Recent developments in the management of haemophagocytic lymphohistiocytosis.

Over the past two decades, the underlying pathophysiology of haemophagocytic lymphohistiocytosis (HLH) (synonyms: haemophagocytic syndrome, macrophage activation syndrome) has been well recognised. Cytokine storm plays a major role, which derives from an inappropriate immune reaction caused by proliferating and activated T-cell or natural killer (NK) cells associated with macrophage activation and inadequate apoptosis of immunogenic cells. Many biological parameters reflecting activity of disease or response to treatment have been identified, in particular, serum ferritin has been confirmed to be one of the markers for HLH. The common types of HLH consist of non-hereditary (acquired) infection-associated disease such as Epstein-Barr virus (EBV)-haemophagocytic lymphohistiocytosis (HLH) and hereditary (familial) disease such as FHL, in which, at the molecular level, dysfunctional perforin was clarified. Regarding the therapeutic strategies, prompt differential diagnosis of underlying disease is essential and choice of treatment should be based on the risk (low or high) of prognosis, where either cyclosporin A, steroids or iv. immunoglobulin (IVIG) may be indicated as initial treatment for low-risk patients, with etoposide-containing regimens for high-risk patients. Significant improvement of prognosis has been obtained by incorporating intensive supportive care at the disease onset and prompt introduction of immunosuppressants to control cytokine storm. Subsequent immunochemotherapy and haemopoietic stem cell transplantation have contributed significantly to further improve survival of hereditary and refractory HLH patients.