‘Aggressively’ controlling inflammation, symptoms critical in managing VEXAS syndrome
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Staying ahead of inflammation and managing the broad range of symptoms is key to controlling VEXAS syndrome, according to data presented at ACR Convergence 2021.
Lorena Wilson, PhD, NP, of the inflammatory disease section at the National Human Genome Research Institute at the NIH, outlined the acronym that gave VEXAS syndrome its name.
The V stands for vacuolated myeloid and erythroid precursors; the E is for the E1 enzyme— mutations in the UBA1 gene lead to lack of the cytoplasmic E1 enzyme. The X denotes that the UBA1 gene is on the X chromosome, while the A indicates an autoinflammatory reaction marked by severe inflammation that is steroid dependent. The S is for somatic mutations in UBA1 restricted to myeloid origin cells.
Wilson reviewed a case that exemplified some of the clinical characteristics that mark VEXAS syndrome. These include multisystemic manifestations such as fever, periorbital edema, ear or nose inflammation, chondritis, or inflammatory eye disease. Cardiopulmonary complications include effusions, thrombotic events or myocarditis. Hepatosplenomegaly may occur, along with migrating arthralgias or arthritis. Skin involvement can include different kinds of lesions, while neutrophilic dermatosis or vasculitis may also be present. “Males complain of testicle pain,” Wilson said.
“Some patients present gradually,” Wilson added. “In others, a main event can occur and trigger the onset of VEXAS.”
Clinicians should be aware that any or all these symptoms may progress, depending on the patient. “They may progress to myelodysplastic syndromes or multiple myelomas,” Wilson said.
Regarding treatment, Wilson stressed that patients can be “fully responsive” to steroids. While she also suggested increasing dosage as the disease progresses, she warned of the potential complications associated with long-term steroid use.
In terms of therapies that induce a partial response, tofacitinib (Xeljanz, Pfizer) has been used as a steroid-sparing agent. The janus kinase (JAK) inhibitor ruxolitinib (Opzelura, Incyte) also has shown efficacy in this regard.
Hypomethylating agents may also be used if there is bone marrow involvement, according to Wilson. To that point, bone marrow transplant can also “effectively cure” VEXAS syndrome, but the risk/benefit profile of this intervention should be carefully considered.
Interleukin-1 inhibitors should be avoided due to severe injection site skin reactions.
Wilson also offered some pearls for rheumatologists to carry back to the clinic. “The main takeaway here is that if you have a patient come to you with chronic inflammation and one or a combination of any of the clinical features [reported above], they should definitely be considered for VEXAS genetic testing,” she said.
If there is another important consideration, it is to monitor patients for flares in their symptomatology, according to Wilson. She suggested that erythrocyte sedimentation rate (ESR) and C-reactive protein should be on the radar of a rheumatologist treating a patient with suspected VEXAS syndrome. “You also want to monitor for thrombotic events,” she said. “You want to control inflammation aggressively with the use of glucocorticoids, but, at the same time, you want to monitor for steroid toxicity.”
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Wilson L. Abstract 6S410. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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