David Adams battled a disease he couldn’t name for half a decade. He was in and out of the hospital several times a year. His inflamed joints made his hands feel as if they had been 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 genitals, which was his first sign that something was really wrong.
“At the beginning of 2016, I started having some really painful effects in the male anatomy,” says Adams, now 70. “After that, again, a lot of fatigue — my GP was having blood tests done at the time, 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 he might have cancer.
Adams’ symptoms continued, with even more fatigue, pneumonia, and a large rash below his waist. He tried at least a dozen medicines, visited about two dozen doctors, and nothing helped.
In 2019, worsening symptoms forced him to take early retirement after his decades-long career in clinical data systems. But he remained in the dark about what was causing the trouble.
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 with 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 “dizzy 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, meaning the mysterious and sometimes deadly inflammatory condition 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.
Since its discovery, VEXAS cases have occasionally been reported in medical research, but the study reveals new estimates of its prevalence.
The research, published Tuesday in the journal 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 probably go unrecognized because doctors don’t really consider this a broader diagnosis,” said Dr. David Beck, an assistant professor in the Department of Medicine at NYU Langone Health and a lead author of the study.
VEXAS syndrome is not hereditary, so people who have it do not pass the disease on to their children. But the UBA1 gene is located on the X chromosome, so the syndrome is an X-linked disease. It mainly affects males, who carry only one X chromosome. Women have two X chromosomes, so if they have a mutation in a gene on one X chromosome but not the other, they are generally unaffected.
“It’s present in 1 in 4,000 men over the age of 50. So we think it’s a disease that needs to be thought about in terms of testing for individuals who have the symptoms,” said Beck, who also led the federal research team that researched the disease. identified. shared UBA1 mutation among VEXAS patients in 2020.
“The advantage of VEXAS syndrome is that we have a test. We have a genetic test that can directly help make the diagnosis,” he said. “It’s just a matter of patients meeting the criteria — that’s older individuals with systemic inflammation, low blood counts, who really don’t respond to anything other than steroids — and then pleading with their doctors for genetic testing to make a diagnosis. to get.”
Adams, who became a patient of Beck’s, said getting a diagnosis — and understanding the cause of his symptoms — was life-changing.
“It was really incredibly liberating to get 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 his colleagues from the NIH, New York University, Geisinger Research and other institutions analyzed data on 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 suspected” variant.
Only three of the 12 are still alive. A five-year survival rate of 63% has previously been 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 had been diagnosed with rheumatologic conditions, such as psoriasis of the skin or sarcoidosis, which causes swollen nodules in the body. They all had anemia or low blood cell counts.
“No one had been clinically diagnosed with VEXAS syndrome before,” Beck said.
The finding “emphasizes the importance of being able to single out these patients, diagnose them and start the aggressive therapies or treatments to control their inflammation,” he said.
VEXAS — an acronym for five clinical features of the disease — has no standardized treatment or cure, but Beck said the symptoms can be treated with medications such as the steroid prednisone or other immunosuppressants.
“But the toxicity of prednisone over the years is a challenge. There are other anti-inflammatory drugs that we use, but they are only partially effective at this point,” he said. “A 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.”
While the new study provides estimates of the prevalence and symptoms of VEXAS syndrome, the data isn’t representative of the entire United States, and Beck said more research needs to be done on a larger, more diverse group of people.
Some men may be hesitant to seek medical care for VEXAS symptoms, but Adams said it could save their lives.
“Eventually it’s going to get so bad that you end up as my first hospitalization, where you’re on the verge of death,” Adams said. “You don’t want to be in that situation.”
Adams has taken prednisone to relieve his symptoms, and it has helped. But because steroid use can have side effects, such as cataracts and weight gain, he’s been working with his doctors to find other therapies so he can reduce his intake of the medication.
Beck and colleagues are studying targeted therapies for VEXAS syndrome and are conducting stem cell bone marrow transplant trials at the NIH.
“There are many different facets of the disease,” said Dr. Bhavisha Patel, a hematologist and researcher in the National Heart, Lung and Blood Institute’s Hematopoiesis and Bone Marrow Failure Laboratory, said in a press release from the NIH last month..
“I believe that’s the challenge when we think about treatment, because it’s so heterogeneous,” says Patel, who was not involved in the new study.
“Both at NIH and globally, the groups committed to VEXAS are looking for medical therapies they can offer to other patients who are not eligible for bone marrow transplantation,” she said. “We continue to collaborate on many projects to further categorize this disease and ultimately come up with the best treatment options.”