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Keywords:

  • Remitting seronegative symmetrical synovitis with pitting edema;
  • Color Doppler ultrasound;
  • Ultrasound contrast;
  • Magnetic resonance imaging;
  • Hand

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Objective

To assess the value of gray-scale ultrasound (US), color Doppler ultrasound (CDUS), contrast-enhanced CDUS, and magnetic resonance imaging (MRI) in the diagnostic evaluation of the hands in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE).

Methods

Eight patients (5 men, 3 women; mean ± SD age 69.3 ± 7.2 years) with clinical diagnosis of RS3PE syndrome underwent US, CDUS, contrast-enhanced CDUS, and MRI. US was performed with a linear array transducer operating at 12 MHz. The US contrast agent (SHU 508; Levovist, Schering, Germany) was intravenously infused in a concentration of 300 mg/ml at a rate of 1 ml/minute.

Results

All patients showed symmetric subcutaneous edema and synovitis of tendons and finger joints on both US and MRI. Vascularity was detected subcutaneously in tendon sheaths and in the joint synovia on CDUS and MRI. Detection of increased vascularity was improved after contrast administration compared with unenhanced CDUS (P < 0.01).

Conclusion

Ultrasound, CDUS, contrast-enhanced CDUS, and MRI are valuable tools in the diagnostic evaluation of involved anatomic structures in patients with RS3PE. Contrast-enhanced CDUS is superior to CDUS in assessment of inflammatory edema, effusion, and synovitis.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is associated with different rheumatologic and neoplastic diseases, typically in elderly men. An abrupt onset of pitting edema of the dorsum of the hands associated with synovitis of the wrist carpus, small joints, and tendon sheaths are described clinical features (1–3). A laboratory test for diagnosing RS3PE is not yet available. Magnetic resonance imaging (MRI) is the only imaging technique that has been previously used for the diagnostic evaluation and followup of RS3PE (4). MRI has shown to be helpful and provides useful information; however, availability and costs may limit its use.

Gray-scale ultrasound (US) has proven to be a useful imaging method for evaluation of joints and superficial structures (5). In addition, color Doppler ultrasound (CDUS) enables characterization of inflammatory activity in synovial proliferation and depicts soft-tissue hyperemia in musculoskeletal inflammatory disease by assessing blood flow in vessels at specific sites (6, 7). However, this technique is limited in the detection of slow flow and flow in small vessels. The addition of recently developed microbubble-based US contrast agents improve the detection of low-volume blood flow by increasing the signal-to-noise ratio (8, 9).

To the best of our knowledge, there are no published data about the use of US, CDUS, and contrast-enhanced CDUS in RS3PE. The purpose of this study was to assess the value of US, CDUS, contrast enhanced CDUS, and MRI in the diagnostic evaluation of hands in patients with RS3PE.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Patients.

Eight consecutive patients (5 men, 3 women) recruited from the rheumatology outpatient clinic of the University Hospital of Innsbruck, with a mean ± SD age of 69.3 ± 7.2 years and clinical diagnosis of RS3PE, underwent US, CDUS, contrast-enhanced CDUS, and MRI examination. The study was conducted according to the Declaration of Helsinki and a signed informed consent was obtained from each patient.

The patients were examined by a single rheumatologist. All patients presented with typical RS3PE as described by McCarty et al (1) and fulfilled the criteria of Olive et al (10), namely: bilateral pitting edema of both hands, sudden onset of polyarthritis, age >50 years, and absence of rheumatoid factor (RF). The rapid response to corticosteroid treatment (methylprednisolone at oral doses of 8–20 mg) confirmed the clinical diagnosis.

The erythrocyte sedimentation rate (by the Westergren method) was 42 ± 23 mm/first hour (normal <10), and the C-reactive protein (by nephelometry) was 3.78 ± 3.71 mg/dl (normal <0.7). RF (by enzyme-linked immunosorbent assay for IgM-RF) tested negative in all patients. HLA–B27 was positive in 1 of 8 patients, and low-titer antinuclear antibodies were found in 1 of 8 patients. Standard radiographs of the hands were performed to detect joint erosions.

