Diagnostic and Therapeutic Challenge: VEXAS Syndrome with Multisystem Inflammation and Myelodysplasia: A Case Report

Abstract

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is an adult-onset autoinflammatory disorder caused by somatic UBA1 mutations linking systemic inflammation with haematologic dysfunction. We report a 59-year-old man presenting with fatigue, fevers, and severe macrocytic anaemia (haemoglobin 8.1 g/dL, MCV >120 fL), mild thrombocytopenia, and markedly elevated inflammatory markers. Autoimmune and malignancy workup was negative. Bone marrow biopsy showed hypercellularity with multilineage dysplasia and cytoplasmic vacuolisation, and genetic testing confirmed a somatic UBA1 mutation. High-dose glucocorticoids led to rapid resolution of inflammatory manifestations and normalisation of inflammatory markers; however, cytopenias progressed despite erythropoiesis-stimulating agents and ruxolitinib, with haemoglobin declining to <7 g/dL, resulting in transfusion dependence. The patient is undergoing evaluation for allogeneic haematopoietic stem cell transplantation (HSCT). This case highlights VEXAS syndrome as an aggressive haematoinflammatory disorder with limited responsiveness to conventional and targeted therapies and emphasises early consideration of advanced strategies, including HSCT, in selected patients.