Clinical profile and outcomes of children with Hemophagocytic Lymphohistiocytosis (HLH) in the PICU of a tertiary care children’s hospital

Abstract

Background : Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening syndrome of immune dysregulation leading to excessive cytokine production and multi-organ dysfunction. The Incidence of HLH varies between 1 per 5,000 to 1 per 1,00,000 in different studies. Diagnosis of HLH requires high suspicion as severe sepsis with organ dysfunction is a close differential. Differentiation of primary & secondary HLH is also difficult. Early recognition is very important for the timely institution of the treatment Methods : We conducted a retrospective analysis of children admitted to the PICU between January 2007 to July 2017 who were diagnosed to have HLH using HLH-2004 criteria. Demographic, clinical & laboratory parameters, treatment details & outcomes were recorded. Outcomes of secondary HLH treated with cytotoxic chemotherapy were compared with those treated with immuno-modulatory therapy alone. Results : Out of 6678 children admitted to the PICU during the study period, 47 were diagnosed with HLH. Ten children had primary HLH and 37 had secondary HLH. Forty two (89%) children had fever, 40 (85%) splenomegaly, 43 (91%) bicytopenia, 45 (95%) hyperferritinemia, 41 (87%) hemophagocytosis in the bone marrow, 44 (93%) low fibrinogen levels and 32 (68%) had high triglyceride levels. Among those with primary HLH, 6 were familial and 4 were immunodeficiency related. Mutation analysis by next generation sequencing was positive in 2 children with familial HLH. In our analysis, the different aetiologies for secondary HLH were Dengue (12 patients), Epstein Barr Virus (6 patients), Scrub typhus, Staphylococcus aureus, Sphingomonas, Typhoid and Adenovirus (each 1 patient) and the rest (14 patients) had culture negative sepsis. The overall PICU mortality rate was 55.3%. Mortality rate of primary HLH was 80% when compared to 48.6% in secondary HLH. In children with secondary HLH, 14 were treated with corticosteroids & Intravenous Immune Globulin (IVIG) only (immune-modulatory therapy group) and the remaining 27 children received Steroids, Etoposide, Cyclosporine +/- IVIG (Cytotoxic chemotherapy group). Mortality was higher in children with secondary HLH who received cytotoxic chemotherapy (52%) when compared to immunomodulatory therapy (28%) alone. Conclusion : The incidence of HLH in this population of critically ill children (7/1000) is higher than those reported elsewhere. Secondary HLH was more common than primary. Outcomes of secondary HLH were better in those treated with Immunomodulatory therapy alone.