VEXAS Syndrome: A Case Series From a Single-Center Cohort of Italian Patients With Vasculitis

Abstract

Objective: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach.

Methods: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin-activating enzyme E1 (UBA-1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue.

Results: Seven 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 UBA-1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients.

Conclusion: To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA-associated vasculitis reported herein warrants further investigation.

Figure 1

A, Bone marrow aspirate from patient 7, showing evidence of dysplasia and cytoplasmic vacuolization of the erythroid and myeloid precursor cells. B, Higher‐magnification view of the bone marrow aspirate from patient 7, showing dysplasia (neutrophils with pseudo Pelger‐Huët anomaly) and cytoplasmic vacuolization of the erythroid precursor cells (blue arrows) and myeloid precursor cells (red arrow). Stained with May‐Grünwald‐Giemsa stain; original magnification × 400 in A; × 1,000 in B.