Dietary treatment of eosinophilic gastrointestinal disorders in children.

PURPOSE OF REVIEW: To provide an overview of recent developments on dietary treatment of eosinophilic gastrointestinal disorders (EGID) in children. RECENT FINDINGS: Food antigens are the main triggers of eosinophilic esophagitis (EoE); however, currently available allergy tests cannot reliably identify eliciting antigens. Studies evaluating the six-food empiric elimination diet (6FED-milk, wheat/gluten, egg, soy/legumes, nuts and fish/seafood) have shown histological remission rates of 72%. Milk, egg, wheat/gluten, and, to a lesser extent, soy/legumes were the most frequent food triggers with only one or two culprit foods identified for most patients. A 4-food elimination strategy afforded a 64% remission rate. A step-up two-four-six food elimination diet generated a 43% remission rate at the two-food elimination stage, and similar reported rates for 4FED and 6FED. Endoscopic procedures were reduced by a 20% compared with 6FED. In a prospective study including 63 children, exclusive milk elimination has been effective in 44% of them. Controlled elimination and reintroduction with histological assessment is necessary. SUMMARY: Dietary therapy of EoE has evolved from more restrictive to less restrictive diets to provide better balance between efficacy vs. nutritional deficiencies and quality of life. Data on efficacy of dietary therapy in other EGIDs are very scarce.

Strategy for Food Reintroduction Following Empiric Elimination and Elemental Dietary Therapy in the Treatment of Eosinophilic Gastrointestinal Disorders.

PURPOSE OF REVIEW: This review presents the available data regarding efficacy of nutritional therapy, highlighting clinical decision points and a strategy for reintroduction of foods following an elemental diet for treatment of eosinophilic gastrointestinal disorders. RECENT FINDINGS: Elemental and empiric elimination diets are highly effective treatments for eosinophilic gastrointestinal diseases. Standardization in the reintroduction phase, after utilizing the diet for disease remission, is lacking. Clinicians are confronted with multiple challenges regarding the best practice for food reintroduction and identification of potential dietary triggers including order of foods being challenged and duration between endoscopic procedures. Individualization is required for preference and adherence to optimize quality of life and treatment success for this burdensome and life altering immune driven gastrointestinal disorder. Age specific concerns for children, teenagers, and adults should be assessed using a patient centric approach.

Retrospective study of budesonide in children with eosinophilic gastroenteritis.

BACKGROUND: The effectiveness of budesonide (BUD), a locally active steroid, on eosinophilic gastroenteritis (EGE) is not well understood. This study is to retrospectively evaluate the efficacy of BUD in children with EGE. METHODS: Forty-four children, diagnosed with EGE, were enrolled from 2013 to 2017 in our center. According to patients' preference, all the patients were treated with dietary elimination (DE) and montelukast therapy, or combined with prednisone (PRED)/BUD. Patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Twenty-four patients (7 PRED, 7 BUD, 10 DE) received therapy for ≥8 weeks, followed by repeat endoscopy and biopsies. Histological response was defined as <20 eos/hpf (eosinophils per high-power field). RESULTS: Significant number of patients in DE+PRED (6/7, 85.7%) and DE+BUD (6/7, 85.7%) groups achieved histological response than in the DE group (3/10.30%) (p = 0.024). Mean post-treatment peak eos/hpf in the DE+PRED group was 16.57 ± 6.85 vs. 10.00 ± 5.07 in the DE+BUD group vs. 36.60 ± 24.57 in the DE group (p = 0.009). Change of eos/hpf from pre- to post-treatment was -49.86 ± 45.02 vs. -34.29 ± 23.44 in the BUD group vs. -0.3 ± 23.95 in the DE group (p = 0.011). There were no significant differences between DE+PRED and DE+BUD groups (p = 0.470, p = 0.363, respectively). CONCLUSION: BUD is effective in the treatment of EGE and has similar effectiveness with PRED.

Pilosebaceous targeting by isotretenoin-loaded invasomal gel for the treatment of eosinophilic pustular folliculitis: optimization, efficacy and cellular analysis.

