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Musculoskeletal Imaging |
1 From the Departments of Radiology (H.S., K.H.) and Medicine (A.T.), Division of Clinical Immunology, Jichi Medical School, Tochigi-ken, Japan. From the 1997 RSNA scientific assembly. Received March 26, 1998; revision requested May 7; final revision received November 9, 1999; accepted November 19. Address correspondence to H.S., Department of Radiology, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa-ken 227-8501, Japan (e-mail: sugimo-h@sannet.ne.jp).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Fifty subjects (nine men and 41 women) with polyarthralgia who were suspected of having early-stage RA on the basis of clinical and radiographic findings were selected to undergo gadolinium-enhanced MR imaging of the hands. The MR imaging criterion for the diagnosis of early RA was bilateral enhancement in both wrists and/or the metacarpophalangeal and/or proximal interphalangeal joints. Follow-up continued until a final diagnosis was determined. Two patients left the study before the end of follow-up.
RESULTS: Final diagnoses were established after a mean follow-up of 776 days: rheumatoid arthritis in 26 patients and nonrheumatoid disease in 22. Use of the MR imaging criterion yielded the correct diagnosis in 25 patients with RA and three false-positive results in three patients without RA. As compared with the traditional format and classification tree criteria of the American Rheumatism Association, the MR imaging criterion allowed detection of seven and six additional patients with true RA, respectively.
CONCLUSION: The introduction of MR imaging into the diagnostic criteria for early RA may contribute to more accurate diagnosis in patients suspected of having RA and thus allow an earlier decision to start proper medication.
Index terms: Arthritis, rheumatoid, 43.711 • Hand, MR, 43.121411, 43.121415, 43.12143
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The diagnosis of RA is based primarily on clinical findings, but it is sometimes difficult even for the trained rheumatologist to differentiate cases of early-stage RA from those of other diseases with joint manifestations. Magnetic resonance (MR) imaging has reportedly (5,6) enabled clinicians to visually detect bone erosion and active synovitis long before the changes are visible on conventional radiographs. In a previous study (6) with patients with definite RA and control patients, we demonstrated that the detection of active synovitis by means of MR imaging can increase diagnostic accuracy with the 1987 American Rheumatism Association (ARA) revised criteria for the classification of RA. The results of that study suggested that periarticular contrast material enhancement of the wrists and/or the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joints in both hands is indicative of RA.
On the basis of the outcome of that study (6), the next question to address is the diagnostic value of MR imaging in patients with possible early-stage RA in whom the diagnosis is equivocal and who present with polyarthralgia without radiographic evidence of RA. Therefore, this study was planned as a prospective investigation of the accuracy of MR imaging for demonstration of active synovitis of both hands in patients with possible early-stage RA, with the goal of differentiating patients with true RA from those without RA.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The patients had clinically possible early-stage RA and had presented with polyarthralgia (persistent arthralgia of three or more joint areas) without radiographic evidence of RA. They agreed to undergo contrast-enhanced MR imaging as part of their diagnostic work-up. Informed consent was obtained from all patients before participation in the study. Patients who, at the time of entry, apparently fulfilled the diagnostic criteria for other rheumatic diseases, including systemic lupus erythematosus, dermatomyositis and/or polymyositis, progressive systemic sclerosis, mixed connective tissue disease, and Behçet disease, were excluded from the cohort. The reason for this exclusion was that results from our previous study (6) showed that periarticular synovial enhancement of the wrist, MCP, and/or PIP joints in both hands on MR images is often observed in patients with these diseases. In addition, we were aware that those diseases are readily diagnosed on the basis of extraarticular systemic manifestations, the results of blood tests, or both. Patients with erosion or unequivocal cortical decalcification on the initial radiograph of the hands obtained at the time of presentation were excluded as well, because this study was designed to investigate the demonstration of RA before the occurrence of characteristic radiographic changes.
Posteroanterior and oblique hand radiographs in all patients were interpreted by one author (H.S.), who used a magnifying glass to detect any erosion or cortical decalcification. Radiography of the hands was performed before MR imaging. The mean interval between MR imaging and radiography was 58 days (range, 0–97 days).
MR Imaging Technique
MR imaging of the hand was performed with a 1.5-T superconducting magnet (MRT 200 FX/II; Toshiba, Tokyo, Japan), equipped with a circular surface coil 20 cm in diameter. The patient was placed in the prone position with the arm to be examined extended overhead toward the midline and the hand positioned in the center of the coil. The wrist was positioned palm downward and secured with restraining bands. Flexion contracture of the joint, if present, was corrected with relatively tight compression of the hand against the surface coil by means of a plastic board. This resulted in alignment of the metacarpal bones with the phalanges.
