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.

Thrombosis in VEXAS syndrome

“…In addition, functional studies of aberrant neutrophils [1] showed enhanced spontaneous neutrophil extracellular trap (NET) formation which can lead to endotheliitis, and platelet activation and aggregation. Evidence of cutaneous, pulmonary and systemic vasculitis [1,4,5] as well as ANCA-associated vasculitis [19] reflects multisystem autoinflammation. The presence of pathological antiphospholipid antibodies could enhance thrombogenesis by upregulation of tissue factor production and complement activation, leading to the activation of platelets and monocytes as well as promotion of the coagulation cascade [20].…”

Patients with VEXAS diagnosed in a Danish tertiary rheumatology setting have highly elevated inflammatory markers, macrocytic anaemia and negative autoimmune biomarkers

“…The presence of autoimmune biomarkers has not been systematically reported in previous reports of VEXAS patients; however, there has been reports of ANCA-positive patients with VEXAS as well as patients with antiphospholipid antibodies. 8 Thus, the lack of autoantibodies in the present case series, should not lead to premature conclusions of negative autoimmune biomarkers in VEXAS.…”

Das VEXAS-Syndrom

“…Darüber hinaus wurde auch das Vorkommen bei einer Vielzahl von Vaskulitiden, darunter ANCA-assoziierte Vaskulitis 9 , Behçet-Syndrom 10 , Polyarteriitis nodosa oder Großgefäßvaskulitis berichtet 4 .…”