Hemophagocytic lymphohistiocytosis

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with severe acute course leading to fatal outcome without adequate treatment. Due to its rapidly developing symptoms requiring timely treatment, it is very important that all pediatricians are well-educated about the clinical findings and diagnostic criteria of HLH. Its clinical presentation is characterized by fever, hepatosplenomegaly, less frequently rash and/or adenopathy. Laboratory analysis frequently shows bi- / pancytopenia, hyperferritinemia, hypertriglyceridemia and hypofibrinogenemia. Hemophagocytosis, one of the defining phenomena of the disease, is displayed by activated macrophages. The disease is caused by multisystem inflammation initiated by prolonged and intensive activation of antigen presenting cells and CD8+ T lymphocytes, as well as incompetence of cytotoxic T cells and natural killer cells to eliminate the pathogens. So far, a large number of gene defects leading to primary HLH have been elucidated. However, a great many patients have no obvious genetic cause and the disease may also develop as a secondary complication of infection, autoimmunity or malignancy. Adequate treatment should be started as soon as diagnostic criteria are fulfilled, without waiting for genetic diagnosis, since the secondary HLH carries a high mortality risk even in adults and in older children too. Intensive immunosuppressive treatment leads to clinical amelioration, however allogeneic hematopoietic stem cell transplantation is the only curative treatment for primary HLH. Therapy should be provided by an experienced medical team with skills for diagnosis and treatment of HLH.