Epidemiology and Outcomes of Neonatal Hemophagocytic Lymphohistiocytosis

Abstract

ObjectivesNeonatal hemophagocytic lymphohistiocytosis (HLH) is a rare entity. The objective of the study was to describe the prevalence, clinical characteristics, interventions and outcomes of neonates diagnosed with HLH in the United States.MethodsA retrospective analysis of 2009, 2012, and 2016 Kids' Inpatient Database was performed. Neonates discharged/died with a diagnosis of HLH were identified and analyzed.ResultsAmong 11,130,055 discharges, 76 neonates had a diagnosis of HLH. Fifty-two percent (95% CI: 38.6–63.6) were males and 54% (95% CI: 39.7–68.5) were white. Herpes simplex infection was present in 16% (95% CI: 9.2–28.1). 24.4% (95% CI: 14.5–37.9) received chemotherapy, 11.5% (95% CI: 5.2–23.6) IVIG and 3.6% (95% CI: 0.8–14.4) allogenic hemopoietic stem cell transplantation. Organ dysfunction was commonly seen and severe sepsis was documented in 26.6% (95% CI: 16.4–39.9). Median LOS was 16 (IQR 7–54) days. The mortality was 42% (95% CI: 30.8–55).ConclusionsHLH is a rare diagnosis and carries a high mortality in neonates. Herpes simplex virus is the most common infection associated with neonatal HLH. HLH should be considered in the differential diagnosis in neonates presenting with multi-organ dysfunction or sepsis.

Neonatal hemophagocytic lymphohistiocytosis: A meta‐analysis of 205 cases

“…Balakumar et al. reported that 42% of patients died, 41% of patients were discharged home, and 12% required home healthcare 7 . Many patients in our study (63%) died within the period of reporting.…”

“…First, cases in our study were published over nearly 40 years, whereas Balakumar et al. reported data from 2009, 2012, and 2016 7 . Second, cases in our study were from 31 different countries, while Balakumar et al.…”

“…The differential diagnosis for NALF includes nHLH, gestational alloimmune liver disease (GALD), sepsis, viral infections, metabolic hepatology, transient abnormal myelopoiesis, and hypoperfusion injury 8,9 . In an epidemiologic analysis, Balakumar and colleagues (2022) found that liver failure occurred in 35% of nHLH cases and that liver failure was the only organ dysfunction independently associated with increased mortality on multivariable analysis 7 . The epidemiologic methodology used by Balakumar et al.…”

“…8,9 In an epidemiologic analysis, Balakumar and colleagues (2022) found that liver failure occurred in 35% of nHLH cases and that liver failure was the only organ dysfunction independently associated with increased mortality on multivariable analysis. 7 The epidemiologic methodology used by Balakumar et al ( 2022) utilized ICD-9 and ICD-10 codes and, similar to other studies that use large databases, was limited by coding accuracy. 7 When possible, we distinguished between liver failure and liver injury using accepted definitions of these clinical entities; we found that liver failure (24%) or liver injury (68%) occurred in most published cases of nHLH.…”

“…However, diagnosis is difficult due to this condition's rarity and multiplicity of clinical presentations 6 . Balakumar and colleagues (2022) found the epidemiologic prevalence of nHLH to 0.06 per 10,000 infant discharges 7 . Statistically, very few pediatric hematologists/oncologists and intensivists will see more than one case of nHLH over their entire career.…”