Food allergy, dermatologic diseases, and anaphylaxis
Food protein-induced enterocolitis syndrome: Case presentations and management lessons

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Enterocolitis induced in infants by cow's milk and/or soy protein has been recognized for decades. Symptoms typically begin in the first month of life in association with failure to thrive and may progress to acidemia and shock. Symptoms resolve after the causal protein is removed from the diet but recur with a characteristic symptom pattern on re-exposure. Approximately 2 hours after reintroduction of the protein, vomiting ensues, followed by an elevation of the peripheral blood polymorphonuclear leukocyte count, diarrhea, and possibly lethargy and hypotension. The disorder is generally not associated with detectable food-specific IgE antibody. There are increasing reports of additional causal foods, prolonged clinical courses, and onset outside of early infancy, leading to description of a food protein-induced enterocolitis syndrome. The disorder poses numerous diagnostic and therapeutic challenges. The purpose of this report is to delineate the characteristic clinical features and review the possible pathophysiologic basis to frame a rational strategy toward management.

Section snippets

Case presentation

A female patient presented at the age of 14 months for evaluation of possible allergy to cow's milk (CM) and soy proteins. The patient was a full-term female infant initially breast-fed. At 4 weeks of age, a CM-based formula was used to supplement breast-feeding, and over a 2-week period, the patient developed frequent episodes of vomiting, poor weight gain, and small specks of blood in her stools. Soy-based formula was substituted but was discontinued in 2 days because of continued vomiting.

Case discussion

It is clear that the physicians caring for this infant with vomiting and lethargy were initially considering possible infection. Even if the reader has neglected to note the title of this article, suspicion that this infant actually had a food-allergic disorder should be high. Indeed, the child became ill on 3 occasions when CM protein was ingested (and possibly when soy was substituted) and was well when not ingesting these proteins. This infant had 2 somewhat distinct patterns of reaction:

Histology

Infantile FPIES is a diagnosis that is generally made clinically; therefore, there are no series in which biopsies are performed solely in patients with this diagnosis. However, several case series include patients who fulfill criteria for a diagnosis of FPIES and describe varied and nonspecific histologic features.4, 10, 11, 19, 20, 21 Colonic biopsies in symptomatic patients reveal crypt abscesses and a diffuse inflammatory cell infiltrate with prominent plasma cells; small bowel biopsies

Pathophysiology

Van Sickle et al22 noted that in vitro stimulation of PBMCs with the causal antigen in children with FPIES resulted in greater cell proliferation than in children with negative challenges, an observation that in retrospect indicated the response as immune-mediated (allergy) rather than intolerance. Hoffman et al23 also showed a proliferative response in affected children, but the stimulation index was not significantly different compared with controls, and the test result could not reliably

Differential diagnosis

A full discussion of the many disorders that could result in infants variably experiencing vomiting, diarrhea, and poor growth, possibly progressing to dehydration, lethargy, and shock, are beyond the scope of this discussion. In regard to nonallergic causes, infection is the one most likely, and most importantly, considered. Metabolic disorders and necrotizing enterocolitis, particularly for newborn, preterm infants, should also be considered. Several gastrointestinal disorders may present in

Diagnosis

Skin prick tests are typically negative, but if positive, the risk for a reaction, including typical anaphylaxis, is greater and may require an alteration in diagnostic approach.2, 6 Assessment of in vitro lymphocyte responses to food stimulation for diagnosis has not reached clinical utility.22, 29 Hypothetically, the atopy patch test, used with variable clinical utility for atopic dermatitis34, 35 or eosinophilic gastroenteritis,36 may have a role in diagnosis of gastrointestinal allergy

Case report: clinical course

The patient presented was evaluated at 14 months of age. Skin prick tests were negative to CM and soy. The patient was tolerating a variety of solid foods. We chose to perform an oral food challenge to soy because only approximately 50% who are reactive to milk also react to soy.6, 7 Further, the clinical history was not very clear for a soy reaction; she tried soy for only 2 days and may have been experiencing residual symptoms from the milk reaction. It was only 7 months since her latest

Another case presentation

A male patient was initially breast-fed with no maternal dietary restriction. He had mild reflux symptoms, and at age 5 months, an H-2 blocker was prescribed, and rice was added to breast milk on occasion to thicken the feedings. At 6 months of age, he developed repetitive vomiting and lethargy and was admitted to the hospital for a sepsis evaluation. During the hospitalization, he had several mucous, bloody stools. With intravenous hydration, he improved clinically, and all cultures were

Features of FPIES caused by solid foods

There are increasing reports of FPIES induced by foods other than CM and soy.6, 7, 8, 13, 14 Nowak-Wegrzyn et al7 reported 14 patients identified over a 5-year period from 2 US academic centers, and Levy and Danon8 reported 6 patients over a 7-year period from an allergy clinic in Israel. Clinical features of these 21 patients are partly summarized in Table IV. Of note, 65% of these patients already had FPIES from milk or soy. Delayed diagnosis is particularly common for these patients,

General management approaches

As illustrated by the 2 cases presented here and the available literature as summarized in Table IV, an approach to diet must take into consideration the reaction history, age of the child, number of foods involved, results of tests for IgE antibody, and results of oral food challenges. Data are limited, and on the basis of a few case series and reports, it is not possible to suggest a specific course of action applicable to all situations. Presented here are the authors' opinions based on the

Summary and unresolved issues

Pediatricians and other primary care providers are at the front line in the diagnosis of FPIES, and efforts to educate them are underway.44 The characteristic clinical pattern of reactions can aid the allergist in verifying a diagnosis, and partnership with a gastroenterologist can be helpful in ruling out other entities. Ultimately, oral food challenges are needed to confirm the diagnosis in some cases, and certainly to evaluate for tolerance. Clinical data have been summarized here to assist

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    Disclosure of potential conflict of interest: None disclosed.

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