VEXAS syndrome is more common than previously estimated and a specific type of rheumatic condition

VEXAS syndrome represents hemocyte, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, and somatic vacuoles, with rheumatic and hematologic features caused by somatic and pathogenic variants in UBA1. indicate. clinical symptoms. According to a study published in Journal of American Medical Association (JAMA),¹ The condition is much more common than previously estimated, affecting approximately 13,200 men and 2,300 women over the age of 50 in the United States. This prevalence is higher than other rheumatic diseases such as myelodysplastic syndrome and vasculitis.

“Since VEXAS syndrome has been found to be more common than many other types of rheumatic disease, physicians should consider this when faced with patients with persistent, unexplained inflammation and low blood cell counts, or anemia. We need to add the disease to the list of potential diagnoses,” said geneticist and principal investigator David Beck, M.D., Ph.D. Beck, an assistant professor of medicine and biochemistry and molecular pharmacology at NYU Langone Health, led the research team that originally identified his UBA1 mutation in his VEXAS patients.

Symptoms of autoimmune conditions include fever of unknown origin and low blood oxygen levels in patients with other diseases such as rheumatoid arthritis (RA), blood cancers and lupus. Although the syndrome is rare, it has a high mortality rate, with about half of patients dying within five years of diagnosis.

A retrospective observational study used genomic confirmation methods to identify UBA1 variants in exome data obtained from 163,096 patients (mean age 52.8 years, 61% female, 94% Caucasian) within a single US community health system. were analyzed to assess the prevalence of pathogenicity. Variants and clinical manifestations. The clinical phenotype was determined based on his Geisinger Electronic Health Record (EHR) data from January 1996 to his January 2022. Outcome measures included the presence of rheumatic, pulmonary, cutaneous, and hematologic manifestations in patients with somatic UBA1 variants using bone marrow biopsy pathology analysis. In vitro enzyme assays, laboratory data, and EHR data.

In total, 11 patients had somatic mutations at known pathogenic UBA1 loci, all of whom reported clinical manifestations consistent with VEXAS syndrome. The syndrome affected men significantly more than women (9 vs. 2, respectively). Seven (64%) patients had arthritis and 36% (n = 4) had rheumatic diseases such as dermatomyositis, sarcoidosis, psoriasis and polymyalgia rheumatoid arthritis. Although 45% (n = 5/11) had no rheumatoid and/or hematological diagnosis previously associated with VEXAS syndrome, all patients had predominantly macrocytic (91%, n = 10/11) with concomitant thrombocytopenia (91%, n = 10/11).

One male patient had a pathogenic variant prior to onset of VEXAS symptoms, and two female patients had disease with a heterozygous variant. In addition, her previously unreported UBA1 variant was found in one of her symptomatic patients. Ultimately, his disease-causing UBA1 variant was associated with 1 in 13,591 unrelated participants, 1 in 4,269 male participants aged 50 and older, and his in 26,238 female participants aged 50 and older. Discovered in

As data were obtained from single-center regional cohorts of predominantly European descent, results may not be generalizable to other geographic locations and ethnicities. Additionally, researchers could not account for missing data for treatments, tests, or findings from external clinicians that were not captured in the Geisinger EHR.

Future studies in unselected, genetically diverse patients will help to better define the disease prevalence and phenotypic spectrum in the general population. Researchers raise awareness of her VEXAS syndrome among clinicians as Janus kinase (JAK) inhibitors, bone marrow transplantation, and high-dose steroids have been shown to effectively control certain symptoms was intended to

“Our study provides the first glimpse of how common VEXAS syndrome is in the United States, especially among men who happen to have the highest mortality rate from it,” Beck concluded.

reference:

Beck DB, Bodian DL, Shah V, Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndromes in other clinical populations. jam. 2023;329(4):318-324. doi:10.1001/jama.2022.24836