肝炎相关性再生障碍性贫血合并噬血细胞综合征1例并文献复习

doi:10.7499/j.issn.1008-8830.2409118

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摘要患儿，男，4岁，因皮疹、间断腹痛3 d，发现血常规结果异常半天入院。初期以急性黄疸型肝炎和全血细胞减少为主要表现。患儿病情进展迅速，入院后出现反复发热，皮肤及巩膜黄染加重，肝脾大且进行性加重，肝功能损伤及骨髓衰竭程度持续恶化，细胞因子水平持续上升，排除了感染、自身免疫性疾病、肿瘤、遗传代谢性疾病及中毒等疾病，该患儿诊断为肝炎相关性再生障碍性贫血（hepatitis-associated aplastic anemia, HAAA）合并噬血细胞综合征（hemophagocytic lymphohistiocytosis, HLH）。经过糖皮质激素、血浆置换、静脉注射免疫球蛋白及护肝治疗，患儿症状得到部分缓解。再生障碍性贫血合并HLH较为少见，尤其是HAAA合并HLH，更为罕见、隐匿及凶险。该文报道1例HAAA合并HLH的病例，并对文献已报道的病例资料进行归纳总结，为该病的早期诊断、治疗提供参考。

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关键词 ：肝炎相关性再生障碍性贫血, 噬血细胞综合征, 儿童

Abstract：A 4-year-old boy was admitted to the hospital with a 3-day history of rash and intermittent abdominal pain, during which abnormal results from routine blood tests were discovered. Initially, he presented with acute jaundice hepatitis and pancytopenia. The patient's condition progressed rapidly, with recurrent fever, worsening jaundice of the skin and sclera, and progressively worsening hepatosplenomegaly. Liver function impairment and bone marrow failure continued to deteriorate, while cytokine levels continued to rise. After excluding infections, autoimmune diseases, tumors, genetic metabolic disorders, and toxicities, the patient was diagnosed with hepatitis-associated aplastic anemia (HAAA) complicated by hemophagocytic lymphohistiocytosis (HLH). Following treatment with corticosteroids, plasma exchange, intravenous immunoglobulin, and liver protection therapy, the patient's symptoms partially alleviated. Aplastic anemia complicated by HLH is relatively uncommon, and HAAA complicated by HLH is even rarer, often presenting insidiously and severely. This paper presents a case of HAAA complicated by HLH and summarizes previously reported cases in the literature, providing references for the early diagnosis and treatment of this condition.

Key words： Hepatitis-associated aplastic anemia Hemophagocytic lymphohistiocytosis Child

收稿日期: 2024-09-23

通讯作者: 罗森林，女，主治医师。Email：senlinluo@csu.edu.cn。 E-mail: senlinluo@csu.edu.cn

作者简介: 周鑫，女，硕士研究生；

引用本文:

周鑫,陈晓宇,文川等. 肝炎相关性再生障碍性贫血合并噬血细胞综合征1例并文献复习[J]. 中国当代儿科杂志, 2025, 27(4): 465-471.

ZHOU Xin,CHEN Xiao-Yu,WEN Chuan et al. A case of hepatitis-associated aplastic anemia complicated by hemophagocytic lymphohistiocytosis and literature review[J]. CJCP, 2025, 27(4): 465-471.

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http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2409118 或 http://www.zgddek.com/CN/Y2025/V27/I4/465

