Joint tenderness was associated with ultrasound abnormalities more consistently than patient-reported joint pain among anti-cyclic citrullinated peptide–positive patients with musculoskeletal symptoms but no clinical arthritis, according to a cross-sectional analysis published in BMJ Open.
The exploratory findings did not establish a clinical scanning strategy but may inform prospective studies evaluating whether physical examination findings could help guide ultrasound assessment in selected patients at risk of rheumatoid arthritis.
Researchers analyzed baseline data from 323 of 451 participants in the CCP Study, a prospective observational cohort based in Leeds, UK. The analysis was restricted to participants whose physical examination, pain questionnaire, and ultrasound scan were completed on the same day.
Eligible participants were aged 18 years or older, tested positive for anti-cyclic citrullinated peptide antibodies, and had a new nonspecific musculoskeletal complaint without clinical arthritis or a history of inflammatory arthritis. Patients with fibromyalgia at baseline were excluded from the analysis.
A rheumatologist assessed joint tenderness by palpation. Participants separately marked regions in which they had experienced pain during the previous week. Unlike the joint-specific tenderness examination, the pain questionnaire grouped some anatomical sites, including the hands and fingers and the feet and toes.
Ultrasound examinations evaluated gray-scale synovitis, power Doppler activity, tenosynovitis, and erosions in the wrists and selected joints of the hands, elbows, knees, ankles, and feet. The protocol changed during recruitment from 2008 to 2020, and elbows, knees, ankles, and tendons were not assessed in all participants. Tendon imaging was available in 153 participants.
The researchers evaluated joint-level associations using generalized estimating equation logistic models that accounted for multiple joints within the same patient and adjusted for age and sex. Ultrasound findings were analyzed as present or absent rather than according to their full severity scores.
In pooled analyses, joint tenderness was associated with gray-scale abnormalities, power Doppler activity, tenosynovitis, and erosions. The broadest associations were observed for power Doppler activity and gray-scale abnormalities. Patient-reported joint pain was associated with gray-scale abnormalities, power Doppler activity, and tenosynovitis but was not significantly associated with erosions.
At individual joint sites, tenderness showed the broadest pattern of association with power Doppler activity. Statistically significant associations were identified at the wrist and selected metacarpophalangeal, proximal interphalangeal, elbow, knee, and metatarsophalangeal joints.
The joint-specific findings were not uniform, however. Several estimates were imprecise because ultrasound abnormalities were uncommon at individual anatomical sites. Tenderness was significantly associated with tenosynovitis only at the wrist in the joint-specific analysis.
Patient-reported pain showed a more selective pattern. It was associated primarily with gray-scale abnormalities in several hand, elbow, and foot joints and with power Doppler activity at the wrist, second proximal interphalangeal joint, elbow, and first and second metatarsophalangeal joints. Combining tenderness with patient-reported pain generally did not produce significantly stronger associations than tenderness alone.
Absence of tenderness had negative predictive values greater than 96% for power Doppler activity at most joints. The value was lower at the wrist, at approximately 91%. Negative predictive values were also generally high for tenosynovitis and erosions, although several estimates were in the low to mid-90% range.
These values require cautious interpretation because power Doppler activity, tenosynovitis, and erosions were uncommon at many joints. Positive predictive values were generally limited, meaning that tenderness did not reliably indicate that an ultrasound abnormality would be present.
The wrist may also represent an important exception to any future tenderness-guided strategy. Power Doppler activity occurred in some wrists without tenderness or reported pain, and the researchers cautioned that omitting asymptomatic wrists could miss subclinical abnormalities.
The researchers emphasized that the analysis did not evaluate prediction of rheumatoid arthritis or assess effects on clinical management and that the findings did not constitute recommendations for ultrasound scanning strategies. Although 26% of the analyzed cohort subsequently developed rheumatoid arthritis, progression was not an outcome of the cross-sectional models.
Other limitations included adjustment for only age and sex, regional rather than joint-specific patient pain reporting, dichotomization of ultrasound scores, protocol and equipment changes during the prolonged recruitment period, low event counts at some joints, and the absence of formal intraobserver or interobserver reliability testing. Standardized operator training, calibration, and quarterly image reviews were performed.
Because the cohort was limited to anti-cyclic citrullinated peptide–positive patients without clinical arthritis and excluded patients with fibromyalgia, the findings may not extend to anti-cyclic citrullinated peptide–negative patients, patients with established rheumatoid arthritis or swollen joints, or patients with fibromyalgia.
Disclosures: The study was supported by the National Institute for Health Research Leeds Biomedical Research Centre. The funder had no role in the study design, data collection, analysis, interpretation, manuscript preparation, or decision to submit the manuscript. Garcia-Montoya reported receiving honoraria and educational or meeting support from Novartis. Other researchers reported grants, consulting fees, honoraria, speaker fees, meeting support, or advisory roles involving AbbVie, AnaptysBio, AstraZeneca, Bristol Myers Squibb, Galapagos, Gilead, Janssen, Lilly, Novartis, Samsung, Sandoz, and Serac Life Sciences.
Source: BMJ Open
