Differences in the symptomatic phase preceding ACPA-positive and ACPA-negative RA: a longitudinal study in arthralgia during progression to clinical arthritis

Burgers, L.E.; Steenbergen, H.W. van; Brinck, Robin M. ten; Huizinga, Tom W J; Mil, Annette H M van der Helm-van

doi:10.1136/annrheumdis-2017-211325

Cited by 60 publications

(49 citation statements)

References 16 publications

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“…UA is, as shown, a population that is mostly autoantibody negative. The notion that ACPA-negative patients have a lower frequency of foot involvement is supported by a recent finding done at symptom level in patients with arthralgia suspicious for progression to RA; ACPA-negative patients less often had symptoms in the lower extremities than ACPA-positive patients [19]. In the UA patients studied here, the frequency of foot involvement at joint examination was lower than hand involvement (lower number of tender and swollen joints) (Table 1), and also, MR-detected tenosynovitis of the feet was less frequent than in the hand (21% versus 57% on group level).…”

Section: Discussionmentioning

confidence: 82%

What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?

et al. 2019

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Background: MRI-detected subclinical joint inflammation in the hand joints of patients with undifferentiated arthritis (UA) predicts progression to rheumatoid arthritis (RA). It is unknown if adding MRI of the foot increases predictive accuracy compared to the hand alone. Methods: 1.5-T contrast-enhanced MRI of the unilateral foot (MTP-1-5) and hand (MCP-2-5 and wrist) was performed in 123 patients presenting with UA (not fulfilling the 2010 RA criteria) and scored for bone marrow edema (BME), synovitis and tenosynovitis. Symptom-free controls (n = 193) served as a reference for defining an abnormal MRI. Patients were followed for RA development ≤ 1 year, defined as fulfilling the classification criteria or initiation of disease-modifying antirheumatic drugs because of the expert opinion of RA. The added predictive value of foot MRI to hand MRI was evaluated. Results: Fifty-two percent developed RA. Foot tenosynovitis was predictive (OR 2.55, 95% CI 1.01-6.43), independent of BME and synovitis (OR 3.29, 95% CI 1.03-10.53), but not independent of CRP and number of swollen joints (OR 2.14, 95% CI 0.77-5.95). Hand tenosynovitis was also predictive independent of BME and synovitis (OR 3.99, 95% CI 1.64-9.69) and independent of CRP and swollen joints (OR 2.36, 95% CI 1.04-5.38). Adding foot tenosynovitis to hand tenosynovitis changed the sensitivity from 72 to 73%, specificity from 59 to 54% and AUC from 0.66 to 0.64; the net reclassification index was − 3.5. Conclusion: MRI-detected tenosynovitis of the foot predicts progression to RA. However, adding MRI of the foot does not improve the predictive accuracy compared to MRI of the hand alone. In view of cost reduction, the performance of foot MRI for prognostic purposes in UA can be omitted.

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Section: Discussionmentioning

confidence: 82%

What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?

et al. 2019

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“…Studying the preclinical phase of seronegative rheumatoid arthritis poses a unique and important challenge now beginning to be addressed [ 23 ▪ ]. Of interest, patients with this subgroup of disease typically describe a shorter symptom duration when they present with arthritis, but with evidence for more prominent IL-6-mediated lymphocyte activation in the periphery, compared with their seropositive counterparts [ 24 , 25 ], consistent with a more ‘explosive’, pro-inflammatory component to the natural history of seronegative disease (Fig.…”

Section: Cytokines As Coordinators Of Pre-clinical Rheumatoid Arthritmentioning

confidence: 99%

What are the dominant cytokines in early rheumatoid arthritis?

Ridgley

Anderson

Pratt

2018

Current Opinion in Rheumatology

127

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Purpose of reviewRheumatoid arthritis is a systemic disease of evolving immune dysregulation that culminates in joint destruction and disability. The principle by which pro-inflammatory cytokines may be therapeutically targeted to abrogate disease is well established, but has yet to translate into reliable cures for patients. Emerging insights into cytokine-mediated pathobiology during rheumatoid arthritis development are reviewed, and their implications for future treatment strategies considered.Recent findingsAccumulating data highlight cytokine perturbations before the clinical onset of rheumatoid arthritis. Some of these have now been linked to the arthritogenic activation of autoantibodies and associated pain and bone destruction in affected joints. These observations suggest cytokines may trigger the transition from systemic immunity to arthritis. Cytokine exposure could furthermore ‘prime’ synovial stromal cells to perpetuate a dominant pro-inflammatory environment. By facilitating cross-talk between infiltrating immune cells and even sustaining ectopic lymphoid structure development in some cases, cytokine interplay ultimately underpins the failure of arthritis to resolve.SummarySuccessful therapeutic stratification will depend upon an increasingly sophisticated appreciation of how dominant players amongst cytokine networks vary across time and anatomical space during incipient rheumatoid arthritis. The prize of sustained remission for all patients justifies the considerable effort required to achieve this understanding.

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“…ACPA-positive and ACPA-negative disease have different risk factors, presumed differences in pathogenesis and known dissimilarities in speed in progressing from CSA to IA. 14 However despite these differences, the observations on joint level on the relation between subclinical inflammation in the CSA phase and clinical synovitis in the IA phase were roughly similar in both groups. Larger studies validating these findings are required.…”

Section: Discussionmentioning

confidence: 87%

Development of clinically apparent synovitis: a longitudinal study at the joint level during progression to inflammatory arthritis

2018

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IntroductionSubclinical inflammation, detected by MRI, in patients with arthralgia is predictive for development of inflammatory arthritis (IA). However, within patients that develop IA, the course of inflammation at the joint level during this transition is unknown. This longitudinal study assessed progression of inflammation at the joint level.Methods350 joints (unilateral metacarpophalangeals (MCPs), wrist, metatarsophalangeal (MTP) joints) of 35 patients presenting with clinically suspect arthralgia (CSA) that progressed to IA were studied at presentation with CSA and subsequently when clinical synovitis was first identified at joint examination (median time interval 17 weeks). At both time points, subclinical inflammation (bone marrow oedema, synovitis, tenosynovitis) was evaluated with MRI and joint examination was performed.ResultsAt presentation with CSA, 71 joints showed subclinical inflammation. During progression to IA, 20% of these joints had resolution of inflammation, 60% had persistent inflammation and 20% progressed to clinical synovitis. Of all joints that had developed clinical synovitis (n = 45), no prior subclinical inflammation was detected in 69%. Similar results were observed for anticitrullinated protein antibodies (ACPA)-positive and ACPA-negative patients.ConclusionsThis longitudinal study demonstrated moderate correlations between joints with subclinical inflammation and joints that developed clinical synovitis. These data imply that IA development is a more systemic rather than a locally outgrowing process.

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Differences in the symptomatic phase preceding ACPA-positive and ACPA-negative RA: a longitudinal study in arthralgia during progression to clinical arthritis

Abstract: This study is the first showing that ACPA-positive and ACPA-negative patients have clinical differences in the symptomatic phase preceding clinical arthritis. This contributes to the notion that ACPA-positive and ACPA-negative RA develop differently.

Cited by 60 publications

References 16 publications

What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?

What is the additional value of MRI of the foot to the hand in undifferentiated arthritis to predict rheumatoid arthritis development?

What are the dominant cytokines in early rheumatoid arthritis?

Development of clinically apparent synovitis: a longitudinal study at the joint level during progression to inflammatory arthritis

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