Abstract
VEXAS syndrome is a recently characterized hemato-inflammatory disorder caused by somatic mutations in the X-linked UBA1 gene in hematopoietic progenitor cells; however, it remains poorly characterized in Chinese populations. We retrospectively analyzed 4,512 consecutive patients with hematologic abnormalities at a Chinese academic hospital between June 2023 and July 2024, identifying 16 male VEXAS patients (median age 61.5 years, range 30y - 74y). All patients presented with anemia and lymphopenia, with or without neutropenia and thrombocytopenia. Diagnoses included CCUS, MDS, MGUS, as well as novel phenotypes of primary myelofibrosis and a nonspecified hemolytic disorder. Most patients (11/16, 68.8%) exhibited constitutional symptoms and typical autoinflammation-associated multiorgan involvement, including skin lesions, ear chondritis, pulmonary infiltration, and deep vein thrombosis et al. Hypercellular bone marrow was commonly seen in core biopsies and 11 patients (68.8%) exhibited typical vacuoles in myeloid and erythroid progenitors. Canonical UBA1 pathogenic variants were detected in 13/16 (81.3%) of patients, with p.M41V being the dominant mutation. Three infrequent variants were also identified: c.118-1G>C, p.S56P, and p.S621C. Corticosteroids and immunosuppressants commonly provided symptomatic relief, while variable hematologic responses were achieved with androgens and erythropoiesis-stimulating agents. As a relatively large cohort of VEXAS syndrome characterizing Chinese patients, this study demonstrates a higher incidence than previously suggested and challenges the prevailing notion that VEXAS syndrome is a rare disorder. VEXAS should be considered in patients with cytopenia, regardless of comorbid systemic symptoms or multiorgan involvement, necessitating UBA1 testing for early diagnosis and appropriate therapy. Increased awareness among hematologists is critical to facilitate early diagnosis through UBA1 variant testing. This can prevent unnecessary diagnostic procedures and guide timely interventions, including preemptive stem cell transplantation.