Ultrasound techniques.

Immediately after clinical examination, US, CDUS, and contrast-enhanced CDUS were performed by a radiologist, blinded to the findings of clinical examination and MRI. US and MRI examinations of one hand in each patient were performed within 24 hours.

US was performed with a high-resolution transducer operating at 10–12 MHz (VFX5-13 Sonoline Elegra; Siemens Medical Systems-Ultrasound Group, Issaquah, WA) with a Doppler frequency of 6–9 MHz. The US examination was standardized for reproducibility, including longitudinal and transverse US scans with the joints in 20° of palmar flexion of the second, third, and fourth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints; the flexor and extensor tendons of the second, third, and fourth finger; and the subcutaneous tissue from the volar and dorsal aspect. Special attention was paid to adjusting the penetration depth and focal zones to the different depths of the 3 anatomic structures and to using standardized settings for each level in each patient, mainly dependent on the amount of pitting edema. Care was taken to apply the least pressure possible, especially for the examination of the subcutaneous tissue level. We used a gel standoff pad (Sonar Aid, Geistlich; Wolhusen, Switzerland) in all cases.

The US examination was performed under a constant room temperature of 70°F (21°C). Digital image storage and videotape records were produced on each case. US was performed to evaluate alterations of joints, tendon sheaths, and subcutaneous tissue. Joint effusion or synovitis was present when the echogenic joint capsule was elevated by a hypoechoic intraarticular thickening. Thickening of the tendon sheaths was defined with values >1 mm (11, 12). To the best of our knowledge, there are no proven data in the literature about normal thickness of the subcutaneous tissue. According to our own experience on healthy subjects (unpublished data), we defined normal subcutaneous structures of the hand with an upper limit of 10 mm. Dynamic active and passive US examination was performed to evaluate gliding ability of the tendons.

Color Doppler ultrasound.

CDUS examination was performed to detect synovial vascularization of joints and tendons and vascularization of the subcutaneous tissue. Detection of vascularization enables improved differentiation between fluid and synovitis in hypoechoic thickening of joints and tendon sheaths. Vascularization was graded subjectively based on the intensity of color flow signals using a score of 0–3, as described previously (9).

CDUS was performed in both the color Doppler frequency and the color Doppler amplitude (power Doppler) modes. Standardized machine settings with appropriate frequency and color velocity scale were chosen and remained fixed throughout the CDUS and contrast-enhanced CDUS study (transmit power 500 mW/cm2, a low-pass wall filter, and medium persistence). These settings were chosen to maximize sensitivity to low-velocity and low-volume blood flow. The color Doppler gain was optimized by increasing gain until noise appeared and then reducing gain just enough to suppress the noise (usually 60–70% gain). Color Doppler amplitude gain was optimized by turning up the gain until first noise appeared in the background (75–85% gain). The window (color box) was restricted to the areas studied: subcutaneous area, tendon area, and joint area. After visualization of color-flow signals, pulse-waved spectral Doppler imaging was performed using the lowest filter setting (125 Hz) and the smallest scale available that would display the Doppler waveforms as large as possible without aliasing. A spectral Doppler tracing was obtained to confirm that the color Doppler signals represented true arterial or venous flow.

Contrast-enhanced CDUS.

The US contrast agent (SHU 508; Levovist, Schering, Berlin, Germany) was administered intravenously. Fifteen milliliters were used at a concentration of 300 mg/ml by continuous slow infusion technique at a rate of 1 ml/minute using a Secura FD perfusor (Braun, Maria Enzersdorf, Austria). This infusion technique provides uniform, optimal contrast enhancement for up to 20 minutes. Subsequently, color Doppler frequency mode, color Doppler amplitude mode, and pulsed-wave spectral Doppler imaging were performed with the same technique as in the unenhanced imaging study. US findings were rated on both CDUS and contrast-enhanced CDUS.

