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.
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Henter JI, Horne A, Arico M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.PubMedCrossRefGoogle Scholar
Gaffey MJ, Frierson Jr HF, Medeiros LJ, Weiss LM. The relationship of Epstein-Barr virus to infection-related (sporadic) and familial hemophagocytic syndrome and secondary (lymphoma-related) hemophagocytosis: an in situ hybridization study. Hum Pathol. 1993;24:657–67.PubMedCrossRefGoogle Scholar
Atteritano M, David A, Bagnato G, et al. Haemophagocytic syndrome in rheumatic patients. A systematic review. Eur Rev Med Pharmacol Sci. 2012;16:1414–24.PubMedGoogle Scholar
Fung KM, Chakrabarty JH, Kern WF, et al. Intravascular large B-cell lymphoma with hemophagocytic syndrome (Asian variant) in a Caucasian patient. Int J Clin Exp Pathol. 2012;5:448–54.PubMedGoogle Scholar
Wang SA. Lymphohistiocytic hemophagocytosis. In: Medeiros LJ, editor. Diagnostic pathology: lymph nodes and spleen with extranodal sites. 1st ed. Altona: Amirsys; 2011. p. 3-78–87.Google Scholar
Sumegi J, Barnes MG, Nestheide SV, et al. Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis. Blood. 2011;117:e151–60.PubMedCrossRefGoogle Scholar
Ramanan AV, Baildam EM. Macrophage activation syndrome is hemophagocytic lymphohistiocytosis—need for the right terminology. J Rheumatol. 2002;29:1105; author reply.PubMedGoogle Scholar
Grom AA. Macrophage activation syndrome and reactive hemophagocytic lymphohistiocytosis: the same entities? Curr Opin Rheumatol. 2003;15:587–90.PubMedCrossRefGoogle Scholar
Schaer DJ, Schleiffenbaum B, Kurrer M, et al. Soluble hemoglobin-haptoglobin scavenger receptor CD163 as a lineage-specific marker in the reactive hemophagocytic syndrome. Eur J Haematol. 2005;74:6–10.PubMedCrossRefGoogle Scholar
Bode SF, Lehmberg K, Maul-Pavicic A, et al. Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocytosis. Arthritis Res Ther. 2012;14:213.PubMedCrossRefGoogle Scholar
Kleynberg RL, Schiller GJ. Secondary hemophagocytic lymphohistiocytosis in adults: an update on diagnosis and therapy. Clin Adv Hematol Oncol. 2012;10:726–32.PubMedGoogle Scholar
Milone MC, Tsai DE, Hodinka RL, et al. Treatment of primary Epstein-Barr virus infection in patients with X-linked lymphoproliferative disease using B-cell-directed therapy. Blood. 2005;105:994–6.PubMedCrossRefGoogle Scholar