Newly Diagnosed VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome in a Patient Presenting...

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described inflammatory disease characterized by recurrent autoimmune manifestations, such as chondritis and uveitis, in the setting of classic laboratory abnormalities, including elevated inflammatory markers and macrocytic anemia. It is caused by an acquired mutation in the UBA1 gene within the myeloid lineage, ultimately resulting in cell death and systemic inflammation. Timely diagnosis can help expedite treatment and encourage monitoring for complications of the disease, most notably a predilection to infections. A 77-year-old male presented to the emergency room due to new-onset fevers and shortness of breath. His history was notable for six months of non-specific symptoms such as fatigue and weight loss, as well as recurrent inflammatory syndromes, including uveitis and joint swelling. At one point, he was treated empirically with steroids due to concern for giant cell arteritis; however, biopsy did not confirm this diagnosis. Labs were notable for significantly elevated inflammatory markers and a macrocytic anemia. His hospitalization was notable for acute hypoxemic respiratory failure requiring high-flow nasal cannula oxygen. His condition improved with broad-spectrum antibiotics, and he was ultimately diagnosed with Legionella pneumonia when Legionella PCR from pleural fluid returned positive. Prior to discharge, genetic testing for the UBA1 gene mutation and bone marrow biopsy demonstrating vacuolization of myeloid precursors confirmed the diagnosis of VEXAS syndrome. He was started on prednisone and azacitidine in the outpatient setting, which led to significant improvement in symptoms, inflammatory markers, and cell counts.