Objectives: Identifying patients that will develop RA among those presenting with undifferentiated arthritis (UA) remains a clinical dilemma. Although MRI is helpful according to EULAR... Show moreObjectives: Identifying patients that will develop RA among those presenting with undifferentiated arthritis (UA) remains a clinical dilemma. Although MRI is helpful according to EULAR recommendations, this has only been determined in UA patients not fulfilling 1987 RA criteria, while some of these patients are currently considered as RA because they fulfil the 2010 criteria. Therefore, we studied the predictive value of MRI for progression to RA in the current UA population, i.e. not fulfilling RA classification criteria (either 1987 or 2010 criteria) and not having an alternate diagnosis. Additionally, the value of MRI was studied in patients with a clinical diagnosis of UA, regardless of the classification criteria. Methods: Two UA populations were studied: criteria-based UA as described above (n = 405) and expert-opinion-based UA (n = 564), i.e. UA indicated by treating rheumatologists. These patients were retrieved from a large cohort of consecutively included early arthritis patients that underwent contrast-enhanced MRI scans of hand and foot at baseline. MRIs were scored for osteitis, synovitis and tenosynovitis. Patients were followed for RA development during the course of 1 year. Test characteristics of MRI were determined separately for subgroups based on joint involvement and autoantibody status. Results: Among criteria-based UA patients (n = 405), 21% developed RA. MRI-detected synovitis and MRI-detected tenosynovitis were predictive for progression to RA. MRI-detected tenosynovitis was independently associated with RA progression (odds ratio (OR) 2.79; 95% CI 1.40, 5.58), especially within ACPA-negative UA patients (OR 2.91; 95% CI 1.42, 5.96). Prior risks of RA development for UA patients with mono-, oligo- and polyarthritis were 3%, 19% and 46%, respectively. MRI results changed this risk most within the oligoarthritis subgroup: positive predictive value was 27% and negative predictive value 93%. Similar results were found in expert-opinion-based UA (n = 564). Conclusion: This large cohort study showed that MRI is most valuable in ACPA-negative UA patients with oligoarthritis; a negative MRI could aid in preventing overtreatment. Show less
Sidhu, N.; Wouters, F.; Niemantsverdriet, E.; Helm-van Mil, A.H.M. van der 2021
Objectives: New onset undifferentiated large joint inflammatory arthritis can be diagnostically challenging. It is unknown how often these patients progress to RA, and how they can be identified at... Show moreObjectives: New onset undifferentiated large joint inflammatory arthritis can be diagnostically challenging. It is unknown how often these patients progress to RA, and how they can be identified at first presentation. We assessed clinical and serological features associated with RA development in patients with an undifferentiated mono- or oligo-articular large joint arthritis, and with keen interest in whether an MRI of the small joints of the hand and foot would aid diagnosis. Methods: Leiden Early Arthritis Clinic includes 4018 patients; this prospective study follows 221 consecutively included patients with new onset undifferentiated large joint arthritis. Baseline clinical data and serology were obtained. Forty-five patients had MRIs (hand and foot). MRIs were scored according to the OMERACT RAMRIS. Univariable and multivariable logistic regression were assessed. Test characteristics, predictive values and net reclassification index (NRI) for RA were determined. Results: Patients mostly presented with knee or ankle mono-arthritis. During the 12 months' follow-up 17% developed RA. Autoantibody positivity (ACPA and/or RF) and MRI-detected synovitis in hands and feet were independently associated with RA development in multivariable analyses [odds ratio 10.29 (P = 0.014) and 7.88 (P = 0.017), respectively]. Positive predictive value of autoantibodies, MRI-detected synovitis and combination of both features was 63%, 55% and 100%, respectively. The addition of MRI-detected synovitis to autoantibody status improved diagnostic accuracy (NRI 18.1%). Conclusion: In patients presenting with undifferentiated large joint arthritis, 17% will develop RA. Autoantibody positivity and subclinical synovitis are independent predictors. The data suggest MRI of small joints is beneficial for early identification of RA in large joint arthritis. Show less
