Rheumatoid arthritis (RA) is a chronic disease characterized by synovial membrane inflammation with a symmetric polyarticular pattern, resulting in swelling, pain, stiffness, and damage that lead to deformities and functional impairment.1

Given the heterogeneous nature of RA, disease status assessment is important for achieving optimal outcomes. To evaluate disease activity, tools like Disease Activity Score based on 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI) were developed and are currently use as part of the approach in patients with RA.2,3 The DAS28 generates a score based on tender and swollen joints, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), and the Visual Analog Scale (VAS) for pain.3 This score can be calculated using either CRP (DAS28-CRP) or ESR (DAS28-ESR). CRP, however, is a more direct marker of inflammation and is more sensitive to short-term changes. Both measurements have a linear relationship, but they are not interchangeable within individuals.4

Rheumatic regional pain syndromes (RRPS) are clinical disorders characterized by pain and functional impairment of tendons, ligaments, bursa, or fascia in the appendicular MS system.5 Rotator cuff tendinopathy (RCT) represents the most common cause of RRPS,6 compromising the stabilization of the glenohumeral joint and impairing shoulder movement.

RCT presents with pain and weakness due to anatomical or functional impairment. It encompasses a variety of shoulder conditions such as tendinitis, tendinosis, subacromial bursitis and shoulder impingement.7,8

Patients with RA have about 50% higher risk of developing rotator cuff disease,9 this may be attributed to the chronic inflammation characteristic of the disease, which affects the glenohumeral joint surface.10 However, it is important to consider that shoulder pain in these patients is not necessarily attributable to RA alone.

Undiagnosed tendinopathy of the shoulder in patients with RA may be associated with poorer outcomes. Therefore, we aimed to assess the difference in disease activity scores between RA patients with RCT and those without it, considering ultrasound pathological findings.

We conducted an observational, cross-sectional, comparative study from January 2022 to January 2023 in a rheumatology outpatient clinic in a referral hospital. This study was approved by the IRB with the registration number: RE22-00001.

Patients

Patients (age≥18 years) with shoulder pain who met the 2010 ACR/EULAR classification criteria for rheumatoid arthritis11 during the study period were eligible. Exclusion criteria included a prior diagnosis of RCT by clinical examination and a history of adhesive capsulitis/frozen shoulder or peripheral nerve injury associated with shoulder trauma. Patients underwent clinical examination to determine the presence of RCT and were assigned to the RA+RCT group. They were then referred for ultrasound examination. These patients were included consecutively until the target sample size was reached. Subsequently, RA patients without clinical signs of RCT were selected through consecutive convenience sampling and matched by sex and age, forming the RA without RCT group. The matched patients were recruited within the same week as their corresponding counterparts underwent ultrasound. The patient flow is illustrated in Fig. 1. All patients gave consent prior to inclusion in this study.

Fig. 1.

Patient flow diagram.

Ultrasound

A musculoskeletal ultrasound (MSUS) examination of both shoulders was performed using the scanning technique proposed by the 2017 EULAR standardized procedures for ultrasound imaging in rheumatology.16 MSUS was performed with MyLab50® Xvision equipped with a 5/7.5/10MHz Mindray 7L4a linear probe, guided by an MSUS expert who was blinded to patients’ clinical and laboratory data at the time of the examination. Imaging was required to differentiate and verify RCT from disease activity. The anterior, lateral, and posterior aspects of the joint were scanned. Synovitis was defined according to the published definitions of Outcome Measures in Rheumatology (OMERACT).17 Cases of joint effusion, acromioclavicular synovitis, or glenohumeral synovitis were attributed to RA activity. Representative ultrasound images are shown in Figs. 2 and 3 illustrating findings in a patient with RA without RCT and another with RA+RCT, respectively

Fig. 2.

Ultrasound findings in a patient with rheumatoid arthritis without rotator cuff tendinopathy. Images of the left shoulder showing active synovitis and arthrosis of the acromioclavicular and glenohumeral joints. (A1) Longitudinal grayscale view of the anterior glenohumeral joint. (A2) Corresponding Doppler view. (B1) Grayscale image of the left acromioclavicular joint. (B2) Doppler image of the same region. (C1) Posterior glenohumeral joint in grayscale. (C2) Doppler image of posterior glenohumeral joint.

Fig. 3.

Ultrasound findings in a patient with rheumatoid arthritis and rotator cuff tendinopathy. Images of the right shoulder showing degenerative changes in the acromioclavicular and glenohumeral joints, with no evidence of synovitis. (A1) Grayscale longitudinal view of the anterior glenohumeral joint. (A2) Corresponding Doppler image. (B1) Grayscale images of the acromioclavicular joint. (B2) Doppler signal of the same region. (C1) Posterior glenohumeral joint in grayscale. (C2) Corresponding Doppler image.