	1 韩迎弟, 王颖韶, 白洁. 噬血细胞性淋巴组织细胞增生症发病机制的研究现状[J]. 国际输血及血液学杂志, 2020, 43(3): 222-228. DOI: 10.3760/cma.j.cn511693-20191129-00186.
	2 国家卫生健康委办公厅. 儿童再生障碍性贫血诊疗规范（2019年版)[J]. 全科医学临床与教育, 2019, 17(11): 965-969. DOI: 10.13558/j.cnki.issn1672-3686.2019.011.002.
	Rauff B, Idrees M, Shah SA, et al. Hepatitis associated aplastic anemia: a review[J]. Virol J, 2011, 8: 87. PMID: 21352606. PMCID: PMC3052191. DOI: 10.1186/1743-422X-8-87.
	Gonzalez‐Casas R, Garcia‐Buey L, Jones EA, et al. Systematic review: hepatitis-associated aplastic anaemia:a syndrome associated with abnormal immunological function[J]. Aliment Pharmacol Ther, 2009, 30(5): 436-443. PMID: 19508613. DOI: 10.1111/j.1365-2036.2009.04060.x.
	Fu L, Zhang J, Wang R, et al. Clinical characteristics of hepatitis-associated aplastic anemia in children[J]. Ann Hematol, 2024, 103(2): 397-404. PMID: 38082101. DOI: 10.1007/s00277-023-05566-y.
	Hasegawa D, Kojima S, Tatsumi E, et al. Elevation of the serum Fas ligand in patients with hemophagocytic syndrome and Diamond-Blackfan anemia[J]. Blood, 1998, 91(8): 2793-2799. PMID: 9531589.
	Salem S, Langlais D, Lefebvre F, et al. Functional characterization of the human dendritic cell immunodeficiency associated with the IRF8K108E mutation[J]. Blood, 2014, 124(12): 1894-1904. PMID: 25122610. PMCID: PMC4168344. DOI: 10.1182/blood-2014-04-570879.
	Cohen JI. Primary immunodeficiencies associated with EBV disease[J]. Curr Top Microbiol Immunol, 2015, 390(Pt 1): 241-265. PMID: 26424649. PMCID: PMC6349415. DOI: 10.1007/978-3-319-22822-8_10.
	9 张利平, 李志刚, 王天有. 原发性噬血细胞性组织细胞增生症的遗传学研究进展[J]. 国际儿科学杂志, 2018, 45(7): 497-500. DOI: 10.3760/cma.j.issn.1673-4408.2018.07.001.
	Arduini A, Marasco E, Marucci G, et al. An unusual presentation of purine nucleoside phosphorylase deficiency mimicking systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome[J]. Pediatr Rheumatol Online J, 2019, 17(1): 25. PMID: 31118063. PMCID: PMC6532153. DOI: 10.1186/s12969-019-0328-3.
	Miller PG, Niroula A, Ceremsak JJ, et al. Identification of germline variants in adults with hemophagocytic lymphohistiocytosis[J]. Blood Adv, 2020, 4(5): 925-929. PMID: 32150605. PMCID: PMC7065469. DOI: 10.1182/bloodadvances.2019001272.
	Parisi C, Candela-Cantó S, Serrano M, et al. Life-threatening secondary hemophagocytic lymphohistiocytosis following vagal nerve stimulator infection in a child with CHD2 myoclonic encephalopathy: a case report[J]. Childs Nerv Syst, 2020, 36(11): 2851-2856. PMID: 32170405. DOI: 10.1007/s00381-020-04558-x.
	Forster M, Moran T, Beaven A, et al. Novel ZAP-70-related immunodeficiency presenting with Epstein-Barr virus lymphoproliferative disorder and hemophagocytic lymphohistiocytosis[J]. Case Reports Immunol, 2021, 2021: 6587323. PMID: 34239742. PMCID: PMC8238617. DOI: 10.1155/2021/6587323.
	Sharma M, Tyagi R, Loganathan SK, et al. Reticular dysgenesis exacerbated by hemophagocytic lymphohistiocytosis and the presence of unusual histiocyte-like cells in bone marrow[J]. Immunobiology, 2021, 226(6): 152143. PMID: 34598034. DOI: 10.1016/j.imbio.2021.152143.
	Picod A, Martino S, Cervera P, et al. Deregulated JAK3 mediates growth advantage and hemophagocytosis in extranodal nasal-type natural killer/T-cell lymphoma[J]. Haematologica, 2022, 107(9): 2218-2225. PMID: 35511669. PMCID: PMC9425324. DOI: 10.3324/haematol.2021.280349.
