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

Abstract

The identification of biomarkers that help identify individuals at imminent risk of progression to rheumatoid arthritis (RA) is of crucial importance for disease prevention. In recent years, several studies have highlighted the value of musculoskeletal (MSK) ultrasound (US) in predicting progression to inflammatory arthritis (IA) in individuals ‘at-risk’ of RA. These studies have highlighted the following main aspects: first, in RA-related autoantibody-positive individuals, MSK symptoms seem to develop before ‘sub-clinical’ joint inflammation occurs on US. Second, the detection of ‘sub-clinical’ synovitis (and/or bone erosions) greatly increases the risk of IA development in these ‘at-risk’ individuals. US has a potential key role for better understanding the ‘pre-clinical’ stages in individuals ‘at-risk’ of RA, and for the early identification of those individuals at high risk of developing IA. Further research is needed to address questions on image analysis and standardization. In this review, we provide an overview of the most relevant studies which have investigated the value of US in the prediction of RA development in individuals ‘at-risk’ of RA who have MSK symptoms, but no clinical evidence of IA. We highlight recent insights, limitations, and future perspectives of US use in this important population.

Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum

“…asymptomatic first-degree relatives vs individuals with MSK symptoms and RA-related antibodies), distribution and number of joints or tendons involved and the type of US pathological findings detected (e.g. grey-scale synovitis, PD signal) [ 32 ]. In the current study, progressors were found to have a median of 2 joints with US subclinical synovitis (IQR 1.0–3.0) prior to inflammatory arthritis development.…”

Utility of testing for third-generation anticyclic citrullinated peptide (anti-CCP3) antibodies in individuals who present with new musculoskeletal symptoms but have a negative second-generation anticyclic citrullinated peptide (anti-CCP2) antibody test

“…3 Additionally, genetic predisposition, subclinical inflammation on MRI and ultrasound (US), as well as certain cellular markers (eg, circulating B-cell and T-cell biomarkers), have been described as specific risk factors for RA development in 'at-risk' populations. [8][9][10][11] Most recently, Fab-linked glycans of ACPA have also been shown to be associated with the development of RA. [12][13][14] In 'at-risk' cohorts around the globe, individuals are identified and invited for participation in trials based on the presence of musculoskeletal (MSK) symptoms and a positive ACPA test.…”

Editorial: Ultrasound in rheumatology—A polyhedric imaging tool

“…Previous studies have shown the promising role of US in improving the prediction for the development of RA in individuals “at-risk” for this disease ( 6 ). In the current Research Topic, Harnden et al reviewed the value of available imaging modalities for this purpose, including US, but also conventional radiography, magnetic resonance imaging (MRI), quantitative computed tomography (CT) and nuclear imaging, and the rationale for their use in the main populations “at-risk” of RA.…”