A Quantitative Assessment of Mucosal Eosinophils in the Gastrointestinal Tract of Children Without Detectable Organic Disease.

BACKGROUND: Accurate measurements of mucosal eosinophil concentrations in gastrointestinal tracts of healthy children are necessary to differentiate health and disease states in general, and better define eosinophilic gastrointestinal diseases. STUDY: We retrospectively reviewed gastrointestinal biopsies from children with macroscopically normal endoscopies, who, after a minimal follow-up of one year, were not diagnosed with any organic disease. Peak eosinophil concentrations and distributions were assessed from each segment of the gastrointestinal tract. RESULTS: Three centers (Italy, United Kingdom, and Israel) contributed 202 patients (median age 13 years IQR 9.5-15.5, range 1-18 years). Median (IQR, range) eosinophil concentrations (eos/mm2) were: esophagus 0 (0-0, 0-84), stomach 0 (0-4, 0-84), duodenal bulb 20 (13-30, 7-67), second part of duodenum 20 (13-29, 0-105), terminal ileum 29 (14-51, 0-247), cecum 53 (37-89, 10-232), ascending colon 55 (25-84, 0-236), transverse colon 38 (21-67, 4-181), descending colon 29 (17-59, 0-114), sigmoid colon 25 (13-40, 0-215) and rectum 13 (4-28, 0-152). Significant geographical variance was present, however, no differences in eosinophil concentrations were identified between children with resolving symptoms vs. those with functional diagnoses, nor across age groups. CONCLUSIONS: Standardized eosinophil concentrations from the gastrointestinal tracts of children without organic disease will serve to better define both health and disease states. No differences were found between resolved symptoms vs. functional diagnoses nor between age groups in this pediatric cohort.

Sustained Remission of Eosinophilic Esophagitis Following Discontinuation of Dietary Elimination in Children.

Eosinophilic esophagitis (EoE), when left untreated, may progress from an inflammatory to a fibrostenotic phenotype. Inflammation generally recurs after treatment withdrawal. Thus, long-term treatment has been recommended. Here, we describe a cohort of children with EoE who achieved clinical and histologic remission with elimination diets, and maintained sustained untreated remission (SUR) despite re-introduction of all eliminated food allergens.

Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER).

OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ±â€Š33.5 months and age at diagnosis was 8.9 ±â€Š4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.

Leukemoid reaction in the pediatric population: etiologies, outcome, and implications.

Leukemoid reaction (WBC > 30,000/µL) may indicate significant medical conditions, mostly infectious. Prompted by the lack of population-based data on the presentation, characteristics, and necessary workup in children with leukemoid reaction, we searched the database of a tertiary pediatric medical center for all children presented with at least one WBC count of ≥ 30,000/µL in 2009-2014. Demographic, clinical, and laboratory parameters were recorded. Children admitted with WBC < 30,000/µL served as controls. Pneumonia was the most common diagnosis in the leukemoid reaction group, with a 5.5-fold higher prevalence of pleuropneumonia than in the control group. The leukemoid group had a longer average hospital stay (7.5 vs. 5.5 days). Patients with WBC ≥ 50,000/µL had a sixfold higher rate of leukemia than patients with a lower count. There was a significant association of leukemia with low platelet count, low levels of C-reactive protein, and high levels of uric acid and lactate dehydrogenase. CONCLUSION: Children presented with a leukemoid reaction are at high risk of pneumonia, especially pleuropneumonia, and a long hospital stay. Those with WBC ≥ 50,000/µL have a sixfold higher risk of leukemia. For prompt diagnosis, clinicians should be aware of the variables associated with leukemia. What is Known: • Leukemoid reaction has been associated with infectious diseases. • Leukemoid reaction at presentation in adults is correlated with high morbidity and mortality. What is New: • Children with leukemoid reaction are at high risk of pleuropneumonia. • We did not observe increased mortality in children with a leukemoid reaction.

Giardia lamblia Diagnosed During Upper Gastrointestinal Endoscopy: Clinical Manifestation, Histopathologic Findings and the Association With Celiac Disease.

BACKGROUND: Giardia lamblia may be found incidentally during upper gastrointestinal (GI) endoscopy, including when biopsies are taken for celiac disease (CeD) diagnosis. We aimed to study the clinical presentation and histopathology of G. lamblia and determine its association with CeD. METHODS: A retrospective case series of pediatric patients diagnosed with G. lamblia based on intestinal biopsies between January 1999 and January 2023. Baseline data; demographics, symptoms, celiac serology, stool testing, macroscopic and histopathologic findings. Follow-up data; treatment and repeated celiac serology. RESULTS: Of 38 patients with G. lamblia , 15 (39.5%) were female, mean age of 6.7 (±4.8 SD) years. Clinical symptoms; GI 19/38 (50%), growth retardation and/or iron deficiency anemia 8/38 (21.1%) or a combination 11/38 (28.9%). Celiac serology was positive in 13/38 (34.2%). Duodenal endoscopic findings; normal (n = 23, 60.5%), nodularity (n = 12, 32.4%), erosions in 2 (5.4%) and scalloping in 1 (2.7%). Histopathology; normal villi 24/38 (63.2%), villous shortening with increased intraepithelial lymphocytes (IEL) 5/38 (13.2%), isolated IEL 3/38 (7.9%) and duodenitis in 6/38 (15.8%). Children with positive CeD serology were younger (4 vs. 8.1 years, P = 0.019), had fewer GI symptoms (23.1% vs. 64%, P = 0.017) and a higher rate of villous shortening with increased IEL (38.5% vs. 0, P < 0.001) versus children with negative serology. On follow-up, metronidazole treatment was recommended to all but was documented to be given in 22/38 (57.9%). Among the 13 children with positive CeD serology, serology normalized in 10 (77%). CONCLUSIONS: G. lamblia is a rare histopathologic finding in children. It may be an incidental finding in CeD or may cause false positive celiac serology.

