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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 12  |  Issue : 1  |  Page : 6-11

Ultrasonographic evaluation of joint involvement in rheumatoid arthritis: Comparison with conventional radiography and correlation with disease activity parameters


1 Department of Medicine, Jaipur National University, IMSRC, Jaipur, Rajasthan, India
2 Department of Medicine, SMS Medical College, Jaipur, Rajasthan, India
3 Department of Cardiology, Metro Mass Hospital, Mansarovar, Jaipur, Rajasthan, India
4 Department of Radiology, Niramaya Hospital, Jaipur, Rajasthan, India

Date of Web Publication23-Feb-2017

Correspondence Address:
Renu Saigal
33, Muktanand Nagar, Gopalpura Bypass, Tonk Road, Jaipur - 302 018, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.199123

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  Abstract 

Background: Ultrasound (US) including power Doppler (PD) are increasingly being used to evaluate joint involvement in rheumatoid arthritis (RA). Aim of this study was to evaluate joint involvement in RA by US including PD and gray scale imaging and its comparison with conventional radiographic changes and correlation with disease activity parameters.
Methods: Patients with RA of less than 3.5 years disease duration were subjected to detailed clinical examination and laboratory investigations. After X-ray imaging (posterior-anterior view) of both hand joints, PD and gray scale US examination of 14 joints of both hands was performed and mean cumulative flow signal score (CFS) was calculated. Disease activity score (DAS28) was also calculated for each patient.
Results: Out of total 57 patients evaluated, 54 had abnormal findings on US as compared to only 17 having radiographic abnormalities. US could detect erosions in 29 patients including all of the fourteen patients who had radiographically detectable erosions. On US evaluation, radiocarpal joint was involved most frequently. The mean CFS was 1.17 ± 1.64 in patients who were in remission (DAS28 <2.6), 3.00 ± 3.46 in patients having low disease activity (DAS28 2.6–3.2), 5.25 ± 4.22 in patients with moderate disease activity (DAS28 3.2–5.1), and 6.95 ± 3.84 in patients with high disease activity (DAS28 > 5.1). The difference in CFS among these groups was statistically significant (P < 0.01). In 5 out of 12 patients with DAS28 <2.6, i.e., in remission, CFS were high showing subclinical synovitis. Mean CFS correlated significantly with DAS28 (r = +0.42, P < 0.05); C-reactive protein (r = +0.50, P < 0.05); and erythrocyte sedimentation rate (r = +0.39, P < 0.05).
Conclusions: US detected CFS which an indicator of ongoing inflammation in RA patients with clinical remission (DAS28 <2.6). US is more sensitive than conventional radiography for detection of erosions. CFS on PD had a significant correlation with markers of disease activity.

Keywords: Power Doppler, rheumatoid arthritis, ultrasonography


How to cite this article:
Saigal R, Goyal L, Maharia H, Sharma M, Agrawal A. Ultrasonographic evaluation of joint involvement in rheumatoid arthritis: Comparison with conventional radiography and correlation with disease activity parameters. Indian J Rheumatol 2017;12:6-11

How to cite this URL:
Saigal R, Goyal L, Maharia H, Sharma M, Agrawal A. Ultrasonographic evaluation of joint involvement in rheumatoid arthritis: Comparison with conventional radiography and correlation with disease activity parameters. Indian J Rheumatol [serial online] 2017 [cited 2017 Apr 29];12:6-11. Available from: http://www.indianjrheumatol.com/text.asp?2017/12/1/6/199123


  Introduction Top


In rheumatoid arthritis (RA), synovitis appears to be the primary abnormality responsible for structural joint damage.[1] Angiogenesis is an important feature in pannus formation which plays a crucial role in destruction of joint. Doppler ultrasound (US) can detect pathological vascularization within joints and changes in the periarticular soft tissues, thus can demonstrate the presence of active inflammation, which can be correlated with the neoangiogenesis in the synovium. Power Doppler (PD) is a valid tool for the detection and quantification of synovial vascularization.[2]

