Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation

Leticia Castillo, Joseph Carcillo

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

In an effort to attain earlier diagnoses in children with hemophagocytic lymphohistiocytosis (HLH), the International Histiocyte Society has now broadened their diagnostic criteria to no longer differentiate primary (HLH) and secondary hemophagocytic lymphohistiocytosis (SHLH). Five of the following eight diagnostic criteria needed to be met: 1) fever, 2) cytopenia of two lines, 3) hypertriglyceridemia and/or hypofibrinogenemia, 4) hyperferritinemia (>500 μg/L), 5) hemophagocytosis, 6) elevated soluble interleukin-2 receptor (CD25), 7) decreased natural killer-cell activity, and 8) splenomegaly can also commonly be found in patients with sepsis, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), and macrophage activation syndrome (MAS). Nevertheless, the therapeutic options for these are radically different. Chemotherapy and bone marrow transplant have been used for treatment of HLH/SHLH, whereas antibiotics and supportive treatment are used in severe sepsis/SIRS and MODS. MAS is treated with limited immune suppression. Outcomes are also different, SHLH has a mortality rate around 50%, whereas pediatric septic shock and MODS have a mortality of 10.3% and 18%, respectively, and severe sepsis in previously healthy children has a mortality rate of 2%. MAS has a mortality rate between 8% and 22%. Because SHLH and severe sepsis/SIRS/MODS/MAS share clinical and laboratory inflammatory phenotypes, we recommend extreme caution when considering applying HLH therapies to children with sepsis/SIRS/MODS/MAS. HLH therapies are clearly warranted for children with HLH; however, a quantitative functional estimate of cytotoxic lymphocyte function may be a more precise approach to define the overlap of these conditions, better identify these processes, and develop novel therapeutic protocols that may lead to improved treatments and outcomes.

Original languageEnglish (US)
Pages (from-to)387-392
Number of pages6
JournalPediatric Critical Care Medicine
Volume10
Issue number3
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

Macrophage Activation Syndrome
Hemophagocytic Lymphohistiocytosis
Systemic Inflammatory Response Syndrome
Sepsis
Inflammation
Phenotype
Mortality
Therapeutics
Histiocytes
Hypertriglyceridemia
Interleukin-2 Receptors
Splenomegaly
Septic Shock
Natural Killer Cells
Early Diagnosis

Keywords

  • Hemophagocytic lymphohistiocytosis
  • Macrophage activation syndrome
  • Multiorgan dysfunction syndrome
  • Sepsis
  • Systemic inflammatory response syndrome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Critical Care and Intensive Care Medicine

Cite this

@article{eece39000c2b4c7680cf3e1c15b067c0,
title = "Secondary hemophagocytic lymphohistiocytosis and severe sepsis/systemic inflammatory response syndrome/multiorgan dysfunction syndrome/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation",
abstract = "In an effort to attain earlier diagnoses in children with hemophagocytic lymphohistiocytosis (HLH), the International Histiocyte Society has now broadened their diagnostic criteria to no longer differentiate primary (HLH) and secondary hemophagocytic lymphohistiocytosis (SHLH). Five of the following eight diagnostic criteria needed to be met: 1) fever, 2) cytopenia of two lines, 3) hypertriglyceridemia and/or hypofibrinogenemia, 4) hyperferritinemia (>500 μg/L), 5) hemophagocytosis, 6) elevated soluble interleukin-2 receptor (CD25), 7) decreased natural killer-cell activity, and 8) splenomegaly can also commonly be found in patients with sepsis, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), and macrophage activation syndrome (MAS). Nevertheless, the therapeutic options for these are radically different. Chemotherapy and bone marrow transplant have been used for treatment of HLH/SHLH, whereas antibiotics and supportive treatment are used in severe sepsis/SIRS and MODS. MAS is treated with limited immune suppression. Outcomes are also different, SHLH has a mortality rate around 50{\%}, whereas pediatric septic shock and MODS have a mortality of 10.3{\%} and 18{\%}, respectively, and severe sepsis in previously healthy children has a mortality rate of 2{\%}. MAS has a mortality rate between 8{\%} and 22{\%}. Because SHLH and severe sepsis/SIRS/MODS/MAS share clinical and laboratory inflammatory phenotypes, we recommend extreme caution when considering applying HLH therapies to children with sepsis/SIRS/MODS/MAS. HLH therapies are clearly warranted for children with HLH; however, a quantitative functional estimate of cytotoxic lymphocyte function may be a more precise approach to define the overlap of these conditions, better identify these processes, and develop novel therapeutic protocols that may lead to improved treatments and outcomes.",
keywords = "Hemophagocytic lymphohistiocytosis, Macrophage activation syndrome, Multiorgan dysfunction syndrome, Sepsis, Systemic inflammatory response syndrome",
author = "Leticia Castillo and Joseph Carcillo",
year = "2009",
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doi = "10.1097/PCC.0b013e3181a1ae08",
language = "English (US)",
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AU - Castillo, Leticia

AU - Carcillo, Joseph

PY - 2009/5/1

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N2 - In an effort to attain earlier diagnoses in children with hemophagocytic lymphohistiocytosis (HLH), the International Histiocyte Society has now broadened their diagnostic criteria to no longer differentiate primary (HLH) and secondary hemophagocytic lymphohistiocytosis (SHLH). Five of the following eight diagnostic criteria needed to be met: 1) fever, 2) cytopenia of two lines, 3) hypertriglyceridemia and/or hypofibrinogenemia, 4) hyperferritinemia (>500 μg/L), 5) hemophagocytosis, 6) elevated soluble interleukin-2 receptor (CD25), 7) decreased natural killer-cell activity, and 8) splenomegaly can also commonly be found in patients with sepsis, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), and macrophage activation syndrome (MAS). Nevertheless, the therapeutic options for these are radically different. Chemotherapy and bone marrow transplant have been used for treatment of HLH/SHLH, whereas antibiotics and supportive treatment are used in severe sepsis/SIRS and MODS. MAS is treated with limited immune suppression. Outcomes are also different, SHLH has a mortality rate around 50%, whereas pediatric septic shock and MODS have a mortality of 10.3% and 18%, respectively, and severe sepsis in previously healthy children has a mortality rate of 2%. MAS has a mortality rate between 8% and 22%. Because SHLH and severe sepsis/SIRS/MODS/MAS share clinical and laboratory inflammatory phenotypes, we recommend extreme caution when considering applying HLH therapies to children with sepsis/SIRS/MODS/MAS. HLH therapies are clearly warranted for children with HLH; however, a quantitative functional estimate of cytotoxic lymphocyte function may be a more precise approach to define the overlap of these conditions, better identify these processes, and develop novel therapeutic protocols that may lead to improved treatments and outcomes.

AB - In an effort to attain earlier diagnoses in children with hemophagocytic lymphohistiocytosis (HLH), the International Histiocyte Society has now broadened their diagnostic criteria to no longer differentiate primary (HLH) and secondary hemophagocytic lymphohistiocytosis (SHLH). Five of the following eight diagnostic criteria needed to be met: 1) fever, 2) cytopenia of two lines, 3) hypertriglyceridemia and/or hypofibrinogenemia, 4) hyperferritinemia (>500 μg/L), 5) hemophagocytosis, 6) elevated soluble interleukin-2 receptor (CD25), 7) decreased natural killer-cell activity, and 8) splenomegaly can also commonly be found in patients with sepsis, systemic inflammatory response syndrome (SIRS), multiorgan dysfunction syndrome (MODS), and macrophage activation syndrome (MAS). Nevertheless, the therapeutic options for these are radically different. Chemotherapy and bone marrow transplant have been used for treatment of HLH/SHLH, whereas antibiotics and supportive treatment are used in severe sepsis/SIRS and MODS. MAS is treated with limited immune suppression. Outcomes are also different, SHLH has a mortality rate around 50%, whereas pediatric septic shock and MODS have a mortality of 10.3% and 18%, respectively, and severe sepsis in previously healthy children has a mortality rate of 2%. MAS has a mortality rate between 8% and 22%. Because SHLH and severe sepsis/SIRS/MODS/MAS share clinical and laboratory inflammatory phenotypes, we recommend extreme caution when considering applying HLH therapies to children with sepsis/SIRS/MODS/MAS. HLH therapies are clearly warranted for children with HLH; however, a quantitative functional estimate of cytotoxic lymphocyte function may be a more precise approach to define the overlap of these conditions, better identify these processes, and develop novel therapeutic protocols that may lead to improved treatments and outcomes.

KW - Hemophagocytic lymphohistiocytosis

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KW - Systemic inflammatory response syndrome

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