European Journal of Pediatrics

, Volume 166, Issue 2, pp 95–109 | Cite as

Familial and acquired hemophagocytic lymphohistiocytosis

Review

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of severe hyperinflammation caused by the uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. Cardinal signs and symptoms are prolonged fever, hepatosplenomegaly and pancytopenia. Characteristic biochemical markers include elevated triglycerides, ferritin and low fibrinogen. HLH occurs on the basis of various inherited or acquired immune deficiencies. Impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is shared by all forms of HLH. Genetic HLH occurs in familial forms (FHLH) in which HLH is the primary and only manifestation, and in association with the immune deficiencies Chédiak-Higashi syndrome 1 (CHS 1), Griscelli syndrome 2 (GS 2) and x-linked lymphoproliferative syndrome (XLP), in which HLH is a sporadic event. Most patients with acquired HLH have no known underlying immune deficiency. Both acquired and genetic forms are triggered by infections, mostly viral, or other stimuli. HLH also occurs as a complication of rheumatic diseases (macrophage activation syndrome) and of malignancies. Several genetic defects causing FHLH have recently been discovered and have elucidated the pathophysiology of HLH. The immediate aim of therapy in genetic and acquired HLH is suppression of the severe hyperinflammation, which can be achieved with immunosuppressive/immunomodulatary agents and cytostatic drugs. Patients with genetic forms have to undergo stem cell transplantation to exchange the defective immune system with normally functioning immune effector cells.

In conclusion, awareness of the clinical symptoms and of the diagnostic criteria of HLH is crucial in order not to overlook HLH and to start life-saving therapy in time.

Keywords

Histiocytosis Hemophagocytosis Immune deficiency Bone marrow transplantation Review 

Abbreviations

CHS 1

Chédiak-Higashi syndrome 1

CSF

cerebrospinal fluid

CNS

central nervous system

CTL

cytotoxic T lymphocyte

EBV

Epstein-Barr virus

FHLH

familial hemophagocytic lymphohistiocytosis

GS 2

Griscelli syndrome 2

HLH

hemophagocytic lymphohistiocytosis

IAHS

infection-associated hemophagocytic syndrome

IL

interleukin

INF-γ

interferon γ

LAHS

lymphoma-associated hemophagocytic syndrome

MIP1-α

macrophage inflammatory protein 1-α

MRT

magnetic resonance tomography

NK cell

natural killer cell

sCD25

α-chain of the soluble interleukin-2 receptor

SCT

stem cell transplantation

sJRA

systemic-onset juvenile rheumatoid arthritis

TNF-α

tumor necrosis factor α

VAHS

virus-associated hemophagocytic syndrome

XLP

x-linked lymphoproliferative syndrome

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Hematology and Oncology, Children’s HospitalUniversity of HamburgHamburgGermany
  2. 2.Zentrum für Frauenheilkunde, Kinder- und Jugendmedizin, Klinik für Pädiatrische Hämatologie und OnkologieUniversitätskrankenhaus EppendorfHamburgGermany

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