Ruxolitinib as a therapeutic option in VEXAS syndrome: a case report

VEXAS syndrome was first described in 2020 and is a novel adult-onset autoinflammatory disease caused by a somatic mutation in the UBA1 gene located on the X chromosome. The UBA1 gene is pathogenic due to a substitution of methionine （p.Met41）, the 41st amino acid specified in the gene. VEXAS syndrome has diverse clinical manifestations and findings, including myeloid and erythrocyte precursor cell vacuoles, macrocytic anemia, neutrophilic inflammation of the skin, pulmonary infiltrates, polychondritis of the ears and nose, deep vein thrombosis, and systemic vasculitis. The effective treatment options for VEXAS syndrome are unclear, except for high-dose corticosteroids. Another recognized therapeutic option for VEXAS syndrome is ruxolitinib, a Janus kinase inhibitor. We used ruxolitinib in an about 50-year-old Japanese man diagnosed with VEXAS syndrome based on the identification of a UBA1 mutation and typical clinical presentation. We compared the clinical data with and without the use of ruxolitinib. Ruxolitinib administration （5mg/day） resulted in a decrease in the maximum daily body temperature from 38.9℃ to 38.6℃ and improvements in inflammatory indicators （C-reactive protein; from 1.29 mg/dL to 0.375 mg/dL）; however, the patient's transfusion dependence progressed due to hemopoietic dysfunction. The patient did not achieve afebrility and complete resolution of symptoms when taking ruxolitinib. The amount of prednisolone was increased while he was receiving ruxolitinib compared with when he was not taking ruxolitinib （prednisolone; 17.5mg/day, 10mg/day, respectively）. In conclusion, although ruxolitinib is a potential treatment option for VEXAS syndrome, the present case report is insufficient to confirm its therapeutic efficacy.