Dilated lymphatics can be visualized by high-frequency US according to Chersevani et al (13). They were visualized as subcutaneous hypoechoic bands like a hypoechoic network, formed by thin bands parallel and perpendicular to the skin, without vessel characteristics, no compressibility, and without signs of blood flow in the CDUS or contrast-enhanced CDUS (13). Synovial proliferation of extensor and flexor tendons was diagnosed when enlarged peritendinous structures revealed vascularity detected by CDUS or contrast-enhanced CDUS. Articular synovitis was diagnosed when vascularization in hypoechoic joint thickening was detected.

Magnetic resonance imaging.

MRI was performed with a Magnetom Vision 1.5 Tesla unit (Siemens, Erlangen, Germany) using the following pulse sequences: coronal T1-weighted spin echo, coronal T2-weighted fast spin-echo sequences (645/20 [repetition time msec/echo time msec] and 3338/96, respectively), coronal gradient echo T1-weighted sequence (512/15, flip 30), axial T1-weighted spin echo, axial T2-weighted fast spin-echo sequences, (675/12 and 4,784/95, respectively), and coronal and axial T1-weighted spin-echo sequence after administration of a gadolinium contrast agent at the dosage of 0.1 ml/kg (Magnevist; Schering). A dedicated phased-array wrist coil was used. Two averages were obtained. Section thickness was 2 mm, with a 0.2-mm gap intersection. The matrix size was 256 × 256. The field of view was 16 cm.

Patients were positioned prone with their arms extended above the head. To reduce patient motion, we taped the finger to the adjacent finger and the tuft. The MRI evaluation included the diagnosis of effusion in tendon sheaths, joints, distension of lymphatics, and subcutaneous tissue thickening. Contrast enhancement was evaluated for the presence of synovial proliferation in tendon sheaths and joints.

Statistical analysis.

The degree of vascularization was assessed subjectively by using a scale defining no color-flow signals as grade 0; 1–5 color-flow signals as grade 1; 6–10 color-flow signals as grade 2; and 11 or more color-flow signals as grade 3.

The data were analyzed using StatView software (version 4.02; Abacus Concepts, Berkeley, CA). Differences between CDUS and contrast-enhanced CDUS for the detection of vascularity (grade 0 versus grade >0) were evaluated with the McNemar test. Differences between the degree of vascularization on CDUS and contrast-enhanced CDUS among all patients were evaluated by the Wilcoxon's matched-pairs signed-rank test (14). A P value < 0.05 was defined as significant. For the purpose of this comparison, we used the highest grade of vascularity identified in each patient.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Radiographs

The radiographs demonstrated subtle signs of osteoarthritic changes without evidence of erosions.

Ultrasound findings.

US and CDUS.

US examinations were technically successful for all MCP and PIP joints, flexor and extensor tendons, and overlying subcutaneous tissue of the second, third, and fourth fingers. Pitting edema showed hypoechoic dilated tubular structures that were interpreted as lymphatics. These findings were mainly on the dorsum of the hand, with associated thickened subcutaneous soft tissue. Hyperechoic bands representing connective septa as described by Chersevani et al (13) were delineated in the subcutaneous tissue (Figure 1A).

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Figure 1. Ultrasound (US), color Doppler ultrasound (CDUS), contrast-enhanced CDUS, and magnetic resonance imaging (MRI) findings in a 63-year-old woman with remitting seronegative symmetrical synovitis with pitting edema of the hand. A, Axial US shows subcutaneous edema with extensive hypoechoic dilatation of lymphatics (arrows). B, CDUS shows subcutaneous thickening with vascularity (grade 1) (arrows). C, Contrast-enhanced CDUS demonstrates increased vascularity at the extensor apparatus (grade 3) and the subcutaneous tissue (arrows). D, Axial T1-weighted MRI shows increased subcutaneous fluid at the radial aspect of the dorsal wrist (white arrows) and thickening of the extensor apparatus (black arrows). E, Contrast-enhanced MRI shows enhancement at the dorsal wrist (white arrows) and of the extensor apparatus (black arrows).

