To the Editor:
Guandalini and Newland express concern that other diagnoses of the upper gastrointestinal tract will be missed if the diagnosis of celiac disease (CD) is made without performing an upper endoscopy. We thank the authors for pointing out this issue and the journal for affording us the chance to respond.
The authors report the results of their retrospective chart review with endoscopic findings in 115 children with anti-TG2 antibody concentrations >10 times the upper limit of normal. According to the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines on the diagnosis of CD, these patients would qualify for the option to omit the biopsies under the following conditions in addition to the high TG2 antibody concentrations: symptoms suggestive of CD, positive anti-endomysial antibodies in a second blood sample, HLA-DQ2 or -DQ8 positivity, and informed consent after discussion with a pediatric gastroenterologist (1). In 11 of 115 patients, abnormal findings were reported; however, we would consider some of them less relevant or part of the celiac pathology. For example, Helicobacter pylori infection does not need to be treated in the absence of erosions and ulcerations (2). Chronic superficial or lymphocytic gastritis are common findings in children with untreated CD (3,4) and should resolve with a gluten-free diet. The remaining patients had different types of esophagitis, one of them with eosinophilic infiltrations. No information is provided as to whether the diagnosis of esophagitis was based on macroscopic findings with mucosal breaks (erosions, ulcerations) or histology only.
Untreated CD causes dysmotility with delayed gastric emptying because of reduced secretion of gastrointestinal hormones in the presence of enteropathy. This may predispose to gastroesophageal reflux and esophagitis, but again, dysmotility will resolve after normalization of the small bowel mucosa with a gluten-free diet. In addition, it is unclear how many unselected control children would show any esophageal pathology. The Kalixanda study reports findings in 1000 population-based adults who underwent upper endoscopy with multiple biopsies. Even in the absence of any symptoms, 9.5% were found to have erosive esophagitis. This proportion reached 20% to 36% in individuals complaining of occasional to daily symptoms (5). In the same study, definite or probable eosinophilic esophagits (EoE) was identified in 1.1%, and eosinophilic infiltrations were related to reflux esophagitis (6). It has been suggested that EoE is more frequent than expected in patients with CD; however, a recent meta-analysis on incidence and prevalence of EoE in children reported a prevalence ranging from 1.1% to 5.1% in CD compared with 2.1% to 4.9% in children who underwent endoscopy for abdominal pain (7).
The data point to the dilemma that a concurrent disease may be responsible for the symptoms leading to medical attention, and CD essentially may be asymptomatic. Symptomatology and clinical judgment are important elements of the ESPGHAN guidelines. In cases in which the type of gastrointestinal symptoms (mainly abdominal pain) indicates the possibility of additional pathology, it is at the discretion of the managing physician to perform an endoscopy already at the beginning of the clinical workup. Although CD cannot be diagnosed after starting the diet, an endoscopical search for additional pathology can be performed at any later time in those children whose symptoms do not respond to a gluten-free diet. This would still spare a majority from the invasive procedure.
In conclusion, we believe that the findings observed by Guandalini and Newland do not justify changing the ESPGHAN guidelines and the option to omit duodenal biopsies. At the same time, we strongly support their recommendation to follow-up on these children receiving a gluten-free diet and evaluate those in whom symptoms do not resolve.
1. Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr
2. Koletzko S, Jones NL, Goodman KJ, et al. Evidence-based guidelines from ESPGHAN and NASPGHAN for Helicobacter pylori
infection in children. J Pediatr Gastroenterol Nutr
3. Bhatti TR, Jatla M, Verma R, et al. Lymphocytic gastritis in pediatric celiac disease. Pediatr Dev Pathol
4. Nenna R, Magliocca FM, Tiberti C, et al. Endoscopic and histological gastric lesions in children with celiac disease: mucosal involvement is not only confined to the duodenum. J Pediatr Gastroenterol Nutr
5. Ronkainen J, Aro P, Storskrubb T, et al. Gastro-oesophageal reflux symptoms and health-related quality of life in the adult general population--the Kalixanda study. Aliment Pharmacol Ther
6. Ronkainen J, Talley NJ, Aro P, et al. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population-based Kalixanda study. Gut
7. Soon IS, Butzner JD, Kaplan GG, et al. Incidence and prevalence of eosinophilic esophagitis in children: systematic review and meta-analysis. J Pediatr Gastroenterol Nutr