|Year : 2019 | Volume
| Issue : 4 | Page : 290-296
The relationship between US7 ultrasound joint scoring system and disease activity score DAS28 in rheumatoid arthritis: A study in Indian population
Saurabh Maheshwari1, Samar Chatterjee1, Amar T Atal2, DS Grewal3, Vibhuti Maria4
1 Department of Radiodiagnosis and Imaging, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India
3 Department of Radiodiagnosis and Imaging, Command Hospital (SC), Pune, Maharashtra, India
4 Department of Ophthalmology, Armed Forces Medical College, Pune, Maharashtra, India
|Date of Web Publication||31-Dec-2019|
Dr. Samar Chatterjee
Department of Radiodiagnosis and Imaging, Armed Forces Medical College, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: US7 (7 joint ultrasound score) is an emerging ultrasound (US) joint scoring system for the assessment of disease activity in patients with Rheumatoid Arthritis (RA).
Methods and Material: The study was conducted at a tertiary care center in Southern India. Sixty-two patients of RA were recruited for this cross-sectional observational study. Patients' clinical & laboratory parameters were used to calculate the disease activity score DAS28. Grayscale and Power Doppler Ultrasound (GSUS & PDUS) were performed to calculate US7 score.Statistical analysis used: Spearman's rank-order correlation, Pearson interclass correlation and ROC (receiver operating characteristic) curve analysis were performed.
Results: Median DAS28 value was 4.04 with one patient in clinical remission. There was a statistically significant positive correlation (r=0.262) between synovitis by GSUS score & DAS 28 (p-value = 0.040) and synovitis by PDUS score and DAS 28 (r=0.340, p-value = 0.004). No significant correlation was found between DAS28 and tenosynovitis or erosions score. ROC curve analysis yielded the p values of 0.04 and 0.004 for synovitis by GSUS and synovitis by PDUS respectively in differentiating between the patients with low (DAS groups 1 & 2) and high disease activity (3 & 4).
Conclusions: There is good correlation of the synovitis component of US7 score with DAS28. However, relationship of tenosynovitis and erosions with disease activity is questionable according to our results. An 'abbreviated US7' score with detection of only synovitis may be more suitable. This requires further validation.
Keywords: 28-Joint count Disease Activity Score, grayscale ultrasound, joint ultrasound, power Doppler ultrasound, rheumatoid arthritis, US7
|How to cite this article:|
Maheshwari S, Chatterjee S, Atal AT, Grewal D S, Maria V. The relationship between US7 ultrasound joint scoring system and disease activity score DAS28 in rheumatoid arthritis: A study in Indian population. Indian J Rheumatol 2019;14:290-6
|How to cite this URL:|
Maheshwari S, Chatterjee S, Atal AT, Grewal D S, Maria V. The relationship between US7 ultrasound joint scoring system and disease activity score DAS28 in rheumatoid arthritis: A study in Indian population. Indian J Rheumatol [serial online] 2019 [cited 2020 Nov 28];14:290-6. Available from: https://www.indianjrheumatol.com/text.asp?2019/14/4/290/269123
| Introduction|| |
Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by a symmetric, peripheral polyarthritis. Early detection of the inflammatory process plays a key role in both diagnostic and therapeutic procedures in RA. Currently, the most commonly used clinical instrument to determine the disease activity in RA is the 28-joint count Disease Activity Score (DAS28 C-reactive protein [CRP]), which indirectly denotes the joint inflammatory status.
Ultrasound (US) is a sensitive imaging technique for the assessment of anatomical changes, disease activity, and therapeutic efficacy in patients with RA. The US is more sensitive than clinical examination and predicts joint destruction.,, The semi-quantitative US scoring system, US7 score, has been proposed to assess established RA and other inflammatory arthropathies. As an objective method, US7 is supposed to overcome the subjectivity of clinical scoring systems in RA.
