During development of rheumatoid arthritis, intermetatarsal bursitis may occur before clinical joint swelling: a large imaging study in patients with clinically suspect arthralgia.

OBJECTIVES Intermetatarsal bursitis (IMB) represents juxta-articular synovial inflammation of the intermetatarsal bursae. Recent MRI-studies identified IMB as feature of early RA, but whether IMB already occurs in the pre-arthritic phase is unknown. We performed a large MRI-study in clinically suspect arthralgia (CSA) to assess the occurrence and prognostic value of IMB. METHODS 577 consecutive CSA-patients underwent contrast-enhanced MRI of the forefoot, metacarpophalangeal joints and wrist. MRIs were evaluated for subclinical synovitis/tenosynovitis/osteitis in line with the RA MRI scoring system (summed as RAMRIS-inflammation) and for IMB. IMB was considered present if uncommon in the general population at the same location (i.e. size scored above the 95th-percentile in age-matched symptom-free controls). The relation of IMB with other MRI-detected subclinical inflammation synovitis/tenosynovitis/osteitis) was studied. Cox-regression assessed the association with clinical arthritis development during median 25 months follow-up. ACPA-stratification was performed. RESULTS At presentation with CSA, 23% had IMB. IMB was more frequent in ACPA-positive than ACPA-negative CSA (47% vs 19%,p< 0.001). Patients with IMB were more likely to also have subclinical synovitis (OR 3.4 (95%CI 1.8-6.5)) and tenosynovitis (5.9(2.8-12.6)). IMB conferred higher risk of developing arthritis (HR 1.6(1.0-2.7) adjusted for other subclinical inflammation). IMB-presence predicted arthritis development in ACPA-positive CSA (adjusted HR 2.2(1.0-4.7)), but not in ACPA-negative CSA-patients (0.8(0.4-1.7)). CONCLUSION Approximately a quarter of CSA-patients have IMB, which is frequently accompanied by subclinical synovitis and tenosynovitis. IMB precedes development of clinical arthritis, particularly in ACPA-positive CSA. These results reinforce the notion that juxta-articular synovial inflammation is involved in the earliest phases of RA-development.