Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: fevers, myalgia, arthralgia, auricular chondritis, and erythema nodosum

After 3 years of follow-up, repeated blood tests showed an increasing macrocytosis and persistent cytopenias: the patient's white blood cell count was 6 × 109 per L (normal 4·0–11·0), neutrophils 4·2 × 109 per L (normal 2·0–8·0), lymphocytes 0·6 × 109 per L (normal 1·2–3·5), haemoglobin concentration 10·8 g/dL (normal 13·5–17·0), mean corpuscular volume 119 fL (82–98), and platelets 146 × 109 per L (normal 150–400). Sanger sequencing of a peripheral blood sample from the patient showed a mutation affecting methionine-41 (c.122 T>C; p.Met41Thr) of the UBA1 gene and we made a diagnosis of the recently described X-linked inflammatory disease: vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome (appendix). Allogeneic stem-cell transplantation has been successful in a small number of patients and gene therapy is an area of active investigation (video).