Early diagnosis of RA is important because early aggressive treatment reduces the long-term disability.[3] For early detection of subclinical synovitis, clinical examination, and laboratory tests are limited in their usefulness. Radiographic changes occur late and may not be detected early in the disease course.[4],[5]

In the early course of RA, application of US including both PD and gray scale imaging has been shown to be more sensitive than clinical examination in determining synovitis.[6] US is an easily available, noninvasive, relatively inexpensive, radiation-free, and reliable technique for scanning of multiple joints at the time of consultation and recent improvement in technology coupled with portability and safety makes US the first choice imaging investigation for the evaluation of musculoskeletal diseases.

US can evaluate various features of both intra-articular (effusion, synovial hypertrophy and vascularity, marginal erosions) and extra-articular disease (tenosynovitis, enthesopathy).[7],[8],[9],[10]

US is more reliable for detecting joint effusion and synovial hypertrophy compared with magnetic resonance imaging.[9] US provides a quick correlation between clinical features and imaging findings which help in accurate diagnosis and management of RA.

The aim of this study was to evaluate joint involvement in RA by US (combination of both PD and gray scale imaging) and its comparison with radiographic changes and its correlation with disease activity parameters.


  Methods Top


Patients and assessments

Patients with RA of less than 3.5 years duration, diagnosed according to 1987 revised criteria of the American College of Rheumatology,[11] who attended the Rheumatology Clinic, at a tertiary care center of western India, from August 2008 to July 2009, were included in this study. Disease duration of <3.5 years was taken arbitrarily so that we can assess the US findings (such as effusion, vascularity, synovial hypertrophy, and marginal erosions) in early as well as established RA.

Baseline data were collected regarding detailed disease history, and each patient was subjected to complete rheumatologic assessment including clinical, laboratory, and radiologic evaluation.

Laboratory investigations, namely, complete blood count, erythrocyte sedimentation rate (ESR) (measured by Westergren method), fasting blood glucose, liver, and kidney function tests were performed in each patient. Rheumatoid factor (RF) and C-reactive protein (CRP) levels were estimated by turbidimetry.

Disease activity was assessed according to disease activity score of 28 joints (DAS28).[12] The DAS28 >5.1 was high disease activity; DAS28 3.2–5.1 moderate disease activity; DAS28 <3.2 low disease activity; and DAS28 <2.6 indicated remission in RA patients.

Conventional radiographs of both hands in posteroanterior view were taken. These were evaluated for both erosions and joint space narrowing by an experienced radiologist who was blinded to the clinical and laboratory data of the patients.[13]

Ultrasonography

US of both hands was done on the same day of a clinical visit by a single, trained sonologist who was blinded to the clinical, laboratory, and radiographic data of the patients. Power Doppler ultrasonography (PDUS) was done using Sonosite Micromaxx Color Doppler US System with high frequency 12 MHz 25-mm broadband linear array transducer. Pulse repetition frequency was kept between 0.5 and 1 kHz with low wall filter.

Gray scale images of 14 joints ( first to fifth metacarpophalangeal [MCP] joints, radiocarpal joints, ulnocarpal joints) of both hands were obtained in longitudinal and in transverse planes from the dorsal and the palmar aspects. Flow was assessed in two perpendicular planes and confirmed by pulsed wave Doppler spectrum to exclude artifacts.[14]

For assessment of synovial PD, a region was selected including a combination of the bony margins, joint space, and surrounding tissue (depending on the joint size).

For synovial vascularity, flow signal in the synovium was semi-quantitatively graded as follows: No flow signal in the synovium (Grade 0); mild flow signal: The presence of separate dot signals or short linear signals (Grade 1); moderate flow signal: The presence of clearly discernible vascularity with either many small vessels or several long vessels with or without visible branching, though involving less than half the area of the synovium (Grade 2); severe flow signal: The presence of vessels involving more than half the area of synovium (Grade 3).[15] Cumulative flow signal (CFS) was calculated as the sum of scores obtained from fourteen joints in each patient.