Previous studies on the pattern of RA in Indian population show the difference from the Western world in the form of the milder disease and relative lack of systemic symptoms. This study was an attempt to assess the value of US7 as a marker of disease activity in RA in the Indian population and its correlation with DAS28 CRP.
| Subjects and Methods|| |
Sixty-two patients of RA fulfilling the 2010 American College of Rheumatology/European League against Rheumatism (EULAR) criteria referred from indoor or outdoor hospital services were examined with B-mode (grayscale) and power Doppler at a tertiary care center in South India. All the patients were examined once during the study period by a single operator. The study was approved by the institutional ethics committee. Informed written consent was obtained from all the patients.
Sample size calculation
According to the previous literature, the correlation between synovitis score by grayscale US (GSUS) and power Doppler US (PDUS) and DAS28 CRP was 0.39 and 0.35, respectively. To attest this correlation (r) in our study population, with a power (β) of 80% and alpha error (α) of 5%, the sample size (N) was calculated using the standard formula.
The sample size calculated for GSUS and PDUS was 47 and 62, respectively. Thus, a sample size of 62 was finally decided upon.
Initial clinical and laboratory evaluation
All the cases were referred to the department of rheumatology for assessment of clinical parameters required for calculating the DAS28 CRP score. All the patients were evaluated by a single rheumatologist. The examining rheumatologist was blinded to the US findings. This included calculation of swollen 28-joint count (SJC28) and tender 28-joint count (TJC28). In addition, patients' general health during the preceding 7 days was measured on the Visual Analog Scale (VAS) of 0–100, where 0 is “no activity” and 100 is “highest activity possible.” Testing for CRP (normal value <5 mg/l) was performed in all the patients. Values of erythrocyte sedimentation rate (normal value <20 mm fall in the 1st h), rheumatoid factor (normal value <24 IU/ml), and anticyclic citrullinated peptide (normal value <20 units/ml) were recorded if available.
Values of TJC28, SJC28, CRP, and VAS were used to calculate DAS28 using the standard formula:
Disease activity was graded by the following clinical classification criteria:
- DAS28 CRP < 2.6 = Clinical remission
- DAS28 CRP 2.6–3.2 = Mild disease activity
- DAS28 CRP 3.2–5.2 = Moderate disease activity
- DAS28 CRP > 5.2 = Severe disease activity.
In addition, the following data were recorded for all the patients: age, sex, height, weight, onset of symptoms, current disease-modifying antirheumatic drugs (including tumor necrosis factor-alpha inhibitors and glucocorticoids), and duration of therapy.
The US examination was performed using NextGen Logiq E portable US (GE Medical Systems, Milwaukee, Wisconsin, USA) with “hockey stick” transducer of 8–18 MHz.
The selected joints of the wrist, hand, and foot of the clinically dominant side were sonographically examined for all the patients in the standardized manner recommended by EULAR. A total of seven joint regions were examined using GSUS and PDUS including wrist, second and third metacarpophalangeal joints (MCP2 and MCP3), second and third proximal interphalangeal joints (PIP2 and PIP3), and second and fifth metatarsophalangeal joints (MTP2 and MTP5). All the patients were scanned by a single operator. The following parameters were adopted for standardized scanning of all the patients:
- Transducer frequency: 16 MHz for GSUS and 10 MHz for PDUS
- Gain: 40 for GSUS and 20 for PDUS
- Pulse repetition frequency for PDUS: 1.0
- Wall filter: 76 for PDUS.
GSUS was used to score synovitis, tenosynovitis, and erosions. Synovitis was scored from 0 to 3 on the basis of semi-quantitative score proposed by Szkudlarek et al. Tenosynovitis was scored 0 or 1 depending on its absence or presence, respectively. Erosions were defined as per the Outcome Measures in Rheumatology (OMERACT) musculoskeletal US (MSUS) group definition as interruption of bone surface in two perpendicular planes and were scored 0 (absent) or 1 (present).
Power Doppler ultrasound
PDUS was used to score synovitis and tenosynovitis. Synovitis was scored from 0 to 3 on the basis of semi-quantitative score proposed by Szkudlarek et al. Tenosynovitis was also scored from 0 to 3 as per four-grade semi-quantitative scoring system recommended by the OMERACT MSUS group.
