Hemophagocytic lymphohistiocytosis (HLH), is an uncommon hematologic disorder. It is a life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages characterised by proliferation of morphologically benign lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. It is classified as one of the cytokine storm syndromes.
HLH clinically manifests with fever, hepatosplenomegaly, lymphadenopathy, jaundice and a rash.
The current diagnostic criteria for HLH are
1. A molecular diagnosis consistent with HLH. These include the identification of pathologic mutations of PRF1, UNC13D, or STX11.
2. Fulfillment of five out of the eight criteria below:
- Fever (>100.4 degrees F)
- Cytopenias affecting at least two of three lineages in the peripheral blood:
- Haemoglobin <9 g/100 ml (in infants <4 weeks: haemoglobin <10 g/100 ml)
- Platelets <100×109/L
- Neutrophils <1×109/L
- Hypertriglyceridemia (fasting, greater than or equal to 265 mg/100 ml) and/or hypofibrinogenemia (≤ 150 mg/100 ml)
- Ferritin ≥ 500 ng/ml
- Haemophagocytosis in the bone marrow, spleen or lymph nodes
- Low or absent natural killer cell activity
- Soluble CD25 (soluble IL-2 receptor) >2400 U/ml (or per local reference laboratory)
In addition, in the case of familial HLH, no evidence of malignancy should be apparent.
The prognosis is guarded with an overall mortality of 50%.
Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with CNS involvement.
In secondary cases treatment of the cause, where possible, is indicated. Additionally treatment for HLH itself is usually required.
While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.