Serial CO₂ hand baths are associated with improved microvascular parameters and Raynaud-related symptoms in systemic sclerosis: A controlled feasibility study

BACKGROUND: Raynaud's phenomenon (RP) in systemic sclerosis (SSc) is driven by microvascular dysfunction. Previous work showed acute hemodynamic improvement after a single CO₂ hand bath in SSc. We investigated the effects of serial CO₂ hand baths on blood flow and symptom burden. METHODS: In this controlled feasibility study, fourteen patients with SSc and severe RP and fourteen age-matched healthy controls underwent daily CO₂ hand baths for 7 consecutive days. Primary endpoint was change in Doppler-derived resistance index (RI) from baseline to day 7 (both groups). Secondary endpoints included Raynaud Condition Score (RCS), attack frequency and duration. RESULTS: Baseline RI was significantly higher in SSc than in healthy controls (0.80 ± 0.02 vs. 0.73 ± 0.03, p < 0.001). Following intervention, RI decreased significantly in both groups (SSc: mean change -0.17, 95% CI [-0.20,-0.13], p < 0.001, controls: mean change -0.11, 95% CI [-0.13,-0.09], p < 0.001), with no significant between-group difference at day 7 (0.64 vs. 0.62, p = 0.889). In SSc, RCS improved progressively, exceeding the minimal clinical difference at day 4 (median change -1.6, p = 0.001) and reaching -3.0 points by day 7, with significant reductions in attack frequency and duration (both p ≤ 0.001). No adverse events occurred. CONCLUSION: Serial CO₂ hand baths were associated with progressive changes in Doppler-derived vascular parameters and patient-reported RP outcomes in SSc. Post-treatment RI values were comparable to those of healthy controls, and the minimal clinical difference was exceeded from day 4 onward. Randomized controlled trials are needed.