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Shear wave elastography imaging in the assessment of skin stiffness in Egyptian patients with systemic sclerosis/scleroderma
Abstract
Background
The modified Rodnan skin score (mRSS) is a commonly used tool for the evaluation of skin involvement in scleroderma patients, however, it has many fallacies such as low objectivity and lack of inter-observer. In recent years, shear-wave elastography (SWE) proved to be an important assessment tool in the quantification of skin involvement in systemic sclerosis patients. In this study, we aimed to evaluate ultrasound and elastography findings in patients with systemic sclerosis and to clarify the effectiveness of elastosonography in the assessment of disease severity.
Methods
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This prospective analytical study was conducted on 25 clinically diagnosed patients of scleroderma who subjected to shear wave elastography referred from Rheumatology and Rehabilitation Department, Faculty of Medicine, in our University to the Diagnostic Radiology department, they were compared with 25 age and sex matched healthy controls.
Results
High statistically significant difference (p-value < 0.001) was found in skin stiffness by elastography in cases group (median = 15 and inter-quartile range (IQR) = 11–21.5) when compared with control group (median = 10.5, IQR = 9.5–11.5), there was discrimination between cases group and control group was at a cut off level of > 13.6, with 58% sensitivity, 94% specificity.
Conclusions
The shear wave elastography helped in early skin stiffness detection and assessment in scleroderma/systemic sclerosis patients, with less influence of clinical features and greater sensitivity and specificity.
Keywords:
Systemic sclerosis
Ultrasound
Shear wave elastography
Skin stiffness
Skin thickness
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Background:
Scleroderma, also termed systemic sclerosis (SSc) is an autoimmune disease that involves multiple organs including the skin. Its hallmark is tissue fibrosis (1).
Skin involvement is characteristic of the disease, it can be disabling. It’s also a predictor of internal organs involvement and mortality. It has been reported that improvement in skin involvement with treatment correlates with good outcome and prognosis (1).
The European League Against Rheumatism and the American College of Rheumatology (ACR/EULAR) classification criteria were published in 2013. The presence of skin involvement of the fingers extending proximal to the metacarpophalangeal joints is sufficient for to classify a patient as systemic sclerosis. In the absence of this finding, seven findings should be identified and score: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nail fold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Patients with a score ≥ 9 are considered to have definite systemic sclerosis (scleroderma). Sensitivity was 91% and specificity was 92% in the validation sample (2).
The Modified Rodnan Skin Score (MRSS) is the most common clinical method of evaluation of skin involvement, is obtained by pinching 17 designated areas in the body and scoring the level of skin thickening from 0–3 (where 0 = uninvolved, 1 = mild thickening, 2 = moderate thickening and 3 = severe thickening) at each site. A total score is obtained ranging from 0–51 for the 17 areas. The severity of skin involvement, as evaluated by the MRSS, is predictive of disease outcome: patients with lower skin scores (relative to baseline) after 2 year of treatment had good prognostic outcomes (3).
MRSS is a commonly used tool for severity and prognosis assessment in SSc in clinical trials (3).
Although the MRSS is the most commonly used tool in assessing SSc, the MRSS is highly subjective with significant intra and inter-observer reliability. Skin fibrosis can be detected using ultrasound which is actively used for assessing various fibrotic skin disorders. However, it cannot quantify skin stiffness. SWE has the ability to visualize skin and measure the skin viscoelasticity using the same ultrasound system. Further studies of SWE may provide a quantitative technique for assessing SSc (4).
Aim of this study
In our study we aimed to assess the value of shear wave elastography imaging in assessment of skin stiffness in Egyptian patients with systemic sclerosis/scleroderma
Methods
Population of study:
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Clinically diagnosed patients of scleroderma referred from Rheumatology and Rehabilitation Department in our university to the Diagnostic Radiology Department.
We included scleroderma patients fulfilling ACR/EULAR classification criteria for systemic sclerosis, both males and females, age range 16–70 years.
We excluded patients having: skin infections and skin lesions, skin burns or injury and prisoners (who don’t have the authority to give a written consent).
The study was a cross sectional analytical study with convenient sample of population selected.
The study was conducted from April 2023 till July 2024.
All patients underwent full history taking and clinical examination.
Laboratory data were collected from patient’s follow-up sheet (rheumatoid factor, ESR, CRP, CBC, ANA).
