我国儿童慢性无菌性骨髓炎临床特征及疗效分析: 多中心回顾性研究

Clinical Features and Treatment Outcomes of Chronic Nonbacterial Osteomyelitis in Children: A Multicenter Study in China

  • 摘要:
      目的  分析我国儿童慢性无菌性骨髓炎(chronic nonbacterial osteomyelitis, CNO)的临床特点及治疗效果,为CNO临床诊疗提供参考和借鉴。
      方法  收集2014年3月至2022年8月就诊于国内5家医学中心(复旦大学附属儿科医院、中国医学科学院北京协和医院、南京医科大学附属儿童医院、重庆医科大学附属儿童医院和吉林大学第一医院)且符合纳入与排除标准的CNO患儿临床资料,并根据治疗方案分为单纯非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAID)组、传统抗风湿病药物(disease modifying anti-rheumatic drugs,DMARD)组、肿瘤坏死因子拮抗剂(tumor necrosis factor inhibitor,TNF-i)组、双膦酸盐组、双膦酸盐+TNF-i组,比较各组临床特征并采用改良医师总体评估评分进行疗效评价。
      结果  共纳入58例CNO患儿,男女比例约为1.15(31例比27例);平均发病年龄为(8.5±3.4)岁,平均确诊年龄为(9.8±3.2)岁;中位随访时间为10.9(5.0,30.1)个月;近3年共确诊46例(79.3%);发热31例(53.4%)、骨痛和/或关节痛54例(93.1%)、红细胞沉降率升高51例(87.9%)、C反应蛋白升高45例(77.6%);常见骨受累部位为下肢骨,其中股骨42例、胫骨41例,3例就诊时即存在椎骨压缩性骨折;33例骨活检结果为亚急性或慢性骨髓炎;各治疗组缓解率无统计学差异(P=0.562),双膦酸盐+TNF-i组11个月缓解率为60.0%,NSAID组和DMARD组11个月缓解率分别为55.6%和33.3%;NSAID组和TNF-i组12个月缓解率分别为66.7%和52.4%;共40例随访时间≥6个月,随访终点治疗缓解率为81.3%。
      结论  我国多中心CNO患儿临床表现缺乏特异性,以骨痛和/或关节痛为主要临床特点,可伴有发热、外周血白细胞基本正常、C反应蛋白和/或红细胞沉降率升高,各治疗组疗效相似,目前NSAID抗炎治疗为临床首选治疗方案。

     

    Abstract:
      Objective  To investigate the clinical features and treatment outcomes of chronic non-bacterial osteomyelitis (CNO) from five tertiary pediatric rheumatology services in China and provide possible treatment options for clinicians.
      Methods  In this multicenter, retrospective study, pediatric patients diagnosed with CNO in Children's Hospital of Fudan University, Peking Union Medical College Hospital, Children's Hospital of Nanjing Medical University, Children's Hospital of Chongqing Medical University and the First Hospital of Jilin University from March 2014 to August 2022 were included. According to the treatment plan, the patients were divided into nonsteroidal anti-inflammatory drugs (NSAID) group, traditional disease modifying anti-rheumatic drugs (DMARD) group, tumor necrosis factor inhibitor (TNF-i) group, bisphosphonate group, and bisphosphonate+TNF-i group, and physician global assessment score was used to evaluate the efficacy.
      Results  Retrospective data analysis showed that the disease was more common in boy sthan girls(31 vs. 27), and the average age at onset of symptoms was 8.5±3.4 years, the mean age of diagnosis was 9.8±3.2 years, and the Median follow-up was 10.9(5.0, 30.1) months. A total of 46 cases (79.3%) were diagnosed in the last 3 years. Bone pain and / or arthralgia was the predominant symptom in 54(93.1%) patients followed by fever in 31(53.4%) patients. Raised inflammatory markers (ESR and CRP) were present in 87.9% and 77.6% of the patients. The most frequently affected bones were lower limb bones, including 42 cases of femur and 41 cases of tibia; 3 patients had compression fractures of the vertebrae at the time of diagnosis. Bone biopsy was conducted in 33 cases, and subacute or chronic osteomyelitis manifested with inflammatory cells infiltration were detected. The remission rate was not statistically different between treatment groups (P=0.562), with the remission rate at 11 months in the bisphosphonate+TNF-i group being 60.0%, 55.6% and 33.3% in the NSAID and DMARD groups respectively; 66.7% and 52.4% in the NSAID and TNF-i groups respectively at 12 months. A total of 40 patients were followed up for ≥6 months, with the remission rate of 81.3%.
      Conclusions  Our multicenter study describes the features and outcomes of CNO patients in China. The characteristics of CNO children from multiple centers in China were lack of specificity. Bone pain and/or arthralgia were the main clinical symptoms, accompanied by fever, normal white blood cells, and raised inflammatory markers (CRP and/or ESR). Although anti-inflammatory treatment regimens were different, the efficacy of the treatment groups was similar. Anti-inflammatory therapy is currently the first choice.

     

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