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Systemic sclerosis
Original research
A stretchable hardness sensor for the assessment of skin disease in systemic sclerosis
  1. Xiuyuan Wang1,
  2. Mengyang Liu2,
  3. Tianbao Ye3,
  4. Junxia Huang1,
  5. Xinzhi Xu1,
  6. Ming Li1,
  7. Xuefeng Zhao2,
  8. Hongliang Lu2 and
  9. Ji Yang1
  1. 1Department of Dermatology, Zhongshan Hospital Fudan University, Shanghai, China
  2. 2Fudan University, Shanghai, China
  3. 3Shanghai Sixth People's Hospital, Shanghai, China
  1. Correspondence to Ji Yang; yang.hua{at}yeah.net

Abstract

Objective To determine the validity of a hardness sensor to objectively assess skin induration in patients with systemic sclerosis, and to compare the hardness sensor with the modified Rodnan skin score (MRSS) and a durometer.

Methods The skin induration was measured in two assessments: a Latin square experiment to examine the hardness sensor’s intraobserver and interobserver reliability; and a longitudinal cohort to evaluate the distribution of hardness sensor measurements, the correlation between hardness sensor, durometer and MRSS, and the sensitivity to change in skin hardness. Other outcome data collected included the health assessment questionnaire (HAQ) disability index and Keitel function test (KTF) score.

Results The reliability of the hardness sensor was excellent, with high intraobserver and interobserver intraclass correlation coefficients (0.97; 0.96), which was higher than MRSS (0.86; 0.74). Interobserver reproducibility of hardness sensor was only poor in abdomen (0.38), yet for durometer it was poor in face (0.11) and abdomen (0.33). The hardness sensor score provided a greater dynamic evaluation range than MRSS. Total hardness sensor score correlated well with MRSS (r=0.90, p<0.001), total durometer score (r=0.95, p<0.001), HAQ disability index (r=0.70, p<0.001) and KTF score (r=0.66, p<0.001). Change in hardness sensor score also correlated with change in MRSS (r=0.78, p<0.001), total durometer score (r=0.85, p<0.001), HAQ disability index (r=0.76, p<0.001) and KTF score (r=0.67, p<0.001).

Conclusion The hardness sensor showed greater reproducibility and accuracy than MRSS, and more application sites than durometer; it can also reflect patients’ self-assessments and function test outcomes.

  • Systemic Sclerosis
  • Scleroderma, Systemic
  • Outcome and Process Assessment, Health Care

Data availability statement

Data are available upon reasonable request. All quantified data may be available on reasonable request but patients’ data are not available to the public.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/rmdopen-2023-003512

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    WHAT IS ALREADY KNOWN ON THIS TOPIC

    • The assessment of skin induration in systemic sclerosis (SSc) is important yet difficult to quantify only through manual skin scoring. Additional methods that are more precise and objective are crucial for clinical use.

    WHAT THIS STUDY ADDS

    • This study showed the hardness sensor measurements of skin induration in patients with SSc are simple, reliable, precise and demonstrate greater reproducibility and applications compared with manual skin scoring and durometer.

    HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

    • Our study results encourage the hardness sensor as a complementary outcome measure to manual skin scoring in clinical trials of patients with SSc.

    Introduction

    Systemic sclerosis (SSc) is a high-mortality connective tissue disease characterised by fibrosis of the skin and internal organs.1 Following an initial phase of induration, the dermis undergoes collagen infiltration, resulting in increased hardness and thickness.2 Concurrently, sclerosis of the subcutaneous connective tissue causes dermal tethering and restricted skin mobility.3 Skin disease serves as a predictor of visceral involvement and correlates with the prognosis of patients with SSc; amelioration of skin disease is associated with improved survival rates.4 5 Thus, a dependable measure for assessing the skin disease is significant and imperative.