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CDUS showed hypervascularization of the subcutaneous soft tissue in 5 of 8 patients (62.5%) (Figures 1B and 2D). All patients revealed peritendinous hypoechoic thickening with hypervascularization (10 of 24 extensor tendons, 5 of 24 flexor tendons) diagnosed as synovial proliferation. Hypoechoic thickening of MCP and PIP joints was found in 37 of 96 joints (38.5%) (Figure 2A). Nine of 96 joints (9.3%; MCP and PIP ventrally and dorsally) showed signs of vascularization on CDUS (Figure 2B).

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Figure 2. Ultrasound (US), color Doppler ultrasound (CDUS), and contrast-enhanced CDUS findings in 57-year-old patient with remitting seronegative symmetrical synovitis with pitting edema of the hand. A, Longitudinal US shows increased hypoechoic thickening (arrows) at the proximal interphalangeal (PIP) joint. B, Unenhanced CDUS shows grade 1 vascularity in the increased hypoechoic thickening of the PIP II joint. C, Corresponding contrast-enhanced CDUS demonstrates increased vascularity at the PIP II joint (arrows) (grade 2). D, CDUS shows extensive subcutaneous thickening (arrows) at the ulnar dorsal wrist with grade 1 vascularity. E, Contrast-enhanced CDUS demonstrates increased vascularity of the ulnar dorsal wrist (arrows) (grade 3).

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During dynamic US examination, no impaired gliding ability of the tendons was detected.

Contrast-enhanced CDUS.

Increased vascularity of the subcutaneous tissue was found after contrast administration in 8 of 8 patients on the dorsal side and in 2 of 8 on the ventral side (Figure 2E). Four patients with hypervascularization on CDUS showed an increase of vascularity to grade 3 after contrast administration. Four patients showed grade 2 and 2 patients showed grade 1 vascularity on contrast-enhanced CDUS.

With contrast-enhanced CDUS, the distended tendon sheaths of extensor and flexor tendons showed vascularity of grade 1 in 10 of 48, grade 2 in 14 of 48, and grade 3 in 11 of 48 (Figure 1C). Increased vascularity was found in 22 of 96 joints (23%; PIP and MCP joints), showing vascularization grade 1 in 18 of 96 and grade 2 in 4 of 96 (Figure 2C). Hypoechoic joint thickening without vascularization was found in 15 of 96 joints (15.6%) and therefore interpreted as joint fluid/effusion. Comparison of vascularity detected by CDUS and contrast-enhanced CDUS shows that contrast-enhanced CDUS is more sensitive for the detection of vascularity (P < 0.01) (Table 1). Contrast-enhanced CDUS also showed a significant increase in the grade of vascularity compared with CDUS (P < 0.01) (Table 2).

Table 1. Vascularity grades detected by CDUS and contrast-enhanced CDUS*
 Grade
0123
  • *

    The numbers are based on the imaging findings of 1 hand (ventral and dorsal; second, third, and fourth fingers) of each patient. CDUS = color Doppler ultrasound.

Subcutaneous structures    
 CDUS 5 of 16 (31.3%)11500
 Contrast-enhanced CDUS 10 of 16 (62.5%)6244
Tendon sheaths    
 CDUS 15 of 48 (31.2%)33780
 Contrast-enhanced CDUS 35 of 48 (72.9%)13101411
Joints    
 CDUS 9 of 96 (9.4%)81900
 Contrast-enhanced CDUS 22 of 96 (22.9%)151840
Table 2. CDUS and contrast-enhanced CDUS findings in subcutis, tendon sheaths, and joints*
 CDUSContrast-enhanced CDUS
  • *

    Values are the mean ± SD grade of vascularity. CDUS = color Doppler ultrasound.

  • P < 0.01 versus CDUS.

  • P < 0.01 versus joint vascularity.

Subcutis0.31 ± 0.51.38 ± 1.2
Tendon sheaths0.31 ± 0.61.02 ± 1.1
Joints0.09 ± 0.30.27 ± 0.5

Magnetic resonance imaging.

