Abstract
Objective
To evaluate the risk of immune-mediated rheumatic disease (IMRD) development among adult patients with temporomandibular disorders (TMDs) and to assess the risk factors for developing IMRD among patients with TMDs.
Methods
A retrospective single-center cohort study that included patients between January 1, 2018 and June 30, 2024. Patients ≥ 18 years old with newly diagnosed TMDs according to the TMD diagnostic criteria, who had ≥ 3 follow-up visits at the center for maxillofacial surgery and dental medicine clinics, Galilee medical center, were included.
Results
A total of 1,129 patients presented with TMDs, 130 patients met the inclusion criteria, of whom 114 (88%) were females. The most common temporomandibular joint (TMJ) symptoms were pain and click sounds in 128 (98.5%) and 24 (18.5%) of patients, respectively. Out of 130 patients with TMDs, 3 patients (2.3%) were diagnosed with IMRD (2 with rheumatoid arthritis (RA) (1.5%), and 1 with familial Mediterranean fever (0.8%)). The median follow-up was 39.9 months (IQR 29.1–51.6), and all patients contributed a total of 431.4 person-years at risk. The incidence rate for IMRD in patients with TMDs in our study was 695.4 per 100,000-person year, and for RA in particular was 463.6 per 100,000-person year None of the evaluated risk factors, including gender, TMJ pain, or other joints pain showed a significant association with the subsequent development of IMRD.
Conclusion
In this small retrospective cohort, patients with TMDs have higher incidence of IMRD compared to estimated incidence in the general population, especially RA.
Keywords: temporomandibular joint, immune-mediated rheumatic disease, rheumatoid arthritis
Background
The Temporomandibular joint (TMJ) is a complex synovial joint between condylar head of the mandible to the glenoid fossa of the temporal bone, creating a bilateral craniomandibular articulation.1,2 It plays a crucial role in oral functions such mastication and speech production. Temporomandibular disorders (TMDs), a group of multifactorial musculoskeletal conditions can impact the TMJ, causing symptoms such as pain, clicking or crepitus, swelling and limited jaw mobility. These symptoms may significantly affect an individual’s quality of life, resulting in functional impairment and disability.3,4 According to a recent systematic review, TMDs prevalence is approximately 31% among adults and 11% among children and adolescents.5 Recently, the diagnosis of TMDs has significantly improved with the introduction of updated TMD diagnostic criteria (DC/TMD).6 These criteria encompass the most common TMDs, including painful (local myalgia, myofascial pain, myofascial pain with referral, arthralgia, and headache attributed to TMD) and non-painful TMDs (disc displacement, degenerative joint disease, and joint subluxation), based on symptoms history, physical examination, and imaging studies. The etiology of TMDs is often multifactorial influenced by both physical and psychosocial factors, making it challenging to pinpoint the exact cause of symptoms.7 Additionally, as with other synovial joints, the TMJ may be involved in inflammatory arthritic disorders and, therefore, immune-mediated rheumatic diseases (IMRD), such as rheumatoid arthritis (RA), should be considered in patients with TMD.8
Studies have reported a wide range of TMDs prevalence among patients with IMRDs, varying from 8% to 93%.9 This variation arises from differences in diagnostic criteria, studies design, assessment methods, sample sizes, and disease duration across studies.9 Additionally, no clinical or radiographic findings are pathognomonic for specific rheumatologic diseases in patients with TMDs.8 Moreover, TMJ involvement during the course of IMRD is typically unexpected, and tend to emerge at later stages of the disease.8
TMDs are considered not only a consequence of IMRDs, but also a predicting factor for their development.9 Since early diagnosis of IMRDs is crucial to prevent chronic and irreversible damage, it is very important to aim for early diagnosis of such diseases. Currently, data on the prevalence of TMDs as an initial sign of IMRDs is very limited, and prior studies have not analyzed the incidence of IMRDs in patients presenting with TMDs.
It is worth noting that TMJ examination is not routinely performed when screening and monitoring IMRD patients in rheumatology clinics.8 This highlights the importance of increasing awareness among rheumatologists, dentists, oral medicine specialists, and head and neck maxillofacial surgeons regarding TMJ’s involvement as an early sign of various rheumatic diseases. Early referral can facilitate early diagnosis and treatment, aiming to prevent irreversible damage.
