Esophageal inflammation in infants with gastroesophageal reflux symptoms and persistent distress

Abstract

Rationale It is not known whether esophagitis in infants with persistent distress is caused by primary gastroesophageal reflux (GER) and acid-peptic mucosal injury, or by food-associated allergic inflammation. Methods 49 infants (mean age 4.8 ± 2.2 months) underwent 24-hour esophageal pH monitoring and lower esophageal biospies for investigation of GER symptoms and persistent distress. A reflux index >10% was considered abnormal. Biopsies were examined for eosinophils, neutrophils, macrophages, as well as CD3+, CD4+ and CD8+ lymphocytes. 27 of the infants also underwent double-blind placebo-controlled food challenges (DBPCFC) for suspected cow milk allergy (CMA). Results 10 (22%) infants had abnormal GER on pH monitoring, and 14 (29%) had histological esophagitis. 17 infants had challenge-proven non-IgE mediated CMA. Esophageal eosinophil numbers were significantly higher in infants with esophagitis than in those without (9.8 ± 14.6 vs 0 ± 0; p<0.0001). Esophagitis was associated with significantly increased CD4+ cells (34.7 ± 23.5 vs 7.1 ± 4.3; p=0.02) and macrophages (11.9 ± 8.6 vs 3.1 ± 2.8; p=0.04) in the lamina propria, but no difference in lymphocyte or macrophage numbers was found for the esophageal epithelium (CD4+: 9.4 ± 7.3 vs 7.7 ± 7.7; p=0.52). Furthermore, there were no significant differences in the numbers of eosinophils, neutrophils, lymphocytes or macrophages in infants with or without abnormal GER. Numbers of epithelial CD8+ cells were significantly lower in infants with CMA compared to those found tolerant on DBPCFC (8.2 ± 9.5 vs 20.7 ± 11.6; p<0.05). Conclusions Esophagitis in distressed infants is characterized by significantly increased numbers of eosinophils, CD4+ lymphocytes and macrophages in the lamina propria. Numbers of CD8+ lymphocyte are signficantly reduced in the esophageal epithelium of infants with CMA.