Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, PR China.
Department of Immunology, College of Basic Medical Science, Dalian Medical University, Dalian, PR China; Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, PR China.
Semin Arthritis Rheum. 2020 Oct;50(5):1022-1039. doi: 10.1016/j.semarthrit.2020.06.004. Epub 2020 Jun 17.
OBJECTIVE: Infection is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients. We conducted a systematic review and meta-analysis to investigate the clinical characteristics and risk factors of infection in SLE by comparing demographic factors, laboratory data, clinical features, and therapeutic factors between infection and non-infection SLE patients. METHODS: PubMed, Embase, and Cochrane databases were searched systematically without restricting the language or year (up to September 2019) by using MeSH terms and keywords pertaining to SLE and infection. Three independent reviewers selected all observational studies based on the established inclusion criteria. Odds ratio (OR) and standardized mean difference (SMD) along with 95% confidence intervals (CI) were used and the analyses were carried out by using a random/fixed-effects model. When necessary, different subgroup and sensitivity analyses were conducted. Study quality was assessed by the modified version (nine-star scoring system) of the Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by funnel plots, and Egger's and Begg's tests. RESULTS: In total, we included 39 studies (3709 infection SLE patients and 10526 non-infection SLE patients) based on the inclusion criteria. Compared with the SLE patients without infection, we found that infected SLE patients had a significantly higher incidence rate of the following: 1) lymphopenia (OR = 2.738 95%CI (1.017-7.376), P = 0.046, I = 81.4%), 2) thrombocytopenia (OR = 1.61 95%CI (1.4-1.85), P<0.001, I = 0%), 3) anemia (OR = 2.294 95%CI (1.402-3.755), P = 0.001, I = 83.0%), 4) hypoproteinemia (OR = 2.336 95%CI (1.408-3.876), P = 0.001, I = 84.2%), 5) C3 consumed (OR = 1.890 95%CI (1.190-3.002), P = 0.007, I = 77.4%), 6) diabetes mellitus (OR = 3.890 95%CI (2.450-6.160), P < 0.001, I = 0%), 7) elevated creatinine (OR = 1.954 95%CI (1.646-2.320), P < 0.001, I = 0.0%), 8) renal involvement (OR = 2.692 95%CI (2.000-3.623), P < 0.001, I = 76.0%), 9) serositis (OR = 3.877 95%CI (0.995-15.110), P = 0.051, I = 79.1%), and 10) use of steroid immunosuppressants (OR = 3.116 95%CI (1.959-4.957), P < 0.001, I = 77.9%). Furthermore, infected SLE patients had a significantly higher mean dose of prednisone (SMD = 2.088 95%CI (1.196-2.981), P < 0.001, I = 97.8%). In addition, SLE patients with infection showed a significantly lower incidence of antimalarial drug use (OR = 0.634 95%CI (0.451-0.892), P = 0.009, I = 56.0%). Infected SLE patients had a significantly higher level of 1) 24-h urinary protein (SMD = 0.560 95%CI (0.300-0.810), P < 0.001, I = 0%), 2) CRP (SMD = 0.437 95%CI (0.184-0.691), P = 0.001, I = 68.6%), and 3) SLE Collaborating Clinics damage index (SDI) (SMD = 0.451 95%CI (0.238-0.664), P < 0.001, I = 0.0%), along with a significantly lower level of albumin (SMD = -0.400 95%CI (-0.610--0.200), P < 0.001, I = 0.0%). After adjustment for false discovery rate (FDR), lymphopenia and serositis were no longer associated with the occurrence of infection; however, the remaining factors were still associated with infection in SLE. According to the nine-star scoring system of NOS, 71.79% of the studies were considered as high methodological quality (low risk of bias). No significant publication bias, except for renal involvement, was detected from funnel plots or Egger's and Begg's test, while this publication bias of renal involvement did not impact the pooled estimates. CONCLUSION: We identified many factors including thrombocytopenia, anemia, hypoproteinemia, hypocomplementemia, hypoalbuminemia, higher level of CRP, higher SDI score, renal involvement and diabetes mellitus that were associated with infection in SLE patients. In addition, glucocorticoids (especially high-dose) and immunosuppressants (e.g. cyclophosphamide) rendered SLE patients more susceptible to infection, while antimalarial drug administration (hydroxychloroquine) was a protective factor against infection in SLE patients. SLE patients with the above clinical characteristics and risk factors might be at high risk from infection, which might contribute to the early identification of infection in SLE patients for better prognosis.
