Veeraraghavan Gopal, Therrien Amelie, Degroote Maya, McKeown Allison, Mitchell Paul D, Silvester Jocelyn A, Leffler Daniel A, Leichtner Alan M, Kelly Ciaran P, Weir Dascha C
Division of Gastro-enterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.
Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, United States.
World J Gastroenterol. 2021 Apr 7;27(13):1311-1320. doi: 10.3748/wjg.v27.i13.1311.
Non-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.
To determine the incidence, clinical characteristics and underlying causes of NRCD in children.
Retrospective cohort study performed at Boston Children's Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH's Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.
Six hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.
NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.
难治性乳糜泻（NRCD）被定义为乳糜泻（CeD）患者尽管接受无麸质饮食（GFD）但症状仍持续存在。关于儿科人群中NRCD的文献很少。
确定儿童NRCD的发病率、临床特征和潜在病因。
在波士顿儿童医院（BCH）进行回顾性队列研究。在BCH乳糜泻项目数据库中识别出2008年至2012年间通过血清学阳性和符合马什III型组织学的十二指肠活检确诊为CeD的18岁以下儿童。从诊断时间到2015年9月对病历进行纵向回顾。NRCD被定义为开始GFD后6个月仍有持续症状，并详细记录NRCD的病因以及症状演变。将6个月时无症状的儿童（反应者）与NRCD组进行比较。此外，收集并比较反应者和NRCD患者在CeD诊断时的体征和症状，以确定GFD治疗6个月时NRCD的任何潜在预测因素。
共纳入616名儿童。91名（15%）符合NRCD标准。大多数为女性（77%）。诊断时腹痛[比值比（OR）1.8，95%置信区间（CI）1.1 - 2.9]、便秘（OR 3.1，95%CI 1.9 - 4.9）和无腹胀（腹胀的OR为0.4，95%CI 0.1 - 0.98）与NRCD相关。NRCD归因于多种诊断，麸质暴露（30%）和便秘（20%）是最常见的原因。NRCD的其他原因包括乳糖不耐受（9%）、胃食管反流（8%）、功能性腹痛（7%）、肠易激综合征（3%）、抑郁/焦虑（3%）、嗜酸性食管炎（2%）、食物过敏（1%）、饮食失调（1%）、胃溃疡（1%）、淋巴细胞性结肠炎（1%）、吞气症（1%）和不明原因（13%）。64%的NRCD儿童在随访中病情改善。
在儿童中，尤其是女性，≥6个月GFD后出现NRCD很常见，并且与便秘和/或腹痛的初始表现症状相关。麸质暴露是最常见的原因。
