A Case of VEXAS Syndrome Initially Masked as Myelodysplastic Syndrome: Importance of Marrow Vacuolization and UBA1...

BACKGROUND VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently recognized autoinflammatory disorder of adulthood caused by somatic mutations in the UBA1 gene. It is characterized by systemic inflammation, cytopenias, and frequent overlap with myelodysplastic syndromes (MDS). Because of its clinical heterogeneity, diagnosis is often delayed or confounded by coexisting autoimmune or hematologic disorders. CASE REPORT We describe a male patient presenting with hyperchromic macrocytic anemia initially suspected to indicate MDS. Extensive diagnostic evaluation revealed no evidence of monoclonal gammopathy or autoimmune activity consistent with systemic lupus erythematosus, which had been part of the patient's medical history. Bone marrow analysis showed vacuolization of erythroid and myeloid precursors, and molecular testing identified a UBA1 missense mutation (c.122T>C, p.Met41Thr), confirming the diagnosis of VEXAS syndrome. Additional MDS-like features were present. Given the overlap with MDS, treatment with the hypomethylating agent azacitidine was initiated. CONCLUSIONS This case highlights the diagnostic challenges of VEXAS syndrome, particularly in patients with preexisting autoimmune conditions. The observation of bone marrow vacuolization proved decisive for diagnosis. Azacitidine was chosen based on its potential dual benefit in controlling both the clonal hematopoiesis and systemic inflammation. Emerging evidence indicates that azacitidine may be effective even in non-MDS VEXAS, providing a promising therapeutic approach in the absence of standardized treatment. Early recognition and molecular confirmation of UBA1 mutations are essential for accurate diagnosis and management of this rare but increasingly recognized condition.