中国儿童Blau综合征临床特点和治疗分析-全国多中心研究

张俊梅; 赵晓珍; 唐雪梅; 赵伊楠; 李丽; 高凤乔; 史昕炜; 金燕樑; 张宇; 曹兰芳; 尹薇; 肖继红; 邝伟英; 邓江红; 王江; 檀晓华; 李超; 李士朋; 薛海燕; 刘翠华; 刘小惠; 赵冬梅; 陈雨青; 郑雯洁; 李彩凤

doi:10.12376/j.issn.2097-0501.2022.03.005

文章导航 > 罕见病研究 > 2022 > 1(3): 252-258

张俊梅, 赵晓珍, 唐雪梅, 赵伊楠, 李丽, 高凤乔, 史昕炜, 金燕樑, 张宇, 曹兰芳, 尹薇, 肖继红, 邝伟英, 邓江红, 王江, 檀晓华, 李超, 李士朋, 薛海燕, 刘翠华, 刘小惠, 赵冬梅, 陈雨青, 郑雯洁, 李彩凤. 中国儿童Blau综合征临床特点和治疗分析-全国多中心研究[J]. 罕见病研究, 2022, 1(3): 252-258. doi: 10.12376/j.issn.2097-0501.2022.03.005

引用本文:

ZHANG Junmei, ZHAO Xiaozhen, TANG Xuemei, ZHAO Yi'nan, LI Li, GAO Fengqiao, SHI Xinwei, JIN Yanliang, ZHANG Yu, CAO Lanfang, YIN Wei, XIAO Jihong, KUANG Weiying, DENG Jianghong, WANG Jiang, TAN Xiaohua, LI Chao, LI Shipeng, XUE Haiyan, LIU Cuihua, LIU Xiaohui, ZHAO Dongmei, CHEN Yuqing, ZHENG Wenjie, LI Caifeng. Clinical Characteristics and Treatment of Blau Syndrome in Chinese Children-a National Multicenter Study[J]. Journal of Rare Diseases, 2022, 1(3): 252-258. doi: 10.12376/j.issn.2097-0501.2022.03.005

Citation:

ZHANG Junmei, ZHAO Xiaozhen, TANG Xuemei, ZHAO Yi'nan, LI Li, GAO Fengqiao, SHI Xinwei, JIN Yanliang, ZHANG Yu, CAO Lanfang, YIN Wei, XIAO Jihong, KUANG Weiying, DENG Jianghong, WANG Jiang, TAN Xiaohua, LI Chao, LI Shipeng, XUE Haiyan, LIU Cuihua, LIU Xiaohui, ZHAO Dongmei, CHEN Yuqing, ZHENG Wenjie, LI Caifeng. Clinical Characteristics and Treatment of Blau Syndrome in Chinese Children-a National Multicenter Study[J]. Journal of Rare Diseases, 2022, 1(3): 252-258. doi: 10.12376/j.issn.2097-0501.2022.03.005

引用本文:

Citation:

ZHANG Junmei, ZHAO Xiaozhen, TANG Xuemei, ZHAO Yi'nan, LI Li, GAO Fengqiao, SHI Xinwei, JIN Yanliang, ZHANG Yu, CAO Lanfang, YIN Wei, XIAO Jihong, KUANG Weiying, DENG Jianghong, WANG Jiang, TAN Xiaohua, LI Chao, LI Shipeng, XUE Haiyan, LIU Cuihua, LIU Xiaohui, ZHAO Dongmei, CHEN Yuqing, ZHENG Wenjie, LI Caifeng. Clinical Characteristics and Treatment of Blau Syndrome in Chinese Children-a National Multicenter Study[J]. Journal of Rare Diseases, 2022, 1(3): 252-258. doi: 10.12376/j.issn.2097-0501.2022.03.005

中国儿童Blau综合征临床特点和治疗分析-全国多中心研究

doi: 10.12376/j.issn.2097-0501.2022.03.005

张俊梅^{1, *},
赵晓珍^{1, *},
唐雪梅²,
赵伊楠¹,
李丽¹,
高凤乔¹,
史昕炜¹,
金燕樑³,
张宇²,
曹兰芳⁴,
尹薇⁵,
肖继红⁶,
邝伟英¹,
邓江红¹,
王江¹,
檀晓华¹,
李超¹,
李士朋¹,
薛海燕⁴,
刘翠华⁷,
刘小惠¹,
赵冬梅¹,
陈雨青¹⁰,
郑雯洁¹¹,
李彩凤^1, ,

1.
国家儿童医学中心首都医科大学附属北京儿童医院风湿科，北京 100045
2.
重庆医科大学附属儿童医院风湿免疫科，重庆 400014
3.
上海交通大学医学院附属上海儿童医学中心风湿免疫科，上海 200127
4.
上海交通大学医学院附属仁济医院儿科，上海 200001
5.
武汉儿童医院风湿免疫科，武汉 430016
6.
厦门大学附属第一医院儿科，厦门 361003
7.
郑州大学附属儿童医院河南省儿童医院郑州儿童医院肾脏风湿科，郑州 450018
8.
江西省儿童医院风湿免疫科南昌大学附属儿童医院，南昌 330000
9.
新疆乌鲁木齐市第一人民医院(儿童医院)风湿免疫科，乌鲁木齐 830001
10.
安徽省儿童医院内分泌风湿免疫科，合肥 230051
11.
温州医科大学附属育英儿童医院儿童风湿科，温州 325000

基金项目:

北京市医院管理局儿科学科协同发展中心专项经费资助 XTCX201819

^*张俊梅和赵晓珍为共同第一作者

详细信息

通信作者:
李彩凤，E-mail：caifeng_li@yeah.net

中图分类号: R725.9
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- 被引次数: 0
出版历程
- 收稿日期: 2022-05-26
- 录用日期: 2022-06-05
- 网络出版日期: 2022-09-06

Clinical Characteristics and Treatment of Blau Syndrome in Chinese Children-a National Multicenter Study

1.
Department of Rheumatology, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health, Beijing 100045, China
2.
Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China
3.
Department of Rheumatology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
4.
Department of Pediatrics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China
5.
Department of Rheumatology and Immunology, Wuhan Children's Hospital, Wuhan 430016, China
6.
Department of Pediatrics, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China
7.
Department of Nephrology and Rheumatology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou 450018, China
8.
Department of Rheumatology and Immunology, Jiangxi Provincal Children's Hospital, the Affiliated Children's Hospital of Nanchang University, Nanchang 330000, China
9.
Department of Rheumatology and Immunology, Xinjiang Urumqi Children's Hospital, Urumqi 830001, China
10.
Department of Endocrinology, Rheumatology and Immunology, Anhui Provincial Children's Hospital, Hefei 230051, China
11.
Department of Paediatric Rheumatology, the 2^nd Affiliated Hospital and Yuying Children's Hospital of WMU, Wenzhou 325000, China

Funding:

Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority XTCX201819

More Information

Corresponding author: LI Caifeng, E-mail: caifeng_li@yeah.net

摘要

摘要: 目的研究中国儿童Blau综合征的人口学特征、临床特点、基因型和表型的相关性及治疗情况，使该病能早期诊断并及时治疗。方法回顾性分析全国11家中心2006年5月至2022年4月住院的中国儿童Blau综合征患者72例，收集其年龄、性别、家族史等一般信息及临床资料、化验检查及治疗用药情况。结果 Blau综合征患者南北方分布较为均匀，无明显的地域倾向性。平均发病年龄(14.30±12.81)月，确诊年龄(55.18±36.22)月。35%的Blau综合征患者发病年龄在1岁之前，全部患者发病均在5岁之前。87.50%(63/72)患者出现肉芽肿性关节炎，65.28%(47/72) 患者出现皮疹，36.11%(26/72)患者出现眼部受累，27.78% (20/72)患者出现发热，15.28%(11/72)患者出现肺部受累。Blau综合征出现肉芽肿性关节炎表现的风险最大，其次为皮疹、眼部受累、发热。病程前25个月，出现皮疹的风险最大。病程25~84个月，发生关节炎的风险最大。Blau综合征主要的基因突变类型为p.R334Q和p.R334W，携带p.R334Q突变的患者有相对较高的发热[35.71%(5/14)vs. 14.29%(1/7)，P=0.43]和眼部受累[42.86%(6/14)vs. 28.57% (2/7)，P=0.51]发生率。在p.R334W突变的患者中，有相对较高的皮疹发生率[85.71% (6/7)vs. 64.29% (9/14)，P=0.59]。45例(62.50%)患者应用糖皮质激素和甲氨蝶呤的联合治疗。22例患者在糖皮质激素和甲氨蝶呤治疗的基础上加用TNF-α拮抗剂。结论中国儿童Blau综合征不同临床表现出现的风险由高至低依次为关节炎、皮疹、眼部受累、发热。主要治疗药物为糖皮质激素和甲氨蝶呤，可根据情况加用生物制剂。
- Blau综合征 /
- 人口学特征 /
- 临床表现 /
- 治疗
Abstract: Objective To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome. Methods Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected. Results The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate. Conclusions The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.
- Blau syndrome /
- demographic characteristics /
- clinical manifestations /
- treatment
注释:

作者贡献：李彩凤负责研究设计；张俊梅、赵晓珍负责数据分析、论文撰写；唐雪梅、赵伊楠、李丽、高凤乔、史昕炜、金燕樑、张宇、曹兰芳、尹薇、肖继红、邝伟英、邓江红、王江、檀晓华、李超、李士朋、薛海燕、刘翠华、刘小惠、赵冬梅、陈雨青、郑雯洁负责临床资料收集。

利益冲突：所有作者均声明不存在利益冲突。

HTML全文

图 1 Blau综合征患者的发病率

A. Blau综合征总发病率；B. Blau综合征不同临床表现的风险预测

Figure 1. Incidence in patients with Blau syndrome

下载: 全尺寸图片幻灯片

图 2 72例Blau综合征患者的治疗现状

A.传统治疗的现状; B.生物制剂应用的现状

Figure 2. Treatment status of 72 patients with Blau syndrome

下载: 全尺寸图片幻灯片

表 1 72例儿童Blau综合征患者的人口学和临床特征

Table 1. Demographic and clinical characteristics of 72 children with Blau syndrome

指标	例数	百分比(%)
籍贯：北方	39	54.17
家族史	17	23.61
性别：女	32	44.44
发病年龄(x±s，个月)	14.30±12.81	-
确诊年龄(x±s，个月)	55.18±36.22	-
发热	20	27.78
皮疹	47	65.28
肉芽肿性关节炎	63	87.50
眼部受累	26	36.11
高血压	1	1.39
骨软骨瘤	2	2.78
听力损害	4	5.56
肾脏受累	1	1.39
血管炎	24	33.33
心脏受累	4	5.56
肺部受累	11	15.28
中枢神经系统受累	2	2.78
中国北方：中国南北方划分以秦岭——淮河为界，此线以北，定义为北方

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