诊断性抗结核治疗在鉴别儿童克罗恩病与肠结核时评估工具和时点的诊断准确性研究

目的 探讨诊断性抗结核治疗在鉴别儿童克罗恩病(CD)与肠结核(ITB)中评估工具及其合适的鉴别时点。 方法 回顾性收集临床和病理难以判断CD或ITB且明确结核或抗酸染色阳性的病例，剔除入院前曾经抗结核治疗或应用免疫抑制剂和先天免疫缺陷合并结核感染。活检干酪样坏死，或病理抗酸染色阳性，或肠外活动性结核，或 PPD皮试强阳性，或细菌涂片阳性者，接受诊断性抗结核治疗，于诊断性抗结核治疗前（基线），治疗后3、6和12个月时，行儿童CD活动指数（PCDAI)评分、肠镜评估。诊断性抗结核治疗ITB确诊依据Logan修订的per Paustian标准。抗结核均采用2~3HRZE/7~10HR方案。 结果 26例难以判断CD或ITB的患儿完成了基线、3、6和12个月时的PCDAI评分和肠镜评估进入本文分析，ITB 组17例，CD 组9例，2组一般情况、临床表现、实验室检测指标、肠镜表现、小肠MRE表现、病理组织学表现、抗结核治疗时间和抗结核治疗方案差异无统计学意义。ITB组治疗3、6和12个月较基线PCDAI评分下降≥12.5分或不同时点PCDAI评分≤10分分别为6、14和16例；其中3个月较基线、6个月较3个月 、12个月较6个月PCDAI评分下降≥12.5分分别为6、4、4例。CD组治疗3、6和12个月较基线PCDAI评分下降≥12.5分或不同时点PCDAI评分≤10分分别为1、2、1例。ITB组和CD组，6个月时肠镜评估痊愈＋明显好转分别为76.5%（13/17）和22.2%（2/9），12个月时痊愈＋明显好转分别为94.1%（16/17）和11.1%（1/9），差异有统计学意义（Fisher精确检验，P=0.000）。以诊断性抗结核治疗ITB确诊标准作为金标准，3和6个月时PCDAI评分阳性预测值分别为85.7%和86.7%，6个月时肠镜评估阳性预测值86.7%；6个月时PCDAI评分+肠镜评估特异度88.9%，阳性预测值92.9%；12个月时PCDAI评分+肠镜评估阳性预测值（94.1%）比6个月时提高了1.2%。 结论 诊断性抗结核治疗过程中，难以判断有ITB或CD患儿临床症状好转较肠镜好转快，PCDAI评分+肠镜评估可作为难以判断ITB或CD患儿评估工具，诊断性抗结核治疗6个月时为最佳时点。

A clinical diagnostic accuracy study on the evaluation tool and time points of anti-tuberculosis trial treatment for differentiating between pediatric Crohn's disease and intestinal tuberculosis

Objective To investigate the evaluation standard and proper time point of anti-tuberculosis trial treatment for differential diagnosis between Crohn's disease (CD) and intestinal tuberculosis (ITB) in children. Methods Patients who were suspected CD or ITB by clinical symptoms and pathological examination, and confirmed with tuberculosis infection or positive acid-fast bacilli stain were retrospectively reviewed. Patients who had a history of anti-tuberculosis or immunosuppressant treatment and were diagnosed with congenital immunodeficiency disease combined with tuberculosis infection were excluded. Patients with caseous necrosis, positive acid-fast bacilli stain, extra-intestinal active tuberculosis, positive PPD test, positive bacterial smear test were administrated with anti-tuberculosis trial treatment. Pediatric Crohn's Disease Activity Index (PCDAI) and endoscopic evaluation were analyzed at 3, 6 and 12 months. ITB was confirmed by Paustian's criteria with Logan's modification and CD by pathological examination. Trial of anti-tuberculosis treatment were with 2-3 months of HRZE and 7-10 months OF HR. Results A total of 26 patients suspected CD or ITB were enrolled in this study. All cases were done PCDAI and endoscopic evaluation, 17 of them were diagnosed with ITB, 9 were with CD. No significant differences were found in clinical characteristics, laboratory index, endoscopy, small bowel MRE test, pathological examination, duration of anti-tuberculosis treatment and anti-tuberculosis drugs. In ITB group, the decrease of PCDAI ≥12.5 or the PCDAI≤10 between 3 months and baseline, between 6 months and baseline, between 12 months and baseline occurred in 6, 14 and 16 cases, respectively; whereas in CD group, the data were 1, 2 and 1 case, respectively. Mucosal healing and improvement rates of lesions at 6 months of treatment in ITB and CD group were 76.5% and 22.2%, respectively; the rate at 12 months was 94.1% and 11.1%, respectively (Fisher's exact test, P=0.000). To use success of anti-tuberculosis trial treatment as a golden standard, the positive predictive values of PCDAI at 3 and 6 months were 85.7% and 86.7%, respectively. The positive predictive value of endoscopic evaluation at 6 months was 86.7%. The specificity of PCDAI plus endoscopic evaluation was 88.9%, the positive predictive value was 92.9% which was 1.2% lower than that value at 12 months (94.1%). Conclusion With lack of special markers for differential diagnosis between CD and ITB, some cases still need to receive anti-tuberculosis trial treatment. In the course of anti-tuberculosis treatment, the improvement of clinical symptoms goes quickly compared with endoscopic evaluation. PCDAI plus endoscopic evaluation at 6 months of anti-tuberculosis trial treatment can be used as the best tool and time point for differentiating between ITB and CD in children.