Detailed Histologic Evaluation of Eosinophilic Esophagitis in Pediatric Patients Presenting with Dysphagia or Abdominal Pain and Comparison of the Histology between the Two Groups.

EoE in children presents with four main symptoms. Most common symptoms exhibited by our clinic population are dysphagia (D) and abdominal pain (AP). Despite similar treatments, we found in an earlier study that the outcomes between these two groups were different. Therefore, we investigated if there exist any histological differences between these groups that could further our knowledge of EoE. Aim. To compare esophageal histology in detail, apart from the eosinophil count, between EoE-D and EoE-AP. Method. Biopsies of patients with EoE-D and EoE-AP were reevaluated for 10 additional histological criteria, in addition to the eosinophil count. Results. Both groups had 67 patients; peak mean eosinophil was 33.9 and 31.55 for EoE-D and EoE-AP (p < 0.05). Eosinophilic microabscesses, superficial layering of eosinophils, and epithelial desquamation were twice as common and significant in EoE-D group than EoE-AP. Eosinophil distribution around rete pegs was also significantly higher in EoE-D group. The remaining criteria were numerically higher in EoE-D, but not significant, with the exception of rete peg elongation. Conclusion. EoE-D patients have significantly higher eosinophils compared to EoE-AP, and the level of inflammation as seen from eosinophil microabscesses, superficial layering, desquamation, and the distribution around rete pegs is significantly higher.

Eosinophilic Esophagitis in Children and Adolescents with Abdominal Pain: Comparison with EoE-Dysphagia and Functional Abdominal Pain.

Aim. Compare EoE-AP with EoE-D for clinical, endoscopy (EGD), histology and outcomes and also with FAP-N. Method. Symptoms, physical findings, EGD, histology, symptom scores, and treatments were recorded for the three groups. Cluster analysis was done. Results. Dysphagia and abdominal pain were different in numbers but not statistically significant between EoE-AP and EoE-D. EGD, linear furrows, white exudates were more in the EoE-D and both combined were significant (p < 0.05). EoE-D, peak and mean eosinophils (p 0.06) and eosinophilic micro abscesses (p 0.001) were higher. Follow-Up. Based on single symptom, EoE-AP had 30% (p 0.25) improvement, EoE-D 86% (p < 0.001) and similar with composite score (p 0.57 and <0.001, resp.). Patients who had follow-up, EGD: 42.8% with EoE-AP and 77.8% with EoE-D, showed single symptom improvement and the eosinophil count fell from 38.5/34.6 (peak and mean) to 31.2/30.4 (p 0.70) and from 43.6/40.8 to 25.2/22.8 (p < 0.001), respectively. FAP-N patients had similar symptom improvement like EoE-D. Cluster Analysis. EoE-AP and FAP-N were similar in clinical features and response to treatment, but EoE-D was distinctly different from EoE-AP and FAP-N. Conclusion. Our study demonstrates that EoE-AP and EoE-D have different histology and outcomes. In addition, EoE-AP has clinical features similar to the FAP-N group.

Continuous 48-Hour Wireless Esophageal pH Monitoring in Children: Comparison Between Days 1 and 2.

AIM: Comparison of days 1 and 2 to each other and to the total recording of 48 hours in continuous 48-hour wireless esophageal pH monitoring in children. METHODS: A retrospective study of 105 patients who underwent 48-hour pH monitoring (Bravo) studies between January 1992 and June 2010 was performed. Reflux variables were compared between days 1 and 2. RESULTS: A total of 58 (55.2%) patients were men. The number of reflux episodes, number of long reflux >5 minutes, duration of the longest reflux (minutes), time pH <4 (minutes), fraction time pH <4 supine (%), fraction time pH <4 upright (%), reflux index, and DeMeester score did not differ between days 1 and 2. CONCLUSIONS: No effect of anesthesia was observed on the gastroesophageal reflux parameters on children.

Esophageal perforation: An uncommon initial manifestation of eosinophilic esophagitis.

EoE-Perforation: Eosinophilic esophagitis (EoE) is commonly observed in children and young adults. Common manifestations of EoE include dysphagia and food impaction in adolescents and adults, whereas children present with failure to thrive, regurgitation, or heartburn and abdominal pain. We describe two patients presenting with esophageal perforation and EoE. Diagnosing perforation promptly is critical to minimize and/or to avoid the multitude of complications resulting from esophageal perforation and to treat EoE because if left untreated, this condition may result in the recurrence of perforation, major morbidity, or rarely death.

Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Esomeprazole for the treatment of GERD in infants ages 1-11 months.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study.

BACKGROUND: Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents. METHODS: This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits. RESULTS: Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units. CONCLUSION: GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents. TRIAL REGISTRATION: D9614C00098; ClinicalTrials.gov Identifier NCT00241501.

Safety and symptom improvement with esomeprazole in adolescents with gastroesophageal reflux disease.

OBJECTIVES: The primary objective was to assess the safety of esomeprazole 20 or 40 mg once daily in adolescents with clinically diagnosed gastroesophageal reflux disease (GERD). A secondary aim was to assess changes in GERD symptoms after esomeprazole therapy. PATIENTS AND METHODS: In this multicenter, randomized, double-blind study, adolescents ages 12 to 17 years inclusive received esomeprazole 20 or 40 mg once daily for 8 weeks. Adverse events and changes in clinical parameters (eg, physical examination, laboratory measurements) were evaluated to assess safety. Patients or their parents or guardians scored symptom severity daily, and investigators scored overall GERD symptom severity every 2 weeks using a 4-point scale. RESULTS: In the 148 adolescents with safety data, treatment-related and non-treatment-related adverse events were reported by 75% and 78% of patients in the esomeprazole 20- and 40-mg groups, respectively. Twenty-two patients (14.9%) experienced adverse events that were considered related to treatment; the most common were headache (8%, 12/148), abdominal pain (3%, 4/148), nausea (2%, 3/148), and diarrhea (2%, 3/148). No serious adverse events or clinically important findings in other safety assessments were observed. At baseline, 68% (100/147) had heartburn, 63% (93/147) had epigastric pain, 57% (84/147) had acid regurgitation, and 15% (22/147) had vomiting symptoms. Symptom scores decreased significantly in both the esomeprazole 20-mg and 40-mg groups by the final study week (P < 0.0001). Investigators rated 63.1% (94/149) of the patients as having moderate or severe symptoms at baseline; at the final visit, this percentage decreased significantly to 9.3% (13/140; P < .0001). CONCLUSIONS: In adolescent patients with GERD, esomeprazole 20 or 40 mg daily for 8 weeks was well tolerated, and GERD-related symptoms were significantly reduced from baseline values in both groups.

Efficacy of lansoprazole in the treatment of gastroesophageal reflux disease in children.

OBJECTIVES: To assess the efficacy of lansoprazole for the relief of symptoms due to gastroesophageal reflux disease (GERD) in children 1 to 11 years of age. In addition, the efficacy in healing of erosive esophagitis (EE) was determined in those children with EE who were enrolled in the study. METHODS: In this phase I/II, open-label, multicenter (11 sites) U.S. study, children with symptomatic GERD, EE by endoscopy, and/or intraesophageal pH < 4 for greater than 4.2% of the time based on 24-hour pH testing were assigned, on the basis of body weight, to lansoprazole 15 mg (< or = 30 kg) or 30 mg (> 30 kg) once daily for 8 to 12 weeks. At the discretion of the investigator, the dosage of lansoprazole was increased up to 60 mg daily in children who continued to be symptomatic after 2 weeks of treatment. Symptom response was assessed by investigator interview and daily diary. Esophagitis healing was evaluated by repeat endoscopy after 8 and, if applicable, 12 weeks of treatment. RESULTS: Sixty-six children were enrolled. At week 8, 78% (21/27) of the children with EE at baseline had healed; the remaining six children were healed by week 12 (100%, 6/6). By investigator interview, 70% of children experienced resolution or improvement in their overall symptoms of GERD by their final visit. Statistically significant reductions from baseline in the severity of each symptom were reported with the exceptions of wheezing, hematemesis, and melena. Based on daily diary data, improvement in overall GERD symptoms was reported in 76% (47/62) of all children. With few exceptions, significant (P < 0.05) reductions from baseline occurred during each of the 2-week treatment intervals of the study period in the percentage of days and the average daily severity of GERD symptoms, the percentage of days antacid was used, and the average number of antacid tablets used per day. CONCLUSION: In children 1 to 11 years of age, lansoprazole is efficacious in healing EE and in relieving GERD-related symptoms.

