Systemic inflammation with myelodysplastic features: VEXAS syndrome

A man in his early 80s presented with transfusion-dependent macrocytic anaemia, steroid-responsive headaches and recurrent inflammatory flares. Broad infectious, autoimmune and haematological investigations were negative, yet symptoms relapsed each time prednisolone was tapered. The coexistence of refractory inflammation, giant cell arteritis-like features and progressive cytopenias prompted targeted sequencing, which uncovered a somatic UBA1 p.Met41Thr mutation and confirmed vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Empirical antimicrobials and high-dose steroids provided only brief control. Ruxolitinib followed by subcutaneous azacitidine stabilised inflammatory markers, enabled gradual steroid tapering and reduced hospitalisations although anaemia remained. This case highlights key diagnostic and management principles. First, clinicians should consider VEXAS in older men with overlapping vasculitic and myelodysplastic features. Second, molecular testing should be pursued even when marrow vacuoles are subtle. Thirdly, multidisciplinary care combining steroid-sparing immunomodulators with clonal-directed therapy is essential.