Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society.

H EMOPHAGOCYTIC lymphohistiocytosis (HLH) is an important differential diagnosis in infants with prolonged fever and hepatosplenomegaly. This disorder is often rapidly fatal, but successful therapy has recently been described. The child with HLH typically also develops anemia and thrombocytopenia as well as marked hypertriglyceridemia. Cerebral symptoms may complicate the course. The pathophysiology is thought to be mediated through a defect in the immunomodulation resulting in an unrestricted release of inflammatory cytokines. Histiocytic nonmalignant syndromes in children can be grouped in Langerhans’ cell histiocytosis (LCH) (previously called Histiocytosis X) and histiocytoses of mononuclear phagocytes of which HLH is by far the most common.’ HLH embraces the frequently indistinguishable conditions familial hemophagocytic lymphohistiocytosis (FHL)* and virus-associated hemophagocytic syndromes.3 We present diagnostic criteria for HLH. The diagnosis is frequently not established while the patient is alive, which reflects the difficulties in making the diagnosis.4 Recent therapeutic advances in chemotherapy and bone marrow transplantation have emphasized the need for diagnostic tools and of well established diagnostic criteria.5,6 Uniform nomenclature and diagnostic criteria are also desirable and recommended for research purposes and for use in publications. To further facilitate making the diagnosis of this frequently misunderstood disorder, a general picture of the disease is also presented that includes the clinical, laboratory, and histological findings. All of the histiocytoses syndromes are considered to be reactive except those in the category malignant histiocytic disorders.7 In HLH the predominant histiocyte is the normal monocyte/ macrophage, ie, of the phagocytic cell type, frequently apparent in a mixed lymphohistiocytic infiltrate, in contrast to LCH where the main cell has the cytologic features of the Langerhans’ cell8 Differentiation between these groups of histio-