系统性红斑狼疮继发真菌感染影响因素分析^*

Influencing Factors for Secondary Fungal Infections in Systemic Lupus Erythematosus

摘要

目的 探讨系统性红斑狼疮（systemic lupus erythematosus，SLE）患者继发真菌感染的影响因素。方法 回顾性选取2021年6月-2025年1月我院收治的310例SLE患者作为研究对象，根据有无继发真菌感染分为未感染组和感染组，经倾向性评分法（propensity score matching，PSM）进行5：1匹配后，未感染组和感染组分别纳入患者230例、46例。分析SLE患者继发真菌感染现状，通过Logistic回归分析SLE患者继发真菌感染的影响因素，并采用受试者工作特征（receiver operating characteristic，ROC）曲线评估模型预测效能，构建预测SLE患者继发真菌感染的列线图模型。结果 在纳入的310例SLE患者中真菌感染46例（14.84%），以肺部感染（50.0%）和胃肠道感染（23.9%）为主。匹配分组后，二元Logistic回归分析结果显示，狼疮活动度（OR=10.734，95%CI=2.015～57.184）、抗菌药物应用时间（OR=13.826，95%CI=2.995～63.822）、CRP（OR=9.927，95%CI=1.024～96.188）、白细胞计数（OR=11.784，95%CI=1.568～88.553）、补体C4（OR=16.392，95%CI=3.899～68.909）、24 h Pro（OR=9.391，95%CI=1.195～73.813）均为SLE患者继发真菌感染的独立危险因素（P<0.05）。ROC曲线评估显示，狼疮活动度、抗菌药物应用时间、C反应蛋白、白细胞计数、补体C4、24 h尿蛋白对SLE患者继发真菌感染均有一定的预测能力，六者联合预测的曲线下面积（area under the curve，AUC）为0.821，95%CI为0.720～0.922，优于单一指标（AUC 0.593~0.672）。此六者联合纳入构建列线图模型。结论 狼疮活动度、抗菌药物应用时间、CRP、WBC、补体C4、24 h Pro是SLE患者继发真菌感染的影响因素。

Abstract

Objective To investigate the influencing factors for secondary fungal infections in patients with systemic lupus erythematosus (SLE). Methods A total of 310 SLE patients admitted to our hospital between June 2021 and January 2025 were retrospectively enrolled. They were divided into an infection group and a non-infection group based on the presence or absence of secondary fungal infections. After 5:1 matching using propensity score matching (PSM), 230 patients in the non-infection group and 46 patients in the infection group were included in the final analysis. The characteristics of secondary fungal infections in patients with SLE were analyzed. Logistic regression analysis was performed to identify factors associated with secondary fungal infections, and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the model. A nomogram model for predicting secondary fungal infections in SLE patients was subsequently established. Results Among the 310 SLE patients enrolled, fungal infection occurred in 46 cases (14.84%), predominantly involving the lung (50.0%) and the gastrointestinal tract (23.9%). After PSM, binary logistic regression analysis revealed that lupus disease activity (odds ratio [OR] = 10.734, 95% CI: 2.015-57.184), duration of antibiotic use (OR = 13.826, 95% CI: 2.995-63.822), C-reactive protein (CRP) (OR = 9.927, 95% CI: 1.024-96.188), white blood cell (WBC) count (OR = 11.784, 95% CI: 1.568-88.553), complement C4 (OR = 16.392, 95% CI: 3.899-68.909), and 24-hour urine protein (24 h Pro) (OR = 9.391, 95% CI: 1.195-73.813) were independent risk factors for secondary fungal infections in SLE patients (allP < 0.05). ROC curve analysis demonstrated that lupus disease activity, duration of antibiotic use, CRP, WBC count, complement C4, and 24 h Pro all demonstrated predictive value for secondary fungal infections. The combined model incorporating all 6 indicators achieved an area under the ROC curve (AUC) of 0.821 (95% CI: 0.720-0.922), outperforming any individual indicator (AUC range: 0.593-0.672). A nomogram prediction model was subsequently established based on these 6 indicators. Conclusion Lupus activity, duration of antibiotic use, CRP, WBC, complement C4, and 24 h Pro are the influencing factors of secondary fungal infection in SLE patients.