The detailed findings of both imaging modalities are shown in Table 3. In brief, subcutaneous edema with maximal extension at the middorsum of the hand showed contrast enhancement in 8 of 8 patients (100%) dorsally and in 2 of 8 (25%) ventrally. Enhancement of thickened extensor and flexor tendon sheaths revealed synovial proliferation in 30 of 48 tendons (62.5%; Figure 1D, 1E) and additional small amounts of fluid in 22 of 48 tendon sheaths (45.8%). Enhancement of articular synovial proliferation was found in 22 of 96 joints (22.9%; Figure 3A, 3B) and small joint effusions in 21 of 96 joints (21.8%; Figure 3C). Contrast-enhanced CDUS showed comparable results to MRI in the detection of inflammatory changes (Table 4).

Table 3. Comparison of US and MRI findings*
 US n (%)MRI n (%)
  • *

    Ultrasound (US) findings are defined as alteration detected by gray-scale US. Magnetic resonance imaging (MRI) findings are based on the detection of alterations by all used sequences but without contrast administration. MCP = metacarpophalangeal joint; PIP = proximal interphalangeal joint.

Subcutaneous tissue thickening,  ventral and dorsal (n = 16)10 (62.5)10 (62.5)
Tendon sheath thickening  
 Dorsal: extensor (n = 24)24 (100)24 (100)
 Ventral: flexor (n = 24)15 (62.5)16 (66.6)
Second through fourth finger joint  thickening, ventral and dorsal  (n = 48)  
 MCP17 (35.4)17 (35.4)
 PIP20 (41.6)22 (45.8)
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Figure 3. Magnetic resonance imaging (MRI) findings in 57-year-old patient from Figure 2 with remitting seronegative symmetrical synovitis with pitting edema of the hand. A, Coronal T1-weighted MRI shows small metacarpophalangeal (MCP) II joint thickening (white arrows), subcutaneous thickening at the MCP II area (single white arrow), and extensive subcutaneous thickening at the ulnar wrist (black arrows). B, Contrast-enhanced MRI shows discrete enhancement at the MCP II joint (white arrow) and enhancement at the dorsal wrist (black arrows). C, Coronal gradient echo T1-weighted MRI detects a small amount of fluid in the MCP II (white arrows) and fluid subcutaneously (black arrows).

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Table 4. Comparison of CDUS, contrast-enhanced CDUS, and contrast-enhanced MRI findings*
 CDUS n (%)Contrast-enhanced CDUS n (%)MRI n (%)
  • *

    Ultrasound (US) findings are defined as increased hypoechoic thickening. Color Doppler ultrasound (CDUS), contrast-enhanced CDUS, and magnetic resonance imaging (MRI) findings are based on the detection of vascularity. MCP = metacarpophalangeal joint; PIP = proximal interphalangeal joint.

Subcutaneous tissue thickening, ventral and  dorsal (n = 16)5 (31.3)10 (62.5)10 (62.5)
Tendon sheath thickening   
 Extensor (n = 24)10 (41.7)23 (95.8)23 (95.8)
 Flexor (n = 24)5 (20.8)13 (54.2)13 (54.2)
Second through fourth finger joint thickening,  ventral and dorsal   
 MCP (n = 48)7 (14.6)17 (35.4)17 (35.4)
 PIP (n = 48)2 (4.2)5 (10.4)5 (10.4)

Results of this study have shown that US, CDUS, contrast-enhanced CDUS, and MRI can be used to detect synovial proliferation in hands of patients with RS3PE.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES

Although clinical examination usually allows for diagnosis of RS3PE, Schaeverbeke et al (15) reported that RS3PE was diagnosed retrospectively in 9 of 24 patients. The diagnostic gap between determination of RS3PE and clinical findings requires imaging to establish the final diagnosis. MRI has been utilized for the diagnostic evaluation of RS3PE and has shown to be useful (3). Cantini et al (4) described improved detection of joint synovitis by MRI in comparison with clinical examination, which was limited due to extensive swelling. However, MRI has its well-known limitations.

