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. 2018 Nov 21;20(1):260.
doi: 10.1186/s13075-018-1756-z.

Sequence of joint tissue inflammation during rheumatoid arthritis development

R M Ten Brinck  1 , H W van Steenbergen  2 , A H M van der Helm-van Mil  2   3
Affiliations

Sequence of joint tissue inflammation during rheumatoid arthritis development

R M Ten Brinck et al. Arthritis Res Ther. .

Abstract

Objective: Subclinical 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.

Methods: Patients 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.

Results: At 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.

Conclusion: Increased 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.

Keywords: Imaging; Inflammation; Rheumatoid arthritis.

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Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

The study was approved by the medical ethics committee of the Leiden University Medical Centre, which is named Commissie Medische Ethiek (CME), under Ethics Approval Number NL38832.058.11. All patients signed informed consent.

Consent for publication

All authors consented for publication of the manuscript.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of selection of rheumatoid arthritis (RA) patients studied from the total CSA cohort. Patient characteristics of the different groups are provided in Additional file 1 (Table S2). DMARD disease-modifying antirheumatic drug, MR magnetic resonance, MRI magnetic resonance imaging
Fig. 2
Fig. 2
Magnetic resonance imaging (MRI) features of joint inflammation and erosions in patients that developed rheumatoid arthritis (RA). MRI was performed at presentation with arthralgia and at diagnosis of RA. MRIs were not made in the asymptomatic phase but the course of local inflammation before presentation with arthralgia was estimated by comparisons with age-matched symptom-free persons (1:2 ratio to patients). Since these data were not measured longitudinally, data are presented in dashed lines. *p < 0.05. CSA clinically suspect arthralgia
Fig. 3
Fig. 3
Magnetic resonance imaging (MRI) features of joint inflammation and erosions in patients that developed rheumatoid arthritis (RA) stratified for anti-citrullinated protein antibody (ACPA) status. MRI was performed at presentation with arthralgia and at diagnosis of RA. MRIs were not made in the asymptomatic phase but the course of local inflammation before presentation with arthralgia was estimated by comparisons with age-matched symptom-free persons (1:2 ratio to patients). Since these data were not measured longitudinally, data are presented in dashed lines. *p < 0.05 by paired t test. CSA clinically suspect arthralgia
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