We used a clinically oriented phenotype-first approach to identify patients with VEXAS syndrome from a single-center cohort of Italian patients with vasculitis.
The clinical records of 147 consecutive male patients followed in our vasculitis clinic from 2013 to date were retrospectively reviewed. All patients with a diagnosis of vasculitis and inflammatory manifestations resistant to treatment, persistently elevated inflammatory markers, and hematologic abnormalities were identified. Bone marrow aspirates were reviewed for the presence of vacuoles. Sequencing of UBA1 was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue.
7 patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA1 (for 1 patient it was a post-mortem diagnosis). All 3 patients had evidence of the characteristic vacuoles at bone marrow aspirate, and all 3 patients met the definite WHO criteria for myelodysplastic syndrome. Cytogenetic analysis showed a normal karyotype in all 3 patients. We report the first case of VEXAS syndrome associated with ANCA-associated vasculitis.
Our data emphasize the need to consider VEXAS syndrome when evaluating patients with many different forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA associated vasculitis needs further investigations.