Statistical analysis

Microsoft Excel® and SPSS® version 17 for Windows® version 7 were used for data storage and analysis. Continuous variables were expressed as mean ± standard deviation. Unpaired Student's t-test, analysis of variance test, and Chi-square test were used to determine statistical difference between variables. Pearson's coefficient was used to investigate the correlation between the two variables. Statistical significance was set at P ≤ 0.05.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.


  Results Top


The study population consisted of total 57 subjects, female outnumbered male patients and age ranged from 21 to 75 years (mean - 40.14 ± 11.89) [Table 1]. CFS correlated significantly with the other variables of disease activity, namely, CRP levels [Figure 1]a, DAS28 [Figure 1]b, and ESR [Figure 1]c.
Table 1: Demographic, clinical, and laboratory data of rheumatoid arthritis patients

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Figure 1: Correlation of cumulative flow signal score with various variables. Strongest correlation was between cumulative flow signal and C-reactive protein levels (r = +0.5, P < 0.05 (a). Statistically significant correlations were also seen for disease activity score 28 (r = 0.42, P < 0.05) (b); and erythrocyte sedimentation rate (r = +0.39, P < 0.05) (c)

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Ultrasound findings

Overall, 54 out of total 57 patients of RA had positive findings, namely, synovial hypertrophy, joint effusion, bony erosions and/or increased vascularity on ultrasonographic evaluation thus indicating ongoing disease process [Figure 2]a. These included all of the 17 subjects with radiographic changes and 37 cases without radiographic changes, thus adding to the better disease detection ability of US [Table 2].
Figure 2: Ultrasonography of hand joints of rheumatoid arthritis patient (a) power Doppler study synovial thickening with flow signals. (b) Gray scale imaging of hand joints showing erosion at wrist joint (arrow)

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Table 2: Comparison between joint involvement as detected on radiography and on ultrasonography

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Erosions were seen in 14 patients by conventional radiographs, while 29 patients showed erosions on US showing higher sensitivity of latter [Table 3] and [Figure 2]b.
Table 3: Comparison between ultrasound and X-ray in detecting erosions

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A total of 570 MCP joints, 114 radiocarpal and 114 ulnocarpal joints were examined in 57 subjects. On US evaluation, radiocarpal joint involvement was most frequently involved among the three joint areas, present in 63 joints of 39 subjects. Total joints involved were 46 ulnocarpal joints in 30 patients and 51 MCP joints in 25 subjects [Table 4].
Table 4: Severity of joint involvement by cumulative flow signal score on power Doppler ultrasonography examination

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DAS28 showed low disease activity in 4 patients, moderate disease activity in 20 patients and high disease activity in 21 patients. Twelve patients had DAS28 <2.6, i.e., they were in remission [Table 5].
Table 5: Cumulative flow signal score values across different subgroups

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The mean CFS was 1.17 ± 1.64 in patients who were in remission (DAS28 <2.6), 3.00 ± 3.46 in patients having low disease activity (DAS28 2.6–3.2), 5.25 ± 4.22 in patients with moderate disease activity (DAS28 3.2–5.1), and 6.95 ± 3.84 in patients with high disease activity (DAS28 > 5.1). The difference in CFS among these groups was highly significant statistically [Table 5]. RF positivity did not show significant association with high CFS as compared to RF-negative subjects. CRP levels showed significant association with CFS (P < 0.01) [Table 5].

An important observation was that out of 12 patients having clinical remission (DAS28 <2.6), five showed abnormal CFS (mean 2.8) indicating ongoing synovitis while other seven had zero CFS. Similarly, out of four patients with low disease activity (DAS28 2.6–3.2), two showed abnormal CFS (mean 3) while the other two had zero CFS on US. Hence, US detected high CFS (ongoing disease activity, i.e., synovitis) in RA cases in remission (DAS28 <2.6).

