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系统性红斑狼疮与损害:过去 20 年发生了哪些变化?

Systemic lupus erythematosus and damage: What has changed over the past 20 years?

机构信息

Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Division of Rheumatology, University of Toronto, Toronto, Canada; University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital Lupus Clinic, Toronto, Canada.

Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Best Pract Res Clin Rheumatol. 2023 Dec;37(4):101893. doi: 10.1016/j.berh.2023.101893. Epub 2023 Nov 22.

Abstract

The young age of onset and chronic/relapsing nature of systemic lupus erythematosus (SLE) make SLE patients prone to develop and accrue organ damage as a result of long-standing disease activity and side effects of treatment. There is a growing interest in objectifying damage and identifying its risk factors. Still, the lack of therapeutic alternatives has led to difficulties in avoiding immunosuppressives particularly corticosteroids, which have been implicated in a large spectrum of organ damage in SLE patients. Moreover, it continues to be very challenging to determine what actually causes damage in different organ-systems. Cardiovascular disease continues to be one of the leading types of damage in patients with SLE, reported as early as 1976. Since then, many researchers have focused on identifying SLE or treatment-related and traditional risk factors. The same considerations are valid for other conditions, such as the occurrence of metabolic syndrome, osteoporosis, avascular necrosis, susceptibility to infections, etc. On the other hand, diverse risk factors contribute to the development of chronic kidney disease (CKD) in SLE. Most evidence suggests that high initial levels of serum creatinine, hypocomplementemia, nephrotic range proteinuria, concomitant uncontrolled hypertension, Black and Hispanic ancestry, non-adherence to treatment, and biopsy findings such as diffuse proliferative lupus nephritis (LN), a high chronicity index, tubular atrophy, and tubulointerstitial inflammation are risk factors for progression to end stage renal disease (ESRD) in LN. While cardiovascular disease, CKD and infections are leading causes of mortality in patients with SLE, hospitalizations are caused mostly by SLE disease flares and infections. Cognitive impairment and mood disorders are common in SLE but continue to impose a challenge on how to measure, manage and decipher the underlying pathogenesis. Nevertheless, they have a great impact on SLE patients' health-related quality of life (HRQoL) and social functioning. Also, skin manifestations, such as alopecia and scaring, cataracts, and sicca symptoms result in a significant decrease in HRQoL. In light of recent developments in SLE treatment, we can expect to enter a period of new-age targeted therapies that will enable us to reduce disease activity and glucocorticoid usage further and positively alter the trajectory of damage development and accrual in SLE.

摘要

红斑狼疮(SLE)的发病年龄较轻,且具有慢性/复发性,这使得 SLE 患者容易因长期疾病活动和治疗副作用而发生器官损伤和累积器官损伤。人们越来越关注器官损害的客观化和识别其危险因素。然而,由于缺乏治疗替代方案,特别是免疫抑制剂(如皮质类固醇)的使用,这与 SLE 患者的多种器官损害有关,因此难以避免使用这些药物。此外,确定不同器官系统中哪些因素实际导致损伤仍然非常具有挑战性。心血管疾病仍然是 SLE 患者的主要损伤类型之一,早在 1976 年就有报道。从那时起,许多研究人员一直致力于确定 SLE 或治疗相关和传统危险因素。对于其他疾病,如代谢综合征、骨质疏松症、骨坏死、易感染等,也有同样的考虑。另一方面,多种危险因素导致 SLE 患者发生慢性肾脏病(CKD)。大多数证据表明,血清肌酐初始水平高、低补体血症、肾病范围蛋白尿、同时伴有未控制的高血压、黑人和西班牙裔血统、不遵医嘱以及活检发现如弥漫性增生性狼疮肾炎(LN)、慢性指数高、肾小管萎缩和肾小管间质炎症等是 LN 进展为终末期肾病(ESRD)的危险因素。尽管心血管疾病、CKD 和感染是 SLE 患者死亡的主要原因,但住院主要是由于 SLE 疾病活动和感染。认知障碍和情绪障碍在 SLE 中很常见,但仍然对如何测量、管理和解释潜在的发病机制构成挑战。尽管如此,它们对 SLE 患者的健康相关生活质量(HRQoL)和社会功能有很大影响。此外,皮肤表现,如脱发和瘢痕、白内障和干燥症状,会导致 HRQoL 显著下降。鉴于 SLE 治疗的最新进展,我们有望进入一个新时代的靶向治疗时期,这将使我们能够进一步降低疾病活动度和糖皮质激素的使用,并积极改变 SLE 患者的器官损伤发展和累积轨迹。

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