All patients had ultrasound gray scale imaging and share wave elastography (SWE) scan.
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This study had ethical committee approval of our faculty under the cord (MS 362–2023).
The study was done using an ultrasound machine (TOSHIBA Aplio 500) using the Superficial probe (12–14 MHz) for B-mode, and shear wave elastographic examination.
The scan was done by two skilled radiologists with a 7 and 20 years of experience, no significant inter-observer variabilities detected.
Position
The patients were placed in sitting position.
Conventional B-mode US assessment
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plenty of gel was placed instead of using a gel pad to decreased the probe pressure, the patients were sitting in a comfortable position with their forearm resting on a billow, images were obtained at the forearm skin dorsal aspect 10 cm above the wrist joint, skin thickness was measured.
Shear wave elastography
SWE examination was performed over the B-mode US image, the transducer was kept in a stable position. The measurements were obtained without pressure to reduce the compression artifact.
Elasticity was evaluated using a color-coded image superimposed on a B-mode image, when the cine loop is stable showing parallel lines, we freezed it. Three random measurements were taken placing the region of interest (ROI) over the selected areas, the mean and standard deviation (SD) values were recorded and expressed in kilopascals (kPa).
Statistical analysis
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Results were obtained using Statistical Program for Social Science (SPSS) version 24. Qualitative data were expressed as frequency and percentage. Quantitative data were expressed as mean ± SD for normally distributed data or median (IQR) for not normally distributed data. Mean (average): the central value of a discrete set of numbers, specifically the sum of values divided by the number of values. Standard deviation (SD): is the measure of dispersion of a set of values. A low SD indicates that the values tend to be close to the mean of the set, while a high SD indicate that the values are spread out over a wider range. Median: The middle number; found by ordering all data points and picking out the one in the middle (or if there are two middle numbers, taking the mean of those two numbers). IQR (inter-quartile range): is a measure of statistical dispersion, which is the spread of the data. It is defined as the difference between the 75th and 25th percentiles of the data. Probability (P-value) P-value < 0.05 was considered significant, P-value > 0.05 was considered insignificant.
Results
This cross sectional analytical study was done on 25 cases and 25 control groups, no statistically significant difference (p-value = 0.638) between studied groups (cases and control groups) as regard age. In cases group, mean age was 40.9 ± 13.3 with range of 20–64 years. In control group, mean age was 39.04 ± 15.2 with range of 20–65 years (Table 1).
Table 1
Comparison of age between studied groups
 
Cases group (N = 25)
Gender
Male
1
4%
Female
24
96%
Disease duration (years)
Mean ± SD
8.05 ± 4.8
Min - Max
0.3–19
There were 1 male (4%) and 24 females (96%) in case group. As regard disease duration, the mean disease duration cases group was 8.05 ± 4.8 years with minimum disease duration of 0.3 years and maximum disease duration of 19 years (Table 2).
Table 2
Description of gender and disease duration in Cases group
 
Cases group (N = 25)
Symptoms of onset
INTERSTITIAL LUNG DISEASE
18
72%
Cardiac
9
36%
GIT
19
76%
MSK
24
96%
Raynound’s phenomenon
No
0
0%
Yes
25
100%
Clinical type
Diffuse
1
4%
Limited
24
96%
ANA
Negative
1
4%
Positive
24
96%
There were interstitial lung disease (ILD) symptoms in 18 (72%) patients, cardiac symptoms in 9 patients (36%), GIT symptoms in 19 patients (76%) and MSK symptoms in 24 patients (96%). All studied patients (100%) in cases group had Raynaud’s phenomenon, Clinical type of the disease was limited in 24 patients (96%) and diffuse in 1 patient (4%), The ANA testing was positive in 24 patients (96%) and negative in 1 patient (4%) (Table 3).
Table 3
Description of clinical and laboratory data in Cases group
 
Cases (N = 25)
Control (N = 25)
MW
P-value
Skin thickness by US
Median
1.4
1.5
1057.5
0.182 NS
IQR
1.17–1.7
1.3–1.7
MW: Mann Whitney U test NS: p-value > 0.05 is considered non-significant
No statistically significant difference (p-value = 0.182) was found between studied groups (cases and control groups) as regard skin thickness by US. In cases group, median skin thickness by US was 1.4 with IQR of 1.17–1.7. In control group, median skin thickness by US was 1.5 with IQR of 1.3–1.7 (Table 4).
