The Lethal VEXAS Syndrome is More Common Than Doctors Believed

A strange new illness might be responsible for severe, inexplicable inflammation in older men. Now, scientists have their first good look at who the disease strikes and how frequently.

VEXAS syndrome, an illness discovered simply two years ago, impairs almost 1 in 4,000 men over 50, scientists estimate January 24 in JAMA. The disease also manifests in older women, though much less often.

More than 15,000 individuals in the United States may be struggling with the syndrome, states study coauthor David Beck, a clinical geneticist at NYU Langone Health in New York City. Those numbers indicate that medical professionals should watch for VEXAS, Beck states. “It is underrecognized and underdiagnosed. Plenty of physicians are not yet familiar with it.”

Beck’s group identified VEXAS syndrome in 2020, connecting mutations in a gene called UBA1 to a collection of symptoms, including fever, low blood cell count, and inflammation. His team’s new study is the first to estimate just how frequently VEXAS occurs in the general population– and the results are surprising. “It’s more common than we believed,” states Emma Groarke, a hematologist at the National Institutes of Health in Bethesda, Md., who was not involved with the study.

What are the symptoms of VEXAS syndrome?

Individuals with the disease might experience a variety of symptoms throughout the body, including:

• Painful skin rashes
• Swelling and pain in the ears, nose, and joints
• Cough and shortness of breath
• Blood vessel swelling
• Fever
• Extreme fatigue
• Anemia
• Low blood cell count
• Blood clots

VEXAS often appears later in life — after people somehow obtain UBA1 mutations in their blood cells. Patients may feel tremendous fatigue and lethargy and have skin rashes, Beck states. “The disease is progressive, and it’s severe.” VEXAS can additionally be lethal. His team discovered that once an individual’s symptoms start, the median survival time is about ten years.

Until late 2020, nobody knew there was a genetic thread linking VEXAS syndrome’s otherwise unexplained symptoms. Individuals may be diagnosed with other afflictions, including polyarteritis nodosa, an inflammatory blood disease, and relapsing polychondritis, a connective tissue disorder, before being diagnosed with VEXAS.

To ballpark the variety of VEXAS-affected individuals, Beck’s team rummaged through the electronic health records of more than 160,000 people in Pennsylvania in collaboration with the NIH and Geisinger Health. In individuals over 50, the disease-causing UBA1 mutations appeared in roughly 1 in 4,000 men. Among women in that age group, approximately 1 in 26,000 had the mutations.

A genetic test of the blood can assist doctors in diagnosing VEXAS, and treatments like steroids and various other immunosuppressive medications, which tamp down swelling, can alleviate symptoms. Groarke and her NIH colleagues have also started a small phase II clinical trial testing bone marrow transplants to switch patients’ diseased blood cells for healthy ones.

Beck claims he intends to boost awareness about the disease, though he recognizes that there is much more work. In his team’s study, for example, the vast majority of individuals were white Pennsylvanians, so researchers do not know how the disease impacts other populations. Scientists also do not recognize what stimulates the blood cell mutations nor how they stimulate an inflammatory craze in the body.

“The more patients that are diagnosed, the more we’ll discover the disease,” Beck states. “This is just one step in the process of finding more effective treatments.”

Read the original article on Science News.

Read more: New Tau Regulators and Therapeutic Targets for Neurodegenerative Disorders Discovered