Symptoms, risks… we know more about this new auto-inflammatory disease that kills half of affected patients, thanks to a recent American study.
- The letters that make up the name of the syndrome, “VEXAS”, represent some of its biological characteristics: V for vacuoles in blood cells, E for the X-linked enzyme E1, A for autoinflammatory and S for somatic.
- Previous research led by Dr. Beck traced the origins of VEXAS syndrome to a genetic mutation – a change in the alphabetic code that makes up DNA – within the UBA1 gene (ubiquitin-like modifier activating enzyme 1).
- This enzyme generally helps break down proteins.
VEXAS syndrome is a medical mystery to doctors and scientists. This new autoinflammatory disease linked to somatic mutations in the UBA1 gene was first observed in 2020. Three years later, a team from NYU Grossman School of Medicine reveals more about this rare disorder with a relatively high mortality rate. high, on the occasion of a new study published on January 24 in the Journal of the American Medical Association (JAMA).
According to the study, in the United States, approximately 13,200 men and 2,300 women over the age of 50 suffer from VEXAS syndrome. In France, in 2021, 116 cases had been identified, again with a majority of men (96%), with a median age of 71 years, according to an article by The Journal of Internal Medicine.
What are the symptoms of VEXAS syndrome?
Up to half of patients with VEXAS die within five years of diagnosis. The most common symptoms include seemingly inexplicable fevers and low blood oxygen levels in people diagnosed with other conditions, including rheumatoid arthritis, lupus and blood cancer. Some symptoms of VEXAS even have to do with an innate immune system, which can lead to inflammation.
Overall, the NYU Grossman research team hopes their findings will help educate doctors and the public about this misunderstood syndrome. Importantly, the researchers add that high-dose steroids, JANUS kinase inhibitors, and bone marrow transplantation have all been shown to be effective in controlling some symptoms associated with VEXAS.
“Now that we know that VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians should add this condition to their list of potential diagnoses when faced with patients with persistent, unexplained inflammation and low blood cell count, or anemia”says the study’s geneticist and principal investigator, David Beck, in a Press release.
What are the chances of having VEXAS syndrome?
Statistically, the study data indicates that one in 4,269 older American men (over 50) and one in 26,238 older women have or are at risk of developing the syndrome. The study authors point out that these numbers are higher than many other inflammatory conditions, such as vasculitis and myeloid dysplasia syndrome.
To arrive at these estimates, the research team assessed the electronic medical records of adult patients who volunteered to participate in the “Geisinger MyCode” community health initiative. This program has been collecting data for more than 25 years from patients at more than 10 Geisinger hospitals in central and northeastern Pennsylvania in the United States. Almost all of the patients who agreed to have their DNA tested were Caucasian, and half were over 60.
In the future, Dr. Beck and his team plan to analyze patient records in more diverse groups, particularly those with higher rates of rheumatological and blood diseases. They hope this will promote a better understanding of who is most at risk for VEXAS syndrome. Researchers also want to continue to search for additional genetic causes, test new therapies for treatment, and even develop a blood test for UBA1 to aid in diagnosis.
