VEXAS Unraveled

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disorder associated with systemic inflammation. Cardiac involvement is rare (<12%). CASE SUMMARY: A 72-year-old man with myelodysplastic syndrome presented with sepsis progressing to shock, despite resolution of prior infection and the lack of a new infection. He developed severe nonischemic cardiomyopathy with a left ventricular ejection fraction decline from 65% to 12% with an unremarkable cardiac angiogram, intermittent fevers, and pancytopenia. Genetic testing confirmed VEXAS syndrome. After multidisciplinary discussions, initiation of corticosteroids, interleukin-1 blockade, and Janus kinase inhibition led to recovery of cardiac function to a 54% left ventricular ejection fraction. DISCUSSION: This case highlights VEXAS syndrome as an under-recognized inflammatory cause of cardiomyopathy. Restored cardiac function, a rarely reported finding, underscores the role of multidisciplinary management and targeted immunomodulatory therapy. TAKE-HOME MESSAGES: VEXAS should be considered in older men with refractory systemic inflammation and new cardiomyopathy. Early immunotherapy may reverse cardiac dysfunction.