关键词

系统性红斑狼疮 / 真菌感染 / 影响因素 / 倾向性评分法

Key words

Systemic lupus erythematosus / Fungal infection / Influencing factors / Propensity score matching

参考文献

[1] De Campos M R, Della F C P, Solórzano C L V, et al. A destructive nasal skin lesion caused by fungal infection in a systemic lupus erythematosus patient[J]. Clin Rheumatol, 2023, 42(5): 1487. DOI: 10.1007/s10067-023-06544-5.

[2] Restrepo-Escobar M, Granda-Carvajal P A, Aguirre D C, et al. Predictive models of infection in patients with systemic lupus erythematosus: a systematic literature review[J]. Lupus, 2021, 30(3): 421. DOI: 10.1177/0961203320983462.

[3] 杨建敏, 王怡佳, 杨惠芳, 等. 系统性红斑狼疮患者淋巴细胞亚群和TLR9及TLR2预测继发真菌感染的临床价值[J]. 中华医院感染学杂志, 2025, 35(4): 523. DOI: 10.11816/cn.ni.2025-240750.

[4] Yang J M, Wang Y J, Yang H F, et al. Clinical values of lymphocyte subsets, TLR9 and TLR2 in prediction of secondary fungal infection in patients with systemic lupus erythematosus[J]. Chin J Nosocomiol, 2025, 35(4): 523. DOI: 10.11816/cn.ni.2025-240750.

[5] Roe K. Increased fungal infection mortality induced by concurrent viral cellular manipulations[J]. Lung, 2023, 201(5): 467. DOI: 10.1007/s00408-023-00642-6.

[6] Maturo F, Rambaud S C. On the use of propensity score matching in biomedicine and pulmonology[J]. Arch Bronconeumol, 2022, 58(9): 637. DOI: 10.1016/j.arbres.2021.12.010.

[7] 钟会英, 谢立虎, 欧大明, 等. 系统性红斑狼疮患者JAK/STAT信号通路表达与继发深部真菌感染的关联[J]. 中华医院感染学杂志, 2022, 32(15): 2294. DOI: 10.11816/cn.ni.2022-212243.

[8] Zhong H Y, Xie L H, Ou D M, et al. Relationship between expressions of JAK/STAT signaling pathways and secondary deep fungal infection in patients with systemic lupus erythematosus[J]. Chin J Nosocomiol, 2022, 32(15): 2294. DOI: 10.11816/cn.ni.2022-212243.

[9] 中华医学会风湿病学分会, 国家皮肤与免疫疾病临床医学研究中心, 中国系统性红斑狼疮研究协作组. 2020中国系统性红斑狼疮诊疗指南[J]. 中华内科杂志, 2020, 59(3): 172. DOI: 10.3760/cma.j.issn.0578-1426.2020.03.002.

[10] Chinese Rheumatology Association, National Clinical Research Center for Dermatologic and Immunologic Diseases, Chinese Systemic Lupus Erythematosus Treatment and Research Group. 2020 Chinese guidelines for the diagnosis and treatment of systemic lupus erythematosus[J]. Chin J Intern Med, 2020, 59(3): 172. DOI: 10.3760/cma.j.issn.0578-1426.2020.03.002.

[11] 中华医学会重症医学分会. 重症患者侵袭性真菌感染诊断与治疗指南(2007)[J]. 中华内科杂志, 2007, 46(11): 960. DOI: 10.3760/j.issn:0578-1426.2007.11.031.

[12] Chinese Medical Association, Society of Critical Care Medicine. Guidelines for the diagnosis and treatment of invasive fungal infections in vritically ill patients (2007)[J]. Chin J Intern Med, 2007, 46(11): 960. DOI: 10.3760/j.issn:0578-1426.2007.11.031.

[13] Touma Z, Gladman D D, Zandy M, et al. Identifying a response for the systemic lupus erythematosus disease activity 2000 glucocorticoid index[J]. Arthritis Care Res (Hoboken), 2021, 73(9): 1243. DOI: 10.1002/acr.24261.

[14] Hennessee I, Benedict K, Bahr N C, et al. Incidence and risk factors for invasive fungal infections in patients initiating tumor necrosis factor-alpha inhibitors for inflammatory bowel disease and rheumatoid arthritis[J]. Clin Infect Dis, 2025, 80(2): 364. DOI: 10.1093/cid/ciae444.

[15] Alqurashi M, Alqatari S, Alzaher M Z, et al. Recurrent non-lactational fungal abscesses in a systemic lupus erythematosus patient: causation or mere association? A case report and literature review[J]. Med Arch, 2022, 76(5): 391. DOI: 10.5455/medarh.2022.76.391-394.

