This cross-sectional, analytical, prospective study was carried out in Otorhinolaryngology-Head and Neck Surgery and Rheumatology Department of Adam Malik General Hospital, Sumatera Utara, Indonesia from January to June 2015. Based on consecutive sampling method, the number of subjects studied was as many as 38 subjects in the period of six months, consisting of 19 subjects as RA group and 19 subjects as non-RA group for comparison. Patients who met the ARA criteria [12] were included in the RA group. While other joints disease patients who did not meet ARA criteria were included in the non-RA group. This study has gained ethical clearance from the Health Research Ethical Committee of Sumatera Utara University and informed consent from all subjects.

Inclusion criteria: patient’s aged 16-50 years with no history of earache, congenital hearing loss, ear infections, ear trauma, acoustic trauma, etc., affecting the auditory function were included.

Exclusion criteria: patient’s diagnosed with systemic disease such as diabetes mellitus, hypertension, hyperlipidemia, etc., were excluded.

RA diagnosis was conducted by rheumatologist according to criteria of ARA. RA diagnosis can be confirmed if these four criteria were occurred and lasted for six weeks; stiffness of joints in the morning, arthritis of ≥3 joints, hand joints arthritis, symmetric arthritis, rheumatoid factor of serum, rheumatoid nodules, or radiographic changes. The subjects were recorded based on gender, age, disease duration and presence of rheumatoid nodule and then underwent laboratory evaluation of ESR and platelet count. In addition, clinical examination of ears, nose, throat, head, and neck was performed by otorhinolaryngologist. Through this examination, it was found that all 38 subjects had normal tympanic membranes.

With respect to all study subjects, examination of pure tone audiometry and tympanometry were conducted by the same examiner in a soundproof chamber. The pure tone audiometry examination was conducted by using AD-28 Interacoustic Clinical Audiometer (Interacoustic, Assens, Denmark). The measurement was performed based on the ascending method (Hughson-Westlake, up 5, down 10 method) [13]. The air conduction thresholds were measured for 250-8000 Hz. The bone conduction thresholds were measured for 250-4000 Hz. Masked Pure Tone Audiometry was done if there was a difference of ≥40 dB between the air conduction threshold of the test ear and the bone conduction threshold of the opposite ear or when the air-bone gap of the poor ear which was under the test was ≥10 dB [14]. Hearing threshold was computed as the average of 0.5-4 kHz in dBHL. Audiograms are classified according to WHO criteria; normal hearing (≤25 dBHL), mild (26-40 dBHL), moderate (41-60 dBHL), severe (61-80 dBHL), and profound (≥81 dBHL) hearing loss [15]. Hearing loss was classified by SNHL if the air conduction and bone conduction >25 dBHL, CHL if obtained air-bone gap ≥10 dBHL at least two consecutive frequencies, or MHL if the air conduction and bone conduction >25 dBHL with air-bone gap ≥10 dBHL at least two consecutive frequencies [16]. The subject was deemed to have a hearing loss if one or both of his ears have a hearing loss. To assess the difference in the mean of air conduction, bone conduction, the value of air-bone gap, and the threshold was taken the highest threshold value between the two ears.

Tympanometry examination was conducted by interacoustics AA222 impedance audiometer (Interacoustic, Assens, Denmark). Tympanometry was conducted in auto tympo mode. The patient must swallow 8-10 times so the over or under pressure that the tympanic membrane caused in the middle ear is equalized. Different types of tympanogram were obtained by computing the compliance of tympano-ossicular system against various pressure changes [17]. Tympanogram was categorised based on A, As, Ad, B, or C type according to Jerger J [18].

ESR, platelet count, rheumatoid nodule presence, the types and the degrees of hearing impairment, as well as the types of tympanogram were presented in description. The correlation of diseases duration, ESR, and platelet count and hearing threshold were analysed using Pearson’s Chi-square test. The difference in the mean of air and bone conduction thesholds, air-bone gap values, as well as hearing thresholds were analysed using independent samples t-test. The correlation between RA and hearing impairment was analysed using Pearson’s Chi-square test. Statistical test performed using SPSS (SPSS Inc., Chicago, IL, USA) version 17.0. A p-value <0.05 considered statistically significant.

