MedGen

Hemophagocytic syndrome (HPS) is a rare immune disease (see this term) and a potentially life-threatening disorder characterized by cytokine storm and overwhelming inflammation causing fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis in bone marrow, liver, spleen or lymph nodes. It can be either primary due to a genetic defect (primary hemophagocytic lymphohistiocytosis ; see this term), or secondary to malignancies, to infections, most commonly with viruses such as Epstein-Barr virus or cytomegalovirus, human immunodeficiency virus, or to autoimmune disorders such as systemic lupus erythematosus or adult-onset Still disease (secondary hemophagocytic lymphohistiocytosis) (see these termes). [from ORDO]

Familial hemophagocytic lymphohistiocytosis-5 with or without microvillus inclusion disease (FHL5) is an autosomal recessive hyperinflammatory disorder characterized clinically by fever, hepatosplenomegaly, pancytopenia, coagulation abnormalities, and other laboratory findings. Some patients have neurologic symptoms due to inflammatory CNS disease. There is uncontrolled and ineffective proliferation and activation of T lymphocytes, NK cells, and macrophages that infiltrate multiple organs, including liver, spleen, lymph nodes, and the CNS. The phenotype is variable: some patients may present in early infancy with severe diarrhea, prior to the onset of typical FHL features, whereas others present later in childhood and have a more protracted course without diarrhea. The early-onset diarrhea is due to enteropathy reminiscent of microvillus inclusion disease (see MVID, 251850). The enteropathy, which often necessitates parenteral feeding, may be the most life-threatening issue even after hematopoietic stem cell transplantation (HSCT). More variable features include sensorineural hearing loss and hypogammaglobulinemia. Treatment with immunosuppressive drugs and chemotherapy can ameliorate signs and symptoms of FHL in some patients, but the only curative therapy for FHL is HSCT. HSCT is not curative for enteropathy associated with the disorder, despite hematologic and immunologic reconstitution (summary by Meeths et al., 2010; Pagel et al., 2012; Stepensky et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL, HLH), see 267700. [from OMIM]

Familial hemophagocytic lymphohistiocytosis (fHLH), defined as the presence of biallelic pathogenic variants in one of four genes (PRF1, STX11, STXBP2, or UNC13D), is an immune deficiency characterized by the overactivation and excessive proliferation of T lymphocytes and macrophages, leading to infiltration and damage of organs including the bone marrow, liver, spleen, and brain. Familial HLH usually presents as an acute illness with prolonged and high fever, cytopenias, and hepatosplenomegaly. Rash and lymphadenopathy are less common. Individuals with fHLH may also exhibit liver dysfunction and neurologic abnormalities. Although manifestations of fHLH are usually evident within the first months or years of life and may develop in utero, symptomatic presentation can occur throughout childhood and into adulthood. Median survival in untreated infants with fHLH who develop active disease is less than two months after onset of manifestations; progressive manifestations of fHLH, organ dysfunction, invasive infection, and bleeding account for the majority of deaths. Use of etoposide-containing regimens such as the HLH-94 and HLH-2004 protocols followed by allogeneic hematopoietic stem cell transplantation (HSCT) has improved survival. [from GeneReviews]

Familial hemophagocytic lymphohistiocytosis-2 (FHL2) is an autosomal recessive disorder of immune dysregulation with onset in infancy or early childhood. It is characterized clinically by fever, edema, hepatosplenomegaly, and liver dysfunction. Neurologic impairment, seizures, and ataxia are frequent. Laboratory studies show pancytopenia, coagulation abnormalities, hypofibrinogenemia, and hypertriglyceridemia. There is increased production of cytokines, such as gamma-interferon (IFNG; 147570) and TNF-alpha (191160), by hyperactivation and proliferation of T cells and macrophages. Activity of cytotoxic T cells and NK cells is reduced, consistent with a defect in cellular cytotoxicity. Bone marrow, lymph nodes, spleen, and liver show features of hemophagocytosis. Chemotherapy and/or immunosuppressant therapy may result in symptomatic remission, but the disorder is fatal without bone marrow transplantation (summary by Dufourcq-Lagelouse et al., 1999, Stepp et al., 1999, and Molleran Lee et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of FHL, see 267700. [from OMIM]

Hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder clinically diagnosed based on the fulfillment of 5 of 8 criteria, including fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low or absent natural killer (NK) cell activity, hyperferritinemia, and high soluble IL2 receptor levels (IL2R; 147730). The disorder typically presents in infancy or early childhood. Persistent remission is rarely achieved with chemo- or immunotherapy; hematopoietic stem cell transplantation is the only cure (summary by Muller et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL), see 267700. [from OMIM]

Secretion of the contents of cytolytic granules at the immunologic synapse is a highly regulated process essential for lymphocyte cytotoxicity. This process requires the rapid transfer of perforin (170280)-containing lytic granules to the target cell interface, followed by their docking and fusion with the plasma membrane. Familial hemophagocytic lymphohistiocytosis is a genetically heterogeneous condition characterized by defective cytotoxicity. For a more detailed description of FHL, see 267700. [from OMIM]

A disorder resulting from an abnormality in the immune system. [from NCI]

A rare cutaneous lesion composed of eosinophilic histiocytes, which are often multinucleated. The lesions are yellow-brown papules affecting any part of the body. Patients are usually adult men. The prognosis is excellent. -- 2003 [from NCI]

Group of disorders which feature accumulations of active HISTIOCYTES and LYMPHOCYTES, but where the histiocytes are not LANGERHANS CELLS. The group includes HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SINUS HISTIOCYTOSIS; xanthogranuloma; reticulohistiocytoma; juvenile XANTHOGRANULOMA; xanthoma disseminatum; as well as the lipid storage diseases (SEA-BLUE HISTIOCYTE SYNDROME; and NIEMANN-PICK DISEASES). [from MONDO]

An excessive number of histiocytes (tissue macrophages). [from HPO]

The magnitude of INBREEDING in humans. [from MeSH]

Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome with an onset usually occurring within a few months or less common several years after birth. [from MONDO]

Proliferation of HISTIOCYTES in response to viral, bacterial, fungal, or parasitic infections. [from MeSH]