Case Presentation: An 82-year-old male presented to the ED with fevers and shortness of breath. Two years prior, he was started on steroid therapy and intermittent tocilizumab for possible giant cell arteritis (GCA) given his complaints of jaw claudication, headache, elevated CRP and intermittent fevers; temporal artery biopsy was not conclusive for GCA. NM PET scan from that time was negative for evidence of large vessel vasculitis. On admission, the patient was febrile and hypoxic, with acute kidney injury, thrombocytopenia and anemia. He had a morbilliform rash to his chest, back and lower extremities. On day three he developed pancytopenia. The patient was admitted to the ICU for acute hypoxic respiratory failure and started empirically on IV antibiotics for possible pneumonia. The infectious workup was negative. CT scan of the chest ruled out pulmonary embolism and showed variable infiltrates. A bronchoscopy was performed showing findings consistent with acute alveolar hemorrhage. Prior ANA screens had been negative. ANA titer this admission was 1:80. Hospital course was complicated by acute respiratory failure requiring multiple ICU admissions associated with steroid tapering. A bone marrow biopsy showed hypercellular (90%) marrow with sideroblastic anemia, megakaryocyte atypia with mild plasmacytosis with morphologic atypia. Myeloid malignancy panel was positive for UBA-1 mutation related to VEXAS syndrome and TP53 mutation. Hematology and Rheumatology collaborated with the NIH for a treatment plan and he was started on high-dose steroid taper and tocilizumab infusions. He was discharged on day 37.
Discussion: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, first identified by Beck et al. in 2020, is caused by somatic mutations in the UBA1 gene in hematopoietic precursor cells [1]. Mutations in the E1 enzyme cause autoinflammation and hematologic symptoms which can result in significant morbidity and mortality. VEXAS syndrome commonly presents as a progressive systemic inflammatory disease in men above the age of 50 [2]. Patients often present with intermittent fevers, fatigue, myalgia, and inflammatory symptoms which affect the skin, cartilage, joints, lungs, and blood vessels [3]. Due to the vast symptomatology and broad differential associated with these clinical symptoms, the diagnosis of VEXAS can be difficult and highlights the importance of awareness of this condition. Common inflammatory manifestations seen in patients with VEXAS syndrome include Sweet’s syndrome, relapsing polychondritis, and polyarteritis nodosa [2]. Individuals also present with hematologic disorders including cytopenias and macrocytic anemia [1]. According to the National Heart Lung and Blood institute, “based on a review of health records of more than 160,000 adults, VEXAS occurred in 1 out of every 4,269 men older than age 50” [4]. Treatment is multidisciplinary and calls for collaboration with multiple medical specialists including rheumatology, infectious disease, hematology and oncology, and pulmonology.
Conclusions: Here, we present a rare case of VEXAS syndrome to increase awareness among clinical practitioners. Further research is necessary to better understand the prevalence, disease and treatment options.