title: Hemophagocytic lymphohistiocytosis in imported pediatric visceral leishmaniasis in a nonendemic area.
abstract: OBJECTIVE
  To describe characteristics of visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis (HLH) with focus on diagnostic clues and pitfalls, including the frequency of central nervous system (CNS) involvement, and to determine the efficacy of liposomal amphotericin B (L-AmB).
  
  
  METHODS
  We retrospectively analyzed clinical and laboratory features, diagnostic procedures, and treatment of 13 patients with HLH with imported visceral leishmaniasis, reported to the German HLH reference center (1999-2012).
  
  
  RESULTS
  The spectrum of presentations was indistinguishable from patients with hereditary HLH or with acquired HLH because of infections with other pathogens. In 8 patients, disease onset occurred before the age of 2 years, coinciding with the typical age of manifestation of primary HLH. Two patients had mild nonspecific CNS findings. Misleading antiviral IgM (n = 6) and autoantibodies (n = 2) led to inaccurate interpretation of the etiology of HLH, sometimes with inappropriate therapeutic consequences. False negative results for Leishmania were obtained by initial bone marrow microscopy in 6/13, serology in 1/12, bone marrow culture in 2/5, and polymerase chain reaction of peripheral blood in 1/3 patients, and all bone marrow samples tested were Leishmania-positive by polymerase chain reaction (n = 7). L-AmB was administered to 12 patients, 5 of whom had no prior HLH-directed immunosuppressive therapy; sodium stibogluconate was administered to 1 patient. Persistent remission was achieved in 11 cases. Two patients required repeated or prolonged L-AmB therapy.
  
  
  CONCLUSIONS
  Awareness of diagnostic pitfalls may save patients from unnecessary toxic treatment. CNS involvement is rare. L-AmB shows efficacy in visceral leishmaniasis-associated HLH.
authors.affiliation: Center of Chronic Immunodeficiency, University Medical Center, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Sebastian F N
authors.initials: SF
authors.lastname: Bode
authors.affiliation: Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bogdan
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital, Münster, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Beutel
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital, Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Behnisch
authors.affiliation: Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Greiner
authors.affiliation: Department of Pediatrics, Charité, Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Henning
authors.affiliation: Department of Pediatrics, Evangelisches Krankenhaus, Bielefeld, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Jorch
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, University Medical Center, Hamburg, Germany; Department of Pediatric Gastroenterology and Hepatology, University Hospital Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jankofsky
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Jakob
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schmid
authors.affiliation: Department of Pediatrics, Asklepios Klinik Nord, Hamburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Veelken
authors.affiliation: Center of Chronic Immunodeficiency, University Medical Center, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vraetz
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Medical Center, Hamburg, Germany.
authors.forename: Gritta
authors.initials: G
authors.lastname: Janka
authors.affiliation: Center of Chronic Immunodeficiency, University Medical Center, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Medical Center, Hamburg, Germany. Electronic address: k.lehmberg@uke.de.
authors.forename: Kai
authors.initials: K
authors.lastname: Lehmberg
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use; D000913:Antibodies, Protozoan / Q000097:blood; D000981:Antiprotozoal Agents / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood; D001853:Bone Marrow / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D007898:Leishmaniasis, Visceral / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000913:Antibodies, Protozoan; D000981:Antiprotozoal Agents; D001323:Autoantibodies; D016054:DNA, Protozoan; C068538:liposomal amphotericin B; D000666:Amphotericin B