November 2018

Non-invasive measurement of sclerosis in cutaneous cGVHD patients with the handheld device Myoton: a cross-sectional study

Authors: Fuyao Chen, Laura E. Dellalana, Jocelyn S. Gandelman, Arved Vain, Madan H. Jagasia & Eric R. Tkaczyk

Affiliations: Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA

Journal: Nature - Bone Marrow Transplantation - October 2018, Volume 54, 616–619(2019) (DOI: 10.1038/s41409-018-0346-7)

Chronic graft-versus-host disease (cGVHD) is the leading cause of long-term mortality and morbidity after stem cell transplantation (SCT). Skin is the most commonly affected organ [1]. Skin manifestations of cGVHD are broadly divided into two categories: erythema and sclerosis. Among patients being treated for cGVHD, 20% develop sclerosis within 3 years of transplant, leading to significant disability [2]. The current standard for monitoring cGVHD sclerosis is the NIH Skin Score [3]. However, this scoring system is subjective, coarse, and unreliable [4]. Sclerosis measurement by exam is difficult due to ill-defined borders and paucity of reliable visible changes. Sclerosis scores among multiple observers rarely exhibit substantial agreement, with a minimal reliable change detection of 17–26% BSA.

Developing a quantitative and reproducible measurement of sclerosis was deemed a top priority in the 2014 NIH Consensus on Response Criteria for cGVHD.

Serial skin biopsy is not practical to assess treatment response and histology is generally non-specific [7]. A magnetic resonance Imaging study of 15 cGVHD patients was able to identify abnormalities in the dermis, subcutaneous tissue, and muscle [8]. Ultrasound has shown differences in normalized shear wave speed in a study of four healthy controls versus five cGVHD patients [9]. Neither technology has yet advanced to large studies or widespread clinical use.

In this study, we investigated the feasibility of using an affordable tool to rapidly and directly measure cutaneous sclerosis in cGVHD patients. We employed the MyotonPRO, a commercially available, non-invasive handheld device developed to measure muscle biomechanical properties. It has been applied in diverse fields [10], but has not yet been used in dermal disorders.

The Durometer is another handheld device that appears similar to the MyotonPRO at first inspection. However, the underlying principle and function are very different between the two devices. The Durometer is designed for determining surface hardness by measuring the amount of force required to produce an indentation. Therefore, the Durometer reading is highly dependent on the force applied by the individual conducting the measurement.
By contrast, the MyotonPRO applies a fixed mechanical impulse, and calculates biomechanical properties based on the tissue’s inherent response.
The Durometer has been used to measure skin hardness in patients with scleroderma, but no results have been published in cGVHD [12].

Our results demonstrate that the MyotonPRO can objectively distinguish between healthy subjects and cGVHD patients with severe sclerosis.
Limitations of this preliminary study include small sample size and limitation to NIH Score three patients, which makes it difficult to assess generalizability of results. While our results indicate that skin stiffness measurements are significantly greater in patients with severe sclerotic cGVHD than healthy controls, further investigation is required to determine whether this translates to patients with mildmoderate disease. Further device development is also needed to assess the degree to which the Myoton is isolating skin and subcutaneous tissue. In this study, one observer performed all measurements, so the results do not speak to the interobserver reproducibility of the device. We have taken the first step toward developing a new method to objectively measure sclerotic GVHD disease. Reproducibility, generalizability, and the relative contributions of different soft tissue layers to the Myoton signal remain to be determined. If prospective longitudinal studies can correlate stiffness value changes to clinical disease progression, the Myoton can become an important tool for monitoring patient course and treatment response in sclerotic cGVHD.