疑似自身免疫疾病的内脏利什曼病 2 例

Visceral leishmaniasis with suspected autoimmune disease ：A report of 2 cases

摘要

内脏利什曼病（visceral leishmaniasis，VL）是一种罕见的寄生虫感染，其显著特征包括 B 细胞过度活跃进而导致多种自身抗体阳性，可能模拟自身免疫性疾病的临床表现和抗体谱。本文报告 2 例初诊疑似自身免疫性疾病的 VL 患者，从临床表现、体格检查、实验室检查、诊断及治疗等方面探讨 VL 与自身免疫性疾病的异同点。病例1为 69 岁女性患者，因不规则发热入院，体格检查示脾大，实验室检查提示全血细胞减少及抗核抗体谱异常。首次骨髓穿刺提示增生性骨髓象，外周血异型淋巴细胞占比约 6% ，初始考虑自身免疫性疾病，但激素治疗效果不佳。进一步完善感染、肿瘤等相关筛查，积极行二次骨髓穿刺，检出杜氏利什曼原虫无鞭毛体（利-杜小体），核酸检测证实杜氏利什曼原虫感染，确诊 VL。病例2为41岁男性患者，因发热、腹胀就诊，体格检查同样示脾大，伴抗核抗体谱异常，治疗过程中检出杜氏利什曼原虫感染，最终诊断为 VL 继发噬血细胞综合征。2 例患者均表现为反复发热、纳差、脾大，伴全血细胞减少及抗核抗体谱异常，初始均疑似自身免疫性疾病，后经相关检查确诊 VL。VL 的确诊金标准是通过骨髓、淋巴结或脾脏穿刺检出利-杜小体，骨髓穿刺阳性率约80％~90％，但临床中可能因穿刺部位局限等因素导致漏检，需及时进行二次穿刺。此外，脾大伴三系减少的患者多就诊于血液科或风湿免疫科，而非感染科，易导致误诊、漏诊。希望本文能为临床医生早期诊断 VL 提供一定的诊治思路。

Abstract

Visceral leishmaniasis（VL）is a rare parasitic infection characterized by distinctive fea- tures，including the overproduction of various autoantibodies by B cells，which may mimic manifestations and antibody profiles associated with autoimmune diseases.In this report，we presented two patients diag- nosed with visceral leishmaniasis who were initially suspected of having an autoimmune disease.We dis- cussed the similarities and differences between visceral leishmaniasis and autoimmune diseases based on clinical presentation，physical examination findings，laboratory tests，diagnosis，and treatment.Case 1 involved a 69-year-old female patient who was admitted to the hospital due to irregular fever.Physical examination revealed splenomegaly.Laboratory investigations indicated pancytopenia along with an abnor- mal autoantibody profile.The initial bone marrow aspirate demonstrated：Proliferative changes in the bone marrow，and abnormal lymphocytes in peripheral blood accounting for approximately 6％.Auto- immune disease was initially considered，and hormone therapy did not respond well.Further screening for immunological disorders，infections，tumors，and other related conditions was conducted.A second bone marrow aspirate was performed actively which revealed Leishman-Donovan body.Subsequent nuc- leic acid detection of pathogenic microorganisms confirmed the presence of Leishmania through real-time fluorescence PCR analysis；thus，confirming a diagnosis of visceral leishmaniasis.Case 2 involved a 41-year-old male patient who presented with fever and abdominal distension.Similar to Case 1，physical examination also showed splenomegaly alongside an abnormal autoantibody profile.During treatment，he tested positive for Leishmania infection and was ultimately diagnosed with visceral leishmaniasis compli- cated by hemophagocytic syndrome.The symptoms observed in the two patients included recurrent fever， anorexia，and splenomegaly.To further investigate the cause of pancytopenia and to rule out factors such as surgery，infection，tumors，and other related conditions，an abnormal antinuclear antibody profile was assessed.The initial misdiagnosis pointed towards autoimmune diseases；however，during treatment，vis- ceral leishmaniasis infection was identified，leading to a final diagnosis of visceral leishmaniasis.The gold standard for diagnosing visceral leishmaniasis involves detecting Leishmania bodies through aspiration of bone marrow，lymph nodes，or spleen.The positive rate for bone marrow puncture is approximately 80% to 90％.However，clinical practice may encounter missed detections due to limitations associated with the puncture site.This underscores the necessity for secondary punctures when warranted.Addi- tionally，patients presenting with splenomegaly accompanied by trilineage cytopenia often seek care from Department of Hematology or Department of Rheumatology and Immunology rather than Department of In- fection.This tendency can contribute to both misdiagnosis and missed diagnoses.It is hoped that this case report will offer valuable insights for clinicians in enhancing their diagnostic capabilities and impro- ving the clinical detection rates of visceral leishmaniasis.

