Patient with VEXAS syndrome misdiagnosed, research reveals 13,200 men, 2,300 women affected, genetic sequencing key to diagnosis, treatments being studied.
Hector Campos, a patient in the NBC medical drama Chicago Med, presented with shortness of breath, erratic fever, and swollen, itchy ears. His wife reported that he had tested negative for COVID-19. After initially misdiagnosing his symptoms as pneumonia and a bacterial infection, a test revealed widespread inflammation, and fellow ER surgeon Dean Archer suggested it might be VEXAS, a rare autoinflammatory syndrome. In 2020, clinical genetics researcher David Beck and his colleagues identified VEXAS in a study published in the New England Journal of Medicine.
Beck was impressed with the accuracy of the depiction of VEXAS in popular media, as the clinical manifestations were spot on. The initial paper focused on severe cases, but a study published in JAMA in 2021 found that VEXAS affects 13,200 men and 2,300 women over age 50 in the U.S. alone. The syndrome is caused by a somatic mutation on the X chromosome, which only men have, making them more prone to the disease.
The study found that the 11 participants with VEXAS mutations were all anemic and had abnormally large red blood cells and a low platelet count, but some of the more severe symptoms associated with VEXAS were not present. This suggests that there may be a broader spectrum of severity when it comes to cases of VEXAS syndrome. The researchers also found that the two women retrospectively identified as having VEXAS syndrome only suffered from the VEXAS-related mutation on one of their X chromosomes, not both. This is due to X-inactivation, a process in which one of a female’s two X chromosomes is silenced throughout their cells.
Currently, there are no treatments for VEXAS approved by the FDA, but a phase II clinical trial is underway to study whether blood stem cell transplants can treat or cure the syndrome. Scientists are still trying to figure out how a mutation in the gene that encodes E1 leads to the widespread inflammation seen in cases of VEXAS. If an individual is an older individual with systemic inflammation, low blood counts, and no clear diagnosis, they should contact their doctor about genetic testing for VEXAS syndrome, as it may help lead to better treatments.