HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH Sample Clauses

HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH. HLH is a syndrome characterized by a severe impairment or absence of cytotoxic function by NK and CD8+ T cells with striking activation of the immune system. HLH comprises primary (genetic/familial) HLH and secondary HLH, both clinically described by a dysregulation of the immune system leading to a profound hypercytokinaemia with deleterious consequences on various tissues and organs7. Primary HLH is a heterogeneous autosomal recessive disorder found to be more prevalent with parental consanguinity. Primary HLH is mostly seen in infancy and early childhood with an estimated prevalence in Europe of 1/50,000 live births8. The disease is invariably fatal with a median survival of less than 2 months after diagnosis, if untreated9;10. The impaired cytotoxic function present in HLH leads to hypercytokinemia and heamophagocytosis. These in turn cause all the typical symptoms of HLH11-13: • Prolonged fever • Splenomegaly • Cytopenia • Hyperferritinemia • Hypertriglyceridemia • Hypofibrinogenemia • Lymphohistiocytic infiltrate, bone marrow hypoplasia, meningeal infiltrate. Among the cytokines dramatically elevated in HLH patients are: IFNγ, interleukin (IL)-6, IL-10, tumour necrosis factor (TNF) α, IL-8, macrophage colony stimulating factor (MCSF) and granulocyte- macrophage colony-stimulating factor (GM-CSF). HLH can also occur during the course of an infection, a rheumatic or a neoplastic disease and in this case it is referred to as secondary HLH. Secondary HLH presents with the same signs and symptoms of primary forms and can be equally severe. The current treatment of secondary HLH is aimed at addressing the cause of the underlying disease. This is certainly the case for HLH caused by infections such as Leishmaniasis. Of note, the presence of certain infections, in particular viral infections such as those due to CMV or EBV, is very often the trigger for the manifestation of primary forms of HLH. This observation is also supported by the evidence that in animal models of primary HLH14-17, infection with lymphocytic choriomeningitis virus (LCMV) is required for the development of the disease. When HLH manifests during a neoplastic disease, in particular an hematological malignancy, often the severity of the patient condition requires the immediate treatment of HLH, prior to specifically addressing the underlying disease. The presence of signs and symptoms of HLH in patients suffering from a rheumatic disease, such as systemic Juvenile Idiopathic Arthritis (sJI...