目的：感染是系统性红斑狼疮（SLE）患者发病和死亡的主要原因之一。我们进行了一项系统评价和荟萃分析，通过比较感染和非感染 SLE 患者的人口统计学因素、实验室数据、临床特征和治疗因素，来探讨 SLE 患者感染的临床特征和危险因素。
方法：我们系统地检索了 PubMed、Embase 和 Cochrane 数据库，使用与 SLE 和感染相关的 MeSH 术语和关键词，未对语言或年份进行限制（截至 2019 年 9 月）。由三位独立的评审员根据既定纳入标准选择所有观察性研究。采用比值比（OR）和标准化均数差（SMD）及其 95%置信区间（CI），并采用随机/固定效应模型进行分析。必要时，进行不同的亚组和敏感性分析。采用改良的（九星评分系统）纽卡斯尔-渥太华量表（NOS）评估研究质量，并通过漏斗图、Egger 和 Begg 检验评估发表偏倚。
结果：根据纳入标准，我们共纳入了 39 项研究（3709 例感染 SLE 患者和 10526 例非感染 SLE 患者）。与未感染的 SLE 患者相比，我们发现感染 SLE 患者的以下情况发生率显著更高：1）淋巴细胞减少症（OR=2.738，95%CI（1.017-7.376），P=0.046，I²=81.4%），2）血小板减少症（OR=1.61，95%CI（1.4-1.85），P<0.001，I²=0%），3）贫血（OR=2.294，95%CI（1.402-3.755），P=0.001，I²=83.0%），4）低蛋白血症（OR=2.336，95%CI（1.408-3.876），P=0.001，I²=84.2%），5）补体 C3 消耗（OR=1.890，95%CI（1.190-3.002），P=0.007，I²=77.4%），6）糖尿病（OR=3.890，95%CI（2.450-6.160），P<0.001，I²=0%），7）血肌酐升高（OR=1.954，95%CI（1.646-2.320），P<0.001，I²=0.0%），8）肾脏受累（OR=2.692，95%CI（2.000-3.623），P<0.001，I²=76.0%），9）浆膜炎（OR=3.877，95%CI（0.995-15.110），P=0.051，I²=79.1%），和 10）使用皮质类固醇和免疫抑制剂（OR=3.116，95%CI（1.959-4.957），P<0.001，I²=77.9%）。此外，感染 SLE 患者的泼尼松平均剂量明显更高（SMD=2.088，95%CI（1.196-2.981），P<0.001，I²=97.8%）。此外，感染 SLE 患者使用抗疟药物的发生率显著较低（OR=0.634，95%CI（0.451-0.892），P=0.009，I²=56.0%）。感染 SLE 患者的 1）24 小时尿蛋白（SMD=0.560，95%CI（0.300-0.810），P<0.001，I²=0%），2）C 反应蛋白（SMD=0.437，95%CI（0.184-0.691），P=0.001，I²=68.6%）和 3）SLE 协作临床疾病指数（SDI）（SMD=0.451，95%CI（0.238-0.664），P<0.001，I²=0.0%）水平明显更高，而白蛋白（SMD=-0.400，95%CI（-0.610--0.200），P<0.001，I²=0.0%）水平明显更低。经过假发现率（FDR）调整后，淋巴细胞减少症和浆膜炎与感染的发生不再相关，但其余因素与 SLE 感染仍相关。根据 NOS 的九星评分系统，71.79%的研究被认为具有较高的方法学质量（低偏倚风险）。漏斗图或 Egger 和 Begg 检验未发现除肾脏受累外的其他显著发表偏倚，而肾脏受累的发表偏倚并不影响汇总估计值。
结论：我们发现了许多与 SLE 患者感染相关的因素，包括血小板减少症、贫血、低蛋白血症、低补体血症、低白蛋白血症、更高的 C 反应蛋白水平、更高的 SDI 评分、肾脏受累和糖尿病。此外，糖皮质激素（尤其是大剂量）和免疫抑制剂（如环磷酰胺）使 SLE 患者更容易感染，而抗疟药物（羟氯喹）的使用是 SLE 患者感染的保护性因素。具有上述临床特征和危险因素的 SLE 患者可能面临较高的感染风险，这可能有助于早期识别 SLE 患者的感染，从而改善预后。
Arthritis Res Ther. 2024-3-4
Open Access Rheumatol. 2023-7-27
Ther Adv Musculoskelet Dis. 2022-2-14
Zotero 插件