Table 4
Comparison of US skin thickness between studied groups
 
Cases (N = 25)
Control (N = 25)
MW
P-value
Elastography results
Median
15
10.5
523.5
< 0.001 HS
IQR
11–21.5
9.5–11.5
MW: Mann Whitney U test HS: p-value < 0.001 is considered highly significant
There was high statistically significant (p-value < 0.001) increased skin thickness by Elastography in cases group (median = 15 and IQR = 11–21.5) when compared with control group (median = 10.5, IQR = 9.5–11.5) (Table 5).
Table 5
Comparison of Elastography skin stiffness between studied groups
 
Cut off
AUC
Sens.
Spec.
PPV
NPV
p-value
U/S
< 1.4
0.57
54%
64%
60%
58.2%
0.189
Elastography
> 13.6
0.79
58%
94%
90.6%
69.1%
< 0.001
PPV: positive predictive value AUC: Area under curve
NPV: negative predictive value Sens: Sensitivity and Spec.: Specificity
Using ROC curve, it was shown that: US can be used to discriminate between cases group and control group at a cutoff level of < 1.4, with 54% sensitivity, 64% specificity, 60% PPV and 58.2% NPV (AUC = 0.57 and p-value = 0.189). Elastography can be used to discriminate between cases group and control group at a cutoff level of > 13.6, with 58% sensitivity, 94% specificity, 90.6% PPV and 69.1% NPV (AUC = 0.79 and p- value < 0.001) (table 6, Fig. 1).
Discussion
Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune disease characterized by systemic fibrosis of the skin and internal organs and by vasculopathy (5). Skin involvement in the form of skin thickening and sclerosis are hallmarks of SSc, and skin involvement is an integral part of SSc classification criteria (2). Accurate evaluation of the severity and rate of progression of skin lesions is crucial because it is closely related to disease activity, gravity and outcome (6).
In our study we aimed to assess the value of shear wave elastography imaging in assessment of skin stiffness in Egyptian patients with systemic sclerosis/scleroderma
As a practical and non-invasive method for identifying and assessing rheumatic disorders, US has gained popularity recently. By monitoring the rate at which shear waves propagate and computing the tissue's Young's modulus, shear wave elastography (SWE) evaluates tissue stiffness quantitatively (7).
This cross sectional analytical study was conducted on 25 clinically diagnosed patients of scleroderma who subjected to SWE matched with 25 age and sex matched healthy controls.
In our cases group, mean age was 40.9 ± 13.3 with range of 20–64 years. In control group, mean age was 39.04 ± 15.2 with range of 20–65 years with no statistical significant difference between studied groups.
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Likely, the study was conducted by Yang et al (8). on 37 Patients with SSc and 37 healthy controls, the mean age was 42.0 ± 14.6 (12–72) years in SSc patients and 43.1 ± 15.3 (12–78) years with no statistical significant difference between studied groups.
In our study, there were 1 male (4%) and 24 females (96%) in Case group. Similarly, a longitudinal study included 21 SSc patients and 15 healthy controls. T. Santiago et al (9) revealed that 18 (85.7) out of 21 patients were females.
With reference to disease duration, the mean disease duration in our cases was 8.05 ± 4.8 years with minimum disease duration of 0.3 years and maximum disease duration of 19 years.
T. Santiago et al (9) detected that the median duration of the disease since diagnosis was 10.0 (5.5–14.0) years.
There was ILD symptoms in 18 patients (72%), cardiac symptoms in 9 patients (36%), GIT symptoms in 19 patients (76%) and MSK symptoms in 24 patients (96%). All studied patients (100%) in Cases group had Raynaud’s phenomenon.
An Egyptian pilot study that included 62 SSc patients, reported that 39 (62.9%) patients suffered from ILD symptoms, 29 (46.8%) Cardiac involvement and 42 (67.7%) patients with MSK involvement Hend and Marwa (10). Similar to our study, Santiago et al (11). detected that 40 (100%) had Raynaud’s phenomenon.