Multiple coronal MR images of the hand were obtained by using a fat-suppressed T1-weighted spin-echo sequence (repetition time msec/echo time msec = 380/20, 4-mm section thickness with 1-mm intersection gap, matrix size of 256 x 224, two signals acquired, field of view of 20 cm) before and after contrast enhancement. Contrast-enhanced images were obtained after bolus injection of 0.1 mmol/kg gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) into a vein in the contralateral arm. For fat suppression, a 1-3-3-1 binomial pulse sequence combined with the Dixon opposed technique was used. The injection of gadopentetate dimeglumine was performed after first-order shimming to complete the imaging within 3 minutes after injection. When MR images are obtained within a few minutes after injection of gadopentetate dimeglumine, the diffusion of the contrast material into joint effusion is negligible, and fibrotic pannus is not as intensely enhanced as is active synovitis. With this technique, the area of enhancement corresponds to the anatomic distribution of active synovitis (7–9).
A total of seven sections were obtained. With this sequence, full-thickness images of the hands were obtained in all patients. The entire structure of the hand was depicted in the imaging field, including the distal radioulnar joint and the distal interphalangeal joints. All subjects underwent MR imaging of each hand on separate days, and the interval between these two imaging sessions was more than 24 hours to exclude the residual effect of contrast material from the prior examination.
Working MR Imaging Criterion for RA
In a preliminary study (6), we determined the normal appearance of contrast-enhanced MR images of the hands. In that study, no intense enhancement was observed in the wrists and hands of asymptomatic volunteers when strict controls of both the MR technique and the injection timing were maintained. Further, a comparison between nonenhanced and enhanced images helped prevent erroneous interpretations of insufficient fat saturation as contrast enhancement.
Our previous study (6) with patients with definite RA and control subjects demonstrated that intense bilateral contrast enhancement in the wrists and/or MCP and/or PIP joints in both hands are indicative of RA. On the basis of these results, we tentatively determined the working criterion for the diagnosis of early RA using MR imaging. When enhancement was seen bilaterally in the wrist, MCP, and/or PIP joints of both hands in a patient with clinically possible early-stage RA who presented with polyarthralgia but no radiographic evidence of RA and who did not fulfill the diagnostic criteria for the other rheumatic diseases (ie, systemic lupus erythematosus, dermatomyositis and/or polymyositis, progressive systemic sclerosis, mixed connective tissue disease, or Behçet disease), the patient was categorized as having RA. The MR imaging criterion may be considered to correspond to a combination of the third and fourth criteria of the 1987 ARA revised criteria for the classification of RA: arthritis of hand joints and symmetric arthritis (10). When the enhancement was seen only in the wrist, MCP, and/or PIP joints of one hand or was not seen in either hand, the patient was not categorized as having RA (ie, non-RA disease). Bilateral involvement of wrist, MCP, or PIP joints without absolute symmetry was an acceptable finding for our criterion, as long as the abnormal enhancement was seen in the same joint areas. Abnormal enhancement in the same joint areas was indicative of arthritic changes, for example, in the PIP joint(s) of the right hand and in the PIP joint(s) of the left hand. Therefore, the criterion did not necessitate absolutely symmetric changes as long as the PIP joints are involved bilaterally. All MR images were interpreted and reported by one radiologist (H.S.).
Data Analysis
The RA or non-RA diagnosis was established after clinical follow-up, which allowed confident judgment. The average follow-up from the first to the final clinical visit was 776 days (range, 117–2,161 days). The final diagnosis of RA was based on physical findings compatible with RA and/or radiographic changes specific for RA, as well as the exclusion of other diseases that can manifest as polyarthralgia regardless of MR imaging findings. Two patients discontinued visits to our clinic without making available any further medical records. Therefore, because the diagnosis of RA was undetermined in these two patients, they were excluded from the study analysis. Follow-up MR imaging was performed in 15 patients at an average 292 days (range, 126–396 days) after initial MR imaging.
The diagnostic effectiveness of the MR imaging criterion was compared with that of the traditional format and of the classification tree of the 1987 ARA revised criteria for RA (10). Radiologic progressions were assessed by using the method of Larsen et al (11). Grading was as follows: grade 0, normal findings; grade 1, slight abnormality; grade 2, definite early abnormality; grade 3, medium destructive abnormality; grade 4, severe destructive abnormality; and grade 5, mutilating abnormality. One author (H.S.) performed the comparison and grading of all radiographs.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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On the initial radiographs, grade 0 changes were present in 27 patients, and grade 1 changes were present in 21 patients. Radiographic change was assessed in 18 patients who underwent follow-up radiography. Radiographic progression was seen in 10 patients: Seven developed bone erosion, and three developed osteopenia. Radiographic progression was observed exclusively in the patients with RA. One patient showed improvement of osteopenia on follow-up radiographs.
Nineteen patients fulfilled four or more criteria of the 1987 ARA revised criteria for the classification of RA (traditional format) at the beginning of follow-up. The remaining seven patients with true RA eventually fulfilled at least four of the ARA traditional format criteria by the end of the study. Two of eight patients with true RA who did not fulfill the diagnostic criteria of the ARA traditional format at the time of entry into the study later developed erosion that could be observed on follow-up radiographs.
