Comparative study of the detection of joint injury in early-stage rheumatoid arthritis by magnetic resonance imaging of the wrist and finger joints and physical examination

Authors


Abstract

Objective

To verify whether magnetic resonance imaging (MRI)–proven joint injury is sensitive as compared with joint injury determined by physical examination.

Methods

MRI of the wrist and finger joints of both hands was examined in 51 early-stage rheumatoid arthritis (RA) patients by both plain and gadolinium diethylenetriaminepentaacetic acid–enhanced MRI. Synovitis, bone edema, and bone erosion (the latter two included as bone lesions at the wrist joints); metacarpophalangeal joints; and proximal interphalangeal joints were considered as MRI-proven joint injury. Japan College of Rheumatology–certified rheumatologists had given a physical examination just before the MRI study. The presence of tender and/or swollen joints in the same fields as MRI was considered as joint injury on physical examination. The association of MRI-proven joint injury with physical examination–proven joint injury was examined.

Results

A total of 1,110 sites were available to be examined. MRI-proven joint injury was found in 521 sites, whereas the other 589 sites were normal. Physical examination–proven joint injury was found in 305 sites, which was significantly low as compared with MRI-proven joint injury (P = 1.1 × 10−12 versus MRI). Joint injury on physical examination was not found in 81.5% of the sites where MRI findings were normal. Furthermore, an association of the severity of MRI-proven joint injury with that of joint injury on physical examination was clearly demonstrated (P = 1.6 × 10−15, rs = 0.469).

Conclusion

Our present data suggest that MRI is not only sensitive but accurately reflects the joint injury in patients with early-stage RA.

Introduction

Magnetic resonance imaging (MRI) has been postulated to be more sensitive than clinical examination for the detection of inflammatory and destructive joint changes in early-stage rheumatoid arthritis (RA) (1, 2); however, a precise study regarding the accuracy of MRI-proven joint injury as compared with joint injury determined by physical examination remains to be clarified. Although Sugimoto et al have shown in an earlier study that MRI-proven synovitis is useful in diagnosing early-stage RA in conjunction with physical examination (3), there is a limitation about this report since a number of examinations were small and bone edema as well as bone erosion were not included.

From this point of view, we have tried to find an association of MRI-proven joint injury, including synovitis, bone edema, and bone erosion, with joint injury determined by physical examination. We have compared 1,110 sites of the wrist and finger joints from 51 patients with early-stage RA and concluded that MRI is not only sensitive but accurately reflects the joint injury in patients with early-stage RA.

Patients and Methods

Patients.

The Early Arthritis Clinic opened in 2001 as part of the Unit of Translational Medicine, Department of Immunology and Rheumatology, Graduate School of Biomedical Sciences, Nagasaki University. Patients are referred from an area in the Western part of Japan, Nagasaki Prefecture, which has approximately 450,000 inhabitants. From this clinic, 51 early-stage RA patients were recruited for the present study. Their disease status was formally confirmed by a Japan College of Rheumatology–certified rheumatologist in our department, and a diagnosis of RA was made based on the 1987 criteria of the American College of Rheumatology for RA (4). Baseline clinical manifestations and variables included sex, age, localization of tender and/or swollen joints, morning stiffness, C-reactive protein level (measured by latex turbidimetric immunosorbent assay; Daiichi Pure Chemicals), IgM rheumatoid factor (IgM-RF) positivity (measured by latex-enhanced immunonephelometric assay, cutoff value 14 IU/ml; Dade Behring), positive status for anti–cyclic citrullinated peptide (anti-CCP) antibodies (measured by enzyme-linked immunosorbent assay, cutoff value 4.5 units/ml; DIASTAT Anti-CCP, Axis-Shield), HLA–DRB1 genotyping, and MRI of both the wrist and finger joints, as previously described (5–8). All of the variables were examined on the same day, as previously reported (5–8). Specifically, joint injury examined by physical examination was verified just before taking the MRI. Each patient provided a signed consent form to participate in the study, which was approved by the Institutional Review Board of Nagasaki University.

