Serum Tumstatin and Vascular Endothelial Growth Factor Levels in Patients with Rosacea: A Cross-Sectional Case–Control Study

Background/Objectives: Angiogenesis is a core feature of rosacea and vascular endothelial growth factor (VEGF) is upregulated in lesional skin, yet serum tumstatin, an endogenous angiogenesis inhibitor, has not been measured in rosacea. Methods: In this cross-sectional case–control study, serum VEGF and tumstatin were measured by enzyme-linked immunosorbent assay in 44 patients with rosacea and 44 age- and sex-comparable controls, with each analyte measured on a single plate. Results above the upper limit of quantification were treated as censored. Groups were compared with the Mann–Whitney U test and Tobit regression adjusted for age, sex and body mass index. Results: Both biomarkers were lower in rosacea: median VEGF 3.39 versus 5.50 ng/mL (p < 0.001; adjusted geometric mean ratio 0.71, 95% CI 0.58–0.86) and tumstatin 13.27 versus >20 ng/mL (p < 0.001; ratio 0.70, 95% CI 0.56–0.87). The analytes were very strongly correlated (ρ = 0.95), also within the measuring range (ρ = 0.91). Neither correlated with the Rosacea Area and Severity Index, disease duration or subtype, and discrimination was modest (area under the curve 0.72 and 0.70). Conclusions: In this preliminary single-centre study, serum VEGF and tumstatin were lower in patients with rosacea. Because the two analytes covaried to a degree that suggests a shared analytical factor, the samples were measured in singlicate, the kits were not validated in-house, many results exceeded the calibrated range, and VEGF concentrations (control median 5.50 ng/mL) exceeded published serum values from other immunoassays (≈0.04–0.23 ng/mL) more than tenfold, an analytical explanation cannot be excluded; the findings require confirmation with validated assays before any biological interpretation.