    The modified Rodnan skin score (MRSS), a summary of manual skin scores at 17 skin locations, is widely applied and has become the standard primary outcome measure of skin involvement in clinical trials in SSc.6 Despite being easy to use, this manual approach is controversial due to its limitations, including its inability to do quantitative evaluation, difficulty identifying minute but clinically relevant changes, and low intraobserver and interobserver consistency.7 8 To overcome these shortcomings, many research teams have tried to apply shear-wave elastography ultrasound and acoustic radiation force impulse imaging to the assessment of skin involvement in SSc in recent years.9 10 Although these measurements have proven to be valid and reliable for the assessment of skin thickness and elasticity, they require specialised instrumentation and trained medical technicians, which comes with high costs. There is still an urgent need for additional methods that are both precise, objective and accessible.

    Flexible electronics are taking on more and more important roles in wearable healthcare.11 High-performance sensors with emerging transduction principles, micro–nano structures, and functional nanomaterials have been broadly investigated in recent years.12 13 We focus on this emerging field and believe that a stretchable hardness sensor with simple structure, easy-to-readout signal and layer-by-layer manufacturing process will be practical and reliable.14 So, in our previous work, we fabricated a wearable stretchable hardness sensor integrating a piezoresistive strain sensor and a piezoresistive pressure sensor to fulfil the sensation of applied force and deformation simultaneously.15

    This study was designed to determine the validity, reliability and applicability of the hardness sensor as an outcome measure for skin disease when compared with MRSS and a digital durometer.

    Methods

    Study participants

    From August 2021 to February 2023, a total of 5 healthy participants and 37 patients diagnosed as SSc according to the 2013 American College of Rheumatology/EULAR SSc classification criteria at Zhongshan Hospital, Shanghai, were enrolled in this study.16 All participants are divided into two cohorts: a Latin square cohort including 5 patients with SSc and a longitudinal cohort including 32 patients with SSc and 5 healthy participants (table 1). The treatment experiences and plans of patients were not uniform. The Latin square cohort was performed to explore the intraobserver and interobserver reliability of hardness sensor measurements, MRSS and durometer measurements.17 Five physicians experienced in MRSS technique examined five patients with diffuse cutaneous SSc (four women, one man, age range 39–65 years) twice on alternate days. The baseline data from the longitudinal cohort were used to determine the distribution range of hardness sensor score at different skin sites and to provide convergent construct validity by correlating hardness sensor measurements with MRSS, durometer measurements and other indices. Of the 32 patients in the longitudinal cohort, 22 had repeat measurements over 3–9 months apart, and 5 healthy participants had repeat measurements at the month 6. The follow-up data were used to assess the sensitivity to change of the hardness sensor.

    View this table:
    Table 1

    Clinical data of 42 study subjects in the 2 study cohorts

    Hardness sensor

    A stretchable and conformal hardness sensor integrating a strain sensor and a pressure sensor was developed to assess the hardness of patients’ skin quantitatively. The sensor can attach to the skin and sense the applied force as well as deformation simultaneously (figure 1A). The ratio of pressure sensor output and strain sensor output was defined as the hardness sensor output, which increased as the hardness of the touched material increased. In the experiment, the output of the pressure sensor was set to 0.1. More details of the fabrication process and manipulation of the hardness sensor are elaborated on in our previous study.15 It is important to note that factors such as age, gender, ethnicity and body mass index can influence the baseline measurements of skin hardness by both the hardness sensor and durometer. Therefore, we guaranteed that there was no significant differences between SSc group and healthy controls in these factors (table 1). Hardness sensor score was taken at 17 predetermined landmark sites in online supplemental table 1 adapted from MRSS and past studies.7 18

    Figure 1
    Figure 1

    Demonstration of hardness sensor and durometer operation. (A) Appearance of the hardness sensor and illustration of its use on the extended side of forearm. (B) Illustration of the durometer testing on the extended side of forearm. The physician was required to make the durometer perpendicular to the skin surface and try to press the durometer on the landmark sites with its own gravity when testing.