In this study, the mean age of RA group was 32.84±1.96 years old and non-RA group was 39.26±1.89 years old. Age and gender distribution in both groups were not significant (p>0.05). RA patients were undergoing treatment with anti inflammatory drugs. Steroids used were methylprednisolone or prednisone, while the non steroid drugs used were diclofenac sodium or paracetamol. In addition, patients also took Disease Modifying Antirheumatic Drugs (DMARDs) like chloroquine ormethotrexate. Non-RA patients were under ongoing treatment with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like diclofenac sodium, meloxicam, ibuprofen or acetaminophen. Patients in both groups consumed them in single dosage or combination. Sodium diclofenac was the major drug used in both groups. [Table/Fig-1] shows the subjects clinical characteristics.

The most common type of hearing loss was SNHL which was 10 RA patients (52.6%), of which 7 were bilateral and 3 were unilateral. CHL was found in 3 patients (15.8%), of which 1 was bilateral and 2 were unilateral. MHL was only found in 2 patients (10.5%), both of which are bilateral. In addition, normal hearing was foundin 4 patients (21.05%) [Table/Fig-2].

[Table/Fig-2]:

Proportion of hearing impairment types in both groups.

The data are expressed as percentage (%).

RA-Rheumatoid Arthritis; non RA-without Rheumatoid Arthritis; SNHL- Sensorineural Hearing Loss; CHL- Conductive Hearing Loss; MHL- Mixed Hearing Loss

Mild SNHL was the most common finding in RA as many as 8 patients (38.1%), which of 5 were bilateral and 3 remaining unilateral. It was followed by moderate and severe degree [Table/Fig-3].

[Table/Fig-3]:

Proportion of hearing impairment degrees in RA group.

The data are expressed as percentage (%)

SNHL- Sensorineural Hearing Loss; CHL- Conductive Hearing Loss; MHL- Mixed Hearing Loss

The most common type of tympanogram was type A in RA group, i.e., 12 patients (63.16%), and non-RA group were 16 patients (84.21%). As type tympanogram was found in 6 patients (31.57%) of RA group, of which 4 were bilateral and 2 were unilateral. While in the non-RA group, As type tympanogram was found in 2 patients (10.53%), where both bilateral. Unilateral Ad type tympanogram was found in 1 patient (5.26%) in RA group [Table/Fig-4].

[Table/Fig-4]:

Proportion based on tympanogram types of both groups. The data are expressed as %. RA, rheumatoid arthritis; non-RA, without rheumatoid arthritis.

A significant correlation (p<0.05) of disease duration and ESR with hearing loss degree in RA group was obtained using Pearson’s Chi-square test [Table/Fig-5].

Mean of air and bone conduction thresholds as well as air-bone gap values in RA group was higher than those in non-RA group in all frequencies. A significant difference (p<0.05) was obtained in air-bone gap values at 500 Hz to 4000 Hz [Table/Fig-6].

For the purpose of investigating the correlation of RA and hearing impairment, statistical analysis was done. A p-value <0.05 was obtained by using Pearson’s Chi-square test.

This showed a significant correlation of RA and hearing impairment [Table/Fig-7].

In this study, a significant correlation was obtained between disease duration increased and hearing threshold increased in RA group. This showed that the longer patients with RA have the disease, their hearing threshold is increased. Öztürk A et al., found that the longer disease duration, the higher stage of the disease [19]. Longer disease duration caused longer disease effect and ototoxic effect on the auditory system [5].

In this study, a significant correlation was found between increased ESR and increased hearing threshold in RA group. Dikici O et al., have reported that increase in ESR was correlated with disease duration, and that platelet count is correlated with hearing threshold [5]. Takatsu M et al., also found that increased ESR was significantly correlated with SNHL in RA patients [10]. Elevation in ESR and rheumatoid nodules often found in subjects of this study showed disease activity [5,8]. Hearing impairment was correlated with disease activity [5,10]. When the ESR increases, the more joints were involved [20]. The increased ESR was lead to vasculitis which is an extra-articular manifestation of RA [21]. However, contrast result found in platelet count. Normal platelet count, as substantially found in this study, was because of therapy performed. NSAIDs, DMARDs, and steroids consumed by the subjects of this study can reduce platelet count [22].

In this study, mild degree SNHL was most prevalent in the RA group. Based on the literature, SNHL is reported to be up to 72% [4]. The pathophysiology of hearing loss in RA patients is not fully known. Although retrocochlear involvement has been reported, most literature reports that cochlear pathology is the cause. The structure of the inner ear is disturbed by vasculitis, neuritis, and the ototoxic drugs used in treatment [5,8]. In a study conducted by Baradaranfar MH and Doosti A [7], there was a significant difference of hearing threshold at the frequency of 8000 Hz among the RA patients with the comparison group. They claim that cochlear damage is the cause.