This study aimed to investigate the incidence of IMRDs among TMDs patients with relatively chronic course, as well as to examine predictors and risk factors for developing IMRDs in patients with TMDs.
Methods
This is a single-center retrospective historical cohort study with longitudinal follow-up, that included patients between January 1, 2018 and June 30, 2024. Patients ≥ 18 years old with newly diagnosed TMD according to the DC/TMD diagnostic criteria, who had ≥ 3 follow-up visits (3 months’ time gap between the follow visits) at the center for maxillofacial surgery and dental medicine clinics, Galilee medical center, were included. Patients who had less the 3 follow-up visits were excluded, to avoid the inclusion of acute TMDs that are mostly non-rheumatic.
Exclusion criteria included patients previously diagnosed with any IMRDs before being included in the study: RA, spondyloarthropathies (SPA) including psoriatic arthritis and ankylosing spondylitis, and connective tissue diseases including systemic sclerosis (SSc), systemic lupus erythematosus (SLE), Sjogren’s syndrome, idiopathic inflammatory myopathies (IIM), Behcet’s disease, Familial Mediterranean Fever (FMF), and sarcoidosis.Patients with a history of fibromyalgia before 2018 were also excluded. Patients younger than 18 years old, or patients with a medical history of TMJ/facial surgery, head and neck injury, malignancy, or radiation therapy were excluded from the study.
Ethics Approval Declaration
Research ethical approval was obtained from the Internal institutional review board of at Galilee Medical Center (Galilee Medical Center Ethics Committee), in accordance with the Declaration of Helsinki, approval number 016J-23-NHR.
Informed consent was waived due to the retrospective nature of the study.
Study Outcome
The primary endpoint was incident IMRD during the follow-up period.
Data Collection
Demographic and clinical data were collected from the electronic medical records for all included patients. Demographic data included age, sex, ethnicity, and previous medical history. Clinical data included TMJ signs and symptoms including pain [site, severity – according to visual analogue scale (VAS), quality, radiation, frequency, and duration, deviation of the mandible, dysfunction, swelling, facial asymmetry, tenderness of TMJ area, limitation of mandibular movement, maximum mouth opening, and TMJ sounds (clicking/crepitation).
Laboratory tests results included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-nuclear antibody (ANA), and anti-citrullinated peptide (anti-CCP). These results were collected back up to 2 years before inclusion in the study until the last follow-up visit.
Results of TMJ imaging studies including panoramic TMJ X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) were recorded and included data regarding joint-space narrowing, synovial enhancement, condylar erosions, flattening, and bone sclerosis. Imaging studies were reviewed on the bases of standardized methods.
Laboratory testing and imaging studies, we not performed routinely as part of a standardized protocol. Instead, these investigations were ordered in a symptom-driven manner, at the discretion of the treating maxillofacial surgeon, based on clinical suspicion of inflammatory or systemic disease.
Definition of IMRD
An IMRD diagnosis included RA, SpA, SSc, SLE, IIM, Behcet’s disease, Sjogren’s syndrome, FMF, and sarcoidosis.
Fibromyalgia diagnosis was not considered an IMRD.
Diagnostic Criteria Used for Rheumatic Diseases
Cases of incident rheumatic disease were identified according the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) system codes. Diagnosis confirmation by rheumatologist was mandatory for incident cases.
No predefined criteria or thresholds for rheumatology referral were applied. Referrals were initiated according to the treating physician clinical judgment during routine care.
Statistical Analysis
The chi-square test was used to compare categorical variables and the student-t test or the Mann–Whitney test for continuous variables, as appropriate. Categorical variables will be presented as numbers and frequencies (N and %) and continuous variables as means and standard deviations (M, SD) or medians and interquartile ranges (M, IQR), as appropriate. All demographic, clinical, and laboratory parameters were compared between patients who developed IMRD and those who did not. Patients whose data regarding IMRDs development was missing, was treated as contributing to the risk (until the end of follow-up) but did not develop the outcome. Due to the small number of incident cases, no regression models were performed. Two-sided p-value less that 5% was considered statistically significant. All analysis was performed using SPSS, 27th version.
Results
During the study period, a total of 1129 patients were diagnosed with TMDs, of whom, 130 patients (11.5%) met the inclusion criteria of the study. Figure 1 presents a flowchart of the study population.
