Indian Journal of Rheumatology

ORIGINAL ARTICLE
Year
: 2017  |  Volume : 12  |  Issue : 4  |  Page : 194--198

Assessment of extent of skin involvement in scleroderma using shear wave elastography


Anupam Wakhlu1, Abhra Chandra Chowdhury2, Namita Mohindra3, Saumya Ranjan Tripathy1, Durga Prasanna Misra4, Vikas Agarwal4,  
1 Department of Rheumatology, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; Department of Rheumatology and Clinical Immunology, The Mission Hospital, Durgapur, West Bengal, India
3 Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
4 Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Correspondence Address:
Vikas Agarwal
Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareli Road, Lucknow - 226 014, Uttar Pradesh
India

Abstract

Introduction: Scleroderma (systemic sclerosis [SSc]) is a rare autoimmune disease which manifests as fibrosis in the skin and other internal organs. Conventionally, the modified Rodnan skin score (MRSS) has been used to quantify the extent of skin fibrosis (resulting in skin tightness) in SSc. This technique, although widely validated, is limited by the requirement of a trained, experienced assessor. Recent literature suggests that utilization of the objective ultrasound-based assessment of skin fibrosis utilizing shear wave elastography (SWE) may be a more robust technique to detect early skin tightness in SSc. Methods: We evaluated the use of SWE (assessed by an experienced radiologist) in 24 patients with SSc compared with 16 healthy controls. Results: Our patients were predominantly females, with median disease duration of 1.5 years and median MRSS of 17. There was minimal intraobserver variation in the assessment of SWE. Patients with SSc had higher SWE values (mean elasticity [Emean]) compared to healthy controls at most assessed sites for the MRSS. The Emeancorrelated significantly at all sites with the MRSS scores. At the sites where MRSS was scored as 0 (normal), the Emeanin patients with SSc was higher when compared with similarly clinical normal skin in patients with SSc, suggesting potential early involvement of these areas of the skin with fibrosis. Conclusion: SWE is a promising tool to objectively assess skin fibrosis in SSc and may be useful in detecting early, subclinical skin involvement in this disease.



How to cite this article:
Wakhlu A, Chowdhury AC, Mohindra N, Tripathy SR, Misra DP, Agarwal V. Assessment of extent of skin involvement in scleroderma using shear wave elastography.Indian J Rheumatol 2017;12:194-198


How to cite this URL:
Wakhlu A, Chowdhury AC, Mohindra N, Tripathy SR, Misra DP, Agarwal V. Assessment of extent of skin involvement in scleroderma using shear wave elastography. Indian J Rheumatol [serial online] 2017 [cited 2020 Sep 20 ];12:194-198
Available from: http://www.indianjrheumatol.com/text.asp?2017/12/4/194/211091


Full Text



 Introduction



Scleroderma or systemic sclerosis (SSc) is a rare systemic autoimmune disease, predominantly affecting young females, characterized by excessive collagen deposition and fibrosis in the skin, lungs, gastrointestinal tract, and other internal organs of the body.[1] The resultant skin tightening is the hallmark of this disease and causes significant morbidity due to limitation of finger movements, mouth opening, and restriction of chest expansion. There are two variants of SSc, limited or diffuse, the latter involving skin proximal to the elbows and the knees.[2] Clinical quantification of skin tightening is usually done by the modified Rodnan skin score (MRSS),[3] which grades skin tightening from 0 to 3 in seventeen areas of the body (fingers, hands, forearms, arms, face and neck, chest, abdomen, thighs, legs, feet) with a maximum score of 51. Although extensively validated and used in clinical trials, the MRSS is limited by the requirement of a trained and experienced assessor to accurately assess the extent of skin involvement. Clinically, evident skin fibrosis is thought to be a sign of advanced disease. Hence, there has been an emphasis in recent times to detect early, subclinical skin involvement as well as to accurately assess the extent of skin fibrosis using objective techniques including ultrasound.

