Abstract:

VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized autoinflammatory disease involving multiple systems, caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. Since the disease was first reported in 2020, the number of cases has increased rapidly worldwide, and single case and case series have also been reported in China. VEXAS syndrome predominantly occurs in middle-aged and elderly males, with complex and diverse clinical manifestations that often involve multiple systems, including fever, skin lesions, chondritis, pulmonary infiltrates, vasculitis, and macrocytic anemia, making it prone to misdiagnosis as other rheumatic or hematologic diseases. Diagnosis of VEXAS syndrome highly relies on UBA1 gene sequencing, which should be performed in patients with characteristic clinical presentations mentioned above and vacuolization of myeloid and erythroid precursor cells observed in bone marrow biopsy. The treatment of VEXAS syndrome is highly challenging, and there is currently no comprehensive standardized treatment guideline. Glucocorticoids are the first-line treatment for controlling acute inflammation, but most patients exhibit steroid dependence. Traditional immunosuppressants are mostly ineffective or difficult to sustain, while Janus kinase (JAK) inhibitors, interleukin-6 (IL-6) inhibitors, and hypomethylating agents have shown good efficacy in some patients. Allogeneic hematopoietic stem cell transplantation is currently the only method that can cure VEXAS syndrome, but the benefits and risks for patients must be strictly evaluated. Targeted precision therapy against UBA1-mutant clones may become a future research direction.

Key words: VEXAS syndrome, Ubiquitin-like modifier activating enzyme 1 gene, Clonal hematopoiesis