With reference to clinical type of the disease, it was limited in 24 patients (96%) and diffuse in 1 patient (4%). slightly similar to ours, Cai et al. (12) revealed that sixteen patients were classified with dcSSc and 50 with lcSSc. While, Yang et al. (8) detected that 49 patients (49%) were limited while 51 patients (51%) were diffuse.
Anti-nuclear Aab (ANA) are routinely evaluated as they are important in diagnosis and prognosis biomarkers Chepy et al., (14). Among our patients, ANA was Positive in 24 patients (96%) and Negative in 1 patient (4%).
This was in line with Tania Santiago et al (9) study which detected that ANA was Positive in 20 patients (95.2%). Also, Santiago et al (11) detected that all patients had circulating antinuclear antibodies (ANAs) Cai et al (12) revealed that ANA was Positive in 61 patients (92.4%).
On contrary, a prospective study that done by Tumsatan et al. (13) on 29 patients with SSc and a 29 control population, showed that 28 (96.6%) of patients were diffuse SSc and limited in one patient.
This heterogeneity may be explained by different sample size and ethnic group.
In the current study, the median skin thickness by US was 1.4 with IQR of 1.17–1.7 in cases group. Also, the median skin thickness by US was 1.5 with IQR of 1.7 in control group with no statistical significant difference between the studied groups.
Santiago et al. (11) reported that ultrasound elastography was significantly higher in -SSc patients than in controls in the dorsum of the right and left hand (p = 0.02). While, In the left thigh, left leg, right and left foot, and face, ultrasound was quantitatively and greatly higher SSc patients, although not significantly different from controls.
The above discrepancies of skin thickness measurement results could be related to the extent of skin involvement of study patient populations, probably also related to the difference in SSc subtypes.
Our study showed high statistically significant (p-value < 0.001) increased skin thickness by Elastography in Cases group (median = 15 and IQR = 11–21.5) when compared with Control group (median = 10.5, IQR = 9.5–11.5).
Similar results reported by Cai et al. (12) who found that in patients with SSc, the value of SWE in all 17 mRSS areas was significantly higher than that of the healthy control group [54.95 (45.95, 66.55) vs 41.10 (39.18, 45.45) m/s, P < 0.001]. Also, Tumsatan et al. (13) detected that by using SWE, SSc patients had thicker and stiffer skin than the control group for all the areas of the forearms. SSc patients had overall skin greater thicknesses than the control group with the mean difference of 27.82 (95%CI 22.63–33.01, p < 0.001). Likely,, Santiago et al. (11) reported that shear-wave velocity numbers were significantly higher in SSc patients than in controls in the following skin areas: the dorsum of the right hand [1.94 (0.40) vs 1.61 (0.24); p = 0.0001], the dorsum in the left hand [1.82 (0.36) vs 1.65 (0.25); p = 0.025], right proximal phalanx [2.09 (0.60) vs 1.68 (0.24); p = 0.001] and left proximal phalanx [2.13 (0.82) vs 1.66 (0.27); p = 0.004].
Our results are in line with previous studies Chen et al., (15); Tânia Santiago et al., (11); Sobolewski et al., (16). This may indicate that SWE is a valuable tool for the evaluation of skin lesions in SSc and that it might have the potential to detect asymptomatic and subclinical skin involvement in SSc patients. This study emphasizes on the value of SWE in SSc in early detection and follow-up of skin involvement in those patients.
In the present study, US can be used to discriminate between Cases group and Control group at a cutoff level of < 1.4, with 54% sensitivity, 64% specificity, 60% PPV and 58.2% NPV (AUC = 0.57 and p-value = 0.189).
Elastography in our study can be used to discriminate between Cases group and Control group at a cutoff level of > 13.6, with 58% sensitivity, 94% specificity, 90.6% PPV and 69.1% NPV (AUC = 0.79 and p-value < 0.001).
A study of that included 30 SSc patients and 30 controls, reported that the optimal cut-off SWE values for separating groups was determined as 10.5 kPa and 1.87 m/s, the sensitivity was 93% and the specificity was 97% Tanyeri and Çildağ, (17). While, Cai et al. (12) SWE could effectively differentiate SSc patients from healthy controls, with an AUC of 0.851 (95% CI 0.787, 0.915).
Conclusions
The most common manifestations among our patients was musculoskeletal manifestations, all of our patients had Raynaud’s phenomenon. Most of them was with limited subtype and positive ANA test.
