Azathioprine-induced hypersensitivity reaction mimicking sepsis in a patient with systemic lupus erythematosus

A 21-year-old woman with a history of systemic lupus erythematosus presented to the emergency department with acute-onset nausea, vomiting, and fevers. Two weeks prior, she was started on azathioprine 50 mg daily by her outpatient rheumatologist; the dose was up-titrated to 100 mg when repeat blood work showed no drug toxicity. The morning after increasing her dose, she was awoken by recurrent emesis. At presentation, she was febrile, tachycardic, and hypotensive. Her exam showed mild, generalised abdominal tenderness but was otherwise unremarkable. Lab work demonstrated elevated inflammatory markers, elevated liver transaminases, and stable hypocomplementemia. Chest X-ray and computed tomography abdomen/pelvis were unrevealing. She was given intravenous fluids and broad-spectrum antibiotics, and azathioprine was held. A thorough infectious workup returned negative. A flare of her systemic lupus erythematosus was considered but deemed an unlikely explanation of her systemic inflammatory response syndrome. With azathioprine discontinuation, she made a rapid, near-complete recovery within 24 h of admission, suggesting a diagnosis of azathioprine hypersensitivity syndrome. This case exemplifies the difficulty in distinguishing azathioprine hypersensitivity from mimickers such as infection and underlying autoimmune disease flare. Prompt recognition of hypersensitivity can lead to appropriate discontinuation of the drug and prevent future morbidity.