Figure 1.
Flowchart of patient selection for the retrospective longitudinal TMD cohort. Adults (≥18 years) diagnosed according to DC/TMD criteria at Galilee Medical Center (2018–2024) with ≥3 follow-up visits were included after applying predefined exclusion criteria.
Abbreviations: GMC, Galilee Medical Center; TMD, Temporomandibular disorders; DC/TMD, Updated temporomandibular disorders diagnostic criteria; IMRD, Immune-mediated rheumatic disease.
The demographics and baseline clinical characteristics of the study population are shown in Table 1. TMJ symptom characteristics, physical examination, and imaging studies’ findings are presented in Table 2. The mean age of the patients in our study was 38.1±14.25 years. The study included 114 females (88.0%), 70 patients (53.8%) were Arabs and 60 (46.2%) were Jews. Only 9 patients (6.9%) had comorbidities, six of them had hypertension. The most common TMJ symptoms were pain and click sounds in 128 (98.5%) and 24 (18.5%) of patients, respectively, and 68 patients (52.3%) had bilateral TMJ complaints.
Table 1.
Demographics and Baseline Clinical Characteristics of Study Population
| Characteristic | Value |
|---|---|
| Total number of patients, n (%) | 130 (100%) |
| Mean age (years ± SD) | 38.1 (±14.25) |
| Female, n (%) | 114 (87.7%) |
| Arabs, n (%) | 70 (53.8%) |
| Jews, n (%) | 60 (46.2%) |
| Medical history, n (%) | 9 (6.9%) |
| Asthma | 1 (0.8%) |
| Cardiovascular disease | 1 (0.8%) |
| Diabetes mellitus | 1 (0.8%) |
| Hypertension | 6 (4.6%) |
| Musculoskeletal pain, n (%) | 9 (6.9%) |
| Hands | 5 (3.9%) |
| Back | 4 (3.1%) |
| Neck | 3 (2.3%) |
| Feet | 2 (1.6%) |
Table 2.
TMJ Symptom Characteristics, Physical Examination and Imaging Study’s Findings
| 1. Patient Symptoms | |||
| TMJ complaint, n (%) | Para functional, n (%) | ||
| Pain | 128 (98.5%) | Normal | 108 (83.1%) |
| Limitation | 24 (18.5%) | Clenching/bruxism | 19 (14.6%) |
| Clicks/sounds | 24 (18.5%) | Biting | 3 (2.3%) |
| Locking | 7 (5.4%) | ||
| Closure change | 1 (0.8%) | ||
| Side, n (%) | VAS, n (%) | ||
| Bilateral | 68 (52.3%) | Mild | 4 (3.1%) |
| Right TMJ | 28 (21.5%) | Moderate | 38 (29.2%) |
| Left TMJ | 29 (22.3%) | Severe | 85 (65.4%) |
| Missing | 5 (3.8%) | Missing | 3 (2.3%) |
| 2. Physical examination | |||
| TMJ sounds, n (%) | Mouth opening limitation, n (%) | ||
| Normal | 69 (53.1%) | Not observed | 30 (23.1%) |
| Clicking | 46 (35.4%) | Observed | 100 (76.9%) |
| Crepitation | 10 (7.7%) | ||
| Clicking and crepitation | 4 (3.1%) | ||
| Missing | 1 (0.8%) | ||
| Face asymmetry, n (%) | TMJ swelling, n (%) | ||
| Normal | 113 (86.9%) | Observed | 1 (0.8%) |
| Right | 11 (8.5%) | Not observed | 129 (99.2%) |
| Left | 4 (3.1%) | ||
| Open bite | 2 (1.5%) | ||
| Masticatory muscle tenderness, n (%) | TMJ palpation tenderness, n (%) | ||
| None | 10 (7.7%) | None | 31 (23.8%) |
| Right | 25 (19.2%) | Right | 31 (23.8%) |
| Left | 20 (15.4%) | Left | 35 (26.9%) |
| Bilateral | 75 (57.7%) | Bilateral | 33 (25.4%) |
| Left loading test, n (%) | Right loading test, n (%) | ||
| Normal | 58 (44.6%) | Normal | 53 (40.8%) |
| Contralateral | 29 (22.3%) | Contralateral | 22 (16.9%) |
| Ipsilateral | 35 (26.9%) | Ipsilateral | 48 (36.9%) |
| Missing | 8 (6.2%) | Missing | 7 (5.4%) |
| Pro/retrusion, n (%) | |||
| Normal | 129 (99.2%) | ||
