Hemophagocytic lymphohistiocytosis

In hematology, hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes.

There are inherited (primary HLH) and acquired (secondary HLH) forms. The inherited form is due to genetic mutations and usually presents in infants and children, with a median age of onset of 3-6 months. Familial HLH is an autosomal recessive disease, hence each sibling of a child with familial HLH has a twenty-five–percent chance of developing the disease, a fifty-percent chance of carrying the defective gene (which is very rarely associated with any risk of disease), and a twenty-five–percent chance of not being affected and not carrying the gene defect. Genes that are commonly mutated in those with primary HLH lead to defective lymphocyte (natural killer cell and cytotoxic T-cell) function. The mutated genes are PRF1 (perforin-1), UNC13D, STX11, and STXBP2. Secondary HLH usually presents in adulthood (usually in people with genetic changes predisposing them to the disease) after exposure to a trigger. Common triggers leading to secondary HLH include infections, cancer, or autoimmune diseases. The incidence of all forms of HLH was estimated to be 4.2 cases per 1 million people in a population based study from England in 2018, but the true incidence is not known. The incidence of HLH (especially secondary HLH) is thought to be underestimated as the clinical signs and symptoms are very similar to sepsis.