Hemophagocytic Lymphohistiocytosis in Imported Pediatric Visceral Leishmaniasis in a Nonendemic Area

• Published in: The Journal of pediatrics Vol. 165; no. 1; pp. 147 - 153.e1
• Main Authors: Bode, Sebastian F.N., MD, Bogdan, Christian, MD, Beutel, Karin, MD, Behnisch, Wolfgang, MD, Greiner, Jeanette, MD, Henning, Stephan, MD, Jorch, Norbert, MD, Jankofsky, Martin, MD, Jakob, Marcus, MD, Schmid, Irene, MD, Veelken, Norbert, MD, PhD, Vraetz, Thomas, MD, Janka, Gritta, MD, Ehl, Stephan, MD, Lehmberg, Kai, MD
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.07.2014
• Subjects: 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; Pediatrics; Polymerase Chain Reaction; Retrospective Studies; Treatment Outcome; HLH; Central nervous system; CNS; Cerebrospinal fluid; Immunofluorescence test; Polymerase chain reaction; Hemophagocytic lymphohistiocytosis; L-AmB; Liposomal amphotericin B; Natural killer; IFT; CSF; EBV; Epstein-Barr virus; NK; PCR
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2014.03.047

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.