Improved Outcomes in Eosinophilic Esophagitis with Higher Medication Possession Ratio.

Eosinophilic esophagitis (EoE) disease activity can be caused by treatment non-adherence. Medication possession ratio (MPR) is an established metric of medication adherence. A higher MPR correlates with better outcomes in several chronic diseases, but MPR has not been investigated with respect to EoE. A retrospective cohort study was performed using an established EoE registry for the years 2005 to 2020. Treatment periods were identified, MPRs were calculated, and medical records were assessed for histologic remission (<15 eos/hpf), dysphagia, food impaction, stricture occurrence, and esophageal dilation that corresponded to each treatment period. In total, 275 treatment periods were included for analysis. The MPR in the histologic remission treatment period group was 0.91 (IQR 0.63-1) vs. 0.63 (IQR 0.31-0.95) for the non-remission treatment period group (p < 0.001). The optimal MPR cut-point for histologic remission was 0.7 (Sen 0.66, Spec 0.62, AUC 0.63). With MPRs ≥ 0.7, there were significantly increased odds of histologic remission (odds ratio 3.05, 95% confidence interval 1.79-5.30) and significantly decreased odds of dysphagia (OR 0.27, 95% CI 0.15-0.45), food impaction (OR 0.26, 95% CI 0.11-0.55), stricture occurrence (OR 0.52 95% CI 0.29-0.92), and esophageal dilation (OR 0.29, 95% CI 0.15-0.54). Assessing MPR before repeating an esophagogastroduodenoscopy may decrease unnecessary procedures in the clinical management of eosinophilic esophagitis.

The Uniformed Services Constipation Action Plan: An Effective Tool for the Management of Children with Functional Constipation.

OBJECTIVE: To implement and to evaluate the effectiveness of the Uniformed Services Constipation Action Plan (USCAP) in our gastroenterology clinic for children with functional constipation. STUDY DESIGN: This implementation science study included toilet-trained subjects aged 4 years and older who met the Rome IV criteria for functional constipation. Children were block randomized to receive either the USCAP or control. All clinic functional constipation plans recommended subjects continue pharmacotherapy for 4 months. Endpoints measured were clinical outcomes (resolution of functional constipation and achievement of a Pediatric Bristol Stool Form Scale [PBSFS] score of 3 or 4), patient-related outcomes (health-related quality of life [HRQoL] total scale score), and health confidence outcomes (Health Confidence Score [HCS]). RESULTS: Fifty-seven treatment group subjects (44%) received a USCAP (52% male; mean age, 10.9 [4.9] years) compared with 73 controls (56%; 48% male; mean age,10.9 [5.3] years). A PBSFS score of 3 or 4 was achieved by 77% of the treatment group compared with 59% of controls (P = .03). Subjects from the treatment group were more likely than the controls to endorse adherence to the 4-month course of pharmacotherapy (P < .001). Subjects who received a USCAP had greater improvements in HRQoL total scale score by the end of the project (P = .04). CONCLUSIONS: The USCAP is a simple, inexpensive tool that has the potential to improve global outcomes for functional constipation in children and should be recommended as standard clinical practice.

Development and Implementation of DIGEST: The Digital Interactive Gastroenterology Education Suite for Trainees.

INTRODUCTION: Clinical clerkship curricula should exist to provide rotating learners on subspecialty rotations with consistent exposure to specific topics geared toward the discipline of interest, such as pediatric gastroenterology (GI). We aim to describe our experience developing and implementing DIGEST: the Digital Interactive Gastroenterology Education Suite for Trainees, a novel, online GI curriculum delivered to virtual, rotating learners during the coronavirus (COVID-19) pandemic stay-at-home order. MATERIALS AND METHODS: A general needs assessment in 2019 identified a lack of standardized educational experience amongst the rotating learners on pediatric GI service. The COVID-19 pandemic compelled us to transition our curriculum from our institution's secure share drive to the GOOGLE classroom. A program evaluation was undertaken and included learner responses to content and confidence questionnaires and a health care professions education (HPE) expert's response to a course quality assessment rubric. RESULTS: Feasibility-the final DIGEST product was free of charge to create but incurred direct and indirect costs of time and training on behalf of the authors. Acceptance-7 possible learners participated and responded to the questionnaires (100% response rate). Learners reported a superior learning experience and increased confidence with DIGEST. An HPE expert reported that the course design of DIGEST met or exceeded expectations in all categories. CONCLUSIONS: DIGEST is a novel pediatric GI curriculum for rotating learners that could be rapidly deployed, or adapted, for a wide range of clinical disciplines within the Military Health System.

