Sebastian F N Bode1, Christian Bogdan2, Karin Beutel3, Wolfgang Behnisch4, Jeanette Greiner5, Stephan Henning6, Norbert Jorch7, Martin Jankofsky8, Marcus Jakob9, Irene Schmid10, Norbert Veelken11, Thomas Vraetz1, Gritta Janka12, Stephan Ehl1, Kai Lehmberg13. 1. Center of Chronic Immunodeficiency, University Medical Center, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany. 2. Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany. 3. Department of Pediatric Hematology and Oncology, University Hospital, Münster, Germany. 4. Department of Pediatric Hematology and Oncology, University Hospital, Heidelberg, Germany. 5. Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland. 6. Department of Pediatrics, Charité, Berlin, Germany. 7. Department of Pediatrics, Evangelisches Krankenhaus, Bielefeld, Germany. 8. Department of Pediatric Gastroenterology and Hepatology, University Medical Center, Hamburg, Germany; Department of Pediatric Gastroenterology and Hepatology, University Hospital Bonn, Germany. 9. Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany. 10. Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Germany. 11. Department of Pediatrics, Asklepios Klinik Nord, Hamburg, Germany. 12. Department of Pediatric Hematology and Oncology, University Hospital Medical Center, Hamburg, Germany. 13. Department of Pediatric Hematology and Oncology, University Hospital Medical Center, Hamburg, Germany. Electronic address: k.lehmberg@uke.de.
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.
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.