Unmasking Vexas Syndrome: A Rare Case with Crescentic Glomerulonephritis.

Abstract

Introduction: VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammation, and somatic) syndrome is a newly recognized autoinflammatory hematologic condition due to mutations in the UBA1 gene. This case demonstrates its clinical variability, such as neutrophilic dermatosis, pulmonary disease, and a rare presentation with acute kidney injury and glomerulonephritis.

Case description: A 77-year-old man with a history of benign prostatic hyperplasia, osteoarthritis, and patent foramen ovale presented with fatigue, night sweats, weight loss, and recurrent rashes, diagnosed as neutrophilic dermatosis. Laboratory results were pancytopenia and nephrotic-range proteinuria, and imaging revealed mediastinal lymphadenopathy and pulmonary ground-glass opacities. Bone marrow biopsy showed hypercellularity with vacuolization of myeloid and erythroid precursors. Renal biopsy revealed proliferative necrotizing and crescentic glomerulonephritis. Genetic analysis confirmed the UBA1 p.Met41Val mutation, diagnosing VEXAS syndrome. Treatment with corticosteroids, tocilizumab, and mycophenolate mofetil initially improved the symptoms, but steroid dependence continued. Severe pancytopenia necessitated changing to azacitidine after a year, and the patient was assessed for stem cell transplantation. His course was additionally complicated by neutrophilic pulmonary alveolitis.

Conclusion: VEXAS syndrome presents with recurring fever, arthritis, pulmonary and cutaneous involvement, and cytopenias. Diagnosis needs to be entertained in the context of cryptic cytopenias and antineutrophil cytoplasmic antibodies (ANCA)-negative vasculitis. Renal involvement is atypical, especially in ANCA negative cases. Treatment continues to remain difficult, with the initial first-line therapy as high-dose glucocorticoids, with the alternative options being Janus kinase inhibitors, interleukin-6 inhibitors, and stem cell transplant. The case highlights the value of identifying both characteristic and atypical presentations of VEXAS syndrome. Prompt genetic testing is essential in diagnosis, and management entails a multidisciplinary strategy.

Learning points: VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammation, and somatic) syndrome should be considered in patients with unexplained cytopenias, systemic inflammation, or atypical vasculitis.VEXAS syndrome is caused by a mutation of the UBA1 p.Met41Val gene.VEXAS syndrome usually presents itself as glomerulonephritis in antineutrophil cytoplasmic antibodies (ANCA) positive patients. However, it can be rarely present in ANCA negative patients too.