Secondary hemophagocytic lymphohistiocytosis in pediatric patients: a single-center experience

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. In children, secondary HLH may occur with infection, rheumatologic disease, malignancy, or metabolic disorders and is often difficult to diagnose because it overlaps with sepsis and other severe inflammatory states. We aimed to describe the etiologies, clinical features, treatment patterns, and outcomes of pediatric secondary HLH at a single tertiary center.

We performed a retrospective review of children diagnosed with secondary HLH between April 2007 and June 2022. Diagnosis was based on HLH-2004 criteria. Demographic, clinical, laboratory, treatment, and outcome data were analyzed descriptively.

Sixteen children were included, with a median age at diagnosis of 34 months (range, 2.5-174); 62.5% were male. Infections were the most common trigger (56.3%), followed by rheumatologic disease/macrophage activation syndrome (18.8%), metabolic disorders (12.5%), malignancy (6.3%), and Langerhans cell histiocytosis (LCH) (6.3%). At presentation, fever and cytopenias affecting at least two lineages were present in 93.8%, splenomegaly in 87.5%, and hemophagocytosis in 81.3%. Hyperferritinemia was present in all patients. All patients received HLH-directed therapy together with treatment of the underlying trigger. Thirteen patients achieved complete remission, one had partial response, and two had refractory disease. Overall survival was 87.5%. Both deaths occurred in high-risk noninfectious HLH associated with Wolman disease and refractory LCH, whereas no deaths occurred in infection-associated HLH.

Pediatric secondary HLH was most commonly infection-associated and had favorable outcomes when recognized early and treated promptly. In contrast, metabolic disease- and LCH-associated HLH were linked to refractory disease and mortality.