Osteopathic medical student Nova Southeastern University College of Osteopathic Medicine Davie, Florida
Introduction: As a disease-modifying anti-rheumatic medication, azathioprine alleviates rheumatoid arthritis, inflammatory bowel disease, and prevents kidney transplant rejection. The literature limits azathioprine’s hematologic side effect profile to bone marrow suppression causing leukopenia, thrombocytopenia, and pancytopenia. However, a rare side effect of azathioprine not commonly discussed in the literature includes eosinophilia and severe transaminitis. Although limited studies have identified eosinophilia over a chronic use of immunosuppressive agents, very few have focused on azathioprine-induced eosinophilia and severe transaminitis in a female patient over an acute, one-month period.
Case Study: A twenty-year-old female with a history of systemic lupus erythematosus with lupus nephritis class III presents with nausea and weakness. Initial laboratory findings showed pancytopenia, bilirubinemia, severe transaminitis, elevated inflammatory markers, and proteinuria. Ultrasound of the abdomen was significant for mild hepatomegaly and gallbladder sludge. EGD demonstrated a gastric ulcer. Pathology revealed chronic inflammatory cells and eosinophilia within the lamina propria with rare neutrophils or eosinophils involving glands and minor focal glandular branching. MRCP showed no obstruction of the biliary system. The patient was started on methylprednisolone, pantoprazole, and sucralfate. Nausea and acid reflux improved. A liver biopsy revealed prominent macrosteatosis and acute intrahepatocellular cholestatic hepatitis. Due to the possibility of a drug-induced reaction, azathioprine was discontinued, and the patient’s transaminitis and eosinophilia resolved. The patient was discharged on oral steroids, cyproheptadine, and sucralfate.
Discussion: This case illustrates acute eosinophilia and severe hepatotoxicity associated with azathioprine use in a female patient. Through purine synthesis inhibition, azathioprine converts into active metabolites that are incorporated into replicating DNA and impede division. These metabolites produce the myelosuppression associated with azathioprine use. Although myelosuppression is extensively documented in medical research, eosinophilia is another hematologic manifestation that presents in patients taking azathioprine through a potentially similar mechanism. Through idiosyncratic cholestatic reactions and endothelial cell injury, azathioprine causes hepatotoxicity. The literature predominately reviews exclusively male patients with transaminitis after two to twelve months of initiating azathioprine therapy. Although hepatotoxicity is commonly associated with azathioprine use, severely elevated transaminitis in an acute period of less than one month for a female patient is rarely documented. According to osteopathic principles, the body’s capacity to self-regulate should not be compromised when choosing medications with harmful side effect profiles. Based on the osteopathic tenet of rational treatment, further evaluation is needed to ensure prompt assessment of liver function tests and complete blood counts in patients taking azathioprine.
