Eosinophilic Gastroenteropathies and Gastrointestinal Food Allergy in Childhood

Eosinophilic Gastroenteropathies and Gastrointestinal Food Allergy in Childhood

Eosinophilic Gastroenteropathies (Eosinophilic Esophagitis, Gastroenterocolitis, and Gastritis)

Gastrointestinal food allergies are a spectrum of disorders that result from adverse immune responses to dietary antigens. The named disorders include immediate gastrointestinal hypersensitivity (anaphylaxis), oral allergy syndrome, allergic eosinophilic esophagitis, gastritis, and gastroenterocolitis; dietary protein enterocolitis, proctitis, and enteropathy; and celiac disease. Additional disorders sometimes attributed to food allergy include colic, gastroesophageal reflux, and constipation. The pediatrician faces several challenges in dealing with these disorders because diagnosis requires differentiating allergic disorders from many other causes of similar symptoms, and therapy requires identification of causal foods, application of therapeutic diets and/or medications, and monitoring for resolution of these disorders.

This heterogeneous group of eosinophilic gastroenteropathies has in common an eosinophilic inflammation of the gut. The nomenclature used to describe particular disorders relates to the locations of eosinophilia; the depth and severity of eosinophilic inflammation influences the symptoms. Named subtypes include allergic eosinophilic gastritis, allergic eosinophilic gastroenterocolitis, and allergic eosinophilic esophagitis. The symptoms caused by these disorders overlap those caused by many other pathologic gastrointestinal processes: postprandial nausea, dysphagia, abdominal pain, vomiting, and diarrhea, and if inflammation is very dense, obstruction can result. Small bowel involvement may result in protein-losing enteropathy and weight loss. Serosal involvement can induce eosinophilic ascites. The disorder requires confirmation of an eosinophilic infiltration of the gut by biopsy (sometimes patchy) and elimination of other causes of eosinophilia, such as parasites, inflammatory bowel disease, and vasculitis. All age groups may be affected, and the disorder has been diagnosed in preterm infants with symptoms that overlap those of necrotizing enterocolitis. Peripheral eosinophilia is sometimes observed (∼50% of patients). The pathophysiologic basis of the disorder has remained elusive, and the role of allergens is debated. At least a subset of those with the disorder are food responsive and reactive to the usual causative agents (eg, milk, egg, wheat, soy) but with an increased degree of multiple food allergies. In patients with food-responsive eosinophilic gastroenteropathies, the pathophysiological mechanisms seem to include both cell-mediated and IgE antibody-mediated forms.

Perhaps the most common type of eosinophilic gastroenteropathy and most difficult to diagnose and manage is allergic eosinophilic esophagitis. This disorder is particularly challenging to diagnose because the symptoms overlap those of GER. Patients with allergic eosinophilic esophagitis have a predominance of dysphagia (∼85%), and there is an overrepresentation of young, atopic male patients. Although symptoms overlap those of GER, in some patients reflux is absent on pH probe. Some authors have evaluated the number of eosinophils per high-power field as a means to differentiate this disorder from GER, and when the numbers exceed 7, especially when they are >24, allergic and/or intrinsic eosinophilic inflammation is likely. In this scenario, medical treatment for GER may fail, but anti-inflammatory medications such as oral steroids have proved efficacious. The ability of dietary management to ameliorate the inflammation has been provedmbut is not universally curative. Orenstein et al52 documented positive prick skin tests or RASTs in 13 of 19 children with eosinophilic esophagitis (median: 7 foods). Dietary elimination was undertaken in 12 of the 13 with positive tests. Of 10 who were compliant with the diet, all were believed to benefit with resolution of symptoms. Seven of the patients had concomitant therapies (steroid, 3; antireflux medications, 2; cromolyn, 1; or fundoplication, 1); however, lapses in the diet were accompanied by recurrence of symptoms in the months after diagnosis despite the other therapies. In a study that specifically addressed the role of food allergy in children with eosinophilic esophagitis, Kelly et al evaluated patients for whom standard GER treatment or fundoplication failed (6 patients) and who had persistent eosinophilia on esophageal biopsy. These patients were placed on a very restricted diet (1–2 solid foods, eg, apple, corn) and an amino acid-based formula. Eight of 10 patients became symptom-free, and 2 had significant reduction in symptoms within 2 to 6 weeks after starting the dietary program. The patients also demonstrated a decline in the median numbers of eosinophils from 40 to 0.5/high-power field. The causal foods were primarily milk, soy, egg, peanut, and wheat. The correlation of causal foods with positive skin test results was poor, and improved diagnostic methods are under investigation. Oral steroids have been effective, including case reports of high-dose inhaled/swallowed steroids (eg, the off-label use of inhaled steroids sprayed into the mouth and swallowed), and additional anti-inflammatory therapies such as cromolyn and leukotriene antagonists have been tried but require additional study. A trial of an elemental diet may prove beneficial in many of these patients, but the process of identifying causal allergens is time-consuming and often frustrating. If there is a response to elimination diets—which entails at least 6 weeks on the diet and may require a biopsy to confirm—then foods are slowly added back into the diet. The onset of symptoms after addition of a problematic food may be delayed, adding to the diagnostic difficulties.

The natural course of the allergic eosinophilic gastroenteropathies is not well-defined. For at least some patients, the disorder seems to be long-lived and can continue (or present) through adulthood with a waxing and waning course with an element of improvement over time.

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