Spatial frequency domain imaging for assessment of skin fibrosis in systemic sclerosis: a prospective cohort study

Systemic sclerosis is an autoimmune disease with no approved skin-directed therapies. The modified Rodnan skin score (mRSS) is the standard measure of skin involvement in systemic sclerosis, but it has limitations. There is an unmet need for a non-invasive skin outcome measure that is objective, biologically anchored to dermal fibrosis, and scalable for multicentre trials. We evaluated spatial frequency domain imaging (SFDI), a wide field, non-contact optical method as a systemic sclerosis skin outcome measure.

This single-centre, prospective, cohort study was done at the Division of Rheumatology at the Boston Medical Center (Boston, MA, USA). Eligible patients were aged 18 years or older with systemic sclerosis fulfilling the 2013 American College of Rheumatology-European League Against Rheumatism classification criteria. Control participants were people aged 18 years or older without autoimmune disease or known skin pathology. For all participants, exclusion criteria included skin malignancy, wounds or rashes at SFDI measurement sites (dorsal hands, forearms, and fingers). Participants in the pilot phase completed one study visit with SFDI, mRSS assessment, and optional forearm biopsy. In the expanded protocol phase, participants had a baseline visit, with follow-up visits once every 3 months during the first year and once every 6 months thereafter for 3 years. At each study visit, SFDI, high-frequency ultrasound, and durometry were done in all participants, and mRSS was assessed in patients with systemic sclerosis. Optional forearm biopsy and blood collection was done at baseline in consenting participants. Main analyses assessed baseline associations of SFDI parameters (diffuse reflectance [R_d] and reduced scattering coefficient [μ_s']) with mRSS and correlations with histological features of skin involvement in forearm biopsies (dermal fibrosis, collagen content, myofibroblast staining, epidermal and dermal thickness, and additional histological features). Linear mixed-effects models were used for associations and Spearman models for correlations. People with lived experience of systemic sclerosis were not involved in the study design.

Between Oct 17, 2019, and June 18, 2025, 54 patients with systemic sclerosis and 30 healthy control participants were enrolled across the pilot and expanded protocol phases. The final analysis included 49 participants with systemic sclerosis and 25 control participants; biopsy samples were obtained from 34 participants with systemic sclerosis and 16 control participants. 38 (78%) of 49 participants with systemic sclerosis were female, 11 (22%) were male, 34 (69%) were White, and mean age was 50 years (SD 16). 20 (80%) of 25 control participants were female, five (20%) were male, 14 (56%) were White, and mean age was 49 years (SD 14). R_d and μ_s' were significantly lower in the systemic sclerosis cohort than in the control cohort across all mRSS strata, including sites where mRSS was 0. For each one-point increase in local mRSS there was a decrease in R_d (β=-0·0028, 95% CI -0·0050 to -0·0006; p=0·014) and μ_s' (β=-0·0158, 95% CI -0·0314 to -0·0003; p=0·047). SFDI correlations were weak to moderate with mRSS (r ranged from -0·38 to -0·48) and moderate with histological fibrosis (r ranged from -0·34 to -0·52).

SFDI provides an objective, non-invasive measure of skin involvement in systemic sclerosis that aligns with established clinical, imaging, and histological assessments. These findings support its potential as a quantitative outcome measure for evaluating skin disease in systemic sclerosis, consistent with Outcome Measures in Rheumatology principles.

National Institutes of Health, National Scleroderma Foundation, Scleroderma Clinical Trials Consortium.