VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by UBA1 somatic mutations and is characterized by late-onset systemic autoimmune inflammation and blood abnormalities such as cytopenia, vacuolation of myeloid/erythroblastic cells, and myelodysplastic syndrome (MDS). It is often resistant to immunosuppressive therapy, and no treatment strategy has been established. A 65-year-old man presented with palpable erythema, fever, macrocytic anemia, and arthralgia. He was subsequently diagnosed with MDS complicated by Sweet’s disease. Treatment with azacitidine was initiated due to suspected skin invasion by MDS cells and resistance of the skin rash to steroid therapy. Next-generation sequencing of bone marrow samples prior to treatment initiation revealed the presence of UBA1 p.M41L (VAF 0.38) and DNMT3A p.L605fs mutations (VAF 0.184). Based on the findings of systemic inflammation, a diagnosis of VEXAS syndrome was made. The fever and skin rash improved with azacitidine therapy. In conclusion, somatic mutations in UBA1 should be explored in patients with MDS exhibiting systemic autoimmune inflammation. Furthermore, azacitidine may be a good treatment option for systemic autoinflammation in MDS associated with VEXAS syndrome.© 2023. Japanese Society of Hematology.
