VEXAS syndrome unmasked from relapsing polychondritis and infection mimicry: a case-based review.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a UBA1-driven hemato-inflammatory disorder that mimics relapsing polychondritis, vasculitis, and myelodysplastic syndromes, often causing diagnostic delay. We describe a case presenting with relapsing polychondritis-like features and summarize, through a focused literature review, its diagnostic pathway and therapeutic implications. A 74-year-old man presented with three weeks of fever, auricular and nasal chondritis, iritis, and pulmonary infiltrates. Inflammatory markers were elevated with macrocytic anaemia. Antimicrobial therapy failed, whereas glucocorticoids produced rapid defervescence and clinical improvement. Bone-marrow examination revealed cytoplasmic vacuoles in myeloid precursors with dysplastic features. Sanger sequencing of UBA1 exon 3 on peripheral-blood DNA identified the canonical variant c.122T > C, p.(Met41Thr) as a mixed C/T chromatogram peak at codon 41. At structured 6-month follow-up the patient remained relapse-free on glucocorticoids. The genetic finding nevertheless supported the diagnosis. Diagnostic difficulty arises from clinical heterogeneity. A practical pathway emerges: recognition of relapsing polychondritis and infection presentations, evaluation of macrocytosis and cytopenias, bone-marrow examination for precursor vacuoles, UBA1 sequencing with adequate analytic sensitivity, and exclusion of mimics. Glucocorticoids are first-line; steroid-sparing options-interleukin-1 and interleukin-6 inhibitors, Janus kinase inhibitors, and allogeneic hematopoietic stem cell transplantation-are selected by phenotype, severity, and transplant eligibility. VEXAS syndrome should be suspected in older adults with refractory inflammation and unexplained cytopenias. Early recognition of marrow vacuolization and UBA1 sequencing with adequate analytic sensitivity may shorten diagnostic delay and facilitate risk-adapted treatment.