Abstract
ObjectiveSubclinical joint inflammation in patients with arthralgia is predictive for progression to rheumatoid arthritis (RA). However, the time course of progression for bone marrow edema (osteitis), synovitis, and/or tenosynovitis is unsettled. This longitudinal study assessed the course of magnetic resonance imaging (MRI)-detected subclinical joint inflammation during progression to RA.MethodsPatients that progressed from clinically suspect arthralgia (CSA) to RA underwent 1.5-T MRI of the metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints at presentation with arthralgia and at first identification of synovitis assessed through physical examination (n = 31). MRIs were evaluated for osteitis, synovitis, tenosynovitis, and erosions by two readers, blinded for clinical data and order in time. To estimate changes in MRI scores between the asymptomatic state and CSA onset, scores of MRI features at CSA baseline were compared with scores from age-matched symptom-free persons.ResultsAt presentation with CSA, synovitis and tenosynovitis scores were higher than scores from age-matched symptom-free persons (p = 0.004 and p = 0.001, respectively). Anti-citrullinated protein antibody (ACPA)-positive arthralgia patients also had increased osteitis scores (p = 0.04). Median duration between presentation with arthralgia and RA development was 17 weeks. During progression to RA, synovitis and osteitis increased significantly (p = 0.001 and p = 0.036, respectively) in contrast to tenosynovitis and erosion scores. This pattern was similar in both ACPA subsets, although statistical significance was reached for synovitis and osteitis in ACPA-negative but not ACPA-positive RA.ConclusionIncreased tenosynovitis and synovitis scores at CSA onset and the increase in synovitis and osteitis during progression to RA suggest an ‘outside-in’ temporal relationship of arthritis development, in particular for ACPA-negative RA. For ACPA-positive RA, further studies are needed.
Highlights
Rheumatoid arthritis (RA) can be diagnosed at the time patients present with clinically detectable inflammatory arthritis
It has been suggested that RA is a primary bone marrow disease which subsequently encroaches upon the synovial membrane; this is the ‘inside-out hypothesis,’ with osteitis preceding synovitis, a hypothesis that has become popular after imaging and histological studies revealed the presence of osteitis at ten Brinck et al Arthritis Research & Therapy (2018) 20:260 locations with magnetic resonance imaging (MRI)-detected osteitis in patients with RA [4, 7, 8]
Extrapolation to humans would suggest that tenosynovitis rather than synovitis or osteitis is the primary feature of joint inflammation [10]
Summary
Rheumatoid arthritis (RA) can be diagnosed at the time patients present with clinically detectable inflammatory arthritis (swollen joints). It has been postulated that synovitis is an initial process that is succeeded by bone involvement This is the traditional ‘outside-in hypothesis,’ presuming that inflammation of the synovium precedes bone marrow edema (or osteitis) [3,4,5,6,7]. It has been suggested that RA is a primary bone marrow disease which subsequently encroaches upon the synovial membrane; this is the ‘inside-out hypothesis,’ with osteitis preceding synovitis, a hypothesis that has become popular after imaging and histological studies revealed the presence of osteitis at ten Brinck et al Arthritis Research & Therapy (2018) 20:260 locations with MRI-detected osteitis in patients with RA [4, 7, 8]. Temporal relationships are yet unknown and can be discovered by longitudinal imaging studies that start in pre-arthritis phases of the disease
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