January 30, 2023

Recently identified inflammatory disease VEXAS syndrome may be more common than thought, study suggests

6 min read


David Adams spent half a decade battling an illness he couldn’t name. He was in and out of the hospital several times a year. His swollen joints made his hands feel as if they were squeezed into gloves – and he could no longer play his beloved classical and jazz guitars.

He had constant fever and fatigue. He even developed pain and swelling in his penis, the first sign that something was really wrong.

Adams, now 70, said, “At the end of 2016, I started with some really painful effects in male anatomy.” Then, again, a lot of fatigue – blood tests were done by my primary care physician at the time. , and my white blood cell count was very, very low.”

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

Adams’ symptoms continued, with more fatigue, pneumonia and a large bruise below her back. He tried at least a dozen medications, saw about two dozen doctors, and nothing seemed to help.

In 2019, worsening symptoms forced him to retire early from his decades-long career in clinical data systems. But he remained in the dark as to what caused the troubles.

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

Adams had an appointment with her rheumatologist at the time, and when she went into the office, she noticed that her therapist was “dizzying like a little baby.”

His doctor had a paper copy in his hand. New England Journal of Medicine Description of the discovery of VEXAS syndrome.

Adams had the answer.

“For the first time, the symptoms had a one-to-one relationship,” he said. “It was quite a shock.”

An estimated 1 in 13,500 people in the U.S. may have VEXAS syndrome, a new study suggests, which means the mysterious and sometimes Malignant inflammatory disorders may be more common than previously thought.

In contrast, genetic disorders Spinal muscular atrophy Affects 1 in 10,000 people. Huntington’s disease Occurs in about 1 in every 10,000 to 20,000 people.

Since its discovery, occasional cases of VEXAS have been reported in clinical research, but studies show new estimates of its prevalence.

The research was published in the journal Tuesday. Jamasuggests that 1 in 13,591 people in the United States carry the mutation. The UBA1 genewhich develop later in life and cause VEXAS syndrome.

Dr. David Beck, assistant professor at NYU Langone Health, studies UBA1 gene mutations in VEXAS patients.

“This study is showing that there are potentially tens of thousands of patients in the United States who have this disease, and the majority of them are probably going undiagnosed because physicians are actually misdiagnosing it as a more widespread diagnosis. Not understanding,” he said. Dr. David Beckassistant professor in the Department of Medicine at NYU Langone Health and a lead author of the study.

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

“It’s present in 1 in 4,000 men over the age of 50. So we think it’s a disease that should be thought about in terms of testing people who have symptoms,” Beck said. who also led the federal research team that identified the disease. 2020 shared UBA1 mutations among VEXAS patients.

“The advantage of VEXAS syndrome is that we have a test. We have a genetic test that can help provide a direct diagnosis,” he said. “It’s just a question of patients who meet the criteria — who are older people with systemic inflammation, low blood counts, who aren’t really responding to anything other than steroids — then getting evaluated by their doctors. Advocating genetic testing for

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

“It was really incredibly freeing to evaluate,” he said.

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

For the new study, Beck and colleagues at the NIH, New York University, Geisinger Research and other institutions analyzed data from 163,096 patients at health systems in central and northeastern Pennsylvania from January 1996 to January 2022, using electronic health systems. Includes records and blood. Samples

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

Only three of the 12 are still alive. The five-year survival rate is 63%. has been previously reported. With VEXAS.

Of 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 were diagnosed with rheumatologic diseases, such as psoriasis or sarcoidosis, which cause inflammatory nodules in the body. All had anemia or low blood cell counts.

“Nobody had ever been clinically diagnosed with VEXAS syndrome before,” Beck said.

The finding “emphasizes how important it is to be able to screen out these patients, diagnose them and start aggressive treatment or aggressive treatment to get their inflammation under control,” he said.

VEXAS — an acronym for Five Clinical Features of the Disease — has no standard treatment or cure, but Beck said the symptoms can be treated with drugs like the steroid prednisone or other immunosuppressants.

“But the toxicity of prednisone over the years is challenging. There are other anti-inflammatory drugs that we use, but they are only partially effective at this time,” he said. “One treatment for these individuals that we’ve seen to be very effective is bone marrow transplantation. That comes with its own risks, but that’s only indicative of the severe nature of the disease.

While the new study helps provide an estimate 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 on a larger, 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’s going to get bad enough that you end up like my first hospitalization, where you’re at death’s door,” Adams said. “You don’t want to be in that situation.”

Adams has been taking prednisone to ease her symptoms, and it has helped. But because steroid use can cause side effects such as cataracts and weight gain, they are working with their doctors to find other treatments so they can reduce their use of the medication.

Beck and his colleagues are studying. Targeted therapies VEXAS syndrome, as well as for holding Stem cell bone marrow transplant trials At the NIH

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

“I believe that’s what’s difficult when we think about treatment, because it’s so heterogeneous,” said Patel, who was not involved in the new research.

“At NIH and around the world, groups that have dedicated themselves to VEXAS are looking for medical treatments to offer to other patients who are not eligible for bone marrow transplants,” he said. They said. “We continue to collaborate on many projects to further classify this disease and ultimately come up with better treatment options.”

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