	Yan H, Mo Y, Liu S, et al. Case report: hemophagocytic lymphohistiocytosis in a child with primary immunodeficiency infected with Talaromyces marneffei[J]. Front Immunol, 2022, 13: 1038354. PMID: 36532052. PMCID: PMC9755863. DOI: 10.3389/fimmu.2022.1038354.
	Fratini ES, Migliavacca M, Barzaghi F, et al. Hemophagocytic inflammatory syndrome in ADA-SCID: report of two cases and literature review[J]. Front Immunol, 2023, 14: 1187959. PMID: 37435083. PMCID: PMC10331599. DOI: 10.3389/fimmu.2023.1187959.
	18 吴婷婷, 唐亮, 胡豫. 噬血细胞综合征的病因和诊断[J]. 临床血液学杂志, 2024, 37(9): 677-682. DOI: 10.13201/j.issn.1004-2806.2024.09.015.
	Cicalese MP, Gerosa J, Baronio M, et al. Circulating follicular helper and follicular regulatory T cells are severely compromised in human CD40 deficiency: a case report[J]. Front Immunol, 2018, 9: 1761. PMID: 30131802. PMCID: PMC6090258. DOI: 10.3389/fimmu.2018.01761.
	de Renty C, Ellis NA. Bloom's syndrome: why not premature aging?: a comparison of the BLM and WRN helicases[J]. Ageing Res Rev, 2017, 33: 36-51. PMID: 27238185. PMCID: PMC5124422. DOI: 10.1016/j.arr.2016.05.010.
	a?da? D, Sürücü N, Tan ?, et al. Autoinflammation in addition to combined immunodeficiency: SLC29A3 gene defect[J]. Mol Immunol, 2020, 121: 28-37. PMID: 32151906. DOI: 10.1016/j.molimm.2020.02.014.
	Salzer E, Santos-Valente E, Klaver S, et al. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ[J]. Blood, 2013, 121(16): 3112-3116. PMID: 23319571. PMCID: PMC3630826. DOI: 10.1182/blood-2012-10-460741.
	van de Geer A, Nieto-Patlán A, Kuhns DB, et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease[J]. J Clin Invest, 2018, 128(9): 3957-3975. PMID: 29969437. PMCID: PMC6118590. DOI: 10.1172/JCI97116.
	Knight SW, Heiss NS, Vulliamy TJ, et al. Unexplained aplastic anaemia, immunodeficiency, and cerebellar hypoplasia (Hoyeraal-Hreidarsson syndrome) due to mutations in the dyskeratosis congenita gene, DKC1[J]. Br J Haematol, 1999, 107(2): 335-339. PMID: 10583221. DOI: 10.1046/j.1365-2141.1999.01690.x.
	Wang H, Tu M, Fu R, et al. The clinical and immune characteristics of patients with hepatitis-associated aplastic anemia in China[J]. PLoS One, 2014, 9(5): e98142. PMID: 24845454. PMCID: PMC4028298. DOI: 10.1371/journal.pone.0098142.
	Camitta BM, Thomas ED, Nathan DG, et al. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality[J]. Blood, 1976, 48(1): 63-70. PMID: 779871.
	Bacigalupo A, Hows J, Gluckman E, et al. Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA working party[J]. Br J Haematol, 1988, 70(2): 177-182. PMID: 3056497. DOI: 10.1111/j.1365-2141.1988.tb02460.x.
	Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis[J]. Pediatr Blood Cancer, 2007, 48(2): 124-131. PMID: 16937360. DOI: 10.1002/pbc.21039.
	Chandar R, Chandrasekaran V, Jagadisan B, et al. Hemophagocytic lymphohistiocytosis in a child with very severe aplastic anemia: double jeopardy resulting in fatality[J]. J Pediatr Hematol Oncol, 2017, 39(1): e43-e45. PMID: 27548335. DOI: 10.1097/MPH.0000000000000671.
	30 宋敏, 王建宁, 孟庆奇, 等. 噬血细胞综合征合并慢性再生障碍性贫血1例报告并文献复习[J]. 中国误诊学杂志, 2012, 12(5): 1012-1014.
	Yashima A, Narigasawa Y, Ishida Y, et al. Hemophagocytic syndrome due to miliary tuberculosis in the course of aplastic anemia[J]. Rinsho Ketsueki, 1998, 39(5): 392-397. PMID: 9637891.
