Benedikt Ostendorf, Axel Scherer, Ulrich Mödder, and Matthias Schneider

ARTHRITIS & RHEUMATISM Vol. 50, No. 7, July 2004, pp 2094 2102 DOI 10.1002/art.20314 2004, American College of Rheumatology Diagnostic Value of Magnetic Resonance Imaging of the Forefeet in Early Rheumatoid Arthritis When Findings on Imaging of the Metacarpophalangeal Joints of the Hands Remain Normal Benedikt Ostendorf, Axel Scherer, Ulrich Mödder, and Matthias Schneider Objective. To investigate the diagnostic role of magnetic resonance imaging (MRI) of the forefeet in patients with early rheumatoid arthritis (RA) in whom findings on MR images of the hands are normal and conventional radiographs of the hands and feet do not show erosions. Methods. The study group comprised 25 patients with early RA (disease duration of <12 months) in whom erosions were not demonstrated on conventional radiographs of the hands and feet. These patients underwent MRI of the clinically dominant hand to detect signs of arthritis. If results of MRI of the hand were normal according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA-MRI scoring system (RAMRIS), MRI of the dominant forefoot was performed. The MRI protocol comprised coronal and sagittal T1-weighted spin-echo (before and after administration of contrast medium), coronal fatsuppressed short tau inversion recovery sequences, coronal and sagittal T2-weighted turbo spin-echo sequences, and axial fat-suppressed T1-weighted spinecho sequences after administration of contrast medium. MRI of the forefeet was analyzed on the basis of a modified RAMRIS. Results. MRI revealed pathologic findings in the hands of 15 of 25 patients (edema in 9 patients, synovitis in 12, erosions in 6, defects in 3). In 10 patients with a Benedikt Ostendorf, MD, Axel Scherer, MD, Ulrich Mödder, MD, Matthias Schneider, MD: Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany. Address correspondence and reprint requests to Benedikt Ostendorf, MD, Center for Rheumatology, Department of Nephrology and Rheumatology, Heinrich-Heine University of Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany. E-Mail: ostendorf@ med.uni-duesseldorf.de. Submitted for publication September 20, 2003; accepted in revised form March 5, 2004. mean disease duration of 9.4 weeks, hand MRI scans were normal according to RAMRIS. Four of these 10 patients had tenosynovitis of the finger flexor tendons (there was no OMERACT criterion for tenosynovitis). RAMRIS analysis of the corresponding MRI scans of the forefeet of these patients revealed signs of edema in 7 patients, synovitis in all 10 patients (at the third metatarsophalangeal [MTP] joint in 7, at the fourth MTP joint in 6, at the first MTP joint in 4, and at the fifth MTP joint in 2 patients), tenosynovitis of the foot flexor tendons in 2 patients, erosions at the second and third MTP joints in 1 patient, and a single defect at the first MTP joint in 1 patient. Conclusion. RAMRIS analysis of MRI scans of the forefeet detected synovitis and bone edema in patients with early RA in whom MRI of the finger joints was normal. MRI of the forefeet contributes an additional tool aimed at earlier and more accurate diagnosis and thus might allow an earlier decision to start appropriate medication in patients with early RA. Magnetic resonance imaging (MRI) has a potential for disclosing early signs of inflammation and joint destruction in rheumatoid arthritis (RA) that is superior to that of conventional radiography and clinical examination of the knee (1,2), wrist (3,4), or hand and finger joints (5 9). Diagnosing destructive RA during its early stage is crucial to the implementation of active and aggressive treatment, which is expected to alleviate RA joint damage, thereby reducing functional deterioration and improving the long-term outcome (10 12). Conventional radiography of both the hands and feet is the traditional method used to diagnose RA (13). MRI investigations comparing images of the hands and feet of patients with early RA showed typical bony changes 2094

