Validity of the rheumatoid arthritis MRI score applied to the forefeet using the OMERACT filter: a systematic literature review

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Walking disabilities are associated with tenosynovitis at the metatarsophalangeal joints: a longitudinal MRI‐study in early arthritis

Pathophysiology and treatment of rheumatic disease

Reliability of Magnetic Resonance Imaging (MRI) scoring of the metatarsophalangeal joints of the foot according to the Rheumatoid Arthritis MRI Score

Objective. The Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is validated for hand MRI. Its reliability applied to metatarsophalangeal (MTP 1-5) joints is unknown and was studied in early arthritis and clinically suspect arthralgia.Methods. Patients underwent 1.5 Tesla MRI of MTP, metacarpophalangeal (MCP 2-5), and wrist joints. Two paired readers scored bone marrow edema (BME), synovitis, tenosynovitis, and erosions. Interreader reliability was assessed of 441 consecutive early arthritis patients at baseline, 215 by 2 readers, and the remaining 226 by 2 different readers. Two readers scored baseline MRI of 82 consecutive patients with clinically suspect arthralgia, and 40 randomly selected patients by 9 readers. Intrareader reliability was determined on a random set of 15 early arthritis patients, scored twice by 2 readers. For change scores, 30 early arthritis patients with baseline and 1-year followup MRI were scored by 2 readers. Intraclass correlation coefficients (ICC), Bland-Altman (BA) plots, and smallest detectable change (SDC) were determined. MRI data of MTP joints were compared to wrist and MCP joints.Results. Interreader ICC and mean scores in early arthritis were BME ICC 0.91-0.92 (mean 1.5 +/- SD 2.6), synovitis 0.90-0.92 (1.3 +/- 1.7), tenosynovitis 0.80-0.85 (1.1 +/- 1.8), and erosions 0.88-0.89 (0.7 +/- 1.0). In patients with clinically suspect arthralgia, ICC were comparable. Intrareader ICC for inflammatory MRI features were 0.84-0.98, for erosions 0.71 (reader 1), and 0.92 (reader 2). Change score ICC were = 0.90, except erosions (0.77). SDC were = 1.0. BA plots showed no systematic bias. Reliability scores of MTP joints were similar to MCP and wrist joints.Conclusion. Status and change MRI scores of BME, synovitis, tenosynovitis, and erosions of MTP joints can be assessed reliably by RAMRIS.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Increased frequency of intermetatarsal and submetatarsal bursitis in early rheumatoid arthritis: a large case-controlled MRI study

Background: The forefoot is a preferential location for joint and tendon sheath inflammation in rheumatoid arthritis (RA). It also contains bursae, of which the intermetatarsal bursae have a synovial lining. Some small imaging studies suggested that intermetatarsal bursitis (IMB) and submetatarsal bursitis (SMB) are involved in RA, but their association has not been thoroughly explored. Healthy control studies suggested that lesion size might be relevant. We studied the relation between IMB and SMB in early RA, compared to other arthritides and healthy controls, and the relevance of lesion sizes. Methods: Six hundred and thirty-four participants were studied: 157 consecutive patients presenting with early RA, 284 other arthritides, and 193 healthy controls. All underwent unilateral contrast-enhanced MRI of the forefoot at presentation. Two readers independently scored IMB and SMB and measured transverse and dorsoplantar diameters, blinded to clinical data. Subsequently, consensus was reached. Intra-reader ICC was 0.89. Logistic regression models were used, and test characteristics were calculated. Results: IMB and SMB associated with RA independent of each other (P < 0.001) and independent of age, gender, BMI, RA-MRI inflammation, and anti-CCP-antibodies (P = 0.041). Sensitivity for RA of IMB was 69%, and for SMB 25%. Specificity for IMB was 70% compared to other arthritides, and 84% compared to healthy controls. For SMB, this was 94% and 97% respectively. Regarding lesion size, the groups had considerable overlap: no cut-off size for RA could be distinguished with high sensitivity and specificity. Conclusion: Intermetatarsal and submetatarsal bursitis associated with early rheumatoid arthritis, contributing to the emerging evidence that inflammation of juxta-articular soft tissues is an early feature of RA

