Dubai, United Arab Emirates (CNN) — David Adams has been fighting an unknown disease for 5 years. He was in and out of the hospital several times a year. As a result of his arthritis, his hands felt as if they were being squeezed into gloves, and he could no longer play the classical and electric guitars he loved.
He was constantly suffering from heat and fatigue. He even developed pain and swelling in his genitals, which was the first sign that something was wrong.
“In early 2016, the disease started to have some really painful effects on the male anatomy,” said Adams, now 70. He continued, “After that, he felt very tired again, and at that point his primary care doctor asked him to take a blood test, and it was found that my white blood cell count was very low.”
Next, Adams, who lives in Alexandria, Virginia, visited a hematologist, a pulmonologist, a urologist, a rheumatologist, and then a dermatologist. Some of them thought he might have cancer.
Adams’ symptoms continued, with him feeling increasingly tired, suffering from pneumonia, and a severe rash below his waist. He tried no less than 12 medications, and visited about 20 doctors, without results.
In 2019, his symptoms worsened, prompting him to retire early from his decades-long career in clinical data systems. But he remained ignorant of the cause of his problems.
Finally, in 2020, scientists at the National Institutes of Health discovered a rare genetic disorder, which they called VEXAS syndrome, that wreaks havoc on the body through inflammation and problems in the blood.
Adams had an appointment with his rheumatologist at the time, and when he entered his office, he saw that his doctor “was as cheerful as a little child”.
He was holding a copy of a study published in the New England Journal of Medicine detailing the discovery of VEXAS syndrome.
Accordingly, Adams got the expected answer, and said: “For the first time, there was a direct correlation with the symptoms. It was a huge shock to me.”
The vast majority are misdiagnosed
A new study suggests that 1 in about 13,500 people in the United States may develop Vicksas syndrome, which means that the mysterious, and sometimes fatal, inflammatory disorder may be more common than previously thought.
While the genetic disorder, spinal muscular atrophy, affects about 1 in 10,000 people, Huntington’s disease affects about 1 in 10,000 to 20,000 people.
Since the discovery of Vexas syndrome, occasional cases have been reported in medical research, but the study has revealed new estimates of its prevalence.
About 1 in 13,591 people in the United States have mutations in the UBA1 gene, which develops later in life and causes Vexas syndrome, the research, published in the journal JAMA, reported on Tuesday.
About this discovery, Dr. David Beck, assistant professor in the Department of Medicine at NYU Langone Health and the lead author of the scientific research, said, “This study shows that there may be tens of thousands of patients in the United States with this disease, and most of them have not been identified because they have this syndrome because Doctors don’t consider it a common diagnosis.”
Vexas syndrome is not hereditary, 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 mostly affects men because they only carry one X chromosome, while women have two X chromosomes, so if they have a mutation in a gene on one X chromosome but not the other, they generally won’t be affected.
“We find it in 1 in 4,000 men over the age of 50. So we think it’s a disease that should be thought of in terms of screening individuals with symptoms,” said Beck, who also led the federal research team that identified the UBA1 mutation among patients with Vexas syndrome in 2020. .
“The benefit of Vexas syndrome is that we have a test. We have a genetic test that can directly help with the diagnosis,” he said. “It’s a matter of patients who meet the criteria, who are older, who have systemic inflammation, who have low blood counts, who don’t really respond to anything but steroids, and whose doctors ask them to do genetic testing to get a diagnosis,” he added.
Adams, who became Beck’s patient, said that finally getting the diagnosis, and understanding the cause of his symptoms, had changed his life.
The severe nature of the disease
For the new study, Beck and colleagues at the National Institutes of Health, New York University, Geisinger Research, and other institutions analyzed data on 166,096 patients enrolled in a central and northeastern Pennsylvania health system between January 1996 and January 2022, including electronic health records and blood samples. .
They discovered that 11 patients had the disease-causing UBA1 mutation, and 12 had “very suspicious” mutations.
Only three of the 12 are still alive. The five-year survival rate after Vexas syndrome was previously reported to be 63%.
Of the 11 patients in the new study who had disease-causing mutations in UBA1, only two were women. Seven had arthritis as a symptom, and four were diagnosed with rheumatic diseases, such as psoriasis of the skin or sarcoidosis, which causes swelling in the body. All had anemia, or low blood cell counts.
“None of them had ever been clinically diagnosed with Vexas syndrome,” Beck noted.
He added that the findings “underscore the importance of being able to select these patients, give them a diagnosis and initiate aggressive therapies to control their inflammation.”
VEXAS, an acronym for Five Clinical Characteristics of the Disease, has no cure or standardized treatment, but Beck argues that symptoms can be controlled through the use of medications such as the steroid prednisone or other immunosuppressants.
“The level of toxicity of prednisone over the years has been a challenge. There are other anti-inflammatory drugs that we use, but they are only partially effective at the moment,” he noted. He added, “One of the treatments that we have seen very effective in individuals is bone marrow transplantation. This comes with its own risks, but this only underscores the severe 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 in a larger and more diverse group of people.
Some men may be reluctant to seek medical attention for Vicksas symptoms, but Adams said doing so could save their lives.
Adams takes prednisone to relieve his symptoms, and it helps. But because steroid use can have side effects such as cataracts and weight gain, he has been working with his doctors on finding other treatments so he can reduce his medication intake.
“Many different aspects”
Beck and his colleagues are studying targeted therapies for Vexas syndrome, as well as conducting stem cell bone marrow transplant trials at the National Institutes of Health.
Dr. Bhavisha Patel, a hematologist and researcher at the National Heart, Lung, and Blood Institute’s Blood Formation and Bone Marrow Failure Laboratory, noted in an NIH press release last month that “there are many different aspects of the disease.”
Patel, who was not involved in the new study, thought, “This is the challenge we face when we think about treatment, because (the disease) is very heterogeneous.”
“Both at the National Institutes of Health and around the world, groups dedicated to VEXAS are looking for medical therapies to offer to other patients who are not eligible for a bone marrow transplant,” she said. “We continue to collaborate on many projects in order to further classify this disease and ultimately come up with the best treatment options,” she added.
