Hearing Function in Adults with Rheumatoid Arthritis: A Scoping Review for Preventive Audiology Planning

Abstract

Rheumatoid arthritis (RA) is a disease which affects the joints and bones of individuals diagnosed with this condition. Little remains known about the possible impact of this disease on hearing function, particularly the possibilities of preventive audiology in low-and-middle-income countries (LMICs). The study aimed to review published evidence on hearing function in adults with RA. A scoping review of literature from January 2010 to August 2020 was conducted using Sage, ScienceDirect, PubMed, Scopus, Medline, ProQuest and Google Scholar. Studies published in English which reported on the audiological function in adult individuals with RA were included in the review. From 832 initial title records, 18 articles were included into the final scoping review. A qualitative analysis of the reviewed evidence revealed four themes: (1) hearing loss occurs—causality still unclear; (2) nature, degree and configuration of the hearing loss varies; (3) systematic and standardized assessment battery required; and (4) sensitive and specific measures for early detection needed. The occurrence of hearing loss in this population ranges between 21.3 and 66.6%, and this increased where advanced sensitive measures such as ultrahigh frequency and otoacoustic emission (OAEs) measures were included in the test battery. Many audiological tests were used in the studies in order to identify the presence and type of hearing loss in these individuals, with basic audiometry testing being the most commonly used. The most prevalent type of hearing loss was found to be a high frequency sensorineural hearing loss (SNHL), with mixed (MHL) and conductive hearing losses (CHL) being present in some of the individuals. Causal links between RA and hearing loss remains unclear. Although there are limited studies which have reported on the audiological function in the population with RA, the studies which have been reviewed seem to establish an association between RA and the presence of hearing loss. The published high prevalence of hearing loss in this population, when compared to healthy control groups raises implications for well-designed studies that utilize sensitive audiologic diagnostic measures, with clear inclusion and exclusion criteria to ensure more accurate causal links establishment between RA and hearing loss in this population.

Introduction

Rheumatoid arthritis (RA) is defined as a chronic, progressive, inflammatory, autoimmune disorder which most commonly affects the synovial joints as it results in particular (in the joint) and extra-articular (outside of the joint) pain and damage [1]. This disorder is associated with continuous and progressive disability with associated socioeconomic difficulties for the individual and family affected, as well as early onset death [1–3]. The disorder causes hyperplastic synovium, cartilage damage as well as bone erosion of the diarthrodial joints and causes destruction of the articular and periarticular tissues [3, 4]. Patients who have been diagnosed with RA experience an array of symptoms such as stiff joints, tender joints, swollen joints, fatigue, loss of appetite and fever [1]. These patients may also experience other disorders or difficulties which may be as a result of the RA itself.

According to Emamifer and Hansen [2], one of the co-morbid conditions that patients with RA may experience is hearing loss. The hearing loss may be as a result of the RA causing damage to specific parts of the ear and therefore resulting in a loss of hearing; or it may be as a result of the medication/s that the patients are prescribed since these may be ototoxic in nature. For example, Lobo et al. [5] and Nasution and Haryuna [6] report that the middle ear ossicular joints, which include the incudo-malleolar joint as well as the incudo-stapedial joint, are true diarthrodial joints and can therefore be affected by RA. The possible involvement of these middle ear joints can lead to audiological impact of RA in the form of a conductive hearing loss (CHL) [7]. Therefore, early detection and diagnosis of the disease, as well as clear understanding of the possible impact of the prescribed medications on hearing function, has implications for prevention of the erosion of the joints as well as the progression of the disease [3], and consequently prevention of hearing loss in this population.

The debilitating clinical signs of RA can be treated through a variety of medications including biological, conventional, glucocorticoids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDS), as well as Disease Modifying Anti Rheumatic Drugs (DMARDS) [1, 8]. These medications are important to prevent further destruction and deterioration of the patient’s joints, however, they do not cure RA [1].

Published evidence highlights the importance of early diagnosis for RA to prevent the progression and destruction outcomes of the disease, including prevention of extraarticular manifestations [7, 9, 10]. These manifestations cause the involvement of other bodily organs, hence the involvement of the organs of the inner ear, such as the cochlea, and a resulting sensorineural hearing loss (SNHL) [11, 12].

