January 25, 2023 – A recently discovered inflammatory disease called VEXAS syndrome is more widespread and dangerous than previously thought. A new genetic analysis suggestsAlthough the disease is rare, researchers estimate that it affects tens of hundreds of men within the United States and infrequently goes undiagnosed.
“Is VEXAS really more common than we think and are patients hiding in plain sight? The answer is yes,” says Mayo Clinic rheumatologist Matthew J. Koster, who has studied the disease but was not involved in the brand new research project. At his facility, he says, one patient with the disease is treated every week or two weeks.
Researchers first described VEXAS syndrome in 2020 and gave it its name, which stands for several of its features – vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic. The disease is linked to a gene mutation that appears to disrupt the best way the body identifies dysfunctional proteins in order that they will be eliminated.
“The disease is quite severe,” says lead study writer David Beck, MD, PhD, assistant professor within the department of drugs at NYU Langone Health.
Patients with this condition “present with a range of clinical symptoms affecting different parts of the body and are treated by different medical specialties.”
Symptoms can include anemia – a low level of red blood cells within the body – and inflammation affecting the skin, lungs, bones, cartilage and joints. “These symptoms are often confused with other rheumatic or hematological diseases.” [blood] diseases,” says Beck. “However, this syndrome has a unique cause, is treated otherwise, requires additional monitoring and will be much more serious.”
According to Beck, who helped discover the disease, hundreds of people have been diagnosed with VEXAS syndrome in the short time since it was defined. In some cases, the disease is said to be fatal.
For the new study, researchers looked for relevant variants in genetic data from 163,096 people (average age 52.8 years; 94% white, 61% women) who were patients at ten hospitals in Pennsylvania from 1996 to 2022.
Eleven people (nine men, two women) had the probable variants and all suffered from anemia.
Just over half of the patients – 55% – had a clinical diagnosis previously associated with VEXAS syndrome. “This implies that barely lower than half of the patients didn't have a transparent associated clinical diagnosis,” says Beck. “VEXAS syndrome is an example of a multisystem disease where patients and their symptoms can wander away in the gang.”
Going forward, doctors should look for patients who have unexplained inflammation and various symptoms that cannot be diagnosed or do not respond to initial treatments. “These patients often suffer from anemia, have low platelet counts and elevated inflammatory markers within the blood, and are depending on corticosteroids,” which weaken the immune system, he says.
According to Koster, the disease is so widespread that “doctors should consider that some patients whose disease doesn't reply to treatment may very well have VEXAS.”
VEXAS will be diagnosed through genetic testing.
As for treatment, Beck says the disease will be partially controlled by drugs designed to tame the immune system. Additionally, he says, bone marrow transplants have shown signs of effectiveness.