Matthijssen, X.M.E.; Wouters, F.; Sidhu, N.; Niemantsverdriet, E.; Helm-van Mil, A. van der 2021
Objectives Clinically evident tenosynovitis can be seen in established rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA,... Show moreObjectives Clinically evident tenosynovitis can be seen in established rheumatoid arthritis (RA). Imaging research has recently shown that tenosynovitis at small joints occurs in early RA, contributes to typical RA symptoms (including joint swelling) and is infrequent in healthy controls. Imaging-detectable tenosynovitis is often not recognisable at joint examination, hence its prevalence can therefore be underestimated. We hypothesised that if MRI-detectable tenosynovitis is a true RA feature, the sensitivity for RA is high, in both anti-citrullinated protein antibodies (ACPA)-positive and ACPA-negative RA, and lower in other diseases that are associated with enthesitis (such as spondyloarthritis (SpA) and psoriatic arthritis (PsA)). So far, no large MRI study addressed these questions. Methods Consecutive patients with early arthritis (n=1211) from one healthcare region underwent contrast-enhanced 1.5T MRI of hand and foot at diagnosis. MRIs were scored for synovitis and tenosynovitis by two readers blinded for clinical data. All included patients with ACPA-positive RA (n=250), ACPA-negative RA (n=282), PsA (n=88), peripheral SpA (n=24), reactive arthritis (n=30) and self-limiting undifferentiated arthritis (UA; n=76) were studied. Sensitivity was calculated. Results The sensitivity of tenosynovitis in RA was 85%; 88% for ACPA-positive RA and 82% for and ACPA-negative RA (p=0.19). The sensitivity for RA was significantly higher than for PsA (65%; p=0.001), SpA (53%; p<0.001), reactive arthritis (36%; p<0.001) and self-limiting UA (42%; p<0.001). The observed sensitivity of MRI synovitis was 91% in RA and ranged from 83% to 54% in other groups. Conclusions MRI-detected tenosynovitis has a high sensitivity for early ACPA-positive and ACPA-negative RA. This supports that both juxta-articular (tenosynovitis) and intra-articular synovial involvement is characteristic of RA. Show less
Matthijssen, X.M.E.; Wouters, F.; Sidhu, N.; Helm-van Mil, A.H.M. van der 2021
Objective Fatigue in rheumatoid arthritis (RA) is hypothesised to be caused by inflammation. Still similar to 50% of the variance of fatigue in RA cannot be explained by the Disease Activity Score ... Show moreObjective Fatigue in rheumatoid arthritis (RA) is hypothesised to be caused by inflammation. Still similar to 50% of the variance of fatigue in RA cannot be explained by the Disease Activity Score (DAS), nor by background or psychological factors. Since MRI can detect joint inflammation more sensitively than the clinical joint counts as incorporated in the DAS, we hypothesised that inflammation detected by MRI could aid in explaining fatigue in RA at diagnosis and during the follow-up.Methods 526 consecutive patients with RA were followed longitudinally. Fatigue was assessed yearly on a Numerical Rating Scale. Hand and foot MRIs were performed at inclusion, after 12 and 24 months in 199 patients and were scored for inflammation (synovitis, tenosynovitis and osteitis combined). We studied whether patients with RA with more MRI-inflammation were more fatigued at diagnosis (linear regression), whether the 2-year course of MRI-inflammation associated with the course of fatigue (linear mixed models) and whether decrease in MRI-inflammation in year 1 associated with subsequent improvement in fatigue in year 2 (cross-lagged models). Similar analyses were done with DAS as inflammation measure.Results At diagnosis, higher DAS scores were associated with more severe fatigue (p<0.001). However, patients with more MRI-inflammation were not more fatigued (p=0.94). During 2-year follow-up, DAS decrease associated with improvement in fatigue (p<0.001), but MRI-inflammation decrease did not (p=0.96). DAS decrease in year 1 associated with fatigue improvement in year 2 (p=0.012), as did MRI-inflammation decrease (p=0.039), with similar effect strength.Conclusion Sensitive measurements of joint inflammation did not explain fatigue in RA at diagnosis and follow-up. This supports the concept that fatigue in RA is partly uncoupled from inflammation. Show less
