Eosinophilic esophagitis in children: Updates and practical aspects of management for allergists in a non‐tertiary care private practice setup

Background: Eosinophilic esophagitis (EoE) is a chronic immune and/or antigen-mediated disease characterized by eosinophilic infiltration of mucosa (≥15 eosinophils per high power field) without any secondary etiology. Non‐immunoglobulin E mediated mechanisms predominate in EoE. Objective: This review concentrated on a stepwise approach for the allergist working in non‐tertiary care private practice. Methods: A medical literature search that focused on several areas of the latest developments in the diagnosis and management of EoE was conducted. Results: There has been a steady increase in the prevalence and incidence of EoE. Clinical symptoms can vary from dysphagia to failure to thrive, depending on the age at presentation; some children develop adaptive behaviors to compensate for dysphagia, such as food preferences and slow eating. The diagnosis is based on a high index of clinical suspicion and is confirmed with endoscopy with biopsies after ruling out other causes of esophageal eosinophilia. Treatment options may include dietary therapy, pharmacologic therapies, or combination therapy. Therapeutic options may also include endoscopic dilation for stricturing disease. Conclusion: Providers should be aware of recent recommendation changes in the diagnostic workup, the role of skin-prick testing, and role of the proton-pump inhibitor as first-line therapy for EoE. Also, clinicians should be aware of the emerging role of empiric dietary therapy as a preferable therapeutic option when compared with the testing-directed diet and the elemental diet. Furthermore, topical glucocorticoid therapies are available, and new developing therapies are being investigated. Reevaluation of esophageal mucosa with biopsies is required approximately 2 months after therapy for a response and after a change in therapies to confirm continued resolution.

Clinical and Nutritional Impact of a Semi-Elemental Hydrolyzed Whey Protein Diet in Patients with Active Crohn’s Disease: A Prospective Observational Study

Background: Malnourishment is a common complication in patients with Crohn’s disease. Methods: An observational, prospective study was conducted to assess the nutritional status, disease activity, and stool frequency at baseline and after 12 weeks of treatment with a semi-elemental diet in patients with active Crohn’s disease. Results: A total of 144 patients with Crohn’s disease were included. The nutritional status improved after treatment, resulting in 76.1% of patients at low risk of malnourishment, 20.4% moderately malnourished, and 8.5% severely malnourished after 12 weeks of treatment. Nutritional status improvement was associated with the number of nutritional supplements. Mean albumin levels and body mass index (BMI) improved after 12 weeks of nutritional treatment (from 3.0 g/dL to 3.7 g/dL and from 20.2 kg/m2 to 21.1 kg/m2, respectively). A significant decrease in HBI was found after 12 weeks of nutritional treatment (from 10.2 to 3.7). The mean number of stools per day decreased with the 12 week semi-elemental diet (from 4.6 stools/day to 1.7 stools/day). Conclusion: In this observational study, the semi-elemental diet seemed effective in improving the nutritional status, disease activity, and stool frequency in patients with active Crohn’s disease.

Chyle leak following total colectomy for ulcerative colitis: a case report and review of the literature

Chyle leak is a rare complication in colorectal surgery. It occurs due to disruption of the lymphatic drainage network in the abdomen or retroperitoneum. We describe the first reported case of chyle leak following total colectomy for inflammatory bowel disease. Our patient underwent total colectomy for severe ulcerative colitis not responsive to medical treatment. Four days postoperatively, a milky fluid was noted in the drainage bag. Analysis of the fluid confirmed chyle. The patient remained well and was successfully managed conservatively with a fat-free elemental diet and was discharged from hospital on day 12 postoperatively. A review of the literature suggests that conservative management with dietary modification is a common and effective management strategy; however, medical and surgical options exist for refractory cases.