Skin fibrosis can be assessed ultrasonographically [4] by determining dermal thickness; however, this again is a marker of established disease. Hence, techniques such as ultrasonographic shear wave elastography (SWE), which assess quantitatively the extent of skin fibrosis, have garnered attention. SWE assesses the elasticity of skin utilizing ultrasound, with a decrease in elasticity suggesting skin fibrosis. This technique not only objectively assesses extent of cutaneous involvement but also detects subclinical fibrosis which may be more amenable to therapeutic modulation than established, clinically evident, skin thickening. With this background, we decided to study the use of SWE in our patients with SSc compared with healthy controls. Specifically, we assessed the ability of SWE to differentiate skin involvement in patients with SSc and healthy controls at the various sites assessed using the MRSS and its correlation with MRSS.

 Methods



Twenty-four patients with SSc attending the outpatient departments of tertiary care centers for Clinical Immunology and Rheumatology in North India and 16 healthy controls without any skin disease were included after seeking informed consent. These subjects were subjected to a thorough clinical assessment by an experienced rheumatologist, including assessment of the extent of skin thickening at 17 sites (fingers, hands, forearms, arms, face and neck, chest, abdomen, thighs, legs, feet) to calculate the MRSS. Skin tightening was graded from 0 to 3 (0 - normal skin, 1 - minimal skin tightening, 2 - moderate skin tightening, 3 - hide-bound skin). These subjects were then subjected to ultrasonographic examination at these 17 sites on the same day to assess the Young's modulus of elastography in kilopascal (kPa) utilizing SWE by an experienced, trained radiologist.

Real-time supersonic SWE was performed to assess the elasticity of skin [5],[6] (using Aixplorer; SuperSonic Imagine, Aix-en-Provence, France, with a linear array transducer 4–15 MHz). The probe was placed very gently at right angles to the skin and enough ultrasound gel was applied to create a gel offset, taking care to avoid tissue compression and keep the transducer stationary during acquisitions. The software of the machine displayed elastograms as an overlay in dual mode alongside grayscale images. The SWE map suspended on the B-mode image was placed at the upper part of the screen with the B-mode image at the lower part, and the color scale of elasticity values displayed on right of the image, with red representing hardness and blue softness. The elasticity value of skin at each site was measured using the Q-Box. The integrated SWE software allowed for placement of circular regions of interest (ROI) within the elastography window and automatically displayed shear modulus data (in kPa) for the ROIs. The diameter of the box was set at 1.0 mm. The maximum, minimum, and mean elasticity (Emean) values of the tissues in the box were calculated by the system automatically.

SWE was performed at each of the sites three times, and a mean of these three values (in kPa) was taken for individual analysis. The Young's modulus at the different sites (fingers, hands, forearms, arms, face and neck, chest, abdomen, thighs, legs, feet) was compared between patients with SSc and healthy controls. At these individual sites, correlation between MRSS and SWE was determined. Further analysis was done to compare the Young's modulus at clinically uninvolved areas (MRSS = 0) in patients with SSc with the clinically normal skin of healthy controls.

Ethical approval

The study was approved by the ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.

 Results



Our patients were predominantly females, with median disease duration of 1.5 years and median MRSS of 17. A majority had diffuse scleroderma (19/24). The clinical characteristics are summarized in [Table 1]. The age and sex distribution of patients and controls were comparable.{Table 1}

Patients with SSc had significantly higher median values of SWE Emean assessed using the Young's modulus of elastography (in kPa) at the fingers, hands, forearms, arms, face and neck, and feet. However, this was not noted at the chest, abdomen, thighs, and arms, which were also the areas least commonly involved in our patients as evidenced by the number of patients with a MRSS of 0 at these sites [Table 2]. [Figure 1] (forearm) and [Figure 2] (thigh) are representative images of SWE from skin of patients with SSc and healthy controls, respectively.{Table 2}{Figure 1}{Figure 2}

Further, we correlated the MRSS at the individual sites with Emean and found a significant moderate correlation between these two techniques at most of the individual sites [Table 3], suggesting the ability of SWE to pick up clinically evident skin fibrosis assessed using the MRSS. We also wanted to assess whether SWE was able to identify subclinical skin involvement in patients with SSc in those areas which scored a MRSS of 0. For this, we compared the Emean in those areas with clinically normal skin patients with SSc with the scores derived from all the areas of healthy skin in healthy controls. We found that the Emean was significantly higher in clinically uninvolved areas of patients with SSc (median 26.38 kPa, interquartile range 17.39–32.32 kPa) compared to healthy controls (median 19.45 kPa, inter-quartile range 14.98–25.3, P = 0.0005 using Mann–Whitney U-test) [Figure 3]. Minimal intraobserver variability assessed using Cornbach's alpha was seen in the assessment of SWE using Emean [Table 4].{Table 3}{Figure 3}{Table 4}

 Discussion



We found that skin elastography scores assessed in patients with SSc were higher than in healthy controls, with good correlation between clinically assessed MRSS and ultrasonographically assessed Young's modulus of elastography. SWE scores were higher in uninvolved areas of skin than in healthy controls, suggesting ability to detect subclinical or preclinical skin fibrosis.

