Intermetatarsal Bursitis, a Novel Feature of Juxtaarticular Inflammation in Early Rheumatoid Arthritis Related to Clinical Signs: Results of a Longitudinal Magnetic Resonance Imaging Study

Abstract

Objective Intermetatarsal bursae in the forefeet possess a synovial lining similar to joints and tendon sheaths. Inflammation of these bursae (intermetatarsal bursitis [IMB]) was recently identified as specific for early rheumatoid arthritis (RA). The present study was undertaken to determine if IMB is indeed an RA feature by assessing the following: 1) the association with other local inflammatory measures (synovitis, tenosynovitis, and osteitis), 2) the association with clinical signs, and 3) whether it responds to disease‐modifying antirheumatic drug (DMARD) therapy similarly to other local inflammatory measures. Methods One hundred fifty‐seven consecutive early RA patients underwent unilateral contrast‐enhanced 1.5T forefoot magnetic resonance imaging (MRI) at diagnosis. MRIs were evaluated for IMB presence and for synovitis, tenosynovitis, and osteitis in line with the RA MRI Scoring (RAMRIS) system (summed as RAMRIS inflammation). MRIs at 4, 12, and 24 months were evaluated for IMB presence and size in patients who had IMB at baseline and received early DMARD therapy. Logistic regression and generalized estimating equations were used. Anti–citrullinated protein antibody (ACPA) stratification was performed. Results Sixty‐nine percent of RA patients had ≥1 IMB. In multivariable analysis on bursa level, presence of IMB was independently associated with local presence of synovitis and tenosynovitis, with odds ratios (OR) of 1.69 (95% confidence interval [95% CI] 1.12, 2.57) and 2.83 (95% CI 1.80, 4.44), respectively, but not osteitis. On the patient level, IMB presence was most strongly associated with tenosynovitis (OR 2.92 [95% CI 1.62, 5.24]). IMB presence was associated with local joint swelling (OR 2.7 [95% CI 1.3, 5.3]) and tenderness (OR 1.7 [95% CI 1.04, 2.9]) independent of RAMRIS inflammation. During treatment, IMB size decreased between 0 and 12 months. This decrease associated with decrease in RAMRIS inflammation, which was driven by synovitis decrease. Within ACPA‐positive and ACPA‐negative RA, similar results were obtained. Conclusion IMB particularly accompanies inflammation of the synovial lining of joints and tendon sheaths, showed a similar treatment response after DMARD initiation, and associates with typical clinical signs. These findings suggest that IMB represents a frequently present novel RA feature of juxtaarticular synovial inflammation.

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

“…Interestingly, the prevalence of IMB (regardless of size) in ACPA-positive CSA was similar to previously reported in early ACPA-positive RA (64% and 70%, respectively, P = 0.14), whereas in ACPA-negative CSA the prevalence was lower than in ACPA-negative RA (31% vs 69%, P < 0.001) [ 10 ]. Moreover, in the current study, IMB associated with clinical arthritis development only in ACPA-positive CSA.…”

“…In addition, IMB precedes clinical arthritis, particularly in ACPA-positive individuals. Together with previous results showing that IMB is highly prevalent in RA at diagnosis, this suggests that intermetatarsal bursae are one of the target tissues early involved in RA [ 10 ].…”

“…CSA patients with IMB had MTP tenderness slightly more often than patients without IMB, but this was not statistically significant ( Table 1 ). This is in contrast to early RA patients, where IMB presence has been shown to contribute to joint tenderness [ 10 ]. Possibly, IMB severity may increase during development of arthritis and does not yet reach the threshold of inducing tenderness in the phase of CSA.…”

“…IMB was therefore defined as contrast-enhancement of the bursa in the superior intermetatarsal space, with or without rim enhancement on ≥2 consecutive slices in the axial and coronal plane [ 9 ]. At each of the four superior intermetatarsal spaces, IMB presence and size were recorded by a single trained reader as published previously [ 10 ]. For IMB size, the dorsoplantar dimension was used because the bursae are confined transversally by the metatarsal heads and may, theoretically, distend in dorsoplantar direction more freely [ 26 ].…”

“…Recently, an MRI study showed that IMB is present in two-thirds of early RA patients and is highly specific for RA in comparison to healthy controls [ 9 ]. Moreover, IMB frequently accompanies other RA-related synovial inflammation (synovitis and tenosynovitis), contributes to local joint swelling and tenderness and seems responsive to treatment with DMARDs [ 10 ]. Therefore, IMB may be considered a novel feature of juxta-articular synovial inflammation in RA.…”