	Nagata H, Fujino T, Muramatsu A, et al. Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis subsequent to rabbit antithymocyte globulin administration and successfully treated with rituximab in a patient with aplastic anemia[J]. Rinsho Ketsueki, 2018, 59(4): 407-413. PMID: 29743400. DOI: 10.11406/rinketsu.59.407.
	Stéphan JL, Galambrun C, Pozzetto B, et al. Aplastic anemia after Mycoplasma pneumoniae infection: a report of two cases[J]. J Pediatr Hematol Oncol, 1999, 21(4): 299-302. PMID: 10445893. DOI: 10.1097/00043426-199907000-00011.
	Kumakura S, Ishikura H, Kobayashi S. Hemophagocytic syndrome, a possible association with aplastic anemia?[J]. Intern Med, 2003, 42(12): 1262-1264. PMID: 14714972. DOI: 10.2169/internalmedicine.42.1262.
	Celkan T. Aplastic anemia presenting as hemophagocytic lymphohistiocytosis[J]. Turk J Haematol, 2010, 27(1): 38-42. PMID: 27265797.
	魏昂, 马宏浩, 张利平, 等. 以噬血细胞综合征为首发表现的肝炎相关性再生障碍性贫血五例分析[J]. 中华儿科杂志, 2020, 58(3): 213-217. PMID: 32135593. DOI: 10.3760/cma.j.issn.0578-1310.2020.03.010.
	Matsunawa M, Kawakami K, Hisatake J, et al. Hepatitis-associated aplastic anemia preceded by a hemophagocytic syndrome-like state[J]. Rinsho Ketsueki, 2003, 44(10): 1010-1014. PMID: 14639947.
	Min KW, Jung HY, Han HS, et al. Ileal mass-like lesion induced by Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in a patient with aplastic anemia[J]. APMIS, 2015, 123(1): 81-86. PMID: 25243347. DOI: 10.1111/apm.12308.
	Maciejewski J, Selleri C, Anderson S, et al. Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro[J]. Blood, 1995, 85(11): 3183-3190. PMID: 7538820.
	Kojima S, Matsuyama K, Kodera Y, et al. Circulating activated suppressor T lymphocytes in hepatitis-associated aplastic anaemia[J]. Br J Haematol, 1989, 71(1): 147-151. PMID: 2521796. DOI: 10.1111/j.1365-2141.1989.tb06289.x.
	Bowen DG, Warren A, Davis T, et al. Cytokine-dependent bystander hepatitis due to intrahepatic murine CD8 T-cell activation by bone marrow-derived cells[J]. Gastroenterology, 2002, 123(4): 1252-1264. PMID: 12360486. DOI: 10.1053/gast.2002.36058.
	Ikawa Y, Nishimura R, Kuroda R, et al. Expansion of a liver-infiltrating cytotoxic T-lymphocyte clone in concert with the development of hepatitis-associated aplastic anaemia[J]. Br J Haematol, 2013, 161(4): 599-602. PMID: 23419100. DOI: 10.1111/bjh.12259.
	Brown KE, Tisdale J, Barrett AJ, et al. Hepatitis-associated aplastic anemia[J]. N Engl J Med, 1997, 336(15): 1059-1064. PMID: 9091802. DOI: 10.1056/NEJM199704103361504.
	Kagan WA, Ascens?o JA, Pahwa RN, et al. Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis[J]. Proc Natl Acad Sci U S A, 1976, 73(8): 2890-2894. PMID: 1085449. PMCID: PMC430791. DOI: 10.1073/pnas.73.8.2890.
	Lu J, Basu A, Melenhorst JJ, et al. Analysis of T-cell repertoire in hepatitis-associated aplastic anemia[J]. Blood, 2004, 103(12): 4588-4593. PMID: 14988156. DOI: 10.1182/blood-2003-11-3959.
	Morales-Mantilla DE, King KY. The role of interferon-gamma in hematopoietic stem cell development, homeostasis, and disease[J]. Curr Stem Cell Rep, 2018, 4(3): 264-271. PMID: 30148048. PMCID: PMC6096761. DOI: 10.1007/s40778-018-0139-3.
	Chatterjee S, Dutta RK, Basak P, et al. Alteration in marrow stromal microenvironment and apoptosis mechanisms involved in aplastic anemia: an animal model to study the possible disease pathology[J]. Stem Cells Int, 2010, 2010: 932354. PMID: 21048856. PMCID: PMC2963319. DOI: 10.4061/2010/932354.