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Diagnostic Tests For Food Hypersensitivity

The evaluation for adverse food reactions begins by attempting to define whether the patient is suffering from a nonimmunologic intolerance or from an immune reaction, which can be IgE- or nonIgE-mediated. The following must be established if possible: 1) the identity  and quantity of the food allergen suspected of provoking the reaction, 2) the time elapsed between the ingestion of the suspected food and  the onset of symptoms, 3) a complete description of the symptoms elicited and the duration of the reactions, 4) whether similar symptoms  have occurred in the past when the food was eaten and the therapeutic measures taken, and 5) whether other factors (eg, exercise) appear  necessary for symptoms to develop. Diet diaries sometimes are useful for the infant as an adjunct to the history; however, with the frequent  use of processed foods and prepackaged meals, this may be difficult in the older child and adolescent. Parents are asked to keep a  chronologic record of symptoms and foods ingested, generally for no longer than a week. The diary then is reviewed to correlate ingestion  of specific food with the development of symptoms.  An elimination diet can be used as a diagnostic and therapeutic test when the history suggests that certain foods may be provoking  the specific symptoms. Foods and all "hidden" sources of those foods suspected of inducing symptoms are eliminated from the patient's diet  for 1 to 2 weeks. In chronic disorders (such as atopic dermatitis or chronic diarrhea), additional factors may be contributing to symptoms.  Therefore, failure to resolve symptoms during the elimination period does not completely rule out a food hypersensitivity.  In cases in which food hypersensitivity or intolerance is suspected but no specific foods can be incriminated, a brief trial (ie, 2 to  4 weeks) of an oligoantigenic or elemental diet may be helpful. If symptoms persist unabated during that period, it is very unlikely that food  is a contributing factor. If symptoms appear to improve, further characterization of the sensitivity may be pursued by allergy skin tests or  serum IgE antibody tests.

These should be performed prior to initiating the elimination diet because the presence or absence of food  allergen-specific IgE antibodies is useful for counseling patients. When compared with the double-blind, placebo-controlled oral food  challenge (described below), prick skin tests have been found to have excellent negative predictive accuracies for IgE-mediated food allergy but poor positive predictive accuracies. The major problem with skin testing for foods as well as with many serum IgE antibody tests for foods has been the lack of potent,  stable, and pure standardized allergen solutions. At times, a few food allergens produce false-positive reactions secondary to an irritating  effect on the skin.

The results of food skin tests must be interpreted carefully because there may be a discrepancy between the production  of clinical symptoms and positive skin tests to foods. In the practice setting, an open or single-blind oral food challenge may be used to screen for allergic reactions to food. However, in cases in which multiple food allergies are diagnosed, positive responses should be confirmed by double-blind, placebo-controlled food  challenges (DBPCFCs). DBPCFCs are the gold standard for diagnosing food allergies and have been used successfully in both children and adults for examining a variety of food-related complaints. The choice of foods used in DBPCFCs is based on history, skin test (or serum IgE antibody) results, or foods suspected on the basis of elimination diets. DBPCFC testing should be performed by a specialist or an experienced clinician; it is not a procedure suited for most primary care practices. (For details see Bock 1988 in Suggested Readings.) Diagnosis of nonIgE-mediated food hypersensitivity such as malabsorption syndromes and eosinophilic gastroenteritis is facilitated  by endoscopy and intestinal biopsy prior to and after the child is placed on an elimination diet. In the malabsorption syndromes, villous  atrophy may be partial or complete and often is patchy. Consequently, multiple biopsies may be required to exclude this diagnosis, especially in young children. IgA antigliadin and IgA antiendomysial antibodies can be measured to screen for celiac disease. However, this diagnosis  depends on demonstrating biopsy evidence of villous atrophy and inflammatory infiltrate while the patient is ingesting gluten, resolution of  biopsy findings after 6 to 12 weeks of gluten elimination, and recurrence of biopsy changes following reinstitution of gluten. Food-induced enterocolitis and colitis syndromes may require an oral food challenge in the office or hospital. A positive challenge will provoke occult or grossly apparent blood in the stools, an increase in stool neutrophils and eosinophils over baseline, and an increase in the total peripheral blood neutrophil count of 3500 cells/mm³ over baseline at 6 to 8 hours after the challenge. 

The diagnosis of food allergy requires a careful history, physical examination, selective skin or serum IgE antibody tests in cases  of suspected IgE-mediated disorders, appropriate exclusion diets, and sometimes blinded provocation challenges. At present, there is no  evidence of the diagnostic utility for the following assays: quantitation of food-specific serum IgG or IgG4 antibodies, serum food antigen-antibody complex assays, cytotoxic food testing, tests of lymphocyte activation (proliferation, interleukin-2, or leukocyte inhibitory factor studies), or sublingual or intracutaneous neutralization or provocation. Once food allergy or hypersensitivity has been diagnosed definitively, the only proven form of therapy is strict elimination of the offending food. This requires considerable time (and ideally a dietitian) to educate the patient on spotting all forms of "hidden foods" and assuring a nutritionally sound diet.

Teaching patients to read food labels is necessary to ensure good compliance with an elimination diet.  Patients who have IgE-mediated food allergies also must be prepared to treat accidental ingestions; this includes using injectable epinephrine  and oral liquid antihistamines. In addition, patients must be prepared to go to the nearest emergency facility for further treatment when  indicated. The role of breastfeeding and food allergen avoidance in the prevention of atopy and food allergy remains controversial. However, it appears that breastfeeding (especially when the mother avoids major allergens--milk, egg, peanut, fish--during lactation) and/or the use of hydrolyzed infant formulas can prevent some atopic dermatitis and food allergy in high-risk infants, but whether it actually prevents  respiratory allergy is not yet clear.