Proliferative Synovitis, an Ultrasound Pattern Associated with ACPA positive Patients, Erosive Disease and Enhanced Need to Change Therapy in Rheumatoid Arthritis

Objectives: To analyze ultrasound (US) differences between rheumatoid arthritis (RA) patients according to their autoantibody status and characterize the clinical, immunological and radiological features associated with the US pattern of seropositive patients.Methods: We collected clinical and immunological data along with bilateral hand US images of RA patients. Serum biomarkers, MRI of dominant hand and immunostaining of synovial biopsies were performed.Results: Two hundred and five RA patients were collected (84.8% seropositive). No significant differences in disease activity/therapy were found according to autoantibodies status. An extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal that we called US Proliferative Synovitis (US PS) was present in 55.5% of seropositive and 16.1% of seronegative patients, (p=0.0001). In the multivariate analysis, erosions [OR 4.90 CI 95% (2.17-11.07). p=0.0001] and ACPA [OR 3.5 CI 95% (1.39-10.7), p=0.09] but not RF status [OR 0.74 CI 95% (0.31-1.71), p=0.483] were independently associated with the presence of US PS. Ninety-four per cent of joints with US PS scored 2-3 in RAMRIS synovitis sub-index. At synovial level, US PS was significantly associated with higher density of vessels (p=0.042). Moreover, significantly higher serum levels of angiogenic and inflammatory cytokines were found in patients with US PS. After a mean of 46 months of follow-up, US PS was independently associated with change of therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016).Conclusions: ACPA+ RA was associated with US PS. This US pattern significantly detected erosive disease and an enhanced need to change therapy in the long-term.