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Familial and acquired hemophagocytic lymphohistiocytosis

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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.

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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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  1. Department of Hematology and Oncology, Children’s Hospital, University of Hamburg, Hamburg, Germany

    Gritta E. Janka

  2. Zentrum für Frauenheilkunde, Kinder- und Jugendmedizin, Klinik für Pädiatrische Hämatologie und Onkologie, Universitätskrankenhaus Eppendorf, Martinistrasse 20, 20246, Hamburg, Germany

    Gritta E. Janka

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Janka, G.E. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr 166, 95–109 (2007). https://doi.org/10.1007/s00431-006-0258-1

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