Abstract
Chronic graft-versus-host disease (cGVHD) is a severe complication in long-term survivors of allogeneic hematopoietic stem cell transplantation. This disease is challenging to manage clinically due to a lack of validated tools to quantitatively measure skin sclerosis. The current gold standard for measuring skin sclerosis is the NIH Skin Score which has only moderate agreement among clinicians and experts. To more accurately assess skin sclerosis in cGVHD, the Myoton and durometer devices can be used to directly measure biomechanical parameters of the skin. However, the reproducibility of these devices is not known in patients with cGVHD. To determine this reproducibility, three observers independently measured 10 anatomic sites in each of seven patients with sclerotic cGVHD using the Myoton and durometer. Clinical reproducibility was measured by mean pairwise differences (U-statistic) and intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs). Mean pairwise differences, expressed in true physical units, were used to report typical errors for each anatomic site and device. Mean pairwise differences were less than 11% of the average overall values for all five Myoton parameters and durometer hardness. These were lower for Myoton creep (4.1%), relaxation time (4.7%), and frequency (5.1%) than decrement (9.0%), stiffness (10.4%), and durometer hardness (9.0%). Myoton parameters creep, relaxation time, and frequency showed promise for capturing skin biomechanics more accurately than Myoton stiffness, decrement, or durometer hardness. Mean pairwise differences trended highest in the shin and volar forearm and lowest in the dorsal forearm. The interobserver ICC for overall (averaged across all measured body sites of a patient) creep (0.94; 95% CI 0.87–1.00), relaxation time (0.96; 95% CI 0.90–1.00), and frequency (0.95; 95% CI 0.88–1.00), trended higher than that for decrement (0.43; 95% CI 0.00–0.88), stiffness (0.92; 95% CI 0.81–1.00), and durometer hardness (0.82; 95% CI 0.61–1.00). Similar trends were observed in healthy participants. These findings can help clinicians design better studies to assess therapeutic response to new cGVHD treatments and support the interpretation of future measurements.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors are grateful for the patients and volunteers who participated in this research. The authors would also like to thank Professor Frank Harrell for his advice on U-statistics during biostatistics clinics and informal discussions at Vanderbilt University Medical Center. We also thank Crystal Herron, PhD, ELS, of Redwood Ink LLC for editorial services in preparing the manuscript for publication. This work was supported by Career Development Award Number IK2 CX001785 from the United States Department of Veterans Affairs Clinical Science R&D Service and NIH K12 CA090625.
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SG, LB, and ET wrote the main manuscript text. Study conceptualization was carried out by ET and AV. Data was collected by FC, AH, and KZ. Data was curated by FC, LB, ZK, HS and SG. Formal data analysis was carried out by HC and LB. SG and ZK performed validation. ET and MJ provided supervision. HS, SG all authors reviewed the manuscript.
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Arved Vain, PhD, invented the Myoton but has no financial interest in the device. Madan Jagasia, MD is currently the Chief Executive Officer of Obsidian Therapeutics. Eric Tkaczyk, MD, PhD, has served on the GVHD advisory board of Incyte. The remaining authors have no conflicts of interest to disclose.
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Ghosh, S., Baker, L., Chen, F. et al. Interrater reproducibility of the Myoton and durometer devices to quantify sclerotic chronic graft-versus-host disease. Arch Dermatol Res 315, 2545–2554 (2023). https://doi.org/10.1007/s00403-023-02626-1
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DOI: https://doi.org/10.1007/s00403-023-02626-1