[16] Roberts J E, Faino A, Bryan M A, et al. Hospitalization and mortality due to infection among children and adolescents with systemic lupus erythematosus in the United States[J]. J Rheumatol, 2024, 51(9): 891. DOI: 10.3899/jrheum.2023-1219.

[17] 陈艳, 谢丽斯, 邓新杰, 等. 系统性红斑狼疮合并真菌感染外周血Toll样受体9和MX1与CCR5表达及意义[J]. 中华医院感染学杂志, 2022, 32(13): 1973. DOI: 10.11816/cn.ni.2022-211907.

[18] Chen Y, Xie L S, Deng X J, et al. Expression of toll-like receptor 9, MX1 and CCR5 in peripheral blood of systemic lupus erythematosus patients complicated with fungal infection and their significance[J]. Chin J Nosocomiol, 2022, 32(13): 1973. DOI: 10.11816/cn.ni.2022-211907.

[19] 李情情, 岳倩文, 钱亚云, 等. 儿童系统性红斑狼疮合并感染的临床特征及危险因素分析[J]. 西部医学, 2024, 36(3): 422. DOI: 10.3969/j.issn.1672-3511.2024.03.019.

[20] Li Q Q, Yue Q W, Qian Y Y, et al. Analysis of clinical features and risk factors of childhood-onset systemic lupus erythematosus with infection[J]. Med J West China, 2024, 36(3): 422. DOI: 10.3969/j.issn.1672-3511.2024.03.019.

[21] Drummond R A, Desai J V, Ricotta E E, et al. Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria[J]. Cell Host Microbe, 2022, 30(7): 1020. DOI: 10.1016/j.chom.2022.04.013.

[22] Bruera S, Ventura M J, Agarwal S K, et al. The utility of erythrocyte sedimentation rate, C-reactive protein, and procalcitonin in detecting infections in patients with systemic lupus erythematosus: a systematic review[J]. Lupus, 2022, 31(10): 1163. DOI: 10.1177/09612033221106157.

[23] Carvalho J S, Carvalho M G, Reis E A, et al. Infection in hospitalized patients with systemic lupus erythematosus: proposal of an algorithm for diagnosis[J]. J Clin Rheumatol, 2022, 28(3): 113. DOI: 10.1097/RHU.0000000000001811.

[24] Huang P Q, Du H, Chen H B, et al. Invasive pulmonary fungal infections in children with severe human adenovirus type 7 pneumonia: a retrospective study[J]. Pediatr Neonatol, 2022, 63(4): 388. DOI: 10.1016/j.pedneo.2022.03.004.

[25] 徐舟舟. IL-17、IL-8及补体C3、C4水平与系统性红斑狼疮活动性关系分析[J]. 成都医学院学报, 2024, 19(4): 654. DOI: 10.3969/j.issn.1674-2257.2024.04.020.

[26] Xu Z Z. Relationship between IL-17, IL-8, C3, and C4 levels and the activity of systemic lupus erythematosus[J]. J Chengdu Med Coll, 2024, 19(4): 654. DOI: 10.3969/j.issn.1674-2257.2024.04.020.

[27] 杨琦, 郭楠, 栗晓斌, 等. 24小时尿蛋白, 尿液亚硝酸盐, 尿沉渣细菌定量计数诊断肾病综合征合并尿路感染的价值[J]. 浙江医学, 2024, 46(23): 2521. DOI: 10.12056/j.issn.1006-2785.2024.46.23.2024-652.

[28] Yang Q, Guo N, Li X B, et al. The 24 hour urine output, urine nitrite and quantitative count of urinary sediment bacteria for diagnosis of urinary tract infec-tion in patients with nephrotic syndrome[J]. Zhejiang Med J, 2024, 46(23): 2521. DOI: 10.12056/j.issn.1006-2785.2024.46.23.2024-652.

[29] 惠迪, 张丽华, 任语谦, 等. 狼疮性肾炎继发侵袭性肺曲霉病的临床特征及预后[J]. 肾脏病与透析肾移植杂志, 2024, 33(1): 16. DOI: 10.3969/j.issn.1006-298X.2024.01.003.

[30] Hui D, Zhang L H, Ren Y Q, et al. Clinical characteristics and prognosis of invasive pulmonary aspergillosis in patients with lupus nephritis[J]. Chin J Nephrol Dial Transplant, 2024, 33(1): 16. DOI: 10.3969/j.issn.1006-298X.2024.01.003.

基金资助

*国家自然科学基金青年项目(82402109)