| Retrusion | 1 (0.8%) | ||
| 3. Imaging studies | |||
| X-ray (panoramic), n (%) | CT scan, n (%) | ||
| Normal | 86 (66.2%) | Normal | 6 (4.6%) |
| Erosions | 15 (11.5%) | Erosions | 10 (7.7%) |
| Subchondral cysts | 0 | Subchondral cysts | 6 (4.6%) |
| Joint space narrowing | 20 (15.4%) | Joint space narrowing | 2 (1.5%) |
| Joint space widening | 2 (1.5%) | Arthritic changes | 10 (7.7%) |
| Joint asymmetry | 11 (8.5%) | Not performed | 110 (84.6%) |
| Missing | 10 (7.7%) | ||
| MRI scan, n (%) | |||
| Not performed | 35 (26.9%) | ||
| Normal | 19 (14.6%) | ||
| Disc displacement | 68 (52.3%) | ||
| Synovial enhancement | 14 (10.8%) | ||
| Erosions | 3 (2.3%) | ||
| Subchondral cysts | 2 (1.5%) | ||
| Arthritic changes | 8 (6.2%) | ||
| Missing | 4 (3.1%) | ||
| 4. Therapy and outcomes | |||
| First line therapy, n (%) | Outcome after therapy, n (%) | ||
| Conservative | 105 (80.8%) | Improved | 104 (80%) |
| Surgery | 2 (1.5%) | No change | 19 (14.6%) |
| Arthroscopic procedure | 23 (17.7%) | Worse | 4 (3.1%) |
| Missing | 3 (2.3%) | ||
Abbreviations: TMJ, Temporomandibular joint; VAS, Visual Analogue Scale; CT, Computed Tomography; MRI, Magnetic Resonance Imaging.
TMJ physical examination findings are shown in Table 2. The most common findings observed on examination were TMJ sounds and TMJ palpation tenderness among 60 (46.2%) and 99 (76.2%) patients, respectively.
Two thirds of patients had normal TMJ panoramic X-ray. Erosions were observed in 11 patients (8.5%) and joint space narrowing in 20 patients (15.4%). TMJ CT scan was performed in 20 patients (15.4%), and erosions were detected in 10 patients (50%). The majority of patients (70%) had TMJ MRI imaging and abnormal findings were demonstrated among most of them; 68 patients (52.3%) had disc displacement on MRI, while synovial enhancement was detected in 14 patients (10.8%).
With regard to therapy, 80% of patients were treated conservatively while 23 had arthroscopic procedures and two patients underwent maxillofacial surgery.
IMRD Development During Follow-Up Period
During the follow-up period, 3 patients (2.3%) were diagnosed with IMRD – two patients with RA (1.5%), and one with FMF (0.8%). A hundred and twenty-seven (97.7%) patients with TMDs did not develop IMRD during the follow-up period (Table 3). Patients were followed from inclusion to the study until the earliest of the following: incident IMRD, death, lost to follow-up, or end of follow-up by June 30, 2024. The median follow-up was 39.9 months (IQR 29.1–51.6), and all 130 patients contributed a total of 431.4 person-years. The incidence rate for IMRD in patients with TMDs in our study was 695.4 per 100,000-person year (95% CI 143.4–2032.3), and for RA in particular was 463.6 per 100,000-person year for RA (95% CI 56.1–1674.7).
Table 3.
Incident Immune-Mediated Rheumatic Disease During Follow-Up Period
| IMRD Developed During Follow-Up, n (%) | |
| Yes | 3 (2.3%) |
| No | 127 (97.7%) |
| IMRD diagnosis | |
| FMF | 1 (0.8%) |
| RA | 2 (1.53%) |
Abbreviations: IMRD, immune-mediated rheumatic disease; FMF, Familial Mediterranean fever; RA, Rheumatoid arthritis.
All three patients were females, and the presenting symptom among all cases was TMJ joint pain (Table 4). One patient had TMJ limitation but none had TMJ clicks/sounds.
Table 4.
