Abstract

Background:While the central role of bone erosions in the pathogenesis and diagnosis of patients with rheumatoid arthritis (RA) is widely recognized, their prevalence, pattern, and relationship with subclinical synovitis in individuals at-risk of RA (positive autoantibodies without clinical arthritis) is not well understood.Objectives:To investigate, in individuals at-risk of RA, the prevalence and distribution of ultrasound (US) bone erosions, their correlation with subclinical synovitis at joint level, and their association with the development of inflammatory arthritis (IA).Methods:Baseline US scans of 2ndgeneration anti-cyclic citrullinated peptide (CCP) positive at-risk subjects with musculoskeletal symptoms (without clinical arthritis) taking part in the Leeds CCP study were analyzed. The presence of bone erosions was evaluated in the classic sites for RA damage: the II and V metacarpophalangeal (MCP) joints, and the V metatarsophalangeal (MTP) joints1. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1 + power Doppler signal ≥12. Only subjects with ≥1 follow-up visit were included in the progression analysis (n=400). Progression to IA was defined as the development of clinical synovitis in ≥1 one joint.Results:US bone erosions: prevalence, distribution, and association with subclinical synovitisA total of 2514 joints, in 419 subjects were evaluated.Bone erosions were found in ≥1 joint in 41/419 subjects (9.8%), in 55/2514 joints (2.2%). The prevalence of bone erosions was significantly higher in the V MTP than in the MCP joints (p<0.01). They were detected in 42 V MTP (31 subjects; 7.4%), in 10 II MCP (10 subjects; 2.4%), and in 3 V MCP (3 subjects; 0.7%) joints. US synovitis was detected in 22/55 joints (40%) with bone erosions, in 17/41 subjects (42%). It was found in 48.6% of the V MTP, in 20% of the II MCP and in none of the V MCP joints with bone erosions. A significant correlation between bone erosions and synovitis in the same joint was detected (Cramer’s V=0.22, p<0.01).Seven out of the 55 joints (12.7%) with bone erosions were tender on physical examination: 14.3% of the V MTP, 10% of the II MCP, and none of the V MCP joints.US bone erosions: predicting development of IAA total of 122 subjects (30.5%) developed IA (median follow-up: 301 days, IQR 112-721). The hazard ratios of the US findings for the development of IA (adjusted for age, sex, smoking, anti-CCP and rheumatoid factor titer) are reported in Table 1.Table 1.EverAt 1 yearAt 3 yearsHR (95%CI)P valueHR (95%CI)P valueHR (95%CI)P valuePresence of bone erosion in ≥1 joint (any joint)3.98(1.82-8.7)<0.013.57(1.7-7.5)<0.013.48(1.63-7.4)<0.01- in the II MCP joints2.4(0.52-11.08)0.261.07(0.2-5.76)0.941.67(0.38-7.04)0.5- in the V MCP joints1.37(0.06-31)0.850(N/A)10(N/A)1- in the V MTP joints4.79(1.97-11.63)<0.015.23(2.32-11.8)<0.015.43(2.28-12.92)<0.01Presence of bone erosion and synovitis in the same joint (any joint)3.9(1.19-12.77)0.026.03(2.07-17.55)<0.013.91(1.29-11.85)0.02Presence of bone erosion and synovitis in the same V MTP joint5.08(1.37-18.9)0.027.03(2.28-21.71)<0.014.89(1.48-16.19)<0.01Presence of bone erosion in >1 joint (any joint)10.63(1.87-60.42)<0.015.68(1.66-19.5)<0.017.26(1.67-31.66)<0.01IA free survival rates are showed in Figures 1 and 2.Figure 1.Figure 2.Conclusion:The feet appear to be an early site for damage in individuals at-risk of RA. US bone erosions were mainly detected in asymptomatic joints, but frequently in association with subclinical synovitis. In individuals at-risk of RA, bone erosions in the V MTP joints are more predictive than in the hands (II and V MCP joints) for the development of IA.

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