Newly discovered Vexas syndrome may affect thousands more Americans than previously thought

The patient, Hector Campos, came to the emergency department with shortness of breath, an irregular fever, and swollen and itchy ears. Campos tested negative for COVID-19, his wife explained. “What do you think this might be?” Campos asked the chief of emergency medicine, Ethan Choi, who was similarly baffled by the man’s symptoms.

Scary right? But it’s not real — Campos and Choi are both characters on the NBC medical drama Chicago Med. Over the course of the episode, which aired in March 2021, Choi initially misdiagnoses Campos’ symptoms as pneumonia and a bacterial infection, but the test returns widespread inflammation. Campos’ condition rapidly deteriorates, and the team of doctors is alarmed until fellow surgeon Dean Archer suggests it might be VEXAS, a rare autoinflammatory syndrome. Gene sequencing eventually finds a mutation that confirms the diagnosis, and Choi begins treating the patient.

The episode is fictional, but images like this are surprisingly accurate for real-life cases of VEXAS, said David Beck, a clinical genetics researcher at New York University Grossman School of Medicine. “In terms of clinical manifestations, they were spotted right away,” he told The Daily Beast. Beck should know: He and his colleagues named the syndrome the first time in a study Posted in The New England Journal of Medicine in 2020. “I was affected, in fact, by the portrayal in popular media, because [it shows] They have read the newspaper.”

However, these representations of VEXAS syndrome tend to highlight severe cases, in part because the NEJM paper did as well. Of the 25 cases the researchers studied, 10 of the patients died of causes related to VEXAS.

But recent research has expanded the definition of the VEXAS condition to include a milder aspect. in paper published in gamma it is january. 24Beck and his colleagues surveyed the genetic sequence reads of more than 160,000 people to determine how common VEXAS syndrome really is, and how its symptoms manifest in patients. The research team found that nine male patients and two female patients in their study had mutations that caused VEXAS.

As a result, the researchers estimated that the syndrome affects about 13,200 men and 2,300 women over the age of 50 in the United States alone.

“It’s exciting to go from trying to understand a small number of patients to finding the same genetic cause and the same disease in tens of thousands of individuals,” Beck said. “Not only do we know that there are many patients who are suffering, who are not diagnosed, or who are not receiving the treatment that could help them and are just taking a step in that direction; it is also amazing that you can still make these kind of discoveries despite all the Ongoing biomedical research.

VEXAS is an acronym that stands for several of the key features of the syndrome. In each case of the syndrome, the patient has a gene mutation coding for the E1 enzyme. The mutation occurs on a gene located on the X chromosome, which you may remember from biology class, is a sex chromosome — men only have one, which makes them more likely to have VEXAS. The mutation is somatic, which means it is acquired during life rather than being inherited from either parent. This last feature, which gives VEXAS its “S,” is crucial: Because VEXAS is caused by a somatic mutation, the syndrome is not transmissible and only occurs in older patients, usually over the age of 50, Beck said.

Beck emphasized that this type of research is made possible by recent advances in genetic sequencing that have made it readily available and affordable to patients. All study participants sought care at a Geisinger healthcare facility in central and northeastern Pennsylvania between 1996 and 2022. Collaboration between Geisinger and Regeneron Genetics Center To map genetic diversity across the human genome, the participants’ exomes—the regions of their genome that encode proteins—were sequenced.

All 11 participants who were found to have mutations in the E1 enzyme gene were anemic and the vast majority had abnormally large red blood cells and low platelet counts – all symptoms consistent with VEXAS syndrome. Importantly, some of the more severe symptoms associated with VEXAS, such as costochondritis (which caused Campos’s ears to swell), were not present in these patients. This indicates that there may be a broader spectrum of severity when it comes to cases of VEXAS syndrome.

Another puzzling aspect of the study was the fact that the two women who were retrospectively identified as having VEXAS syndrome only had the VEXAS-related mutation on their One of their X chromosomes, not both. “It’s baffling to us,” Beck said, since researchers originally thought Vicksas only affected men. “We’ve been slowly getting to know more females with the disease, and we don’t understand why that is.” One phenomenon at play could be X inactivation, a process in which one of the female’s X chromosomes is silenced throughout her cells.

Future analyzes will be crucial to understanding the prevalence of the syndrome in diverse populations, the study authors write, because 94 percent of the participants in Geisinger’s group were white.

Currently, there is There are no cures for VEXAS It has been approved by the Food and Drug Administration, but a Phase II clinical trials It is currently being studied whether blood stem cell transplants can treat or cure the syndrome. In 2022, a team of French researchers publishes A study suggests that such a transplant can lead to complete remission, but such a procedure is not without its risks.

On the research front, Beck said scientists are still trying to figure out how a mutation in the gene that encodes E1 leads to the widespread inflammation seen in VEXAS cases. This enzyme starts a process for a cell to get rid of proteins it no longer needs, and more research is underway to determine how a dysfunctional E1 enzyme affects this process.

“If you’re a senior with systemic inflammation, low blood counts, no clear diagnosis, and you need steroids but you don’t have any clear diagnosis,” you should contact your doctor about genetic testing for Vexas syndrome, Beck said.

“It may help improve your treatments — and at least clear your prognosis,” he said.