VEXAS syndrome, a newly identified inflammatory disease, may be more common than previously thought, study suggests | CNN



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David Adams spent half a decade fighting a disease he couldn’t name. He was in and out of the hospital several times a year. His swollen joints made his hands feel like gloves had been put on them, and he could no longer play his beloved classical and jazz guitars.

He had constant fevers and fatigue. He even developed pain and swelling in his genitals, which was his first sign that something was seriously wrong.

“In late 2016, I started having some really painful effects on the male anatomy,” said Adams, now 70. , and my white blood cell count was very, very low.”

Next, Adams, who lives in Alexandria, Virginia, saw a hematologist, a pulmonologist, a urologist, a rheumatologist, and then a dermatologist. Some of them thought that she might have cancer.

Adams’ symptoms continued, with more fatigue, pneumonia and a large rash below her waist. She tried at least a dozen medications, saw about two dozen doctors, and nothing helped.

In 2019, worsening symptoms forced him to take early retirement from his decades-long career in clinical data systems. But he remained in the dark about what was causing the problems.

Finally, in 2020, scientists at the National Institutes of Health discovered and named a rare genetic disorder: VEXAS syndrome, which wreaks havoc on the body through inflammation and blood problems.

Adams had an appointment with his rheumatologist at the time, and when he walked into the office, he saw that his doctor “was queasy like a little kid.”

In his doctor’s hands was a copy of an article in the New England Journal of Medicine detailing the discovery of VEXAS syndrome.

Adams had his answer.

“For the first time, there was a one-to-one correlation of symptoms,” he said. “It was quite a shock.”

An estimated 1 in 13,500 people in the United States may have VEXAS syndrome, a new study suggests, which means the mysterious and sometimes The deadly inflammatory disorder may be more common than previously thought.

By comparison, the genetic disorder spinal muscular atrophy affects about 1 in 10,000 people, and Huntington’s disease occurs in about 1 in 10,000 to 20,000 people.

Occasional cases of VEXAS have been reported in medical research since its discovery, but the study reveals new estimates of its prevalence.

The research, published Tuesday in JAMA, suggests that about 1 in 13,591 people in the US have mutations in the UBA1 gene, which develop later in life and cause VEXAS syndrome.

“This study shows that there are probably tens of thousands of patients in the US who have this disease, and the vast majority of them are probably not being recognized because doctors aren’t really looking at this as a broader diagnosis,” he said. Dr. David Beck, an assistant professor in the NYU Langone Health Department of Medicine and lead author of the study.

VEXAS syndrome is not inherited, so people with it do not pass the disease on to their children. But the UBA1 gene is on the X chromosome, so the syndrome is an X-linked disease. It predominantly affects males, who carry only one X chromosome. Females have two X chromosomes, so if they have a mutation in a gene on one X chromosome but not on the other, they are usually not affected.

“It’s present in 1 in 4,000 men over the age of 50. So we think it’s a disease to think about in terms of testing for individuals who have symptoms,” said Beck, who also led the federal investigative team. who identified the shared UBA1 mutation among VEXAS patients in 2020.

“The benefit of VEXAS syndrome is that we have a test. We have a genetic test that can directly help make the diagnosis,” she said. “It’s just a matter of patients who meet the criteria, who are older people with systemic inflammation, low blood counts, who really aren’t responding to anything other than steroids, and then advocate for their doctors to have genetic testing to get a diagnosis”.

Adams, who became Beck’s patient, said finally getting a diagnosis, and understanding the cause of his symptoms, was life-changing.

“It really was incredibly liberating to have the diagnosis,” he said.

“You can’t fight your enemy unless your enemy has a name,” he added. “We finally had something we could point to and say, ‘Okay, we understand what’s going on. This is VEXAS. “

For the new study, Beck and colleagues from the NIH, New York University, Geisinger Research and other institutions analyzed data from 163,096 patients in a health system in central and northeastern Pennsylvania from January 1996 to January 2022. , including electronic health records and blood tests. samples

Eleven of the patients had a disease-causing UBA1 variant and a 12th person had a “highly suspicious” variant.

Only three of the 12 are still alive. A 5-year survival rate of 63% was previously reported with VEXAS.

Among the 11 patients in the new study who had pathogenic variants in UBA1, only two were women. Seven had arthritis as a symptom and four had been diagnosed with rheumatic diseases, such as psoriasis of the skin or sarcoidosis, which causes inflamed lumps on the body. All had anemia or low blood cell counts.

“None had previously been clinically diagnosed with VEXAS syndrome,” Beck said.

The finding “is emphasizing the importance of being able to select these patients, give them the diagnosis and start aggressive therapies or aggressive treatments to keep their inflammation under control,” he said.

VEXAS, an acronym for five clinical features of the disease, has no standardized treatment or cure, but Beck said symptoms can be controlled with medications such as the steroid prednisone or other immunosuppressants.

“But the toxicities of prednisone over the years are challenging. There are other anti-inflammatory drugs that we use, but they are only partially effective at the moment,” he said. “One treatment for individuals that we have seen to be very effective is bone marrow transplantation. That carries its own risks, but that only underscores the serious nature of the disease.”

Although the new study helps provide estimates of the prevalence and symptoms of VEXAS syndrome, the data is not representative of the entire United States, and Beck said more research is needed in a larger and more diverse group of people.

Some men may be hesitant to seek medical attention for VEXAS symptoms, but Adams said doing so could save their lives.

“Eventually, it will get so bad that you’ll end up like my first hospitalization, where you’re near death,” Adams said. “You don’t want to be in that situation.”

Adams has been taking prednisone to relieve his symptoms and it has helped. But because steroid use can have side effects like cataracts and weight gain, she has been working with her doctors to find other therapies that allow her to reduce her medication use.

Beck and his colleagues are studying targeted therapies for VEXAS syndrome, as well as conducting bone marrow stem cell transplantation trials at the NIH.

“There are many different facets to the disease,” said Dr. Bhavisha Patel, a hematologist and investigator in the Bone Marrow and Hematopoiesis Failure Laboratory at the National Heart, Lung, and Blood Institute, in an NIH news release. last month..

“I think that’s what poses a challenge when we think about treatment, because it’s so heterogeneous,” said Patel, who was not involved in the new study.

“Both at NIH and around the world, groups that have engaged in VEXAS are seeking medical therapies to offer to other patients who do not qualify for bone marrow transplantation,” he said. “We continue to collaborate on many projects to further categorize this disease and ultimately find the best treatment options.”

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