Calculation of ultrasound 7 score
GSUS and PDUS findings were recorded to calculate US7 score under five categories, including synovitis score by GSUS (out of 27), synovitis score by PDUS (out of 39), tenosynovitis score by GSUS (out of 7), tenosynovitis score by PDUS (out of 21), and joint erosion score by GSUS (out of 14).
We performed statistical analysis using SPSS statistical software (SPSS, Chicago, IL, USA). Spearman's rank-order correlation was performed to determine the correlation between the DAS 28 score and the components of US7 score. We calculated Cohen's kappa statistic to see the concordance between DAS28 CRP and synovitis by GSUS/synovitis by PDUS. We also performed receiver operating characteristic (ROC) curve analysis to assess the sensitivity and specificity of US-detected synovitis in differentiating between the patients with low disease activity (DAS Groups 1 and 2) and high disease activity (3 and 4). P < 0.05 was considered statistically significant.
| Results|| |
Our study population ranged from 24 to 74 years of age, with a median value of 44 years. There was an equal number of male (n = 31) and female (n = 31) patients. This is different from the usual female predominance of RA and is partly due to the fact that most of our study population belonged to armed forces. The duration of treatment ranged from 0 to 15 years in the study population, with a median duration of 4 years. The patients were divided into four standard groups on the basis of the DAS28 CRP scores with the Group I (DAS28 CRP <2.60), Group II (DAS28 CRP – 2.61–3.20), Group III (DAS28 CRP – 3.21–5.20), and Group IV (DAS28 CRP >5.21) containing 1, 7, 4, and 47 patients, respectively.
The median TJC28/SJC28 scores were 7/3 with the maximum values of 23/10 and minimum values of 0/0. These values are illustrated in the box and whisker plot in [Figure 1]. The median VAS score was 25 (range: 5–50). The median CRP was 10.5 (range: 0.99–470) mg/L.
|Figure 1: Box and whisker plots showing distribution of 28 tender joint count and 28 swollen joint count|
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US evidence of synovitis was seen in 52 patients (83.8%) on GSUS and 55 patients (88.7%) on PDUS. This difference may either reflect the presence of Doppler signal in normal joints or the presence of disease activity without synovial proliferation (previously reported by Botar-jid et al.). The median score of synovitis on GSUS was 3 (range: 0–17), and the median score of synovitis on PDUS was 4 (range: 0–9). Examples of synovitis by GSUS and PDUS and its sequel are illustrated in [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d and [Figure ]3a, [Figure 2]b, [Figure 2]c, [Figure 2]d.
|Figure 2: 44-year-old male had a 28-joint count Disease Activity Score of 3.65. Power Doppler ultrasound (a, b and d) and grayscale ultrasound (c) images show (a) confluent vessel signals in the thickened synovium of the second metacarpophalangeal joint representing Grade III synovitis. (b) Normal synovium shown at the third metacarpophalangeal joint at identical Doppler settings. (c) Synovial thickening at the second metatarsophalangeal joint which is extending to the diaphysis of second metatarsal representing Grade III synovitis. (d) Single-vessel signals within thickened synovium at the second metatarsophalangeal representing Grade I synovitis|
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Tenosynovitis was seen in 30 patients (48.3%) on GSUS and 35 patients (56.4%) on PDUS. The median score of tenosynovitis on GSUS was 0 (range: 0–3), and the median score of tenosynovitis on PDUS was 1 (range: 0–4).