MRI OF FOREFEET IN DIAGNOSIS OF RA 2095 Table 1. Demographic and clinical details as well as hand MRI and forefeet MRI scoring data according to the OMERACT/RAMRIS (18,19) in 10 patients with early RA* OMERACT score, RAMRIS system, MTP joints 1 5 Patient/ age/sex Disease duration, weeks DAS28 OMERACT score, MRI MCP MTP Erosion Defect Bone edema Synovitis, method 1 (0 3 points) Synovitis, method 2 (millimeters) 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 Sum score 1/43/M 10 3.67 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 2 0 0 0 0 1 4 2/34/F 10 4.23 0 0 0 0 0 0 0 0 0 0 0 3 4 6 0 0 2 2 3 0 0 3 3 6 0 32 3/71/M 6 4.04 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 2 4/52/F 8 4.53 0 2 1 0 0 0 0 0 0 0 0 6 5 0 0 0 1 1 0 0 0 8 7 0 0 31 5/26/F 16 4.46 0 0 0 0 0 0 0 0 0 0 0 2 4 3 0 2 3 3 3 0 2 3 4 3 0 32 6/69/F 12 3.79 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 2 2 3 3 2 1 2 3 3 2 24 7/39/F 6 3.85 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 0 2 0 0 4 8/31/F 8 4.16 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 3 0 0 0 0 4 0 8 9/36/M 10 4.81 0 0 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0 2 3 0 0 0 2 4 0 14 10/39/F 8 4.63 0 0 0 0 0 0 0 0 0 0 0 3 10 10 0 1 0 3 3 0 1 0 6 7 0 44 Sum score 0 2 1 0 0 1 0 0 0 0 0 14 23 23 1 6 8 16 18 4 5 16 27 27 3 * The mean age of patients was 45.1 years; mean disease duration was 9.4 weeks; mean Disease Activity Score in 28 joints (DAS28) was 4.22. Patient 2 had tenosynovitis of the second through fourth hand flexor tendons (score 1 ); patient 4 had tenosynovitis of the second through fifth hand flexor tendons (score 1 ); patient 5 had tenosynovitis of the third hand extensor tendon (score 1 ); patient 8 had tenosynovitis of the fourth foot flexor tendon (score 1 ); patient 10 had tenosynovitis of the second hand flexor tendon (score 1 ). MRI magnetic resonance imaging; RA rheumatoid arthritis; OMERACT Outcome Measures in Rheumatology Clinical Trials; RAMRIS RA-MRI scoring system; MTP metatarsophalangeal; MCP metacarpophalangeal.

2096 OSTENDORF ET AL despite conventional radiographs being normal (14). The fact that conventional radiography has been found to reveal bony erosions in the foot earlier than in the hand joints (15,16) suggests that the feet may be primarily affected in very early RA (17). Therefore, the purpose of our study was to investigate, in patients with early RA and normal MR images of the hands, the diagnostic role of MRI of the forefeet for measuring features of early inflammation such as edema, synovitis, or even incipient osteodestruction, using the RA-MRI scoring system (RAMRIS) (18) of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group (19). PATIENTS AND METHODS Patients. Twenty-five patients (17 women and 8 men ages 18 years and older [mean age 49 years, range 25 74 years]) with early RA diagnosed according to the criteria of the American College of Rheumatology (formerly, the American Rheumatism Association) (20) were recruited from the Early Arthritis Clinic of the Outpatient Department of Rheumatology of the Heinrich-Heine University. Patients with early RA (disease duration of 12 months) were eligible for the study. The mean disease duration was 5.89 months (range 6 weeks to 12 months). Medications used by the patients at the time of study entry included nonsteroidal antiinflammatory drugs; none of the patients had previously received disease-modifying antirheumatic drugs (DMARDs) or corticosteroids. The assessment of general disease activity was based on the Disease Activity Score in 28 joints (DAS28) (Tables 1 and 2) (21,22). Conventional hand (posteroanterior, oblique) and foot (anteroposterior, oblique) radiographs were performed for all patients and were scored according to the method proposed by Larsen et al (23). Subject to their radiographs being graded as nonerosive (Larsen grade 0 or 1), 25 patients underwent MRI analysis of the clinically dominant hand to detect signs of arthritis according to RAMRIS (18). If MRI of the hand was normal according to RAMRIS (n 10), MRI of the clinically dominant forefoot was performed. Clinically dominant was defined as the site more tender to pressure and/or with signs of redness and/or hyperthermia and/or swelling. Protocol for MRI of the hand. A 1.5T MRI whole-body scanner (Siemens Magnetom Vision; Munich, Germany) was used for the MRI examinations. MRI of the second to fifth metacarpophalangeal (MCP) joints of the dominant hand was performed. The hand was fixed within a flexible surface coil (CP flex large). MRI was used to obtain sequences, as follows: coronal T2-weighted turbo spin-echo (TSE) sequences (repetition time [TR]/echo time [TE] 3,500/100 msec, slice thickness 3 mm, field of view [FOV] 10 15 cm, matrix size 512 224 pixels, acquisition time 3 minutes, 50 seconds), coronal fatsuppressed short tau