Correlation of ultrasound with other parameters of disease activity

When CFS was analyzed for correlation with various variables, the significant correlation was obtained between CFS and CRP levels (r = +0.5, P < 0.05) and significant correlations were also obtained for DAS28 (r = +0.42, P < 0.05) and ESR (r = +0.39, P < 0.05) [Figure 1].


  Discussion Top


US (combination of both PD and gray scale imaging) has emerged as a reliable tool to diagnose subclinical synovitis and to quantify inflammatory arthritis and thus can help in taking therapeutic decisions in RA patients.[16],[17],[18],[19] This has been proven time and again that early detection of ongoing inflammatory process in the joint is crucial for initiating treatment and affects the overall prognosis of the patient.[16],[17] Signs of periarticular inflammation like tenosynovitis herald the onset of inflammation in RA. Conventional radiography (CR) fails to detect these subtle signs of subclinical synovitis and periarticular inflammation.[18],[19]

Positive signals on PD was a good indicator of active synovitis histopathologically.[20]

In this study, US showed higher sensitivity than CR for detecting abnormalities like erosions [Table 2] and [Table 3]. The US detected 15 more patients with erosive disease as compared to CR [Table 3].

Statistically significant difference of CFS was found in RA patients in clinical remission, low, moderate, or high disease activity and in patients with positive or negative CRP levels [Table 5]. The presence of abnormal CFS (mean 2.8) in 5 patients with DAS28 <2.6 (i.e., remission) showed ongoing inflammatory burden and necessitated enhanced the therapeutic planning.

It was also demonstrated that the presence of CFS correlated significantly with the other variables of disease activity, namely, CRP levels, DAS28, and ESR [Figure 1]a,[Figure 1]b,[Figure 1]c, making it suitable as a potential maker of disease activity and a tool for grading disease severity.

Naredo et a1.[21] also highlighted the better correlation of US findings with CRP and ESR than clinical assessment. Overall, US was found to be a more reliable technique to detects bore erosions than radiography in early RA.[22]

US has several limitations also, for example, it is considered to be an operator-dependent technology with poor repeatability; deeper structures are difficult to visualize as the higher frequency transducers have lower tissue penetration, and negative PD flow cannot exclude an active synovitis.[20] In present study also two patients with low disease activity had zero CFS. Another limitation of US is its inability to detect bone marrow edema which is a predictor of future development of erosions and is easily detected on MRI.[23]

Our study had certain limitations. First, Intraobserver variability assessment was not done in this study. Second, as this was an observational study and healthy controls were not taken for comparison of US and X-ray findings.

In our small study we found that US was more sensitive than CR for detection of erosions. US including PDUS and gray scale imaging detected CFS (an indicator of ongoing inflammation) in clinically quiescent RA. US reliably predicted disease severity and had a significant correlation with other validated markers of disease activity. Ultrasound therefore appears to be a useful adjunct in the management of patients with RA.

Acknowledgment

The authors are thankful to Dr. Meenu Bagarhatta (Department of Radiodiagnosis, SMS Medical College, Jaipur) for her inputs in writing of this manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Conaghan PG, O'Connor P, McGonagle D, Astin P, Wakefield RJ, Gibbon WW, et al. Elucidation of the relationship between synovitis and bone damage: A randomized magnetic resonance imaging study of individual joints in patients with early rheumatoid arthritis. Arthritis Rheum 2003;48:64-71.  Back to cited text no. 1
    
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Walther M, Harms H, Krenn V, Radke S, Faehndrich TP, Gohlke F. Correlation of power Doppler sonography with vascularity of the synovial tissue of the knee joint in patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum 2001;44:331-8.  Back to cited text no. 2
    
