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

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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 5.1). The difference in CFS among these groups was statistically significant (P < 0.01). In 5 out of 12 patients with DAS28
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Address for correspondence:
Dr. Renu Saigal,
33, Muktanand Nagar,
Gopalpura Bypass, Tonk Road,
Jaipur ‑ 302 018, Rajasthan, India.
E‑mail: saigalrenu53@gmail.com
Abstract
Background: Ultrasound (US) including power Doppler (PD) are increasingly being used to
evaluate joint involvement in rheumatoid arthris (RA). Aim of this study was to evaluate
joint involvement in RA by US including PD and gray scale imaging and its comparison with
convenonal radiographic changes and correlaon with disease acvity parameters.
Methods: Paents with RA of less than 3.5 years disease duraon were subjected to detailed
clinical examinaon and laboratory invesgaons. Aer X-ray imaging (posterior-anterior
view) of both hand joints, PD and gray scale US examinaon of 14 joints of both hands was
performed and mean cumulave ow signal score (CFS) was calculated. Disease acvity
score (DAS28) was also calculated for each paent.
Results: Out of total 57 paents evaluated, 54 had abnormal ndings on US as compared to
only 17 having radiographic abnormalies. US could detect erosions in 29 paents including
all of the fourteen paents who had radiographically detectable erosions. On US evaluaon,
radiocarpal joint was involved most frequently. The mean CFS was 1.17 ± 1.64 in paents
who were in remission (DAS28 <2.6), 3.00 ± 3.46 in paents having low disease acvity
(DAS28 2.6–3.2), 5.25 ± 4.22 in paents with moderate disease acvity (DAS28 3.2–5.1), and
6.95 ± 3.84 in paents with high disease acvity (DAS28 > 5.1). The dierence in CFS among
these groups was stascally signicant (P < 0.01). In 5 out of 12 paents with DAS28 <2.6,
i.e., in remission, CFS were high showing subclinical synovis. Mean CFS correlated signicantly
with DAS28 (r = +0.42, P < 0.05); C-reacve protein (r = +0.50, P < 0.05); and erythrocyte
sedimentaon rate (r = +0.39, P < 0.05).
Conclusions: US detected CFS which an indicator of ongoing inammaon in RA paents
with clinical remission (DAS28 <2.6). US is more sensive than convenonal radiography for
detecon of erosions. CFS on PD had a signicant correlaon with markers of disease acvity.
Key Words: Power Doppler, rheumatoid arthris, ultrasonography
Ultrasonographic Evaluation of Joint Involvement in Rheumatoid Arthritis:
Comparison with Conventional Radiography and Correlation with Disease
Activity Parameters
Renu Saigal, Laxmikant Goyal1, Hariram Maharia2, Meenakshi Sharma3, Abhishek Agrawal1
Department of Medicine, Jaipur Naonal University, IMSRC, 1Department of Medicine, SMS Medical College, 2Department of Cardiology, Metro Mass
Hospital, Mansarovar, 3Department of Radiology, Niramaya Hospital, Jaipur, Rajasthan, India
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.
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Introducon
In rheumatoid arthris (RA), synovis appears to be
the primary abnormality responsible for structural joint
damage.[1] Angiogenesis is an important feature in pannus
formaon which plays a crucial role in destrucon of
joint. Doppler ultrasound (US) can detect pathological
vascularizaon within joints and changes in the periarcular
so ssues, thus can demonstrate the presence of
acve inammaon, which can be correlated with the
neoangiogenesis in the synovium. Power Doppler (PD) is a
valid tool for the detecon and quancaon of synovial
vascularizaon.[2]
Early diagnosis of RA is important because early aggressive
treatment reduces the long-term disability.[3] For early
detecon of subclinical synovis, clinical examinaon,
and laboratory tests are limited in their usefulness.
Radiographic changes occur late and may not be detected
early in the disease course.[4,5]
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DOI:
10.4103/0973-3698.199123
Original Article
Received: June, 2016
Accepted: August, 2016
Published: February, 2017
[Downloaded free from http://www.indianjrheumatol.com on Monday, December 10, 2018, IP: 182.68.50.212]
Saigal, et al.: US evaluation in rheumatoid arthritis
Indian Journal of Rheumatology ¦ Volume 12 ¦ Issue 1 ¦ March 20177
In the early course of RA, applicaon of US including
both PD and gray scale imaging has been shown to be
more sensive than clinical examinaon in determining
synovis.[6] US is an easily available, noninvasive, relavely
inexpensive, radiaon-free, and reliable technique for
scanning of mulple joints at the me of consultaon and
recent improvement in technology coupled with portability
and safety makes US the rst choice imaging invesgaon
for the evaluaon of musculoskeletal diseases.
