Assessment of skin in patients with systemic sclerosis using high-frequency ultrasound and shear wave elastography: A comparative study with histology, molecular and clinical parameters.

Objective: Ultrasound (US) has been proposed as a potential tool for assessing skin fibrosis in systemic sclerosis (SSc). However, a large-scale comparison of US-based assessment with histological markers of skin fibrosis has not been reported. We evaluated the US-based skin assessments for their face validity (differentiation between involved SSc and healthy control [HC] skin), construct validity (comparison to modified Rodnan Skin score [mRSS]), and criterion validity (comparison to histological and gene expression fibrosis markers).

Method: Twenty HCs and 52 SSc patients underwent clinical and US assessment followed by a forearm skin biopsy. Predefined areas were assessed on the finger, hand, and forearm bilaterally. mRSS, US, histological and molecular (RT-qPCR) evaluations were performed by blinded, independent assessors. Dermal thickness, echogenicity, and elastography were assessed using a high-frequency GE LOGIQ P9 ultrasound machine.

Result: Except in the hand area, the US variables could not differentiate between HC and clinically affected SSc skin (face validity). There was only a weak to moderate correlation between US-based measurements and mRSS in the hand and finger areas (construct validity). US-based thickness showed moderate correlation with histological thickness (Rs=0.43, 0.002), but no statistically significant correlations with other histological or gene expression markers of fibrosis in SSc patients (criterion validity).

Conclusion: High-frequency US assessment of SSc skin does not show consistent and strong face, construct, or criterion validity. The role of this assessment tool remains limited, underscoring the need for further development of a quantitative and accurate tool for assessing SSc skin fibrosis.