Multimodal ultrasonographic muscle assessment in patients with systemic sclerosis and correlations with body composition

Introduction Patients with systemic sclerosis (SSc) can present with a variable muscle involvement ranging from sub-clinical to severe. The pathogenesis of sclerodermic myopathy involves different pathways such as vasculopathy, athrophy, inflammation, fat sostitution, and fibrotic changes. Additionally, patients with SSc show an increased risk of sarcopenia compared to the general population unrelated to myopathic damage. Muscle loss either by sarcopenia or myopathic damage have been associated in these patients with increased mortality and reduced quality of life. However, few studies have focused on the available imaging options to assess, study, and screen the muscle involvement in SSc. Aim The aim of the present work is to describe the ultrasound findings related to muscle mass, quality, and stiffness in patients with SSc and the correlations between the different ultrasound muscle assessment methods and between ultrasound muscle assessment and muscle strength. Additionally, the study aims to explore the correlation between ultrasound muscle assessment and body composition and with SSc clinical variables. Methods This was an observational multicentric cross-sectional study performed on patients with SSc consecutively recruited at the Rheumatology Unit, University of Verona and Leeds Institute of Rheumatic and Musculoskeletal Medicine. In all patients, we performed an ultrasound of the quadriceps muscle, measuring its thickness, echogenicity (using a semi-quantitative modified Heckmatt scale [mHS] and grey-scale histogram analysis [GSA]), and stiffness (measured by shear-wave elastography [SWE]). Muscle strength was assessed using the hand grip (HG) test, and disability was measured using the Health Assessment Questionnaire (HAQ). In the cohort of Verona, the patients underwent a total body Dual-energy X-ray Absorptiometry (DXA) to measure lean mass, fat mass and bone mineral density (BMD). Appendicular skeletal muscle mass/height2 (ASM/m2) was calculated to define sarcopenic patients. Results Overall, a total of 76 patients with SSc were assessed (45 in Leeds and 31 in Verona). QM thickness was significantly inversely correlated with muscle echogenicity (mHS: ρ=-0.335; p=0.008, GSA: ρ=-0.322; p=0.005). Additionally, mHS and GSA displayed a good correlation between them (ρ=0.569; p<0.001). SWE was inversely correlated with QM thickness (ρ=-0.279; p=0.016) and directly associated with muscle echogenicity (mHS: ρ=0.349; p=0.02). HG was positively correlated with QM thickness (ρ=0.379; p=0.003) and inversely correlated with muscle echogenicity (mHS: ρ=-0.327; p=0.012) and stiffness (ρ=-0.566; p<0.001). Regarding body composition, the QM thickness was directly correlated with lean mass in the lower limbs (ρ=0.545; p<0.001), with total lean mass (ρ=0.652; p<0.001) and ASM/m² (ρ=0.603; p<0.001). Echogenicity mHS was inversely associated with lean mass in the lower limbs (mHS: ρ=-0.327; p=0.015, GSA: ρ=-0.292; p=0.031) and directly associated with fat mass at the lower limbs (GSA: ρ=0.368; p=0.006). Stiffness was negatively correlated with fat mass at the lower limbs (ρ=-0.318; p=0.017). Additionally, echogenicity was inversely associated with whole-body lean mass and ASM/m² and stiffness was not correlated with whole-body assessment. Regarding bone-mass, the QM thickness was positively correlated with BMD, while echogenicity was inversely correlated with BMD and stiffness did not result correlated with BMD. Conclusion In this study, ultrasound has proven to be an effective tool for evaluating muscle involvement in systemic sclerosis, providing valuable information on muscle mass, quality, and stiffness, while correlating with functional outcomes related to sarcopenia, such as handgrip strength. Additionally, multimodal ultrasound muscle assessment has proven to be a promising tool for investigating changes in local and global body composition, allowing us to assess the relationship between muscle and bone in this group of patients, representing a potential novel screening tool for muscle health and sarcopenia in clinical practice.