Gastrointestinal Manifestations of Food Allergy

Shereen M. Reda

Pediatr Health. 2009;3(3):217-229.

Abstract and Introduction

Abstract

Gastrointestinal food allergies are not rare in infants and children. Symptoms include vomiting, reflux, abdominal pains, diarrhea and constipation. Clinical diagnosis requires the exclusion of nonimmunologic diseases that have similar gastrointestinal symptoms. In food allergy, the immune reactions involved can be immunoglobulin (Ig)E-mediated, cell-mediated or both. Symptoms in other target organs are common in cases of IgE-mediated disorders, but not in the cell-mediated disorders in which symptoms are usually localized to the gut. Diagnosis utilizes detailed medical history, clinical evaluation, skin testing, food-specific IgE antibodies, responses to elimination diet and oral food challenges. Endoscopic biopsies are essential in cell-mediated disorders and allergic eosinophilic gastropathies. Treatment includes avoidance of the offending food by a restriction diet in children and the use of hydrolyzed or amino acid-based formulas in young infants. Topical and/or systemic corticosteroids can also be used in eosinophilic esophagitis. Current research is aimed at improving the diagnostic tools and therapeutic options available to patients.

Introduction

Infants and children often present to clinicians with food-related gastrointestinal (GI) problems that are commonly perceived by the parents to be a food allergy. However, not every case is a true food allergy. There are several nonallergic conditions^[1] that have similar GI symptoms to those of food allergies and, thus, nonallergic conditions should be excluded before a definite diagnosis of food allergy is established (Box 1).

Food allergy is an adverse immune response to food protein(s)^[2] and affects as many as 6-8% of children below 3 years of age and approximately 4% of adults in the USA.^[3] Any food can cause allergy, however, the most common foods that produce allergy in infant and children are cow's milk, hen's egg, soybeans, wheat, peanut, tree nuts, fish and shellfish. In GI food allergies, the underlying immune responses may be IgE-mediated, cell-mediated or both (Box 2). Unlike the acute manifestations seen in IgE-mediated food hypersensitivity, cell-mediated reactions have relatively subacute or chronic symptoms that are difficult to discriminate from gastroenteritis.^[2,3,4,5] Delayed diagnosis may result in significant growth retardation, anemia and severe malnutrition in the worst cases.^[6]

This review will focus on the current knowledge of various GI food allergic disorders in terms of clinical picture, methods of diagnosis, and treatment.

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Abstract and Introduction
IgE-mediated Gastrointestinal Disorders
Non-IgE Mediated Gastrointestinal Disorders
Other Gastrointestinal Disorders with Unproven Food Allergies
Diagnostic Tests
Treatment
Prevention
Natural History
Conclusion
Future Perspective
References
Sidebar: Executive Summary

Table 1. Cell-mediated gastrointestinal food allergy disorders.
Criteria	Dietary protein proctocolitis	Dietary protein enteropathy	Dietary protein enterocolitis
Onset age	First 1-2 months	First 6 months	First day to first year
Symptoms	Mild symptoms (healthy baby with blood-streaked stools ± diarrhea)	Severe symptoms (failure to thrive, nonbloody diarrhea, vomiting, malabsorption, edema ± anemia)	More severe symptoms (failure to thrive, bloody diarrhea, vomiting, distension, dehydration, sometimes mimicking sepsis)
Laboratory	Mild eosinophilia and occult blood in stools	Leukocytosis and hypoalbuminemia	Leukocytosis, hypoalbuminemia, acidosis and methemoglobinemia
Allergen	Breast milk (60%) or cow's milk/soy formula fed	Cow's milk, soy, cereals, egg and seafood	Cow's milk, soy, rice, poultry and seafood
Biopsy	Focal/diffuse colitis	Small bowel injury/villous atrophy	Intestinal villous injury and crypt abscesses
Prognosis	Resolves within 1 year	Resolves within 2-3 years	With treatment, 90% resolve wihtin 2-3 years

Box 1. Food intolerance (nonimmunologic adverse reactions).
Direct toxic effects: bacterial or viral contamination (gastroenteritis), toxins and food additives. Enzyme deficiency (lactase). Inborn error of metabolism (phenylketonuria and galactosemia). Pharmacological properties (tyramine in cheese). Anatomical defect (pyloric stenosis and Hirschsprung's disease). Cystic fibrosis. Malignancy. Overfeeding.

Box 2. Classification of food allergy in the gastrointestinal tract.
IgE-mediated Type I hypersensitivity. Rapid onset. Positive skin-prick test and/or in vitro radioallergosorbent test. Symptoms: itching of lips, angioedema, vomiting and abdominal cramps with or without symptoms in other targets (urticaria, rash, wheezing and anaphylaxis).
Non-IgE mediated Type IV hypersensitivity (cell mediated). Late onset. Negative skin-prick test and radioallergosorbent test. Symptoms are usually confined to the gut: vomiting, diarrhea, abdominal pain or colic and failure to gain weight.
Mixed IgE & non-IgE-mediated (allergic eosinophilic gastropathies) Variable onset. Peripheral eosinophil count, skin-prick test and serum results are inconclusive. Symptoms are confined to the gut and vary according to the site of eosinophilic inflammation.

