Clinical characteristics and a screening tool for VEXAS syndrome: a case-control study from China

Abstract Background VEXAS syndrome is a severe autoinflammatory disease characterized by systemic inflammation, rheumatic manifestations, and hematologic abnormalities. Its clinical heterogeneity and overlap with other conditions complicate diagnosis. No case series have been reported from China. This study aimed to (1) describe the clinical features of Chinese patients with VEXAS syndrome and (2) propose screening recommendations to facilitate earlier identification. Methods We conducted a retrospective cohort study at Peking Union Medical College Hospital, enrolling 57 male patients with unexplained systemic inflammation and hematologic abnormalities. UBA1 gene sequencing was performed using bone marrow or peripheral blood samples. Clinical and laboratory data were extracted from electronic medical records. A screening model was developed using LASSO regression based on core features of confirmed cases and externally validated in two independent cohorts undergoing UBA1 sequencing. Results Among 57 suspected cases, 21 carried pathogenic UBA1 variants. Compared with non-VEXAS patients, VEXAS patients more frequently showed older age at onset, skin lesions, chondritis, macrocytic anemia, and characteristic bone marrow vacuolization. Importantly, skin lesions were the initial presenting symptom in over half of VEXAS patients, whereas fever predominated in the non-VEXAS group. Rare manifestations included glomerulonephritis, acute cerebral infarction, and pulmonary arterial involvement. A novel UBA1 variant (p.Thr318Met) was also identified. A screening model incorporating age at onset, skin lesions, chondritis, macrocytic anemia, and bone marrow vacuoles demonstrated good sensitivity and specificity in an external validation cohort. Conclusion This study is the first to characterize the clinical features of VEXAS syndrome in a Chinese population and to delineate its phenotypic spectrum. The proposed screening tool provides a practical aid for clinicians in identifying suspected cases and may facilitate improved diagnostic pathways and patient outcomes.