Erosions were seen in twenty patients (32.2%). The median score of erosions on US was 0 (range: 0–4). Example of erosion is illustrated in [Figure 3]c.
|Figure 3: 54-year-old female had a 28-joint count Disease Activity Score of 5.26. Grayscale ultrasound (a) and power Doppler ultrasound (b-d) images show (a) synovial thickening at the wrist joint which is bulging over the line linking the tops of the periarticular bone representing Grade III synovitis. (b) Single-vessel signals within thickened synovium at the same joint representing Grade I synovitis. (c) Contour deformity of the proximal phalanx at third proximal interphalangeal joint, likely to represent a sequela of rheumatoid arthritis. (d) Single-vessel signals within the thickened synovium at the second metatarsophalangeal joint representing Grade I synovitis by power Doppler ultrasound|
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Correlation of the 28-joint count Disease Activity Score with components of ultrasound 7 score
The correlation analysis between DAS28 CRP and synovitis by GSUS score and synovitis by PDUS score yielded Spearman's correlation coefficients (ρ) to be 0.262 (P = 0.040) and 0.340 (P = 0.004), respectively.
The correlation analysis between DAS28 CRP and tenosynovitis by GSUS score and tenosynovitis by PDUS score yielded no significant correlation, with ρ being 0.066 (P = 0.612) and 0.156 (P = 0.225), respectively. There was also no significant correlation between DAS28 CRP and erosion scores, with ρ being 0.396 (P = 0.283).
The pattern of joint involvement was similar for synovitis and tenosynovitis with the wrist joint being the most commonly involved followed by MCP2 joint. The most common site for erosion was MCP2.
These correlations are shown as scatter plots in [Figure 4] and [Figure 5].
|Figure 4: Scatter plots showing the correlation between 28-joint count Disease Activity Score and synovitis by grayscale ultrasound|
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|Figure 5: Scatter plots showing the correlation between 28-joint count Disease Activity Score and synovitis by power Doppler ultrasound|
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In addition, we calculated Cohen's kappa statistic to deduce concordance between DAS28 CRP and various US parameters. Cohen's kappa was calculated to see the concordance between DAS28 CRP and syonvitis by GSUS & synovitis by PDUS with results summarized in [Table 1]. We used two cutoff values of DAS28 CRP to calculate this statistic. These were 2.6 (to determine the ability of US in discriminating between inactive and active diseases) and 3.2 (to determine the ability of US in discriminating between inactive/mild disease activity and moderate/severe disease activity).
|Table 1: Value of Cohen's kappa statistic between various studied variables. Interpretation of kappa Altman|
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On selecting the cutoff value of 2.6, there was a poor concordance between DAS28 CRP and both the US parameters. This is likely due to the skewed distribution of our study population, where we had only one patient with DAS28 CRP value of 2.6 or less. On selecting the cutoff value of 3.2, we found a fair agreement (k = 0.351) between DAS28 CRP and synovitis by GSUS and a very good agreement (k = 0.924) between DAS28 CRP and synovitis by PDUS.
ROC curve analysis yielded the P = 0.04 for synovitis by GSUS and P = 0.004 for synovitis detected by PDUS (P< 0.05 is significant) in differentiating between the patients with low disease activity (DAS Groups 1 and 2) and high disease activity (3 and 4). ROC curves are illustrated in [Figure 6]. For the diagnosis of high disease activity, looking at all cutoff values for synovitis by GSUS, the optimal cutoff determined by maximal Youden's index was >1 (sensitivity: 0.74 and specificity: 0.62). The optimal cutoff for synovitis by PDUS was >3 (sensitivity: 0.64 and specificity: 0.75).
|Figure 6: Receiver operating characteristic curves comparing synovitis by grayscale ultrasound and synovitis by power Doppler ultrasound against 28-joint count Disease Activity Score|
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| Discussion|| |
MSUS has emerged as a reliable instrument to monitor disease activity with the ability to pick up persisting low disease activity with normal acute-phase reactants and composite DASs. However, its exact place in the management of RA is still under debate. US also suffers from the logistical challenges in the form of a need for expensive specialized equipment, steep learning curve, operator dependency, and increase in total time spent on evaluating each patient.
