"secondary (acquired), more common in adults, often triggered by infections, malignancies or autoimmune diseases."
"Onset after HSCT is often delayed >30 days and may be triggered by infection or immune reconstitution. CAR T cell–associated HLH is particularly frequent with CD22 CAR T cells, affecting up to one third of recipients and typically occurs later than cytokine release syndrome."
"In secondary HLH, glucocorticoids +/- IV immune globulin and anakinra (IL-1 inhibitor) may be sufficient. In severe, nonresponsive or progressive secondary HLH with CNS involvement weekly etoposide is recommended. Ciclosporin is less commonly used in adults except in macrophage activation syndrome (MAS-HLH). Novel agents such as emapalumab (anti–IFN-γ), ruxolitinib (JAK inhibitor) and alemtuzumab (anti-CD52) can be used for refractory or relapsed HLH, with good reported survival rates for emapalumab and alemtuzumab. Anakinra crosses the blood-brain barrier and can be used for CNS involvement 21."
"viral (most common), including EBV 2,3, HIV, HHV-8, CMV, COVID-19"
"viral (most common), including EBV 2,3, HIV, HHV-8, CMV, COVID-19"
"In secondary HLH, glucocorticoids +/- IV immune globulin and anakinra (IL-1 inhibitor) may be sufficient. In severe, nonresponsive or progressive secondary HLH with CNS involvement weekly etoposide is recommended. Ciclosporin is less commonly used in adults except in macrophage activation syndrome (MAS-HLH). Novel agents such as emapalumab (anti–IFN-γ), ruxolitinib (JAK inhibitor) and alemtuzumab (anti-CD52) can be used for refractory or relapsed HLH, with good reported survival rates for emapalumab and alemtuzumab. Anakinra crosses the blood-brain barrier and can be used for CNS involvement 21."
"bacterial, including Coxiella burnetii (Q fever 17)"
"FHL2 (PRF1, which encodes perforin)"
"FHL3 (UNC13D)"
"FHL4 (STX11)"
"FHL5 (STXBP2)"
"X-linked lymphoproliferative disease type 1 (SH2D1A) and type 2 (BIRC4)"
"Griscelli syndrome type 2 (RAB27A)"
"Chediak-Higashi syndrome (LYST)"
"lysinuric protein intolerance (SLC7A7)"
"non-specific lesions of high T2/FLAIR signal in the cerebral and cerebellar hemispheres, including both white matter and deep gray matter structures 18"
"Mortality rates range from 5-80% depending on age and associations. The highest mortality occurs in malignancy-associated HLH 21. Adults generally have a poorer outcome than children 21. Central nervous system involvement and severe pulmonary disease are associated with higher risk of irreversible damage and death 21."
Expected headings
"Associations"
"Chest"
"Abdomen"
"Brain"
"HLH and cytokine release syndrome (CRS) are subtypes of cytokine storm syndrome. CRS is a supraphysiologic immune response driven by IL-6, most commonly following immune therapy (e.g., CAR T-cells), with mandatory fever at onset and possible hypotension, hypoxaemia and organ dysfunction, but does not require cytopaenias, hyperferritinaemia or haemophagocytosis. Although there are some common features, the pathogenesis, cytokine profile and treatment differ, (tocilizumab for CRS). HLH and CRS can overlap, especially in the context of CAR T-cell therapy, where HLH-like manifestations may be considered a variant or severe form of CRS (sometimes termed CARHLH) 26."
"In secondary HLH, glucocorticoids +/- IV immune globulin and anakinra (IL-1 inhibitor) may be sufficient. In severe, nonresponsive or progressive secondary HLH with CNS involvement weekly etoposide is recommended. Ciclosporin is less commonly used in adults except in macrophage activation syndrome (MAS-HLH). Novel agents such as emapalumab (anti–IFN-γ), ruxolitinib (JAK inhibitor) and alemtuzumab (anti-CD52) can be used for refractory or relapsed HLH, with good reported survival rates for emapalumab and alemtuzumab. Anakinra crosses the blood-brain barrier and can be used for CNS involvement 21."