In this study, it was found that air conduction thresholds mean and bone conduction thresholds mean in RA group were higher at all frequencies. SNHL in RA is found to be heavier at lower frequencies [23,24] although some other researchers reported that the SNHL is found at high frequencies [7,19,25]. SNHL at lower frequencies is thought to be a manifestation of earlier hearing loss [24] which is not caused by outer hair cell dysfunction [25]. While SNHL at high frequencies can be caused by the influence of autoimmunity [26] as well as toxic effects of analgesic drugs consumed on the inner ear marked by partial loss of perception of high tone [27].

This study proves that hearing loss is often found in RA patients. In this study, significant correlation was found between RA with hearing loss based on statistical analysis. In this study, the study subjects in the RA group were undergoing treatment with NSAIDs, steroids, and/or DMARDs including methotrexate and hydroxychloroquine. Similarly, subjects in the non-RA group consisting of patients with other joints diseases are also undergoing treatment with NSAIDs or steroids. This suggests that the SNHL in the RA group as probably the vasculitis process due to the ototoxic drugs used in treatment. Although the ototoxic effects of immunosuppressive drugs and the anti inflammatory drugs used in RA treatment are rare, some cases have been published with respect to side effects of methotrexate, hydroxychloroquine, and salicylate [9,28]. In a prospective study, there was also reported a correlation between the use of non-steroidal anti-inflammatory drugs such as methotrexate, hydroxychloroquine, salicylate, and D-penicillamine with SNHL [5,8]. In addition, Choy E suggested that when rheumatoid ossicular joint fixation occurs, the inner ear protective mechanism is inhibited by intrinsic and extrinsic traumas [2]. A number of possible pathologies of SNHL have been described by previous studies mainly as auditory neuropathy and destruction of the cochlear hair cells or the inner ear due to immune complex deposition, and drug-induced ototoxicity [4].

In this study, CHL was the most common type of hearing loss after SNHL. The prevalence of CHL in RA patients was reported to be lower than that of SNHL, only up to 24.3% [9]. Damage to joints and ligaments of auditory ossicles has been reported as the cause. Incudomalleolar and incudostapedial joints are true diarthroses that have a risk of RA [4-6,23]. The As type tympanogram found in this study shows an increase in stiffness of ossicular joints. Inflammation in active disease and fibrosis in ossicular chain can reduce static compliance and cause conduction disturbance [5]. While Ad type tympanogram also found in this study can occur due to vasculitis which resulted in inadequate perfusion of the ossicles, especially in long process of incus. Necrosis in this structure can cause discontinuity [5,10]. RA can harm incudomalleolar and incudosetapedial joints so that it can change ossicular mechanics in responding the modification of static air pressure [5]. However, when these joints functionally fixed during sound transmission, this condition can occur with no clinical symptoms [4].

In this study, MHL was also found but with a lower porportion than other hearing loss. Previous studies have suggested that MHL was 10.8% [7]. The interactions of T cells, B cells, and proinflammatory cytokines are pathogenic in RA. Pannus as part of synovial membrane is rich in osteoclast degrading bones [2]. The A type tympanogram found in this study shows that damage to the middle ear is a relatively less common finding than damage to the inner ear. However, since significant differences in the mean air-bone gap at frequencies of 500 Hz to 4000 Hz, we believe that damage to the ossicular joints can progress more slowly than damage to the inner ear. This will lead to MHL.

This study did not prove the exact cause of hearing loss in RA. Therefore, further studies should be conducted to investigate the role of various pathologies that occur in RA concerning the hearing loss and the effect of the drugs used in the treatment.

Rheumatoid arthritis can cause hearing loss. We suggest that the cause of hearing loss in this study is due to various processes that occur in the disease such as synovial destruction of incudomalleolar and incudostapedial joints, rheumatoid nodule, auditory neuropathy, destruction of the cochlear hair cells and drug-induced ototoxicity. We recommend regular evaluation of hearing impairment through clinical examination, pure tone audiometry, and tympanometry on patients that consumed ototoxic drugs. Patient’s quality of life can be increased by early detection of hearing impairment and appropriate rehabilitation plan.