[Review] VEXAS syndrome: a comprehensive review of pathogenesis, clinical spectrum, and therapeutic strategies

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Source: The Lancet

Original: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02164-6/fullt...

Published: 2026-01-08T23:30:03Z

VEXAS syndrome is a monogenic disease of adults characterized by refractory systemic inflammation and progressive bone marrow failure.[1] It is caused by acquired somatic mutations in the UBA1 gene, limited to hematopoietic cells.[1][2] Men aged 50 and older are particularly susceptible, with an estimated prevalence of approximately one in 4,000 men.[1] The mutation disrupts the UBA1 enzyme responsible for cellular ubiquitination, which promotes myeloid inflammation difficult to influence with drugs other than glucocorticoids.[1] Clinical signs include systemic inflammation with hematologic changes such as anemia, thrombocytopenia, and vacuoles in myeloid and erythroid precursors in the bone marrow.[1][2][3] They prevail in men in the second half of life due to localization on the X chromosome.[1][2] The diagnosis is confirmed by the presence of vacuoles in the bone marrow and a mutation in the UBA1 gene.[1][3]