Familial and acquired hemophagocytic lymphohistiocytosis

• Published in: European journal of pediatrics Vol. 166; no. 2; pp. 95 - 109
• Main Author: JANKA, Gritta E
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.02.2007; Berlin Springer Nature B.V
• Subjects: Biochemical markers; Biological and medical sciences; Bone marrow; Cell activation; Cell Proliferation; Chediak-Higashi syndrome; Cytokines; Cytokines - secretion; Cytotoxicity; Diagnosis, Differential; Effector cells; Epstein-Barr virus; Ferritin; Fever; Fibrinogen; General aspects; Genetic Predisposition to Disease; Griscelli syndrome; Hematologic and hematopoietic diseases; Hematology; Histiocytosis; Humans; Immune system; Immunity, Cellular; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Immunosuppressive agents; Inflammation; Lymphatic diseases; Lymphocytes; Lymphocytes T; Lymphocytosis; Lymphohistiocytosis, Hemophagocytic - genetics; Lymphohistiocytosis, Hemophagocytic - immunology; Lymphohistiocytosis, Hemophagocytic - pathology; Lymphoma; Macrophages; Medical sciences; Natural killer cells; Other diseases. Hematologic involvement in other diseases; Pancytopenia; Pathophysiology; Patients; Rheumatic diseases; Risk Factors; Stem cell transplantation; T-Lymphocytes - immunology; T-Lymphocytes - secretion; Triglycerides; Tumor necrosis factor-TNF; Immunopathology; Pediatrics; Acquired; Family study; Langerhans cell histiocytosis; Stem cell; Hematopoietic cell; Homograft; Bone marrow transplantation; Hemopathy; Hemophagocytosis; Review; Histiocytosis; Immune deficiency; Hemophagocytic syndrome; Hemophagocytic lymphohistiocytosis; Bone marrow; Immune deficiency Bone marrow transplantation Review; Bibliographic review
• ISSN: 0340-6199; 1432-1076
• DOI: 10.1007/s00431-006-0258-1

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.