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At a glance

Genetic disorder associated with failure to establish an effective immune response to infection. Individual affected with the disease shows clinical symptoms in the first months or years of life. Symptoms include severe infection with fever, hepato- and splenomegaly, cytopenia, and neurological abnormalities. Neurological features include irritability, fatigue, myotonia, seizures, neck stiffness, mental status changes, ataxia, blindness, paralysis, and/or coma. It is caused by normal but overactive histiocytes. Clinical features include fever, hepatomegaly, cytopenia, and neurologic abnormalities. It is a life-threatening medical condition when not treated. Two types have been described, either primary or secondary form. The primary, or “familial,” HLH condition is inherited.

Synonyms

HPLH 1; HLH 1; Familial Hemophagocytic Lymphohistiocytosis Syndrome; Familial Erythrophagocytic Lymphohistiocytosis Syndrome; Familial Histiocytic Reticulosis Syndrome.

Incidence

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 malignancy).

Genetic inheritance

Heterogeneous autosomal recessive inheritance for FLH. HLH can also be acquired. There are five subtypes of inherited HLH that are designated as familial HLH, and Types 1-5. Each subtype is caused by a mutation in a different gene. The genetic cause of Type 1 is currently unknown. Types 2-5 are caused by mutations in the PRF1 gene, the UNC13D gene, the STX11 gene, and the STXBP2 gene, respectively.

Pathophysiology

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 forms.

Diagnosis

Evocated by the association of fever, hepatosplenomegaly, cytopenia, hypofibrinogenemia, hypertriglyceridemia, and hemophagocytosis. Rash may occur. Frequently affects infants from birth to 18 months.

Clinical aspects

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.

Precautions before anesthesia

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.

Anesthetic considerations

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.

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