Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis

Abstract

ObjectivesTo investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA).MethodsBaseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) ≥2 or SH ≥1+power Doppler signal ≥1. Subjects with ≥1 follow-up visit were included in the progression analysis (n=400).ResultsBE were found in ≥1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p<0.01). A significant correlation between BE and US synovitis in the MTP5 joints was detected (Cramer’s V=0.37, p<0.01). The OR for the development of IA (ever) was highest for the following: BE in >1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in ≥1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in ≥1 joint, the OR increased to 16.9 (95% CI 2.1–132.8, p<0.01).ConclusionsIn CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis.

Antibodies to Citrullinated Proteins (ACPA) Associate with Markers of Osteoclast Activation and Bone Destruction in the Bone Marrow of Patients with Rheumatoid Arthritis

“…Pathological bone erosion begins early in RA-in the first months of the clinical disease or even before the onset of clinical symptoms [16,[22][23][24]. This suggests the existence of an additional, at least partially independent from synovial inflammation, mechanism for osteoclast stimulation and bone destruction in RA.…”

What Is the Value of Ultrasound in Individuals ‘At-Risk’ of Rheumatoid Arthritis Who Do Not Have Clinical Synovitis?

“…Most of the studies presented in this review explored the predictive value of US findings in multivariable models also including clinical and serological factors, such as tenderness in the hands or feet, early morning stiffness, or RA-related antibodies [ 23 , 27 , 29 , 30 , 32 ]. This suggests that US has an additional value when used alongside other clinical or serological variables.…”

“…Further studies are needed to explore the diagnostic performances of these definitions in patients at risk without clinical synovitis. We have demonstrated that a targeted US protocol, focused on the classical sites for RA damage (MCP2, MCP5 and MTP5 joints) is useful to predict progression (and its timing) to IA in CCP+ ‘at-risk’ individuals, thus improving risk-stratification and informing the management of these individuals [ 32 ]. Further research is needed to identify the ‘ideal’ scanning protocol, with the optimal predictive accuracy, which could also be applied in real-life clinical settings.…”

“…US bone erosions were predictive for IA development with an OR of 2.9 (95% CI 1.7 to 5.1), p < 0.001 [ 24 ]. In a larger subsequent study of 419 at-risk individuals from the same cohort, the prevalence and distribution of US bone erosions at the classical sites for RA damage (MCP2 and MCP5 joints, and MTP5 joints), and their association with development of clinical arthritis, was investigated [ 32 ]. Bone erosions, identified according to the OMERACT definitions, were detected in ≥1 joint in 41/419 subjects (9.8%); these were associated with progression to IA, and its timing, at patient level.…”

The Role of Ultrasound Across the Inflammatory Arthritis Continuum: Focus on “At-Risk” Individuals

“…Another multivariable analysis on the same population (n = 488) showed that individuals with 1-3 joints with a PD signal or 1-2 with BE were twice as likely to develop IA, those with ≥ 4 joints with a PD signal were more than six times more likely (26). A more recent study (27) analyzed baseline US scans of a further 419 CCP positive at-risk individuals from the Leeds CCP cohort. In this analysis, the most predictive features for the development of clinical arthritis on US were BE in >1 joint or BE combined with synovitis in the MTP5 joint (OR 10.6 [95% CI 1.9 to 60.4] p < 0.01) and 5.1 [95% CI 1.4 to 18.9] p = 0.02] respectively.…”