Histological evaluation of esophageal mucosa in children with acid gastroesophageal reflux.

Abstract

AIM: histological evaluation of esophageal mucosa in children, with regard to the duration of primary acid gastroesophageal reflux (GER) and acid GER secondary to cow's milk allergy and/or other food allergy (CMA/FA) (prospective study). MATERIAL AND METHODS: 264 children of both sexes suspected of GER were enrolled in the study. The age of examined children was 1.5-102 months, mean age 20.78±17.23 months. Pathological acid GER was confirmed with pH-monitoring in 138 children (52.3%). Taking into consideration complex differential diagnosis, including oral food challenge test with potentially noxious nutrient (open or blind study), children were assigned into study groups 1 and 2 (primary and secondary GER). Group 1: 76 patients (28.8%) aged 4-102 months (x=25.2±27.28 months) with primary GER. Group 2: 62 patients (23.5%) aged 4-74 months (x=21.53±17.79 months) with GER secondary to CMA/FA. Children with GERD underwent preliminary and control (after 1 year and 2 years of GERD diagnosis) endoscopic examination of the upper gastroinestinal tract. RESULTS: Intensity of esophagitis was assessed initially in 25 children from group 1 (32.9%), in 29 children from group 2 (46.8%), and in 9 children from group 3 -reference group (28.1%). Histological evaluation revealed infiltration of inflammatory cells, mainly neutrophils and intraepithelial lymphocytes, and also eosinophils in 10 children (13.2%) with primary GER. Infiltration of eosinophils and lymphocytes was found in 5 children (8.1%) with secondary GER. In 8 children (25.0%) with food allergy there were only lymphocytes. Infiltration of neutrophils and lymphocytes and basal zone hyperplasia or infiltration of eosinophils and lymphocytes with elongation of lamina propria papillae was found in 10 children (13.1%) with primary GER and in 20 children (32.2%) with secondary GER. Differentiation of particular types of inflammatory cells in mucosal infiltration characterized histological picture in the following way: neutrophils in 21 children (27.6%) with primary GER, eosinophils in 22 children (35.5%) with secondary GER, lymphocytes in 15 children (19.7%) in children with primary GER and in 15 children (24.2%) with secondary GER. Histological examination of esophageal mucosa after 1 and 2 years of clinical observation and periodical conservative treatment in children with primary and secondary GER revealed significant alleviation of inflammatory abnormalities (with regard to the type of abnormalities and the number of particular types of inflammatory cells). CONCLUSIONS: The value of histological findings obtained in own studies comprises the role of food allergy in pathogenesis of GER and is related to GER's contribution, both direct (primary reflux) and indirect (secondary reflux), to triggering off morphological results and clinical outcomes of esophagitis.

Role of Cellular Immunity in Cow’s Milk Allergy: Pathogenesis, Tolerance Induction, and Beyond

“…Neutrophils, γδ , and NK T cells were accumulated in the chronically inflamed digestive tissues of CMA patients [23–25], but the actual roles of these innate cells are unknown. It is possible that these cells are accumulated in the inflamed sites mainly because of the elevated levels of inflammatory chemokines during chronic allergic reaction and indirectly activated by the circulating inflammatory cytokines, hence contributing to the chronic inflammatory reactions [3].…”

Narrative review of the role of inflammation in gastroesophageal reflux disease. Can food allergies play a part?

“…Although nearly 40% of children with GORD presented with inflammation, 28.1% of children in the control group who had food allergy without acidic reflux, also had first‐degree inflammation. This suggests that an inflammatory process may be present in the esophageal mucosa of some allergic children in the absence of abnormal acid exposure 36 . These children had initially presented with GORD‐like symptoms but were excluded from GORD groups on the basis of pH monitoring.…”

“…It is often stated that children with CMA outgrow their symptoms 22,36,70 . As determined by skin‐prick testing (SPT), atopic patch testing (APT) or parental perception of adverse events following milk ingestion.…”

“…Up to 70% of infants with CMA are found to have hypersensitivity to unrelated food proteins after 5 years, 24 with 20–50% of older children demonstrating clinical symptoms of persistent food allergy, 36 while 40% of adults with identified non‐CM food allergies present with GORD 32 . Therefore, there is evidence to demonstrate that food allergies may progress into later life, as well as enter remission.…”