Gastrointestinal Manifestations of Food Allergy

Shereen M. Reda


Pediatr Health. 2009;3(3):217-229. 

In This Article

Diagnostic Tests

The medical history must provide adequate information to be used as a guide to select the appropriate food(s) to be tested. The physician should establish whether the patient's findings implicate a food-induced allergic disorder and whether an IgE-mediated or cell-mediated mechanism is most likely responsible. Skin-prick tests and measurement of in vitro specific IgE may be useful in identifying specific foods responsible for IgE-mediated disorders. Meanwhile, laboratory studies are of limited value in non-IgE-mediated disorders.[39]

Skin Tests

Skin testing has become an integral part in the evaluation settings of GI food allergic disorders. It should be performed by a specialist for allergy testing and in a hospital equipped for emergency interventions. The intradermal skin testing has been abandoned in infants and children owing to the high false-positive rate and the increased risk of systemic reactions.[34]

Skin-prick Test: This test is considered a safe and rapid (within 15 min) means to assess IgE-mediated food allergy.[9] It can be performed at any age, including in young infants, with useful results. SPT has a high sensitivity (up to 90%) but low specificity (50%).[36,37] The interpretation of SPT results should be coupled with clinical history suggestive of allergy to the tested protein. Therefore, it should not be used to screen patients for allergy by testing with a broad panel of food allergens without considerate clinical history, as it is likely to produce false-positive results. In addition, young infants may be less reactive to SPT yielding false-negative results in some cases.[38,39] There is debate regarding the usefulness of commercial extract versus fresh foods (prick-by-prick),[11] and the optimal cut-off values of SPT to predict a positive OFC are still undetermined.[4,34]

Atopy Patch Test: This is a relatively recent diagnostic tool in cell-mediated food allergies, but is still under research trials and needs standardization in terms of the reagents used in the test, application methods and guidelines for interpretation.[39,40] Reports concerning research works on atopy patch test (APT) have demonstrated that the test is helpful in the diagnosis of GI food allergic disorders.[37] Moreover, the diagnostic accuracy of APT with fresh food is much better than that of commercial APT assay with freeze-dried purified food.[41] In EE, the combined use of SPT and ATP gives high sensitivity and positive-predictive value, which indicates that false-negative results are very unlikely when both tests are negative.[35] This was clear in the study of Spergel and associates who found that the combination of SPT and APT had excellent negative predictive value (88-100%) for all tested foods except milk, which was very low at 41%. The positive predictive value was greater than 74% for most common foods (milk, egg and soy) but dropped off as the food became a less common cause of EE (such as oat: 50% and apple: 57%). They concluded that the combination of SPT and APT in designing a diet plan has high success rate for food elimination or food reintroduction in EE.[42]

In vitro IgE Tests: Food-specific IgE antibodies in the serum can be measured by two methods, the radioallergosorbent test (RAST) and the fluorescent enzyme immunoassay (FEIA) test, to identify food-specific IgE antibodies in vitro. The in vitro test is considered less sensitive than SPT.[37,38,39,40,41] However, serum testing is useful when skin testing cannot be performed, for example in conditions when antihistamines or corticosteroids cannot be discontinued, in children with a history of severe reactions and in those with associated atopic dermatitis.[43,44] In addition, in young children with very high levels of specific IgE who usually have a major risk of adverse reactions to foods, food challenges should not be tried.[39,43]

Gastrointestinal Tests

Several GI procedures are currently used in the diagnostic work-up and follow-up of children with food allergy, especially those with non-IgE-mediated and mixed IgE and non-IgE-mediated disorders.[2,12,23] These include endoscopic procedures, histologic evaluation and esophageal pH monitoring.

Endoscopic biopsy is considered the cornerstone in the investigation for allergic eosinophilic gastroenteropathies.[13,14,15,22] In EE, biopsy should be performed after a period of acid reduction in order to decrease inflammation and make a clear interpretation of biopsy. Usually, eosinophils are absent from the esophagus and the presence of large number of eosinophils (15 or more per high-power field) is considered diagnostic.[14] Any eosinophil in the stomach, greater than 20 in the duodenum, and greater than 30 in the terminal ileum or cecum is suggestive of EG.[12,16] It is also important to look for the normal distribution of eosinophils in the colon, decreasing from cecum to the rectum, to be no more than five eosinophils/high-power field (HPF) in the rectum. Of note, peripheral blood eosinophilia may be found in only 50% of cases.[2,5,9] Recently, it has been demonstrated that the presence of major basic protein on biopsies can be considered a useful confirmatory marker for the diagnosis.[12,13,14,15,16]

The recommendations for the diagnosis and treatment of EE[14] indicated that for histological assessment of EE, endoscopic appearances should be documented and photographed, mucosal pinch biopsy specimen should be obtained from all patients in whom EE is in the differential diagnosis, and biopsy specimens should be obtained from different locations along the length of the esophagus. Biopsy specimens should also be obtained from stomach and duodenum to rule out other diseases such as EG and inflammatory bowel disease. In a retrospective analysis of 341 biopsy specimens from 66 adults with EE, Consalves and colleagues found that with a threshold of 15 eosinophils/HPF, the outcome of one biopsy specimen had a sensitivity of 55% in contrast to a sensitivity of 100% with five biopsy specimens, which indicates that more than one biopsy specimen from different parts of the esophagus are needed to confirm the diagnosis.[45]