A search to the target tissue in which RA-specific inflammation starts: a detailed MRI study to improve identification of RA-specific features in the phase of clinically suspect arthralgia

OBJECTIVE: Based on a unique cohort of clinically suspect arthralgia (CSA) patients, we analysed which combinations of MRI features at onset were predictive for rheumatoid arthritis (RA) development. This was done to increase our comprehension of locations of RA onset and improve the predictive accuracy of MRI in CSA. METHODS: In the discovery cohort, 225 CSA patients were followed on clinical arthritis development. Contrast-enhanced 1.5 T MRIs were made of unilateral metacarpophalangeal (MCP) (2-5), wrist, and metatarsophalangeal (1-5) joints at baseline and scored for synovitis, tenosynovitis, and bone marrow edema. Severity, number, and combinations of locations (joint/tendon/bone) with subclinical inflammation were determined, with symptom-free controls of similar age category as reference. Cox regression was used for predictor selection. Predictive values were determined at 1 year follow-up. Results were validated in 209 CSA patients. RESULTS: In both cohorts, 15% developed arthritis < 1 year. The multivariable Cox model selected presence of MCP-extensor peritendiniti

TREAT Early Arthralgia to Reverse or Limit Impending Exacerbation to Rheumatoid arthritis (TREAT EARLIER): a randomized, double-blind, placebo-controlled clinical trial protocol

Background: We present a study protocol for a randomized, double-blind, placebo-controlled trial that investigates the hypothesis if intervention

The forefoot in early rheumatoid arthritis: Anatomy, imaging and clinical aspects

Rheumatoid arthritis (RA) is a disease of the synovium that involves the small joints of hands and feet. The focus in RA-research, however, has primarily been on involvement of the hands. In this thesis we studied involvement of the forefoot. Throughout this thesis we found that synovitis in the rheumatoid foot affects more than just the joints. In an anatomic study we revealed that the tendon-sheaths in the forefoot also possess a synovial layer. Inflammation of this, detected by MRI that is referred to as tenosynovitis, was an important aspect of RA involvement in the forefoot. In addition, intermetatarsal bursae also detected by MRI are also often inflamed due to disease-involvement. These extra-articular involvements of the synovium that are found in RA importantly contribute to joint swelling and walking disability, and are therefore clinically relevant. Therefore we believe that it is essential for the clinician to pay attention to the forefeet of patients with RA to have a complete idea of disease activityChipsoft, Pfizer, UCB PharmaLUMC / Geneeskund

Improving the feasibility of MRI in clinically suspect arthralgia for prediction of rheumatoid arthritis by omitting scanning of the feet

Objectives. The use of MR-imaging is recommended for the early detection of RA. Next to the small joints of the hands, foot-joints are often involved. Therefore, imaging inflammation of the feet in addition to hands may be informative, but prolongs scan-time and leads to additional costs. We studied the value of MRI of the feet alone and complementary to MRI of the hands in patients with clinically suspect arthralgia (CSA).Methods. 357 consecutively included CSA patients underwent contrast-enhanced 1.5 T-MRI of hand (MCP2-5 and wrist) and foot (MTP1-5) joints at baseline. Scans were scored for synovitis, osteitis and tenosynovitis. After 1 year follow-up, the development of clinically apparent inflammatory arthritis (IA) was studied. Cox regression was performed and test characteristics were evaluated. Sensitivity analyses were performed for the outcome RA-development (2010-criteria).Results. MRI-detected tenosynovitis of the feet was associated with IA-development, independently from synovitis and osteitis hazard ratio (HR) (95%CI) 4.75 (2.38; 9.49), and independently from ACPA and CRP, HR 3.13 (1.48; 6.64). From all CSA patients, 11% had inflammation in hands and feet, 29% only in hands and 3% only in feet. In line with this finding, the addition of MRI-feet to MRI-hands did not increase the predictive accuracy; the sensitivity remained 77%, while the specificity decreased from 66% to 62%. Sensitivity analyses with RA development as outcome showed similar results.Conclusion. Tenosynovitis at the forefeet in CSA predicted IA and RA development. Addition of foot MRI to hand MRI did not increase the accuracy. Foot MRI can be omitted to reduce scan time and costs and increase the feasibility.Pathophysiology and treatment of rheumatic disease

