Background/Purpose: Inflammation of the synovial lining is a hallmark of rheumatoid arthritis (RA). A synovial lining is not only present at synovial joints and tendon sheaths but also at bursae. Inflammation of the synovium-lined intermetatarsal bursae in the forefoot, intermetatarsal bursitis (IMB), was recently identified with MRI. It is specific for early RA and present in 69% of RA patients at diagnosis. During development of RA, MRI-detectable subclinical synovitis and tenosynovitis often occur before clinical arthritis presents. Whether IMB is also present in a pre-arthritis stage is unknown. Therefore, a large MRI-study in patients with clinically suspect arthralgia (CSA) was performed to assess the occurrence of IMB and its association with progression to clinical arthritis.

Methods: We studied 577 consecutive patients presenting with CSA. CSA was defined as recent-onset arthralgia of small joints that is likely to progress to RA based on the clinical expertise of the rheumatologist. Participants underwent unilateral contrast-enhanced 1.5T MRI of the forefoot, metacarpophalangeal (MCP) joints and wrist at baseline. Thereafter patients were followed for detection of clinical arthritis, as identified at physical joint examination by the rheumatologist. Baseline MRIs were evaluated for IMB-presence and -size in dorsoplantar direction at all 4 intermetatarsal spaces. Also synovitis, tenosynovitis and osteitis were assessed in line with the RA MRI scoring system (summed as RAMRIS-inflammation). IMB and RAMRIS-inflammation features were considered positive if uncommon in the general population (i.e. scored above the 95th-percentile of age-matched symptom-free controls). Cox regression analysed the association of IMB with progression to clinical arthritis; multivariable analyses adjusted for RAMRIS-inflammation which is known to associate with progression to clinical arthritis. Analyses were repeated stratified for ACPA-status, since ACPA-positive and ACPA-negative RA harbor differences in pathophysiology.

Results: 23% of CSA-patients had IMB (i.e., dorsoplantar size above the reference in symptom-free controls). IMB was more frequent in ACPA-positive than ACPA-negative CSA-patients (56% versus 19%, p< 0.001). Patients with IMB were more likely to also have subclinical synovitis (OR 2.4 (95%CI 1.2–4.8)) and tenosynovitis (11.5 (5.1–26.2)) on forefoot MRI, but not osteitis (0.8 (0.4–1.7)). Median follow-up was 25 months. Patients with IMB developed clinical arthritis more often than patients without IMB (HR 3.3 (2.1-5.1)). This association was independent of synovitis-, tenosynovitis- and osteitis-presence at the forefoot, MCPs or wrist (adjusted HR 1.7 (1.03–2.7)). IMB predicted clinical arthritis development in ACPA-positive CSA (adjusted HR 2.2 (1.0–5.0)) but not in ACPA-negative CSA patients (0.8 (0.4–1.6)).

Conclusion: A quarter of CSA patients have IMB, which is frequently accompanied by subclinical synovitis and tenosynovitis. IMB precedes the development of clinical arthritis, and in particular the development of ACPA-positive RA. These results reinforce the notion that not only intra- but also juxta-articular synovial inflammation is involved in the development of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/during-development-of-rheumatoid-arthritis-intermetatarsal-bursitis-may-occur-before-clinical-joint-swelling-a-large-mri-study-in-patients-with-clinically-suspect-arthralgia/