Abstract Introduction We report a case of an 87-year-old male presenting with debilitating fatigue and multifocal airspace opacities that improved with corticosteroid therapy, later diagnosed as VEXAS syndrome. Case Presentation An 87-year-old man with a history of atrial fibrillation (on Xarelto), diastolic heart failure, coronary artery disease, sick sinus syndrome status post pacemaker placement, hypertension, and chronic kidney disease presented with profound fatigue and failure to thrive over the last few months. A CT chest showed multifocal consolidative airspace opacities (Figure 1a) interpreted as “non-resolving pneumonia.” Despite multiple antibiotic courses, symptoms persisted. Notably, the patient had no respiratory complaints and maintained oxygen saturation of 98-99% on room air. Bronchoscopy revealed bronchoalveolar lavage (BAL) fluid with lymphocytic predominance, but cultures were negative and transbronchial biopsy was non-diagnostic and lymph node biopsies revealed normal lymphocytic tissue. Hematologic evaluation for plasma cell dyscrasia and amyloidosis was negative, though he was noted to have monoclonal gammopathy of undetermined significance. Additional workup revealed EBV positivity in BAL and serum (IgG+, IgM-), and weakly positive ANA and p-ANCA levels. Rheumatology consultation concluded that clinical features were not consistent with ANCA-associated vasculitis, additionally there was no evidence of diffuse alveolar hemorrhage on bronchoscopy. Empirical prednisone therapy led to a marked improvement in fatigue and interval resolution of the pulmonary opacities (Figure 1b). However, repeated steroid tapering attempts resulted in recurrent weakness, failure to thrive, and anemia, which normalized only during corticosteroid use. Given the relapsing course, bone marrow next-generation sequencing was pursued, identifying a pathogenic UBA1 mutation, confirming VEXAS syndrome. The patient has since been initiated on a JAK2 inhibitor and is tapering off steroids. Conclusion VEXAS syndrome is a late-onset, X-linked autoinflammatory disorder caused by somatic mutations in the UBA1 gene. It typically manifests with systemic inflammation, cytopenias, and multi-organ involvement, including pulmonary infiltrates, fevers, vasculitis, neutrophilic dermatoses, and bone marrow vacuolization of myeloid and erythroid precursors. The disease is often refractory to standard immunosuppressive therapy, with management focusing on corticosteroids and JAK inhibitors. This case underscores the importance of considering VEXAS syndrome in elderly men with unexplained systemic inflammation, autoimmune-like features and hematological abnormalities. This abstract is funded by: None
Chhabria et al. (Fri,) studied this question.