Background/Purpose: Psychosocial factors have been associated with rheumatoid arthritis (RA) outcomes, but have not been well characterized in the early development of RA. We examined the associations of perceived stress, measured by the Perceived Stress Scale-14 (PSS), with joint signs in an anti-cyclic citrullinated peptide (CCP) antibody positive population.

Methods: At community health fairs from 2014-2018, 56 subjects without previously diagnosed RA were found CCP positive through the CCP3 test (Inova). Subjects were recruited into a prospective cohort, and at their immediate post-health fair research visit (baseline) 14 had at least 1 tender joint, 7 had at least 1 swollen joint based on a rheumatologist exam, and 2 were classified as RA by 2010 ACR/EULAR Criteria only. The PSS responses were summed to obtain a total score, in which a higher score indicates greater perceived stress. Additionally, responses on the PSS underwent an explanatory factor analysis which suggested two meaningful factors: 1) perception of control, named ‘helplessness’ and 2) ability to cope with stress, named ‘self-efficacy.’ These factors align with other studies suggesting a two-factor structure for the PSS. T-tests and multivariable logistic regression assessed the associations of PSS-related scores with joint signs.

Results: Individuals with at least 1 tender joint compared to those without a tender joint have a higher total PSS score, higher helplessness or poor self-efficacy sub-scores (Table). A one point increase in the total PSS score was associated with a 12% increase in the odds of having a tender joint. Similarly, increases in the helplessness and self-efficacy sub-scores were associated with a 16% and 21% increase in the odds of tender joints, respectively. A sensitivity analysis removing the two individuals with newly classified RA at their baseline visit found that the absolute differences in the mean total PSS and self-efficacy scores remained, while ORs were slightly attenuated and not significant.

Conclusion: In a cohort of untreated CCP positive individuals, we found a significant association between higher perceived stress and joint tenderness. The ability to cope or control stressors may be an important component of the evolution from CCP positivity to joint signs that could indicate early inflammatory arthritis even if a swollen joint consistent with clear inflammatory arthritis is not seen. Further longitudinal study is needed to better understand the direction of the relationships between these factors, underlying immune dysregulation and transitions to classified RA. This is important because a relationship between perceived stress and clinical signs of disease in individuals at-risk for developing RA may support the incorporation of stress-targeted therapy management and other global health improvement activities, with the potential for increased quality of life.