Silva Marco F, Ferriani Mariana P, Terreri Maria T, Pereira Rosa M, Magalhães Claudia S, Bonfá Eloisa, Campos Lucia M, Okuda Eunice M, Appenzeller Simone, Ferriani Virgínia P, Barbosa Cássia M, Ramos Valéria C, Lotufo Simone, Silva Clovis A
From the Pediatric Rheumatology Unit, and Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo; Pediatric Rheumatology Unit, Universidade Federal de São Paulo; Faculdade de Medicina de Botucatu, São Paulo State University; Irmandade da Santa Casa de Misericórdia de São Paulo; State University of Campinas; Ribeirão Preto Medical School, University of São Paulo; Hospital Infantil Darcy Vargas; Pontifical Catholic University of Sorocaba; Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil.M.F. Silva, MD, Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo; M.P. Ferriani, MD, Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo; M.T. Terreri, MD, PhD, Pediatric Rheumatology Unit, Universidade Federal de São Paulo; R.M. Pereira, MD, PhD, Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo; C.S. Magalhães, MD, PhD, Faculdade de Medicina de Botucatu, São Paulo State University; E. Bonfá, MD, PhD, Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo; L.M. Campos, MD, PhD, Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo; E.M. Okuda, MD, PhD, Irmandade da Santa Casa de Misericórdia de São Paulo; S. Appenzeller, MD, PhD, State University of Campinas; V.P. Ferriani, MD, PhD, Ribeirão Preto Medical School, University of São Paulo; C.M. Barbosa, MD, PhD, Hospital Infantil Darcy Vargas; V.C. Ramos, MD, Pontifical Catholic University of Sorocaba; S. Lotufo, MD, Hospital Municipal Infantil Menino Jesus; C.A. Silva, MD, PhD, Pediatric Rheumatology Unit, Faculdade de Medicina da Universidade de São Paulo.
J Rheumatol. 2015 Dec;42(12):2296-303. doi: 10.3899/jrheum.150142.
To study the prevalence, risk factors, and mortality of invasive fungal infections (IFI) in patients with childhood-onset systemic lupus erythematosus (cSLE).
A retrospective multicenter cohort study was performed in 852 patients with cSLE from 10 pediatric rheumatology services. An investigator meeting was held and all participants received database training. IFI were diagnosed according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group criteria (proven, probable, and possible). Also evaluated were demographic, clinical, and laboratory data, and disease activity [SLE Disease Activity Index 2000 (SLEDAI-2K)], cumulative damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), treatment, and outcomes.
IFI were observed in 33/852 patients (3.9%) with cSLE. Proven IFI was diagnosed in 22 patients with cSLE, probable IFI in 5, and possible IFI in 6. Types of IFI were candidiasis (20), aspergillosis (9), cryptococcosis (2), and 1 each disseminated histoplasmosis and paracoccidioidomycosis. The median of disease duration was lower (1.0 vs 4.7 yrs, p < 0.0001) with a higher current SLEDAI-2K [19.5 (0-44) vs 2 (0-45), p < 0.0001] and current prednisone (PRED) dose [50 (10-60) vs 10 (2-90) mg/day, p < 0.0001] in patients with IFI compared with those without IFI. The frequency of death was higher in the former group (51% vs 6%, p < 0.0001). Logistic regression analysis revealed that SLEDAI-2K (OR 1.108, 95% CI 1.057-1.163, p < 0.0001), current PRED dose (OR 1.046, 95% CI 1.021-1.071, p < 0.0001), and disease duration (OR 0.984, 95% CI 0.969-0.998, p = 0.030) were independent risk factors for IFI (R(2) Nagelkerke 0.425).
To our knowledge, this is the first study to characterize IFI in patients with cSLE. We identified that disease activity and current glucocorticoid use were the main risk factors for these life-threatening infections, mainly in the first years of disease course, with a high rate of fatal outcome.
研究儿童期起病的系统性红斑狼疮（cSLE）患者侵袭性真菌感染（IFI）的患病率、危险因素及死亡率。
对来自10个儿科风湿病诊疗机构的852例cSLE患者进行了一项回顾性多中心队列研究。召开了研究者会议，所有参与者均接受了数据库培训。IFI根据欧洲癌症研究与治疗组织/侵袭性真菌感染协作组及美国国立过敏与传染病研究所真菌病研究组共识组标准（确诊、很可能、可能）进行诊断。还评估了人口统计学、临床和实验室数据，以及疾病活动度[系统性红斑狼疮疾病活动指数2000（SLEDAI-2K）]、累积损伤（系统性红斑狼疮国际协作临床中心/美国风湿病学会损伤指数）、治疗及转归。
在852例cSLE患者中有33例（3.9%）观察到IFI。22例cSLE患者确诊为IFI，5例为很可能IFI，6例为可能IFI。IFI类型为念珠菌病（20例）、曲霉病（9例）、隐球菌病（2例），播散性组织胞浆菌病和副球孢子菌病各1例。与无IFI的患者相比，IFI患者的疾病持续时间中位数较低（1.0年对4.7年，p<0.0001），当前SLEDAI-2K评分较高[19.5（0-44）对2（0-45），p<0.0001]，当前泼尼松（PRED）剂量较高[50（10-60）对10（2-90）mg/天，p<0.0001]。前一组的死亡频率较高（51%对6%，p<0.0001）。逻辑回归分析显示，SLEDAI-2K（比值比1.108，95%置信区间1.057-1.163，p<0.0001）、当前PRED剂量（比值比1.046，95%置信区间1.021-1.071，p<0.0001）和疾病持续时间（比值比0.984，95%置信区间0.969-0.998，p=0.030）是IFI的独立危险因素（Nagelkerke R² 0.425）。
据我们所知，这是第一项描述cSLE患者IFI特征的研究。我们发现疾病活动度和当前糖皮质激素的使用是这些危及生命感染的主要危险因素，主要在疾病病程的最初几年，且致死率很高。
