Department of Pediatrics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Medical Administration, National Health Commission of the People's Republic of China, Beijing, China.
Lancet Child Adolesc Health. 2024 Oct;8(10):762-772. doi: 10.1016/S2352-4642(24)00172-X.
Childhood-onset systemic lupus erythematosus (SLE) is a complex autoimmune disorder that can lead to serious organ damage. Despite the prevalence of SLE among children in Asian countries, treatment guidelines, prognosis, and clinical decision making for children with SLE are limited by gaps in region-specific epidemiological data. The aim of this study was to analyse epidemiological characteristics of childhood-onset SLE and associated organ involvement and in-hospital mortality in China.
In this nationwide study, we searched standardised hospital discharge records submitted to the Hospital Quality Monitoring System (HQMS) between Jan 1, 2016, and Dec 31, 2021, for patients with a diagnosis of childhood-onset SLE based on the 2019 American College of Rheumatology or 2012 Systemic Lupus International Collaborating Clinics classification criteria. We selected records for patients aged 18 years and younger containing relevant ICD 10th revision diagnostic codes (specifically M32) among discharge diagnostic codes. We excluded records for patients younger than 5 years, whose SLE diagnosis was presumed to be monogenic lupus, and for patients with overlap syndromes or unidentified sex. Date of diagnosis (equal to the first hospital discharge date), age, organ involvement, intensive care unit (ICU) treatment, and in-hospital mortality were extracted from the records. Incidence rates for 2017, 2018, 2019, 2020, and 2021 were identified with five washout periods ranging from 12 months (Jan 1-Dec 31, 2016) to 60 months (Jan 1, 2016-Dec 31, 2020). Data were stratified by sex, age relative to puberty onset, organ involvement and concurrent infection at time of diagnosis, human development index of region of residence, hospital level, and hospital type. Incidence trends by sex, age relative to puberty onset, and year were derived by joinpoint regression analysis, with 95% CIs calculated by the Poisson exact method. Major organ involvement was assessed according to definitions in the British Isles Lupus Assessment Group 2004 disease activity index. Outcomes of ICU admission after first diagnosis and in-hospital death after ICU admission were analysed in Cox proportional hazards models, with p values and 95% CIs calculated with the parametric method.
Between Jan 1, 2016, and Dec 31, 2021, the HQMS received 134 956 hospital discharge records containing the M32 discharge diagnostic code for patients aged 18 years or younger. 6286 records were excluded, leaving 128 670 records representing 54 338 patients aged 5-18 years; of these, 43 756 patients (36 153 girls and 7603 boys) received their childhood-onset SLE diagnosis on or after Jan 1, 2017. Between Jan 1, 2017, and Dec 31, 2021, the SLE incidence rate was 3·97 (95% CI 3·93-4·01) per 100 000 person-years, with a declining trend during the 5-year period. Joinpoint analysis showed sex-dependent and age-dependent incidence patterns. After a relatively stable incidence rate among prepubertal children aged 5-7 years, the incidence rate increased among peripubertal children aged 8-12 years by 0·92 cases per 100 000 person-years with each 1-year increase in age (p<0·0001). Among peripubertal children aged 8-12 years, girls showed the largest change in incidence rate, with an increase of 1·64 per 100 000 person-years with each 1-year increase in age (p<0·0001), compared with 0·40 per 100 000 person-years with each 1-year increase in age among boys (p=0·013). The organ systems most affected in patients with childhood-onset SLE were the kidneys (56·8%) and the haematological system (27·8%). Among the 2471 patients admitted to the ICU, 213 (9%) of whom died in ICU, the three organ-related risk factors at initial diagnosis that showed greatest association with progression to critical illness were cardiovascular involvement (adjusted hazard ratio 2·50 [95% CI 2·18-2·87]; p<0·0001), neuropsychiatric SLE (2·10 [1·87-2·37]; p<0·0001), and serositis (2·03 [1·78-2·30]; p<0·0001). Other prominent risk factors for progression to critical illness were concurrent infections with Epstein-Barr virus (1·52 [1·16-1·98]; p=0·0020) or fungi (1·49 [1·22-1·83]; p=0·0001). In total, 396 (0·7%) of 54 338 patients with childhood-onset SLE died in hospital; the most common causes of death were pneumonia (146 [37%]), multi-organ dysfunction syndrome (99 [25%]), and renal failure (75 [19%]). Risk of in-hospital mortality was highest among pubertal children (hazard ratio 2·16 [95% 1·14-4·09]) compared with prepubertal children, and risk of ICU admission was highest among prepubertal children (2·95 [2·16-4·03]) compared with postpubertal children.
These nationwide data on the epidemiology of childhood-onset SLE in the Chinese paediatric population show for the first time a declining trend in incidence rates, rapid rise in puberty-onset rates, and the distinct involvement of vital organs from disease onset to mortality in China. They underscore the complexity of childhood-onset SLE pathogenesis and emphasise the imperative for stratified precision treatment, informed interventions, and health-care planning for childhood-onset SLE.
