Abstract：VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently identified, acquired autoinflammatory disorder driven by somatic mutations in the UBA1 gene. It manifests with severe systemic inflammation and heterogeneous hematologic abnormalities, leading to substantial delays and difficulties in diagnosis. As one of rarely autoinflammatory disease, to date, standardized therapeutic strategy of VEXAS syndrome is not established. We herein described an elderly man presenting with recurrent unexplained fever, auricular chondritis, progressive macrocytic anemia and left calf intramuscular venous thrombosis. Laboratory tests demonstrated that mutiple inflammatory biomarkers including C-reactive protein (CRP), interleukin-6 (IL-6), ferritin, erythrocyte sedimentation rate (ESR), and lactate dehydrogenase (LDH) were elevated obviously. Bone marrow aspirate showed characteristic vacuolization of myeloid precursor cells. After comprehensive multidisciplinary evaluation, infectious diseases, malignancies, and other autoimmune or autoinflammatory disorders were comprehensively excluded. This patient was considered the diagnosis of VEXAS syndrome. Targeted genetic sequencing confirmed a pathogenic somatic UBA1 mutation (c.122T>C, p.Met41Thr). This patient was established the definitive diagnosis of VEXAS syndrome. Considering a high index of clinical suspicion and strikingly elevated serum IL-6 levels, combination of methepredisone(MP 40mg daily), methotrexate (MTX 10mg weekly) and tocilizumab (TCZ 400mg per four weeks) was initiated prior to the availability of genetic results. This approach contributed to rapid and sustained control of systemic inflammation. After treatment, the patient’s fever resolved promptly, anemia improved dramatically, and hemoglobin levels recovered progressively. At the 3-month follow-up, methepredisone was successfully tapered to 10 mg daily. This case emphasizes the critical importance of early recognition of the classical clinical and laboratory features of VEXAS syndrome and highlights the value of multidisciplinary collaboration in its diagnostic workup. Our experience supports that combination of methepredisone and tocilizumab applied for the autoinflammation manifestion could be safe and effective before genetic confirmation, which may provide an early clinical strategy for management of patients with suspected VEXAS syndrome.

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