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

VEXAS syndrome, an illness discovered just two years ago, affects nearly 1 in 4,000 men over 50 years old, scientists estimate January 24 in JAMA. The disease also occurs in older women, though less frequently. Altogether, more than 15,000 people in the United States may be suffering from the syndrome, says study coauthor David Beck, a clinical geneticist at NYU Langone Health in New York City. Those numbers indicate that physicians should be on the lookout for VEXAS, Beck says. “It’s underrecognized and underdiagnosed. A lot of physicians aren’t yet aware of it.”
Beck’s team reported discovering VEXAS syndrome in 2020, linking mutations in a gene called UBA1 to a suite 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 suspected,” says Emma Groarke, a hematologist at the National Institutes of Health in Bethesda, Md., who was not involved with the study.
VEXAS tends to show up later in life ­­— after people somehow acquire UBA1 mutations in their blood cells. Patients may feel overwhelming fatigue, lethargy and have skin rashes, Beck says. “The disease is progressive, and it’s severe.” VEXAS can also be deadly. Once a person’s symptoms begin, the median survival time is about 10 years, his team has found.

Until late 2020, no one knew that there was a genetic thread connecting VEXAS syndrome’s otherwise unexplained symptoms. 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 ballpark the number of VEXAS-affected individuals, Beck’s team combed through electronic health records of more than 160,000 people in Pennsylvania, in a collaboration with the NIH and Geisinger Health. In people over 50, the disease-causing UBA1 mutations showed up in roughly 1 in 4,000 men. Among women in that age bracket, about 1 in 26,000 had the mutations.

A genetic test of the blood can help doctors diagnose VEXAS, and treatments like steroids and other immunosuppressive drugs, which tamp down inflammation, can ease symptoms. Groarke and her NIH colleagues have also started 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, though he recognizes that there’s much more work to do. In his team’s study, for instance, 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 spurs the blood cell mutations, nor how they spark an inflammatory frenzy in the body.

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

For nearly 650 years, the fortress walls in the Chinese city of Xi’an have served as a formidable barrier around the central city. At 12 meters high and up to 18 meters thick, they are impervious to almost everything — except subatomic particles called muons.

Now, thanks to their penetrating abilities, muons may be key to ensuring that the walls that once protected the treasures of the first Ming Dynasty — and are now a national architectural treasure in their own right — stand for centuries more.

A refined detection method has provided the highest-resolution muon scans yet produced of any archaeological structure, researchers report in the Jan. 7 Journal of Applied Physics. The scans revealed interior density fluctuations as small as a meter across inside one section of the Xi’an ramparts. The fluctuations could be signs of dangerous flaws or “hidden structures archaeologically interesting for discovery and investigation,” says nuclear physicist Zhiyi Liu of Lanzhou University in China.
Muons are like electrons, only heavier. They rain down all over the planet, produced when charged particles called cosmic rays hit the atmosphere. Although muons can travel deep into earth and stone, they are scattered or absorbed depending on the material they encounter. Counting the ones that pass through makes them useful for studying volcano interiors, scanning pyramids for hidden chambers and even searching for contraband stashed in containers impervious to X-rays (SN: 4/22/22).

Though muons stream down continuously, their numbers are small enough that the researchers had to deploy six detectors for a week at a time to collect enough data for 3-D scans of the rampart.

It’s now up to conservationists to determine how to address any density fluctuations that might indicate dangerous flaws, or historical surprises, inside the Xi’an walls.