inversion recovery (STIR) sequences (TR/TE/inversion time [TI] 3,975/30/150 msec, slice thickness 3 mm, FOV 10 15 cm, matrix size 256 180 pixels, acquisition time 3 minutes, 30 seconds), and coronal T1-weighted SE sequences (TR/TE 500/15 msec, slice thickness 3 mm, FOV 10 15 cm, matrix size 512 192 pixels, acquisition time 6 minutes, 20 seconds) were obtained before and immediately after intravenous application of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA; 0.1 mmoles/kg of body weight) (Magnevist, Schering, Berlin). Axial T1-weighted fatsuppressed SE sequences (TR/TE 600/15 msec, slice thickness 3 mm, FOV 8 13 cm, matrix size 512 160 pixels, acquisition time 4 minutes, 50 seconds) were obtained after administration of Gd-DTPA. Protocol for MRI of the forefoot. MR imaging of the forefoot was performed using the same hardware as that used for the hand examinations. MRI of the first to fifth metatarsophalangeal (MTP) joints of the clinically dominant foot was performed. The sequences were obtained as follows: sagittal T2-weighted TSE sequences (TR/TE 3,700/96 msec, slice thickness 3 mm, FOV 10 14 cm, matrix size 512 294 pixels, acquisition time 4 minutes, 10 seconds), coronal fat-suppressed STIR sequences (TR/TE/TI 5,300/30/150 msec, slice thickness 3 mm, FOV 10 17 cm, matrix size 256 140 pixels, acquisition time 3 minutes, 40 seconds), and sagittal T1-weighted SE sequences (TR/TE 500/15 msec, slice thickness 3 mm, FOV 10 14 cm, matrix size 512 192 pixels, acquisition time 5 minutes, 30 seconds) were obtained before and immediately after intravenous application of Gd-DTPA (0.1 mmoles/kg of body weight). Axial T1-weighted fat-suppressed SE sequences (TR/TE 740/14 msec, slice thickness 3 mm, FOV 10 15 cm, matrix size 256 192 pixels, acquisition time 4 minutes, 40 seconds) were obtained after administration of Gd-DTPA. MRI evaluation. One experienced rheumatologist (BO) and 2 radiologists (AS and UM) blinded to each patient s identity and clinical data read and scored MR images of the hands and forefeet, in a consensual review. MRI evaluation and scoring of MR images of the hand were performed according to the OMERACT criteria and RAMRIS analysis (18). Definitions of lesions to be scored (OMERACT/ RAMRIS) (18,19). Synovitis was defined as an area in the synovial compartment that shows above-normal post gadolinium enhancement of a thickness greater than the width of the normal synovium. An MRI bone erosion was defined as a sharply marginated bone lesion, with correct juxtaarticular localization and typical signal characteristics, that is visible in 2 planes with a cortical break seen in at least 1 plane. An MRI bone defect was defined as a sharply marginated area of trabecular loss without a visible cortical break. MRI bone edema was defined as a lesion within the trabecular bone, with ill-defined margins and signal characteristics consistent with increased water content. Scoring system for the hand. Bone erosions. Each MCP joint was scored separately for bone erosions. The 0 10-point scale, based on the proportion of eroded bone compared with the assessed bone volume, which was judged on all available images, is as follows: 0 no erosion, 1 1 10% of bone eroded, 2 11 20% of bone eroded, and so forth. For long bones, the assessed bone volume is from the articular surface (or, if absent, its best estimated position) to a depth of 1 cm, whereas it is from the whole bone for carpal bones. Defect. For scoring of bone defects, the scale is 0 10, based on the volume of the defect, as for erosion. Bone edema. Bone edema is scored on a 0 3 scale based on the volume of edema, as follows: 0 no edema, 1

MRI OF FOREFEET IN DIAGNOSIS OF RA 2097 Table 2. Demographic and clinical details as well as MRI scoring data on the hands according to the OMERACT/RAMRIS (18,19) in 15 patients with early RA* OMERACT score, RAMRIS system, MCP joints I V Patient/ age/sex Disease duration, months DAS28 MRI, MCP Erosion Defect Bone edema (0 3 points) Synovitis, method 1 (0 3 points) Synovitis, method 2 (millimeters) 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 2 3 4 5 2 3 4 5 Sum score 11/52/M 12 4.93 0 2 1 0 0 0 0 0 0 0 0 2 1 0 0 2 2 0 0 2 1 0 0 13 12/74/F 7 5.63 0 0 0 0 0 0 0 0 0 0 0 1 1 1 0 3 2 2 0 2 2 1 0 13 13/55/F 11 4.23 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 3 0 0 0 3 0 0 0 7 14/42/F 6 4.90 0 1 3 0 0 0 0 0 0 0 1 1 2 1 0 2 2 2 0 1 1 2 0 19 15/52/F 5 3.73 0 0 0 0 0 0 0 2 0 0 