Lansoprazole in adolescents with gastroesophageal reflux disease: pharmacokinetics, pharmacodynamics, symptom relief efficacy, and tolerability.

OBJECTIVES: To evaluate the pharmacokinetics, pharmacodynamics, symptom relief efficacy, and tolerability of lansoprazole in adolescents between 12 and 17 years of age with gastroesophageal reflux disease (GERD). METHODS: Adolescents with symptomatic, endoscopically and/or histologically proven GERD were enrolled in this multicenter, double-blind trial and randomized to lansoprazole 15 mg or 30 mg once daily for 5 days. RESULTS: Sixty-three adolescents were enrolled in the study. After lansoprazole administration, T(max) occurred at 1.6 hours in those treated with lansoprazole 15 mg and at 1.7 hours in those treated with lansoprazole 30 mg. Dose-proportional increases in lansoprazole C(max) and AUC were observed in the treatment groups. Age, weight, and gender had no significant effect on T(max), C(max), or AUC. Lansoprazole produced significant increases (P < or = 0.05) in mean 24-hour intragastric pH and the percentages of time intragastric pH was above 3 and 4. The majority of adolescents treated with lansoprazole 15 mg (69%, 22/32) or lansoprazole 30 mg (74%, 23/31) demonstrated improvement in their reflux symptoms after 5 days of treatment. Adolescents in both dosage groups exhibited reductions from baseline in the percentage of days and nights with heartburn (or other predominant symptom of GERD), the severity of heartburn, the percentage of days antacids were used, and the number of antacid tablets used per day. Pharyngitis and headache were the most commonly reported side effects among adolescents treated with lansoprazole 15 mg and 30 mg, respectively. Five patients experienced adverse events considered to be possibly treatment-related. One patient with a history of environmental allergies experienced a mild allergic reaction after 3 days of treatment with lansoprazole 15 mg. Among those treated with lansoprazole 30 mg, 4 patients each reported one occurrence of pain (toothache), diarrhea, dizziness, and rash. CONCLUSION: The pharmacokinetic parameters of lansoprazole observed in this study of adolescents are similar to those observed in studies of healthy adults. Lansoprazole 15 mg or 30 mg once daily for 5 days produces significant increases in intragastric pH, effectively relieves symptoms of reflux disease, and is well tolerated in adolescents with GERD.

Pharmacokinetics and pharmacodynamics of lansoprazole in children with gastroesophageal reflux disease.

OBJECTIVES: To evaluate the pharmacokinetics and pharmacodynamics of lansoprazole in children between 1 and 11 years of age with gastroesophageal reflux disease (GERD). METHODS: In a multicenter, open-label trial of pediatric patients with symptomatic GERD, children were assigned, based on their weight, to receive lansoprazole 15 mg (patients weighing < or = 30 kg) or lansoprazole 30 mg (patients weighing > 30 kg) once daily. The effects of lansoprazole on 24-hour median intragastric pH, the percentages of time intragastric pH was above 3 and 4, and pharmacokinetic parameters were assessed at the day-5 visit and compared to baseline. RESULTS: Sixty-six children were enrolled in the study. Mean lansoprazole C(max) values of 790.9 ng/mL and 898.5 ng/mL and T(max) values of 1.5 hours and 1.7 hours were observed in the < or = 30 kg and the > 30 kg body weight treatment groups, respectively. AUC0-24 values of 1707 ng x h/mL and 1883 ng x h/mL and T1/2 values of 0.68 hours and 0.71 hours were observed in the < or = 30 kg and > 30 kg lansoprazole body weight treatment groups, respectively. There was no statistical significant difference in AUC0-24 between the two groups (P = 0.2571). After 5 days of treatment lansoprazole produced significant increases in patients' 24-hour mean intragastric pH and the percentages of time intragastric pH was above 3 and 4 compared to baseline. CONCLUSION: The observed pharmacokinetic properties of lansoprazole in children between 1 and 11 years of age with GERD were similar to those previously observed in healthy adult subjects. Lansoprazole significantly increased the mean 24-hour intragastric pH and the percentages of time intragastric pH was above 3 and 4 when children were dosed with either 15 or 30 mg according to body weight.