Internationally, there are studies which have indicated evidence of hearing loss in patients with RA, with SNHL being the most common type of hearing loss, followed by CHL [2, 13, 14]. Özcan et al. [14] found that the presence of hearing loss was higher in patients with RA than in the control group, with SNHL in this population being attributed to disorders such as vasculitis, neuritis, ototoxicity or immunological disorders [14–16].

A review of literature indicates paucity of evidence on hearing loss and its causes in adults with RA, hence the motivation for the current study, which forms part of a bigger project on preventive audiology in low-and-middle-income countries (LMICs). Published evidence does not provide specific information with regards to the adverse effects of the medications prescribed to this population; and does not yet appear to have established clear causal links between RA and hearing loss in this population. These factors indicate a need for further research in this area in order to be able to influence quality of life of individuals with RA.

Methods

Aim

This study aimed to review published evidence on hearing function in adults with RA.

Research Design

The design of the study was a scoping literature review. A scoping review provides a synopsis of what current evidence there is on a particular topic, to aid healthcare professionals in applying evidence-based practice in their clinical service provision [17].

Data Sources and Literature Search

The researchers began the study by obtaining medical ethical clearance waiver from the University’s medical ethics committee (Ethical clearance waiver number: M200377). Once the study was approved, the researchers gained access to online journal databases in order to begin the search for journal articles related to the topic. The researchers ensured that all ethical principles, according to Spike [18], were adhered to throughout the study. A comprehensive search was performed for articles which reported on adults with RA and hearing function. The computer-aided search was conducted using online journal databases such as Sage, ScienceDirect, PubMed, Scopus, Medline, ProQuest and Google Scholar. The studies were selected according to a predetermined search strategy with specific inclusion and exclusion criteria in order to ensure their relevance to the scoping review. The researchers made use of the following keywords: adults, audiological function, hearing, rheumatoid arthritis. The search was limited to English published titles which reported on individuals with RA and hearing loss, and titles that had been published from January 2010 to August 2020.

The journal articles which were selected on the online journal databases were then separated into groups according to the database from which they were downloaded. The titles, abstracts and papers were reviewed and further separated into groups according to their relevance to the study. The papers that were relevant to the study were reviewed by an additional reviewer in order to ensure the reliability and validity of the selection process.

Article Inclusion/Exclusion Criteria

The following criteria were used to select the articles for the scoping review:

Inclusion criteria

1. Articles published between January 2010 and August 2020. This inclusion criterion was chosen in order to ensure that all articles were relevant and not outdated.

2. Studies published in peer-reviewed journals.

3. Studies focusing on individuals with RA and their hearing status.

4. Studies written in English.

Data Extraction and Synthesis

As depicted in the PRISMA flow diagram, Fig. 1, a total of 832 titles were retrieved from the online journal databases. Of these articles, 205 were excluded as they were duplicate studies. A further 609 studies were excluded as they were not relevant to the study, and these included studies not published in English, and those focusing on audiological function in other types of arthritis or in other autoimmune diseases. 34 abstracts were screened in order to determine their relevance to the study, and a further 8 studies were excluded. A total of 26 articles were fully reviewed and another 8 were excluded, leading to a total of 18 studies being finally included for analysis in the current review.

Fig. 1.

The PRISMA flow diagram showing the inclusion of studies

Data Analysis

Once the relevant studies were selected data from each study was charted according to the specific information which needed to be extracted, in accordance with the specific aims of the study. The data were compiled and collated in a single spreadsheet and imported into Microsoft Excel 2016 (Microsoft Corporation, Redmond, WA, USA) for descriptive thematic narrative analysis.

Validity and Reliability

To ensure validity and reliability in this scoping review, the researchers consistently made use of the specific keywords, took careful cognizance of the inclusion and exclusion criteria for the study, and utilized the same analysis protocol for all manuscripts [19]. Furthermore, reliability and validity were maintained by ensuring open lines of communication between the researchers, who communicated online regularly during the entire process to ensure that conflicts were resolved, with one researcher (RR) making the final decision when disagreements were found. A high level of agreement was found with the overall kappa of 0.87. Following analysis of the data, one independent reviewer, a PhD fellow and an academic in audiology, reviewed the manuscript with its accompanying supportive data for validation of the insights gleaned from the scoping review.

