Flow-Mediated Skin Fluorescence Assessment of Microvascular Function in Connective Tissue Diseases: Associations with Nailfold Capillaroscopic Patterns

Background/Objectives: Microvascular dysfunction is a common early manifestation of connective tissue diseases (CTDs), yet practical non-invasive tools remain limited beyond nailfold capillaroscopy. Flow-mediated skin fluorescence (FMSF), based on changes in nicotinamide adenine dinucleotide (NADH) fluorescence during brachial artery occlusion and reperfusion, is thought to reflect microvascular and mitochondrial function. We investigated whether FMSF differentiates CTD subgroups and how its parameters relate to capillaroscopic findings. Methods: In this exploratory cross-sectional study, we examined 99 adults: 19 with lupus erythematosus (LE), 25 with primary Raynaud phenomenon (PR), 29 within the systemic sclerosis (SSc) spectrum, and 26 healthy controls. FMSF parameters were compared across subgroups and capillaroscopic patterns (normal, nonspecific, scleroderma-like) using false discovery rate (FDR) correction and age adjustment. Results: Ten of 19 FMSF parameters differed among subgroups (all FDR-corrected p ≤ 0.03); after age adjustment, four remained significant (PSD1, endothelial and myogenic oscillations, and hypoxia sensitivity [HS]; all p ≤ 0.023), a gradient driven largely by the SSc spectrum. These differences attenuated to non-significance after excluding vasoactive-treated patients (HS p = 0.29) and when restricted to an overlapping age range (p = 0.06–0.18). Across capillaroscopic patterns, the hyperemic response index and HR max declined toward scleroderma-like patterns (both p = 0.007), but no parameter remained associated with pattern after adjustment for CTD diagnosis. findings: the FMSF signal was largely SSc-driven and sensitive to treatment and age, rather than a robust, disease-independent discriminator. Confirmation in larger, longitudinal cohorts is required.