title: Primary and secondary hemophagocytic lymphohistiocytosis: clinical features, pathogenesis and therapy.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal hyperinflammatory syndrome with prolonged high fever, hepatosplenomegaly and characteristic laboratory findings. HLH may be inherited (primary) or may be secondary to any severe infection, malignancy or rheumatologic condition. The last several years have witnessed an explosion in our understanding of HLH. Of the inherited causes for which the underlying genetic cause is known, most involve abnormalities of proteins important in the exocytosis cytolytic pathway, whereby perforin and granzymes are delivered to a target cell to induce apoptosis. The exact mechanisms underlying this process remain unclear. However, when a known genetic defect is not present, the diagnosis of HLH is still made on a constellation of clinical features and good clinical judgment. Rapid diagnosis is crucial, as early therapy with immunosuppressive agents and/or proapoptotic chemotherapy can be life-saving. This article examines recent advances in our understanding of the pathophysiology, clinical features, diagnosis, etiology and treatment of HLH, as well as the challenges that lie ahead.
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada. sumit.gupta@sickkids.ca
authors.forename: Sumit
authors.initials: S
authors.lastname: Gupta
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
mesh_terms: D017209:Apoptosis; D003602:Cytotoxicity, Immunologic; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D012307:Risk Factors; D033581:Stem Cell Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents