Bode Sebastian F N, Bogdan Christian, Beutel Karin, Behnisch Wolfgang, Greiner Jeanette, Henning Stephan, Jorch Norbert, Jankofsky Martin, Jakob Marcus, Schmid Irene, Veelken Norbert, Vraetz Thomas, Janka Gritta, Ehl Stephan, Lehmberg Kai
Center of Chronic Immunodeficiency, University Medical Center, Freiburg, Germany; Center for Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany.
Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Universitätsklinikum Erlangen, Erlangen, Germany.
J Pediatr. 2014 Jul;165(1):147-153.e1. doi: 10.1016/j.jpeds.2014.03.047. Epub 2014 May 3.
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).
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).
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.
Awareness of diagnostic pitfalls may save patients from unnecessary toxic treatment. CNS involvement is rare. L-AmB shows efficacy in visceral leishmaniasis-associated HLH.
描述内脏利什曼病相关噬血细胞性淋巴组织细胞增生症（HLH）的特征，重点关注诊断线索和陷阱，包括中枢神经系统（CNS）受累的频率，并确定脂质体两性霉素B（L-AmB）的疗效。
我们回顾性分析了1999年至2012年报告给德国HLH参考中心的13例输入性内脏利什曼病合并HLH患者的临床和实验室特征、诊断程序及治疗情况。
其临床表现谱与遗传性HLH患者或因其他病原体感染所致获得性HLH患者难以区分。8例患者发病年龄在2岁之前，与原发性HLH的典型发病年龄相符。2例患者有轻度非特异性CNS表现。误导性的抗病毒IgM（n = 6）和自身抗体（n = 2）导致对HLH病因的错误解读，有时会产生不恰当的治疗后果。13例患者中6例最初骨髓显微镜检查、12例中1例血清学检查、5例中2例骨髓培养以及3例中1例外周血聚合酶链反应检测利什曼原虫结果为假阴性，而所有检测的骨髓样本经聚合酶链反应均为利什曼原虫阳性（n = 7）。12例患者接受了L-AmB治疗，其中5例之前未接受过针对HLH的免疫抑制治疗；1例患者接受了葡萄糖酸锑钠治疗。11例患者实现了持续缓解。2例患者需要重复或延长L-AmB治疗。
认识到诊断陷阱可使患者避免不必要的毒性治疗。CNS受累罕见。L-AmB在内脏利什曼病相关HLH中显示出疗效。
