Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal condition characterized by a pathologic inflammation. The diagnostic criteria for HLH include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, abnormal natural killer cell (NK cell) functional assay, elevated soluble IL-2Ralpha level, and elevated ferritin level (>500 microg/L). Institution of timely therapy in these critically ill patients may be delayed by difficulties establishing the diagnosis. NK cell functional assay and soluble IL-2Ralpha level may require send-out to a specialized lab. However, ferritin level is available on a same-day basis at most institutions. In this study, we examined the utility of quantitative ferritin levels in diagnosing HLH. PROCEDURE: All patients with ferritin values >500 microg/L obtained at Texas Children's Hospital between January 10, 2003 and January 10, 2005 were identified. Patient charts were reviewed for ferritin levels and hospital course. RESULTS: During the study interval, 330 patients had ferritin levels >500 microg/L. Ten of the 330 patients were diagnosed with HLH. A ferritin level over 10,000 microg/L was 90% sensitive and 96% specific for HLH. Another diagnostic category with significantly elevated ferritin level was illness of unknown cause (n = 10), and only two of these patients were fully evaluated for HLH. CONCLUSIONS: Ferritin levels above 10,000 microg/L appear to be specific and sensitive for HLH. In patients without a significant medical history and a new onset of febrile illness with highly elevated ferritin levels, the diagnosis of HLH should be evaluated.