Zheng Qin Ng, n/a
Medical Student
Yong Loo Lin School of Medicine, National University of Singapore, United States
Disclosure information not submitted.
Rajat Bhattacharyya, MD, FRCPCH, FRCPath
Senior Consultant, Paediatric Haematology Oncology
KK Women’s and Children’s Hospital, United States
Disclosure information not submitted.
Rehena Sultana, n/a
Senior Research Associate (Biostatistician)
Duke-NUS Medical School, Singapore, United States
Disclosure information not submitted.
Lee Jan Hau, MBBS, MRCPCH, MCI (he/him/his)
KK Women's and Children's Hospital, Singapore
Singapore, Slovenia
Disclosure information not submitted.
Title: Treatment and Mortality of Hemophagocytic Lymphohistiocytosis (HLH) in Critically Ill Children
Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a complex syndrome of dysregulated immune activation caused by over-activated macrophages, natural killer (NK) and T cells leading to hypercytokinemia with subsequent organ infiltration and systemic morbidity. This systematic review aims to describe organ support mechanisms and treatment modalities employed, and determine the overall pooled mortality rate of critically ill children with HLH.
Methods: Searches were conducted on PubMed, EMBASE, Web of Science, CINAHL and The Cochrane Library from inception until 18 January 2021. Studies involving children aged ≤ 18 years diagnosed with HLH and admitted to the pediatric intensive care unit (PICU) were included. Single-patient case reports, non-English studies and non-PICU studies were excluded. The primary outcome was PICU mortality.
Results: A total of 32 studies (n = 454 patients) were included in this review, of which 19 studies (n = 267 patients) had detailed information on supportive therapies used in the PICU. Mean age of the patients was 73.4 months. Overall pooled mortality rate was 34.8% (158/454). The most frequent etiologies and triggers for HLH were infections (50.7%), primary HLH (13.7%), and autoimmune diseases (10.6%). Mortality rate was significantly higher in children with primary HLH (67.6% vs 30.7%, p = 0.004) compared to secondary HLH. Most commonly used supportive therapies in the PICU were: intubation and mechanical ventilation [94 patients (35.2%)], inotropes and vasopressors [54 patients (20.2%)], continuous renal replacement therapy [40 patients (15.0%)] and extracorporeal membrane oxygenation [33 patients (12.4%)].
Conclusions: The mortality rate of critically ill children with HLH is high. The most common trigger was infection. Primary HLH was associated with significantly poorer prognosis than secondary HLH. More data on specific supportive modalities used in the PICU in future studies will provide a more robust understanding on the resources required to treat critically ill HLH patients to improve patient outcomes.