Acute Fulminant Systemic Granulocytic Vasculitis Involving Arteries and Veins in Vacuoles, E1 Enzyme, X-Linked,...

Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is a disease concept characterized by UBA1 mutation that was first proposed in 2020. We report an autopsy case of VEXAS syndrome that was retrospectively diagnosed 11 years later through genetic analysis of formalin-fixed, paraffin-embedded (FFPE) bone marrow tissue. The patient was a 65-year-old male with hepatitis C who presented with general fatigue followed by fever 2 weeks later. Shortly before death, phlebitis of the extremities and marked leukocytosis became evident. The patient died within 3 weeks of symptom onset. Autopsy revealed granulocytic vasculitis involving small- to medium-sized arteries and phlebitis in various organs, including the lungs, kidneys, liver, and lymph nodes. Concomitant myelodysplastic syndrome (MDS) was confirmed, leading to a diagnosis of MDS-associated vasculitis. Sanger sequencing of FFPE specimens 11 years later revealed a UBA1 mutation (p. Met41Val), confirming VEXAS syndrome. Although VEXAS syndrome is typically characterized by chronic, treatment-refractory inflammation and poor prognosis, autopsy reports are rare. Herein, we report an autopsy case of VEXAS syndrome associated with MDS and systemic vasculitis that presented with a fulminant clinical course.