A readily available and less-expensive imaging method might assist in early diagnosis and treatment of patients with a false-negative clinical examination result. US can detect pannus and joint vascularization, which are associated with disease activity in rheumatoid arthritis (RA) (16). However, gray-scale US is limited in the differentiation between hypoechoic thickening of the joint caused by increased fluid or synovial proliferation, because low-level echoes are often present in joint fluid (7). In this study, US, CDUS, and contrast-enhanced CDUS findings in RS3PE were compared with MRI findings to determine whether contrast-enhanced CDUS might improve the differentiation of synovial proliferation and joint fluid. Hypoechoic joint thickening was noted on gray-scale US in 37 of 96 joints (38.5%), and CDUS showed vascularization in 9 of 37 joints (24.3%) (grade 1), and contrast-enhanced CDUS demonstrated vascularization in 22 of 37 joints (59.5%) (grade 1–2). MRI demonstrated vascularization in the same 22 of 37 joints (59.5%). No intraarticular vascularization was evident in the hypoechoic thickening found sonographically in 15 of 37 joints (40.5%), whereas MRI diagnosed joint effusion in 21 of 96 joints (21.9%) (not outlined in Table 3). Thus, MRI seems to be more sensitive in the characterization of small amounts of joint effusion, even when US shows no thickening. Our results clearly demonstrate that contrast-enhanced CDUS is superior to unenhanced CDUS in the delineation of articular fluid from inflammatory activity, and correlated well with MRI. There is no overestimation of perfusion in contrast-enhanced CDUS compared with the gold standard MRI. As demonstrated in Table 4, even with the use of high-resolution US, MRI has shown to be better in the detection of joint thickening in 3 joints. This relies on the excellent detection of fluid on MRI. Our findings are in line with previously published data (4), which reported that joint synovitis is less frequent and less dominant than inflammation in tendon sheaths in patients with RS3PE. Joint synovitis was less frequent and less dominant than inflammation in tendon sheaths in patients with RS3PE. We could confirm this aspect because both MRI and contrast-enhanced CDUS found only ∼50% of hypoechoic articular thickening to be synovitis, contrary to the extensive presence of tenosynovitis.

Synovial proliferation in tendon sheaths could be depicted with both contrast-enhanced CDUS and MRI in 23 extensor tendons and 12 flexor tendons, whereas CDUS was positive in 10 extensor and 5 flexor tendons only. Thickening of flexor tendons was observed by both US and MRI in 1 case only, with hypervascularization of the tendon itself caused by extensive tenosynovitis.

During dynamic US examination, which is performed by active and passive finger motion, no impaired gliding ability of the tendons was detected. The clinical finding of impairment of finger motion may be explained by synovial tissue proliferation in the tendon sheaths, which was a predominant finding in our study, as well as by effusions in the PIP joints and extensive subcutaneous thickening.

Subcutaneous thickening in RS3PE is characterized by the presence of pitting edema. RS3PE edema is smoother in comparison with other causes of lymphatic edema and rapidly improves with antiinflammatory treatment. The underlying pathogentic mechanism of pitting edema is still not completely clear, but lymphatic involvement with a decreased lymphatic clearance has been described in a few cases associated with RA. In RA, an increased capillary permeability as a result of local inflammation with increased filtration of tissue fluid has been reported. Increased tissue pressure may cause “small vessel congestion” due to edema and synovial proliferation and may explain the poor sensitivity of unenhanced CDUS for subcutaneous vascularization (17).

Because of the improved sensitivity for slow flow with microbubble contrast agents, contrast-enhanced CDUS found hypervascularity (grade 2–3) in the subcutaneous tissue in all patients. In fact, contrast-enhanced CDUS findings correlated better with contrast-enhanced MRI findings than with unenhanced CDUS.

The identification of lymphatics in RS3PE is an important issue, which can be well delineated by high-frequency US as hypoechoic tubular structures (13). CDUS enables the differentiation between vessels and dilated lymphatics, as both can appear as tubular structures. Based on the pharmacologic kinetics of the microbubbles, it is unlikely that contrast-enhanced CDUS is able to enhance dilated lymphatics because the microbubbles are blood pool agents that remain in the blood pool until they dissolve and therefore further allows a better differentiation of small vessels and dilated lymphatics.

