The Juliet Keidan Institute of Pediatric Gastroenterology, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.
Division of Pediatric Gastroenterology, Hospital for Sick Children, Toronto, Canada.
Clin Gastroenterol Hepatol. 2018 Jul;16(7):1089-1097.e4. doi: 10.1016/j.cgh.2018.01.024. Epub 2018 Mar 2.
BACKGROUND & AIMS: Bowel healing is an important goal of therapy for patients with Crohn's disease (CD). Although there have been many studies of mucosal healing, transmural healing (ie, in the bowel wall) has not been investigated in children. We analyzed data from the ImageKids study to determine associations among mucosal, transmural healing and levels of calprotectin and C-reactive protein in children with CD.
We collected data from a multi-center study designed to develop 2 magnetic resonance enterography (MRE)-based measures for children with CD (6-18 years old). In our analysis of 151 children (mean age, 14.2 ± 2.4 years), all patients underwent MRE and a complete ileocolonoscopic evaluation; fecal levels of calprotectin and blood levels of C-reactive protein were measured. Mucosal healing was defined as simple endoscopic severity index in CD score below 3, transmural healing as an MRE visual analogue score below 20 mm, and deep healing as a combination of transmural and mucosal healing.
We identified mucosal healing with transmural inflammation in 9 children (6%), transmural healing with mucosal inflammation in 38 children (25%), deep healing in 21 children (14%), and mucosal and transmural inflammation in 83 children (55%). The median level of calprotectin was lowest in children with deep healing (mean level, 10 μg/g; interquartile range, 10-190 μg/g), followed by children with either transmural or mucosal inflammation, and highest in children with mucosal and transmural inflammation (810 μg/g; interquartile range, 539-1737 μg/g) (P < .001). Fecal level of calprotectin identified children with deep healing with an area under the receiver operating characteristic curve value of 0.93 (95% CI, 0.89-0.98); level of C-reactive protein identified children with deep healing with an area under the receiver operating characteristic curve value of 0.81 (95% CI, 0.71-0.9). A calprotectin cutoff value of 100 μg/g identified children with deep healing with 71% sensitivity and 92% specificity; a cutoff value of 300 μg/g identified children with mucosal healing with 80% sensitivity and 81% specificity.
In a prospective study of children with CD, we found that one-third have healing in only the mucosa or the bowel wall (not both). Levels of fecal calprotectin below 300 μg/identify children with mucosal healing, but a lower cutoff value (below 100 μg/g) is needed to identify children with deep healing. Clinicaltrials.gov no: NCT01881490.
肠愈合是克罗恩病（CD）患者治疗的重要目标。尽管有许多关于黏膜愈合的研究，但在儿童中尚未研究过透壁愈合（即在肠壁内）。我们分析了 ImageKids 研究的数据，以确定儿童 CD 患者黏膜愈合、透壁愈合以及钙卫蛋白和 C 反应蛋白水平之间的相关性。
我们收集了一项多中心研究的数据，该研究旨在为 CD 儿童（6-18 岁）开发 2 种基于磁共振肠造影（MRE）的测量方法。在对 151 名儿童（平均年龄 14.2±2.4 岁）的分析中，所有患者均接受 MRE 和完整的回结肠内镜评估；检测粪便钙卫蛋白水平和血液 C 反应蛋白水平。黏膜愈合定义为 CD 内镜简化评分低于 3，透壁愈合定义为 MRE 视觉模拟评分低于 20mm，深度愈合定义为透壁和黏膜愈合的组合。
我们在 9 名儿童（6%）中发现了黏膜伴有透壁炎症，38 名儿童（25%）中发现了透壁伴有黏膜炎症，21 名儿童（14%）中发现了深度愈合，83 名儿童（55%）中发现了黏膜和透壁炎症。深度愈合的儿童钙卫蛋白中位水平最低（平均水平为 10μg/g；四分位间距为 10-190μg/g），其次是透壁或黏膜炎症的儿童，黏膜和透壁炎症的儿童最高（810μg/g；四分位间距为 539-1737μg/g）（P＜0.001）。钙卫蛋白的粪便水平对深度愈合的受试者工作特征曲线下面积的评估值为 0.93（95%CI，0.89-0.98）；C 反应蛋白对深度愈合的受试者工作特征曲线下面积的评估值为 0.81（95%CI，0.71-0.9）。钙卫蛋白截断值为 100μg/g 时，对深度愈合的儿童的敏感性为 71%，特异性为 92%；截断值为 300μg/g 时，对黏膜愈合的儿童的敏感性为 80%，特异性为 81%。
在一项对 CD 儿童的前瞻性研究中，我们发现三分之一的儿童仅在黏膜或肠壁（而不是两者）愈合。粪便钙卫蛋白水平低于 300μg/g 可识别黏膜愈合，但需要较低的截断值（低于 100μg/g）来识别深度愈合。Clinicaltrials.gov 编号：NCT01881490。
