Vexas Syndrome Without Macrocytosis: A Case Highlighting an Expanding Clinical Phenotype and Diagnostic Delay

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently established adult-onset autoinflammatory disorder caused by somatic mutations in the ubiquitin-activating enzyme 1 (UBA1) gene. The condition predominantly affects men in later stages of life and is characterised by recurrent systemic inflammation, fever, pulmonary involvement, dermatological manifestations, haematological abnormalities, and frequent corticosteroid dependence. Due to its heterogeneous clinical presentation, diagnosis can often be delayed, effectively resulting in significant morbidity and mortality. We report the case of a 78-year-old man who presented with recurrent episodes of high-grade fever, a widespread rash, pulmonary infiltrates, and repeated episodes initially diagnosed as periorbital cellulitis. Despite extensive investigations and multiple courses of antibiotics, no infective source was identified. The patient demonstrated recurrent inflammatory flares that responded to corticosteroids but relapsed during steroid tapering. Over the course of approximately one year, he developed progressive systemic inflammation, constitutional symptoms, pulmonary involvement, and normocytic normochromic anaemia. Following emerging recognition that macrocytosis may not be universally present in VEXAS syndrome, the diagnosis was considered and confirmed by bone marrow examination and genetic testing, demonstrating a pathogenic UBA1b mutation (p.Met41Val, c.121A>G). Unfortunately, the patient deteriorated rapidly and died before the diagnostic results became available. This case highlights the diagnostic challenges associated with VEXAS syndrome, particularly in patients lacking classical haematological features such as macrocytosis. Increased awareness of the expanding phenotypic spectrum of VEXAS syndrome is essential to facilitate earlier diagnosis and timely multidisciplinary management.