Early prediction of erosive joint damage is very important in rheumatoid arthritis (RA) because significant articular damage in patients is evident radiologically within the first few years of the disease.1 This study was designed to confirm whether anti‐cyclic citrullinated peptide antibodies (anti‐CCP Ab) define the subset of patients with early stage RA who have bone marrow oedema, observed by magnetic resonance imaging (MRI).
Patients were referred from the Early Arthritis Clinic, started in 2001 at the First Department of Internal Medicine, Graduate School of Biomedical Sciences, Nagasaki University. After prospective follow up, diagnosis of RA was made by the 1987 criteria for RA of the American College of Rheumatology.2 Eighty patients who gave their informed consent to the protocol that was approved by the Institutional Review Board of Nagasaki University were enrolled in the study.
The disease duration of 80 patients with RA at the entry was <24 months (mean disease duration 4.8 months), and thus these patients had early stage RA. Serological variables at entry were as follows: mean (SD) C reactive protein 1.6 (2.5) mg/ml, matrix metalloproteinase 3 (MMP‐3) positivity 46.3%, anti‐CCP Ab positivity 67.5%, and IgM rheumatoid factor (IgM‐RF) positivity 67.5%. The mean modified Genant‐Sharp score of plain radiographs of both hands at entry was 0.41.
Magnetic resonance images of both wrists and finger joints were taken simultaneously using the 1.5 T system (Sigma, GE Medical Systems, Milwaukee, WI). Images were evaluated for the presence or absence of bone marrow oedema and synovitis in 15 joints of each finger and wrist—that is, the distal radioulnar joint, radiocarpal joint, mid‐carpal joint, 1st carpometacarpal joint, 2nd–5th carpometacarpal joints (together), 1st–5th metacarpophalangeal joints separately, and the 1st–5th proximal interphalangeal joints separately (total 30 joints from both hands).
The severity of synovitis was assessed by the number of joints with synovitis and the rate of enhancement (E‐rate), on a dynamic study by injection of gadolinium‐diethylenetriamine pentaacetic acid. The E‐rate means the vascularity,3,4 by plotting the signal intensity against time in a selected region of interest (about 2–3 mm in diameter) of the site of maximum enhancement in the above‐mentioned 15 joints. Determination of bone marrow oedema was also carried out5,6,7 by two experienced radiologists (MU and ST), and decisions were reached by consensus.
We examined simply and automatically the wrists and finger joints, including proximal interphalangeal joints, by MRI, using the above‐mentioned variables instead of the OMERACT 5 RA‐MRI scoring system.6,7 We divided the 80 patients with early stage RA according to the presence or absence of anti‐CCP Ab (table 1).
Table 1 Comparison of anti‐CCP Ab+ and anti‐CCP Ab− patients.
| Variables | Anti‐CCP Ab+ | Anti‐CCP Ab− | p Value |
|---|---|---|---|
| (n = 54) | (n = 26) | ||
| CRP (mg/ml) | 1.3 (2.0) | 2.2 (3.3) | 0.39* |
| MMP‐3 (%) | 50.0 | 38.5 | 0.33† |
| Number of joints with synovitis | 12.2 (6.4) | 10.3 (6.4) | 0.30* |
| Mean E‐rate of 30 joints | 7.7 (3.0) | 7.4 (2.9) | 0.67* |
| Bone marrow oedema | |||
| % | 64.8 | 38.5 | 0.03† |
| No | 2.8 (3.5) | 1.1 (2.3) | 0.01* |
Data are mean (SD) unless stated otherwise. The proportion of patients with bone marrow oedema was significantly higher in the anti‐CCP Ab+ group than in the anti‐CCP Ab‐ group: *by Mann‐Whitney U test; †by χ2 test.
The proportion of patients with bone marrow oedema was significantly higher in the anti‐CCP Ab+ group than in the anti‐CCP Ab‐ group. In contrast, there were no differences between the two groups for the other variables (for example, CRP, MMP‐3 positivity, number of joints with synovitis, and mean E‐rate of 30 joints).
Division of patients according to the presence or absence of IgM‐RF also showed a higher proportion of patients with bone marrow oedema in those who were anti‐CCP Ab positive than in those negative for the antibody, but the difference was not significant (table 2). However, because 81.5% of anti‐CCP Ab+ patients also possessed IgM‐RF (44/54 patients), anti‐CCP Ab and IgM‐RF are not independent factors for bone marrow oedema. Bone marrow oedema is a forerunner of bone erosion on plain radiography,8 and thus our present data show the additional importance of the presence of anti‐CCP Ab at baseline as an indication of future bone erosion in early stage RA.9
Table 2 Comparison of IgM‐RF+ and IgM‐RF– patients.
| Variables | IgM‐RF+ | IgM‐RF− | p Value |
|---|---|---|---|
| (n = 54) | (n = 26) | ||
| CRP (mg/ml) | 1.5 (2.1) | 2.0 (3.3) | 0.96* |
| MMP‐3 (%) | 51.9 | 34.6 | 0.23** |
| Number of joints with synovitis | 12.1 (5.6) | 10.6 (7.8) | 0.22* |
| Mean E‐rate of 30 joints | 7.6 (3.2) | 7.6 (2.3) | 0.58* |
| Bone marrow oedema | |||
| % | 63.0 | 42.3 | 0.08** |
| No | 2.7 (3.5) | 1.4 (2.7) | 0.07* |
Data are mean (SD) unless stated otherwise. Division of patients by IgM‐RF seropositivity showed a higher proportion of patients with bone marrow oedema compared with those negative for the antibody, but the difference was not significant: *by Mann‐Whitney U test; †by χ2 test.
Acknowledgments
We thank Misses Maiko Kubo, Youko Uchiyama, Nobuko Fukuda, and Kouko Munechika for their technical assistance.
This study was supported by a grant from The Ministry of Health, Labour and Welfare, Japan.
Footnotes
MT and AK contributed equally to this work.
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