Clinical Joint Tenderness in First-Nations First-Degree Relatives of Rheumatoid Arthritis Patients: Examining Factors Associated with Functional Disability and Progression to RA

Abstract

Objectives Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting synovial joints. Prior to the clinical onset of arthritis, autoantibodies and non-specific joint symptoms often appear in the absence of joint swelling. We previously found that functional disability correlates with anti-citrullinated protein antibodies (ACPA) and future RA development. Here, we examine the role of joint tenderness on physical exam in a cohort of First Nations first-degree relatives (FDRs) of RA patients in Manitoba. [1,2] Methods Tender joint counts from a 66-joint assessment were obtained at the inception visit through clinical examination. Serologic data (RF and ACPA) and patient-reported measures of function, pain, and overall wellness were also collected. Results 624 FDR baseline joint tenderness assessments and questionnaires were analyzed. Among these, 211 FDR (33.8%) had at least 1 tender joint on physical exam. Clinical joint tenderness was more common in females (p=0.04), individuals with diabetes (Figure 1A), (p=0.03), those living in urban areas (p<0.0001, compared to rural) and participants reporting ≥30 minutes of morning stiffness (p=0.003). Self-reported joint tenderness in the hands was significantly higher in those who reported hand pain (Figure 1B), (p < 0.0001). Joint tenderness was also higher in individuals who reported functional disability based on the health assessment questionnaire (Figure 1C), (p < 0.0001). Clinical joint tenderness correlated with self-reported fatigue (r = 0.28, p < 0.0001), pain (r = 0.33, p < 0.0001), overall wellness (r = 0.25, p < 0.0001) scores. The presence of ACPA was not associated with joint tenderness (p = 0.82). In contrast, RF titers demonstrated a positive correlation with the total number of tender joints (r = 0.11, p = 0.005) and there was a trend toward increased joint tenderness on examination in RF positive individuals (p=0.15). During follow-up, 20 participants progressed to clinical RA, as previously reported, progressors were younger (p=0.004) and had higher baseline ACPA titers (Figure 1D), (p=0.02). 63.2% of progressors exhibited clinically significant tenderness in at least 1 hand joint however, no individual joints demonstrated a statistically significant difference in tenderness between progressors and non-progressors. Conclusion Joint tenderness is common among First Nations FDRs of RA patients and is linked to worse functional and wellness outcomes, particularly in women, diabetics, and urban residents. These findings underscore the need for early identification and monitoring in high-risk groups. A better understanding of how self-reported symptoms and exam findings relate to future RA risk may improve risk stratification and early intervention. References [1.] Smolik I. J Rheumatol 2013;40:818-24. [2.] Wiens D. J Rheumatol 2024;51:654-62.