National Key Research & Development Program of China.
儿童期起病的系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，可导致严重的器官损害。尽管亚洲国家的儿童中 SLE 较为普遍，但由于缺乏特定于区域的流行病学数据，儿童 SLE 的治疗指南、预后和临床决策仍受到限制。本研究旨在分析中国儿童期起病的 SLE 的流行病学特征以及相关器官受累和住院死亡率。
在这项全国性研究中，我们从 2016 年 1 月 1 日至 2021 年 12 月 31 日的医院质量监测系统（HQMS）中检索了根据 2019 年美国风湿病学会或 2012 年系统性红斑狼疮国际协作临床分类标准的标准医院出院记录，以确定儿童期起病的 SLE 患者。我们从出院诊断代码中选择了包含特定 ICD 第 10 次修订诊断代码（具体为 M32）的 18 岁及以下患者的记录。我们排除了年龄小于 5 岁的患者的记录，这些患者的 SLE 诊断假定为单基因狼疮，以及重叠综合征或不明性别的患者的记录。从记录中提取了发病日期（等于首次住院日期）、年龄、器官受累、重症监护病房（ICU）治疗和住院死亡率。2017 年、2018 年、2019 年、2020 年和 2021 年的发病率是通过五个洗脱期确定的，洗脱期范围为 12 个月（2016 年 1 月 1 日至 2016 年 12 月 31 日）至 60 个月（2016 年 1 月 1 日至 2020 年 12 月 31 日）。根据患者发病时的性别、相对青春期的年龄、器官受累和并发感染、居住地区人类发展指数、医院级别和医院类型对数据进行分层。通过 joinpoint 回归分析得出了按性别、相对青春期的年龄和年份的发病率趋势，95%CI 通过泊松精确法计算。根据英国狼疮评估组 2004 年疾病活动指数的定义评估主要器官受累情况。通过 Cox 比例风险模型分析首次诊断后 ICU 入院和 ICU 入院后院内死亡的结局，p 值和 95%CI 通过参数法计算。
2016 年 1 月 1 日至 2021 年 12 月 31 日期间，HQMS 共收到 134956 份包含 18 岁及以下患者 M32 出院诊断代码的医院出院记录。排除了 6286 份记录，剩余了 128670 份代表 54338 名年龄在 5-18 岁的患者的记录；其中，43756 名（36153 名女孩和 7603 名男孩）在 2017 年 1 月 1 日或之后确诊为儿童期起病的 SLE。2017 年 1 月 1 日至 2021 年 12 月 31 日期间，SLE 的发病率为 3.97（95%CI 3.93-4.01）/10 万人年，呈下降趋势。joinpoint 分析显示，发病率呈性别依赖性和年龄依赖性。在 5-7 岁的青春期前儿童中相对稳定的发病率之后，8-12 岁的青春期儿童的发病率每年增加 1 岁，增加 0.92/10 万人年（p<0.0001）。在 8-12 岁的青春期儿童中，女孩的发病率变化最大，与年龄每增加 1 岁，发病率增加 1.64/10 万人年（p<0.0001）相比，男孩的发病率每年增加 1 岁，发病率增加 0.40/10 万人年（p=0.013）。儿童期起病的 SLE 患者最常受累的器官系统是肾脏（56.8%）和血液系统（27.8%）。在 2471 名入住 ICU 的患者中，213 名（9%）在 ICU 死亡，发病时与进展为危重病相关的三个器官相关危险因素是心血管受累（调整后的危险比 2.50[95%CI 2.18-2.87]；p<0.0001）、神经精神性 SLE（2.10[1.87-2.37]；p<0.0001）和浆膜炎（2.03[1.78-2.30]；p<0.0001）。进展为危重病的其他重要危险因素包括并发 EBV（1.52[1.16-1.98]；p=0.0020）或真菌（1.49[1.22-1.83]；p=0.0001）感染。共有 54338 名儿童期起病的 SLE 患者中的 396 名（0.7%）在医院死亡；死亡的最常见原因是肺炎（146 例[37%]）、多器官功能障碍综合征（99 例[25%]）和肾衰竭（75 例[19%]）。与青春期前儿童相比，青春期儿童的院内死亡率最高（危险比 2.16[95%CI 1.14-4.09]），与青春期后儿童相比，ICU 入院率最高（2.95[2.16-4.03]）。
这些来自中国儿科人群的儿童期起病的 SLE 流行病学的全国性数据首次表明，中国的发病率呈下降趋势，青春期发病的比率迅速上升，从发病到死亡的关键器官受累明显。这些数据突显了儿童期起病的 SLE 发病机制的复杂性，并强调了需要针对特定于疾病的分层精准治疗、干预措施和医疗保健规划。
国家重点研发计划。