0 0 0 0 0 0 0 3 0 0 0 2 0 7 16/25/M 12 3.42 0 0 0 0 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 0 2 17/62/M 10 4.92 0 0 0 0 0 0 0 0 0 0 0 2 0 0 0 2 0 0 0 3 0 0 0 7 18/58/F 9 4.97 1 4 2 0 0 0 0 0 0 0 0 0 0 0 0 2 2 0 0 2 3 0 0 16 19/64/F 10 4.55 0 0 0 0 0 0 2 0 0 0 1 2 1 0 0 0 0 0 0 0 0 0 0 6 20/68/F 8 4.60 0 1 3 1 0 0 0 0 0 0 0 0 0 0 0 2 2 2 0 3 4 3 0 21 21/49/M 6 4.28 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3 3 0 0 3 2 0 0 11 22/61/F 5 5.63 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0 2 2 3 1 2 3 4 1 20 23/51/M 4 4.23 0 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 0 2 24/32/F 10 4.16 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 3 0 0 0 4 0 0 0 8 25/29/F 9 5.61 0 0 2 1 0 0 0 0 0 0 2 1 2 2 0 2 2 2 2 2 3 3 1 27 Sum score 1 8 11 4 0 0 2 2 0 1 4 12 8 5 0 26 17 14 3 27 19 15 2 * The mean age of patients was 51.6 years; mean disease duration was 8.3 months; mean Disease Activity Score in 28 joints (DAS28) was 4.65. Patients 11, 13, 14, 15, 16, 18, 21, 22, 23, 24, and 25 had tenosynovitis of the hand flexor tendons (score 1 ); patient 19 had tenosynovitis of hand extensor tendons (score 1 ). MRI magnetic resonance imaging; RA rheumatoid arthritis; OMERACT Outcome Measures in Rheumatology Clinical Trials; RAMRIS RA-MRI scoring system; MCP metacarpophalangeal.

2098 OSTENDORF ET AL Table 3. Parameter Correlation of clinical parameters and results of MRI forefoot analysis* DAS28 Disease duration Erosion Bone edema Synovitis, method 1 Synovitis, method 2 DAS Disease duration Erosion Bone edema Synovitis, method 1 Synovitis, method 2 * MRI magnetic resonance imaging; DAS28 Disease Activity Score in 28 joints; not significant; highly significant; moderately significant. 1 33% of bone edematous, 2 34 66% of bone edematous, and 3 67 100% of bone edematous. Synovitis. Synovitis was assessed in the second through fifth MCP joints (the first MCP joint was not scored), using 2 methods. For method 1, a 0 3-point scale is used. A score of 0 is normal, while scores of 1, 2, and 3 (mild, moderate, and severe, respectively) increase by thirds the presumed maximum volume of enhancing tissue in the synovial compartment. For method 2, the maximum thickness of enhancing tissue on the axial scan in the slice showing the most thickening is measured in millimeters. Scoring system for the forefoot. For the definition and scoring of joint pathology of the hands and forefeet, RAMRIS was adapted for MRI forefoot evaluation. Arthritic lesions of the forefoot region to be scored on MR images were synovitis, edema, erosion, and defects. In addition to these OMERACT criteria, we used and scored the appearance of tenosynovitis in the hands and feet (i.e., tissue surrounding the tendon showing high signal intensity on T2-weighted sequences, hypointense signal on T1-weighted images, and enhancement on the post Gd-DTPA images). Tenosynovitis was scored semiquantitatively, as follows: 0 not present, 1 present at the flexor tendons, and 1 present at the extensor tendons. In addition to the number of hand joints covered by RAMRIS for synovitis (the second to fifth MCP joints), we added the first MTP joint to the forefoot score, so that all 5 MTP joints (the first through fifth) could be analyzed. Bone edema was scored using a 0 10-point scale for the volume of edema, as follows: 0 no edema, 1 1 10% of bone affected, 2 11 20% of bone affected, and so forth. Statistical analysis. Pearson s chi-square test was used for statistical analysis. Two variables were considered not statistically independent if their chi-square value was highly significant at the 1% level ( ), moderately significant at less than or equal to the 10% level ( ), and not significant at greater than the 10% level. RESULTS According to RAMRIS analysis (18), 15 of the 25 patients with early RA who were investigated had pathologic findings of the hand by MRI. Signs of edema were detected in 9 of these 15 patients, synovitis in 12, erosions in 6, and defects in 3 (Table 2). In addition, signs of tenosynovitis (for which there was no OMERACT criterion), mostly affecting the flexor tendon sheaths, were observed in 12 patients. Synovitis and erosions were predominantly found at the second and third MCP joints, whereas bone edema was seen in all MCP joints, except the fifth MCP joint, without a significant joint pattern. In 10 of 25 patients with early RA (7 women and 3 men, age range 26 71 years [mean 45 years]), MRI