Hemophagocytic lymphohistiocytosis in imported pediatric visceral leishmaniasis in a nonendemic area

J Pediatr. 2014 Jul;165(1):147-153.e1. doi: 10.1016/j.jpeds.2014.03.047. Epub 2014 May 3.

Abstract

Objectives: 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).

Study design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / therapeutic use
  • Antibodies, Protozoan / blood
  • Antiprotozoal Agents / therapeutic use
  • Autoantibodies / blood
  • Bone Marrow / pathology
  • Child
  • Child, Preschool
  • DNA, Protozoan / analysis
  • Female
  • Humans
  • Infant
  • Leishmania donovani / genetics
  • Leishmania donovani / immunology
  • Leishmania donovani / isolation & purification*
  • Leishmaniasis, Visceral / complications*
  • Leishmaniasis, Visceral / diagnosis
  • Leishmaniasis, Visceral / drug therapy
  • Lymphohistiocytosis, Hemophagocytic / diagnosis
  • Lymphohistiocytosis, Hemophagocytic / drug therapy
  • Lymphohistiocytosis, Hemophagocytic / etiology*
  • Male
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antibodies, Protozoan
  • Antiprotozoal Agents
  • Autoantibodies
  • DNA, Protozoan
  • liposomal amphotericin B
  • Amphotericin B