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抗生素使用与巨细胞动脉炎和风湿性多肌痛发病之间的关联:来自E3N-欧洲癌症与营养前瞻性调查的巢式病例对照研究。

Association between antibiotic use and the onset of giant cell arteritis and polymyalgia rheumatica: A nested case-control study from E3N-European Prospective Investigation into Cancer and Nutrition.

作者信息

Pacoureau Lucas, Barde François, Gelot Amandine, Elbaz Alexis, Fournier Agnès, Nguyen Yann, Seror Raphaèle

机构信息

Université Paris-Saclay, UVSQ, Inserm CESP U1018, Gustave Roussy, Villejuif, France.

Service de Médecine Interne, Hôpital Bicêtre, AP-HP.Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

出版信息

J Intern Med. 2025 Nov;298(5):424-437. doi: 10.1111/joim.70000. Epub 2025 Sep 2.

Abstract

OBJECTIVES

To assess the association between infections, assessed by antibiotic reimbursement, and the occurrence of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR).

METHODS

We conducted a nested case-control study from the French cohort E3N-European Prospective Investigation into Cancer and Nutrition, which has followed 98,995 women since 1990. Cases, defined as patients who developed GCA and/or PMR during follow-up, were matched with 20 controls on age and vital status. Infections prior to index date, defined by ≥1 antibiotic reimbursement on the medication claims reimbursement database, were compared between groups using conditional logistic regression models, adjusted for potential confounders. Different time periods before the index date and different antibiotic classes were compared.

RESULTS

A total of 428 GCA/PMR cases (113 GCA, 232 PMR, 83 undefined) were compared to 8560 matched controls. Compared to controls, GCA/PMR cases had higher odds to have any infection in the [0-24] months prior to index date (aOR [95% CI] 1.22 [1.00-1.51]). Considering the 6-month periods prior to index date, the association was stronger when close to index date (1.18 [0.94-1.47]; 0.95 [0.75-1.19] for [0-6] and [18-24] months, respectively). This association was only found among GCA cases (1.63 [1.08-2.48] for [0-24] months), but not among PMR cases. Quinolone reimbursements were the most associated with subsequent GCA (2.07 [1.23-3.49] for [0-12] months).

CONCLUSION

Compared to controls, GCA patients were at higher risk of having used antibiotics in the 24 months prior to the diagnosis. Infections or a disbalanced microbiome could act as a trigger of the disease, although a reverse causation bias cannot be excluded.

摘要

目的

通过抗生素报销情况评估感染与巨细胞动脉炎(GCA)和/或风湿性多肌痛(PMR)发生之间的关联。

方法

我们在法国E3N队列——欧洲癌症与营养前瞻性调查中开展了一项巢式病例对照研究,该队列自1990年以来对98,995名女性进行了随访。病例定义为在随访期间发生GCA和/或PMR的患者,按照年龄和生命状态与20名对照进行匹配。使用条件逻辑回归模型比较两组在索引日期之前(由药物报销数据库中≥1次抗生素报销定义)的感染情况,并对潜在混杂因素进行调整。比较索引日期之前的不同时间段以及不同抗生素类别。

结果

共将428例GCA/PMR病例(113例GCA、232例PMR、83例未明确分类)与8560名匹配对照进行了比较。与对照相比,GCA/PMR病例在索引日期前[0 - 24]个月内发生任何感染的几率更高(比值比[aOR][95%置信区间]为1.22[1.00 - 1.51])。考虑索引日期前的6个月时间段,在接近索引日期时关联更强([0 - 6]个月和[18 - 24]个月时分别为1.18[0.94 - 1.47];0.95[0.75 - 1.19])。这种关联仅在GCA病例中发现([0 - 24]个月时为1.63[1.08 - 2.48]),而在PMR病例中未发现。喹诺酮类药物报销与后续GCA的关联最为密切([0 - 12]个月时为2.07[1.23 - 3.49])。

结论

与对照相比,GCA患者在诊断前24个月内使用抗生素的风险更高。感染或微生物群失衡可能是疾病的触发因素,尽管不能排除反向因果关系偏倚。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b14/12522520/0871e46df8bd/JOIM-298-424-g003.jpg

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