Dataset Information

Morning stiffness precedes the development of rheumatoid arthritis and associates with systemic and subclinical joint inflammation in arthralgia patients.

ABSTRACT:

Objectives

Morning stiffness (MS) is characteristic of RA and associates with markers of systemic and local inflammation in RA patients. In patients with arthralgia, MS is a cardinal symptom to recognize arthralgia at-risk for RA development [i.e. clinically suspect arthralgia (CSA)]. In CSA, MS is also assumed to reflect inflammation, but this has never been studied. Therefore we aimed to study whether MS in CSA patients is associated with systemic and subclinical joint inflammation.

Methods

A total of 575 patients presenting with CSA underwent laboratory investigations and contrast-enhanced 1.5 T MRI of the hand and forefoot (scored according to the Rheumatoid Arthritis MRI Score method). Associations of MS (duration ≥60 min) with the presence of subclinical joint inflammation (synovitis, tenosynovitis and osteitis) and increased CRP (≥5 mg/l) were determined with logistic regression. Additionally, the effect of MS duration (≥30, ≥60 and ≥120 min) was studied.

Results

A total of 195 (34%) CSA patients experienced MS. These patients more often had subclinical synovitis [34% vs 21%; odds ratio (OR) 1.95 (95% CI 1.32, 2.87)], subclinical tenosynovitis [36% vs 26%; OR 1.59 (95% CI 1.10, 2.31)] and increased CRP [31% vs 19%; OR 1.93 (95% CI 1.30, 2.88)] than patients without MS. In multivariable analyses, subclinical synovitis [OR 1.77 (95% CI 1.16, 2.69)] and CRP [OR 1.78 (95% CI 1.17-2.69)] remained independently associated with MS. In CSA patients who later developed RA, and thus in retrospect were 'pre-RA' at the time of CSA, MS was more strongly associated with subclinical synovitis [OR 2.56 (95% CI 1.04, 6.52)] and CRP [OR 3.86 (95% CI 1.45, 10.24)]. Furthermore, associations increased with longer MS durations.

Conclusion

Inflammation associates with MS in the CSA phase that preceded clinical arthritis. These results increase our understanding of MS when assessing arthralgia in clinical practice.

SUBMITTER: Krijbolder DI

PROVIDER: S-EPMC9071544 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Morning stiffness precedes the development of rheumatoid arthritis and associates with systemic and subclinical joint inflammation in arthralgia patients.

Krijbolder Doortje I DI Wouters Fenne F van Mulligen Elise E van der Helm-van Mil Annette H M AHM

Rheumatology (Oxford, England) 20220501 5

<h4>Objectives</h4>Morning stiffness (MS) is characteristic of RA and associates with markers of systemic and local inflammation in RA patients. In patients with arthralgia, MS is a cardinal symptom to recognize arthralgia at-risk for RA development [i.e. clinically suspect arthralgia (CSA)]. In CSA, MS is also assumed to reflect inflammation, but this has never been studied. Therefore we aimed to study whether MS in CSA patients is associated with systemic and subclinical joint inflammation.<h4 ...[more]

PMID: 34401906

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Project description:Background and objectivesAlthough morning stiffness has long been recognized as a characteristic feature of rheumatoid arthritis (RA), it is no more included in the 2010 ACR/EULAR Classification Criteria or in the current major instruments for evaluating disease activity of RA. In this cross-sectional study, we aimed to determine the independent value and the optimal measurement of morning stiffness by clarifying the associations between morning stiffness and synovial inflammation.Patients and methodsWe enrolled 76 consecutive RA patients who underwent musculoskeletal ultrasound examination and agreed to participate in the study. In addition to asking the duration of morning stiffness, we asked patients to complete a diagram which represents the time course of their morning stiffness in the dominant hand. Based on this diagram, we calculated the severity and the diurnal improvement of morning stiffness. We also determined the activity of intra-articular synovitis in 11 joints and tenosynovitis in 8 tendons/tendon compartments in the same hand by using power Doppler (PD) ultrasound with a semiquantitative score (0-3).ResultsFor intra-articular synovitis, swollen/tender joint counts more strongly correlated with total PD scores (ρ = 0.379-0.561, p ≤ 0.001) than did any parameters of morning stiffness (ρ = 0.217-0.314, p = 0.006-0.021). For tenosynovitis, however, the severity on awakening and the improvement of morning stiffness more strongly correlated with total PD scores (ρ = 0.503-0.561, p < 0.001) than did swollen/tender joint counts (ρ = 0.276-0.388, p = 0.001-0.016). Multivariate analyses identified the severity on awakening and the improvement but not the duration of morning stiffness as factors that independently associate with the total tenosynovial PD score.ConclusionsOur data demonstrate a pathophysiological link between morning stiffness and tenosynovitis and also give an insight into the optimal measurement of morning stiffness. Our data support an independent value of evaluating morning stiffness in the management of RA.

Project description:IntroductionIt 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.MethodsWe 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.ResultsMRI 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.ConclusionSubclinical 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.

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Dataset Information

Morning stiffness precedes the development of rheumatoid arthritis and associates with systemic and subclinical joint inflammation in arthralgia patients.

Objectives

Methods

Results

Conclusion

Publications

Morning stiffness precedes the development of rheumatoid arthritis and associates with systemic and subclinical joint inflammation in arthralgia patients.

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