of the hand was normal for edema, synovitis, erosions, and/or defects (Table 1 and Figure 1). This finding must be emphasized, because a normal RAMRIS score for the hand was the inclusion criterion for the additional MRI investigation of the forefeet. In these 10 patients, disease duration ranged from 6 weeks to 16 weeks (mean 9.4 weeks) (Table 1). In patients with early RA and disease duration of 6 weeks (patients 3 and 7), MRI analysis of the forefeet revealed only mild signs of synovitis. In patients with disease duration of 8 10 weeks (patients 1, 2, 4, 8, 9, and 10), signs of bone edema were observed mostly at the second and third MTP joints, and synovitis was observed at the fourth MTP joint. In patients with disease duration of 12 weeks (patients 5 and 6), signs of edema were observed at the second, third, and fourth MTP joints; synovitis was observed at the first through fourth MTP joints in patient 5 and at the first through fifth MTP joints in patient 6. Erosions at the second and third MTP joints were observed in only 1 patient (patient 4), who had a disease duration of 8 weeks. No significant correlation of disease duration with any MRI parameter was demonstrated (Table 3). DAS28 scores in the 10 patients with normal hand MR images ranged from 3.67 to 4.81 (mean 4.22) (Table 1). Because the DAS28 does not include assessment of the feet in patients with RA, we clinically examined the forefeet joints. In 7 of 10 patients, the region of the first through fifth MTP joints was tender to pressure, but no signs of acute swelling were observed. In patients with early RA and a higher mean DAS28

MRI OF FOREFEET IN DIAGNOSIS OF RA 2099 Figure 1. Typical magnetic resonance image (axial T1-weighted fatsuppressed spin-echo sequences of the forefoot), after administration of gadolinium diethylenetriaminepentaacetic acid, for each of the 10 patients with early rheumatoid arthritis. Numbers 1 10 of these images correspond with the patient numbers in Table 1. be bone edema; sy synovitis; er erosion; de defect. ( 4.22; patients 2, 4, 5, 9, and 10), MRI showed signs of severe bone edema, mostly at the second through fourth MTP joints, and additionally showed signs of synovitis, primarily at the fourth MTP joint. Patients with a lower DAS28 ( 4.22; patients 1, 3, 6, 7, and 8) showed almost no signs of edema (patient 8 was given 1 point, by RAMRIS, for the fourth MTP joint), but patients 6, 7, and 8 did have severe synovitis, mostly at the third and fourth MTP joints. One patient with a DAS28 of 3.79 (patient 6) showed signs of severe synovitis in all MTP joints. A highly significant correlation of the DAS28 with the bone edema detected by MRI was found (Table 3). Independently of the clinical assessment, RAMRIS analysis of MR images of the MTP region (first through fifth MTP joints) revealed synovitis in all 10 patients (at the third MTP joint in 7 patients, at the fourth MTP joint in 6 patients, at the first MTP joint in 4 patients, and in the fifth MTP joint in 2 patients). According to method 1 (0 3-point scale, post contrast medium enhancement) (19), synovitis was scored highest at the fourth MTP joint (sum score 18), followed by the third MTP joint (sum score 16). Synovitis as scored by method 2 (thickness in millimeters) (19) was detected mostly at the third and fourth MTP joints (sum score 27 for both) and at the second MTP joint (sum score 16). The detection of bone edema was significantly correlated with the detection of synovitis measured by method 2 (OMERACT ) (Table 3). Tenosynovitis (no OMERACT criterion) was observed in 4 of the 10 patients with normal hand MR images (tenosynovitis of the second through fourth finger flexor tendons in 1 patient, of the second through fifth flexor tendons in 1 patient, of the third extensor tendon in 1 patient, and of the second flexor tendon in 1 patient (Table 1). No patient had tenosynovitis in both the hand and foot. Two patients with normal results of hand MRI had signs of tenosynovitis at the foot flexor tendons. Signs of bone edema were demonstrated in the MTP joints of 7 of 10 patients (in 15 of 50 MTP joints), and synovitis of different degrees, thicknesses, and extensions (scored by methods 1 and 2 [OMERACT]) (19) (Table 1) was observed in all 10 patients investigated (in 23 of 50 MTP joints). Bone edema was detected most intensively at the third and fourth MTP joints (sum score 23 for both). In general, no bone edema could