VEXAS Syndrome: A Comprehensive Review for Dermatologists Part 1: Epidemiology, Pathophysiology, and Clinical Presentations.

Abstract

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly recognized, ubiquitin-activating enzyme E1 (UBA1)-mediated autoinflammatory disorder characterized by treatment-refractory systemic inflammation and diverse cutaneous findings. Dermatologists are uniquely positioned to facilitate early diagnosis because skin involvement occurs frequently and often precedes multi-organ disease. This 2-part continuing medical education series provides an up-to-date overview of VEXAS syndrome. Part 1 reviews epidemiology, pathogenesis, and key clinical and laboratory features, emphasizing dermatologic presentations that should raise suspicion for VEXAS syndrome. Part 2 outlines the diagnostic work-up, including bone marrow findings, definitive UBA1 genetic testing, and management strategies alongside emerging data on prognosis. Together, these articles equip clinicians to recognize VEXAS syndrome, differentiate it from common mimickers, and guide appropriate evaluation and treatment.