Box 3. Factors suggesting food allergy as a cause of gastrointestinal disease.
History of acute reaction following ingestion of a particular food. Exclusion of anatomic, functional, metabolic or infectious disease. Improvement of symptoms with the elimination of suspected allergen. Young age (<3 years). Associated allergic diseases (atopic dermatitis or asthma). Family history of allergic disease.

Sidebar

Executive Summary

Food allergy is an adverse immune response to food protein(s) and affects 6-8% of children less than 3 years of age. Common allergenic foods are cow's milk, soy protein, eggs, wheat, rice, peanut, tree nuts and seafood.

IgE-mediated gastrointestinal disorders

Gastrointestinal anaphylaxis: characterized by acute onset of nausea colicky abdominal pains and diarrhea following food ingestion.
Oral allergy syndrome: symptoms are localized to oropharynx (angioedema). The offenders are pollen proteins that cross-react with some food proteins. Positive skin-prick test with fresh food extract of the allergenic food is diagnostic.

Mixed IgE- & cell-mediated gastrointestinal disorders

Eosinophilic esophagitis (EE): symptoms mimicking gastroesophageal reflux but resistant to antireflux medications. EE should be suspected in any child presenting with unexplained food impaction and it is appropriate to obtain biopsy specimen of the esophagus during removal of the impacted food. Diagnosis necessitates esophageal pH monitoring and biopsy. Topical corticosteroids can be helpful in treatment of some cases.
Eosinophilic gastroenteritis: symptoms include vomiting, diarrhea, abdominal pain, poor weight gain and intestinal obstruction. The diagnosis is confirmed on biopsy findings of eosinophilic infiltration of the gut.

Non-IgE mediated gastrointestinal disorders

Usually affects infants. Symptoms are isolated to the gut mimicking gastroenteritis. The main causal food is cow's milk. Blood tests, stool analysis and atopy patch test may help diagnosis, but confirmed diagnosis is obtained by biopsy, elimination diet and food challenges.
Food protein-induced proctocolitis: characterized by blood streaks in stools in a healthy baby.
Food protein-induced enterocolitis syndrome: symptoms of severe vomiting, diarrhea, dehydration and acidosis, and mimicking sepsis.
Food protein-induced enteropathy: symptoms of vomiting, diarrhea, edema due to protein loss and steatorrhea.

Diagnosis

The main pillars of diagnosis are detailed medical history in order to identify the allergenic food, nature and severity of reaction. The diagnosis is achieved by elimination of the suspected food from the diet and oral food challenge tests. Laboratory and skin tests should be employed according to the disease phenotype such as:
- Skin-prick test is useful in the detection of an IgE-mediated reaction. Interpretation of results should be coupled with clinical history suggestive of allergy to the tested protein.
- Atopy patch test is a recent test for cell-mediated food allergies, but it is still under clinical trials and requires standardization in terms of the reagents used in the test, application methods and guidelines for interpretation.
- In vitro measurement of food-specific IgE antibodies in the serum may be useful in conditions when skin testing cannot be performed.
- Gastrointestinal tests, including endoscopic studies, biopsies and esophageal pH monitoring are used in the diagnostic work-up and follow-up of food protein-induced proctocolitis and EE.
- Elimination diet confirms the diagnosis of food allergy. In young infants, extensive hydrolyzed or amino acid-based formulas are used until clinical improvement is achieved.
- Oral food challenge tests are essential to confirm or rule out the diagnosis of allergy to the tested food, and to determine tolerance.

Treatment

Complete avoidance of the causal food should be stressed.
Restriction diet in children and extensive hydrolyzed or amino acid-based formula is indicated in young infants.
Swallowed fluticasone may be effective in EE.

Prevention

Exclusive breast feeding until the age of 4-6 months.
There is no convincing evidence that maternal manipulation of diet during pregnancy or lactation, use of soy products, or infant dietary restrictions of solid food would prevent allergy.

Natural history

Most gastrointestinal food allergies occurring in infancy are outgrown by 3-5 years of age, except allergic eosinophilic gastropathies.

Conclusion

Gastrointestinal food allergies are common in the pediatric age group and have a wide spectrum of clinical disorders with variable outcome.
Early diagnosis is required to prevent recurrence of severe symptoms and decrease morbidity.
Skin testing and food-specific IgE antibodies are useful but sometimes are inconclusive in the diagnosis of food allergy.
The definite diagnosis requires endoscopic investigations, clear response to an elimination diet and oral food challenges.

Future perspective

Noninvasive, safe and more accurate tests are to be employed in the diagnostic setting of food allergy.
Identifying responsible gene(s) of food allergy will facilitate the detection of children at risk and will enable further therapeutic interventions.
Predictors of severity of reactions and persistence of allergy will provide better management.

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Gastrointestinal Manifestations of Food Allergy

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Sidebar

Sidebar

Executive Summary

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