A Case Study Vignette for a Pediatric Patient With Eosinophilic Esophagitis

Objectives Eosinophilic Esophagitis (EoE) is a chronic inflammatory, immune/antigen-mediated condition of the esophagus. It is common in pediatric patients and can lead to several complications such as esophageal remodeling/fibrosis, growth stunting, and low bone mineral density. Nutrition interventions, such as elimination or elemental diets, are the first therapeutic tool for EoE management along with pharmacological interventions. Methods KS is a 20 month-old female whose weight-for-length has fallen above the 55th percentile since birth. She has a history of gastroesophageal reflux, dysphagia, and aspiration requiring thickened liquids for almost 2 years. During infancy she tolerated milk based thickened formula and transitioned to 1% milk at 1 year. She was diagnosed with EoE during a triple endoscope for laryngeal cleft repair. The pathology revealed rings and furrows in the mid/distal esophagus, and > 20 eosinophils per high powered field (HPF) in distal, mid, and proximal esophagus with evidence of subepithelial fibrosis. At that time she had no dietary restrictions or use of antacids. Since cleft repair, dysphagia improved and she started on a dairy free diet for EoE. However, she experienced an adverse reaction to dairy free nut-based cheese with subsequent positive radioallergosorbent testing to tree nuts. Follow-up endoscopy improved on an 8-week dairy and tree nut free diet, but eosinophils persisted in proximal esophagus with evidence of basal cell hyperplasia. Results The patient was able to make important strides towards remission by eliminating suspected trigger foods, with diagnosis and intervention initiation before signs of inadequate growth or nutrition. Conclusions Nutrition interventions are often imperative to achieve remission of EoE. There are potential nutrition related concerns including increased risk of nutrient deficiencies, inadequate growth, and poor quality of life as the patient follows an elimination/elemental diet. EoE should become a consideration when feeding or swallowing difficulties arise, especially in pediatric patients. Proper diagnosis, tailored interventions, and appropriate monitoring and evaluation with the help of a multidisciplinary team can lead to successful management. Funding Sources N/A.

Regulation of Akt Signaling in Skeletal Muscle Is Altered by Prematurity in a Neonatal Piglet Model

Objectives Preterm birth is a risk factor for growth faltering. We recently showed in a neonatal piglet model of prematurity that premature birth decreases weight gain and skeletal muscle protein synthesis. This is associated with reduced insulin-induced activation of signaling components downstream of Akt but with no change in the activation of the IR/IRS-1/PI3K axis upstream of Akt. The aim of this study was to identify key regulatory molecules involved in Akt activation that are responsible for the differential response of skeletal muscle to insulin in preterm compared to term pigs. Methods Piglets were delivered by cesarean section 11 d (preterm/PT) or 2 d (term/T) before term birth and a jugular vein catheter was placed for delivery of total parenteral nutrition. On day 3, after 4 h fasting, piglets were fasted one additional h or fed an elemental diet (31.5 kcal/kg, 1.3 g/kg carbohydrate, 2.7 g/kg amino acids, and 1.6 g/kg lipid), similar in composition to sow milk, via oral gavage. Longissimus dorsi muscle was collected following euthanasia (fasted state or 60 min after feeding). Positive and negative regulators of Akt activity were determined by immunoprecipitation and immunoblotting assays. Results Akt1 and Akt2 phosphorylation were lower in PT than in T pigs (P < 0.05), whereas Akt3 phosphorylation was not affected by prematurity. The phosphorylation of Akt activators PDK1 and mTORC2, but not FAK, was lower in PT than in T pigs (P < 0.05). The abundance of Ubl4A, a positive regulator of Akt, was lower in PT than in T pigs (P < 0.05). The abundance Akt inhibitors PHLPP and SHIP2, but not PTEN and IP6K1, was significantly higher in PT than in T pigs (P < 0.05). Activation of the phosphatase PP2A was lower in PT than in T pigs (P < 0.05), but its activation was not affected by feeding. However, PP2A activation was inhibited by feeding in T pigs (P < 0.05). Conclusions These results showed that following preterm birth, the postprandial activation of positive regulators of Akt is reduced whereas the activation of negative regulators of Akt is enhanced. Our findings suggest that premature birth impairs the activation of Akt that is essential for channeling dietary nutrients for anabolism and likely contributes to the extrauterine growth faltering of prematurity. Funding Sources NIH and USDA.