US can evaluate various features of both intra-arcular
(eusion, synovial hypertrophy and vascularity, marginal
erosions) and extra-arcular disease (tenosynovis,
enthesopathy).[7-10]
US is more reliable for detecng joint eusion and synovial
hypertrophy compared with magnec resonance imaging.[9]
US provides a quick correlaon between clinical features
and imaging ndings which help in accurate diagnosis and
management of RA.
The aim of this study was to evaluate joint involvement in
RA by US (combinaon of both PD and gray scale imaging)
and its comparison with radiographic changes and its
correlaon with disease acvity parameters.
Methods
Paents and assessments
Paents with RA of less than 3.5 years duraon, diagnosed
according to 1987 revised criteria of the American College
of Rheumatology,[11] who aended the Rheumatology Clinic,
at a terary care center of western India, from August 2008
to July 2009, were included in this study. Disease duraon
of <3.5 years was taken arbitrarily so that we can assess the
US ndings (such as eusion, vascularity, synovial hypertrophy,
and marginal erosions) in early as well as established RA.
Baseline data were collected regarding detailed disease
history, and each paent was subjected to complete
rheumatologic assessment including clinical, laboratory,
and radiologic evaluaon.
Laboratory invesgaons, namely, complete blood count,
erythrocyte sedimentaon rate (ESR) (measured by
Westergren method), fasng blood glucose, liver, and
kidney funcon tests were performed in each paent.
Rheumatoid factor (RF) and C-reacve protein (CRP) levels
were esmated by turbidimetry.
Disease acvity was assessed according to disease acvity
score of 28 joints (DAS28).[12] The DAS28 >5.1 was high
disease acvity; DAS28 3.2–5.1 moderate disease acvity;
DAS28 <3.2 low disease acvity; and DAS28 <2.6 indicated
remission in RA paents.
Convenonal 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 paents.[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
paents. 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 repeon frequency was kept between
0.5 and 1 kHz with low wall lter.
Gray scale images of 14 joints (rst to h
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 conrmed by pulsed wave
Doppler spectrum to exclude arfacts.[14]
For assessment of synovial PD, a region was selected
including a combinaon of the bony margins, joint space,
and surrounding ssue (depending on the joint size).
For synovial vascularity, ow signal in the synovium was
semi-quantavely graded as follows: No ow signal in
the synovium (Grade 0); mild ow signal: The presence
of separate dot signals or short linear signals (Grade 1);
moderate ow 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
ow signal: The presence of vessels involving more than
half the area of synovium (Grade 3).[15] Cumulave ow
signal (CFS) was calculated as the sum of scores obtained
from fourteen joints in each paent.
Stascal analysis
Microso Excel® and SPSS® version 17 for Windows®
version 7 were used for data storage and analysis.
Connuous variables were expressed as mean ± standard
deviaon. Unpaired Student’s t-test, analysis of variance
test, and Chi-square test were used to determine stascal
dierence between variables. Pearson’s coecient was
used to invesgate the correlaon between the two
variables. Stascal signicance was set at P 0.05.
Ethical approval
The study was conducted in accordance with the
Declaraon of Helsinki and was approved by the local
ethics commiee of the instute. Informed wrien consent
was obtained from all paents prior to their enrollment in
this study.
Results
The study populaon consisted of total 57 subjects, female
outnumbered male paents and age ranged from 21 to
75 years (mean - 40.14 ± 11.89) [Table 1]. CFS correlated
signicantly with the other variables of disease acvity,
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Saigal, et al.: US evaluation in rheumatoid arthritis
Indian Journal of Rheumatology ¦ Volume 12 ¦ Issue 1 ¦ March 2017 8
namely, CRP levels [Figure 1a], DAS28 [Figure 1b], and ESR
[Figure 1c].
Ultrasound ndings
Overall, 54 out of total 57 paents of RA had posive ndings,
namely, synovial hypertrophy, joint eusion, bony erosions
and/or increased vascularity on ultrasonographic evaluaon
thus indicang ongoing disease process [Figure 2a]. These
included all of the 17 subjects with radiographic changes and
37 cases without radiographic changes, thus adding to the
beer disease detecon ability of US [Table 2].
Erosions were seen in 14 paents by convenonal
radiographs, while 29 paents showed erosions on US
showing higher sensivity of laer [Table 3 and Figure 2b].
A total of 570 MCP joints, 114 radiocarpal and 114 ulnocarpal
joints were examined in 57 subjects. On US evaluaon,
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 paents and 51 MCP joints in 25 subjects [Table 4].
