Hemophagocytic lymphohistiocytosis: updates and evolving... : Current Opinion in Pediatrics (original) (raw)

HEMATOLOGY AND ONCOLOGY: Edited by Mitchell Weiss

updates and evolving concepts

aDivision of Allergy and Immunology

bDivision of Immunobiology

cDivision of Bone Marrow Transplant and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

Correspondence to Michael B. Jordan, MD, Division of Immunobiology and Division of Bone Marrow Transplant and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave. ML 7038, Cincinnati, OH 45229, USA. Tel: +1 513 636 7287; e-mail: [email protected]

Abstract

Purpose of review

Hemophagocytic lymphohistiocytosis (HLH) is an immune dysregulatory syndrome that is associated with underlying defects of perforin-dependent cytotoxic function. This review seeks to update readers on new scientific insights and evolving clinical concepts related to this rare but fatal disorder.

Recent findings

Clinically, HLH is defined by severe inflammation and potentially fatal damage to a variety of organ systems including the bone marrow, liver, or brain. Recent preclinical studies have increasingly defined HLH as a syndrome of abnormal and excessive T-cell activation, which leads to toxic activation of macrophages and other innate immune cells. Although macrophages have long been suspected to be important for disease development, recent studies have for the first time demonstrated their central role in the development of inflammation-associated cytopenias. In addition to defining new therapeutic targets, these scientific insights suggest significant overlap between HLH and severe inflammation in a variety of clinical contexts. Recent clinical observations are also changing how HLH is conceptualized. Increased recognition of HLH in older children and adults, sometimes in association with classic disease-associated mutations, is challenging the traditional view of HLH as either a distinctly familial or a sporadic disorder.

Summary

Recent scientific and clinical insights are expanding understanding and recognition of HLH, driving an evolution in how it is defined, and suggesting future directions for improving therapy of this disorder.