Results and Discussion

A total of 18 studies formed part of the analysis for this scoping review, with 78% (14) of the studies being from LMICs. Of the fourteen studies from LMICs, only two were from Africa. This demographic profile of studies indicates a gap in either research into hearing function in RA, and/or RA being less prioritized in research as part of ranked burdens of disease in these contexts. In South Africa, for example, quadruple burden of disease consisting of (a) the high maternal and child mortality; (b) the increasing non-communicable diseases (c) the high levels of violence and injuries; and (d) the HIV-TB dual epidemic is what the healthcare system prioritizes. RA would therefore not form a prominent part of the health and research agenda.

A qualitative analysis of the reviewed evidence revealed four themes: (1) hearing loss occurs—causality still unclear; (2) nature, degree and configuration of the hearing loss varies; (3) systematic and standardized assessment battery required; and (4) sensitive and specific measures for early detection needed.

Hearing Loss Occurs—Causality Still Unclear

Of the 18 studies reviewed, 16 indicated occurrence of hearing loss in patients with RA, with 2 studies indicating no significant hearing loss in this group (Fig. 2).

Fig. 2.

Reviewed studies reporting on presence of hearing loss in patients with RA

Ahmadzadeh et al. [15] found the least occurrence of hearing loss with 21.3% of their participants with RA presenting with hearing loss, while Tsirves et al. [12] reported on the highest occurrence of hearing loss in their study with 66.6% of their participants with RA presenting with hearing loss. This high occurrence of documented hearing loss in this population highlights the need for more careful investigations into this sensory function in this population as it has a significant impact on quality of life if intervention is not provided timeously.

It is difficult to ascribe causality of the hearing loss strictly to RA in the studies reviewed as analysis of the case history data reveals a number of confounding variables that could have influenced hearing function in some of the studies. Of the 18 studies reviewed, 13 (72.2%) reported on case history factors that arguably could have been the cause of hearing loss reported rather than RA. These factors were themed as reflected in Table 1, which lists the case history factors in the studies reviewed.

Table 1.

Case history information in the studies reviewed (N = 18)

Case history factor	% Studies that reported on it
Age	17
Family history of early onset hearing loss	39
Noise exposure	56
Ototoxicity	61
History of ear infections	67
History of ear surgery	44
Head and neck growths or abnormalities	22
Signs and symptoms (e.g., otalgia, otorrhea, tinnitus, vertigo)	38
Reports of hearing loss	11
Head trauma	50
Systemic diseases (e.g., diabetes, hypertension, thyroid dysfunction, etc.)	28
RA disease onset and development (disease duration)	68
Neurological symptoms	28

As can be gleaned from Table 1, there is no uniformity in the ear-related case history factors that are documented in this population. The most frequent case history data that was obtained included: history of ear infections, ototoxicity, noise exposure, and the onset and development of RA. Factors such as age, genetic factors, as well as comorbid conditions known to contribute towards hearing loss such as diabetes were least documented in the studies reviewed. Elbeltagy et al. [20], Galarza-Delgado et al. [16] and Jeong et al. [11] considered the age of the participants and its possible influence, presbycusis, on the possible audiological outcomes in this population. These studies considered the possible influence of age of the participants and the influence that presbycusis could have on the audiological function in participants with RA. Pascual-Ramos et al. [7] also reports that participants with RA who were older, presented more frequently with a hearing loss, when compared to younger participants with RA. Therefore, age is a vital factor that needs to be considered when categorizing hearing loss in this population.

Many of the studies which were reviewed, such as the ones by Elbeltagy et al. [20] and Pascual-Ramos et al. [10], stated that hearing loss found in RA patients may be due to the medications which are prescribed in this population. Limited evidence exists to conclude this causal link, therefore an implication for future studies that are longitudinal in nature and allow for monitoring of hearing function following baseline measures prior to prescription of RA medication. Selim et al. [9] also raise the possible impact of additional metabolic diseases on hearing function in individuals with RA, another implication for future studies where interactional effects of possible causes of hearing loss in this population are investigated.