Skin ultrasound may not differentiate patients with SSc from healthy controls, yet the SWE-based assessment system helped in early skin thickness assessment, less influence of clinical features and greater sensitivity to discriminate scleroderma from normal skin.
Limitations
The limitations of our study were relatively small sample size, this may be due to small percentage of population having scleroderma/systemic sclerosis.
The other limitation is that we didn’t do follow up of our patients, we were focused on the value of elastography in the diagnosis of skin stiffness.
List of Abbreviations
ACR/EULAR...............The European League Against Rheumatism and the American College of Rheumatology
ANA................................Anti-nuclear antibodies.
CBC.................................Complete blood picture.
CRP.................................C-reactive protein.
ESR.................................Erythrocyte sedimentation rate
ILD..................................Interstitial lung disease.
IQR..................................Inter-Quartile ratio.
GIT..................................Gastrointerstinal tract.
KPa.................................Kilo-pascal.
mRSS.............................Modified Rodnan skin score
MSK................................Musclo-skeletal system.
PPV.................................Positive predictive value.
NPV................................Negative predictive value.
ROI.................................Region of interest.
SD...................................Standard deviation.
SPSS...............................Statistical Program for Social Science
SS....................................Systemic sclerosis
SSc..................................Scleroderma
SWE...............................Shear-wave elastography
US/USG........................Ultrasound/Ultrasonography.
Electronic Supplementary Material
Below is the link to the electronic supplementary material
Author Contribution
NM and AB analyzed and interpreted the patient data regarding the sonographic assessment of the patients. AH and AB analyzed and interpreted the patient data regarding the ultrasonographic findings. AH, AB and DO revised all the data interpreted by other authors. All authors read and approved the final manuscript. All authors agreed with the content and all gave explicit consent to submit.
Acknowledgement
We thank all the participants and colleagues who provided insight and expertise that greatly assisted the research. We are also grateful for the comments offered by the anonymous peer reviewers.
References:
1.
Yamaguchi, Y., Ono, J., Masuoka, M., Ohta, S., Izuhara, et al. (2013). Serum periostin levels are correlated with progressive skin sclerosis in patients with systemic sclerosis. British journal of dermatology, 168(4), 717–725.
2.
Van Den Hoogen, F., Khanna, D., Fransen, et al. (2013). 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis and Rheumatism, 65(11), 2737–2747.
3.
Li H, Furst DE, Jin H, Sun C, et al (2018). High-frequency ultrasound of the skin in systemic sclerosis: an exploratory study to examine correlation with disease activity and to define the minimally detectable difference. Arthritis Res Ther. Aug 16;20(1).
4.
Zhang, X., Zhou, B., and Osborn, T. (2020). Ultrasound surface wave elastography for assessing scleroderma. Ultrasound in medicine and biology, 46(5), 1263–1269.
5.
Volkmann, E. R., Andréasson, K., and Smith, V. (2023). Systemic sclerosis. The Lancet, 401(10373), 304–318.
6.
Herrick, A. L., Assassi, S., and Denton, C. P. (2022). Skin involvement in early diffuse cutaneous systemic sclerosis: an unmet clinical need. Nature Reviews Rheumatology, 18(5), 276–285.
7.
Taljanovic, M. S., Gimber, L. H., Becker, G. W., et al. (2017). Shear-wave elastography: basic physics and musculoskeletal applications. Radiographics, 37(3), 855–870.
8.
Yang, Y., Tang, X., Zhong, L, et al. (2023). Shear wave elastography-based skin assessment system for systemic sclerosis: a supplement or alternative to conventional ultrasound? Quantitative Imaging in Medicine and Surgery, 13(7), 4405.
9.
Santiago, T., Luis, M., Lima, J., et al (2021). POS0878 ultrasound assessment of dermal thickness and skin stiffness in undifferentiated connective tissue disease at risk for systemic sclerosis 695–696. In: BMJ Publishing Group Ltd.
10.
Hend, H., and Marwa, H. N. (2019). Gender Differences in Egyptian Systemic Sclerosis Patients: A Pilot Study. The Medical Journal of Cairo University, 87, 1911–1916.
11.
Santiago, T., Santiago, M., Coutinho, M., et al (2020). How much of skin improvement over time in systemic sclerosis is due to normal ageing? A prospective study with shear- wave elastography. Arthritis research and therapy, 22, 1–7.
