Chen Houyu, Yang Xiaotao, Huang Yi, Jiao Feng, Bai Houxi, Zhu Ying, Cui Penghao, Jin Haifeng, Guo Yan, Wang Yanchun, Luo Yonghan
Second Department of Infectious Disease, Kunming Children's Hospital, Kunming, Yunnan, China.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China.
Front Cell Infect Microbiol. 2025 May 21;15:1570382. doi: 10.3389/fcimb.2025.1570382. eCollection 2025.
This study aimed to analyze the clinical characteristics and genetic features of children with adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine. The goal was to improve understanding of this condition, provide insights into early diagnosis and intervention, and support stratified management.
Clinical data of 35 children hospitalized at Kunming Children's Hospital between January 2014 and June 2024 with complete records and diagnosed with BCG vaccine adverse reactions were collected. Cases were classified into two groups: disseminated BCG disease (BCG-D) and BCG-itis. Children with primary immunodeficiency (PID) were further divided into severe combined immunodeficiency (SCID) and non-SCID groups. Clinical characteristics, immunological profiles, genetic backgrounds, and outcomes were compared between the groups.
Among the 35 cases, 25 were male, and 10 were female, with a median age of onset of 2 months (1-4 months). Eight cases (22.9%) were diagnosed with BCG-D, while 27 cases (77.1%) were classified as BCG-itis. Sixteen cases (45.7%) were confirmed to have PID, including SCID (7 cases, 20.0%), chronic granulomatous disease (6 cases, 17.1%), Mendelian susceptibility to mycobacterial disease (2 cases, 5.7%), and fas associated via death domain (FADD) gene mutation (1 case, 2.6%). Compared to the BCG-itis group, the BCG-D group exhibited significantly higher rates of fever, hepatosplenomegaly, elevated white blood cell counts, neutrophil counts, and C-reactive protein (CRP) levels, along with lower red blood cell counts and hemoglobin levels (p<0.05). Similarly, the SCID group showed significantly lower age, lymphocyte counts, IgM levels, CD3, CD4, and CD8 cell ratios, but higher CD19 cell ratios and mortality rates compared to the non-SCID group (p<0.05). Twenty-seven (77.1%) cases were discharged after improvement, and eight children (22.9%) succumbed to the condition, including six with SCID gene mutations (representing 85.7% of the total SCID cases), one with an interleukin 12 receptor subunit beta 1(IL12RB1) mutation, and one who was not genetically tested but diagnosed with disseminated BCG disease.
In children presenting with adverse reactions to the BCG vaccine, the presence of fever, hepatosplenomegaly, elevated neutrophil levels, and CRP should prompt evaluation for disseminated BCG disease and assessment of immunological status. Early identification of underlying PID, particularly SCID, is crucial, given the high mortality and poor prognosis associated with the condition, necessitating timely interventions.
本研究旨在分析卡介苗（BCG）疫苗不良反应患儿的临床特征和基因特征。目标是增进对这种情况的了解，为早期诊断和干预提供见解，并支持分层管理。
收集2014年1月至2024年6月在昆明市儿童医院住院的35例记录完整且诊断为卡介苗疫苗不良反应患儿的临床资料。病例分为两组：播散性卡介苗病（BCG-D）和卡介苗炎。原发性免疫缺陷（PID）患儿进一步分为严重联合免疫缺陷（SCID）和非SCID组。比较各组的临床特征免疫谱、基因背景和结局。
35例患儿中，男性25例，女性10例，发病年龄中位数为2个月（1-4个月）。8例（22.9%）诊断为BCG-D，27例（77.1%）分类为卡介苗炎。16例（45.7%）确诊为PID，包括SCID（7例，20.0%）、慢性肉芽肿病（6例，17.1%）、孟德尔分枝杆菌病易感性（2例，5.7%）和死亡结构域相关的Fas（FADD）基因突变（1例，2.6%）。与卡介苗炎组相比，BCG-D组发热、肝脾肿大、白细胞计数、中性粒细胞计数及C反应蛋白（CRP）水平显著更高，而红细胞计数和血红蛋白水平更低（p<0.05）。同样，与非SCID组相比，SCID组年龄、淋巴细胞计数、IgM水平、CD3、CD4和CD8细胞比例显著更低，但CD19细胞比例和死亡率更高（p<0.05）。27例（77.1%）患儿病情好转后出院，8例（22.9%）患儿死亡，其中6例有SCID基因突变（占SCID病例总数的85.7%），1例有白细胞介素12受体亚基β1（IL12RB1）突变，1例未进行基因检测但诊断为播散性卡介苗病。
对于出现卡介苗疫苗不良反应的儿童，发热、肝脾肿大、中性粒细胞水平升高和CRP升高应促使对播散性卡介苗病进行评估并评估免疫状态。鉴于该疾病死亡率高且预后差，早期识别潜在的PID，尤其是SCID至关重要，需要及时干预。
