Drug-Free Remission of VEXAS Syndrome Without Stem Cell Transplantation

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently discovered acquired autoinflammatory disease caused by a point mutation in the UBA1 gene of myeloid progenitor cells. We present a case of an 81-year-old male with VEXAS syndrome. His manifestations included severe cutaneous symptoms, cytopenias, and other organ inflammation, which initially posed a significant diagnostic challenge, given that VEXAS syndrome had only recently been discovered at that time. Multiple therapies were trialed, including courses of antibiotics and immunomodulatory agents. The diagnosis was ultimately confirmed by bone marrow biopsy and genetic testing, with a positive UBA1 mutation with an allele frequency of 10% in the myeloid progenitor cell line. Symptom control was ultimately achieved with methotrexate and chronic prednisone at low-to-moderate doses. Unfortunately, he developed methotrexate-induced bone marrow toxicity, identified during a hospitalization for community-acquired pneumonia; thus, the methotrexate was discontinued. Shortly thereafter, he achieved not only resolution of his autoinflammatory symptoms and hematologic abnormalities, but also clearance of the UBA1 gene mutation. He has since tapered off prednisone entirely and remains in drug-free biochemical and symptomatic remission. This case raises questions about the possible role of higher-intensity initial treatment in the management of VEXAS syndrome to target the bone marrow. Such therapies could include agents that induce temporary myelosuppression with the goal of subsequent treatment-free remission. Furthermore, we hypothesize that his relatively low UBA1 allele frequency may serve as a diagnostic marker for an increased likelihood of remission.