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Tender joint count is part of most composite disease activity scores and treatment targets in rheumatoid arthritis (RA).1 Joint tenderness could represent not only synovial inflammation in the absence of clinical swelling but also factors such as erosive damage and pain sensitisation.2 Ultrasound examination can add information to the clinical evaluation of inflammation.
Joint tenderness did not reflect inflammatory activity when assessed by ultrasound in patients with established RA3 but might be more related to inflammation in early arthritis.4 5 We aimed to explore joint tenderness in DMARD-naïve patients with early RA and assess whether this finding was associated with ultrasound inflammation in the absence of swelling.
The analyses were performed using baseline data from the ARCTIC trial,6 which included assessment of joint tenderness by Ritchie Articular Index and a 44-swollen joint count. The Ritchie Articular Index grades joint tenderness 0–3, with certain joints being treated as a single unit, for example, the metacarpal-phalangeal (MCP) joints. In the ultrasound examination, 32 joints were all dorsally scored semiquantitatively 0–3 for power Doppler (PD), with an ultrasound atlas for reference.6 The wrists were predefined as the joint area of interest since they are commonly involved in RA and were assessed both clinically and by ultrasound. Additionally, in these joints, scoring of tenderness by Ritchie Articular Index could correspond to the more commonly used tender joint count. The presence of ultrasound inflammation was defined as a PD score of minimum one in any of the following areas: the radiocarpal joint, intercarpal joint, radioulnar joint and extensor carpi ulnaris tendon. We then selected only wrists that were clinically nonswollen and examined the association between joint tenderness and PD positivity in these joints by mixed logistic regression models with patient-specific intercept to adjust for within-patient dependencies. The analyses were repeated using generalised estimating equations for robustness. In secondary analyses, we explored tenderness of the MCP joints, but comparability with swelling and ultrasound findings were weakened by the lack of a regular tender joint count. The MCP1–5 had to be scored together as one unit for swelling and PD signal. The association between joint tenderness and grey-scale synovitis was also assessed.
Of the 230 patients, 61% were women, median (IQR) symptom duration of 5.6 (2.8, 10.2) months, swollen joint count of 10 (4, 15), joint tenderness by Ritchie Articular Index 7 (4, 13) and PD score of 7 (3, 14).6 Of the 460 assessed wrists, 282/460 (61%) were clinically nonswollen. Of these, 38/282 (13%) were reported as tender (graded 1 or 2). The frequency of PD score ≥1 in the tender nonswollen wrists was 19/38 (50%) compared with 55/244 (23%) in the nontender nonswollen wrists. This corresponds to an OR of 4.70 (95% CI 1.62 to 13.62, p value <0.001) for PD signal in a tender nonswollen wrist compared with a nontender nonswollen wrist (figure 1). Similar results were found for grey-scale synovitis and for the nonswollen MCP joints. Of the 19 PD positive wrists, 11 had a total PD score of ≥2.
The frequency and OR of ultrasound power Doppler signal in tender vs non-tender non-swollen wrists.
In conclusion, in nonswollen wrists, ultrasound PD activity was more frequent if the wrist was tender. A hypothetic explanation of this finding might be that tender joints at time of RA diagnosis reflect low-grade inflammation, which is not detectable clinically as swelling. In contrast to established RA, these patients with early RA had less joint damage, and central sensitisation due to long-lasting inflammatory activation of pain fibres might not yet be an issue. A limitation of this study is the evaluation of tenderness by Ritchie Articular Index, reducing the number of joint areas available for analysis. The pathophysiology behind a tender joint in early RA should be further explored, and joint tenderness might deserve more attention when aiming for remission in early disease.
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Patient consent for publication
Ethics approval
The study was approved by an independent ethics committee (the regional Committee for Medical and Health research ethics south-east; reference number 2010/744).
Footnotes
Handling editor Josef S Smolen
Contributors All authors were involved in drafting the letter or revising it critically for important intellectual content and approved the final manuscript to be submitted and agreed to be accountable for all aspects of the work. Conception and design of the ARCTIC study: A-BA, ICO, HBH, TU, DvdH, TKK, SL and EAH. Acquisition of data: A-BA, HBH, TU and EAH. Analysis and interpretation of data: NPS, A-BA, ICO, HBH, TU, DvdH, TK, SL and EAH. EAH and SL are shared last authors.
Funding The ARCTIC study has received grants from the Norwegian Research Council, the South-East Health Region in Norway, the Norwegian Rheumatism Association, the Norwegian Women’s public Health Association and unrestricted grant support from AbbVie, Pfizer, MSD, Roche and UCB. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Competing interests Dr NPS reports grants from The South-Eastern Norway Regional Health Authority, during the conduct of the study; Dr Aga reports personal fees from Abbvie, personal fees from Eli Lilly, personal fees from Novartis, personal fees from Pfizer, outside the submitted work; Dr ICO has nothing to disclose; Dr NBH reports personal fees from AbbVie, personal fees from Novartis, personal fees from Lilly, outside the submitted work; Dr TU reports personal fees from Lilly, personal fees from Novartis, outside the submitted work; Dr DvdHv reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma, outside the submitted work; and Director Imaging Rheumatology BV; Dr TKK reports personal fees from Amgen, personal fees from Celltrion, personal fees from Egis, personal fees from Evapharma, personal fees from Ewopharma, personal fees from Hikma, personal fees from Oktal, personal fees from Sandoz, personal fees from Sanofi, personal fees from Abbvie, personal fees from BMS, personal fees from MSD, personal fees from Pfizer, grants from UCB, personal fees from Biogen, personal fees from Eli Lilly, personal fees from Gilead, personal fees from Mylan, personal fees from Novartis, outside the submitted work; Dr EAH reports grants from The Research Council of Norway, grants from The South-Eastern Norway Regional Health Authority, during the conduct of the study; personal fees from Pfizer, from AbbVie, personal fees from Celgene, personal fees from Novartis, personal fees from Janssen, personal fees from Gilead, personal fees from Eli-Lilly, personal fees from UCB, outside the submitted work; Dr SL reports grants from The South-Eastern Norway Regional Health Authority, grants from The Research Council of Norway, grants from Norwegian Women’s Public Health Association, grants from Norwegian Rheumatism Association, grants from AbbVie, grants from UCB Pharma, grants from Pfizer Inc, grants from MSD Norway, grants from Roche Norway, during the conduct of the study.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.