Of the studies reviewed, 38% reported on specific audiological signs and symptoms such as tinnitus, otalgia, otorrhea, as well as vertigo, with only two studies by Galarza-Delgado et al. [16] and Pascual-Ramos et al. [7] reporting on reported subjective hearing loss on case history. The finding of poor correlation between subjective reports of hearing loss versus objective findings, where more cases of hearing loss were identified following audiological assessment than from subjective patient reports, highlights the importance of inclusion of objective assessments over and above just case history taking in the management of RA patients.

When examining the case history information gathered that is directly related to RA as a disease in the participants, only 68% of the studies considered the duration of the RA disease on case history. Duration of the disease ranged from the shortest disease duration with an average of 2 years reported by Alonso et al. [8], to the longest duration with an average of 14.1 years as reported in Rahne et al.’s [21] study. Duration of the disease has implications for disease complication as well as the medications that the patient might have been prescribed, which all have implications for the presenting hearing function status. Such onset and development of the disease enquiry should from part of assessment plans in this population. Of the studies that reported on medications taken, the most frequent medications that were used by the participants in each study included NSAIDs as well as DMARDs such as methotrexate, hydroxychloroquine and sulfasalazine, with evidence of ototoxicity linked to some of them.

Nature, Degree and Configuration of the Hearing Loss Varies

Of the 16 studies that reported on hearing loss in their samples, hearing function findings indicated heterogeneity in the nature (type of hearing loss), degree, as well as configuration of the hearing loss; however, with a clear higher occurrence of bilateral symmetrical high frequency SNHL in this population. All (100%) studies found a SNHL to be the most prevalent type of hearing loss, 6 studies (37.5%) found a CHL to be the second most prevalent type of hearing loss, with MHL being the least occurring type of hearing loss found in this population. The SNHL occurrence rate seemed to increase where sensitive measures such as ultrahigh frequencies [10, 16] and otoacoustic emissions (OAEs) [5, 9, 21] were used in the test battery. The heterogeneity of the hearing loss reported raises questions about the possible causes of hearing loss in this population that requires further enquiry. The high frequency SNHL does seem to increase possibilities of ototoxicity as a leading cause of hearing loss in this population; however, without longitudinal monitoring studies, this causal link is difficult to confirm. Table 2 reflects the reported audiological findings in the studies reviewed.

Table 2.

Reported audiological function in the population with RA (N = 18)