Very few studies have assessed ultrasound elastography as a tool for the assessment of SSc. Iagnocco et al.[7] described the utility of ultrasound elastography in 18 patients with SSc compared with 15 healthy controls. They assessed this technique in the fingers and forearms of these patients and could identify a different pattern of image in the forearms of patients with SSc utilizing B-mode ultrasound, with a blue color homogenously seen in the dermis as opposed to a green color in the dermis of unaffected skin. They could not find a constant reportable pattern in the fingers of patients with SSc. Di Geso et al.[8] studied 22 patients with SSc in whom they assessed the dermal thickness in the second digit of the dominant hand using grayscale ultrasound and ultrasound elastography. They concluded that dermal thickness assessed using ultrasound elastosonography was more accurate than that using grayscale ultrasound alone. Two further studies have tried to quantitate the skin fibrosis by evaluating shear wave velocity using ultrasound elastography. Santiago et al.[9] studied 26 patients with SSc and 17 healthy controls to assess shear wave velocity as a marker of skin elasticity. Similar to our study, they found higher scores of SWE in patients with SSc and healthy controls in most areas except the anterior chest, abdomen, upper arm, leg, and foot. They also found a distinction in elastography scores of unaffected areas when compared with healthy controls, suggesting an ability to identify subclinical or preclinical skin involvement in patients with SSc, akin to our findings. Wang et al.[10] utilized this technique to assess skin involvement in 21 patients with SSc and compared areas of clinically involved skin with uninvolved areas from the same patients as controls. They found significantly higher shear wave modulus scores in areas of involved skin compared to normal skin. They also looked at differences in scores between areas with thickened skin and atrophic skin (late stage of scleroderma) and interestingly found higher shear wave modulus scores in areas of atrophic skin when compared with sclerotic skin. These studies suggest the utility of this technique in not only assessing quantitatively skin fibrosis but also in the staging of disease, with more advanced disease having higher scores.

Accurate objective assessment of skin tightness or skin fibrosis is important not only to distinguish involved skin from healthy skin in scleroderma but also to detect skin involvement before it is clinically detectable. Scleroderma is a disease associated with significant morbidity and mortality,[11] not in the least due to the fact that the disease is quite advanced with resultant fibrosis by the time it is clinically evident. Indeed, most therapies have shown limited efficacy in the reversal of fibrosis. Hence, utilization of SWE as a tool to detect subclinical disease may help identify early scleroderma, which may be more amenable to immunosuppressive therapy to retard progression to clinical disease or arrest the disease at an early stage of fibrosis. SWE may be useful in the setting of clinical trials to assess the efficacy of antifibrotic therapies, numerous of which are in the pipeline,[12],[13] in SSc.

Our study was limited by the small number of patients and lack of a longitudinal follow-up to assess the comparability of SWE with MRSS. Furthermore, we did not perform skin biopsies from clinically uninvolved areas of patients with clinically normal skin to assess whether the increased SWE scores in these patients had histopathologic correlation with the presence of increased dermal collagen deposition. These merit exploration in a further study.

Our study, the first of its kind in an Indian population, demonstrated the feasibility of assessment of skin elastography in patients with SSc as well as the ability of this technique to distinguish involved areas of skin in patients with SSc from that of healthy controls. SWE had a moderate but significant correlation with the MRSS in most areas assessed using the Rodnan skin score. SWE scores were higher in clinically uninvolved areas of patients with SSc compared to healthy controls, suggesting subclinical skin fibrosis in these areas. This technique merits further exploration in a longitudinal cohort of patients with SSc to accurately delineate its exact role in the clinical assessment of scleroderma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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