The common Arg389gly ADRB1 polymorphism affects heart rate response to the ultra-short-acting ß(1) adrenergic receptor antagonist esmolol in healthy individuals.

The ß1-adrenergic receptor (ß1AR) Arg389Gly polymorphism affects responses to orally administered ß1AR antagonists (ß-blockers) in vivo. However, the effect of this polymorphism on the early heart rate response to ß-blockers has not been evaluated. The aim of this study was to determine the effect of the Arg389Gly polymorphism on the inhibition of exercise-induced tachycardia by esmolol, an ultra-short-acting intravenously administered ß1AR antagonist. Healthy nonsmoking White individuals were enrolled on the basis of their ADRB1 genotype, including carriers of 0, 1 or 2 Arg389 alleles (n=9 in each group, total 27, 18 men). Placebo and esmolol were infused consecutively for 10 min each, separated by 30 min. At the end of each infusion, participants performed dynamic handgrip exercise. Heart rate and blood pressure were compared among three ADRB1 genotypes. Carriers of 0, 1, or 2 Arg389 alleles varied significantly in both exercise-induced tachycardia during esmolol (P(ANOVA)=0.030) and esmolol inhibition of exercise-induced tachycardia [0.78±7.70, 5.11±4.05, 10.22±9.78 bpm, respectively (P=0.014)]. The early effect of esmolol on exercise-induced tachycardia was significantly greater among Arg389 than in Gly389 homozygote healthy individuals (NCT01388036).

Intestinal Fatty Acid Binding Protein Levels in Pediatric Celiac Patients in Transition From Active Disease to Clinical and Serological Remission.

Celiac disease (CD) is increasingly diagnosed without endoscopy. As such, the need for accurate serological markers to aid in the diagnosis and follow-up of CD has increased. Intestinal fatty acid binding protein (I-FABP) is a cytosolic protein present in enterocytes, whose blood levels reflect mucosal damage in a reliable and quantifiable way. The aim of this study was to compare I-FABP levels in newly diagnosed patients with CD and to examine changes in levels following 6 months of gluten-free diet (GFD). Methods: A prospective observational case control study of pediatric patients diagnosed with CD, with measurements of tissue transglutaminase IgA (TTG-IgA) and I-FABP levels at diagnosis and after 6 months of gluten free diet were compared to a control group of nonceliac patients. Results: This study included 35 patients and 32 controls. The CD group had higher I-FABP levels at diagnosis compared with the control group (median 641.7 pg/mL versus 334 pg/mL; P < 0.05). I-FABP levels significantly differed between patients presenting with TTG-IgA level 3-10 times the upper limit of normal (ULN) compared with those presenting with values >10 times ULN (median 432.2 pg/mL versus 796.2 pg/mL; P < 0.05). Patients with CD had a significant decrease in median I-FABP levels after 6 months of GFD (median 268.2 pg/mL), paralleling a decrease in TTG-IgA and GFD adherence. Conclusions: I-FABP levels are increased in patients with CD at diagnosis compared with controls and decrease significantly while patients adhere to GFD.

Systemic steroids have a role in treating esophageal strictures in pediatric eosinophilic esophagitis.

BACKGROUND: The role of systemic steroids in the treatment of esophageal strictures in children with Eosinophilic Esophagitis (EoE) is poorly defined. AIMS: To describe a cohort of children with EoE-associated esophageal strictures responding to systemic steroids. METHODS: Retrospective review of medical records of children with EoE and moderate (<9 mm) to severe (<6 mm) strictures, who responded clinically and endoscopically to systemic steroids. RESULTS: Twenty children (median age 10.6 ±â€¯4.2 years; 17 males) from nine centers in six countries were included in the analysis; 16 had moderate and four, severe strictures; 18 had dysphagia or bolus impaction; median diagnostic delay was 8 months (IQR 3.5-35). Eighteen patients received oral systemic steroids (mean dose 1.4 mg/kg/day) for a median of 4 weeks, while two initially received IV steroids. All patients showed clinical improvement and 15/20 became asymptomatic. Stricture resolution at endoscopy was found in 19/20, while histological resolution of EoE (<15 eos/hpf) in 13/20. Only minor side effects were reported: hyperphagia (10/20); weight gain (5/20); hyperactivity (2/20) and acne (1/20). Esophageal dilation was required in 3/20 patients during a median follow-up of 48.5 months (IQR 26.7-73.2). CONCLUSION: Children with EoE and esophageal strictures, may benefit from the use of a short course of systemic steroids, avoiding mechanical dilation.