title: Secondary hemophagocytic lymphohistiocytosis in zoonoses. A systematic review.
abstract: BACKGROUND
  Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that is often fatal despite treatment. It is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of histiocytes with uncontrolled hemophagocytosis and cytokines overproduction. The syndrome is characterized by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinemia. HLH can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections.
  
  
  OBJECTIVE
  To focus on secondary HLH complicating zoonotic diseases.
  
  
  METHODS
  PubMed search of human cases of HLH occurring during zoonotic diseases was performed combining the terms (haemophagocytic or haemophagocytosis or hemophagocytosis or hemophagocytic or erythrophagocytosis or macrophage activation syndrome) with each one of the etiological agents of zoonoses.
  
  
  RESULTS
  Among bacterial diseases, most papers reported cases occurring during brucellosis, rickettsial diseases and Q fever. Regarding viral diseases, most of the cases were reported in patients with avian influenza A subtype H5N1. Among the protozoan zoonoses, most of the cases were reported in patients with visceral leishmaniasis. Regarding zoonotic fungi, most of the cases were reported in AIDS patient with histoplasmosis. No cases of secondary HLH were reported in patient with zoonotic helminthes.
  
  
  CONCLUSIONS
  Zoonotic diseases are an important cause of HLH. Secondary HLH can delay the correct diagnosis of the zoonotic disease, and can contribute to an adverse outcome.
authors.affiliation: Department of Human Pathology, Policlinico G. Martino, Messina, Italy. acascio@unime.it
authors.forename: A
authors.initials: A
authors.lastname: Cascio
authors.forename: L M
authors.initials: LM
authors.lastname: Pernice
authors.forename: G
authors.initials: G
authors.lastname: Barberi
authors.forename: D
authors.initials: D
authors.lastname: Delfino
authors.forename: C
authors.initials: C
authors.lastname: Biondo
authors.forename: C
authors.initials: C
authors.lastname: Beninati
authors.forename: G
authors.initials: G
authors.lastname: Mancuso
authors.forename: A J
authors.initials: AJ
authors.lastname: Rodriguez-Morales
authors.forename: C
authors.initials: C
authors.lastname: Iaria
mesh_terms: D000818:Animals; D015897:Comorbidity; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology* / Q000628:therapy; D015047:Zoonoses / Q000635:transmission*