Deadly VEXAS syndrome is more common than doctors thought

A mysterious new disease may be causing severe, unexplained inflammation in older men. Now researchers have their first good look at who the disease strikes and how often.

VEXAS syndrome, a disease discovered just two years ago, affects nearly 1 in 4,000 men over 50scientists estimate January 24 to be JAMA. The disease also occurs in older women, although less frequently. In total, more than 15,000 people in the United States may have the syndrome, said study co-author David Beck, a clinical geneticist at NYU Langone Health in New York. These numbers indicate that physicians should be on the lookout for VEXAS, Beck says. “It’s under-recognized and under-diagnosed. Many doctors are still unaware of this.

Beck’s team reported discovering VEXAS syndrome in 2020, linking mutations in a gene called UBA1 to a range of symptoms including fever, low blood cell count and inflammation. His team’s new study is the first to estimate how often VEXAS occurs in the general population – and the results are surprising. “It’s more prevalent than we thought,” says Emma Groarke, a hematologist at the National Institutes of Health in Bethesda, Maryland, who was not involved in the study.

VEXAS tends to appear later in life – after people somehow acquire UBA1 mutations in their blood cells. Patients may experience overwhelming fatigue, lethargy and rashes, Beck says. “The disease is progressive and it is serious.” VEXAS can also be fatal. Once a person’s symptoms begin, the the median survival time is about 10 yearshis team found.

Until the end of 2020, no one knew that there was a genetic thread connecting the otherwise unexplained symptoms of VEXAS syndrome. In fact, individuals may be diagnosed with other conditions, including polyarteritis nodosa, an inflammatory blood disease, and relapsing polychondritis, a connective tissue disorder, before being diagnosed with VEXAS.

To estimate the number of people affected by VEXAS, Beck’s team combed through the electronic health records of more than 160,000 people in Pennsylvania, in collaboration with the NIH and Geisinger Health. In people over the age of 50, the pathogen UBA1 mutations occurred in about 1 in 4,000 men. Among women in this age group, about 1 in 26,000 had the mutations.

A genetic blood test can help doctors diagnose VEXAS, and treatments like steroids and other immunosuppressive drugs, which reduce inflammation, can ease symptoms. Groarke and his NIH colleagues also launched a small Phase II clinical trial testing bone marrow transplants as a way to swap patients’ diseased blood cells for healthy ones.

Beck says he hopes to raise awareness about the disease, although he acknowledges there is still a lot of work to be done. In his team’s study, for example, the vast majority of participants were white Pennsylvanians, so scientists don’t know how the disease affects other populations. Researchers also don’t know what triggers the blood cell mutations, or how they trigger an inflammatory frenzy in the body.

“The more patients diagnosed, the more we will learn about the disease,” says Beck. “This is just one step in the process of finding more effective therapies.”