#3-18E. Unmasking VEXAS Syndrome: A New Paradigm in Autoinflammation and Bone Marrow Failure (Lancet, 2026)

Have you ever encountered an older male patient presenting with treatment-refractory systemic inflammation and unexplained macrocytic anemia? This comprehensive review explores VEXAS syndrome, a monogenic autoinflammatory disease caused by acquired somatic mutations in the UBA1 gene within hematopoietic cells. These mutations disrupt the master enzyme of cellular ubiquitination, driving severe myeloid-mediated inflammation and progressive bone marrow failure. A pivotal clinical point highlighted is that hypomethylating agents, specifically azacitidine, can induce both clinical and molecular remission by directly targeting the mutated clone, offering a transformative therapeutic avenue beyond simple symptomatic management. Nevertheless, practitioners should exercise caution during critical appraisal, as the current evidence is primarily based on retrospective cohort studies and case series, lacking randomized controlled trials to establish standardized treatment algorithms. For physicians, recognizing VEXAS is essential because it frequently mimics conditions such as relapsing polychondritis, vasculitis, or myelodysplastic syndrome. Identifying this syndrome early is critical to mitigate the high 5-year mortality rates and the significant risks of severe infection and venous thromboembolism that characterize the disease's clinical course.

Citation: Emma M Groarke, et al. VEXAS syndrome - a comprehensive review of pathogenesis, clinical spectrum, and therapeutic strategies. The Lancet. 2026. DOI: https://doi.org/10.1016/S0140-6736(25)02164-6

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