Study	Authors	Audiological Findings
A survey of relationship between rheumatoid arthritis and hearing disorders	Baradaranfar and Doosti [23]	Sensorineural hearing loss (high frequency) Bilateral Normal middle ear function
Audio-vestibular dysfunction in rheumatoid arthritis: an undervalued extra-articular feature	Elbeltagy et al. [20]	65% Sensorineural hearing loss (high frequency) Bilateral Normal middle ear function
Clinical significance of auditive involvement in rheumatoid arthritis: a case–control study	Alonso et al. [8]	58% Sensorineural hearing loss (irregular configuration) Bilateral and some unilateral Normal middle ear function
Cochlear involvement in patients with systemic autoimmune rheumatic diseases: a clinical and laboratory comparative study	Tsirves et al. [12]	67% Sensorineural hearing loss (irregular—U shaped) Bilateral Mild- moderate Normal middle ear function
Cumulative disease activity predicts incidental hearing impairment in patients with rheumatoid arthritis (RA)	Pascual-Ramos et al. [10]	23% Sensorineural hearing loss, some (8%) mixed (irregular) Bilateral Mild- moderate
Does rheumatoid arthritis have an effect on audio vestibular tests?	Ozkiris et al. [24]	Sensorineural hearing loss (high frequency) Bilateral Mild- moderate Normal middle ear function
Early hearing loss detection in rheumatoid arthritis and primary Sjogren syndrome using extended high frequency audiometry	Galarza-Delgado et al. [16]	37% Sensorineural hearing loss (flat—across all frequencies) Bilateral Mild- moderate Normal middle ear function Ultrahigh frequencies worse thresholds (95% of participants had a hearing loss)
Elevated matrix metalloproteinase-3 level may affect the hearing function in patients with rheumatoid arthritis	Nasution and Haryuna [6]	76% Sensorineural hearing loss (high frequencies), 14% conductive hearing loss, and 9.5% mixed 50% Bilateral, 50% unilateral Mild- moderate (1 severe)
Evaluation of audiometric test results to determine hearing impairment in patients with rheumatoid arthritis: analysis of data from korean national health and nutrition examination survey	Jeong et al. [11]	43% Sensorineural hearing loss (mostly high frequency – 21% low/middle frequency) Bilateral Mild- moderate Normal middle ear function
Hearing impairment in a tertiary-care-level population of mexican rheumatoid arthritis patients	Pascual-Ramos et al. [10]	24% Sensorineural hearing loss (high frequency), 2 mixed hearing loss Bilateral Mild- moderate
Hearing impairment in patients with rheumatoid arthritis: association with anti-citrullinated protein antibodies	Lobo et al. [5]	47% hearing loss, 80% Sensorineural hearing loss, 20% conductive and mixed hearing loss Bilateral Mild- moderate Reduced DPOAE amplitudes in RA when compared to control
Hearing status in patients with rheumatoid arthritis	Ahmadzadeh et al. [15]	12% Sensorineural hearing loss, 7% conductive hearing loss, 2% mixed hearing loss (irregular) Bilateral Mild- moderate DPOAEs not different to control group
Increased risk of sudden sensorineural hearing loss in patients with rheumatoid arthritis: a longitudinal follow-up study using national sample cohort	Lee et al. [25]	Sensorineural hearing loss Bilateral Mild- moderate Normal middle ear function
Interstitial Keratitis and sensorineural hearing loss as a manifestation of rheumatoid arthritis: clinical lessons from a rare complication	Lee et al. [26]	Sensorineural hearing loss Bilateral Severe Normal middle ear function Case study
Peripheral and central auditory pathway function with rheumatoid arthritis	Selim et al. [9]	61% hearing loss, 43.5% Sensorineural hearing loss, 17% mixed hearing loss Bilateral, 11% unilateral Mild- moderate TEOAEs amplitudes significantly lower than in control group Abnormal ABR findings when compared to control group
Prevalence of hearing impairment in patients with rheumatoid arthritis, granulomatosis with polyangiitis (GPA, Wegner's granulomatosis), or systemic lupus erythematosus	Rahne et al. [21]	Sensorineural hearing loss (high frequency) Bilateral Mild-moderate Normal middle ear function Reduced DPOAE amplitudes when compared to control group
Relationship between disease activity and hearing impairment in patients with rheumatoid arthritis compared with controls	Yildirim et al. [4]	Sensorineural hearing loss (high frequency) Bilateral Mild- moderate Normal middle ear function
Retrospective cohort study on risk of hearing loss in patients with rheumatoid arthritis using claims data	Huang et al. [22]	hearing loss Age and comorbidities (hypertension and ischemic heart disease) influencing hearing loss

Systematic and Standardized Assessment Battery Required

All studies reviewed utilized some form of audiological measures to assess hearing function of the participants. Audiological measures used included an array of tests from the basic audiological test battery, such as otoscopy, immittance measures (tympanometry and acoustic reflexes), pure tone audiometry (air conduction and bone conduction), speech audiometry (speech reception thresholds and speech discrimination); as well as more specialized testing such as distortion product otoacoustic emissions (DPOAEs), transient evoked OAEs (TEOAEs) and auditory brainstem response (ABR) measures. Some test batteries included vestibular testing in the form of Vestibular-Evoked Myogenic Potentials (VEMPS), Videonystagmography (VNG), saccade testing, caloric testing, and positional testing. All studies reviewed performed the basic audiological test battery measures, and only 33.3% (6/18) performed additional specialized testing. This lack of consistency in the measures used is one of the significant gaps identified in the review as it negatively influences abilities to compare findings across different studies. Current evidence also indicates that exclusion of sensitive measures in the test battery, such as ultrahigh frequency measures and OAEs may have under-diagnosed a number of patients with RA presenting with hearing loss; and may have also prevented clinicians from implementing preventive measures where early identified changes to hearing function could have been thwarted from getting worse.

