Defining age-related thresholds in hand, wrist, and foot ultrasound: an international, cross-sectional, observational study by the Outcome Measures in Rheumatology Ultrasound Working Group.

BACKGROUND

Despite widespread use of ultrasound in rheumatology, interpretation of findings is predicated on the assumption that healthy individuals show no gradable differences in all joints and across all age ranges. To define the age-related ultrasound thresholds in small joints, this study sought to systematically grade three ultrasound abnormalities (ie, synovial hypertrophy, Doppler signal, and synovial effusion) in the metacarpophalangeal, proximal interphalangeal, wrist, and metatarsophalangeal joints of healthy individuals aged 18-80 years.

METHODS

This multicentre, cross-sectional, observational study recruited healthy individuals from 20 centres across 13 countries in Europe, South America, Asia, and the Middle East. Participants included individuals aged 18-80 years from a range of backgrounds, including university and hospital research staff, health-service workers, students, and volunteers from local advertising or national cohorts. Main exclusion criteria were individuals with previous or current inflammatory joint disease, clinical joint inflammation, recent history of joint trauma, hand osteoarthritis, joint pain, and use of corticosteroids or non-steroidal anti-inflammatory drugs. Participants were classified into three age groups (18-39, 40-59, and 60-80 years) representing young, middle, and older age groups. Clinical and ultrasound assessment of bilateral metacarpophalangeal 1-5, proximal interphalangeal 1-5, wrist, and metatarsophalangeal 1-5 joints were conducted according to European Alliance of Associations for Rheumatology guidelines and severity of ultrasound joint abnormalities was graded using the European Alliance of Associations for Rheumatology-Outcome Measure for Rheumatology synovitis score. The age-related threshold for each joint type was identified using the cumulative 95% prevalence rule. People with lived experience of inflammatory arthritis were involved in the study design and interpretation of results.

FINDINGS: Participants were recruited from Feb 7, 2017, to July 30, 2019. 802 participants were included in the final analysis. 351 (44%) of 802 participants were aged 18-39 years, 302 (38%) were aged 40-59 years, and 149 (19%) were aged 60-80 years. 578 (72%) of 802 participants were female, 224 (28%) were male, 644 (81%) of 799 were White, and the median age was 42 years (IQR 30-56). Of 28 735 joints scanned, 3728 (13%) had at least one ultrasound finding higher than grade 0. The highest proportion of ultrasound findings higher than grade 0 was in metatarsophalangeal 1 (45%), followed by metatarsophalangeal 2 (39%). Doppler signal activity in the metacarpophalangeal, proximal interphalangeal, wrist, and metatarsophalangeal joints and synovial hypertrophy in proximal interphalangeal 2-5, metacarpophalangeal 5, and metatarsophalangeal 5 was minimal in all age ranges. Synovial effusion findings differed by joint type predominantly, but not by age.

INTERPRETATION: Doppler signal in any metacarpophalangeal, proximal interphalangeal, wrist, and metatarsophalangeal joints are likely to be abnormal in all age groups. Normal ultrasound thresholds for synovial effusion and synovial hypertrophy differed by joint type and age. The development of age-specific and joint-specific reference values is an important step towards precision medicine using ultrasound imaging in rheumatology.

FUNDING: None.