What Is VEXAS Syndrome? | Everyday Health
A rare, recently discovered inflammatory disease may strike more people than previously thought, a new study suggests.
Scientists first reported the discovery of a disease they dubbed VEXAS syndrome in a paper published in 2020 in The New England Journal of Medicine (NEJM). At the time, they only identified 25 men in the United States with the condition — and no women. All had similar mutations in a gene called UBA1.
Now, a new paper published in JAMA on January 24, suggests that VEXAS, while still rare, is much more common than scientists initially believed, impacting roughly 1 in 13,600 people. The researchers also found that VEXAS is even more common in older individuals and affects both men and women: Among those 50 and older, researchers estimate a VEXAS prevalence of about 1 in 4,300 men and 1 in 26,200 women.
VEXAS most often occurs in people diagnosed with other autoimmune conditions including lupus, rheumatoid arthritis, and blood cancers.
“The findings of this study are remarkable,” says Matthew Koster, MD, an assistant professor and rheumatologist at the Mayo Clinic in Rochester, Minnesota, who has researched VEXAS but wasn’t involved in the new study. “Many academic and referral centers were wondering: Is VEXAS really more common than we think, with patients hiding in plain sight? And the answer is yes.”
What Is VEXAS Syndrome?
The emerging picture of VEXAS began to come into focus when scientists realized that some people with a complex constellation of symptoms that appear in many autoimmune disorders shared common mutations in the UBA1 gene.
“VEXAS syndrome is characterized by anemia, and inflammation in the skin, lungs, cartilage, and joints. These symptoms are frequently mistaken for other rheumatic or hematologic diseases,” says David Beck, MD, PhD, an assistant professor of at the New York University Grossman School of Medicine in New York City, and lead author of the latest VEXAS study as well as the initial NEJM paper. “However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”
VEXAS results from a genetic mutation that occurs in the bone marrow, but it isn’t inherited. It appears spontaneously and doesn’t appear to pass from parent to child, Dr. Koster says. “Currently, we do not know what might provoke or prompt a mutation like this to occur,” Koster adds.
What Does VEXAS Stand For?
VEXAS is an acronym for many of the disease’s features: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory, and somatic.
While doctors can diagnose the syndrome with genetic testing, these tests aren’t yet widely available, both Drs. Beck and Koster note.
Patients, especially males over 50, with certain symptoms that aren’t explained by other diseases should ask their doctor about whether the cause could be VEXAS, Koster advises. He says these symptoms include:
- Low levels of hemoglobin or platelets in their blood
- Recurring or hard to control inflammatory issues in the joints, skin, eyes, ears, or nose
- Unexplained narrowing or blockages in the veins
“These are patients that should be checked,” Koster says. “If diagnosed with VEXAS syndrome, it’s important to get referred to an institution with a multispecialty practice in hematology and rheumatology that has experience with VEXAS.”
VEXAS Is Deadly and Affects Women as Well as Men
Beck highlights two other key findings from the most recent research on VEXAS: The condition may be more lethal than previously thought, and it may not only impact men.
To calculate the prevalence of VEXAS in the new study, researchers examined genetic data and electronic medical records for more than 163,000 patients who participated in the MyCode Community Health Initiative at Geisinger, a health system in Pennsylvania.
VEXAS killed 75 percent of the 12 patients identified in the new study, up from a death rate of 40 percent among that initial group of 25 men examined in the NEJM study. “The disease is fatal for a variety of reasons, including severe acute episodes of inflammation, blood clots, and infections,” Beck says.
In addition, the new study identified two women with VEXAS, both of whom died. “I think we may have initially underestimated how many women are impacted by this disease, and I expect we will continue to find a substantial, yet smaller, population of females impacted,” Beck says.
One limitation of the new study is that findings from Geisinger, where patients are predominantly of European ancestry, may not reflect the prevalence of VEXAS among people of other backgrounds.
How Is VEXAS Syndrome Treated?
Treatment approaches may vary, and are still being developed as scientists learn more about this new disease. Options for managing symptoms may include steroids or biologics such as tocilizumab (Actemra) and ruxolitinib (Jakafi) to control inflammation, Beck says. Some patients, particularly those with dangerously low levels of hemoglobin and platelets in their blood, might also require blood transfusions or bone marrow transplants.
But there isn’t yet a clear prevention strategy. “We don’t know of any way to prevent or minimize the risk of the disease,” Beck says.