Quantitative Analysis of Tug Sign: An Endoscopic Finding of Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic immune-mediated disorder characterized by esophageal inflammation and dysfunction, with a rising incidence affecting approximately 1:1000 individuals worldwide.1,2 Chronic inflammation can lead to tissue remodeling in the esophagus with fibrosis in the lamina propria that is partially responsible for symptoms and complications of EoE.3,4 At times, a firmness to the esophagus can be appreciated with a noticeable force required to obtain biopsies from EoE. This sensation has been described as the "tug" or "pull" sign.5,6 Recently, with the advent of endoscopic functional luminal impedance, the fibroelastic properties of the esophagus, including diminished compliance and distensibility, have been described in patients with EoE.7 Quantification of these fibroelastic properties of the esophagus may aid in diagnosis and prognosis of EoE. To this date, a method to quantitatively measure the "tug sign" has not been developed. The primary objective of this study was to measure if a quantifiable difference in force is required to obtain endoscopic esophageal biopsies in patients with EoE compared with those without.

Outcomes of eosinophilic esophagitis in patients managed in a multidisciplinary clinic.

Background: Eosinophilic esophagitis is a complex disease with an increasing prevalence. Multidisciplinary teams are often needed to manage this difficult-to-treat condition. Objective: To observe the clinical and histologic outcomes of patients with eosinophilic esophagitis after management in a multidisciplinary clinic. Methods: An observational, retrospective chart review was conducted to include all patients referred to the Walter Reed National Military Medical Center multidisciplinary eosinophilic esophagitis clinic between August 2012 and February 2021. Only patients who had at least one esophagogastroduodenoscopy before referral, one or more visits and endoscopy after multidisciplinary management, and documented clinical symptoms were included. Statistical analysis was performed by using McNemar and Wilcoxon tests. Results: A total of 103 patients were included in the study, with a mean age at diagnosis of 17.9 years. Management in the multidisciplinary clinic was associated with a reduction in solid-food dysphagia by 70.9%, poor growth by 70.8%, and emesis or regurgitation by 87.5%. We observed that 48.5% and 62.1% had histologic remission (<15 eosinophils/hpf) on the initial and any post-multidisciplinary endoscopy, respectively. Only seven patients (5.8%) with two or more visits and endoscopies did not achieve histologic remission. More than two-thirds of the patients (68.9%) required combination therapy to achieve remission. Conclusion: Although an observational study, these findings may suggest that the management of patients with eosinophilic esophagitis in a multidisciplinary clinic may improve the likelihood of clinical and histologic remission. Targeted management with a multidisciplinary approach may reduce overall morbidity and slow disease progression; however, more research is needed.

Early Infant Risk Factors for Pediatric Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory, atopic disease of the esophagus without a clear etiology. Our objective was to identify exposures and conditions in early infancy associated with the development of EoE. METHODS: A case-control study was performed using the Military Health System Database. Subjects diagnosed with EoE from October 2008 to September 2015 were matched 1:2 on age and sex. Early infant risk factors from the first 6 months of life were investigated. RESULTS: A total of 1410 cases with EoE were matched to 2820 controls. The median (interquartile range) age at diagnosis of EoE was 4.2 years (2.1-7.2) and 68.7% were boys. Proton pump inhibitors (adjusted odds ratio [aOR], 2.73; 95% confidence interval [CI] 1.93-3.88), histamine-2 receptor antagonists (aOR, 1.64; 95% CI 1.27-2.13), and antibiotics (aOR, 1.31; 95% CI 1.10-1.56) were associated with EoE. Prematurity (aOR, 1.46; 95% CI 1.12-1.89) and early manifestations of atopic disease such as milk protein allergy (aOR, 2.37; 95% CI 1.26-4.44) and eczema (aOR, 1.97; 95% CI 1.64-2.36) were related to increased odds for EoE. Erythema toxicum in infancy was strongly associated with a diagnosis of EoE (aOR 3.52; 95% CI 1.03-12.04). Infants with feeding difficulty (aOR, 1.45; 95% CI 1.18-1.77) and gastroesophageal reflux disease (aOR, 1.79; 96% CI 1.43-2.26) were also at increased risk for EoE. CONCLUSIONS: Acid-blocking medications and antibiotics during infancy were associated with later diagnosis of EoE. Erythema toxicum neonatorum, an eosinophilic immune phenomenon, was strongly associated with EoE. Identifying early infant risk factors for EoE may help to risk stratify the need for endoscopy.

Longitudinal Evaluation of Noninvasive Biomarkers for Eosinophilic Esophagitis.

