A hemophagocytic syndrome is a systemic, non-neoplastic acute disease presenting with cytopenias and organ infiltration by histiocytes, frequently with hemophagocytosis, and is usually fatal if left untreated.
The term hemophagocytic lymphohistiocytosis (HLH) is used to include primary or familial and secondary causes of hemophagocytic syndromes. The overall incidence is approximately 1.2 in 1 million individuals per year. Primary HLH occurs due to various gene abnormalities affecting apoptosis and usually manifests during infancy or early childhood, and rarely in adulthood. Gene mutations affect cytotoxic cell function and are inherited as autosomal recessive.
Secondary HLH, which is the focus of this chapter, most often affects older children and adults, but also can affect young children. Underlying causes are infections, malignancy, metabolic, or rheumatologic conditions, and immunodeficiency. Associated infections that trigger the syndrome include Epstein-Barr virus (EBV), herpes simplex virus, human immunodeficiency virus (HIV), and cytomegalovirus. Rheumatologic diseases include rheumatoid arthritis, systemic lupus erythematosus, Still disease, and Kawasaki syndrome. Malignancies include acute leukemia and myelodysplastic syndromes, T/NK-cell lymphoma/leukemia, B-cell lineage leukemias, and lymphomas such as intravascular B-cell lymphoma. Immunodeficiency states include infection with human immunodeficiency virus, iatrogenic, or after organ transplantation.
Arthritis Lymphoma Leukemia Germinal Interferon
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