Tissue Vulnerability Revealed by Ultrastructural Skin Analysis as a Surrogate for Arterial Integrity in Two Cases of Vascular Ehlers–Danlos Syndrome

Abstract Clinical presentation and operative outcomes in Vascular Ehlers–Danlos syndrome (VEDS) are heterogeneous. We present two patients with genetically confirmed VEDS who exhibited markedly different iliac pathology phenotypes. One ruptured a common iliac artery at near-normal diameter while the other tolerated a large aortoiliac aneurysm without rupture. The Aortic and Arterial Vulnerability Spectrum (AAVS) is a conceptual framework that characterizes aortic and arterial failure (dissection/rupture) along a continuum of underlying tissue vulnerability, integrating extracellular matrix (ECM) ultrastructure and clinical phenotypes beyond traditional diameter-based models. Using ultrastructural analysis of skin biopsy as a window into arterial integrity, we demonstrate distinct differences in ECM organization that paralleled vascular phenotype. Viewed through the AAVS, these cases show how genotype-driven vulnerability shapes surgical phenotype in VEDS and highlight ultrastructural skin analysis as a tool for ECM assessment and possibly biologic risk stratification.