"HLH and cytokine release syndrome (CRS) are subtypes of cytokine storm syndrome. CRS is a supraphysiologic immune response driven by IL-6, most commonly following immune therapy (e.g., CAR T-cells), with mandatory fever at onset and possible hypotension, hypoxaemia and organ dysfunction, but does not require cytopaenias, hyperferritinaemia or haemophagocytosis. Although there are some common features, the pathogenesis, cytokine profile and treatment differ, (tocilizumab for CRS). HLH and CRS can overlap, especially in the context of CAR T-cell therapy, where HLH-like manifestations may be considered a variant or severe form of CRS (sometimes termed CARHLH) 26."
"HLH and cytokine release syndrome (CRS) are subtypes of cytokine storm syndrome. CRS is a supraphysiologic immune response driven by IL-6, most commonly following immune therapy (e.g., CAR T-cells), with mandatory fever at onset and possible hypotension, hypoxaemia and organ dysfunction, but does not require cytopaenias, hyperferritinaemia or haemophagocytosis. Although there are some common features, the pathogenesis, cytokine profile and treatment differ, (tocilizumab for CRS). HLH and CRS can overlap, especially in the context of CAR T-cell therapy, where HLH-like manifestations may be considered a variant or severe form of CRS (sometimes termed CARHLH) 26."
"Secondary (nonmendelian) HLH is more common in older children and adults, with an overall incidence of all forms of HLH estimated at 4.2 per 1 million population per annum in England. Typical triggers are infections such as Epstein-Barr virus, lymphomas and other malignancies, or autoimmune diseases such as systemic juvenile idiopathic arthritis and adult-onset Still disease 21."
"secondary (acquired), more common in adults, often triggered by infections, malignancies or autoimmune diseases."
"The impaired cytotoxic function of natural killer (NK) cells and T lymphocytes fails to eliminate antigen-presenting cells leading to persistent activation of macrophages and T cells. The resulting cytokine storm manifests with capillary leak, coagulopathy and direct injury to liver, bone marrow, CNS, and/or lungs, presenting as fever, cytopaenias, organomegaly and multiorgan failure."
"The impaired cytotoxic function of natural killer (NK) cells and T lymphocytes fails to eliminate antigen-presenting cells leading to persistent activation of macrophages and T cells. The resulting cytokine storm manifests with capillary leak, coagulopathy and direct injury to liver, bone marrow, CNS, and/or lungs, presenting as fever, cytopaenias, organomegaly and multiorgan failure."
"In secondary HLH, glucocorticoids +/- IV immune globulin and anakinra (IL-1 inhibitor) may be sufficient. In severe, nonresponsive or progressive secondary HLH with CNS involvement weekly etoposide is recommended. Ciclosporin is less commonly used in adults except in macrophage activation syndrome (MAS-HLH). Novel agents such as emapalumab (anti–IFN-γ), ruxolitinib (JAK inhibitor) and alemtuzumab (anti-CD52) can be used for refractory or relapsed HLH, with good reported survival rates for emapalumab and alemtuzumab. Anakinra crosses the blood-brain barrier and can be used for CNS involvement 21."
"The impaired cytotoxic function of natural killer (NK) cells and T lymphocytes fails to eliminate antigen-presenting cells leading to persistent activation of macrophages and T cells. The resulting cytokine storm manifests with capillary leak, coagulopathy and direct injury to liver, bone marrow, CNS, and/or lungs, presenting as fever, cytopaenias, organomegaly and multiorgan failure."
"viral (most common), including EBV 2,3, HIV, HHV-8, CMV, COVID-19"
"lymphoid (lymphomas and leukaemias; most common)"
"systemic juvenile idiopathic arthritis (formerly Still disease; most common)"