Forefoot inflammation in recent-onset ACPA-positive and ACPA-negative RA: clinically similar, but different in underlying inflamed tissues.

Objectives: Although joint swelling is traditionally interpreted as synovitis, recent imaging studies showed that there is also inflammation of tenosynovium and intermetatarsal bursae in the forefoot. We aimed to increase our understanding of differences and similarities regarding forefoot involvement between ACPA-positive and ACPA-negative rheumatoid arthritis (RA) at diagnosis. Therefore, we (1) compared metatarsophalangeal (MTP) joint counts, walking disabilities and inflamed tissues between ACPA groups and (2) studied associations of joint swelling/tenderness and walking disabilities with underlying inflamed tissues within ACPA groups.

Methods: 171 ACPA-positive and 203 ACPA-negative consecutively diagnosed patients with RA had a physical joint examination (swollen joint count-66/tender joint count-68), filled a Health Assessment Questionnaire including the domain walking and underwent MRI of the MTP joints at diagnosis. Synovitis, tenosynovitis, osteitis and intermetatarsal bursitis (IMB) were assessed. Findings in age-matched healthy controls were applied to define abnormalities on MRI.

Results: While ACPA-negative RA patients had more swollen joints (mean SJC 8 vs 6 in ACPA-positives, p=0.003), the number of swollen MTP joints was similar (mean 1 in both groups); walking disabilities were also equally common (49% vs 53%). In contrast, inflamed tissues were all more prevalent in ACPA-positive compared with ACPA-negative RA. Within ACPA-positive RA, IMB was associated independently with MTP-joint swelling (OR 2.6, 95% CI 1.4 to 5.0) and tenderness (OR 3.0, 95% CI 1.8 to 5.0). While in ACPA-negatives, synovitis was associated independently with MTP-joint swelling (OR 2.8, 95% CI 1.4 to 5.8) and tenderness (OR 2.5, 95% CI 1.3 to 4.8). Tenosynovitis contributed most to walking disabilities.

Conclusions: Although the forefoot of ACPA-positives and ACPA-negatives share clinical similarities at diagnosis, there are differences in underlying inflamed tissues. This reinforces that ACPA-positive and ACPA-negative RA are different entities.