Hemophagocytic Lymphohistiocytosis Syndromes

Standage, Stephen W.; Filipovich, Alexandra H.

Hemophagocytic lymphohistiocytosis (HLH) is a non-malignant, life-threatening hyperinflammatory condition resulting from dysregulation of normal innate and adaptive immune responses. Defects in immune effector cell cytotoxic mechanisms have been identified in many HLH syndromes. Infants and children most often present with this condition, but new onset disease may be observed in adults as well. Presenting signs and symptoms include the classic triad of fever, hepatosplenomegaly, and cytopenias, but neurologic impairment, respiratory and cardiovascular embarrassment, liver disease with coagulopathy, diarrhea, and rash may feature prominently. Diagnosis relies upon fulfilling clinical criteria and laboratory assessments including serum ferritin, soluble IL-2 receptor levels, and natural killer (NK) cell function studies. Treatment consists of excellent supportive care for the critically ill. Specific disease modifying therapy employs immunosuppressant medications and often hematopoietic stem cell transplant. HLH syndromes are frequently fatal if untreated. With current interventions survival ranges 60–70 %.