Sensitive and Specific Measures for Early Detection Needed

Nuanced analysis of findings from studies such as that by Pascual-Ramos et al. [10] where ultrahigh frequency audiometry formed part of the test battery, and those by Selim et al. [9], Lobo et al. [5] and Rahne et al. [21] where OAEs were performed; revealed more hearing loss, particularly in the high frequencies; with OAEs indicating cochlea hearing loss (reduced OAE amplitudes) regardless of normal pure tone audiometry findings [5, 9, 21], particularly in high frequencies. This was the finding with all studies reviewed, with the exception of Ahmadzadeh et al.’s [15] findings which indicated no significant difference in OAE findings in participants with RA when compared to the control group. Only 1 study, by Selim et al. [9], conducted ABR testing. In that study, the results found the absolute as well as the inter-wave latencies to be delayed in participants with RA. The lack of other studies that utilized ABR is a gap that exposes our inability to conclude about the neurological integrity of the auditory pathway in patients with RA.

Inclusion of specialized tests is important as these tests are more objective, and they can test more specific anatomical structures along the auditory pathway. OAEs, for example, should be included as they test the functioning of the outer hair cells of the cochlea, and this test is therefore able to provide information with regards to outer hair cell damage which may be as a result of different audiological pathologies, such as ototoxicity [27]. As stated by Elbeltagy et al. [20], it is a possibility that the medication that individuals with RA are prescribed, may cause damage to the ear and lead to an ototoxic hearing loss. Therefore, OAEs would provide vital information with regards to the outer hair cell functioning of the cochlea of these participants and allow for establishment of a possible direct association between the hearing loss and its cause. Similarly, inclusion of ABR testing in the test battery allows for a more accurate representation of the specific site of lesion, as seen in the findings from the one study by Selim et al. [9], which included ABR testing. Comprehensive test battery adoption not only allows for complete results assessing the entire auditory pathway to be obtained, but it also ensures cross-check principle application for validity and reliability of findings to be evaluated. For example, it was noted that in some of the studies which found middle ear involvement in adults with RA on tympanometry, the results did not correlate with the type of hearing loss found in the participants. In the studies performed by Galarza-Delgado et al. [16] and Rahne et al. [21], type As and type Ad tympanograms were recorded in some of the participants with RA, but no CHL or MHL case were found; an unexpected outcome with these tympanometry findings. This, therefore, raises questions about the reliability and validity of findings from these studies, as poor correlation of findings from various audiological measures was present. These findings are unlike those by Lobo et al. [5] and Pascual-Ramos et al. [7], where middle ear involvement was indicated through both tympanometry results and pure tone audiometry findings indicating the presence of CHL and MHL.

From the studies that performed OAE testing, 3 studies found reduced amplitudes in the participants with RA. These results are indicative of some outer hair cell damage in these participants, and this may be directly related to the complications of the disease, or the medications prescribed for the RA [5]. These findings also correlated well with the SNHL which was found in most of the participants with RA in these studies. The results indicate the need for future studies in this area, with inclusion of OAE testing in order to determine the integrity of the outer hair cells of the cochlea, with inclusion of ABR testing to distinguish cochlear versus retrocochlear involvement in this population.

The one study that performed ABR testing, found results which indicated delayed absolute as well as inter-wave latencies in this population. In the study by Selim et al. [9], it was found that some of the participants had absent acoustic reflexes and delayed wave latencies which could be indicative of a retrocochlear pathology, whereas other participants had present acoustic reflexes and delayed wave latencies which may be indicative of a cochlear pathology and a sensory rather than neural hearing loss [9]. ABR testing is an objective test and therefore, the responses may provide a more reliable indication with regards to an individual’s hearing and audiological function. As reliable as ABR is, access to the measure is challenging, particularly in LMICs, as the equipment is expensive, and the testing procedure is time-consuming and may require sedation.

This scoping review has raised a need for future research to focus on more specialized testing such as OAE testing as well as ABR testing for more sensitive and specific information to be gathered with regards to the audiological functioning in this population, with evidence on the specific site of lesion gathered.

Comparing the Above Findings to Evidence on Adults Without RA

Of the 18 studies reviewed, 13 (72.2%) included a control group of participants without RA. These studies allowed for the audiological findings of individuals with RA to be compared to a healthy group of individuals. Table 3 indicates the overall findings between the control and study groups in each study reviewed.

Table 3.