Interestingly, in 2 of our patients, subcutaneous thickening was detected without delineation of extensive lymphatic vessel dilatation, but with extensive vascularity in the unenhanced CDUS examination. We hypothesize that this could represent a very early presentation. It is possible that increased vascularity may be an early finding on CDUS. Later in the course of the disease, vessel compression due to edema might reduce blood flow. Longitudinal studies may be necessary to characterize the sonographic findings of pitting edema during different stages of RS3PE.

In a study by Cantini et al (4), wrist synovitis (which is difficult to detect clinically) was detected in 83% by MRI. This seems to be in line with our findings. Our data give results for US, and we found that only contrast-enhanced US enables an accurate differentiation of synovitis and fluid. However MRI seems to be more sensitive. Cantini et al described a limited dorsal and palmar flexion of both hands and feet, mainly due to tenosynovitis. In our study using dynamic US examination with active and passive finger motion, we could not detect an impaired gliding mobility of the tendon itself. However, the impaired motion was caused by the extensive joint and tendon sheath fluid/synovitis, which is in line with the suggestions of Cantini et al (4).

We note several limitations of our study. First, a single investigator performed the US examinations. Although the investigator was blinded to clinical and MRI findings, we do not have data on intra- and interobserver variability. Second, the grading of the vascularity was subjective. Although a study by Walther et al (18) found a good correlation between subjective grading of vascularity in the pannus of the knee and digital image evaluation, objective assessment by computer-assisted quantification might further improve the value of contrast-enhanced CDUS. The assessment of vascularity using 2 different imaging modalities with different contrast agents (microbubbles are blood pool agents whereas MRI gadolinium leaks into the tissue) is a further limitation. Terslev et al (19) compared power Doppler US with contrast-enhanced MRI using terms like color fraction, color Doppler pixels, and measurements of the resistive index, and they found an association between US and MRI enhancement. Recently, the term color pixel has shown to be helpful for the assessment of vascularity by CDUS in healthy joints (20). Finally, we evaluated a limited small number of patients to establish the value of US, CDUS, contrast-enhanced CDUS, and MRI. Our results for differentiation of effusion and synovial proliferation might be of clinical importance even in other rheumatic conditions and should therefore be evaluated further. As a final point, we note that an advantage of contrast-enhanced CDUS, compared with MRI, is the availability, the lower costs, even using microbubble contrast agents, and its effectiveness as a bedside modality.

US, CDUS, contrast-enhanced CDUS, and MRI have been shown to add detailed information to the clinical examination of involved anatomic structures in patients with RS3PE. Our series demonstrated predominant extraarticular synovial structures involved in the inflammatory process with tenosynovitis of extensor and flexor tendons, and only mild articular synovitis. Increased vascularity could be less detected by CDUS, whereas contrast-enhanced CDUS showed an improved detection with comparable results with MRI. Articular synovial proliferation, which is difficult to assess by clinical examination due to extensive swelling and edema, showed hypoechoic changes on US and increased vascularity on contrast-enhanced CDUS. Contrast-enhanced CDUS was superior to unenhanced CDUS in the detection of hypervascularity in tendons and joints, thus enabling the differentiation of synovial proliferation or effusion, and MRI was the best method for detection of small amounts of effusion.

