Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that affects about 1% of the global population, with a female–male ratio of 3:1. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. However, evidence has accumulated showing that patients suffering from RA can also develop extra-articular manifestations, including cardiovascular disease states, neuropathies, and multiorgan dysfunction. In particular, peripheral nerve disorders showed a consistent impact in the course of the disease (prevalence about 20%) mostly associated to vasculitis of the nerve vessels leading to vascular ischemia, axonal degeneration, and neuronal demyelination. The pathophysiological basis of this RA-associated microvascular disease, which leads to impairment of assonal functionality, is still to be better clarified. However, endothelial dysfunction and alterations of the so-called brain-nerve barrier (BNB) seem to play a fundamental role. This review aims to assess the potential mechanisms underlying the impairment of endothelial cell functionality in the development of RA and to identify the role of dysfunctional endothelium as a causative mechanism of extra-articular manifestation of RA. On the other hand, the potential impact of lifestyle and nutritional interventions targeting the maintenance of endothelial cell integrity in patients with RA will be discussed as a potential option when approaching therapeutic solutions in the course of the disease.

中文翻译：

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类风湿性关节炎的内皮功能障碍和关节外神经系统表现

类风湿性关节炎 (RA) 是一种慢性、系统性、炎症性自身免疫性疾病，影响全球约 1% 的人口，男女比例为 3:1。RA 主要影响关节，随之而来的是关节肿胀和畸形，然后是强直。然而，越来越多的证据表明，患有 RA 的患者也会出现关节外表现，包括心血管疾病状态、神经病变和多器官功能障碍。特别是，周围神经疾病在疾病过程中表现出一致的影响（患病率约为 20%），主要与导致血管缺血、轴突变性和神经元脱髓鞘的神经血管炎有关。这种 RA 相关微血管疾病的病理生理学基础会导致神经功能受损，仍有待更好地阐明。然而，内皮功能障碍和所谓的脑神经屏障 (BNB) 的改变似乎发挥了重要作用。本综述旨在评估 RA 发展过程中内皮细胞功能受损的潜在机制，并确定功能失调的内皮细胞作为 RA 关节外表现的致病机制的作用。另一方面，针对维持 RA 患者内皮细胞完整性的生活方式和营养干预的潜在影响将作为在疾病过程中接近治疗方案时的潜在选择进行讨论。本综述旨在评估 RA 发展过程中内皮细胞功能受损的潜在机制，并确定功能失调的内皮细胞作为 RA 关节外表现的致病机制的作用。另一方面，针对维持 RA 患者内皮细胞完整性的生活方式和营养干预的潜在影响将作为在疾病过程中接近治疗方案时的潜在选择进行讨论。本综述旨在评估 RA 发展过程中内皮细胞功能受损的潜在机制，并确定功能失调的内皮细胞作为 RA 关节外表现的致病机制的作用。另一方面，针对维持 RA 患者内皮细胞完整性的生活方式和营养干预的潜在影响将作为在疾病过程中接近治疗方案时的潜在选择进行讨论。