Characteristics of Patients Diagnosed with Immune-Mediated Rheumatic Disease
| 1. Demographics and Clinical Characteristics | |||
| Female, n (%) | 3 (100%) | ||
| Jews, n (%) Arabs, n (%) |
2 (66.7%) 1 (33.3%) |
||
| Medical History, n (%) | |||
| Arthralgia | 3 (100%) | ||
| Hand | 2 (66.6%) | ||
| Neck | 2 (66.6%) | ||
| 2. Patient symptoms | |||
| TMJ complaint, n (%) | Para functional, n (%) | ||
| Pain | 3 (100%) | Normal | 3 (100%) |
| Limitation | 1 (33.3%) | ||
| Side, n (%) | VAS, n (%) | ||
| Bilateral | 2 (66.6%) | Severe | 3 (100%) |
| Right TMJ | 3 (100%) | ||
| Left TMJ | 2 (66.6%) | ||
| 3. Physical examination | |||
| TMJ sounds, n (%) | Mouth opening limitation, n (%) | ||
| Normal | 3 (100%) | Not observed | 2 (66.7%) |
| Observed | 1 (33.3%) | ||
| Face asymmetry, n (%) | TMJ swelling, n (%) | ||
| Normal | 2 (66.7%) | Not observed | 3 (100%) |
| Right | 1 (33.3%) | ||
| Masticatory muscle tenderness, n (%) | TMJ palpation tenderness, n (%) | ||
| Right | 1 (33.3%) | Right | 1 (33.3%) |
| Bilateral | 2 (66.7%) | Bilateral | 2 (66.7%) |
| Left loading test, n (%) | Right loading test, n (%) | ||
| Normal | 1 (33.3%) | Normal | 1 (33.3%) |
| Contralateral | 1 (33.3%) | Ipsilateral | 2 (33.3%) |
| Ipsilateral | 1 (33.3%) | ||
| Pro/retrusion, n (%) | |||
| Normal | 3 (100%) | ||
| 4. Imaging studies | |||
| X-ray (panoramic), n (%) | CT scan, n (%) | ||
| Normal | 2 (66.7%) | Normal | 3 (100%) |
| Joint asymmetry | 1 (33.3%) | ||
| MRI scan, n (%) | |||
| Normal | 1 (33.3%) | ||
| Disc displacement | 2 (66.6%) | ||
| 5. Therapy and outcomes | |||
| First line therapy, n (%) | Outcome after therapy, n (%) | ||
| Conservative | 2 (66.6%) | No change | 3 (100%) |
| Arthroscopic procedure | 1 (33.3%) | ||
Abbreviations: TMJ, Temporomandibular joint; VAS, Visual Analogue Scale; CT, Computed Tomography; MRI, Magnetic Resonance Imaging.
All patients had normal CT scan and two patients had disc displacement on MRI.
RF, anti-CCP, CRP, and ESR blood tests were not performed for the majority of patients. Furthermore, none of the patients who developed IMRD had erosions or synovial enhancement on MRI scan.
Two patients were treated conservatively for their TMJ symptoms and one patient had arthroscopy.
Risk Factors for IMRD Development
Our analysis demonstrated that none of the assessed risk factors – including gender, TMJ pain, limitation, clicks, or pain in other joints showed a significant association with the subsequent development of IMRD (Table 5).
Table 5.