In conclusion, our study shows that US, CDUS, contrast-enhanced CDUS, and MRI are valuable tools, which may be helpful adjuncts to clinical examination in diagnosing RS3PE.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. REFERENCES
  • 1
    McCarty DJ, O'Duffy JD, Pearson L, Hunter JB. Remitting seronegative symmetrical synovitis with pitting edema: RS3PE syndrome. JAMA 1985; 254: 27637.
  • 2
    Salvarani C, Cantini F, Macchioni P, Olivieri I, Niccoli L, Padula A, et al. Distal musculoskeletal manifestations in polymyalgia rheumatica: a prospective followup study. Arthritis Rheum 1998; 41: 12216.
  • 3
    Salvarani C, Gabriel S, Hunder GG. Distal extremity swelling with pitting edema in polymyalgia rheumatica: report of nineteen cases. Arthritis Rheum 1996; 39: 7380.
  • 4
    Cantini F, Salvarani C, Olivieri I, Barozzi L, Macchioni L, Niccoli L, et al. Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study. Ann Rheum Dis 1999; 58: 2306.
  • 5
    Bianchi S, Martinoli C, Bianchi-Zamorani M, Valle M. Ultrasound of the joints. Eur Radiol 2002; 12: 5661.
  • 6
    Backhaus M, Kamradt T, Sandrock D, Loreck D, Fritz J, Wolf KJ, et al. Arthritis of the finger joints: a comprehensive approach comparing conventional radiography, scintigraphy, ultrasound, and contrast-enhanced magnetic resonance imaging. Arthritis Rheum 1999; 42: 123245.
  • 7
    Newman JS, Adler RS, Bude RO, Rubin JM. Detection of soft-tissue hyperemia: value of power Doppler sonography. AJR Am J Roentgenol 1994; 163: 3859.
  • 8
    Goldberg BB, Liu JB, Forsberg F. Ultrasound contrast agents: a review. Ultrasound Med Biol 1994; 20: 31933.
  • 9
    Klauser A, Frauscher F, Schirmer M, Halpern E, Pallwein L, Herold M, et al. The value of contrast-enhanced color Doppler ultrasound in the detection of vascularization of finger joints in patients with rheumatoid arthritis. Arthritis Rheum 2002; 46: 64753.
  • 10
    Olive A, del Blanco J, Pons M, Vaquero M, Tena X, and the Catalan Group for the Study of RS3PE. The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. J Rheumatol 1997; 24: 3336.
  • 11
    Klauser A, Bodner G, Frauscher F, Gabl M, Zur Nedden D. Finger injuries in extreme rock climbers: assessment of high-resolution ultrasonography. Am J Sports Med 1999; 27: 7337.
  • 12
    Serafini G, Derchi LE, Quadri P, Martinoli C, Orio O, Cavallo A, et al. High resolution sonography of the flexor tendons in trigger fingers. J Ultrasound Med 1996; 15: 2139.
  • 13
    Chersevani R, Tsunoda-Shimizu H, Giuseppetti GM, Rizzato G. Breast. In: SolbiatiL, RizzatoG. Ultrasound of superficial structures. New York: Churchill Livingstone; 1995. p. 186.
  • 14
    Altman DG. Practical statistics for medical research. 1st ed. London: Chapman and Hall; 1991.
  • 15
    Schaeverbeke T, Fatout E, Marce S, Vernhes JP, Halle O, Antoine JF, et al. Remitting seronegative symmetrical synovitis with pitting oedema: disease or syndrome? Ann Rheum Dis 1995; 54: 6814.
  • 16
    Hau M, Schultz H, Tony HP, Keberle M, Jahns R, Haerten R, et al. Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis by high-resolution ultrasound (multidimensional linear array). Arthritis Rheum 1999; 42: 23038.
  • 17
    Russell EB, McCarty DJ, Schwab J, Hanel D, Komorowski R, Stransky G, et al. RS3PE syndrome: no evidence for retroviruses. J Rheumatol 1994; 21: 11056.
  • 18
    Walther M, Harms H, Krenn V, Radke S, Kirschner S, Gohlke F. Synovial tissue of the hip at power Doppler US: correlation between vascularity and power Doppler US signal. Radiology 2002; 225: 22531.
  • 19
    Terslev L, Torp-Pedersen S, Savnik A, von der Recke P, Qvistgaard E, Danneskiold-Samsoe B, et al. Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: a comparative study. Arthritis Rheum. 2003; 48: 243441.
  • 20
    Terslev L, Torp-Pedersen S, Qvistgaard E, von der Recke P, Bliddal H. Doppler ultrasound findings in healthy wrists and finger joints. Ann Rheum Dis 2004; 63: 6448.