1000 Seronegative Celiac Disease: Prevalence and Clinical Features in a Tertiary Referral Center

INTRODUCTION:Celiac disease (CD) is a chronic immune-mediated enteropathy precipitated by exposure to gluten in genetically predisposed individuals.Studies suggest that 7-30% of adult CD patients do not respond completely to a gluten free diet (GFD) and have non responsive celiac disease (NRCD) however little is known about the prevalence and spectrum of NRCD in children.Our aim was to delineate the frequency and clinical characteristics of NRCD in the pediatric celiac population and assess dietician visits in responders and NRCD.We conducted a retrospective study of children less than 18 years of age with biopsy proven CD diagnosed at Boston Children's Hospital (BCH) between January 1 st 2008 and December 31 st 2012.Medical records were reviewed to identify children with NRCD using the following criteria: 1) persistent clinical symptoms beyond 6 months on a GFD or 2) persistently elevated celiac antibody levels, > than 50% above the upper limit of normal at 12 months or < than 20% decline in antibody levels from diagnosis.We identified the number of dietetic counseling visits each subject had at BCH within 120 days of CD diagnosis.Patient data including clinical symptoms were analyzed to identify the characteristics of children with NRCD.RESULTS: 754 children under age 18 were identified in the BCH CD Database and 683 met inclusion criteria.527 CD patients responded to the GFD and 156 patients (22.8%) met criteria for NRCD.In an initial review of a subset of patients with NRCD abdominal pain was the most common celiac presenting symptom at diagnosis and was significantly more common in children with NRCD compared to responders (60.9% vs 51.4%, p=0.0442).Constipation (40.4% vs 26.9%, p=0.002).Abdominal distension or bloating was less frequent in NRCD (5.12% vs 11.95%, p=0.016).Diarrhea, nausea and vomiting were frequent presenting symptoms in both responsive and NRCD and were similarly prevalent.The most frequent causes of NRCD were gluten exposure (40%), constipation (19%), functional bowel disorders (14%) and lactose intolerance (5%).Unlike in adults, refractory celiac disease was very rare in children (1 patient, <1%).There was no statistically significant difference in the number of routine celiac nutrition visits between the responders and NRCD patients (p=0.68) and 10% of patients in both the groups did not have a formal dietary evaluation or counselling.CONCLUSION: NRCD is seen in approximately 23% of children with celiac disease.Abdominal pain and constipation are the most common symptoms.Continued gluten exposure is the most common cause of NRCD, however routine celiac dietary counseling at the initiation of the GFD does not appear to be effective in preventing NRCD due to gluten exposure.Future studies should evaluate methods of improving dietary adherence in the pediatric population.