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

ABSTRACT

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is an autoinflammatory condition with overlapping features of rheumatology and haematology caused by somatic mutations in the UBA1 gene. Patients present with highly variable symptoms and their path towards diagnosis are often complicated and characterised by extensive examinations. It is, therefore, pivotal that clinicians become familiar with the clinical presentation of VEXAS to advance identification of patients with the disease. OBJECTIVES: We aimed to (1) characterise patients diagnosed with VEXAS in a tertiary rheumatology referral centre, (2) identify common rheumatological biomarkers that may distinguish VEXAS from other rheumatic diseases and (3) suggest which clinical findings should motivate genetic testing for VEXAS. METHODS: Patients were identified and diagnosed at the department of Rheumatology, Aarhus University Hospital (AUH), Denmark. Blood samples were examined for VEXAS-associated UBA1 variants by Sanger sequencing at the department of Clinical Immunology, AUH. Clinical and biochemical data were retrieved from the hospital electronic patient chart. RESULTS: Eleven male patients with clinical suspicion of VEXAS underwent sequencing. Five of these carried known VEXAS-associated variants. Median age at diagnosis was 84 (75-87) years. All patients had significantly elevated inflammatory markers with a median C-reactive protein (CRP) of 297 (196-386) mg/L and macrocytic anaemia. None of the patients presented common biomarkers for autoimmunity. CONCLUSION: Danish patients with VEXAS syndrome are men with persistent inflammation, constitutional symptoms and heterogeneous clinical presentations. Shared features for all patients in this study were highly elevated inflammatory markers, macrocytic anaemia and negative autoimmune biomarkers.