‘VEXAS is a recently characterized disease with a lot of unknowns,’ said Physician Editor Bharat Kumar when highlighting this article; ‘fortunately, the ACR has published a guidance statement to help with its diagnosis and management. Be sure to read this article to learn what to watch for and how to treat this rare condition with a genetic component.’
A new guidance document from the ACR provides physicians with key expertise for the diagnosis and management of the rare condition VEXAS (vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome), a multisystem disorder with important rheumatologic impacts.1
VEXAS Background
Scientists first described VEXAS in late 2020.2 Affected individuals acquire pathogenic somatic mutations in the UBA1 gene, which makes the major E1 enzyme responsible for ubiquitylation, an important post-translational modification of peptides. The adult-onset condition is often refractory to treatment and sometimes fatal, occurring with a variety of hematologic and inflammatory features.
David B. Beck, MD, PhD, an assistant professor of medicine and head of the Inflammatory Disease Genetics Clinic at New York University Grossman School of Medicine, New York City, is one of the co-last authors of the recent guidance statement. “We don’t yet have clear studies that have defined the best ways to identify and treat patients,” he says, “but we wanted to set the groundwork for the studies that will come next.”
Dr. Matthew Koster
One of the guidance statement’s co-first authors is Matthew J. Koster, MD, a rheumatologist and associate professor of medicine at the Mayo Clinic, Rochester, Minn. He points out that not all patients have access to centers with VEXAS expertise, at least not for all their care. “It’s important for people providing local assistance in managing these patients to have guidance from experts who have seen it more frequently.”
A multidisciplinary and international panel of experts in VEXAS contributed to the project, including rheumatologists, hematologists, dermatologists, immunologists, infectious disease specialists and others. Relying on a literature review and expert opinion, they created the conditionally recommended guidance statements across four different areas: 1) clinical and laboratory features, 2) mutation screening methods, 3) diagnosis of myelodysplastic syndromes (MDS; present in one-third to one-half of VEXAS patients), and 4) prognosis and management.
Clinical & Laboratory Features
From an epidemiological perspective, clinicians should be most suspicious of VEXAS in men over the age of 50. (The very strong predominance in men is thought to be due to the UBA1 gene’s location on the X chromosome). The condition is genetic, but not thought to be heritable, as it derives from an acquired and not an inherited mutation. A clonal group of cells with mutations in UBA1 come to populate cells with a myeloid lineage, leading to disease symptoms.
