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Dilemmas in diagnosis and management of hemophagocytic lymphohistiocytosis in children

  • Xiao-Jun Xu
  • Yong-Min TangEmail author
Review Article

Abstract

Background

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening entity which is characterized by severe hyperinflammation. Now the HLH-2004 protocol has been widely accepted and clinically used; however, many questions still remain in clinical practice. In this review, we discuss the dilemmas in the diagnosis and treatment of HLH in children.

Data sources

Original research for articles and literature reviews published in PubMed was carried out using the key term “hemophagocytic lymphohistiocytosis”.

Results

As the gene sequencing technology progresses, the range of causal mutations and primary HLH has been redefined. The monoallelic variants may contribute to the pathogenesis of the disease. Many conditions without defective cytotoxicity of T or NK cells may lead to HLH, such as primary immunodeficiency (PID) and dysregulated immune activation or proliferation (DIAP). HLH shares overlapping clinical and laboratory characteristics with severe sepsis, but usually the single values are more pronounced in HLH than sepsis. H score is another approach to help the diagnosis of secondary HLH. Specific Th1/Th2 cytokine patterns are very helpful tools to differentiate HLH (reactivation of HLH) from sepsis. Moreover, it also has been used successfully to stratify the therapy intensity. The treatment of HLH should consider underlying diseases, triggers and severity. HLH-94 is recommended for patients who need etoposide-based therapy.

Conclusions

Dramatic progress has been made during the past decades in understanding the pathophysiology of HLH. However, diagnosis and treatment of HLH remain with many dilemmas because of the heterogeneous nature of the disease. Better understanding new gene defects and more effective diagnostic approaches and salvage regimens are goals for the future.

Keywords

Cytokine Hemophagocytic lymphohistiocytosis Sepsis Transplantation 

Notes

Author contributions

XJX and YMT designed the manuscript; XJX drafted the article which was revised by YMT; both the two authors approved the final version published.

Funding

This study was supported in part by grants from the National Natural Science Foundation of China (No: 81770202) and the Natural Science Foundation of Zhejiang Province (Nos: LY19H080006, LZ12H08001).

Compliance with ethical standards

Conflict of interest

No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

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Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  1. 1.Division of Hematology-Oncology, Children’s Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics of Ministry of EducationZhejiang UniversityHangzhouChina

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