The relation between physical joint examination and MRI-depicted inflammation of metatarsophalangeal joints in early arthritis

Background The relationship between physical joint examination (PE) and MRI-detected inflammation in early inflammatory arthritis has mostly been studied in the hands. Physical examination of MTP joints is considered difficult, and for these joints, this relationship is unknown. Therefore, we studied the concordance of PE with MRI inflammation in MTP joints. Metacarpophalangeal (MCP) joints were included for comparison. Methods One thousand seven hundred fifty-nine MTP(2-5) and 1750 MCP(2-5) joints of 441 consecutive patients with early arthritis underwent PE (for joint swelling) and MRI, all evaluated by two assessors. MRI was scored for synovitis, tenosynovitis, and osteitis (summed MRI inflammation). Synovial intermetatarsal bursae may enlarge upon inflammation and become palpable and were therefore also assessed. Analyses (frequencies, GEE) were performed on joint level. Results PE and MRI were concordant in 79% of MTP joints. Of 1606 non-swollen MTP joints, 83% showed no MRI inflammation and 17% showed subclinical MRI inflammation. Of 153 swollen MTP joints, 48% had MRI inflammation and 52% (79 MTP joints) did not. Of these 79 swollen MTP joints without MRI inflammation, 31 showed intermetatarsal bursitis and 48 joints had none of these MRI abnormalities (this concerned 31% of swollen MTP joints). MTP swelling was statistically independently associated with tenosynovitis (OR 2.21, 95% CI 1.1-4.3) and intermetatarsal bursitis (OR 2.91, 95% CI 1.8-4.8). MTP joints showed subclinical inflammation less often than MCP joints (17% vs. 34%, P < 0.001). Swollen MTP joints showed MRI inflammation less often than swollen MCP joints (48% vs. 88%, P < 0.001). Conclusions The absence of swelling of MTP joints in early arthritis is mostly accompanied by the absence of MRI-detected inflammation. Swollen MTP joints are, in addition to synovitis, also explained by tenosynovitis and intermetatarsal bursitis and partly unexplained by MRI. Their clinical relevance must be determined in longitudinal studies

Which inflamed tissues explain a positive metatarsophalangeal squeeze test? A large imaging study to clarify a common diagnostic procedure

Objectives The squeeze test of MTP joints is frequently used because it is easy and cheap. It is traditionally perceived as a test for synovitis. Besides classic intra-articular synovitis, also tenosynovitis and intermetatarsal bursitis (IMB) represent synovial inflammation, albeit juxta-articularly located. Both are frequently present in RA and occasionally in other arthritides. Therefore we hypothesized that tenosynovitis and IMB contribute to a positive MTP squeeze test. Methods A cross-sectional study design was used. A total of 192 early arthritis patients and 693 clinically suspect arthralgia patients underwent the MTP squeeze test and forefoot MRI at first presentation. MRI measurements in age-matched healthy controls were used to define positivity for synovitis, tenosynovitis and IMB. Logistic regression was used. Results In early arthritis patients, synovitis [odds ratio (OR) 4.8 (95% CI 2.5, 9.5)], tenosynovitis [2.4 (1.2, 4.7)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity. Synovitis [OR 3.2 (95% CI 1.4, 7.2)] and IMB [3.9 (1.7, 8.8)] remained associated in multivariable analyses. Of patients with a positive MTP squeeze test, 79% had synovitis or IMB: 12% synovitis, 15% IMB and 52% both synovitis and IMB. In clinically suspect arthralgia patients, subclinical synovitis [OR 3.0 (95% CI 2.0, 4.7)], tenosynovitis [2.7 (1.6, 4.6)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity, with the strongest association for synovitis in multivariable analysis. Of positive MTP squeeze tests, 39% had synovitis or IMB (10% synovitis, 15% IMB and 13% both synovitis and IMB). Conclusion Besides synovitis, IMB contributes to pain upon compression in early arthritis, presumably due to its location between MTP joints. This is the first evidence showing that MTP squeeze test positivity is not only explained by intra- but also juxta-articular inflammation.Pathophysiology and treatment of rheumatic disease