Comparison of the audiological function in the participants with RA and a group of healthy individuals

Study	Authors	Number of participants with RA	Number of control participants	Overall findings
A survey of relationship between rheumatoid arthritis and hearing disorders	Baradaranfar and Doosti [23]	50	50	The hearing thresholds of the participants with RA were found to be significantly affected in comparison to the control group
Audio-vestibular dysfunction in rheumatoid arthritis: an undervalued extra-articular feature	Elbeltagy et al. [20]	20	20	The participants with RA presented with reduced hearing thresholds when compared to the control group. The reduced hearing thresholds were found to be more specially in the high frequencies. The most prevalent hearing loss was found to be a SNHL. Peripheral involvement of the vestibular system was indicated in the participants with RA in comparison to the control group
Clinical significance of auditive involvement in rheumatoid arthritis: a case–control study	Alonso et al. [8]	45	45	The percentage of RA participants who had a hearing loss was found to be much greater than the healthy control group. Tympanometry results were also affected in many of the RA participants when compared to the control group. This is indicative that the participants with RA are at a higher risk of developing a hearing loss
Cochlear involvement in patients with systemic autoimmune rheumatic diseases: a clinical and laboratory comparative study	Tsirves et al. [12]	60	60	The participants with RA were noted to be at a much higher risk of a SNHL in comparison to their respective control group. The cochlea was found to be mostly affected in these participants
Does rheumatoid arthritis have an effect on audiovestibular tests?	Ozkiris et al. [24]	81	81	Hearing impairment was found more frequently in the participants with RA than in the control group. The hearing loss was noted in the higher frequencies. Vestibular difficulties were only found in 6 participants I the control group but were found in 29 participants with RA. These results indicate audiological and audio-vestibular involvement in patients with RA compared to the healthy individuals
Early hearing loss detection in rheumatoid arthritis and primary Sjogren syndrome using extended high frequency audiometry	Galarza-Delgado et al. [16]	117	251	Sensorineural hearing loss was found to be more prevalent in the participants with RA than in the healthy control group. The results also revealed middle ear involvement in the participants with RA in comparison to the control group
Hearing impairment in patients with rheumatoid arthritis: association with anti-citrullinated protein antibodies	Lobo et al. [5]	43	23	When comparing the audiological findings of the study group to the control group, the participants with RA were noted to have poorer thresholds in air conduction at 6000 Hz in the right ear. DPOAE amplitudes were decreased at 2000 Hz in the participants with RA when compared to the control group, which is indicative of the involvement of the cochlea
Hearing status in patients with rheumatoid arthritis	Ahmadzadeh et al. [15]	42	40	Higher bone conduction thresholds were found in some of the frequencies in the participants with RA however, there were no significant differences found in the presence of SNHL and CHL when comparing the study group and the control group. The findings of the study revealed that there were higher thresholds in the participants with RA however, there was no significant difference when comparing the control group. DPOAEs results were also insignificant when compared to the control group
Increased risk of sudden sensorineural hearing loss in patients with rheumatoid arthritis: a longitudinal follow-up study using national sample cohort	Lee et al. [25]	7 619	30,476	The findings of the study indicate individuals with RA to be at a much greater risk of developing a SSNHL when compared to the control group. The associations between RA and SSNHL was found in participants > 50 years old
Peripheral and central auditory pathway function with rheumatoid arthritis	Selim et al. [9]	46	40	Hearing loss was found in 60.87% of the study group compared to only 20% of the participants in the control group. This study indicates the participants with RA to be at more of a risk of developing a hearing loss in comparison to the healthy control group
Prevalence of hearing impairment in patients with rheumatoid arthritis, granulomatosis with polyangiitis (GPA, Wegner's granulomatosis), or systemic lupus erythematosus	Rahne et al. [21]	22	34	SNHL was the most frequent hearing loss recorded in the participants with RA, however the findings of a SNHL were insignificant when compared to the control group. The findings from the tympanometry results, speech perception and discrimination, DPOAEs as well as acoustic reflexes indicated no significant difference between the participants with RA and the control group
Relationship between disease activity and hearing impairment in patients with rheumatoid arthritis compared with controls	Yildirim et al. [4]	88	50	In the participants with both active RA as well as RA in remission, the pure tone audiometry indicated a significant difference in thresholds when compared to the control group. The increased thresholds that were found at 2000 Hz and 4000 Hz were indicative of a SNHL
Retrospective cohort study on risk of hearing loss in patients with rheumatoid arthritis using claims data	Huang et al. [22]	18,267	73, 068	Participants in the RA cohort were found to be at a much higher risk of developing a hearing loss when compared to the non-RA cohort. There was an increased incidence of hearing loss in the older aged individuals as well as in the RA participants who had comorbidities such as hypertension and ischemic heart disease (IHD). The RA cohort were found to have double the incidence of hearing loss than the non-RA cohort

