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.
A
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).