Comparison of findings on contrast-enhanced MRI of the hand, wrist, and forefoot in healthy controls, two at-risk groups, and patients with rheumatoid arthritis: a cohort study

Background: 

The sensitivity of MRI in detecting joint inflammation in rheumatoid arthritis is well known but its specificity is less discussed. It is important to prevent false positive results and consequent overdiagnosis. Therefore, we aimed to examine MRI-detected inflammation that is less specific for rheumatoid arthritis by evaluating the frequencies of inflammation in healthy controls and in two at-risk groups who have not developed rheumatoid arthritis, compared with patients with rheumatoid arthritis. 

Methods: 

In this cohort study, we performed contrast-enhanced MRIs of the second to fifth metacarpophalangeal, wrist, and first to fifth metatarsophalangeal joints of two at-risk groups (individuals with clinically suspect arthralgia and patients with undifferentiated arthritis who have not developed rheumatoid arthritis within a 2-year and 1-year follow-up period, respectively), and patients with rheumatoid arthritis, from two longitudinal observational cohort studies at Leiden University Medical Centre, Netherlands; the Leiden Early Arthritis Clinic (EAC) and the clinically suspect arthralgia (CSA) cohort. Healthy volunteers were also recruited as controls from Leiden University Medical Centre. MRIs were evaluated for synovitis, tenosynovitis, and osteitis using the Rheumatoid Arthritis MRI Scoring system. Intermetatarsal bursitis was also evaluated. All MRIs were scored by two readers independently of each other and who were blinded for clinical data. Each site was graded 0 (no inflammation), 1 (low), 2 (moderate), or 3 (severe). Increased signal intensity of joints, tendon sheaths, and bones were considered as less specific for rheumatoid arthritis if a similar signal intensity grade was present in more than 5% of the reference group. Comparisons were made in the following age-strata: <40 years, 40–59 years, and ≥60 years. Patient partners were involved in the design of the EAC and CSA cohorts. 

Findings: 

Participants with valid MRI data from the EAC cohort (enrolled Aug 24, 2010, to March 9, 2020]) and the CSA cohort (enrolled April 3, 2012, to April 29, 2021), and 193 healthy volunteers (enrolled between Nov 15, 2013, to Dec 2, 2014) were included. At follow-up, 516 patients had rheumatoid arthritis, 305 had undifferentiated arthritis, and 598 had clinically suspect arthralgia. Of all participants, 1089 (68%) of 1612 were female and 523 (32%) were male, 1105 (94%) of 1160 were White, and mean age was 51 years (SD 14). Grade 2 and 3 synovitis, tenosynovitis, or osteitis did not occur in more than 5% of healthy controls and clinically suspect arthralgia non-converters (of all ages), therefore grade 1 inflammation in these reference populations versus patients with rheumatoid arthritis was evaluated. Grade 1 inflammation was found at a number of sites in the hand, wrist, and forefoot in more than 5% in all reference populations across all age groups, and these locations of inflammation were also frequently seen in patients with rheumatoid arthritis. The frequency of inflammation across all cohorts increased with age. Grade 2 inflammation that occurred in more than 5% was only present in patients with non-progressing undifferentiated arthritis aged 60 years or older. 

Interpretation: 

We describe several low-grade MRI-detected inflammatory findings of the hand, wrist, and forefoot that are less specific for rheumatoid arthritis. These include locations that are regularly inflamed in rheumatoid arthritis. These findings could assist in avoiding overinterpretation when using contrast-enhanced MRI.