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.

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.

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.

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.

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.

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.

Hematochezia caused by eosinophilic proctocolitis in a newborn before oral feeding: a case report.

BACKGROUND: Hematochezia is a frequent symptom in early infancy. However, it occurs very rarely within the immediate neonatal period, and its occurrence before any oral intake is particularly rare. Because of the "congenital" presentation of hematochezia in our patient, we initially considered our case to be a non-classical, potentially severe type of food protein-induced allergic proctocolitis. This diagnosis needs to be confirmed by an abnormal oral challenge test once the hematochezia has disappeared. If such a challenge cannot demonstrate an allergic origin, then the etiology of the hematochezia could be a neonatal transient eosinophilic colitis. Only two similar cases have been described so far. CASE PRESENTATION: We report the case of a black baby boy of African origin born at 36 weeks 5 days of gestational age who presented with massive hematochezia immediately after birth. A rectosigmoidoscopy revealed a severe inflammation associated with diffuse eosinophilic infiltration on biopsy. His clinical outcome was favorable after introduction of an amino acid formula diet. We initially considered our case to be a non-classical, potentially severe type of food protein-induced allergic proctocolitis but reintroduction of standard formula milk at the age of 3 months was successful. So, our patient is the first newborn in Europe who fits the diagnosis of "neonatal transient eosinophilic colitis." CONCLUSIONS: We discuss the possible etiology of "congenital" eosinophilic inflammation of the distal colon and conclude that hematochezia in well-looking neonates, in the absence of negative challenge tests later on, is more likely to be a neonatal transient eosinophilic colitis than an allergic proctocolitis. This new entity could be more frequent than previously thought, changing our medical care strategies for this kind of neonatal symptom.

Eficacia y seguridad de fórmula a base de aminoácidos libres en pacientes pediátricos con gastroenteropatías eosinofílicas / Efficacy and safety of free amino acid formula in pediatric patients with eosinophilic gastroenteropathy

INTRODUCCIÓN: Antecedentes: El presente dictamen expone la evaluación de tecnología de la eficacia y seguridad de la fórmula en base a aminiácidos libres (FAA) respecto a su uso en pacientes con gastroenteropatias eosinofilicas (GE). Aspectos Generales: Las gastroenteropatias eosinofilicas (GE) son un conjunto de enfermedades que se caracterizan por la infiltración de eosinófilos en diversos órganos del cuerpo. Dentro del grupo de las GE se encuentran la esofagitis eosinofílica (EoE) y las gastroenteritis eosinfílicas (EGE). Tecnologia Sanitaria de Interés: Las fórmulas en base a aminoácidos lilbres (FAA) son fórmulas hipoalergénicas que han sido diseñadas para pacientes que requieren ingerir porteínas en su estructura más simples. Las proteínas que componen estas fórmulas están en forma de L-aminiácidos (Nutrition 2000). DEbido a ello, las FAA son llamadas también fórmulas elementales. Estas fórmulas tienen un perfil nutricional completo ya que, además de aportar porteínas, aportan también carbohidratos, lípidos y micronutrientes (Nutrition 2000). La composición nutricional de las FAA varía según el grupo etario y la enfermedad base de la población para la cual están dirigidas. METODOLOGIA: Estrategia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad del uso de fórmulas en base a aminoácidos libres (FAA) en pacientes con gastroenteropatias eosinofílicas (GE). Se dio preferencia a guías de práctica clínica, revisiones sistemáicas con o sin meta-análisis y ensayos clínicos aleatorizados. Asimismo, se consideró extraer información con una estrategia de "bola de nieve" mediante la revisión de las referencias bibliográficas bibliográficas de las guías de páctica clínica, revisiones seleccionadas. RESULTADOS: Sinopsis de la Evidencia: Se realizó la búsqueda bibliográfica y de evidencia científica para el sustento del uso de fórmula en base de aminoácidos libre en pacientes pediátricos con gastroenteropatías eosinofílicas. Así, luego de revisar un total de 520 referencias resultados de la búsqueda bibliográfica, se seleccionaron 18 estudios relevantes. Cuatro referencias fueron selecionadas para ser analizadas. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se presenta la evidencia recabada sobre el uso de la fórmula en base a aminoácidos libres (FAA) en pacientes con gastroenteropatías eosinofilicas (GE). La evidencia encontrada que evalúa el uso de la FAA en pacientes con GE es escasa. Se ha identificado evidencia proveniente de una guía de práctica clínica (GPC) y tres estudios observacionales retrospectivos que evaluán el uso de la FAA en pacientes con esofagitis eosinofílica (EoE). Ninguno de los estudios evaluó el uso de la FAA en pacientes con otros tipos de GE, como gastritis, enteritis y/o colitis eosinofílica. El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI, aprueba el uso de las FAA en pacientes con GE. El presente Dictamen Preliminar tiene una vigencia de dos años a partir de la fecha de publicación.

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.

Perforated duodenal ulcer: An unusual manifestation of allergic eosinophilic gastroenteritis.

Spontaneous perforation of a duodenal ulcer secondary to allergic eosinophilic gastroenteritis (EGE) has not been previously reported. We present such a case in a teenager who presented with peritonitis. After exploration and operative repair of his ulcer, he continued to experience intermittent abdominal pain, and further evaluation revealed eosinophilic gastroenteritis in the setting of multiple food allergies. His EGE resolved after adhering to a restrictive diet. Both duodenal ulcers and EGE are very rarely seen in pediatric patients. EGE has a variable presentation depending on the layer(s) of bowel wall affected and the segment of the gastrointestinal tract that is involved. Once diagnosed, it may respond to dietary changes in patients with recognized food allergies, or to steroids in patients in whom an underlying cause is not identified. Our case highlights the need to keep EGE in the differential diagnosis when treating pediatric patients with duodenal ulcers. The epidemiology, pathophysiology, and treatment of EGE are also discussed, along with a review of the current literature.

Milk-sensitive eosinophilic gastroenteritis in a 2-month-old boy.

Eosinophilic gastroenteritis is a rare disease of unknown aetiology, characterised by eosinophilic infiltration of the gastrointestinal wall with various gastrointestinal manifestations. Clinical presentation and radiological findings are non-specific and there is an overlap with more frequent childhood diseases requiring a high degree of clinical suspicion for accurate diagnosis. We describe a 2-month-old boy with prolonged diarrhoea, vomiting and food refusal. Diagnosis was settled by histology. The treatment with elemental diet was successful, with clinical resolution and catch-up growth.

Effectiveness of dietary allergen exclusion therapy on eosinophilic colitis in Chinese infants and young children ≤ 3 years of age.

Eosinophilic colitis is a well recognized clinical entity mainly associated with food allergies. Empiric treatment options include dietary allergen exclusion (extensively hydrolyzed protein formula and elimination diet), anti-allergy medications (antihistamines and leukotriene receptor antagonists) and corticosteroids. We evaluated the effectiveness of dietary antigen exclusion on clinical remission of eosinophilic colitis in infants and young children. We retrospectively reviewed charts of all infants and children ≤3 years of age who were diagnosed with eosinophilic colitis (defined as mucosal eosinophilia ≥20 hpf-1) from 1 January 2011 to 31 December 2013 at a tertiary children's hospital in China. Forty-nine children were identified with eosinophilic colitis. Elemental formula, simple elimination diet or combination therapy resulted in clinical improvement in 75%, 88.2% and 80% of patients, respectively. In conclusion, eosinophilic colitis in infants and children ≤3 years of age responded well to dietary allergen exclusion.

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.