Rodolfi Stefano, Selmi Carlo
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Department of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Department of Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
Best Pract Res Clin Rheumatol. 2025 May;39(2):102053. doi: 10.1016/j.berh.2025.102053. Epub 2025 Mar 25.
The pathogenesis and pathophysiology of rheumatic diseases is complex and relies on the interaction of different factors. The common view is that the pathological autoimmunity develops in genetically predisposed individuals upon exposure to an environmental trigger. This highlights the importance of recognizing and deconstructing the effects of environmental agents in rheumatic diseases. Several factors have been identified in the last decades, with detrimental or protective effects, impacting not only on disease onset, but also on its natural history. Cigarette smoking has been identified as one of the strongest environmental risk factors, being associated with disease development and severity for several rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and spondyloarthropathies. Moreover, other airborne pollutants, such as silica, solvents, asbestos and metals are recognized risk factors for rheumatic diseases. The effect of some other agents is however not straightforward, of which a remarkable example is alcohol consumption. Alcohol has been associated with both pro- and anti-inflammatory effects, exerting a variable effect on rheumatic diseases depending on quantity and frequency of consumption, as well as sex and ethnicity. Similarly, ultraviolet light exposure has been associated with a higher risk of SLE but lower risk of RA. The relationship between microbial exposure and autoimmunity is also complex: while some infectious agents increase the risk of rheumatic diseases, it is widely accepted that less exposure to microbial agents, particularly during immune system development, increases the risk of autoimmunity. Furthermore, in recent years the spotlight has switched to the human microbiome, as alterations in organ-specific microbiome composition are anticipated to be early participants in the onset of immune-mediated illnesses. The aim of this review is to highlight the most relevant environmental factors and their role in Rheumatology, with a specific focus on proposed pathophysiological effect and correlation with clinical outcomes.
风湿性疾病的发病机制和病理生理学很复杂，依赖于不同因素之间的相互作用。普遍观点认为，病理性自身免疫在具有遗传易感性的个体接触环境触发因素后发展而来。这凸显了认识和剖析环境因素在风湿性疾病中作用的重要性。在过去几十年中已确定了几个因素，它们具有有害或保护作用，不仅影响疾病的发作，还影响其自然病程。吸烟已被确定为最强的环境风险因素之一，与包括类风湿关节炎（RA）、系统性红斑狼疮（SLE）和脊柱关节病在内的多种风湿性疾病的发生和严重程度相关。此外，其他空气传播污染物，如二氧化硅、溶剂、石棉和金属，被认为是风湿性疾病的风险因素。然而，其他一些因素的影响并非一目了然，其中一个显著例子是饮酒。酒精与促炎和抗炎作用都有关联，根据饮酒量、频率以及性别和种族，对风湿性疾病产生不同的影响。同样，紫外线照射与SLE的较高风险相关，但与RA的较低风险相关。微生物暴露与自身免疫之间的关系也很复杂：虽然一些感染因子会增加风湿性疾病的风险，但人们普遍认为较少接触微生物因子，尤其是在免疫系统发育期间，会增加自身免疫的风险。此外，近年来人们的关注焦点已转向人类微生物组，因为预计器官特异性微生物组组成的改变是免疫介导疾病发病的早期参与者。本综述的目的是强调最相关的环境因素及其在风湿病学中的作用，特别关注提出的病理生理效应以及与临床结果的相关性。