MR Imaging Findings
By using the MR imaging criterion, 27 patients were classified as having RA and 21 were classified as having a non-RA condition. Among the patients who were MR criterion–positive for RA, 18 fulfilled the ARA criteria for RA at the time of entry (Fig 1), and seven eventually fulfilled the ARA criteria before the end of the study. Use of the MR imaging criterion resulted in correct diagnosis in 25 of 26 patients with true RA and in three false-positive diagnoses in 22 patients with a non-RA condition. The final diagnoses in the three false-positive cases were cryoglobulinemia, osteoarthritis, and transient arthritis related to a viral infection. Retrospectively, MR images in the patient with osteoarthritis showed incomplete fat suppression around the joints. This area of incomplete fat suppression can lead to erroneous interpretation as active synovitis. In patients with a final diagnosis of transient arthritis related to a viral infection or cryoglobulinemia, MR images showed bilateral intense enhancement in the wrists, PIP joints, and MCP joints (Fig 2).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The present study introduced diagnostic criteria that used MR imaging findings for determination of early-stage RA. The criteria consist of an MR imaging criterion and applicable clinical conditions that indicate possible early-stage RA. In our study, the patients in whom the MR criterion could be applied must have presented with polyarthralgia without radiographic evidence of RA and must not have fulfilled the diagnostic criteria for systemic lupus erythematosus, dermatomyositis and/or polymyositis, progressive systemic sclerosis, mixed connective tissue disease, or Behçet disease. The MR imaging criterion was gadolinium enhancement seen bilaterally in the wrist, MCP, and/or PIP joints (bilateral involvement of wrists, MCP joints, or PIP joints was acceptable without absolute symmetry if abnormal enhancement was seen in the same joint areas). The results of this prospective study showed the high performance of our diagnostic criteria with MR imaging for early RA. The MR imaging criterion could be used to distinguish true RA with high sensitivity (96%) and accuracy (94%) among the patients who fulfilled the clinical conditions.
In comparison with the 1987 ARA revised criteria for the classification of RA, which are based on clinical manifestations and radiographic findings, the MR imaging criterion appears to be a useful tool for assistance in the diagnosis of early RA. Basically, the 1987 ARA criteria for RA were purposefully formulated to facilitate the classification of RA rather than for the clinical diagnosis of the disease (10). Because of the proven reliability, these criteria have been widely accepted and used in clinics. However, there are indications that the criteria yield a lower diagnostic performance in patients with an early stage of disease. In this study, for example, the traditional format and the classification tree of the 1987 ARA criteria showed sensitivities of 69% and 77%, respectively, and accuracies of 81% and 83%, respectively, although the numbers may not represent true values owing to limitations related to our patient population.
We encountered one false-negative result determined on the basis of the MR imaging criterion. MR images in this patient showed monoarthritis in one hand (Fig 3b). Patients with RA may have monoarthritis or oligoarthritis in one hand in the early stage (12,13). This case emphasizes the importance of follow-up examination when the initial MR images reveal active synovitis, even if present in only one hand. If unilateral enhancement was also included as the MR criterion for RA, the sensitivity would have improved from 96% to 100%, but the specificity would have decreased to 82%.
False-negative results occurred on the basis of three subsets of the ARA classification tree. The first subset included patients with arthritis of three or more joint areas (including MCP and wrist joints) who were seronegative for rheumatoid factor and in whom hand radiographs were negative. The second subset included patients who were seropositive for rheumatoid factor but who showed asymmetric oligoarthritis not involving wrist or MCP joint areas. The third subset included patients with oligoarthritis who were seronegative for rheumatoid factor. Together, the three subsets constituted 58% (26 of 48) of the patients in this study. If MR imaging was performed only in those subsets of patients, the number of false-negative results would decrease from six to one. Therefore, the ARA classification tree format may be effectively modified by combining an MR imaging criterion in the definition of these subsets (Fig 6). When this format was used to classify subjects in our series, the sensitivity increased to 96%, and the specificity remained unchanged.
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In conclusion, the results of our prospective study revealed that the MR imaging criterion showed excellent sensitivity and specificity for the diagnosis of early-stage RA. MR imaging can be added as a useful tool for evaluation in patients who are suspected of having early-stage RA.
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FOOTNOTES |
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3 Current addresses: Department of Radiology, Sapporo Medical University, Japan.
Abbreviations: ARA = American Rheumatism Association, MCP = metacarpophalangeal, PIP = proximal interphalangeal, RA = rheumatoid arthritis
Author contributions: Guarantor of integrity of entire study, H.S.; study concepts and design, H.S., A.T.; definition of intellectual content, H.S., K.H.; literature research, H.S.; clinical studies, H.S., A.T.; data acquisition, H.S., A.T., K.H.; data analysis, H.S., K.H.; statistical analysis, H.S.; manuscript preparation and editing, H.S.; manuscript review, H.S., A.T.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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