Demographic and Clinical Characteristics of Patients with and without IMRD
| Characteristic | With IMRD (n=3) |
Without IMRD (n=127) |
p-value |
|---|---|---|---|
| Gender, n (%) | 1.00 | ||
| Female | 3 (100%) | 111 (87.4%) | |
| Ethnicity, n (%) | 0.60 | ||
| Jews | 2 (66.6%) | 58 (45.2%) | |
| Arab | 1 (33.3%) | 69 (54.3%) | |
| Other Joints Pain, n (%) | 1 (33.3%) | 8 (6.3%) | 0.20 |
| TMJ limitation, n (%) | 1 (33.3%) | 23 (18.1%) | 0.46 |
| TMJ clicks, n (%) | 0 | 24 (18.9%) | 1.00 |
| TMJ locking, n (%) | 0 | 7 (5.5%) | 1.00 |
| VAS, n (%) | 0.60 | ||
| Mild | 0 | 5 (3.9%) | |
| Moderate | 0 | 38 (29.9%) | |
| Severe | 3 (100%) | 82 (64.6%) | |
| Parafunctional, n (%) | 1.00 | ||
| Normal | 3 (100%) | 105 (82.7%) | |
| Clenching/Bruxism | 0 | 19 (15%) | |
| Nail biting | 0 | 3 (2.4%) | |
| Mouth opening limitation, n (%) | 1 (33.3%) | 29 (22.8%) | 0.55 |
| Face asymmetry, n (%) | 1 (33.3%) | 16 (12.6%) | 0.35 |
| TMJ swelling, n (%) | 0 | 1 (0.8%) | 1.00 |
| Mastication muscles tenderness, n (%) | 1.00 | ||
| None | 0 | 10 (7.9%) | |
| Unilateral | 1 (33.3%) | 44 (34.6%) | |
| Bilateral | 2 (66.6%) | 73 (57.5%) |
Abbreviations: IMRD, Immune-mediated rheumatic disease; TMJ, Temporomandibular joint; VAS, Visual Analogue Scale.
Discussion
Our study evaluated the risk of developing an IMRD among patients presenting with TMDs to a tertiary maxillofacial surgery and dental medicine center. Among 130 patients fulfilling the eligibility criteria, three patients (2.3%) were diagnosed with IMRD: two patients with RA (1.5%) and one patient with FMF. All patients who developed IMRD were females and presented with TMJ pain as the initial symptom, and no common pre-existing clinical risk factors were identified. However, it should be emphasized that due to the small number of events, the study was not powered enough to detect any possible associations between possible risk factors and incident IMRD. Therefore, our finding should be interpreted cautiously and considered as hypothesis generating rather than solid evidence.
The observed incidence rates of IMRD (695.4 per 100,000 person-years) and RA in particular (463.6 per 100,000 person-years) were higher than those reported for the general population in recent epidemiological studies (approximately 13–40 per 100,000 person-years),10,11 however, these estimates are based on a very small number of incident cases and therefore do not represent precise risk estimates. Our cohort was derived from a referral-based clinical population with high proportion of female patients, both of which are known to influence the observed incidence of RA. In addition, referral-center bias may have enriched the study population with patients who have more severe and persistent TMJ symptoms, potentially increasing the likelihood of underlying inflammatory disease. Therefore, the increased incidence observed in our study should be interpreted cautiously and considered as hypothesis-generating signal that mandates further validation in larger scale studies.
Most studies in the literature that evaluated the incidence of TMDs among patients with juvenile idiopathic arthritis (JIA) and RA demonstrated that these patients are at higher risk of TMDs, and therefore should be observed for symptoms at the initial stage of TMD to prevent disease aggravation.12–15 Other studies reported high prevalence of signs and symptoms of TMDs among fibromyalgia patients, indicating that fibromyalgia could be a risk factor for the development of TMDs.16,17
Recently, Hysa et al addressed in their systematic review the issue of TMDs within IMRDs in the adult population.9 Most studies (77%) investigated TMDs among RA patients, with signs and symptoms prevalence ranging from 8% to 70%. The prevalence of TMDs in SpA, SSc, SLE, Sjogren’s syndrome and IIM were 12%–80%, 20–93%, 18–85%, 24–54%, and 4–26%, respectively.9
The risk factors for TMDs development in RA included female sex, younger age, ACPA positivity, higher disease activity, cervical spine involvement, and cardiovascular and neuropsychiatric comorbidities. In SSc and SLE, TMDs were more frequent among patients with higher disease activity and duration, correlating with the extent of skin fibrosis in SSc and with renal involvement in SLE.9
However, it remains unclear whether an individual presenting with TMD might be at increased risk for developing IMRD. In order to provide insights into this question, we thoroughly searched the literature including PubMed, MEDLINE, and Google Scholar for studies evaluating the risk for developing IMRD, and RA in particular, in patients presenting with TMDs. To our knowledge, no prior studies have investigated this specific association. Therefore, our findings provide preliminary observation suggesting higher incidence of IMRD, particularly RA, among individuals with chronic TMD in selected tertiary care population.
Our results emphasize the need for rheumatologic evaluation of patients presenting with chronic TMD, due to the relatively increased risk for RA development among these patients.
