Introduction: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently identified, somatic mutation-driven, autoinflammatory syndrome primarily affecting older males. In VEXAS, somatic UBA1 mutations drive the clonal expansion of bone marrow-derived myeloid cells that infiltrate and initiate inflammation across the body, leading to diverse symptomology. Due to both the relative novelty of its discovery and rarity of its incidence, unique presentations and their management are vital in our continued understanding of the disease. Case description: We present a case of a 69-year-old male with no notable medical history who initially presented with episcleritis progressing to complete ophthalmoplegia. CT findings showed marked proptosis of the left eye and thickening of the lateral rectus. Over the subsequent months he presented to hospital repeatedly with worsening fibrotic lung disease. Eventually, after developing pancytopenia, a bone marrow biopsy showed histological features of VEXAS and the diagnosis was confirmed through genetic testing. Discussion: This case reveals a novel presentation of VEXAS and demonstrates the rapid progression to multi-organ disease possible in VEXAS. In this case, diagnostic auto-antibody panels all tested negative, and the patient was initially treated with high-dose steroids for suspected ANCA-negative vasculitis. Multiple unsuccessful attempts were made to wean and replace steroids with disease-modifying antirheumatic drugs. Following genetic confirmation of VEXAS, tocilizumab therapy was initiated. Conclusion: Due to the rapidly progressive nature of VEXAS and associated high mortality, early diagnosis is critical. This case highlights the importance of considering a bone marrow biopsy for suspicion of VEXAS when presented with an autoantibody-negative, multi-organ, autoinflammatory syndrome.
Krzowski et al. (Tue,) studied this question.