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一例接受阿达木单抗治疗的患者发生播散性、致命性牛型结核再激活:病例报告及文献复习

Disseminated, fatal reactivation of bovine tuberculosis in a patient treated with adalimumab: a case report and review of the literature.

作者信息

Capoferri Gioele, Ghielmetti Giovanni, Glatz Bettina, Mutke Markus R, Tzankov Alexandar, Stephan Roger, Keller Peter M, Labhardt Niklaus D

机构信息

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.

Section of Veterinary Bacteriology, Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.

出版信息

Infection. 2025 Feb;53(1):481-487. doi: 10.1007/s15010-024-02364-0. Epub 2024 Aug 14.

Abstract

PURPOSE

Tumor necrosis factor inhibitors (TNFi) are known to increase the risk of tuberculosis (TB) reactivation, though cases involving Mycobacterium bovis are rarely reported.

CASE PRESENTATION/RESULTS: We describe a case of disseminated TB with M. bovis in a 78-year-old woman with a negative Interferon-Gamma-Release Assay (IGRA), taking adalimumab due to rheumatoid polyarthritis, which resulted in a fatal outcome. The atypical clinical and histopathological features were initially interpreted as sarcoidosis. The case occurred in Switzerland, an officially bovine tuberculosis-free country. The whole genome sequence of the patient's cultured M. bovis isolate was identified as belonging to the animal lineage La1.2, the main genotype in continental Europe, but showed significant genetic distance from previously sequenced Swiss cattle strains. In a literature review, four cases of bovine tuberculosis reactivation under TNFi treatment were identified, with pulmonal, oral and intestinal manifestations. Similar to our patient, two cases presented a negative IGRA before TNFi initiation, which later converted to positive upon symptomatic presentation of M. bovis infection.

CONCLUSION

This case highlights the diagnostic challenges of TB in immunosuppressed patients, the limited sensitivity of IGRA, and the importance of considering TB reactivation even in regions declared free of bovine tuberculosis. Detailed patient histories, including potential exposure to unpasteurized dairy products, are essential for guiding preventive TB treatment before TNFi initiation.

摘要

目的

已知肿瘤坏死因子抑制剂(TNFi)会增加结核病(TB)复发的风险,不过涉及牛分枝杆菌的病例鲜有报道。

病例呈现/结果:我们描述了一例78岁女性播散性牛分枝杆菌结核病病例,该患者干扰素-γ释放试验(IGRA)结果为阴性,因类风湿性多关节炎正在服用阿达木单抗,最终导致死亡。非典型的临床和组织病理学特征最初被误诊为结节病。该病例发生在瑞士,一个官方宣布无牛结核病的国家。患者培养的牛分枝杆菌分离株的全基因组序列被鉴定为属于动物谱系La1.2,这是欧洲大陆的主要基因型,但与之前测序的瑞士牛菌株存在显著的遗传距离。在文献综述中,我们确定了4例在TNFi治疗下发生牛结核病复发的病例,表现为肺部、口腔和肠道症状。与我们的患者相似,2例在开始使用TNFi之前IGRA结果为阴性,在出现牛分枝杆菌感染症状后转为阳性。

结论

该病例凸显了免疫抑制患者结核病诊断的挑战、IGRA敏感性有限,以及即使在宣布无牛结核病的地区也需考虑结核病复发的重要性。详细的患者病史,包括潜在接触未巴氏消毒乳制品的情况,对于在开始使用TNFi之前指导预防性结核病治疗至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34b8/11825525/d84b870e42f9/15010_2024_2364_Fig1_HTML.jpg

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