Hemophagocytic syndrome in an adolescent with Crohn disease receiving azathioprine and infliximab

Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disorder. It is characterized by excessive proinflammatory cytokine release and proliferation of activated macrophages and lymphocytes that phagocytose erythrocytes, white blood cells, and platelets in the bone marrow. Clinically, it presents with high persistent fever and splenomegaly, often in the context of an acute infection (1). Laboratory signs include peripheral blood cytopenias (affecting at least 2 cell lines), splenomegaly, hypertriglyceridemia (>= 265 mg/dL), hyperferritinemia (>= 500 g/mL), elevated soluble CD25, and/or hypofibrinogenemia (<= 150 mg/dL) (1,2). It is broadly classified into 2 forms. Primary HLH is an inherited autosomal recessive disorder associated with mutations of proteins involved in either the functional secretion of cytotoxic granules, or the delivery of proteases required for apoptosis of target cells. Secondary HLH is associated with certain infections, including Epstein-Barr virus (EBV) infection and other diseases (1). Patients with immunodeficiency or immunosuppression are at risk for infection-associated HLH. Therefore, patients with inflammatory bowel disease (IBD) treated with immunomodulators probably represent a susceptible population (3). We report an adolescent with Crohn disease in whom EBV-associated HLH developed while she was receiving maintenance therapy with azathioprine and infliximab.