    MRSS

    MRSS were calculated using the standard 0, 1, 2 and 3 integer scale (0=normal skin; 3=maximal induration) at 17 body sites (fingers, hands, forearms, upper arms, face, chest, abdomen, thighs, calves and feet).6

    Durometer

    Durometers are used in manufacturing to measure the hardness of materials. In past single-centre or multicentre examinations, the durometer was described as a credible tool for the evaluation of skin induration. However, there is still controversy about the suitable skin sites where the durometer should be applied.19–21 So, a digital durometer (Rex Gauge type OO; Rex Gauge, Buffalo Grove, Illinois) with a continuous scale measured in standard durometer units was also used in this study to be compared with the hardness sensor (figure 1B). Durometer scores were also taken at 17 predetermined landmark sites in online supplemental table 1.

    Other outcome measures

    All patients completed the health assessment questionnaire (HAQ) disability index and Keitel function test (KTF) score.22 23 The HAQ disability index includes eight problem areas, and every area consists of three or four questions scored as 0–3 points according to completion difficulty. The highest score of each area is the area score, and the average score of eight areas was the final score used in the analysis. The KTF score is usually used to assess functional limitations, and we used only nine items of the KTF, including finger flexion, wrist extension and flexion, and forearm pronation and supination in this study.

    Statistical analysis

    In the Latin square cohort, intraobserver and interobserver reliabilities were measured by intraclass correlation coefficients (ICCs). In the longitudinal cohort, the statistical significance was determined by an analysis of the Student’s t-test and then the Mann-Whitney U-test. The correlations were assessed by Spearman’s correlation. Two-sided tests of significance with an alpha level of 0.05 were used for all calculations.

    Result

    Reliability of the hardness sensor was higher than that of MRSS and superior in more skin sites than the durometer

    It is imperative to have good reliability for assessing skin disease in clinical trials of SSc. To investigate the reliability of the hardness sensor and its potential advantages over MRSS and durometer, we compared the intraobserver and interobserver ICCs of these three in the Latin cohort (table 2). Overall, intraobserver and interobserver ICCs for hardness sensor measurements were higher than MRSS (0.97 vs 0.86; 0.96 vs 0.74), yet similar to durometer measurements (0.97 vs 0.97; 0.96 vs 0.94). Intraobserver variability of the hardness sensor was only moderate in the abdomen (0.54) and high in the other measured sites (0.82–0.96). However, intraobserver variability of the durometer was moderate in both the face (0.51) and abdomen (0.53). A similar situation was found in the interobserver variability test. Interobserver variability of hardness sensor was only poor in the abdomen (0.38) and high in the other measured sites (0.76–0.96). But for durometer, it was poor in the face (0.11) and abdomen (0.33) and moderate in the hands (0.70) and upper arms (0.69). All these data showed the hardness sensor was highly reliable and reproducible at all sites except the abdomen. The reliability of the hardness sensor was higher than MRSS and presented better than the durometer in the face, hands and upper arms.

    View this table:
    Table 2

    Reliability of hardness sensor, MRSS and durometer measurements

    Hardness sensor provided a more precise measurement for skin assessment than MRSS

    To explore the variation of hardness sensor score at different sites and to preliminarily verify its validity, baseline hardness sensor score and manual skin score from the longitudinal cohort comprising 32 patients with SSc and 5 healthy controls was collected. We found that, except in the abdomen, the median hardness sensor score increased with a higher given skin score at all skin sites, and the hardness sensor score (continuous) within a skin score (integer) ranged widely (figure 2A–K, table 3). Compared with MRSS, a semiquantitative measurement, the wider range of valid evaluation scope provided by the hardness sensor implied a more precise level for skin involvement assessment. What is more, in the comparison of the hardness sensor score on healthy controls and the skin score of 0, we observed that the maximum value and the range of hardness sensor score were higher with the skin score of 0 than in healthy controls (figure 2A–K, table 3). Sometimes a skin score of 0 for patients with SSc does not mean that the skin is unchanged but rather that the MRSS is unable to capture small but perceptible changes due to its semiquantitative assessment. This was further proof that hardness sensors could capture weak skin changes not captured by MRSS. In addition, the total hardness sensor score was significantly higher in the patients with SSc than in healthy controls (figure 2L). All data above showed the hardness sensor may be a valid and more sensitive method for skin involvement assessment than MRSS.

    Figure 2
    Figure 2

    (A–K) The distribution of the hardness sensor score for 32 patients with systemic sclerosis (SSc) and 5 healthy controls in the longitudinal cohort at different skin sites within the given individual skin severity score. Box plots represented the 25th and 75th percentiles, lines inside the boxes represented the median, and whiskers represented the minimum and maximum values. (L) The total hardness sensor score of patients with SSc and healthy controls. ****P<0.0001.

    View this table:
    Table 3

    Median (range) of hardness sensor score for 32 patients with SSc and 5 healthy controls

    Hardness sensor score was well correlated to MRSS, durometer score, HAQ disability index and KTF score

    To further assess the validity and potential value of the clinical application of the hardness sensor, we evaluated the construct validity of the hardness sensor. Baseline data from 32 patients in the longitudinal cohort revealed that the hardness sensor score was significantly correlated with MRSS (r=0.90, p<0.001) and durometer (r=0.95, p<0.001) (table 4). The hardness sensor score was well correlated with MRSS at all skin sites except the abdomen (r=0.27, p=0.14), while the durometer score has a poor correlation with MRSS at the face (r=0.30, p=0.10) and abdomen (r=0.31, p=0.09). The correlation between the hardness sensor score and durometer score was also worst at the face (r=0.28, p=0.12) and abdomen (r=0.26, p=0.16). The poor performance the durometer presented at the face and abdomen was similar to that in the reliability test, which indicated the hardness sensors had more suitable application sites than the durometer of the skin induration assessment. On the whole, the total hardness sensor score performed a well correlation with MRSS (r=0.90, p<0.001) and total durometer score (r=0.95, p<0.001). There was also a significant correlation between the total hardness sensor score and other outcome measures, including the HAQ disability index (r=0.70, p<0.001) and KTF scores (r=0.66, p<0.001) (figure 3).

    Figure 3
    Figure 3

    The correlation between the total (17-sites) hardness sensor score and modified Rodnan skin score (MRSS) (A), total durometer score (B), health assessment questionnaire (HAQ) disability index (C), Keitel function test (KTF) scores (D) of 32 patients with systemic sclerosis in the longitudinal cohort.

    View this table:
    Table 4

    Correlation between hardness sensor, MRSS and durometer measurements

    Furthermore, we investigated the sensitivity to change of the hardness sensor. The change in total hardness sensor score was correlated with the change in MRSS (r=0.78, p<0.001), total durometer score (r=0.85, p<0.001), the HAQ disability index (r=0.76, p<0.001) and KTF scores (r=0.67, p<0.001) (figure 4A–D). There were no significant changes observed in hardness sensor score before and after in the healthy controls (figure 4E).

    Figure 4
    Figure 4

    The correlation between the change in total (17-sites) hardness sensor score and change in modified Rodnan skin score (MRSS) (A), total durometer score (B), health assessment questionnaire (HAQ) disability index (C), Keitel function test (KTF) scores (D) of 22 follow-up patients with systemic sclerosis in the longitudinal cohort. The comparison of hardness sensor score before and after in the healthy controls (E). ns, not significant.

    Taken together, our data further presented that the hardness sensor was a valid and reliable method for the assessment of skin induration in SSc and demonstrated better applicability than the durometer.

    Discussion

    The current study showed that the stretchable hardness sensor measurements of skin disease in patients with SSc are novel, simple, valid and reliable, and should be considered for use as an outcome measure in clinical trials of SSc.