Fecal microbiome composition in pancreatic cancer cachexia and response to nutrition support.

4129 Background: Pancreatic ductal adenocarcinoma (PDAC) carries a poor prognosis with a 5-year survival rate of 10.0%. Previous studies in stool microbiome indicate that microbiome composition has been associated with therapy response and pathogenesis across multiple cancers, and PDAC patients (pts) with higher bacterial diversity have demonstrated greater long-term survival. The fecal microbiome has not previously been characterized for PDAC pts with cancer cachexia or associated interventions. The study addressed the changes in microbiome over the course of treatment and the association between baseline bacterial composition and outcome in PDAC pts with cachexia. Methods: Stool specimens were collected from the PNCX1 trial (NCT02400398), where all pts were given a semi-elemental diet—enzymatically hydrolyzed protein—with enteral tube feeding. Stool samples (n = 29) were collected at time points aligned with enteral feeding and chemotherapy cycles separated by 6 weeks (C1D1, C2D1, and C3D1) and analyzed using 16S v4 sequencing of the microbiome. Microbiome changes from C1D1 to C3D1, weight stability, and overall survival (OS) were measured alongside microbiome characterization. Results: Pts with a complete set of stool samples were analyzed (n = 6) for differences in microbiome composition across treatment cycles. C3D1 samples were significantly associated with both an increased population of Veillonella and Actinomyces and decreased Bacteroides and Butyricicoccus compared to C1D1. Baseline stool microbiome composition was also evaluated to predict weight stability throughout treatment. In patient stool samples (n = 8) at C1D1, greater abundance of Veillonella (p = 0.0006) and reduced Bifidobacterium (p = 2.62E-5) were linked to greater weight stability. Microbiome alpha-diversity was also characterized using Shannon and Chao1 indices, where stable weight was related to reduced species richness (Chao1, p = 0.0194) but not evenness (Shannon, p = 0.1716). C1D1 patient stool samples were then analyzed and compared to OS (n = 16). Although no significant differences in global microbiome composition were noted between OS < 180 days and OS > 180 days, Parasutterella, Tyzzerella, Phascolarctobacterium, and Lachnoclostridium were identified as more prevalent in OS > 180 days despite their relatively low abundance. Conclusions: We are among the first evaluate stool bacteria changes over treatment course in PDAC pts. While Veillonella was associated with weight stability in a cohort of advanced PDAC pts all receiving enteral feeding, several genera were found in abundance in pts with prolonged OS, though this needs further validation. The potential impact of the gut microbiome and enteral feeding on weight stability is provocative given that cachexia is a hallmark of PDAC and an effective strategy to mitigate this process would be transformative.

A Clinical Perspective on the Dietary Therapies for Pediatric Eosinophilic Esophagitis: The Gap Between Research and Daily Practice

Pediatric eosinophilic esophagitis (ped-EoE) is an immune-mediated pathology affecting 34 per 100.000 children. It is characterized by an esophageal inflammation caused by an immune response towards food antigens that come into contact with the esophageal lining. Depending on the age of the child, symptoms can vary from abdominal pain, vomiting and failure to thrive to dysphagia and food impaction. The diagnosis of this chronic disease is based on the symptoms of esophageal dysfunction combined with an infiltration of more than 15 eosinophils per high-power field and the exclusion of secondary causes. The treatment modalities include the 3Ds: Drugs, allergen avoidance by Diet and/or esophageal Dilation. In this review we focused on the efficacy of dietary approaches in ped-EoE, which currently include the elemental diet (amino acid-based diet), the empiric elimination diet and the allergy test-directed elimination diet. Although several reviews have summarized these dietary approaches, a lack of consistency between and within the elimination diets hampers its clinical use and differences in subsequent reintroduction phases present a barrier for dietary advice in daily clinical practice. We therefore conducted an analysis driven from a clinician’s perspective on these dietary therapies in the management of ped-EoE, whereby we examined whether these variations within dietary approaches, yet considered to be similar, could result in significant differences in dietary counseling.