Hemophagocytic Lymphohistiocytosis: Diagnosis and Management Challenges

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a primary immune system disorder that results from defective cell-to-cell signaling and disruption of inflammatory system homeostasis. This disorder usually affects children, although cases of HLH in adults have been reported (Zhang et al. 2011). HLH usually is initiated by an external stimulus, most commonly by viral infections, but familial cases have also been described (Janka 2006). Epstein-Barr virus is one of the more frequently implicated infections in the pathogenesis of HLH, but many other infections have been associated (Filipovich 2008). There are several inherited gene mutations which have been demonstrated to cause HLH. All of these genes encode proteins that participate in target-cell killing within the immune system and that effect homeostasis of the inflammatory response. Without such a regulatory system, cytokines and other inflammatory mediators are produced unchecked, resulting in fever, multiple organ system failure, pancytopenia, and death in many patients if treatment is not initiated promptly.