Etiologies and Clinical Features of Nonresponsive Celiac Disease in Children Under the Age of 18 Years: ACG Fellows-In-Training Award

Abstract

Introduction: Celiac disease (CD) is a chronic immune-mediated enteropathy precipitated by exposure to gluten in genetically predisposed individuals occurring in 1 % of the general population. The only treatment available is the gluten free diet (GFD) and it is estimated that 7-30% of adults do not respond completely to treatment, referred to as nonresponsive celiac disease (NRCD). Common causes of NRCD in adults include gluten exposure, irritable bowel syndrome, and refractory celiac disease. To our knowledge, all studies of NRCD have been in adults. Our aim was to determine the prevalence and spectrum of NRCD in the pediatric celiac population. Methods: Medical records of all children less than 18 years old diagnosed with biopsy proven CD at Boston Children's Hospital (BCH) between years 2008 and 2012 were reviewed and cases of NRCD were identified. Cases of NRCD were defined as 1) Persistent clinical symptoms beyond 6 months on a GFD or 2) Persistently elevated celiac antibody levels, greater than 50% above the upper limit of normal at 12 months or less than a 20 percent decrease in levels by 6 months after diagnosis. Clinical features including demographics, comorbidities, family history and associated conditions were collected and analyzed for correlation with specific etiologies of NRCD. Results: 754 children under age 18 with biopsy proven CD were diagnosed at BCH between 2008 and 2012. Of these, 177 children met criteria for NRCD for an incidence of NRCD 23.4%. The mean age of celiac diagnosis in the NRCD cohort was 9 years compared to 11 years in the overall cohort. In initial review of a subset of children with NRCD, the most common symptoms were abdominal pain, constipation and GERD seen in 70%, 30% and 15% of the patients, respectively. The most frequent causes of NRCD were gluten exposure in 40%, constipation in 20%, other functional disorders in 10% and lactose intolerance in 5%. 15% of NRCD patients experiencing persistent functional abdominal symptoms had underlying neuropsychiatric illnesses including anxiety, panic attacks, and autism. 10% of the children had a slow fall in celiac antibody levels without any underlying etiology. Conclusion: NRCD is common in children as with adults, with a prevalence of approximately 25%. Similar to in adults, gluten exposure and overlapping functional symptoms are the most common etiologies. Providers caring for pediatric patients with celiac disease should be aware of these common issues.