The recent European Alliance of Associations for Rheumatology (EULAR) guidelines emphasizes the importance of early RA diagnosis and initiation of disease-modifying anti-rheumatic drugs (DMARDs) aiming to achieve early remission and disease control, and optimize long-term patient outcomes through the prevention of joint damage and disability.18 In this context, selective referral for early rheumatologic evaluation may help minimize diagnostic delay in patients with TMDs who exhibit features suggestive of inflammatory arthritis.
Our study has several limitations. First, only adult patients were included; therefore, we were unable to evaluate the incidence and risk factors for JIA, a condition characterized by high prevalence of TMJ involvement. Second, the limited number of incident IMRD cases due to the relatively small cohort restricts statistical power and limits the generalizability of the findings suggesting that our results are most applicable to specialist clinic populations rather than community-based TMD cohorts. Third, patients with fewer than three visits to the maxillofacial surgery and dental medicine clinics were excluded, which may have introduced selection and referral bias. Indeed, this approach represent the practical daycare where mainly patients with more chronic courses are referred for further investigation. Fourth, reliance on ICD codes and internal institutional records may have resulted in under-ascertainment of IMRD diagnosis. Finally, laboratory (RF, anti-CCP, CRP, ESR) and imaging data were incomplete for a substantial proportion of patients as these tests were ordered solely at the discretion of the treating maxillofacial physician, based on clinical suspicion. Importantly, this limitation underscores the clinical relevance of our findings and highlights the need for appropriate referral of selected patients for rheumatologic evaluation when inflammatory arthritis is suspected, aiming for comprehensive laboratory assessment and accurate risk stratification.
In conclusion, our findings suggest an observed increase in the incidence of IMRDs, particularly RA, among patients presenting with TMDs in this single-center cohort. However, given the small number of incident cases, these results should be interpreted with caution and viewed as hypothesis-generating rather than definitive. Rheumatologic evaluation may be considered for selected patients with TMDs, especially those with clinical features suggestive of systemic inflammatory disease. Larger-scale, well-designed prospective studies are needed to further clarify the potential association between TMDs and the risk of IMRD development.
Funding Statement
There is no funding to report.
Abbreviations
TMJ, Temporomandibular joint; TMDs, Temporomandibular disorders; DC/TMD, Temporomandibular disorders diagnostic criteria; IMRD, Immune-mediated rheumatic diseases; RA, Rheumatoid arthritis; SPA, Spondyloarthropathies; SSc, Systemic sclerosis; SLE, Systemic lupus erythematosus; IIM, Inflammatory myopathies; FMF, Familial Mediterranean fever; JIA, Juvenile idiopathic arthritis; VAS, Visual analogue scale; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; RF, Rheumatoid factor; ANA, Anti-nuclear antibody; anti – CCP, Anti citrullinated peptide; CT, Computed tomography; MRI, Magnetic resonance imaging; DMARDs, Disease-modifying anti-rheumatic drugs.
Data Sharing Statement
The data that support the findings of this study are available at Galilee Medical Center, but restrictions apply to the availability of these data, which were used under license for the current study and so are not publicly available. The data are, however, available from the authors upon reasonable request and with the permission of Galilee Medical Center.
Ethics Approval and Consent to Participate
Research ethical approval was obtained from the institutional review board.
Informed consent was waived due to the retrospective nature of the study.
Patient Data Confidentiality Statement
Patient consent for review of medical records was waived by the Galilee Medical Center Ethics Committee due to the retrospective study design. All data were anonymized prior to analysis, and no identifiable information was accessible to the investigators. Data were stored securely with access restricted to authorized research personnel only.
Disclosure
The authors report no conflicts of interest in this work.
