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Home » Topics » Rheumatoid Arthritis
Publish Date August 9, 2022
INCREASED FATIGUE OBSERVED IN PROGRESSIVE CLINICALLY SUSPECT ARTHRALGIA
Sheila Jacobs
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It is possible that immunologic pathways negatively affect long-term changes in
brain functioning in areas that involve fatigue. Credit: Getty Images
In patients with clinically suspect arthralgia (CSA), fatigue increases
gradually toward the development of rheumatoid arthritis (RA), according to
study findings published in Joint Bone Spine.
Researchers conducted a longitudinal study in the Netherlands among patients
with CSA who were consecutively included in the Leiden University CSA cohort and
had at least 1 year of follow-up. The CSA cohort that comprised patients who
have arthralgia of the small joints for less than 1 year that is considered
suspicious for progression to RA.
All patients from the CSA cohort were followed for 2 years for the development
of RA, which was confirmed by the presence of joint swelling during physical
examination by a rheumatologist. Follow-up visits occurred at 4 months, 12
months, 24 months, and more regularly if any increased musculoskeletal symptoms
developed between follow-up visits. All patients in the CSA cohort were not
treated with any disease-modifying antirheumatic drugs (DMARDs), including
corticosteroids, during follow-up.
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A total of 600 patients with CSA were followed for the development of RA.
Another 710 patients with early RA were investigated at diagnosis. Fatigue,
which was evaluated at every visit, was rated on a scale of 0 to 100.
Inflammation was measured with use of the Disease Activity Score in 44 joints
score and C-reactive protein level (DAS44-CRP. Analyses were stratified by
anticitrullinated protein antibody (ACPA) status.
Results of the study showed that in 88 patients with CSA who developed RA,
prearthritis fatigue levels increased gradually over time by 7 points per year
(95% CI, -2 to 16) toward a mean of 48 (95% CI, 41-55) at the development of RA.
Patients with CSA who did not develop RA demonstrated decreasing levels of
fatigue by 4 points per year after baseline (95% CI, -6 to -3; P <.001).
At the onset of CSA, inflammation was associated with fatigue (β=18, which
translates to 18 points more fatigue per point increase in DAS score; P <.01).
This association was stronger than at diagnosis of RA (β=5; P <.001).
Stratified analyses according to ACPA status showed that fatigue in patients who
were both ACPA-negative and ACPA-positive increased to the same extent toward
the development of RA. Patients who were ACPA-negative, however, were more
fatigued than those who were ACPA-positive both before and at the development of
RA (mean difference in fatigue, 13; 95% CI, 1-24; P <.05).
Additionally, fatigue was not significantly associated with inflammation in
patients with ACPA-negative CSA, whereas inflammation and fatigue were
significantly associated in participants with ACPA-positive CSA. The link
between inflammation and fatigue in patients with ACPA-positive CSA was stronger
than in patients with ACPA-positive RA (β=25 and β=9, respectively).
Limitations of the study include the absence of a validated inflammation score
in patients with “pre-RA.” Observed associations between inflammation and
fatigue do not prove causation. The follow-up duration of 2 years may be
insufficient to identify all patients with CSA who converted to RA.
The study authors conclude that the findings from the current study suggest that
DMARD treatment in patients with CSA may decrease the burden of fatigue more
effectively compared with the effect of DMARDs in patients with classified RA,
particularly those who are ACPA-positive. This remains as a topic for future
research.
REFERENCE
Khidir SJH, Wouters F, van der Helm-van Mil AHM, Mulligen EV. The course of
fatigue during the development of rheumatoid arthritis and its relation with
inflammation: a longitudinal study. Joint Bone Spine. Published online June 28,
2022. doi:10.1016/j.jbspin.2022.105432
TOPICS:
Arthralgia Rheumatoid Arthritis
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