    Compared with MRSS, the lower rate of intrarater and inter-rater variation indicates that the hardness sensor provides a method for objective measurement of skin disease in SSc patients, whether study subjects were examined at different times or by different researchers. Furthermore, since MRSS involves only four levels of scoring at each site, smaller but detectable changes in skin disease may not be caught by MRSS in some patients with SSC.7 In contrast, the hardness sensor on a continuous scale provided a greater dynamic range in the assessment of skin induration, and change in the hardness sensor score correlated with that in skin score. The more refined grading provided by the hardness sensor may be crucial for documenting improvements or deteriorations in the skin disease of patients with SSc. The extensive evaluation range of the hardness sensor may serve as a potential solution to the limitations posed by the ceiling and floor effects of manual skin scoring for individual skin sites. Prior research has demonstrated that alterations in skin characteristics among patients with SSc, including aberrant activation of endothelial cells and collagen synthesis, manifest prior to clinical assessment.24 25 Our data showed that the clinically uninvolved skin of patients with SSc had a higher hardness sensor score than the skin of healthy controls in the same sites, which further suggested that skin involvement can be detected earlier with the hardness sensor than MRSS.

    Compared with the durometer, the hardness sensor performed better at more skin sites in the reliability and construct validity tests. We found that the durometer always had poor performance in the abdomen and face, yet only in the abdomen hardness sensor performed weakly. The principle of induration detection by the hardness sensor and durometer is similar, mainly deduced from the relationship between force and deformation. However, the pressure of the durometer is provided by its own gravity. Variability and deviation in durometer scores may arise due to inadequate application of pressure on the bevel, failure to maintain the durometer’s perpendicularity to the skin site plane, or incorrect horizontal positioning of the skin.7 Therefore, on a curved surface like the face, especially the site set on the cheek, the durometer had a bad performance. On the contrary, the hardness sensor fits well to the skin due to the stretchable design based on a flexible material. What is more, the pressure applied to the hardness sensor can be observed by the resistance value, and is thus easier to control than the durometer, which means less deviation. So, we have reasons to believe that the hardness sensor is more suitable for skin induration assessment in patients with SSc than a durometer.

    Our study also demonstrated that the hardness sensor was correlated well with the MRSS and durometer, with good correlation to both site-specific scoring and total score. Moreover, the total hardness sensor score was also well correlated with the HAQ disability index and KTF score. Although hardness sensor scores had a good correlation with skin scores and patient-driven measures of skin disease and disability, differences between hardness sensor and these measures are obvious, meaning that hardness sensor is similar, but not identical to the disease areas captured by these other measures. Thus, in addition to improving accuracy and reproducibility, the hardness sensor may provide additional information on the disease course in SSc. What is more, among the follow-up patients, there is also a correlation between change in the hardness sensor and change in MRSS, durometer, the HAQ disability index and KTF score. The demonstration of sensitivity to change of hardness sensor is a critical aspect of validating this tool for use in clinical trials.

    There are also several limitations of our study. Our data were collected from a single centre and should be confirmed by other researchers. The sample size of subjects in the longitudinal cohort is relatively small.

    In conclusion, the present study suggests that the hardness sensor is a valid, reliable and expandable method for the assessment of skin disease in SSc, and should be considered for use as a complementary outcome measure to MRSS in clinical trials of SSc. Further studies will check the validity of hardness sensor measurements in multicentre and larger trials.

    Data availability statement

    Data are available upon reasonable request. All quantified data may be available on reasonable request but patients’ data are not available to the public.

    Ethics statements

    Patient consent for publication

    Ethics approval

    The protocol was approved by the Ethics Committee of Zhongshan Hospital, Fudan University. ID:Y2021 073. Participants gave informed consent to participate in the study before taking part.

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    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • XW, ML and TY contributed equally.

    • Contributors All authors were involved in drafting the manuscript or revising it critically, and approved the final version. XW had full access to all the data in the study. Manufacture of hardness sensor: ML, XZ and HL. Study design: JY and ML. Data collection and analysis: XW, TY, JH and XX. XW and JY are guarantors, they accept full responsibility for the work and/or the conduct of the study.

    • Funding This study was funded by National Natural Science Foundation of China (82073436).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.