Published online Apr 7, 2021. doi: 10.3748/wjg.v27.i13.1311
Peer-review started: December 3, 2020
First decision: December 21, 2020
Revised: January 4, 2021
Accepted: February 1, 2021
Article in press: February 1, 2021
Published online: April 7, 2021
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.
Addressing an important knowledge gap, this study examines a large cohort of children with CeD providing data on the characteristics, causes and evolution of pediatric NRCD. By characterizing this sub-population of individuals with CeD, we are better equipped to provide clinical guidance and follow-up in those with persistent symptoms.
Through this retrospective cohort study, we sought to determine the incidence, clinical characteristics, and underlying causes of NRCD in children. Additionally, symptom evolution was detailed and compared to identify any potential predictors for NRCD.
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 and compared to identify any potential predictors for NRCD.
Six hundred and sixteen children were included in this retrospective study, of which 91 (15%) met criteria for NRCD, and of this, 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. 64% of children with NRCD improved on follow-up.
NRCD after ≥ 6 mo of 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. Our study highlights the importance of performing a diligent search for the etiologies for NRCD in any celiac child with persistent clinical symptoms despite being on GFD and reinforces the need for close follow up in the first year of a CeD diagnosis.
Although the use of a large pediatric cohort positively contributes to the breadth of knowledge surrounding NRCD, and inclusion of only children who were diagnosed at BCH reduces referral bias, our cohort may differ from populations in other geographic areas. As such, a future direction of note is to extend this project to include pediatric Celiac Disease Programs across the United States, to assess if geographic location is a factor in the manifestation and characterization of NRCD.