Hemophagocytic Lymphohistiocytosis: a Potentially Underrecognized Association with Systemic Inflammatory Response Syndrome, Severe Sepsis, and Septic Shock in Adults

Background: Hemophagocytic lymphohistiocytosis (HLH) was originally described as a genetic disorder of immune regulation, presenting in neonates with protracted fever, hepatosplenomegaly, and cytopenia. A secondary form of HLH, triggered by serious infections, was subsequently described in adults.

Methods: We report three adult patients who presented with systemic inflammatory response syndrome and features consistent with severe sepsis and septic shock, who subsequently received a diagnosis of secondary HLH. We reviewed the relationship between infection-triggered HLH and septic shock from the perspective of the adult intensivist.

Results: The hyperinflammatory pathophysiologic characteristics of HLH and septic shock are closely intertwined. Clinical and laboratory features of HLH and septic shock overlap in some patients, making the syndromes difficult to distinguish. In our experience and review, progressive pancytopenia was the feature most likely to suggest secondary HLH in the adult patient with presumed (or definite) septic shock. Use of other HLH-2004 diagnostic criteria is hindered by the poor operating characteristics of these tests in critically ill adults. Bone marrow aspiration is the most useful diagnostic test, but may yield an initial false-negative result.

Conclusion: The HLH-2004 treatment protocol is not of proven benefit in critically ill adults, but observational data suggest that aggressive immunosuppressive therapy should not be delayed. Further study of HLH in the critical care setting might provide important insights into the pathogenesis and clinical treatment of sepsis.