Fifty-six patients with RA consented and enrolled in the study, 28 were diagnosed with RCT, and 28 were in the comparative group. Socio-demographic and clinical characteristics are summarized in Table 1. Most of the patients were female (96%) with a mean age of 53±12.8 years. The median (IQR) disease duration was 8 (3–11) years. Twenty-three (41%) patients had high blood pressure, 10 (18%) had osteoporosis, and 9 (19%) had diabetes, 36 (64%) were treated with glucocorticoids, and 54 (96%) were taking conventional disease-modifying antirheumatic drugs (csDMARDs). Regarding laterality, 15 (53.6%) patients in the RCT group had right shoulder involvement, 8 (28.6%) had left shoulder involvement, and 5 (17.9%) presented bilateral tendinopathy.

Our study demonstrates that RA patients with RCT exhibit significantly higher DAS28 scores, indicating higher RA activity. The presence of RCT in patients with RA without evident synovitis supports the hypothesis that the increase in disease activity, might be influenced by pain unrelated to joint pathology, which may amplify the overall clinical impression.19 Similar to other non-inflammatory diseases like fibromyalgia,19,20 depression, psychological distress,20 and osteoarthritis,21 RCT could also impact disease activity scores.

The shoulder is a common site of MS pain, affecting a median of 16% of the general population,22 with rotator cuff disorders being the leading cause.23 Patients with RA are at a higher risk of rotator cuff disease, probably due to chronic inflammation and tendon degeneration resulting in weakness of the rotator cuff muscles.9 The shoulder joint accounts for 11–27% of clinimetric indexes24 and significantly contributes to general and pain VAS score, as well as HAQ scores.25 Given its impact, results should be interpreted cautiously, considering the specific characteristics of the pain. Since the shoulder is often one of the last joints affected by RA,26 and RCT is multifactorial – combining extrinsic mechanical compression and tendon overuse/overload,8,27 other factors should be considered before assuming that RCT is a direct consequence of RA. This is also supported by the absence of significant difference among groups when comparing ultrasound signs attributed to RA activity.

The differences in disease activity scores between RA patients with and without RCT highlight the impact on disease perception and management. All patients with RCT exhibited moderate to high disease activity, since the severity of the disease is one of the leading indicators of functional capacity,28 it can be compromised by RCT, as reflected in the HAQ-DI scores.

In contrast, only 2 patients without RCT had high disease activity, and just over half had moderate activity. The rest presented mild activity or were in remission. Probably explained by the fluctuation of symptoms over time and the dynamic nature of RA.

The manage of care in RA follows a treat-to-target approach, requiring regular assessment of disease activity.29 However, if judgments are made solely on DAS28, patients may receive inadequate medical care for their specific disorder, as DAS28 is a supportive tool that represents patient's disease activity but may not fully capture the complexity of an individual patient's clinical presentation. Given this and considering the impact of RCT in RA disease activity scores, an intentional examination of the shoulder is essential when patients complain of shoulder pain and limited range of motion.

As the management of RA and RCT differs, it is necessary to treat RCT specifically. Although painkillers and steroids can alleviate the pain associated with both conditions, RCT requires its own treatment such as active exercise, physical therapy, corticosteroid injections, or even a surgical intervention.9 These address the underlying tendon issues directly, unlike RA treatments which focus on reducing inflammation and immune system activity. By specifically treating RCT, we can improve the accuracy in the assessment of RA disease activity and improve the scores.

Our study has some limitations. Given the cross-sectional nature of the study, by the time of ultrasound performance, patients did not have synovitis which could have led to tendinopathy and shoulder pain. Besides, markers such as VAS, the number of swollen joints, and the number of painful joints are dynamic and can change over time. It is possible that the tendinopathy detected during the evaluation may resulted from previous elevated disease activity, including synovitis in the subacromial space which was not detected at the time of the study. Another limitation is that the ultrasound assessments were conducted by a single operator.

We emphasize that at the time of evaluation, patients did not have synovitis in joints that could lead to shoulder pain. Even though DAS28 score majorly depends on acute reactants factors, we found a significant difference of more than 50mm in VAS between the RCT group and those without it; consistent with the pain contribution of shoulder involvement.27 It is beyond the scope of this study to determine which clinical feature is most responsible for the elevation of the disease activity score; however, it is recommended that further research be undertaken to investigate the relationship between RCT and high disease activity in RA more thoroughly.

RA patients with RCT have higher composite index and disease activity scores than those without RCT. An intentional screening for RCT should be recommended for those patients with shoulder pain and elevated disease activity to achieve optimal patient-tailored care and appropriate treatment management.

All authors contributed to the study's conception and design. Material preparation was performed by JMC, JAEV, DVM, RJCDLG, and LDLCB. RJCDLG and AADLP did the formal analysis and investigation. JMC collected the data. RJCDLG, AEMM, and LGF wrote and prepared the original draft. Review and editing were performed by RJCDLG, DVM, AALP, and LGF. All authors commented on previous versions of the manuscript, read and approved the final manuscript. All authors take full responsibility for the integrity and accuracy of all aspects of the work.

Study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. All patients gave their individual informed consent for processed data and publication before their inclusion in this study. The protocol was approved by the Institutional Ethics and Research Committee (RE22-00001). Patients were aware of what kind of personal data was processed, how would it be used and for which purpose.

We declare no funding that are directly or indirectly related to work submitted for publication. This study didn’t receive benefits from commercial sources.

All the authors in this paper declare no conflict of interest.