440. VEXAS syndrome: clinical case series from a Canadian cohort
Creators: name: Williams1, Stephen
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background/Objectives</strong>: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory condition. It is characterized by vacuolation on bone marrow biopsy and caused by a mutation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. The majority of patients in the literature to date have been males over the age of 50. Clinical manifestations include constitutional symptoms, macrocytic anemia, myelodysplastic syndrome, chondritis, and rash. Patients are typically steroid-dependent and prognosis is poor. This case series adds to the literature by describing the clinical features of our patient cohort, presenting one of the first cases of VEXAS syndrome in a female, and featuring the impacts of different therapeutic interventions in these patients. <strong>Methods:</strong> Patient recruitment was completed by two rheumatologists in the Division of Rheumatology at two academic centres in Western Canada. The patients in our case series were either genetically confirmed VEXAS syndrome patients who were referred for inclusion in this study or patients with clinical presentations suspicious for VEXAS syndrome who were subsequently confirmed to have the causative UBA1 mutation through genetic testing at the National Institutes of Health. <strong>Results:</strong> In our case series we identified 6 patients with VEXAS syndrome. Five patients were male and one patient was female (Turner syndrome). Three <em>UBA1 </em>variants were seen. A range of initial diagnoses were made prior to the confirmation of VEXAS syndrome in our cohort. Three patients were diagnosed with relapsing polychondritis. The others were diagnosed with erythema nodosum, malignancy, and adult-onset Still’s disease vs. vasculitis. Constitutional symptoms, elevated CRP and/or ESR, and macrocytic anemia were seen in all patients. Three patients presented with thrombocytopenia. A positive p-ANCA was noted in one patient, but MPO-ANCA and PR3-ANCA were negative and there were no clinical features suggestive of ANCA-associated vasculitis. Pulmonary capillaritis was noted in one patient who was ANCA negative. Five patients had cutaneous findings. Four of these patients were found to have perivascular lymphocytic infiltration and one patient presented with lupus tumidus. Pulmonary findings were found in four patients and ranged from capillaritis to organizing pneumonia. All patients who required treatment were responsive to steroids. Most other steroid sparing agents were ineffective with a few exceptions. Some patients experienced partial to good response with IL-6 and IL-1 inhibition but were unable to continue treatment due to side effects. One patient had suppression of symptoms with cyclosporine and low dose prednisone, but eventually had a relapse of her disease. She was switched to etanercept with good effect. One patient is on azathioprine and has been able to taper prednisone to 15 mg daily without a flare of symptoms. <strong>Conclusion:</strong> Patients with VEXAS syndrome represent an important cohort of treatment-resistant cases that may mimic other diseases such as relapsing polychondritis or vasculitis. The characteristics of steroid responsiveness and dependence coupled with the presence of constitutional symptoms, macrocytic anaemia, rash, chondritis, and/or pulmonary findings should increase the clinical suspicion of VEXAS syndrome. Moreover, the X-linked nature of this condition does not preclude female patients from being affected. This case series describes one of the few instances of VEXAS syndrome in a woman with Turner syndrome. We suggest the consideration of VEXAS syndrome in individuals with Turner’s who are presenting with compatible symptoms. <strong>Disclosures:</strong> None.