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Is joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis explained by subclinical inflammation? A cross-sectional MRI study.

ABSTRACT: Objectives:The development of RA includes a phase of arthralgia preceding clinical arthritis. The aetiology of symptoms of arthralgia is unclear. Since subclinical joint inflammation is expected to be causally related to pain, we aimed to study associations between subclinical MRI-detected inflammation and pain in patients with arthralgia suspicious for progression to RA. Methods:Unilateral MRIs of the wrist, MCP (2-5) and MTP (1-5) joints of 325 patients who fulfilled the EULAR definition of arthralgia suspicious for progression to RA were scored by two readers on subclinical inflammation (synovitis, bone marrow oedema and tenosynovitis). Associations between MRI-detected inflammation and overall pain severity at patient level (measured using the visual analogue scale), as well as with local joint tenderness, were studied. Analyses were stratified for ACPA. Results:At patient level, synovitis (? = 0.10, P = 0.048) and tenosynovitis (? = 0.11, P = 0.026) associated with the visual analogue scale pain. Of the 1620 imaged joints, 447 (28%) were tender. MRI-detected synovitis associated independently with joint tenderness in all patients (odds ratio 1.74, P < 0.001), and in the ACPA-negative stratum (odds ratio 1.96, P < 0.001). In the ACPA-positive stratum only bone marrow oedema (osteitis) was independently associated with tenderness (odds ratio 2.39, P = 0.005). Sensitivity analyses in patients who developed inflammatory arthritis during follow-up (n = 61) revealed similar associations. Subclinical inflammation was present in 51% of tender joints and 39% of non-tender joints. Conclusion:In patients with arthralgia suspicious for progression to RA, MRI-detected subclinical inflammation is associated with overall pain and local joint tenderness. However, the association is partial, indicating that subclinical inflammation is not the sole explanation of the arthralgia.

SUBMITTER: Burgers LE

PROVIDER: S-EPMC6319603 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Is joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis explained by subclinical inflammation? A cross-sectional MRI study.

Burgers Leonie E LE Ten Brinck Robin M RM van der Helm-van Mil Annette H M AHM

Rheumatology (Oxford, England) 20190101 1

<h4>Objectives</h4>The development of RA includes a phase of arthralgia preceding clinical arthritis. The aetiology of symptoms of arthralgia is unclear. Since subclinical joint inflammation is expected to be causally related to pain, we aimed to study associations between subclinical MRI-detected inflammation and pain in patients with arthralgia suspicious for progression to RA.<h4>Methods</h4>Unilateral MRIs of the wrist, MCP (2-5) and MTP (1-5) joints of 325 patients who fulfilled the EULAR d ...[more]

PMID: 30137540

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Project description:INTRODUCTION: It is known that anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) has a preclinical phase. Whether this phase is also present in ACPA-negative RA is unknown. To determine this, we studied ACPA-negative arthralgia patients who were considered prone to progress to RA for local subclinical inflammation observed on hand and foot magnetic resonance imaging (MRI) scans. METHODS: We studied a total of 64 ACPA-negative patients without clinically detectable arthritis and with arthralgia of the small joints within the previous 1 year. Because of the character of the patients' symptoms, the rheumatologists considered these patients to be prone to progress to RA. For comparisons, we evaluated 19 healthy, symptom-free controls and 20 ACPA-negative RA patients, who were identified according to the 1987 American Rheumatism Association criteria. All participants underwent MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal joints. Synovitis and bone marrow oedema (BME) were scored according to the OMERACT rheumatoid arthritis magnetic resonance imaging scoring system, and the scores were summed to yield the 'MRI inflammation score'. Scores were compared between groups. Among the ACPA-negative arthralgia patients, MRI inflammation scores were related to C-reactive protein (CRP) levels and the tenderness of scanned joints. RESULTS: MRI inflammation scores increased progressively among the groups of controls and ACPA-negative arthralgia and RA patients (median scores?=?0, 1 and 10, respectively; P?<?0.001). The MRI inflammation scores of ACPA-negative arthralgia patients were significantly higher than those of controls (P?=?0.018). In particular, the synovitis scores were higher in ACPA-negative arthralgia patients (P?=?0.046). Among the ACPA-negative arthralgia patients, inflammation was observed predominantly in the wrist (53%). The synovitis scores were associated with CRP levels (P?=?0.007) and joint tenderness (P?=?0.026). Despite the limited follow-up duration, five patients developed clinically detectable arthritis. These five patients had higher scores for MRI inflammation (P?=?0.001), synovitis (P?=?0.002) and BME (P?=?0.003) compared to the other patients. CONCLUSION: Subclinical synovitis was observed in the small joints of ACPA-negative arthralgia patients, and especially in patients whose conditions progressed to clinically detectable arthritis. This finding suggests the presence of a preclinical phase in ACPA-negative RA. Further longitudinal studies of these lesions and patients are required to confirm this hypothesis.

Project description:ObjectiveSubclinical joint inflammation in patients with arthralgia is predictive for progression to rheumatoid arthritis (RA). However, the time course of progression for bone marrow edema (osteitis), synovitis, and/or tenosynovitis is unsettled. This longitudinal study assessed the course of magnetic resonance imaging (MRI)-detected subclinical joint inflammation during progression to RA.MethodsPatients that progressed from clinically suspect arthralgia (CSA) to RA underwent 1.5-T MRI of the metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints at presentation with arthralgia and at first identification of synovitis assessed through physical examination (n?=?31). MRIs were evaluated for osteitis, synovitis, tenosynovitis, and erosions by two readers, blinded for clinical data and order in time. To estimate changes in MRI scores between the asymptomatic state and CSA onset, scores of MRI features at CSA baseline were compared with scores from age-matched symptom-free persons.ResultsAt presentation with CSA, synovitis and tenosynovitis scores were higher than scores from age-matched symptom-free persons (p?=?0.004 and p?=?0.001, respectively). Anti-citrullinated protein antibody (ACPA)-positive arthralgia patients also had increased osteitis scores (p?=?0.04). Median duration between presentation with arthralgia and RA development was 17 weeks. During progression to RA, synovitis and osteitis increased significantly (p?=?0.001 and p?=?0.036, respectively) in contrast to tenosynovitis and erosion scores. This pattern was similar in both ACPA subsets, although statistical significance was reached for synovitis and osteitis in ACPA-negative but not ACPA-positive RA.ConclusionIncreased tenosynovitis and synovitis scores at CSA onset and the increase in synovitis and osteitis during progression to RA suggest an 'outside-in' temporal relationship of arthritis development, in particular for ACPA-negative RA. For ACPA-positive RA, further studies are needed.

Dataset Information

Is joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis explained by subclinical inflammation? A cross-sectional MRI study.

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Is joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis explained by subclinical inflammation? A cross-sectional MRI study.

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