DAS28 showed low disease acvity in 4 paents, moderate
disease acvity in 20 paents and high disease acvity
in 21 paents. Twelve paents had DAS28 <2.6, i.e., they
were in remission [Table 5].
The mean CFS was 1.17 ± 1.64 in paents who were in
remission (DAS28 <2.6), 3.00 ± 3.46 in paents having
low disease acvity (DAS28 2.6–3.2), 5.25 ± 4.22 in
paents with moderate disease acvity (DAS28 3.2–5.1),
and 6.95 ± 3.84 in paents with high disease acvity
(DAS28 > 5.1). The dierence in CFS among these groups
was highly signicant stascally [Table 5]. RF posivity did
not show signicant associaon with high CFS as compared
to RF-negave subjects. CRP levels showed signicant
associaon with CFS (P < 0.01) [Table 5].
An important observaon was that out of 12 paents having
clinical remission (DAS28 <2.6), ve showed abnormal
CFS (mean 2.8) indicang ongoing synovis while other
seven had zero CFS. Similarly, out of four paents with low
disease acvity (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 acvity,
i.e., synovis) in RA cases in remission (DAS28 <2.6).
Correlaon of ultrasound with other parameters
of disease acvity
When CFS was analyzed for correlaon with various
variables, the signicant correlaon was obtained between
CFS and CRP levels (r = +0.5, P < 0.05) and signicant
correlaons were also obtained for DAS28 (r = +0.42,
P < 0.05) and ESR (r = +0.39, P < 0.05) [Figure 1].
Discussion
US (combinaon of both PD and gray scale imaging) has
emerged as a reliable tool to diagnose subclinical synovis
Table 1: Demographic, clinical, and laboratory data of
rheumatoid arthris paents
Parameter Total
Number of paents 57 (100.0)
Male/female 15/42
Age of the paents (years; mean±SD) 40.14±11.89
Disease duraon (months) 19.85±12.06
ESR (mm 1st h) 36.73±30.95
C-reacve protein (mg/dL) 8.79±10.09
DAS28 4.38±1.76
RF ter (IU/mL) 37.85±64.53
CFS score (CFS) 4.85±4.16
On methotrexate (%) 32 (56.14)
On hydroxychloroquine (%) 12 (21.05)
On steroid 0
CFS: Cumulave ow signal, SD: Standard deviaon,
RF: Rheumatoid factor, ESR: Erythrocyte sedimentaon rate,
DAS: Disease acvity score
Table 2: Comparison between joint involvement as
detected on radiography and on ultrasonography
X-ray Ultrasonography (%) Total (%)
Posive ndings Normal
Abnormal 17 (29.82) 0 (0) 17 (29.82)
Normal 37 (64.91) 3 (5.26) 40 (70.17)
Total 54 (94.73) 3 (5.26) 57 (100)
Table 3: Comparison between ultrasound and X-ray in
detecng erosions
Method Erosion detected
(%)
Erosions not detected
(%)
Total
(%)
US 29 (50.87) 28 (49.12) 57 (100)
X-ray 14 (24.56) 43 (75.43) 57 (100)
US: Ultrasound
Table 4: Severity of joint involvement by cumulave
ow signal score on power Doppler ultrasonography
examinaon
Metacarpophalangeal
joints (n=570)
Radiocarpal
joints
(n=114)
Ulnocarpal
joints
(n=114)
Normal 519 51 68
Posive ndings 51 63 46
Grade I 38 12 11
Grade II 12 36 33
Grade III 1 15 2
and to quanfy inammatory arthris and thus can help
in taking therapeuc decisions in RA paents.[16-19] This
has been proven me and again that early detecon of
ongoing inammatory process in the joint is crucial for
iniang treatment and aects the overall prognosis
of the paent.[16,17] Signs of periarcular inammaon
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Saigal, et al.: US evaluation in rheumatoid arthritis
Indian Journal of Rheumatology ¦ Volume 12 ¦ Issue 1 ¦ March 20179
like tenosynovis herald the onset of inammaon in
RA. Convenonal radiography (CR) fails to detect these
subtle signs of subclinical synovis and periarcular
inammaon.[18-19]
Posive signals on PD was a good indicator of acve
synovis histopathologically.[20]
In this study, US showed higher sensivity than CR for
detecng abnormalies like erosions [Tables 2 and 3].
The US detected 15 more paents with erosive disease as
compared to CR [Table 3].
Stascally signicant dierence of CFS was found in RA
paents in clinical remission, low, moderate, or high disease
acvity and in paents with posive or negave CRP
levels [Table 5]. The presence of abnormal CFS (mean 2.8)
in 5 paents with DAS28 <2.6 (i.e., remission) showed
ongoing inammatory burden and necessitated enhanced
the therapeuc planning.