MRI of the wrist and finger joints.

MRI of both the wrist and finger joints was acquired using a 1.5T system (Sigma, GE Medical Systems) with an extremity coil. T1-weighted spin-echo images (repetition time [TR] 450, echo time [TE] 13), STIR images (TR 3,000, TE 12, T1 160), and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)–enhanced images were simultaneously acquired on the same day. All of the MRI studies were performed within 2 weeks after entry. The images were evaluated for bone edema, bone erosion, and synovitis in 15 sites in each finger and wrist: the distal radioulnar joint, the radiocarpal joint, the midcarpal joint, the first carpometacarpal joint, the second through fifth carpometacarpal joints (together), the first through fifth metacarpophalangeal (MCP) joints, and the first through fifth proximal interphalangeal (PIP) joints separately (a total of 30 sites in both hands), as we previously reported (5–8). The presence of synovitis, bone edema, and bone erosion was evaluated according to the methods described by Lassere et al (9) and Conaghan et al (10) and by two experienced radiologists (MU and ST), and decisions were reached by consensus as we previously described (5–8). We included bone edema and bone erosion as bone lesions in the present study. Since the standard definition of joint injury of the wrist and finger joints is documented as the wrist joint, MCP joints, and PIP joints, the wrist joint by physical examination corresponded with the distal radioulnar joint, the radiocarpal joint, the midcarpal joint, the first carpometacarpal joint, and the second through fifth carpometacarpal joints (together) by MRI in the present study. Gd-DTPA–enhanced images were obtained by intravenous injection of 0.1 mmole/kg of Gd-DTPA (Magnevist).

Assessment of the severity of joint injury by physical examination and by MRI.

The severity of joint injury by physical examination was classified, from severe to normal, as both positive swollen and tender joints, either positive swollen or tender joints, or normal findings. The severity of joint injury by MRI was classified, from severe to normal, as both positive bone lesions and synovitis, positive synovitis only, or normal findings. The association of the 2 scores was statistically examined.

Statistical analysis.

Differences between groups were examined for statistical significance using the chi-square test or Spearman's nonparametric correlation coefficients for independence test. A P value less than 0.05 denoted the presence of a statistically significant difference.

Results

Characteristics of the patients.

Table 1 shows the baseline characteristics of 51 patients with RA. Since the median disease duration from the onset of articular manifestations to entry was 5 months, the present study population is considered as early-stage RA. The median Genant-modified Sharp score of the 51 patients at baseline was 0.49, which also identifies as early-stage RA. Rates of seropositivity of IgM-RF and anti-CCP antibodies were 62.7% and 74.5%, respectively. Rates of carriership of HLA–DRB1*0405 allele and HLA–DRB1 shared epitope allele were 44.0% and 56.0%, respectively. These characteristics of autoantibodies and HLA–DR typing mean that the present study population is typical for RA.

Table 1. Demographic features of 51 early-stage rheumatoid arthritis patients*
 Value
  • *

    IgM-RF = IgM rheumatoid factor; anti-CCP = anti–cyclic citrullinated peptide; CRP = C-reactive protein.

Sex, male:female (% female)8:43 (84.3)
Age, median (range) years52 (19–80)
Disease duration, median (range) months5 (1–28)
Distribution of arthritis, % 
 Symmetric82.4
 Only upper extremities27.5
 Both extremities72.5
Genant-modified Sharp score, median (range)0.49 (0–8.58)
Positivity of IgM-RF, %62.7
IgM-RF, median (range) IU/ml18.0 (4.5–395)
Positivity of anti-CCP antibodies, %74.5
Anti-CCP antibodies, median (range) units/ml24.3 (0.6–2,115.3)
Positivity of CRP, %70.0
CRP level, median (range) mg/dl1.14 (0.03–11.13)
Carriership of HLA–DRB1*0405, %44.0 (diploid: 8.0%)
Carriership of HLA–DRB1 shared epitope, %56.0 (diploid: 8.0%)

MRI as not only sensitive but also accurately reflecting the joint injury in patients with early-stage RA.

Table 2 shows a prevalence of MRI-proven joint injury and the joint injury determined by physical examination. MRI-proven joint injury was detected at 46.9% of sites (521 of 1,110 sites), which was significantly higher than the joint injury determined by physical examination (27.4%, 305 of 1,110 sites). Importantly, joint injury determined by physical examination was not found in 81.5% of the sites where MRI findings were normal.

Table 2. Association of MRI-proven joint injury with joint injury determined by physical examination*
 Both swollen and tender jointsEither swollen or tender jointsNormal finding
  • *

    The rate of magnetic resonance imaging (MRI)–proven joint injury was detected at 46.9% of sites (521 of 1,110 sites), which was significantly higher than the joint injury determined by physical examination (27.4%, 305 of 1,110 sites; P = 1.1 × 10−12 by chi-square test). In addition, a clear positive correlation was noted between the severity of MRI-proven joint injury and that of joint injury by physical examination (P = 1.6 × 10−15, rs = 0.469 by Spearman's nonparametric correlation coefficients).

Both bone and synovitis24829
Synovitis8183296
Normal finding4267480

We further investigated an association of the severity of MRI-proven joint injury with that of joint injury determined by physical examination. As shown in Table 2, a clear positive correlation was noted between the two scores.

Discussion

Since the median disease duration from the onset of articular manifestations to entry in 51 patients was 5 months, we suggest that the present data mostly reflect rheumatoid joint injury, other than secondary changes due to osteoarthritis. Additionally, we have screened relatively large numbers of joints by both MRI and physical examination on the same day, indicating that our present data are enough to be qualified for the analysis of an association of MRI-proven joint injury and the joint injury determined by physical examination.

We have recently revealed that MRI-proven symmetric synovitis, bone edema, and bone erosion of the wrist and finger joints are predictive for further development in RA of patients with early undifferentiated arthritis (8). Other investigators have also demonstrated that MRI is a sensitive tool for the assessment of joint inflammation, especially in the early disease course (1, 2). In the small joints of the hands and feet, Szkudlarek et al have also shown the superiority of contrast-enhanced MRI toward the detection of synovitis as compared with physical examination (11, 12). Accordingly, our present data have shown that the prevalence of MRI-proven joint injury is significantly higher than that of joint injury determined by physical examination. These observations may not be nonspecific or may not reflect pseudopositive findings, since the severity of MRI-proven joint injury correlates well with that of joint injury determined by physical examination. Furthermore, more than 80% of the sites where MRI findings are normal did not show the joint injury by physical examination. Taken together, we do suggest that MRI is not only sensitive but also accurately reflects the joint injury in patients with early-stage RA. Since optimal MRI assessment of synovitis requires the use of intravenous gadolinium contrast (1), all of the present cases received both plain and Gd-DTPA–enhanced images as described in the Patients and Methods section. If Gd-DTPA–enhanced images can be omitted, the price of MRI is reduced from $200 to $140 per person. Further investigations are necessary for the evaluation of plain MRI toward joint injury in patients with early-stage RA. Also, the followup investigation will show the accuracy and utility of MRI toward plain radiographic damage as compared with physical examination.

AUTHOR CONTRIBUTIONS

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Tamai had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Tamai, Kawakami, Iwamoto, Kawashiri, Fujikawa, Aramaki, Kita, Okada, Koga, Arima, Kamachi, Yamasaki, Nakamura, Ida, Takao, Origuchi, Aoyagi, Uetani, Eguchi.

Acquisition of data. Tamai, Kawakami, Iwamoto, Kawashiri, Fujikawa, Aramaki, Kita, Okada, Koga, Arima, Kamachi, Yamasaki, Nakamura, Ida, Takao, Origuchi, Aoyagi, Uetani, Eguchi.

Analysis and interpretation of data. Tamai, Kawakami, Aoyagi, Uetani, Eguchi.

Ancillary