A Case of Glucocorticoid-Resistant VEXAS Syndrome Successfully Treated with Baricitinib

Abstract

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, can mimic adult-onset Still’s disease (AOSD) and is often refractory to glucocorticoids. We report a case of VEXAS syndrome in a man in his seventies who had initially been treated as AOSD with interstitial lung disease and large-vessel vasculitis, and who relapsed with high fever, vesiculopustular eruptions, polyarthritis, auricular chondritis, and macrocytic anemia during prednisolone (PSL) tapering. Given the lack of response to PSL escalation and the possibility of VEXAS syndrome, baricitinib, a JAK1/2 inhibitor, was initiated, resulting in rapid clinical and hematologic improvement. Genetic testing identified UBA1 (c.122T>C, p.Met41Thr; variant allele frequency [VAF] 76%), confirming VEXAS syndrome. PSL was tapered to 10 mg/day, and complete remission according to FRENVEX criteria was achieved within 3 months after baricitinib initiation, with no recurrence at 6 months. This case underscores the importance of early UBA1 testing in elderly men with AOSD-like presentations and suggests that baricitinib may serve as a glucocorticoid-sparing therapeutic option in selected cases, although its efficacy should be interpreted cautiously in light of genotype-dependent heterogeneity and the combined effects of JAK1/2 inhibition.