VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) Syndrome
Clinical Syndrome:
• Common Clinical Features: alveolitis, ear and nose chondritis, skin lesions: neutrophilic dermatosis, thromboembolic disease, recurrent fevers, vasculitis
• Hematologic Abnormalities: macrocytic anemia, thrombocytopenia, multiple myeloma, myelodysplastic syndrome (MDS)
Most met criteria for
1) hematologic conditions - multiple myeloma or myelodysplastic syndrome (MDS)
and/or
2) Inflammatory conditions
• relapsing polychondritis (60%)
• Sweet's Syndrome (32%)
• polyarteritis nodosa (12%)
• giant cell arteritis (4%)
Genetic Features:
• somatic mutations in UBA1 gene (X-chromosome) identified in 25 men
• UBA1 = major E1 enzyme that initiates ubiquitylation
• mutations in hematopoietic stem cells including peripheral blood myeloid cells
NEJM Review: https://www.nejm.org/doi/full/10.10
Mithu Maheswaranathan, MD @MithuRheum
#VEXAS #Syndrome #Vacuoles #E1 #Xlinked #Autoinflammatory #Somatic #rheumatology