It was also demonstrated that the presence of CFS
correlated signicantly with the other variables of disease
acvity, namely, CRP levels, DAS28, and ESR [Figure 1a-c],
Table 5: Cumulave ow signal score values across dierent subgroups
DAS28 RF CRP levels
<2.6 2.6-3.2 3.2–5.1 >5.1 Negave Posive <6 mg/dL >6 mg/dL
Number of subjects (%) 12 (21.05) 4 (7.02) 20 (35.09) 21 (36.84) 29 (50.87) 28 (49.13) 38 (67) 19 (33)
Mean CFS 1.17±1.64 3.00±3.46 5.25±4.22 6.95±3.84 5.51±4.14 4.17±4.15 3.57±3.56 7.21±4.45
P<0.01 >0.05 <0.01
CFS: Cumulave ow signal score, RF: Rheumatoid factor, CRP: C-reacve protein, DAS: Disease acvity score
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)
c
b
a
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)
b
a
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Saigal, et al.: US evaluation in rheumatoid arthritis
Indian Journal of Rheumatology ¦ Volume 12 ¦ Issue 1 ¦ March 2017 10
making it suitable as a potenal maker of disease acvity
and a tool for grading disease severity.
Naredo et a1.[21] also highlighted the beer correlaon of
US ndings 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 limitaons also, for example, it is considered
to be an operator-dependent technology with poor
repeatability; deeper structures are dicult to visualize as the
higher frequency transducers have lower ssue penetraon,
and negave PD ow cannot exclude an acve synovis.[20]
In present study also two paents with low disease acvity
had zero CFS. Another limitaon 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 limitaons. First, Intraobserver
variability assessment was not done in this study. Second,
as this was an observaonal study and healthy controls
were not taken for comparison of US and X-ray ndings.
In our small study we found that US was more sensive
than CR for detecon of erosions. US including PDUS
and gray scale imaging detected CFS (an indicator of
ongoing inammaon) in clinically quiescent RA. US
reliably predicted disease severity and had a signicant
correlaon with other validated markers of disease acvity.
Ultrasound therefore appears to be a useful adjunct in the
management of paents with RA.
Acknowledgment
The authors are thankful to Dr. Meenu Bagarhaa
(Department of Radiodiagnosis, SMS Medical College,
Jaipur) for her inputs in wring of this manuscript.
Financial support and sponsorship
Nil.
Conicts of interest
There are no conicts of interest.
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    The aim of this review article was to investigate the pooled sensitivity and specificity of musculoskeletal ultrasound (MSUS) for the detection of synovitis and early bone erosion in the small joint in rheumatoid arthritis (RA). In addition, investigate the pooled sensitivity and specificity of Power Doppler ultrasonography (PDUS) for the detection of synovial hypervascularity in small joints in RA. A systematic literature search of PubMed, Wiley online library, Google Scholar, Research gate, E-book, BioMed Central, the Journal of Rheumatology and Springer Link were investigated from 2001 to 2017. Original researches related to the article written in English including RA, synovitis, bone erosion, grayscale, and PDUS were included in this study. The sample size, study design, sensitivity, and specificity were analyzed. The review summarizes the value of MSUS for the detection of RA as it is the first choice of modality. Results show the acceptable reliability of US for the diagnosis of early bone erosions, synovitis, and synovial hypervascularity.
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    Early and late stages of rheumatoid arthritis differ with respect to the severity of inflammation and the progression rate of irreversible joint destruction. There are no solid data showing that disease mechanisms underlying destructive arthritis differ between the various stages of the disease. Long-term observational studies have shown that rheumatoid arthritis is a severe progressive disease in many patients, highlighting the need for new therapeutic strategies. At present many centers are exploring whether early and aggressive treatment can improve long-term morbidity and mortality.
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    Rheumatoid arthritis (RA) is characterized by a chronic inflammation of the joints, which leads to the destruction of articular cartilage and bone. The degree of joint damage assessed by radiographic imaging represents a key outcome in RA. There are several methods for scoring the joint damage associated with RA. The most widely used are the Sharp and Larsen systems, as well as more recent modifications of each method. Radiographic imaging has several advantages compared with other outcome measures in RA, specifically: X-rays reflect the history of joint pathology, provide a permanent record for serial evaluation, and can be randomized and blinded for objective scoring. Several modifications of these methods have been proposed and employed in the investigation of disease progression. A review of the radiographic progression of RA is presented, as well as a simplified scoring system useful for the evaluation of joint damage in RA in a clinical setting.