January 25, 2023 – A recently discovered inflammatory disease called VEXAS syndrome is more widespread and dangerous than previously understood, A new genetic analysis showsAlthough rare, researchers believe the disorder may affect tens of thousands of men in the U.S. and may often go undiagnosed.
“Is VEXAS really more common than we think? Patients hiding in plain sight? The answer is yes,” said Mayo Clinic rheumatologist Matthew J. Koster, MD, who has studied the disease but was not involved in the new study. Invention project. He said his institution sees a patient with the disease every week or two.
Researchers first described VEXAS syndrome in 2020 and named it for several of its features—vacuole, E1 ubiquitin-activating enzyme, X-linked, autoinflammation, somatocellular. The disease is linked to a genetic mutation that appears to disrupt the way the body recognizes a dysfunctional protein so it can be eliminated.
“This disease is very serious,” said the study’s lead author David Baker, MD, an assistant professor in the Department of Medicine at NYU Langone Health.
Patients with the disease “have a variety of clinical symptoms affecting different parts of the body and are treated by different medical specialists.”
Symptoms may include anemia — low levels of red blood cells in the body — and inflammation affecting the skin, lungs, bones, cartilage, and joints. “These symptoms are often mistaken for other rheumatic or blood disorders [blood] disease,” Baker said. “However, the syndrome has a different etiology, is treated differently, requires additional monitoring, and can be more severe. “
Hundreds of people have been diagnosed with VEXAS syndrome in the short time since it was defined, according to Baker, who helped discover the disease. In some cases, the disease is considered fatal.
In the new study, researchers looked for associated variants in the genetic data of 163,096 people (mean age, 52.8 years; 94% white; 61% female) who were enrolled at 10 Pennsylvania hospitals between 1996 and 2022. patients visiting the clinic.
Eleven individuals (9 males, 2 females) had the likely variant and all were anemic.
The clinical diagnosis was previously associated with VEXAS syndrome in more than half of the patients (55%). “This means that slightly less than half of the patients do not have a clear relevant clinical diagnosis,” Baker said. “VEXAS syndrome represents an example of a multisystem disorder in which patients and their symptoms can become lost in the chaos.”
Going forward, doctors should be on the lookout for patients with unexplained inflammation and a variety of symptoms that go undiagnosed or don’t respond to their first treatments, he said. “These patients are also often anemic, have low platelet counts, have elevated inflammatory markers in the blood, and are dependent on corticosteroids,” which suppress the immune system, he said.
The disease is so common that “clinicians should consider that some patients with disease that do not respond to treatment may actually have VEXAS,” Coster said.
The diagnosis of VEXAS can be made with genetic testing.
As for treatment, Baker said the disease can be partly controlled with drugs designed to tame the immune system. In addition, bone marrow transplants have shown signs of being effective, he said.