Prevalence of VEXAS Appears Higher Than Several Other Rheumatic Diseases

A new study suggests VEXAS syndrome could affect as many as 13,200 men and 2300 women in the United States over age 50. Researchers published their findings online in JAMA.

“VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic variants are associated with a broad spectrum of clinical manifestations,” wrote lead investigator David B. Beck, MD, PhD, of the National Human Genome Research Institute, Bethesda, Maryland, and coauthors. “Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes.”

Before its genetic basis was identified in 2020, VEXAS syndrome was considered a mystery illness but is now categorized as an autoimmune condition. The syndrome often includes unexplained fevers and low blood oxygen levels in patients with rheumatoid arthritis, lupus, and blood cancer. Up to half of patients with VEXAS, which affects mostly men, die within 5 years of diagnosis.

The study offers the first estimates of how common VEXAS syndrome is in a US-based single health system cohort. Researchers analyzed data from the electronic health records of 163,096 mostly White men and women in Pennsylvania who agreed to have their blood DNA screened for signs of genetic disease.

According to the study, 9 men and 2 women, or 1 in every 13,691 participants, harbored the disease-causing UBA1 mutation — all of whom experienced VEXAS symptoms. Statistically, the finding corresponded to 1 in 4269 men and 1 in 26,238 women older than 50 — a prevalence higher than that for vasculitis, myeloid dysplasia syndrome, and other inflammatory conditions, the research team pointed out.

“Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia,” said Dr Beck, who also led the research team that first identified the shared UBA1 mutation among patients with VEXAS syndrome.

The team next plans to analyze individuals from more racially diverse groups, especially those with higher rates of rheumatologic and blood disease. They also aim to investigate other genetic causes of VEXAS syndrome, test new therapies, and develop a blood test for UBA1 to simplify diagnosis.

—Jolynn Tumolo

References:

Beck DB, Bodian DL, Shah V, et al. Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population. JAMA. 2023;329(4):318-324. doi:10.1001/jama.2022.24836

Study offers first glimpse of how many suffer from previously unknown illness. News release. NYU Langone Health/NYU Grossman School of Medicine; January 24, 2023. https://www.sciencedaily.com/releases/2023/01/230124112747.htm. Accessed January 30, 2023.