BACKGROUND: The diagnosis and management of eosinophilic esophagitis (EoE) often requires multiple endoscopies. Serum biomarkers can be elevated in EoE patients, but their clinical utility in diagnosis and assessing response to treatment is not well established. GOALS: To evaluate serum biomarkers in EoE subjects compared with controls and assess longitudinally in response to treatment. STUDY: We conducted a prospective cohort study of children and adults undergoing esophagogastroduodenoscopy for suspected EoE. After completing an 8-week course of proton-pump inhibitor therapy, esophageal mucosal biopsies were obtained, as well as, serum analysis of absolute eosinophil count (AEC), eotaxin-3, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP) and interleukin-5. Subjects with normal endoscopic and histologic findings constituted controls. Those meeting criteria for EoE underwent repeat esophagogastroduodenoscopy and biomarker measurements following treatment with topical steroids for 8 weeks. RESULTS: Median levels of AEC (263.50 vs. 102 cu/mm, P<0.001), ECP (26.98 vs. 5.20 ng/mL, P<0.001) and EDN (31.70 vs. 14.18 ng/mL, P=0.004) were significantly elevated in EoE subjects compared with controls and correlated with esophageal eosinophilia. Levels of AEC (odds ratio, 1.79; 95% confidence interval, 1.28-2.64) and ECP (odds ratio, 1.61; 95% confidence interval, 1.23-2.36) were associated with a diagnosis of EoE. Among the 5 biomarkers evaluated, only AEC significantly predicted esophageal eosinophilia following topical steroid therapy in EoE subjects (P=0.006). CONCLUSIONS: AEC, ECP, and EDN were higher in EoE subjects compared with controls and correlated with degree of esophageal eosinophilia. Furthermore, AEC predicted post-treatment eosinophilia, suggesting a potential role in monitoring EoE disease activity.

Feeding Disorders in Children With Autism Spectrum Disorders Are Associated With Eosinophilic Esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASDs) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE. METHODS: A retrospective matched case-cohort study was performed using the Military Health System database from October 2008 to September 2013. We performed a 1:5 case-control match by age, sex, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined using diagnostic and procedure codes. RESULTS: There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared with controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared with other atopic conditions, among both children with ASD (7.17, 95% confidence interval [CI] 4.87-10.5) and controls (11.5, 95% CI 7.57-17.5). Compared with controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39-1.88). CONCLUSIONS: Children with ASD are more likely to be diagnosed with EoE compared with controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE.

Comparisons of Fluticasone to Budesonide in the Treatment of Eosinophilic Esophagitis.

BACKGROUND: Topical steroids are first-line treatment agents for eosinophilic esophagitis; however, some studies have demonstrated modest efficacy in inducing histologic remission. AIMS: The aim of this study was to determine response to two topical steroids (fluticasone and budesonide), compare their efficacy, and examine patient characteristics which could predict non-response to topical steroids. METHODS: We performed a retrospective review of an established EoE registry. Inclusion criteria were patients >1 year of age who were diagnosed with EoE as defined by the most recent consensus guidelines. All patients were treated with an 8-week course of either swallowed fluticasone or viscous budesonide. Responders were defined as achieving <15 eosinophils per high-power field (eos/hpf) in both proximal and distal esophageal biopsies. Demographic, clinical, endoscopic, and histologic features were examined. RESULTS: The study cohort included 75 EoE patients with a median age of 33 years (range 2-64 years), 71 % adults, 84 % male, and 76 % Caucasian. Overall histologic response rate to topical steroids was 51 %, while clinical response was 71 %. There was no significant differences in histologic response to treatment between children and adults (68 vs. 44 %, p = 0.111). There was no significant difference in response between males and females (47 vs. 73 %, p = 0.191) and between the two types of steroids (48 vs. 56 %, p = 0.632). Responders and non-responders were similar in clinical presentation and baseline endoscopic findings. Following treatment, responders had significantly less peak proximal (4.0 ± 4.4 vs. 46 ± 53, p < 0.001) and distal eosinophil counts (3.5 ± 3.8 vs. 60 ± 47, p < 0.001) compared to non-responders. There were no predictors of response to steroids identified. CONCLUSIONS: Histologic response to treatment was observed in approximately half the cohort, while more than two-thirds experienced clinical response to topical steroids. Response was similar between fluticasone and budesonide. Given the lack of differences in clinical presentation or endoscopic features, predictors of non-response were not seen.

A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations.

BACKGROUND: Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement. AIM: To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB. METHODS: A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered. RESULTS: Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose. CONCLUSION: OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

Swallowed glucocorticoid therapy for eosinophilic esophagitis in children does not suppress adrenal function.