be detected by MRI at the first MTP joint. Only 1 patient showed incipient edema at the fifth MTP joint. Predominant locations for bone edema and synovitis were the second through fourth MTP joints. Eight of 10 patients had no signs of osteodestruction. Slight erosions were found in only 1 patient, at the second and third MTP joints. In 1 patient, an isolated defect at the first MTP joint (1 point by RAMRIS) was detected. DISCUSSION Clinical, laboratory, and radiographic findings often differ in the early stages of RA, and at the time when erosions are first seen by conventional radiography, the disease is often quite established (13). Because the effectiveness of any treatment for RA should be judged on preservation of joint structure, accurate measurement of joint pathology and reliable indicators of

2100 OSTENDORF ET AL outcome are needed earlier in the disease process. In this context, MRI has become a valuable technique for early detection of bone erosions in RA (9). Reports of osteodestruction being detected by conventional radiography earlier and more frequently in the foot than in the hand joints (15 17) provide accumulating evidence that the foot may be primarily affected in the early stages of RA. Therefore, the purpose of our study was to evaluate the diagnostic role of forefoot MRI in early RA. In order to use MRI to assess and analyze incipient arthritis of the forefeet at the earliest time point, we focused on patients with early RA (disease duration of 12 months) who had not received treatment with DMARDs or corticosteroids. To evaluate the diagnostic value of an additional foot MRI scan, patients with early RA were included only when, primarily, conventional radiography of the hands and feet showed no erosions and, secondarily, MRI of the clinically dominant hand was normal according to the OMERACT/RAMRIS (18). In 10 (40%) of 25 patients with early RA, MR images of the hands were negative when scored for RAMRIS parameters such as edema, synovitis, or erosions. Strikingly, we found initial signs of arthritis in the forefoot region (MTP joints). For scoring these MRI findings we adapted the RAMRIS, which was originally developed for analysis of hand MRI (18,19). In addition to the OMERACT set of parameters and joints to be scored, we added the item tenosynovitis to the RAM- RIS, because tenosynovitis is often found early in the course of RA (24), a fact that was confirmed by our findings. To assess tenosynovitis, we simplified the scoring system described by McQueen et al (25) by differentiating absent and present inflammation only at the flexor or extension sheath group. A more detailed analysis of the thickness of the sheath or the degree of inflammation was not included. Because the first MTP joint often is involved in early RA (14), we moreover extended the set of joint regions by adding the first MTP joint. Conversely, inclusion of the first MTP joint will also introduce nonspecific MRI abnormalities from concomitant osteoarthritis, which is very frequent at that site (26). This is the first study to demonstrate that analysis and scoring of forefoot MR images are feasible by using the RAMRIS for hand RA (18). Analysis of MR images of the MTP joints, the earliest site of destructive changes in RA, revealed signs of erosion (at the second and third MTP joints) in 1 patient and an isolated defect at the first MTP joint in another patient; neither of these bony changes had been detected previously by plain radiography. The detection of bony alterations in only 2 patients is in contrast to the findings of Boutry et al (14), who detected bony erosions in 23 (77%) of 30 patients in different MTP joints (first through fifth). This difference might be explained by the longer disease duration of the patients with RA in that study (average duration 12 months), whereas the present study group was characterized by a very short mean disease duration of only 9.4 weeks (range 6 16 weeks). Signs of synovitis, scored by OMERACT methods 1 (points) and 2 (millimeters) (19), were found in all 10 of the patients in our study who had normal MRI of the hand, mostly at the second through fourth MTP joints, and overall in 23 (46%) of 50 MTP joints. Based on the fact that chronic synovitis might finally lead to bone damage, the early detection of synovitis by MRI, measured by either thickness or enhancement, seems to be an important prognostic marker (9). Conaghan et al showed that, in