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Background: Giant cell arteritis (GCA), the leading cause of large vessel vasculitis, is frequently associated with polymyalgia rheumatica (PMR), suggesting a common pathophysiological mechanism. Their etiological mechanism remains unclear. In relation to predisposing genetic background (HLA DR4), several elements in the literature suggest an infectious mechanism as an etiological or triggering factor for these diseases. Epidemiological studies (retrospective cohorts or case-control studies 1-3), based mainly on coding data, have attempted to assess this association. However, the definition and periods of exposure varied between these studies. Objectives: The aim of this study was to assess the association between infections, assessed by antibiotic reimbursement, and the risk of GCA and/or PMR through a nested case-control study from a large prospective cohort. Methods: We conducted a nested case-control study within the French cohort E3N-EPIC (Etude Epidémiologique auprès des femmes de la mutuelle générale de l'Education Nationale), which has been following 98,995 women since 1990. Cases, defined as patients who developed GCA and/or PMR during the follow-up period, were matched with 20 controls based on age and vital status. Infections prior to index date (diagnosis date for cases and the corresponding date for their matched controls) were defined by ≥1 antibiotic reimbursement in the medication claims reimbursement database. These infections were compared between the cases and controls using conditional logistic regression models, adjusted for potential confounders. Different time-periods before the index date, and different classes of antibiotics were compared. Sensitivity analyses using first use of steroids as index date (GCA/PMR diagnosis), to rule out reverse causality. Results: A total of 428 GCA/PMR cases (113 GCA, 232 PMR alone, 83 undefined) were compared to 8,560 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). The association was notably stronger when the infection occurred closer to the index date (1.20 0.97 – 1.49; and 1.00 0.80 – 1.25 for 0–6 and 18–24 months, respectively). This association was only observed among GCA cases (1.62 1.09–2.42 and 1.59 (1.08–2.34), for 0 to 6 and 0 to 12 months, respectively), but not among PMR cases (1.13 0.84–1.51 for 0 to 6 months) (Figure 1). Regarding antibiotic classes, quinolone reimbursements displayed the strongest association with subsequent GCA (2.21 1.12–4.09 for 0 to 6 months). Results were similar in sensitivity analyses. Conclusion: This case-control study, based on a large cohort of French women, showed an increased risk of GCA/PMR after an infectious episode, defined by antibiotic use, in the year preceding diagnosis. The risk was mainly at the expense of GCA cases, and was higher when infections occurred close to the diagnosis, supporting the idea of an infectious antigenic "trigger". Nevertheless, a reverse causality bias cannot totally be ruled out. Furthermore, despite reduced statistical power, quinolone use was strongly and significantly associated with the risk of GCA, raising the hypothesis of an altered microbiota in its pathogenesis. REFERENCES: 1 Stamatis P, Turkiewicz A, Englund M, Jönsson G, Nilsson JÅ, Turesson C, et al. Infections Are Associated with Increased Risk of Giant Cell Arteritis: A Population based Case-control Study from Southern Sweden. J Rheumatol. févr 2021;48(2):251-7. 2 Rhee RL, Grayson PC, Merkel PA, Tomasson G. Infections and the risk of incident giant cell arteritis: a population-based, case-control study. Ann Rheum Dis. juin 2017;76(6):1031-5. 3 Pacoureau L, Barde F, Seror R, Nguyen Y. Association between infection and the onset of giant cell arteritis and polymyalgia rheumatica: a systematic review and meta-analysis. RMD Open. 2023;9(4):e003493. Acknowledgements: The present work was conducted thanks to a donation from SANOFI. Disclosure of Interests: None declared.
Pacoureau et al. (Sat,) studied this question.