Elimination Diet

An elimination diet is employed during the diagnostic settings to confirm whether the suspected food(s) is the cause of allergic symptoms or not, and is also indicated for the treatment of food allergy. Recently, guidelines for the diagnosis and management of cow's milk allergy in infants were proposed in an attempt to aid physicians and general pediatricians while dealing with infants with food allergy.[46] These guidelines highlighted the importance of maintaining breastfeeding in allergic infants with mild-to-moderate manifestations and that elimination diet for the mothers should be constructed according to the causal food. The duration of elimination diet depends on the response of elimination and reintroduction of food, in general, not less than 2 weeks and up to 4 weeks in atopic eczema or allergic colitis. The mothers are advised to receive calcium supplement during the period of elimination diet. Infants with severe symptoms that interfere with normal growth or those not responding to elimination diet of mothers should be referred to a specialist for reassessment. When solid foods are introduced (preferably not before 9-12 months of age), care should be taken to ensure solids are free from the food protein that the infant is allergic to. When considering weaning, infants with cow's milk protein allergy should receive extensive hydrolyzed formulas (eHF) as a source of milk. In formula-fed infants with cow's milk allergy, eHF is the first choice. Amino acid-based formula (AAF) should be reserved for infants refusing eHF because of its bitter taste, or if the symptoms do not improve as some infants may react to the residual allergens in eHF. In some situations, the infant may be initially switched to an AAF, especially if they experience multiple food allergies, specific GI manifestations, or both. In these conditions, the potential benefits of AAF overweigh its higher cost. However, the risk of failure of eHF is no more than 10% in children with cow's milk allergy.[47]

In 97% of young children with EE, elemental diet (AAF) proved to cause resolution of symptoms and to normalize the eosinophil count in the esophagus.[22] However, owing to the unpleasant taste of elemental formulas and their higher cost, Spergel and colleagues demonstrated that an elimination diet, guided by results of combined SPT and APT, led to clinical and histological improvement in 77% of EE patients.[48] Kagalwalla et al. tried another dietary approach. They examined two different diet plans, elemental versus a six-food elimination diet (cow's milk, eggs, soy, wheat, peanuts and seafood), and found that improvement of clinical and histological findings were achieved in 74% of patients on a six-food elimination compared with 88% of patients on an elemental diet.[49]

Oral Food Challenge

The oral challenge is an integral part of the work up for the diagnosis of food allergy. The test can either confirm or rule out the diagnosis of allergy to the tested food.[33] In addition, during follow-up settings, the test is repeated (rechallenge), to assess the timing at which the child might have outgrown allergy to the tested food.

The OFC begins with small amounts of the allergen and the dose is increased as tolerated; the test procedures are best described in other review articles.[34,39] In cases of previous anaphylaxis, a challenge is contraindicated unless SPTs and/or specific IgE measurements show improvement. In such cases, the challenge test should be done in hospital under the supervision of an allergist.[46] The foods selected for testing must be based upon history and results of skin and/or in vitro testing.[30,32] The suspected food should be eliminated for 7 to 17 days before the challenge for IgE-mediated disorders and up to 12 weeks in some GI disorders.[34] The open challenge means the patients knows that the tested food is the one that has caused the symptoms in the past, and this can lead to a bias in interpretation of the response to that food because the patient will be afraid or feel anxious to experience the same symptoms developed in the past. However, this is unlikely to be the case in young infants and open food challenge is considered reliable and practical. The double-blind, placebo-controlled, food challenge (DBPCFC) is considered the gold standard for the diagnosis of food allergies.[3,5,9] It is not liable for bias like open challenge because both the patient and the physician do not know which doses contain the challenge food.[33,36,37]

Several research studies have been published recently on the topic of food challenge aiming to standardize the procedure.[39,50,51,52,53] The main problems with food challenge tests are related to the wide range of symptoms, possibly related to food allergy, that lead to difficulties in the interpretation of the test results and to the optimal timing and dosage of this procedure.[50] The choice of optimal timing should be oriented by the type of symptoms from 2 weeks for GERD and up to 8 weeks in the case of EE.[13,14,15] The choice of open challenge or DBPCFC, or both, is another point of difference. It has been suggested that when multiple foods are suspected, open challenge may help to identify the specific food to be further tested by DBPCFC. Furthermore, open challenge may be suitable for the diagnosis of immediate symptoms (mostly objective) whereas a DBPCFC may be indicated for the diagnosis of delayed symptoms (mostly subjective), or in research settings (Figure 3).[50,51,52] The false-negative rate of DBPCFC is approximately 3%, therefore, negative challenges should always be followed by supervised open feeding of normal portion of the tested food in its commonly prepared state.[53]


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