CONTEXT: Eosinophilic pustular folliculitis is a secondary symptom associated with HIV infection appears as levels of CD4 lymphocyte cells and T4 lymphocyte cell. Isotretinoin, an analog of vitamin A (retinoid) alters the DNA transcription mechanism and interferes in the process of DNA formation. It also inhibits the eosinophilic chemotactic factors present in sebaceous lipids and in the stratum corneum of patients suffering from this ailment. OBJECTIVE: The present research was aimed to formulate isotretenoin-loaded invasomal gel to deliver and target the drug to pilosebaceous follicular unit. METHODS: Nine invasomal formulations (F1-F9) were prepared applying 32 factorial designs and characterized. RESULTS: Formulation F9 was selected as optimized formulation due to optimum results and highest %CDP of 85.94 ± 1.86% in 8 h. Transmission electron microscopy (TEM) suggested uniformity in vesicles shape and size in F9 and developed as invasomal gel (IG). LIMITATIONS: Clinical phase-I, phase-II, and phase-III studies will be required before using on human patients. CONCLUSION: Confocal laser scanning microscopy (CLSM) validates that IG successfully reaches the pilosebaceous follicular unit and further studied on cell line (SZ-95) exhibited IC50 of ≤8 (25 µM of isotretenoin). Cell cycle analysis confirmed IG arrested the cell growth up to 82% with insignificant difference to pure isotretenion.

High Prevalence of Eosinophilic Gastrointestinal Disease in Children With Intestinal Failure.

OBJECTIVES: The aim of the present study was to describe the prevalence and clinical features of gastrointestinal (GI) eosinophilic inflammation among pediatric patients with intestinal failure (IF). METHODS: Medical records of all patients studied in our institution's IF program who underwent GI endoscopy over a 15-year period were reviewed, and clinical, pathologic, nutrition, and laboratory data collected. RESULTS: One hundred five patients underwent 208 GI endoscopic procedures with biopsy. The overall prevalence of eosinophilic inflammation, defined as increased eosinophils in at least 1 tissue type on at least 1 endoscopy, was 39 of 105 (37%). The tissue-specific prevalence of eosinophilic inflammation ranged widely, with the colon/rectosigmoid being the most common (18/68, 26%), followed by the esophagus (17/83, 20%), ileum (9/54, 17%), duodenum (4/83, 5%), and stomach (3/83, 4%). Higher peripheral eosinophil count and hematochezia were associated with eosinophilic inflammation in the colon (P = 0.002 and 0.0004, respectively). The use of a strict elemental diet for 3 months before endoscopy was not associated with a decreased frequency of eosinophilic inflammation in any tissue. CONCLUSIONS: Eosinophilic inflammation is a common histopathological finding in patients with IF. Colonic eosinophilic inflammation is associated with clinical symptoms of GI blood loss, and peripheral eosinophilia, and was not abrogated by a strict elemental diet.

Efficacy of Dietary Treatment for Inducing Disease Remission in Eosinophilic Gastroenteritis.

OBJECTIVES: Various dietary interventions have been used to treat patients with eosinophilic gastroenteritis (EGE). Concrete evidence as to the effectiveness of such treatments in inducing disease remission is, however, lacking. The aim of the study was to systematically review the efficacy of dietary therapies in inducing EGE remission. METHODS: We performed a systematic search for the MEDLINE, EMBASE, and SCOPUS libraries for studies investigating the efficacy of dietary interventions (in both histological and symptomatic remission) for children and adults with EGE and colitis. RESULTS: The search yielded 490 references; 30 were included in the review, with most of these references being "low-quality" individual cases or short case series. No significant publication bias was found. Elemental diets in children were linked to 75.8% of clinical improvement, but few of these patients underwent a histological evaluation. Allergy-testing results have been used scarcely in EGE. Empiric elimination of allergy-associated foods was the most commonly used option. The variable results in terms of symptom relief, however, were scarcely accompanied by histological confirmation. Clinical and methodological heterogeneity hindered the performance of quantitative summaries for the efficacy of dietary therapies in inducing disease remission. CONCLUSIONS: Symptomatic improvements reported for dietary treatment in EGE by most of the available literature are questionable because of the lack of objective evaluation of clinical changes and the very limited assessment of histological remission. Because of the relative lack of well-designed, high-quality studies, the unequivocal use of dietary treatment for patients with EGE and colitis cannot be supported. Further research should be undertaken.

Eosinophilic gastritis in children: clinicopathological correlation, disease course, and response to therapy.

