9) = 40.3, p < 0.001), as well as the
use of AC vs. BC stimulation (F(1, 68) = 70.0, p < 0.001) and
the interaction between the AC/BC mode and disease (F(2,
68) = 19.4, p < 0.001), and between frequency, AC/BC mode,
and disease (F(6.5, 226.0) = 3.8, p < 0.01). The between-
subject factor disease significantly influenced the pure-tone
thresholds (F(2, 68) = 4.5, p < 0.05). For SLE vs. control,
the effect of the disease on the pure-tone thresholds was not
significant, but the effects of frequency (F(1.9, 3.8) = 5.7,
p < 0.01), AC/BC mode (F(1, 58) = 15.6, p < 0.001), disease
× frequency interaction (F(3.8, 108.9) = 3.1, p < 0.05), and
frequency × AC/BC mode interaction (F(3.1, 6.2) = 3.7,
p < 0.05) were significant.
Post hoc comparisons showed significant differences in
AC thresholds between GPA and control patients for al-
most all frequencies and BC thresholds for 0.25 and
0.5 kHz at the right ear. For SLE patients, the AC and
BC pure-tone thresholds were significantly different from
the control group at 0.25–0.5 kHz for the right ear and
0.25–1 kHz for the left ear.

Table 2 Mean pure-tone thresholds for the patient and control groups

Mean pure-tone threshold (standard deviation) (dB HL)

Frequency Rheumatoid arthritis Granulomatosis with polyangiitis Control group S. lupus erythematosus Control group
(kHz)
AC BC AC BC AC BC AC BC AC BC

Right
0.125 11.6 (8.8) 26.6 (23.1) 9.1 (6.5) 14.5 (19.9) 8.3 (6.0)
0.25 10.9 (7.5) 10.0 (7.7) 28.1 (29.3) 11.2 (9.9) 7.5 (8.6) 6.2 (7.9) 14.5 (20.1) 11.8 (11.0) 7.1 (7.7) 5.6 (7.3)
0.5 11.4 (6.0) 10.5 (6.0) 29.4 (30.4) 14.7 (12.2) 10.0 (9.0) 8.0 (8.3) 18.5 (23.0) 13.5 (14.3) 9.4 (8.4) 7.4 (7.8)
1 11.8 (5.5) 11.6 (5.0) 30.9 (30.3) 18.1 (17.0) 11.0 (7.0) 9.3 (7.8) 17.0 (23.6) 14.0 (16.4) 10.2 (6.6) 8.3 (7.5)
2 15.5 (10.2) 13.4 (10.5) 27.2 (27.4) 16.6 (19.3) 12.2 (9.0) 8.8 (9.1) 17.8 (23.) 13.3 (16.4) 10.8 (8.6) 7.3 (8.8)
3 16.4 (13.4) 15.7 (13.0) 30.9 (27.2) 23.1 (20.2) 19.0 (18.4) 17.7 (17.5) 17.3 (24.4) 15.3 (16.8) 15.8 (17.8) 14.4 (17.3)
4 20.0 (16.2) 18.4 (14.2) 38.8 (28.0) 25.9 (19.9) 21.0 (21.0) 17.5 (18.1) 18.5 (23.8) 14.8 (16.1) 17.6 (20.1) 14.3 (17.7)
6 27.7 (22.0) 25.9 (20.5) 45.3 (25.9) 28.4 (18.8) 23.4 (16.8) 19.9 (16.4) 23.2 (23.7) 17.0 (16.1) 20.4 (16.5) 17.0 (16.0)
8 35.5 (23.1) 55.6 (28.2) 28.5 (18.4) 25.8 (27.1) 25.0 (18.2)
Left
0.125 12.3 (8.4) 16.7 (10.1) 9.6 (6.5) 12.8 (12.7) 8.9 (6.2)
0.25 10.0 (7.2) 9.1 (7.3) 15.0 (9.8) 10.3 (8.5) 8.0 (8.9) 6.5 (7.0) 13.5 (13.0) 11.0 (11.3) 7.4 (8.2) 6.0 (6.5)
0.5 12.3 (6.9) 9.8 (5.5) 16.9 (10.8) 11.6 (8.1) 8.8 (8.7) 7.1 (8.1) 14.8 (12.2) 12.5 (13.1) 8.5 (7.9) 6.8 (7.5)
1 12.3 (6.3) 10.7 (5.0) 16.9 (11.2) 11.9 (9.8) 11.0 (7.4) 9.9 (8.0) 17.0 (17.9) 15.2 (16.9) 10.3 (7.3) 8.9 (7.8)
2 15.0 (10.6) 12.7 (10.6) 18.4 (14.7) 15.3 (13.8) 12.2 (9.5) 9.6 (10.3) 17.8 (21.6) 13.8 (17.3) 10.6 (9.2) 7.8 (10.0)
3 18.2 (15.3) 16.8 (13.6) 24.7 (16.0) 22.8 (16.9) 19.2 (16.7) 18.0 (16.3) 19.5 (24.5) 16.0 (17.7) 16.0 (16.4) 14.4 (16.4)
4 23.2 (19.9) 19.6 (17.0) 34.4 (19.5) 25.6 (18.7) 21.7 (17.8) 18.8 (17.6) 20.5 (24.7) 16.0 (17.1) 18.8 (17.5) 16.0 (17.3)
6 25.5 (21.8) 24.3 (20.1) 43.4 (20.6) 32.5 (18.0) 24.9 (16.2) 20.0 (14.5) 24.2 (25.1) 17.8 (18.1) 21.6 (16.5) 17.2 (18.9)
8 36.1 (25.8) 53.1 (26.7) 28.6 (19.3) 28.3 (26.1) 25.2 (19.0)

Italic values indicate a significant difference compared to control

AC air conduction, BC bone conduction, dB HL decibel hearing level
 Clin Rheumatol

Figure 1 shows the 4PTA for AC and BC for all patient and Table 3 Distribution of hearing loss types
control groups and the distribution of normative age- and Frequency (%)
gender-matched hearing thresholds. For RA and GPA, the
disease significantly influenced the 4PTA (F(2, 68) = 5.0, Type of hearing loss Side RA GPA Control SLE Control
p < 0.05). In addition, the disease × AC/BC mode interaction
SNHL Right 36 38 20 24 19
was significant (F(2, 68) = 16.5, p < 0.001). Post hoc tests
Left 27 19 20 27 22
showed significantly poorer thresholds for GPA patients com-
CHL Right 0 19 0 0 0
pared to the control group. For SLE, the effect of the disease
Left 0 13 0 0 0
and all interactions with the disease did not significantly in-
fluence the 4PTA. The mean fine structure of the pure-tone MHL Right 0 0 0 5 0
thresholds was not significantly different between RA Left 0 25 0 5 0
(1.76 dB, SD 0.59 dB), GPA (1.89 dB, SD 0.47 dB), SLE CHL conductive hearing loss, MHL mixed hearing loss, RA rheumatoid
(1.74 dB, SD 0.45 dB), and the control groups (RA, GPA arthritis, SLE systemic lupus erythematosus, SNHL sensorineural hearing
1.85 dB, SD 0.37 dB; SLE 1.71 dB, SD 0.29 dB). loss, GPA granulomatosis with polyangiitis
The distribution of CHL, SNHL, and MHL in all groups is
summarized in Table 3. For RA and GPA, the mean ABG was
significantly influenced by the disease (F(2, 68) = 16.5, Speech perception
p < 0.001), side (F(1, 68) = 5.4, p < 0.05), and the disease ×
side interaction (F(2, 68) = 6.4, p < 0.01). Post hoc tests Figure 2 shows the results of the speech perception testing.
showed larger ABGs for GPA patients (9.1 dB) compared to The disease significantly influenced the SRT for sentences in
RA patients (1.8 dB) and the control (2.4 dB) groups. In GPA noise and the WRS in quiet, but not the SRT for numbers in
patients, the ABGs were larger for the right ear (12.7 dB) than quiet. Post hoc analysis showed significantly reduced WRS
the left ear (5.5 dB). For SLE, the mean ABG was not signif- for GPA patients (81.5%) compared to the control group
icantly influenced by the disease, side, or the disease × side (96.2%). The SRT of the Oldenburg sentence test was signif-
interaction. Table 4 shows the auditory function and their re- icantly worse for the GPA patients (−4.2 dB) compared to the
lation with the remission of the diseases. control group (−5.1 dB). For RA and SLE patients, no

Fig. 1 Average pure-tone hearing RA GPA SLE

thresholds over 0.5, 1, 2, and
4 kHz (4PTA) for male (top) and 0 0 0
female (bottom) patients
(asterisks) compared to controls 20 20 20
(circles). Colors code the right
4PTA (dB HL)

4PTA (dB HL)

4PTA (dB HL)

(red) or left ear (blue). The lines 40 40 40
Male

denote the percentiles of age-

dependent normal values 60 60 60
according to DIN ISO7029
80 RA Right 80 GPA Right 80 SLE Right
RA Left GPA Left SLE Left
Control Right Control Right Control Right
100 100 100
Control Left Control Left Control Left
20 40 60 80 20 40 60 80 20 40 60 80
Age (years) Age (years) Age (years)

0 0 0

20 20 20
4PTA (dB HL)

4PTA (dB HL)

4PTA (dB HL)

40 40 40
Female

60 60 60

80 80 80

100 100 100

20 40 60 80 20 40 60 80 20 40 60 80
Age (years) Age (years) Age (years)
Clin Rheumatol

Table 4 Auditory function and

disease activity Right Left

4PTABC (dB HL) ABG (dB) 4PTABC (dB HL) ABG (dB)

Disease activity Mean SD Mean SD Mean SD Mean SD

Rheumatoid arthritis
In remission 6.5 4.7 0.5 0.7 6.3 5.6 1.5 1.4
Low 13.8 6.8 0.9 1.1 13.0 5.9 2.0 2.0
Middle 16.5 8.9 2.0 0.7 16.8 9.8 3.8 2.7
High 18.8 10.2 1.3 1.3 20.0 11.9 3.3 3.1
Granulomatosis with polyangiitis
In remission 23.8 17.9 18.2 17.3 17.4 12.6 5.3 5.4
Low 12.5 10.4 5.7 8.2 14.5 12.1 5.9 7.6
Control patients 10.9 8.0 2.7 2.2 11.3 8.6 2.0 2.0
Systemic lupus erythematosus
In remission 17.5 18.2 5.2 19.3 20.4 12.5 1.5 3.4
Low 3.1 0.9 3.1 4.7 8.3 0.9 1.0 2.1
Middle 11.6 10.1 2.8 7.0 14.2 2.8 −0.4 1.2
Control patients 9.3 8.0 9.9 8.5 2.7 2.2 2.1 2.1

4PTABC pure-tone average for bone conduction at 0.5, 1, 2, and 4 kHz, ABG air-bone gap, SD standard deviation

significant WRS and SRT differences were found compared to
the control group.
Tympanometry and acoustic reflex
Thirty-nine of the ears in RA patients had a type A
tympanogram (89%), types As and B were each detectable
in 1 ear (2%), and type C in 2 ears (5%). Seventeen of the
ears in GPA patients had a type A tympanogram (52%), types
As and C were documented in 1 ear (3%), and type B in 10
ears (31%). In the control group for RA and GPA, type A
tympanograms were detected in 57 ears (84%), type As in 2
ears (3%), and type B in 9 ears (14%). The distributions were
significantly different between GPA patients and controls for
the right ear only (p < 0.05).
For SLE patients, 33 ears (83%) had a type A tympanogram,
1 ear (2.5%) type AS, 2 ears (5%) type B, and 4 ears (10%) type
C. In the control group for SLE patients, 73 ears (87%) had a
type A tympanogram, 2 ears (2%) type AS, and 9 ears (11%)
type B. The distributions were not significantly different.
In RA patients in whom acoustic reflexes could be mea-
sured, the average number of frequencies was not significantly
different between RA patients (ipsilateral 4.1, SD 3.4; contra-
lateral 3.4, SD 3.3) and controls (ipsilateral 4.9%, SD 2.8;
contralateral 3.9, SD 2.8). In GPA patients, reflexes could be
measured at significantly fewer frequencies (ipsilateral 2.5,
SD 3.2; contralateral 0.6, SD 1.4; p < 0.05). In SLE patients,
the average number of reflexes (ipsilateral 4.4, SD 3.4; con-
tralateral 3.3, SD 3.5) was not significantly different from the
number in the control group (ipsilateral 5.4, SD 2.7; contra-
lateral 4.6, SD 2.9).

Fig. 2 Speech perception for RA, Speech perception in quiet Speech perception in noise
GPA, and SLE patients compared n.s. n.s.
to the respective control (C) 0
groups. The word recognition *
-1
score (WRS) for monosyllables at 100
WRS at 65 dB SPL (%)

a sound pressure level of 65 dB in -2

SRT (dB SNR)

quiet and the 50% speech 80

-3
reception threshold (SRT) for
sentences in noise are depicted. 60 -4
Error bars indicate standard
-5
deviation. *p < 0.05 40
-6

20
-7
*
n.s. n.s.
0
RA GPA C SLE C RA GPA C SLE C

Otoacoustic emissions
DPOAEs could be recorded in almost all patients. Figure 3
shows the DPOAE amplitudes and residual noise for all
groups. The disease did not significantly influence the SNR
values in all measured frequency intervals. However, for the
low- and middle-frequency ranges, the fine structure of the
DPOAE amplitude was significantly influenced by the dis-
ease. The fine structure was significantly more pronounced
in GPA patients (low 3.3 dB, SD 1.7 dB; middle 3.5 dB, SD
1.6 dB) than in the control group (low 1.9 dB, SD 0.9 dB;
middle 2.0 dB, SD 1.2 dB) or RA patients (low 1.7 dB, SD
0.8 dB; middle 1.8 dB, SD 0.9 dB). No difference was ob-
served for the high-frequency range. DPOAE fine structure
amplitudes in the high-frequency range were more pro-
nounced in SLE (2.3 dB, SD 1.1 dB) than in the control group
(1.8 dB, SD 1.1 dB), but not in the low- and middle-frequency
ranges.
Disease-related parameters
Significant correlations were found between several disease-
related parameters and audiological results. For RA patients,
the cumulative steroid dose correlated with the ABG of the
right side (r = 0.51, p < 0.05). For GPA patients, the disease
duration correlated with the ABG of the right side (r = 0.57,
p < 0.05). For SLE patients, the number of organ-specific
manifestations correlated with the ABG of the right side
RA GPA
Amplitude (dB SPL)
20 20
0 0
-20 -20
low high low
middle middle
Control
Amplitude (dB SPL)
20
0 0
-20
low high
middle
Fig. 3 DPOAE amplitudes (filled circles) and residual noise amplitudes
(open circles) for RA, GPA, and SLE patients stratified for low, middle,
and high stimulating frequencies compared to the respective control (C)
groups. Whiskers indicate standard deviation
Clin Rheumatol
(r = 0.52, p < 0.05), and the duration of disease correlated
with the ABG of the right (r = 0.52, p < 0.05) and left ears
(r = 0.56, p < 0.05).
Discussion
Rheumatoid arthritis
In RA patients, neither CHL nor SNHL was observed com-
pared to an age- and gender-matched control group. Because
age is an important factor for the prevalence of SNHL in
general, the prevalence of SNHL must be compared to appro-
priate control groups. Although the percentage of patients
with SNHL was higher among RA patients than the control
group, this difference was not significant. This is in line with
previous observations [4–6], as other investigators observed a
slightly increased prevalence of SNHL in RA patients [8, 9].
However, these results cannot be compared to our data be-
cause either BC measurements or a comparison to a control
group is missing. The increased prevalence of SNHL, CHL,
and MHL reported by Ozcan et al. [11] for both RA and
controls could not be confirmed by our results. We can only
speculate about the reason for this difference. These data were
collected before the introduction of biologic therapy. The re-
sults in Table 4 suggest that disease activity increases hearing
loss. This, however, disease activity was not independent from
age. Thus, as most of our patients had low disease activity or
were in a state of clinical remission, the divergent results could
be explained by differences in disease activity and cumulative
SLE damage between both patient groups.
Amplitude (dB SPL)
20 Effects on the inner and outer hair cells due to vasculitis,
neuritis, or the ototoxicity of medication could not be con-
0
firmed because both the amplitudes and fine structures of
DPOAE and the hearing thresholds were not altered by the
disease. Reduced transitory evoked otoacoustic emission am-
-20
plitudes observed in previous studies [6, 11] could be ex-
plained by the reduced transmission of OAE in CHL patients.
high low high We also found neither CHL nor MHL in RA patients and
middle controls. Acoustic reflexes and tympanograms were not af-
Control fected by the disease. However, the cumulative steroid dose
Amplitude (dB SPL)
20 correlated with the ABG of the right ear. Because the cumu-
lative steroid dose reflects the disease severity, the results sug-
gest that incudostapedial and incudomalleolar joints can be
affected by RA in severe cases [4].
-20
Granulomatosis with polyangiitis
low high Almost all GPA patients had organ-specific manifestations of
middle
the disease. Direct effects on the middle ear by inflammatory
processes may explain the CHL observed in our cohort. CHL
was obvious in almost all measured frequencies and increased
with disease duration, which is in line with previous studies
Clin Rheumatol
[14, 17, 19]. We also found a high prevalence of MHL in the
GPA group. The occurrence of CHL and MHL correlated with
type B tympanogram, and significantly less with measured
acoustic reflexes.
SNHL [20] was observed only with low frequencies, indi-
cating an increasing stiffness of the basilar membrane with
disease duration. This finding is supported by the larger fine
structure of the DPOAE amplitudes observed in this study.
The disease-related hearing loss is relevant for daily life be-
cause speech perception at normal speech level was signifi-
cantly hindered in our GPA patients.
Systemic lupus erythematosus
The prevalence of SNHL was higher in SLE patients than in
the control group. Because the hearing loss was only obvious
at low frequencies, the difference was not significant if the
4PTAs were compared. Combining both ears, the measured
prevalence was within the range observed previously [24, 28,
29]. In addition, the prevalence of MHL, but not solely CHL,
was increased. This finding may be explained by the high
degree of organ-specific manifestations and long disease du-
ration in our group. However, speech perception, DPOAE,
tympanogram type, and acoustic reflexes were not significant-
ly altered in the SLE group. SNHL could be explained by
vasculitis and microinfarctions caused by the deposition of
immune complexes in temporal bone microvessels [21], or
by the loss of spiral ganglion and hair cells and atrophy of
the stria vascularis [22]. Because antiphospholipid antibodies
promote the embolization of microvessels, it would be of in-
terest to investigate whether SLE patients with SNHL have a
higher prevalence of antiphospholipid antibodies or a higher
incidence of antiphospholipid syndrome. Unfortunately, the
sample size of our SLE group was too small to answer this
question. The low-frequency hearing loss in the SLE group is
in accordance with the hypothesis of endolymphatic hydrops
caused by perisaccular deposition of immune complexes [23,
26].
Summarizing discussion
Our GPA and SLE patients had a moderate-to-high risk of
hearing impairment. CHL can be treated by appropriate hear-
ing aids or implantable active hearing devices. In contrast,
SNHL correlated with the loss of sensitive structures in the
cochlea and cannot be replaced equivalently. In our cohort,
RA patients were at low risk of disease-induced hearing loss.
Whether this finding is attributable to progress in the treatment
of RA during the past few years can only be speculated.
However, screening for hearing loss is still important, espe-
cially in RA patients who have poorly controlled disease and
require prolonged treatment with corticosteroids.
Parameters of lipid metabolism were not analyzed in our
study. Hyperlipidemia is correlated with arteriosclerotic
changes, a factor that is of possible influence with respect to
hearing loss. However, hypercholesterolemia has a low risk
for increased sensorineural hearing loss [33].
A limitation of our study is the single-point measurement,
which does not reflect the development of hearing loss over
the course of the disease. Therefore, the time-dependent im-
pact of the treatment could not be analyzed properly. In addi-
tion, the relatively small sample size prevented an analysis of
associations between disease-specific parameters and hearing.
However, to the best of our knowledge, our study is the first to
investigate the hearing system in three distinct rheumatic dis-
orders in parallel, with two age- and sex-matched control
groups. Our data argue for disease-specific differences in the
impairment due to differences in the pathogenesis and thera-
pies for these illnesses.
Acknowledgements We thank Jan-Leif Sommermeyer (Halle/Saale)
for patient recruitment and data recording. We thank Manfred
Mauermann (Oldenburg) for providing the hardware for DPOAE and fine
structure hearing threshold measurements.
Compliance with ethical standards All patients provided written in-
formed consent. The study was approved by the local ethics committee.
Funding This work was supported by intramural funding. No third
party funding was provided.
Disclosures None.
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