3.
Breedveld FC, Dijkmans BA. Differential therapy in early and late stages of rheumatoid arthritis. Curr Opin Rheumatol 1996;8:226-9.  Back to cited text no. 3
    
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van der Heijde DM. Radiographic imaging: The “gold standard” for assessment of disease progression in rheumatoid arthritis. Rheumatology (Oxford) 2000;39 Suppl 1:9-16.  Back to cited text no. 4
    
5.
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7.
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Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.  Back to cited text no. 11
    
12.
van der Heijde DM, van 't Hof M, van Riel PL, van de Putte LB. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol 1993;20:579-81.  Back to cited text no. 12
    
13.
Larsen A. How to apply Larsen score in evaluating radiographs of rheumatoid arthritis in long-term studies. J Rheumatol 1995;22:1974-5.  Back to cited text no. 13
    
14.
Qvistgaard E, Røgind H, Torp-Pedersen S, Terslev L, Danneskiold-Samsøe B, Bliddal H. Quantitative ultrasonography in rheumatoid arthritis: Evaluation of inflammation by Doppler technique. Ann Rheum Dis 2001;60:690-3.  Back to cited text no. 14
    
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Fiocco U, Ferro F, Vezzù M, Cozzi L, Checchetto C, Sfriso P, et al. Rheumatoid and psoriatic knee synovitis: Clinical, grey scale, and power Doppler ultrasound assessment of the response to etanercept. Ann Rheum Dis 2005;64:899-905.  Back to cited text no. 15
    
16.
Brown AK, Conaghan PG, Karim Z, Quinn MA, Ikeda K, Peterfy CG, et al. An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. Arthritis Rheum 2008;58:2958-67.  Back to cited text no. 16
    
17.
Taylor PC, Steuer A, Gruber J, Cosgrove DO, Blomley MJ, Marsters PA, et al. Comparison of ultrasonographic assessment of synovitis and joint vascularity with radiographic evaluation in a randomized, placebo-controlled study of infliximab therapy in early rheumatoid arthritis. Arthritis Rheum 2004;50:1107-16.  Back to cited text no. 17
    
18.
Naredo E, Rodríguez M, Campos C, Rodríguez-Heredia JM, Medina JA, Giner E, et al. Validity, reproducibility, and responsiveness of a twelve-joint simplified power Doppler ultrasonographic assessment of joint inflammation in rheumatoid arthritis. Arthritis Rheum 2008;59:515-22.  Back to cited text no. 18
    
19.
Scirè CA, Montecucco C, Codullo V, Epis O, Todoerti M, Caporali R. Ultrasonographic evaluation of joint involvement in early rheumatoid arthritis in clinical remission: Power Doppler signal predicts short-term relapse. Rheumatology (Oxford) 2009;48:1092-7.  Back to cited text no. 19
    
20.
Koski JM, Saarakkala S, Helle M, Hakulinen U, Heikkinen JO, Hermunen H. Power Doppler ultrasonography and synovitis: Correlating ultrasound imaging with histopathological findings and evaluating the performance of ultrasound equipments. Ann Rheum Dis 2006;65:1590-5.  Back to cited text no. 20
    
21.
Naredo E, Bonilla G, Gamero F, Uson J, Carmona L, Laffon A. Assessment of inflammatory activity in rheumatoid arthritis: A comparative study of clinical evaluation with grey scale and power Doppler ultrasonography. Ann Rheum Dis 2005;64:375-81.  Back to cited text no. 21
    
22.
Wakefield RJ, Gibbon WW, Conaghan PG, O'Connor P, McGonagle D, Pease C, et al. The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: A comparison with conventional radiography. Arthritis Rheum 2000;43:2762-70.  Back to cited text no. 22
    
23.
Sudol-Szopinska I, Kontny E, Maslinski W, Prochorec-Sobieszek M, Warczynska A, Kwiatkowska B. Significance of bone marrow edema in pathogenesis of rheumatoid arthritis. Pol J Radiol 2013;78:57-63.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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