OBJECTIVES: Eosinophilic gastritis (EG), defined by histological criteria as marked eosinophilia in the stomach, is rare, and large studies in children are lacking. We sought to describe the clinical, endoscopic, and histopathological features of EG, assess for any concurrent eosinophilia at other sites of the gastrointestinal (GI) tract, and evaluate response to dietary and pharmacological therapies. METHODS: Pathology files at our medical center were searched for histological eosinophilic gastritis (HEG) with ≥70 gastric eosinophils per high-power field in children from 2005 to 2011. Pathology slides were evaluated for concurrent eosinophilia in the esophagus, duodenum, and colon. Medical records were reviewed for demographic characteristics, symptoms, endoscopic findings, comorbidities, and response to therapy. RESULTS: Thirty children with severe gastric eosinophilia were identified, median age 7.5 years, 14 of whom had both eosinophilia limited to the stomach and clinical symptoms, fulfilling the clinicopathological definition of EG. Symptoms and endoscopic features were highly variable. History of atopy and food allergies was common. A total of 22% had protein-losing enteropathy (PLE). Gastric eosinophilia was limited to the fundus in two patients. Many patients had associated eosinophilic esophagitis (EoE, 43%) and 21% had eosinophilic enteritis. Response to dietary restriction therapy was high (82% clinical response and 78% histological response). Six out of sixteen patients had persistent EoE despite resolution of their gastric eosinophilia; two children with persistent HEG post therapy developed de novo concurrent EoE. CONCLUSIONS: HEG in children can be present in the antrum and/or fundus. Symptoms and endoscopic findings vary, highlighting the importance of biopsies for diagnosis. HEG is associated with PLE, and with eosinophilia elsewhere in the GI tract including the esophagus. The disease is highly responsive to dietary restriction therapies in children, implicating an allergic etiology. Associated EoE is more resistant to therapy.

Eosinophilic gastrointestinal disorder in an infant with feeding dysfunction.

Feeding dysfunction (FD) has recently been considered to comprise a prevalent set of symptoms in eosinophilic gastrointestinal disorders (EGIDs) in young children. We report the case of an 8-month-old girl with an EGID who visited our hospital due to vomiting, poor weight gain and feeding difficulties; her condition was discovered during the examination of the symptoms including FD. Tracheal aspiration and reduced esophageal clearance showed up in a barium swallow test and upper gastrointestinal contrast radiography, respectively. Delayed clearance from the stomach was also detected on gastrointestinal scintigraphy. Gastrointestinal endoscopy and biopsies revealed esophagitis with some eosinophils and duodenitis with eosinophilic inflammation. She was not a likely candidate for eosinophilic esophagitis. On administration of an elemental diet, the patient gained weight. Esophageal and stomach clearance subsequently improved, although the vomiting and FD persisted to some extent. We conclude that it is important to consider other EGIDs as well as eosinophilic esophagitis in the differential diagnosis of FD.

Factors contributing to adherence to dietary treatment of eosinophilic gastrointestinal diseases.

The purpose of the present study was to identify barriers to dietary adherence found in the treatment of children with eosinophilic gastrointestinal diseases (EGIDs) and food allergy. A prospective study using a self-administered survey to parents of children with EGIDs at a national advocacy meeting was completed. Responses from 45 participants describing children ages 1 to 18 years (69% boys) identified that 63% were adherent to food restrictions. Physicians provided dietary instructions more often than dietitians. Nonadherence was associated with lack of school support (P < 0.027). Access to a dietitian may improve the care of children with EGIDs.

Nutritional Aspects of Pediatric Gastrointestinal Diseases.

In the last decade, the role of nutritional management in pediatric gastrointestinal diseases has gained increasing popularity. Disease-specific diets have been introduced as conventional treatments by international guidelines. Patients tend to more willingly accept food-based therapies than drugs because of their relatively "harmless" nature. Apart from a diet's therapeutic role, nutritional support is crucial in maintaining growth and improving clinical outcomes in pediatric patients. Despite the absence of classical "side effects", however, it should be emphasized that any dietary modification might have negative consequences on children's growth and development. Hence, expert supervision is always advised, in order to support adequate nutritional requirements. Unfortunately, the media provide an inaccurate perception of the role of diet for gastrointestinal diseases, leading to misconceptions by patients or their caregivers that tends to overestimate the beneficial role of diets and underestimate the potential adverse effects. Moreover, not only patients, but also healthcare professionals, have a number of misconceptions about the nutritional benefits of diet modification on gastrointestinal diseases. The aim of this review is to highlight the role of diet in pediatric gastrointestinal diseases, to detect misconceptions and to give a practical guide for physicians on the basis of current scientific evidence.

