Discussion
Our data suggest that compared to historical controls, TMJ arthritis is underdiagnosed in CARRA registry patients most likely because there is inadequate assessment of the TMJ via physical examination or imaging. Early diagnosis of TMJ arthritis is important because active arthritis warrants escalation of pharmacologic treatment to limit long-term damage to the joint. It is also important that TMJ involvement (damage and sequalae due to previous TMJ arthritis) is identified, so it can be treated with orthopedic devices or surgery [
8].
The true prevalence of active TMJ arthritis and TMJ involvement is likely underdiagnosed in the clinical environment because of the challenges of assessing the TMJ on exam and the need for advanced imaging to fully evaluate for disease activity [
17]. The MMO is the only clinical examination finding shown to correlate with active TMJ arthritis in several studies [
6,
11]. Patients with JIA should have TID trended over time so that TMJ arthritis can be identified at an early stage. While clinical exam can help identify TMJ arthritis, it likely underestimates the burden of disease. Imaging with MRI is also warranted in patients with JIA [
6,
8]. The combination of imaging and repeat clinical exam is the best clinical practice, as the trend of total incisal distances can suggest a change that may indicate the need to obtain or repeat imaging [
8].
In our analysis, TMJ arthritis was diagnosed in 12.6% of the cohort, which suggests underdiagnosis of TMJ arthritis based on the range of 30–45% prevalence suggested by prior studies [
6,
19]. We suspect that this underdiagnosis is due, at least in part, to limited assessment of the joint in routine clinical practice. Only 67% of patients with JIA had documentation of any form of MMO assessment, and of these, only 13% of patients ever had a TID recorded. Only 5% of patients had an MRI with contrast recorded.
Very few patient-level characteristics were statistically related to having MMO assessed. MMO was more likely to be assessed in female patients, which may be due to female sex being a reported risk factor for TMJ arthritis. There is also strong evidence that young age at JIA onset is a risk factor for TMJ arthritis and damage. More severe and destructive TMJ changes can be seen if TMJ arthritis occurs in young children, as growth can be impaired due to the superficial position of the condylar growth centers [
8]. Despite this known risk factor, MMO assessment did not significantly vary with patient age in our analysis.This may be been becuase clinician do not appreciate this important risk or because they have limited skills in MMO assessment in young children (e.g., assessment in the context of missing teeth). Despite evidence suggesting that TMJ arthritis is quite rare in certain subtypes of JIA, such as ERA, and more common in others, such as polyarticular JIA [
20], the rate of MMO assessment did not vary between subtypes. This could indicate that providers are not aware of which patients might be at higher risk for TMJ arthritis or that some providers perform this screening routinely while others rarely perform it. While there is some evidence that nonwhite race may be correlated with worse outcomes in patients with JIA [
21], there is very little in the literature about any relationship between race and ethnicity and the prevalence of TMJ arthritis. In our analysis, there was no statistically significant difference in the rate of MMO being measured or MRI being obtained between racial and ethnic groups.
As expected, MMO was more commonly documented in patients with a diagnosis of TMJ arthritis. This may have a twofold explanation: providers are more likely to document an MMO in patients with known TMJ disease, and patients with MMOs documented may be more likely to be diagnosed with TMJ arthritis.
Although MMO was consistently performed at some centers, it was typically recorded as greater than or less than 3 finger breadths. The three-finger rule is rarely sensitive enough to appreciate a decrease in MMO indicative of new onset or flare of TMJ arthritis. In this analysis, even when TIDs were collected, there was a wider range of values (3-75 mm) than would be expected, which may be partially attributable to clinicians submitting values that were measured in centimeters that were then transcribed into the registry in millimeters. Alternatively, some clinicians may lack knowledge of how to appropriately measure a TID. Multidisciplinary standardized guidelines for TMJ assessment have been recently published [
10], and we hope that the implementation of these guidelines in clinical practice may introduce more reliable measurements in the future.
MMO and TID alone are insufficient to diagnose TMJ arthritis, and MRI remains the gold standard for diagnosis. MRI was rarely recorded in patients in this cohort. There was no significant association with either race/ethnicity or JIA subtype, MRI was more likely to be obtained in female patients and in older patients, possibly because of the recognition that female patients have a higher rate of TMJ arthritis [
17]. It is possible that older patients have MRIs obtained more regularly because they do not require sedation. However, since young age is associated with increased risk of TMJ disease [
8], it is of concern that imaging is not performed in these children.
MRI with contrast was obtained a total of 499 times in our sample, and 146 of these MRIs were obtained in patients without a documented diagnosis of TMJ arthritis. This suggests that MRIs in some cases were being used diagnostically to determine if TMJ arthritis was present. However, even in those patients with a new diagnosis of TMJ arthritis during the period of our analysis, only 41% had an MRI with contrast of the jaw obtained. It is unclear how providers are diagnosing new active arthritis without contrast enhancement on MRI imaging, the current gold standard to define the disease.
