David Adams spent half a decade battling an illness he couldn’t name. He came and went to the hospital several times a year. His inflamed joints felt like he had been squeezed into gloves – 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 early 2016, I started with 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 he might have cancer.
Adams’ symptoms continued, with even more fatigue, pneumonia and a large rash below the waist. He tried at least a dozen drugs, saw about two dozen doctors, and nothing helped.
In 2019, worsening symptoms forced him to retire early 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 from the National Institutes of Health discovered and named a rare genetic condition: 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 giddy like a little kid.”
In the hands of his doctor was a copy of an article from 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.”
According to a new study, approximately 1 in 13,500 people in the United States may have VEXAS syndrome, which means that the mysterious and sometimes the life-threatening inflammatory disorder may be more common than previously thought.
By comparison, the genetic condition of 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, occasional cases of VEXAS have 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 United States have mutations in the UBA1 gene, which develop later in life and cause VEXAS syndrome.
“This study demonstrates that there are probably tens of thousands of patients in the United States who have this disease, and the vast majority of them are probably unrecognized because doctors don’t really consider it a diagnosis. broader,” said Dr. David Beck, assistant professor in the Department of Medicine at NYU Langone Health and 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 on the X chromosome, so the syndrome is an X-linked disease. It mainly affects men, 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 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 people who have the symptoms,” said Beck, who also led the federal research team that identified the 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 provide the diagnosis,” he said. “It’s just a matter of patients meeting the criteria – who are elderly people with systemic inflammation, low blood counts, who really don’t respond to anything but steroids – then advocating for their doctors to take genetic tests to get a diagnosis.”
Adams, who became a patient of Beck, said finally getting a diagnosis — and understanding the cause of his symptoms — was life-changing.
“It was really incredibly freeing 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, ‘OK, we understand what’s going on. This is VEXAS.’ ”
For the new study, Beck and his colleagues from NIH, New York University, Geisinger Research and other institutions analyzed data from 163,096 patients in a central and northeastern British health system. Pennsylvania, from January 1996 to January 2022, including electronic health records and blood. samples.
Eleven of the patients had a pathogenic UBA1 variant, and a 12th person had a “highly suspicious” variant.
Only three of the 12 are still alive. A five-year survival rate of 63% has already 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 rheumatological conditions, such as skin psoriasis or sarcoidosis, which causes swollen masses in the body. All had anemia or low blood cell counts.
“None had been previously clinically diagnosed with VEXAS syndrome,” Beck said.
The finding “highlights how important it is to be able to select these patients, give them the diagnosis, and start the aggressive therapies or aggressive treatments to control their inflammation,” he said.
VEXAS – an acronym for five clinical hallmarks of the disease – has no standardized treatment or cure, but Beck said symptoms can be managed with drugs like the steroid prednisone or other immunosuppressants.
“But the toxicities of prednisone over the years are difficult. 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 that is very effective is bone marrow transplantation. This carries its own risks, but it 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 needs to be done on a group of larger and more diverse people.
Some men might be hesitant to see a doctor for symptoms of VEXAS, but Adams said it could save their lives.
“Eventually it’s going to get so bad that you’ll end up like my first hospitalization, where you’re on the verge of death,” Adams said. “You don’t want to be in this situation.”
Adams took prednisone to relieve his symptoms, and it helped. But since steroid use can have side effects such as cataracts and weight gain, he worked with his doctors to find other therapies to reduce his drug use.
Beck and his colleagues are studying targeted therapies for VEXAS syndrome, as well as bone marrow stem cell transplant trials at the NIH.
“There are many different facets of the disease,” Dr. Bhavisha Patel, a hematologist and researcher in the Hematopoiesis and Bone Marrow Failure Laboratory at the National Heart, Lung and Blood Institute, said in an NIH press release this month. last..
“I think that’s what’s difficult when you think about treatment, because it’s so heterogeneous,” said Patel, who was not involved in the new study.
“At the NIH and around the world, groups that have dedicated themselves to VEXAS are researching medical therapies to offer 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 provide the best treatment options.”