There are qualitative and quantitative scoring systems available to grade synovitis on Doppler. The semi-quantitative US scoring system, US7 score, is one of the frontrunners in this regard. We selected US7 score out of various available US scoring systems because it is as accurate as other validated US scoring systems with a limited number of joints to be assessed resulting in increased efficiency.,
The US7 score was first proposed by Backhaus et al. in 2009 who demonstrated the positive correlation of DAS28 CRP score with synovitis scores in US7 in patients evaluated at the onset and after 6 months of therapy. They reported a significant correlation with the value of Spearman's correlation coefficient being 0.44 for both GSUS/DAS28 CRP and PDUS/DAS28 CRP which was statistically significant. Our study revealed similar results.
Backhaus et al. also demonstrated that the statistically significant positive correlation of DAS28 CRP score with tenosynovitis scores in US7 (on both GSUS and PDUS) in 120 patients evaluated before and after 6 months of therapy. However, in a later study involving 432 patients, Backhaus et al. could only demonstrate a correlation between DAS28 CRP and tenosynovitis score on PDUS. No correlation was found between the DAS28 score and tenosynovitis on GSUS.
We did not find any significant correlation between tenosynovitis by GSUS/PDUS scores or erosion score and DAS28. This finding requires further evaluation by fresh studies. The fair-to-good concordance of Cohen's kappa statistic for deduction of concordance with PDUS suggests that PDUS may be an adjunctive tool in discriminating between inactive/mild disease activity and moderate/severe disease activity.
We also attempted to evaluate the sensitivity and specificity of US-detected synovitis in differentiating between the patients with low disease activity (DAS Groups 1 and 2) and high disease activity (3 and 4) by performing ROC curve analysis. This yielded an area under curve values of 0.705 and 0.735 for synovitis by GSUS and synovitis by PDUS, respectively, suggesting a “fair” accuracy in classifying patients as per established norms. The optimal cutoff points to differentiate low and high disease activities (by maximal Youden's index) were >1 and >3 for synovitis by GSUS and synovitis by PDUS, respectively.
In our study population, there was only one patient belonging to the clinical remission group by DAS score who showed evidence of subclinical synovitis on PDUS. Subclinical synovitis is a recognized finding with the incidence being as high as 8% in previous studies., There are two possible explanations for this finding. It may be either due to a lack of direct relationship between the synovitis and the degree of joint damage or it may reflect a lack of correlation between US-detected synovitis and indirect markers of disease activity such as DAS28 CRP (which do not directly measure the inflammation at the joint unlike US).
We found the median value of erosions by US score to be 0. Our work yielded a significantly smaller number of erosions, and this difference may reflect a steep learning curve for picking up bony erosions. Specifically, the anatomical variations such as dorsal metacarpal head depressions (seen in up to 37% of the normal population) may be difficult to distinguish from true erosions.
Most of the previous studies conducted on the role of the US7 score in RA have been cohort studies with a lack of cross-sectional observational studies.,,,,, Mendonça et al. studied 32 patients of early RA in an observational study in Brazil to correlate clinical disease activity with the US7 score. However, they only included patients in the early stage of the disease (3–24-month duration). Another cross-sectional study by Kamel et al. included fifty patients with duration of illness ranging from 1 to 37 years.
We could not identify prior published studies conducted on Indian as well as South Asian population assessing the role of the US7 score in RA. Our study shows a reasonable positive correlation between US findings and disease activity in a different geographic group with a different disease pattern and thus reaffirms the utility of joint US.
We acknowledge the limitations of our study in the form of lack of follow-up examinations for the study group to evaluate the temporal change in studied parameters, US examination by a single observer, and the said observer not being blinded to clinical findings.
| Conclusion|| |
Our findings show a significant positive correlation between DAS28 and synovitis scores, an inconsistent relationship between DAS28 CRP and tenosynovitis scores, and a lack of significant correlation between DAS28 CRP and erosion scores. This may lead to the development of a simpler “abbreviated US7” score consisting only of synovitis on GSUS and PDUS.
Furthermore, the US7 score demonstrates fair performance as a diagnostic test in classifying patients according to the disease activity. This warrants further research to establish its role as a possible “biomarker” in the diagnosis and follow-up of patients of RA.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]