关键词

内脏利什曼病 / 自身免疫疾病 / 噬血细胞性淋巴组织细胞增多症

Key words

Visceral leishmaniasis / Autoimmune diseases / Hemophagocytic lymphohistiocytosis

参考文献

[1] Voulgari PV, Pappas GA, Liberopoulos EN, et al. Visceral leish- maniasis resembling systemic lupus erythematosus[J]. Ann Rheum Dis, 2004, 63(10):1348-1349.

[2] 崔银风, 张莉芸, 许珂, 等. 误诊为系统性红斑狼疮的黑热病一例[J]. 中华风湿病学杂志, 2022, 26(1):39-41.

[3] Bueno GCL, Koerich ATS, Burg LB, et al. Visceral leishmaniasis mimicking systemic lupus erythematosus[J]. Rev Soc Bras Med Trop, 2019, 52:e20180208.

[4] 张路钱, 李欣欣, 年云鹏, 等. 2011-2022年陕西省人群黑热病流行特征分析[J]. 中华地方病学杂志, 2023, 42(9): 727-729.

[5] 郑迈, 刘爽, 崔若玫, 等. 误诊为系统性红斑狼疮的黑热病2例[DB/OL]. 中国临床案例成果数据库, 2022, 4(1): E07198.(2022-11-30)[2024-06-28]. https://rs.yiigle.com/cmaid/1435631.

[6] Santana IU, Dias B, Nunes EA, et al. Visceral leishmaniasis mimicking systemic lupus erythematosus:Case series and a sys- tematic literature review[J]. Semin Arthritis Rheum, 2015, 44(6):658-665.

[7] Liberopoulos E, Kei A, Apostolou F, et al. Autoimmune manifes- tations in patients with visceral leishmaniasis[J]. J Microbiol Immunol Infect, 2013, 46(4):302-305.

[8] Chen X, Zhou Q, Liu J, et al. Autoimmune manifestations of vis- ceral leishmaniasis in Chinese patients[J]. Ann Palliat Med, 2021, 10(12):12699-12705.

[9] 毕红霞, 刘焱斌. 《黑热病诊疗方案(2023年版)》解读[J]. 中国抗生素杂志, 2024, 49(7):729-736.

[10] Getnet M, Minaye Dejen A, Abebaw D, et al. Diagnostic accura- cy of serological rk-39 test for visceral Leishmaniasis:Systematic review and meta-analysis[J]. PLoS Negl Trop Dis, 2024, 18 (3):e0011938.

[11] Roberts T, Keddie SH, Rattanavong S, et al. Accuracy of the di- rect agglutination test for diagnosis of visceral leishmaniasis:A sys- tematic review and meta-analysis[J]. BMC Infect Dis, 2023, 23 (1): 782.

[12] 中国医师协会血液科医师分会, 中华医学会儿科学分会血液学组, 噬血细胞综合征中国专家联盟. 中国噬血细胞综合征诊断与治疗指南(2022年版)[J]. 中华医学杂志, 2022, 102 (20):1492-1499.

[13] 陆丹倩, 吴为强, 周梅, 等. 黑热病继发噬血细胞综合征1例[J]. 中国感染与化疗杂志, 2023, 23(5):630-632.

[14] Bode SF, Lehmberg K, Maul-Pavicic A, et al. Recent advances in the diagnosis and treatment of hemophagocytic lymphohistiocyto- sis[J]. Arthritis Res Ther, 2012, 14(3): 213.

[15] 李瑞娟, 康文, 连建奇, 等. 唐都医院 2010-2020年收治的黑热病患者流行病学及临床特征分析[J]. 空军军医大学学报, 2022, 43(8):867-870.

[16] van Griensven J, Diro E. Visceral leishmaniasis:Recent advances in diagnostics and treatment regimens[J]. Infect Dis Clin North Am, 2019, 33(1):79-99.

[17] Melcon-Fernandez E, Galli G, García-Estrada C, et al. Miltefo- sine and nifuratel combination:A promising therapy for the treat- ment of leishmania donovani visceral leishmaniasis[J]. Int J Mol Sci, 2023, 24(2): 1635.

[18] Garg S, Kundu M, Dwivedi AN, et al. Visceral leishmaniasis or systemic lupus erythematosus flare?[J]. Case Reports Immunol, 2012, 2012: 523589.

[19] Tunccan OG, Tufan A, Telli G, et al. Visceral leishmaniasis mimicking autoimmune hepatitis,primary biliary cirrhosis,and systemic lupus erythematosus overlap[J]. Korean J Parasitol, 2012, 50(2):133-136.

[20] Ossandon A, Bompane D, Alessandri C, et al. Leishmania in SLE mimicking an exacerbation[J]. Clin Exp Rheumatol, 2006, 24 (2):186-190.