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.

Keywords: inflammatory arthritis; musculoskeletal ultrasound; power Doppler signal; prediction; rheumatoid arthritis; synovial hypertrophy; ‘at-risk’.

Figure 1

Overview of the pre-clinical phases of RA. Stages along the RA ‘continuum’ defined by the European League Against Rheumatism (EULAR) Standing Committee on Investigative Rheumatology. Legend: MSK: musculoskeletal; RA: rheumatoid arthritis, UA: undifferentiated arthritis.

Figure 2

Representative ultrasound (US) findings in at-risk individuals with musculoskeletal symptoms but without clinical arthritis. Longitudinal (A) and transverse (B) US scan of the dorsal aspect of the 3rd metacarpophalangeal joint. US shows the presence of “active” synovitis, characterized by synovial hypertrophy (arrowheads) with PD signal (red spots) which also envelops the finger extensor tendon (et). (C) Transverse US scan of the flexor pollici longus tendon shows “active” tenosynovitis with synovial effusion (asterisk) and synovial hypertrophy (arrowhead) within the tendon sheath (asterisk) surrounded by PD signal (red spots). (D) Longitudinal US scan of the lateral aspect of the 5th metatarsophalangeal joint. Note the presence of a bone erosion (empty arrow) filled with power Doppler signal (red spots). Legend: et = finger extensor tendon; fpl = flexor pollici longus; mh = metacarpal head; mt = metatarsal head. ((A) Di Matteo, personal images).