Identified in 2020, VEXAS syndrome is a rare, genetically linked disorder with a high death rate. VEXAS syndrome is a disease that causes inflammatory and hematologic (blood) manifestations. The syndrome is caused by mutations in the UBA1 gene of blood cells and acquired later in life. Patients do not pass the disease to their children.

The syndrome includes unexplained fevers and low blood oxygen levels in people with other conditions such as rheumatoid arthritis, lupus and blood cancer. It is an autoimmune condition, linked to inflammation and an overactive immune system.

What are the symptoms of VEXAS syndrome?

Patients with VEXAS can have a wide range of inflammatory symptoms affecting multiple organs including:

  • skin (rashes that can be painful).
  • cartilaginous structures (pain and swelling of the ear and nose).
  • lungs (cough and shortness of breath).
  • joints (swelling and pain).
  • vasculature (inflammation of vessels).

Patients often have fever and extreme fatigue. The hematologic features can include anemia, low platelets, and blood clots. On many occasions patients with VEXAS have associated clinical diagnoses, including relapsing polychondritis, polyarteritis nodosa, sweet syndrome and myelodysplastic syndrome.

How do you diagnose and treat VEXAS syndrome?

A VEXAS diagnosis uses genetic testing, which looks for mutations in the UBA1 gene located in the X chromosome.

There is no standardized treatment for VEXAS currently, however the inflammatory features can be treated with steroids and other immunosuppressants. Some patients may be candidates for bone marrow transplantation. Since VEXAS can affect multiple organs, patients will need a team of doctors—including a rheumatologist and hematologist—to manage their disease.

Who gets VEXAS syndrome?

Research studies indicate that VEXAS is primarily observed in biological males.

“Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia,” said geneticist and study lead investigator Dr. David Beck. He is an assistant professor in the department of medicine and the department of biochemistry and molecular pharmacology at NYU Langone Health in New York City.

Beck also led the federal research team that identified the shared UBA1 mutation among VEXAS patients.

“Our study offers the first glimpse of just how common VEXAS syndrome is in the United States, particularly among men, who also happen to be the most [likely] to die from it,” Beck said in an NYU Langone Health news release.

For the new study, the researchers analyzed the electronic health records of more than 163,000 mostly white men and women in Pennsylvania. Participants agreed to have their blood DNA screened for signs of genetic disease.

Among them, 12 were found to have the UBA1 mutation. All of those 12 had VEXAS symptoms.

This corresponds to 1 in more than 4,200 American men over age 50 and 1 in more than 26,200 American women over 50 who are likely to develop VEXAS. Based on this, researchers said the syndrome may be more prevalent than other inflammatory conditions, including vasculitis and myeloid dysplasia syndrome.

VEXAS stands for many of its characteristics: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory and somatic.

About 13,200 men and 2,300 women are estimated to have VEXAS syndrome. Up to half of people who have it, mostly men, die within five years of diagnosis, according to the study.

High-dose steroids, JANUS kinase inhibitors and bone marrow transplantation may help control symptoms.

The findings were published online Jan. 24 in Journal of the American Medical Association. Funding for the study was provided by the U.S. National Institutes of Health.

What This Means for You

You may be able to control VEXAS symptoms with medications or bone marrow transplantation.

More information

The U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases has more on VEXAS syndrome.

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