Seasonality and latitude as linked environmental factors in Giant Cell Arteritis incidence: A systematic review and meta-analysis

Giant Cell Arteritis (GCA) incidence is influenced by various unexplained factors. Over the past 60 years, studies have investigated seasonal influence on GCA incidence, yielding contradictory results. This systematic review and meta-analysis aim to determine whether there is a pooled seasonal influence on GCA incidence and if it is modulated by latitude. PubMed and Scopus databases were searched for studies on seasonal influence on GCA incidence without date restriction. Articles reporting incidence and describing seasonal or monthly proportions of GCA were considered for inclusion. The primary outcome measured was the Seasonal Incidence Risk Ratio (SIRR) defined as the incidence of GCA in warm seasons (Spring and Summer) over GCA incidence in cold seasons (Autumn and Winter). Meta-analysis of GCA incidence variations with season was performed on the pooled SIRR. Nineteen articles describing GCA incidence and seasonal variations in 39829 patients were included, 10 studies reported a significant seasonal pattern in the incidence of GCA with seven studies reporting a warm seasonal pattern and three studies reporting a cold seasonal while 9 studies did not report a significant seasonal pattern. The pooled SIRR estimate in this meta-analysis was 1.08 (95% CI [0.99-1.17]). We observed a significant reverse correlation between SIRR and the studies’ location latitude r= -0.595 (p=0.015), additionally, we observed an inflexion latitude line in Lyon, France (45.8), all studies performed southern to that line reported higher proportion of warm seasons cases. The pooled SIRR of studies performed southern to the inflexion line was 1.18 (95% CI [1.09-1.28]). this meta-analysis shows a global pooled trend towards a warm seasonal pattern, mainly driven by southern locations of the included studies, linking two largely discussed environmental factors in GCA, in this case, latitude and seasonal influence which should encourage epidemiological research in southern regions of the globe in order to display globally representative data.巨细胞动脉炎（Giant Cell Arteritis, GCA）的发病受多种不明因素影响。近60年来，诸多研究探讨了季节因素对GCA发病的影响，但所得结论相互矛盾。本项系统评价与荟萃分析旨在明确：GCA发病是否存在汇总后的季节相关性，以及该相关性是否受纬度调节。本研究检索了PubMed及Scopus数据库中所有关于季节因素对GCA发病影响的研究，未设置时间限制。纳入标准为：报道了GCA发病情况且描述了该病发病的季节或月度分布的文献。本研究的主要结局指标为季节发病风险比（Seasonal Incidence Risk Ratio, SIRR），定义为温暖季节（春季与夏季）的GCA发病率与寒冷季节（秋季与冬季）的GCA发病率之比。基于汇总后的SIRR开展了GCA发病季节差异的荟萃分析。最终纳入19篇文献，涵盖39829例患者的GCA发病及季节分布数据；其中10项研究报道了GCA发病存在显著的季节模式：7项研究提示温暖季节发病模式，3项研究提示寒冷季节发病模式，剩余9项研究未发现显著的季节分布特征。本次荟萃分析的汇总SIRR估计值为1.08（95%置信区间[0.99, 1.17]）。研究发现SIRR与研究开展地的纬度呈显著负相关（r=-0.595，p=0.015）；此外，我们在法国里昂（北纬45.8°）观察到一个拐点纬度：所有位于该纬度以南的研究均报告了更高比例的温暖季节发病病例。位于该拐点纬度以南的研究的汇总SIRR为1.18（95%置信区间[1.09, 1.28]）。本次荟萃分析显示，整体汇总结果倾向于温暖季节发病模式，这一趋势主要由纳入研究中位于该拐点纬度以南的研究所驱动；本研究关联了GCA研究领域两大被广泛讨论的环境因素——纬度与季节影响，这一发现可推动全球南部地区的流行病学研究，以获取更具全球代表性的发病数据。