Last update:
31-Mar-2011

The histiocytic syndromes comprise a number of related diseases, of which the better known are Langerhans cell histiocytosis (LCH) and hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease with protean manifestations. It can be primary, the congenital form, usually with familial occurrence, or secondary, related to infections, autoimmune diseases and malignancies. Primary HLH is usually transmitted as a recessive autosomal trait and presents clinically within the first year of life, while secondary HLH is sporadic and is seen in older patients and throughout life. HLH represents non clonal cell activation, being an immune dysregulation process, with reduced suppression of the immune response and deficiency in initiating apoptosis of activated cells. Clinical manifestations include anorexia, fever, pallor, jaundice, rash, splenomegaly, hepatomegaly, lymphadenopathy, edema, reduced physical growth, petechiae/ bleeding and symptoms from central nervous system (CNS) or lung involvement. In contrast to LCH, HLH has no specific pathognomonic findings. Diagnosis is based on a combination of clinical and laboratory criteria, and latterly with the detection of mutations of the PRF1, STX11 and UNC13D genes. Frequently, not all of the diagnostic criteria of HLH are present at onset, but they emerge later in the course of the disease. Untreated HLH has a high mortality rate and initiation of appropriate treatment is recommended even in the case of a not fully confirmed diagnosis of HLH, together with removal of the triggering factor (e.g., malignancy). Laboratory evaluation of the involved genes is mandatory. Treatment consists of chemotherapy/immunosuppression; for primary non-responsive and resistant HLH stem cell transplantation is recommended.

Key words: Child, Cytopenia, Hemophagocytic lymphohistiocytosis, Pathogenesis, Therapy.