12.
Cai, R., Lin, Z., Xu, D., et al. (2023). The value of shear wave elastography in diagnosis and assessment of systemic sclerosis. Rheumatology Advances in Practice, 7(3).
13.
Tumsatan, P., Uscharapong, M., Srinakarin, J., et al (2022). Role of shear wave elastography ultrasound in patients with systemic sclerosis. Journal of Ultrasound, 25(3), 635–643.
14.
Chepy, A., Bourel, L., Koether, V., et al. (2022). Can antinuclear antibodies have a pathogenic role in systemic sclerosis? Frontiers in Immunology, 13, 930970.
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Chen, C., Cheng, Y., Zhu, X, et al. (2020). Ultrasound assessment of skin thickness and stiffness: the correlation with histology and clinical score in systemic sclerosis. Arthritis research a therapy, 22, 1–8.
16.
Sobolewski, P., Maślińska, M., Zakrzewski, J.,et al. (2020). Applicability of shear wave elastography for the evaluation of skin strain in systemic sclerosis. Rheumatology International, 40(5), 737–745.
17.
Tanyeri, A., and Çildağ, M. B. (2023). Assessment of the skin with 2 D- shear wave elastography in the systemic scleroderma and its correlation with pulmonary involvement. Journal of Clinical Ultrasound, 51(7), 1205–1211.
Figure legends:
A
Fig. 3
A 31 years female was diagnosed scleroderma 3 years ago with positive serum ANA and classifies as limited scleroderma (involvement of the face, forearm and hand skin), (A and B): skin thickness measurements in grey scale ultrasonography of the forearm showing 1.4 mm in right forearm and 1.5 mm in left forearm, (C and D): mean shear wave elastography stiffness value of the right forearm (18.4 KPa) and left forearm (12.8 KPa)
Table legends:
A
Table 6
Diagnostic performance of skin thickness by U/S and skin stiffness by Elastography in discrimination of studied groups List of tables
 
Cases (N = 25)
Control (N = 25)
Stat. test
P-value
Age (years)
Mean ± SD
40.9 ± 13.3
39.04 ± 15.2
T = 0.47
0.638 NS
Range
20–64
20–65
T: independent sample T test NS: p-value > 0.05 is considered non-significant
Table 1
Table 2
Table 3
Table 4
Table 5
Table 6
Figure 1
A
Fig. 1
ROC curve between Cases group and Control group as regard US and Elastography.
Click here to Correct
Figure 2
A
Fig. 2
A 34-years-old female diagnosed with scleroderma 10 years ago (involvement of the face, forearm and hand skin), with positive ANA and was classified as limited scleroderma, A and B: skin thickness measurements in grey scale ultrasonography of the forearm showing 1.4 mm in right forearm and 1.4 mm in left forearm. C and D: mean shear wave elastography stiffness value of the right forearm (18 KPa.3) and left forearm (15.6 KPa)
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Click here to download actual image
Fig 3
Figure 4
A
Fig. 4
A 35 years old female diagnosed scleroderma 9 years with positive ANA and classified limited scleroderma (involvement of the face, forearm and hand skin), (A and B): skin thickness measurements in grey scale ultrasonography of the forearm showing 2.1 mm in right forearm and 2.3 mm in left forearm, (C and D): mean shear wave elastography stiffness value of the right forearm (21.8 KPa) and left forearm (23.5 KPa).
Click here to Correct
Figure 5
A
Fig. 5
A 53 years old female diagnosed scleroderma 15 years with ANA positive and classified diffuse scleroderma (involvement of the face, forearm and hand skin as well as the anterior trunk and both legs), (A and B): skin thickness measurements in grey scale ultrasonography of the forearm showing 1.1 mm in right forearm and 1 mm in left forearm, (C and D): mean shear wave elastography stiffness value of the right forearm (11.06 KPa) and left forearm (11 KPa)
Click here to Correct
Figure 6
A
Fig. 6
A 33 years old healthy female, (A and B): skin thickness measurements in grey scale ultrasonography of the forearm showing 1.8 mm in right forearm and 1.7 mm in left forearm, (C and D): mean shear wave elastography stiffness value of the right forearm (10.8 KPa) and left forearm (9.3 KPa)
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