Efficacy of an elimination diet in a patient with eosinophilic gastroenteritis : a pediatric case with multiple food allergies.

Eosinophilic gastrointestinal disorders are chronic inflammatory diseases in which eosinophils highly infiltrate into gastrointestinal tissue, resulting in gastrointestinal dysfunction. Here, we report a case of pediatric eosinophilic gastroenteritis (EGE). A 7-year-old boy with multiple food allergies (cow milk, hen's egg, fish,shellfish, and chicken) was admitted to our hospital because of continuous abdominal pain and vomiting. His soy allergy had been diagnosed to have oral tolerance based on an oral food challenge at the age of 6 years. He was diagnosed with EGE based on biopsy findings showing eosinophilic infiltration ( 20 eosinophils per high-power field) into the gastrointestinal mucosa. A diet eliminating soy, wheat, beef, pork, rice, and sesame in addition to the food that had already been eliminated and oral corticosteroids improved his symptoms and peripheral eosinophilia. A relapse of both abdominal pain and peripheral eosinophilia after the reintroduction of soy or pork identified them as foods causative of EGE. This report highlights the utility of elimination diets in improving EGE symptoms and the subsequent reintroduction of offending foods in identifying causative foods. Furthermore,EGE onset should be considered when introducing potentially allergic food in the management of food allergy. J. Med. Invest. 66 : 201-204, February, 2019.

Eosinophilic esophagitis, gastroenteritis, and colitis in a patient with prior parasite exposure.

Eosinophilic gastrointestinal disorders (EGID) comprise a spectrum of inflammatory diseases that can affect any segment of the gastrointestinal tract. The pathogenesis of these conditions is complex; differentiating between primary and secondary forms of these disorders can be clinically challenging. We report a case of primary EGID in a patient with remote parasite exposure, whose symptoms were initially attributed to irritable bowel syndrome. Endoscopy revealed the rare finding of EGID involving the entire gastrointestinal tract; symptoms improved with an elimination diet. This case raises the possibility of a link between prior parasite exposure and development of EGID, and underscores the necessity of exploring alternative diagnoses in patients with presumed IBS who present with severe symptoms.

Nutritional management of eosinophilic esophagitis.

Eosinophilic esophagitis has been increasingly described in pediatric and adult literature. Several pediatric studies have indicated that food allergies are responsible for more than 90% of pediatric cases. There are three different dietary approaches to the management of eosinophilic esophagitis: (1) the elemental diet, (2) the removal of foods based on allergy testing, and (3) the removal of the foods that most commonly cause eosinophilic esophagitis. This article discusses the nutritional risks and benefits of each approach.

Eosinophilic esophagitis: is it all allergies?

Eosinophilic esophagitis (EE) is an increasingly recognized disorder in the adult population, most often manifested by symptoms of dysphagia and food impaction. Mechanisms involving eotaxin-3, interleukin 5, and signal transducer and activator of transcription 6 have been studied and may represent future therapeutic targets. Patients commonly have a personal and family history of atopy, and both food allergies and aeroallergens have also been investigated as triggers of EE. Traditional allergy-testing methods, including skin prick testing and specific IgE testing, have been used to identify food and environmental allergies. However, new studies suggest that patch testing could add to diagnostic accuracy in EE because the disorder might not be a classic type I allergic response. Although studies of treatment of adults with EE have thus far focused on swallowed fluticasone proprionate, many trials in children have assessed the efficacy of food elimination and elemental diets. These diets, which have been extremely successful in reducing symptoms, have also been shown to induce histological improvement and remission. No similar studies have been conducted in adults; the tolerability of such an intervention may prove more difficult in this population. This article reviews the underlying pathophysiology of EE and describes evolving options for more accurately identifying food and environmental allergies. We also discuss the pediatric trials using food elimination and avoidance diets and suggest that this type of intervention may be an important area of future research in the adult population.

Evidence for Involvement of IL-9 and IL-22 in Cows' Milk Allergy in Infants.

Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows' milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows' milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows' milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows' milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions.