Interobserver Reproducibility of the Myoton and Durometer Devices to Measure Skin Stiffness and Hardness in Chronic Cutaneous Graft-Versus-Host Disease Patients

Abstract

INTRODUCTION There is an unmet need for quantitatively measuring skin sclerosis to track the progression of sclerosis in chronic cutaneous graft-versus-host disease (cGVHD). Two candidate technologies are the Myoton, a noninvasive device to assess soft tissue biomechanics, and the durometer, an industrial device measuring surface hardness. Both devices have been shown to have high reproducibility in the context of healthy skin,1 but the reproducibility of these devices in sclerotic cGVHD is critical missing information in designing longitudinal studies measuring sclerosis in cGVHD patients. We directly compared the interobserver reproducibility of these devices to measure skin stiffness and hardness in sclerotic cGVHD patients. METHODS The skin stiffness and hardness were measured in seven patients with sclerotic cutaneous cGVHD by three blinded observers with Myoton and durometer on 20 body sites. To estimate the clinical repeatability to differentiate amongst patients, the intraclass correlation coefficients (ICC) was calculated from a single measure, absolute agreement, linear mixed model on log scale. Mean coefficient of variation across the three observers and minimal detectable change (MDC95) were calculated to estimate device ability to track change within patients. RESULTS Patient overall hardness/stiffness interobserver ICCs were 0.92 [0.82 - 1.00] for Myoton and 0.82 [95% confidence interval 0.61 - 1.00] for durometry. The Myoton had superior reproducibility to durometry in calves and upper arms, but was inferior in the dorsal forearms. Coefficients of variation across observers were under 10% and the overall normalized MDC95 was 22 to 23% for both devices. CONCLUSIONS Both the Myoton and durometer devices exhibit high reproducibility to measure skin stiffness/hardness in sclerotic cutaneous cGVHD, and the Myoton trended towards higher reproducibility when compared to the durometer. The interobserver ICCs of both devices to measure sclerotic cGVHD patients is significantly higher than the typical range of ICCs (0.21-0.60)2 associated with clinical exam-based measurement of moveable sclerosis. Prospective longitudinal study following patients over time is warranted to validate the use of skin stiffness measurements to monitor disease progression and treatment response in cGVHD patients. ACKNOWLEDGEMENTS This work is partially supported by Career Development Award Number IK2 CX001785 from the United Sates Department of Veterans Affairs Clinical Science R&D (CSRD) Service. REFERENCES Dellalana LE, Chen F, Vain A, Gandelman JS, Poldemaa M, Chen H, Tkaczyk ER. Reproducibility of the durometer and myoton devices for skin stiffness measurement in healthy subjects. Skin Research and Technology. 2019; 25(3): 289-293Mitchell SA, Jacobsohn D, Thormann Powers KE, et al. A multicenter pilot evaluation of the National Institutes of Health chronic graft-versus-host disease (cGVHD) therapeutic response measures: feasibility, interrater reliability, and minimum detectable change. Biol Blood Marrow Transplant. 2011;17(11):1619-1629. Disclosures Jagasia: Kadmon: Consultancy; Janssen: Research Funding; Incyte: Consultancy. Tkaczyk:Incyte: Consultancy.

Optimal Biomechanical Parameters for Measuring Sclerotic Chronic Graft-Versus-Host Disease

“…The myotonometer is a promising potential response measure instrument, but many questions must be answered prior to clinical implementation (Table 10). The device has demonstrated high interoperator reliability in measuring stiffness in healthy controls and sclerotic cGVHD patients (Chen et al, 2019;. A recent longitudinal study in sclerotic cGVHD patients showed that stiffness measurements over time correlated with clinically important changes in disease (Baker et al, 2021).…”

“…The device simultaneously extracts five biomechanical parameters, dynamic stiffness, oscillation frequency, relaxation time, creep, and decrement. It has shown high inter-operator reliability to measure dynamic stiffness in healthy controls and sclerotic cGVHD patients (Chen et al, 2019;. While a previous study demonstrated the dynamic stiffness parameter's ability to differentiate sclerotic patients from healthy volunteers, it did not examine other available parameters and lacked post-HCT controls .…”

Longitudinal tracking of skin dynamic stiffness to quantify evolution of sclerosis in chronic graft-versus-host disease

“…S3 (all subjects). Both PD patients (8,9) corresponded to positive outlier slopes (Fig. 1b) in dynamic stiffness (18 N/m/month; 36 N/m/month).…”

“…S2). Three patients (patients 1, 2, 7) had PR, two (8,9) had PD, and five (3, 4, 5, 6, 10) had SD. Patient 7 had a reduction in NIH skin score from 3 to 2; no other patients had changes in skin score.…”

“…We observed high inter-session variability in patients' measurements. Given the Myoton has demonstrated high inter-rater reliability in healthy volunteers and sclerotic cGVHD patients [8,9], the discrepancy may relate to day-to-day variations affecting stiffness, such as hydration [10] and time of day [11]. Additionally, while our protocol was developed for a standard examination table [5], some measurements in this study were performed in a reclining infusion chair due to space limitations.…”