Development of clinically apparent synovitis: a longitudinal study at the joint level during progression to inflammatory arthritis

Abstract

Introduction: Subclinical inflammation, detected by MRI, in patients with arthralgia is predictive for development of inflammatory arthritis (IA). However, within patients that develop IA, the course of inflammation at the joint level during this transition is unknown. This longitudinal study assessed progression of inflammation at the joint level.

Methods: 350 joints (unilateral metacarpophalangeals (MCPs), wrist, metatarsophalangeal (MTP) joints) of 35 patients presenting with clinically suspect arthralgia (CSA) that progressed to IA were studied at presentation with CSA and subsequently when clinical synovitis was first identified at joint examination (median time interval 17 weeks). At both time points, subclinical inflammation (bone marrow oedema, synovitis, tenosynovitis) was evaluated with MRI and joint examination was performed.

Results: At presentation with CSA, 71 joints showed subclinical inflammation. During progression to IA, 20% of these joints had resolution of inflammation, 60% had persistent inflammation and 20% progressed to clinical synovitis. Of all joints that had developed clinical synovitis (n = 45), no prior subclinical inflammation was detected in 69%. Similar results were observed for anticitrullinated protein antibodies (ACPA)-positive and ACPA-negative patients.

Conclusions: This longitudinal study demonstrated moderate correlations between joints with subclinical inflammation and joints that developed clinical synovitis. These data imply that IA development is a more systemic rather than a locally outgrowing process.

Keywords: inflammation; mri; outcome measures; rheumatoid arthritis.

Figure 1

Schematic depiction of categories of inflammation in 350 small joints during progression from clinically suspect arthralgiato inflammatory arthritis. Presence of subclinical joint inflammation was detected by MRI. An MR inflammation score ≥1 (sum of bone marrow oedema, synovitis or tenosynovitis in one joint, average of two readers) was defined as subclinical inflammation. At the time of IA development, individual joints could show clinically detectable joint swelling at physical examination, while this was per definition not possible at presentation with arthralgia. Please note that the y-axis indicates categories of inflammation (below MRI-detection limit of inflammation/above MRI-detection limit but under clinical detection limit of synovitis at physical examination/above clinical detection limit of synovitis at physical examination (ie, clinically detectable joint swelling)), not absolute MRI-inflammation scores.

Figure 2

Examples of MRI at presentation with clinically suspect arthralgia (CSA) (top panel) and at IA development (bottom panel), showing joints (A) from no inflammation to clinical synovitis and (B) resolution of subclinical inflammation. Presented in (A) are: (top panel) left MCP joints with no subclinical inflammation as detected by MRI, and (bottom panel) left MCP joints of the same patient with synovitis in MCP5 and tenosynovitis in MCP2 and 5. According to clinical examination the patient developed clinical synovitis in the left MCP2 (depicted), left MCP5 (depicted), left proximal interphalangeal (PIP)2 and right PIP5 joints (both not imaged). From a different patient (B) are presented: (top panel) right wrist joint with tenosynovitis in the extensor carpi ulnaris tendon, and (bottom panel) right wrist joint of the same patient without MRI-detected subclinical inflammation despite progression to inflammatory arthritis at the patient level. The patient developed clinically apparent synovitis in the left PIP3 joint (not imaged). All images were made in T1-weighted fast spin echo (FSE) sequence with frequency selective fat saturation in the axial plane after gadolinium contrast injection.