Genetic disorder associated with failure to establish
an effective immune response to infection. Caused by normal but overactive
histiocytes. Clinical features include fever, hepatomegaly, cytopenia, and
neurologic abnormalities. Lethal if not treated.
1:50,000 live births. Two forms are described: (1)
primary or familial hemophagocytic lymphohistiocytosis (FHL), a
heterogeneous autosomal recessive disorder, and (2) secondary or acquired
HLH (related to systemic infection, immunodeficiency, or underlying
Heterogeneous autosomal recessive inheritance
Proliferation of activated macrophages and
histiocytes, which phagocytose other cells (red and white blood cells,
platelets), leading to the clinical symptoms. Spleen, lymph nodes, bone
marrow, liver, and central nervous system are preferential sites of
involvement. The role of perforin and NK cells has been evocated in familial
Evocated by the association of fever,
hepatosplenomegaly, cytopenia, hypofibrinogenemia, hypertriglyceridemia, and
hemophagocytosis. Rash may occur. Frequently affects infants from birth to
Patients can present with coagulopathy with an
increased partial thromboplastin time. Jaundice is often present as a
consequence of hyperbilirubinemia. Lymphadenopathy, malaise, anorexia with
weight loss, and failure to thrive can occur. Neurologic abnormalities
including seizures have been observed. The skin can be involved in a variety
of ways; clinically best characterized as erythroderma, generalized purpuric
macules and papules, or morbilliform eruptions.
Preoperative evaluation must concern
localization of infection and identification of the causal agent. Preoperative
laboratory investigations should include full blood count, liver function
(bilirubinemia, albuminemia, aspartate aminotransferase, alanine
aminotransferase), and triglyceride.
Strict asepsis is needed. Coagulopathy
and thrombopenia should be corrected if necessary and may require more
transfusions than expected. Regional anesthesia is not contraindicated but
should be avoided in case of infection or severe thrombopenia.
Repeated nitrous oxide administration
should be avoided. Hepatotoxic drugs or drugs with hepatic metabolism should
be avoided. Prophylactic antibiotics may consider immunologic status.
Arico M, Allen M, Brusa S: Haemophagocytic lymphohistiocytosis: Proposal
of a diagnostic algorithm based on perforin expression. Br J Haematol
Dufourcq-Lagelouse R, Pastural E, Barrat FJ, et al: Genetic basis of
hemophagocytic lymphohistiocytosis syndrome [review]. Int J Mol Med