Of the 13 studies which included a control group as part of their study design, 11 studies (84.6%) found a significant difference in the audiological function of the participants with RA when compared to the healthy control group. These studies that included control groups provide stronger support for RA having some influence in hearing function. The degree and nature of the hearing loss, as well as clear causal links remain gaps requiring further investigating.

When comparing the audiological function of participants with RA to healthy individuals, patients with RA present with hearing loss, which was noted to be more frequently a SNHL. A majority (68.75%) of the studies which reported hearing loss in this population included control groups. This is advantageous as it made it easier for the studies to compare the audiological findings with a healthy group of age and sex matched individuals, which allowed for determination of the difference between the groups and whether audiological function is compromised in the population with RA. Of all 13 studies that included a control group, all used age and sex matched, healthy control subjects. This is vital as certain human characteristics can be altered according to an individual’s age as well as their sex. Therefore, the reliability and validity of the study outcomes would be compromised if age and sex matched control subjects were not recruited. 11 studies (84.6%), such as the ones performed by Özkiris et al. [17], Selim et al. [9], and Galarza-Delgado et al. [16], found a significant difference in the audiological function of the participants with RA in comparison to the control group findings. These findings are indicative of a higher risk of the development of hearing loss in the participants with RA. However, these findings conflict with the ones from the studies performed by Rahne et al. [21] and Ahmadzadeh et al. [15], where no significant difference in the audiological function between the two groups could be found, and therefore no risk of a hearing loss in the population with RA established.

Conclusion

Evidence reviewed reveals significant gaps in the knowledge base around RA and hearing function. Occurrence of hearing loss in this population seems to be confirmed by studies reviewed, with bilateral high frequency SNHL being the most prevalent; however, the methodologies adopted in the majority of the studies, which exclude objective sensitive audiological measures, limit conclusions that can be drawn. This uncertainty includes the lack of definitive causality links of the hearing loss to either RA as a primary cause, RA consequences as a secondary cause, or RA treatments as a tertiary cause in the form of ototoxicity. Implications for future studies that include sensitive assessment measures and longitudinal designs for audiological monitoring, if ototoxicity is a cause worth investigating, are raised. Clinically, current evidence highlights the importance of including audiological assessment in the management of patients with RA, with referral for baseline measures prior to treatments—at the minimum; with monitoring forming part of the management plan. Such an approach will facilitate early detection and intervention of hearing loss, thus contributing towards preventive healthcare; an approach to health that is cost-effective within resource-constrained contexts such as LMICs [28].

Abbreviations

RA

Rheumatoid arthritis

SNHL

Sensorineural hearing loss

MHL

Mixed hearing loss

CHL

Conductive hearing loss

NSAIDS

Non-steroidal anti-inflammatory drugs

DMARDS

Disease modifying anti rheumatic drugs

LMIC

Low- and middle-income country

ABR

Auditory brainstem response

OAEs

Otoacoustic emissions

DPOAEs

Distortion product OAEs

TEOAEs

Transient evoked OAEs

VEMPS

Vestibular-evoked myogenic potentials

VNG

Videonystagmography

DPOAEs

Distortion product otoacoustic emissions

TEOAEs

Transient evoked otoacoustic emissions

Authors' contributions

Conceptualization, RR and KKS; Methodology, RR and KKS; data collection, RR; Formal Analysis, RR and KKS; Investigation, RR and KKS; Writing—Original Draft Preparation, RR and KKS; Writing—Review & Editing, KKS; Supervision, KKS. Revisions, KKS. All authors read and approved the final manuscript.

Funding

The authors thank the National Institute for the Humanities and Social Sciences (NIHSS) for providing financial assistance for the publication of this manuscript.

Declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional ethics committee (University of the Witwatersrand’s Medical Human Research Ethics Committee: Ethical clearance waiver number: M200377).