儿童内脏利什曼病相关性噬血细胞性淋巴组织细胞增生症四例临床分析

Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis：report of four childhood cases

目的总结分析4例内脏利什曼病（VL）相关性噬血细胞性淋巴组织细胞增生症（HLH）患儿的临床资料，提高继发性HLH诊治水平。方法回顾性总结两家医院近期诊断的4例VL—HLH患儿的临床特征及诊治经过。结果本组4例患儿男3例、女1例，均来自于明确VL疫区或具有明确疫区生活史。以长期发热、肝脾肿大、外周血全血细胞减少为显著临床表现，结合相关实验室检查均符合HLH诊断标准。2例患儿接受HLH化疗并有效，表现为体温恢复正常和脾脏回缩等，但持续贫血为突出临床特征。病程早期骨髓检查和（或）rk39免疫试纸条法检测均无阳性发现，是导致漏诊和误诊的重要原因。结论VL是导致继发性HLH的1种少见基础疾病。对来自VL疫区或具有疫区生活史的患儿，HLH鉴别诊断时应充分考虑VL可能性，需反复骨髓检查和（或）免疫学检查，早期诊断，及时予VL特异性治疗。

Objective The clinical features of four cases of visceral leishmaniasis （VL） -associated hemophagoeytic lymphohistiocytosis （VL-HLH） were retrospectively analyzed for the purpose of helping the diagnosis of secondary HLH. Method Clinical data of three childhood cases of VL-HLH documented in our hospital and one case diagnosed in the Capital Institute of Pediatrics was reviewed retrospectively, with particular emphasis on peculiar clinical manifestations and on clues to the diagnosis of this relatively rare disease entity. Result Three children were from endemic areas of VL, and the other one had lived in endemic area for one year, which was revealed by detailed history-taking. Clinically, VL-HLH is characterized by persistent fever, hepatosplenomegaly and pancytopenia, which is similar to those of HLH, and is one of the important reasons of delayed diagnosis or misdiagnosis. Based on the HLH-2004 protocol, all the four cases met the diagnostic criteria of HLH. In addition, bone marrow aspirate and immunologic detection of VL-specific antibody via rk39 dipstick test during the early disease course of VL-HLH yielded negative results. Two cases who received HLH-targeted therapy responded reasonably well, with rapid temperature normalization and spleen retraction. Nevertheless, Hb remained lower than normal, which we believed to be related to persistent red cell destruction by the invading parasite Leishmania donovani. Conclusion VL, a parasitic disease caused by Leishmania donovani, which is currently endemic just in 6 provinces in China, shares similar clinical picture of HLH and is an easily ignored underlying cause of secondary HLH. We suggest that VL should be in the list of differential diagnosis for any patients with HLH who lives in or has a definite travel history to endemic areas. Repeated bone marrow studies are highly warranted to make a definite diagnosis of VL, because bone marrow aspirate or rk39 dipstick test during early disease course might yield negative results. Although VL-HLH responds quite well to HLH-tailored chemotherapy, specific therapy against VL must be given to prevent disease recurrence, and HLH-targeted chemotheraov might be discontinued to orevent chemotherapy-related toxieities.