In our analysis, there were 40 patients for whom only non-MRI imaging was performed, including ultrasound, X-ray, CT scan, or other imaging. Seven of these patients also had an MRI with contrast obtained, and 23 of these patients had a diagnosis of TMJ arthritis, so it is possible that this imaging was being used for follow-up of known disease, surgical planning, or other purposes as opposed to diagnosis.
There was tremendous variance in the clinical examination of the TMJ with MMO and MRI between sites of care. This demonstrates that certain providers evaluate the TMJ as part of their routine workflow, while other providers do not. Similarly, there was significant variation in the frequency of obtaining MRIs between sites of care, which also suggests high interprovider variability. Interestingly, there was very little overlap in the sites at which MMO was performed regularly and in the sites at which MRI was obtained regularly. This is challenging to interpret, as we would expect that abnormalities in MMO would trigger MRI assessment, and this likely implies some inaccuracies in data abstraction or documentation.
Overall this data demonstrates that the TMJ is being inadequately assessed in clinical practice. We suspect that this is multifactorial. One barrier may be lack of provider education on this important topic. In fact, recent work has demonstrated that pediatric rheumatologists self-report a lack of confidence in their ability to assess the TMJ and that trainees have limited understanding of how to appropriately measure an MMO [
22]. It is also possible that they are not ordering MRIs for their patients due to cost and the need for sedation. Providers may also have concerns about the accuracy of TMJ MRI interpretations and how to act on evidence of TMJ arthritis. Research is needed in these areas to improve clinician confidence in assessing and treating this important joint.
There are several limitations of this study. We relied on observational data from the CARRA Registry, which is a convenience sample. Not all patients who are cared for at an individual site are enrolled in the CARRA Registry, and although we do not have reason to believe that the patients enrolled in the Registry are significantly different from the overall clinic population, there may be some sampling bias. This multicenter cohort mostly captures data from academic centers and from children cared for by pediatric rheumatologists. We would suspect that this may overestimate the degree to which MMO/MRI are being performed, as patients cared for at nonacademic centers may have less access to sedation services for MRIs, and adult rheumatologists may have less awareness of TMJ arthritis. Abstractions of TMJ-related data fields into the database may be incomplete and/or not reflect clinical assessment. The data fields related to the TMJ were newly added at the time of our analysis, and completion rates may increase over time. In most centers, research coordinators collect the data for the CARRA registry, and it might be that providers perform MMO assessment but do not record the information adequately for data extraction. In this case, the likelihood of the provider using the MMO as a longitudinal measurement is minimal. Similarly, it is possible that MRIs are being performed but not extracted into the CARRA Registry. Additionally, while the CARRA Registry collects information on whether the patient has ever had a diagnosis of active TMJ arthritis there is no agreed upon registry definition for active TMJ arthritis.
Our study is the first analysis of provider assessment of the TMJ in a multicenter cohort in real-world clinical practice outside of an orthodontic clinic or a research study. Although the observational data might cause under- or over-estimation, this would not fully account for the low frequency of MMO and MRI assessments that are documented in the registry. Recent studies have found significant TMJ involvement in adult patients with JIA [
19,
23], and our data suggest that these sequelae will continue to occur as our current population ages. Our analysis clearly demonstrates that site of care is more associated with TMJ assessments than patient-level characteristics, suggesting that provider practice patterns rather than patient level chracteristics drive these differences. Comprehensive education of providers might improve the assessment of the TMJ in patients with JIA to help prevent long-term complications. This education should include the importance of TID assessment and how to most reliably measure MMO. The value of imaging and the importance of obtaining MRI with contrast in these patients could be another focus for provider education. We hope that further research and educational initiatives can improve accurate and timely diagnosis and treatment for this complicated, underdiagnosed form of arthritis.
Acknowledgements
This work could not have been accomplished without the aid of the following organizations: The NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) & the Arthritis Foundation. We would also like to thank all participants and hospital sites that recruited patients for the CARRA Registry. The authors thank the following CARRA Registry site principal investigators, sub-investigators and research coordinators: R. Aamir, K. Abulaban, A. Adams, C. Aguiar Lapsia, A. Akinsete, S. Akoghlanian, M. Al Manaa, A. AlBijadi, E. Allenspach, A. Almutairi, R. Alperin, G. Amarilyo, W. Ambler, M. Amoruso, S. Angeles-Han, S. Ardoin, S. Armendariz, L. Asfaw, N. Aviran Dagan, C. Bacha, I. Balboni, S. Balevic, S. Ballinger, S. Baluta, L. Barillas-Arias, M. Basiaga, K. Baszis, S. Baxter, M. Becker, (A) Begezda, E. Behrens, E. Beil, S. Benseler, L. Bermudez-Santiago, W. Bernal, T. Bigley, C. Bingham, (B) Binstadt, (C) Black, B. Blackmon, M. Blakley, J. Bohnsack, A. Boneparth, H. 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