OBJECTIVE: The purpose of this study was to examine the effect of chronic swallowed glucocorticoids on adrenal function during the treatment of eosinophilic esophagitis (EoE) in children. METHODS: Serum cortisol levels were obtained in children with EoE pre- and post-treatment with swallowed glucocorticoids. Exclusion criteria included those on any additional steroid therapy. Once diagnosed with EoE by esophageal biopsy, subjects were treated based on current standard of care with either swallowed fluticasone or budesonide. At the time of follow-up, esophagogastroduodenoscopy and blood sampling was repeated. Both pre- and post-treatment serum cortisol samples were collected fasting, between 07:00 and 10:00, and determined using a competitive binding method assay. The distribution of differences in cortisol levels between the pre- and post-treatment samples satisfied the assumption for normality and were subsequently analyzed using the paired t-test. RESULTS: Pre- and post-treatment serum cortisol levels were examined in 14 children who met clinical and histological diagnostic criteria for EoE. Mean age was 10.1 years (range 2-17 years) with 71% male and 29% female subjects. Swallowed glucocorticoid treatment included fluticasone in 79% and budesonide in 21% of subjects. Mean dosage of fluticasone was 704 µg daily (range 220-880 µg daily) and budesonide 0.8 mg daily (range 0.5-1 mg daily), along with a mean treatment length of 17 weeks (range 8-43 weeks). No significant difference in serum cortisol was found following treatment with swallowed fluticasone or budesonide (mean change 1.9 µg/dL, p=0.75, SD of the change=21.2). CONCLUSIONS: Swallowed glucocorticoid therapy does not appear to significantly affect the adrenal axis in children, and therefore, may represent a safe therapy for EoE.

Video capsule endoscopy impacts decision making in pediatric IBD: a single tertiary care center experience.

BACKGROUND: Little is known about the impact of video capsule endoscopy (VCE) on decision making in pediatric patients with IBD. Moreover, few studies have reported on the outcomes of treatment changes made based on VCE findings. Our aim was to identify the added value of VCE in pediatric patients in a tertiary IBD center with established or suspected IBD, by assessing changes in treatments and outcomes before and after VCE. METHODS: A retrospective chart review was performed in children with established (n = 66) or suspected (n = 17) IBD who underwent VCE. Diagnostic classifications, treatments, and clinical outcomes before and 1 year after VCE were compared. RESULTS: Primary indications for VCE included patients treated for Crohn's disease (CD) with poor growth or active symptoms (60%), patients with ulcerative colitis/IBD-unclassified (19%), and suspected IBD (20%). Abnormal VCE was seen in 86% of patients with CD, of whom 75% underwent treatment escalation. One year after VCE, patients with CD improved in growth (mean z-scores at baseline and 12 months, -0.5 and 0.2, respectively; P < 0.0001), mean body mass index (18.3 and 19.8, respectively; P = 0.004), mean erythrocyte sedimentation rate (25 versus 16, respectively; P = 0.012), and median Harvey-Bradshaw Index (2 and 0, respectively; P = 0.003). VCE revealed more extensive disease than concurrent imaging modalities in 43% of the patients with CD. VCE "ruled out" IBD in 94% who had suspected IBD, whereas 50% with presumed ulcerative colitis/IBD-unclassified had a diagnosis changed to CD. CONCLUSIONS: VCE provides additional clinical information that impacted management of pediatric patients with IBD in a tertiary IBD center and was associated with improved outcomes.

Thickened gastrointestinal wall findings on computed tomography in children: a reason for endoscopy?

OBJECTIVES: Bowel wall thickening on computed tomography (CT) scans in children may raise concern for inflammatory bowel disease (IBD). The significance of this radiological finding is unclear. Our purpose was to evaluate the clinical outcomes with regard to IBD in children with no known underlying disease, presenting with abdominal pain and thickened bowel wall on CT scan. METHODS: A retrospective analysis of pediatric patients with abdominal pain and CT findings of thickened bowel wall was performed between 2006 and 2010. Endoscopic findings, clinical variables, and follow-up assessments were evaluated. RESULTS: Fifty-six patients presenting with abdominal pain and thickened bowel wall findings on CT scan were identified. Overall, 30 (54%) had terminal ileum wall thickening, 17 (30%) had isolated colonic wall thickening, and 9 (16%) had other small bowel wall thickening. Of the 56 patients, 21 (38%) underwent endoscopy, of which 14 (67%) had positive findings-11 (79%) had histologic evidence of chronic colitis, and 5 (36%) had duodenitis/ileitis. Ultimately, 11/56 (20%) were diagnosed as having IBD, 8/56 (14%) with functional abdominal pain/constipation, 9/56 (16%) appendicitis, 10/56 (18%) infectious gastroenteritis, and 18/56 (32%) with miscellaneous diagnoses. Median levels of erythrocyte sedimentation rate, C-reactive protein, albumin, and platelet count were significantly abnormal in the IBD group compared to the non-IBD group. Additional follow-up of those who did not undergo endoscopic evaluation revealed no new diagnoses of IBD. CONCLUSIONS: The presence of thickened bowel wall on CT scans is a nonspecific finding in children. Laboratory evaluation may help distinguish which patients require additional evaluation and endoscopy.