early RA, synovitis appears to be the primary abnormality, and bone damage occurs in proportion to the level of synovitis but not in the absence of synovitis (27). We observed synovitis, without erosive changes, at the fifth MTP joint in 2 patients (20%); the fifth MTP joint is where erosion is most likely to start, according to the findings on plain radiography (17). Boutry et al found synovitis at the fifth MTP joint in 22% of the investigated MTP joints, with no significant difference in appearance between the second through fifth MTP joints (14). In this context, it must be pointed out that our MRI protocol included use of a T1- weighted fat-suppressed SE sequence after gadolinium administration, which is not listed in the core set of MRI acquisitions proposed by OMERACT (19), although this sequence is known to display the highest contrast between enhanced synovitis and surrounding tissue. In addition to erosions and synovitis, we found signs of bone edema in 7 of 10 patients (when using T1-weighted fat-suppressed SE and STIR sequences), predominantly and most intensively at the third and fourth MTP joints (sum score 23) (Table 1). Bone edema is known as a very early marker of inflammation and, in addition to synovitis, as a strong individual predictor of bone erosion in the MRI evaluation of hand RA, carrying a 6.5-fold risk of bone damage at the same site within 1 year (25,28). Longitudinal studies of patients with early RA showed that the total synovial volume in the finger joints and the presence of bone edema seem to be predictive of the number of bone erosions 1 year later and may be used in screening (9). As shown in our study, bone edema seems to be a typical MRI feature in patients with early RA, which usually

MRI OF FOREFEET IN DIAGNOSIS OF RA 2101 might not be found in patients with only nonspecific arthralgia (29). Because T1-weighted fat-suppressed SE and STIR sequences were not used by Boutry et al, detection of the early arthritis marker bone edema failed in that study (14). In general, signs of edema are not detectable by clinical examination and imaging modalities such as conventional radiography and ultrasonography; therefore, assessment of bone edema remains the domain of the MRI technique. Concerning clinical data, we found bone edema combined with synovitis as a sign of early inflammation in the forefeet region in the 5 patients who had a higher mean DAS28 ( 4.22). In patients with lower disease activity (DAS28 4.22), only synovitis of mild degree (1 point by RAMRIS) was detected, with almost no signs of edema. Statistical analysis (Pearson s chi-square test) revealed a significant correlation of the DAS28 with the detection of bone edema and a moderate correlation with the assessment of synovitis measured in millimeters (Table 3). This finding is in contrast to the DAS28 core criteria set (21,22), which does not include joint tenderness and swelling of the feet in patients with RA, and to the results reported by Klarlund et al (6), who found only a poor correlation of the synovial membrane volume measured by quantitative MRI of finger joints with the presence of inflammation and laboratory markers (e.g., erythrocyte sedimentation rate and rheumatoid factor). A limitation of our study was the MRI investigation of only 1 extremity (hand or foot), with the risk of arthritic lesions remaining undetected, although singleextremity MRI delivers higher MRI quality. In this study we mainly focused on MCP joints and not on the total hand including the wrist, in order to have more precise MRI analysis of that joint region, which is the primary site of RA. Another point of discussion is the transfer and extension of the existing MRI hand scoring system RAMRIS (19) to another joint region, such as the forefoot. Further studies are therefore needed to validate use of RAMRIS for evaluation of the rheumatoid joints of the foot in terms of interreader agreement and active-controlled clinical trials assessing treatment effects on MRI parameters such as edema and synovitis, which should be potentially reversible. The results of our study strongly suggest that MRI of the forefeet can be used as an additional diagnostic instrument in early RA, particularly in patients whose clinical features persist but whose conventional radiographs do not demonstrate erosions, and for whom even MRI findings of the hands are normal. 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