Progressive Macrocytic Anemia Over 14 Years Leading to the Diagnosis of VEXAS Syndrome in a Patient Initially Diagnosed With Adult-Onset Still’s Disease: A Case Report

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized autoinflammatory disease caused by somatic mutations in UBA1. Its clinical features include recurrent fever, systemic inflammation affecting multiple organs, and progressive hematologic abnormalities such as macrocytic anemia. Because these manifestations overlap with other autoinflammatory diseases, including adult-onset Still's disease (AOSD), the diagnosis can be challenging. In this case report, we describe a patient initially diagnosed with AOSD who was ultimately found to have VEXAS syndrome five years later due to progressive macrocytic anemia. The patient developed recurrent fever and skin rash but did not have macrocytic anemia at onset. Over the subsequent five years, his mean corpuscular volume progressively increased. Bone marrow biopsy revealed no evidence of malignancy but showed vacuoles in myeloid and erythroid progenitor cells. Based on these findings, VEXAS syndrome was suspected, and UBA1 testing identified the pathogenic p.Met41Thr variant, confirming the diagnosis. This case highlights that macrocytic anemia may not be present in the early phase of VEXAS syndrome. In patients diagnosed with AOSD who later develop or progressively worsen macrocytic anemia, clinicians should consider VEXAS syndrome and perform UBA1 variant testing.