References
- 1.Buescher JJ. Temporomandibular joint disorders. Am Family Phys. 2007;76(10):1477–12. [PubMed] [Google Scholar]
- 2.Chang CL, Wang DH, Yang MC, Hsu WE, Hsu ML. Functional disorders of the temporomandibular joints: internal derangement of the temporomandibular joint. Kaohsiung J Med Sci. 2018;34(4):223–230. doi: 10.1016/j.kjms.2018.01.004 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Aliko A, Ciancaglini R, Alushi A, Tafaj A, Ruci D. Temporomandibular joint involvement in rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Int J Oral Maxillofacial Surg. 2011;40(7):704–709. doi: 10.1016/j.ijom.2011.02.026 [DOI] [PubMed] [Google Scholar]
- 4.Kapos FP, Exposto FG, Oyarzo JF, Durham J. Temporomandibular disorders: a review of current concepts in aetiology, diagnosis and management. Oral Surgery. 2020;13(4):321–334. doi: 10.1111/ors.12473 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Valesan LF, Da-Cas CD, Réus JC, et al. Prevalence of temporomandibular joint disorders: a systematic review and meta-analysis. Clinical Oral Investigations. 2021;25(2):441–453. [DOI] [PubMed] [Google Scholar]
- 6.Schiffman E, Ohrbach R, Truelove E, et al. Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications: recommendations of the International RDC/TMD consortium network and orofacial pain special interest group. J Oral Facial Pain Headache. 2014;28(1):6–27. doi: 10.11607/jop.1151 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Li DTS, Leung YY. Temporomandibular disorders: current concepts and controversies in diagnosis and management. Diagnostics. 2021;11(3):459. doi: 10.3390/diagnostics11030459 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Covert L, Mater HV, Hechler BL. Comprehensive management of rheumatic diseases affecting the temporomandibular joint. Diagnostics. 2021;11(3):409. doi: 10.3390/diagnostics11030409 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Hysa E, Lercara A, Cere A, et al. Temporomandibular disorders in immune-mediated rheumatic diseases of the adult: a systematic review. Semin Arthritis Rheumatism. 2023;61:152215. doi: 10.1016/j.semarthrit.2023.152215 [DOI] [PubMed] [Google Scholar]
- 10.Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising? results from olmsted county, minnesota, 1955–2007. Arthritis Rheum. 2010;62(6):1576–1582. doi: 10.1002/art.27425 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hitchon CA, Khan S, Elias B, Lix LM, Peschken CA. Prevalence and incidence of rheumatoid arthritis in canadian first nations and non-first nations people: a population-based study. J Clin Rheumatol. 2020;26(5):169–175. doi: 10.1097/RHU.0000000000001006 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Arvidsson LZ, Smith HJ, Flatø B, Larheim TA. Temporomandibular joint findings in adults with long-standing juvenile idiopathic arthritis: CT and MR imaging assessment. Radiology. 2010;256(1):191–200. doi: 10.1148/radiol.10091810 [DOI] [PubMed] [Google Scholar]
- 13.Bayar N, Kara SA, Keles I, Koç MC, Altinok D, Orkun S. Temporomandibular joint involvement in rheumatoid arthritis: a radiological and clinical study. Cranio. 2002;20(2):105–110. doi: 10.1080/08869634.2002.11746198 [DOI] [PubMed] [Google Scholar]
- 14.Byun SH, Min C, Choi HG, Hong SJ. Increased risk of temporomandibular joint disorder in patients with rheumatoid arthritis: a longitudinal follow-up study. J Clin Med. 2020;9(9):3005. doi: 10.3390/jcm9093005 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Kroese JM, Volgenant CMC, Crielaard W, et al. Temporomandibular disorders in patients with early rheumatoid arthritis and at-risk individuals in the Dutch population: a cross-sectional study. RMD Open. 2021;7(1):e001485. doi: 10.1136/rmdopen-2020-001485 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Fraga BP, Santos EB, Farias Neto JP, Macieira JC, Onofre AS, Bonjardim LR. Signs and symptoms of temporomandibular dysfunction in fibromyalgic patients. J Craniofacial Surgery. 2012;23(2):615–618. doi: 10.1097/SCS.0b013e31824cd81a [DOI] [PubMed] [Google Scholar]
- 17.Velly AM, Look JO, Schiffman E, et al. The effect of fibromyalgia and widespread pain on the clinically significant temporomandibular muscle and joint pain disorders: a prospective 18-month cohort study. J Pain. 2010;11(11):1155–1164. doi: 10.1016/j.jpain.2010.02.009 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Smolen JS, Landewé RBM, Bergstra SA, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheumatic Dis. 2023;82(1):3–18. doi: 10.1136/ard-2022-223356 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available at Galilee Medical Center, but restrictions apply to the availability of these data, which were used under license for the current study and so are not publicly available. The data are, however, available from the authors upon reasonable request and with the permission of Galilee Medical Center.