The diagnosis and management of adverse food reactions is a challenge for pediatricians and other primary care providers. Children of all ages may present with a variety of symptoms that parents have attributed to constituents of the diet. An approach has been devised to aid pediatricians in the evaluation of these children. The process begins with a detailed history. This history may be used to classify the problem into categories of symptoms and possible mechanisms. When common food offenders are suspected of causing symptoms, it is reasonable to obtain in vitro tests that may then be used to decide whether elimination of certain foods is indicated and whether a referral to an allergist is needed. Using this approach, the physician may be able to identify children who are experiencing food-allergic symptoms and aid frustrated families in dealing with problems that have not had apparent solutions. The application of specific testing and the assessment of the results are discussed. Also reviewed are the techniques used by allergists so that pediatricians may help families understand procedures that will be recommended and performed.
- double-blind placebo-controlled food challenge
- CAP System fluorescent enzyme immunoassay
- radioallergosorbent test
- oligoantigenic diet
- prick skin test
- food hypersensitivity
- immunoglobulin E-mediated food hypersensitivity
- non–immunoglobulin E-mediated food hypersensitivity
A systematic approach to the diagnostic evaluation of adverse food reactions will enable the pediatrician to make the appropriate diagnosis in children with potential food allergy.1,2 This discussion outlines 1 such approach and suggests methods for primary care physicians as well as specialists to use for this purpose. When a few basic steps are followed, it is possible to identify children who are likely to need specialist intervention and those for whom it is unnecessary or may be postponed. Both in vivo and in vitro tests that may be helpful in guiding the evaluation to a definitive answer are considered.
CLASSIFICATION–IMMUNOGLOBULIN E-MEDIATED VERSUS NON–IMMUNOGLOBULIN E-MEDIATED
Earlier in this supplement, we learned about different immunologic mechanisms involved in adverse food reactions. One classification scheme differentiates immunoglobulin E (IgE)-mediated and non–IgE-mediated mechanisms. Unfortunately, patients do not present with an obvious mechanism of disease in many cases. Rather, they present with patterns of symptoms that must then be differentiated into correct diagnostic categories. It is helpful when considering these diseases to differentiate immediate- from later-onset reactions. This classification may be easily obtained from the history. Although the term “allergy” is most often used in connection with IgE-mediated reactions, it may also be used to refer to non–IgE-mediated immunologic reactions. The critical factor is that the immune system can be shown to be involved in the pathophysiology of the illness. Table 1 presents a scheme that includes a differential diagnosis of adverse food reactions that occur in children and incorporates both immunologic mechanisms and time of onset of symptoms.
As with all problems in medicine, the acquisition of the history is the most important component of the evaluation. Although patient histories of food allergy are notoriously inaccurate,1,2 they provide information that will assist in selecting appropriate diagnostic tests and, more important, will provide information for designing a diagnostic food challenge, either early in the course of the evaluation or at some time in the future. In addition, the history is often useful in the primary care setting to decide whether a referral is needed and whether that referral might ultimately lead to a food challenge.
There are a few crucial historical facts to be ascertained (Table 2). The parents (or patient) should be asked to describe the sequence of symptoms that occurred at the time of the adverse food reaction. One should try to obtain a description of each reaction that has occurred, but this may not be possible or they all may be similar. It is also important to determine, when possible, the quantity of food that has triggered the reaction and to inquire whether there seems to be any relationship between the quantity of food ingested and the nature and sequence of the symptoms. Try to determine the number of occasions on which the reaction has occurred for each food. The timing of onset of symptoms is also crucial information for determining the observation period of food challenges. A thorough description of the most recent reaction is also very important in designing challenges. The details of the most recent reaction may be more helpful than those of more distant reactions. At times, the acquisition of the history is a process involving multiple discussions. Patients or parents may be asked to record all of the reactions that they can recall. Records may be obtained from other physicians and hospital emergency departments where individuals may have been seen during severe episodes. It is often important to document the physical examination and the treatment during these previous emergency department and physician visits to predict accurately the severity of future reactions. When patients and parents are reporting reactions for the first time, they may seem to recall all of the details being sought, but after contemplation, they often recall additional, important facts.
For the allergist, the history not only suggests a diagnosis but also must provide sufficient detail so that an appropriate, safe challenge may be designed. For the pediatrician, the main purpose should be to decide whether the history suggests whether the patient experienced a true food allergy. If the history is of an immediate reaction and suggests the possibility of IgE involvement, then it guides the physician toward specific testing and ultimately whether a referral to an allergist would be appropriate. However, when a patient has a history of an anaphylactic reaction, it is crucial to obtain enough detail to attempt to predict future reactions and provide an emergency plan and medications, if indicated. For example, if a severe reaction has occurred on a single occasion after the ingestion of a tiny amount of food, then the chance that another severe reaction (or perhaps an even more severe reaction) could occur with the ingestion of a large amount of allergen is great. Furthermore, if a skin reaction (urticaria, generalized atopic dermatitis) has occurred only from contact and the food is ingested in the future, then a systemic reaction may occur.3
Behavioral and neurologic symptoms are also frequently attributed to food allergy. Alternative practitioners often state that these are “food sensitivities,” not food allergy, although the distinction is unclear. There is no significant body of research documenting adverse food reactions of any type being responsible for isolated childhood behavioral disorders. There is a body of research, using blinded food challenges, demonstrating a lack of correlation between ingestion of suspect foods, additives, etc and the reproducible elicitation of behavioral or neurologic symptoms.4,5 A brief but helpful review of this subject has been published by Warner.6
The physical examination is directed toward stigmata of atopic disease. Because atopic manifestations may be quiescent, the physical examination may be unremarkable. The skin is the most obvious place to begin, looking for atopic dermatitis (eczema) or urticaria. In children with extensive, severe atopic dermatitis, food hypersensitivity is more likely than in children who have more intermittent problems or very mild disease.7–9 Urticaria from food hypersensitivity occurs in temporal proximity to the ingestion of the food and usually lasts a few hours. For urticaria to occur daily, the culprit food must be consumed daily. Therefore, chronic urticaria is rarely attributable to food hypersensitivity.
Symptoms of food hypersensitivity are common in the gastrointestinal tract. Chronic diarrhea and recurrent abdominal pain are rarely accompanied by physical findings unless the child has been so ill that he or she is losing weight. We are occasionally asked to see children who are failing to thrive, but food hypersensitivity as a cause of failure to thrive is very unusual. Children with failure to thrive from food hypersensitivity would have to have true allergy to multiple foods and a very poor caloric intake. (There are a few reports of children with failure to thrive because parental beliefs about multiple food hypersensitivity have resulted in such severely restricted diets that the children did not receive adequate caloric or nutrient intake.)10 Children who do have food protein-induced gastrointestinal disease often have failure to thrive and multiple physical signs of chronic illness.11
The respiratory system presents, perhaps, the most difficult portion of the evaluation. Children often have chronic respiratory symptoms including rhinitis, sinus disease, recurrent or chronic otitis media, chronic cough, and asthma that some parents attribute to food hypersensitivity. The physical examination should seek signs of each of these conditions. However, ongoing research has consistently demonstrated that isolated respiratory symptoms are very unlikely in the absence of gastrointestinal and/or cutaneous symptoms. Therefore, the physician is often confronted with the issue of how to be helpful in identifying the occasional child in whom this is an issue.
One means by which pediatricians may be helpful to families before making referrals to specialists is the use of elimination diets (Table 3). Patterns of illness that may be characteristic of food allergy, which have been presented in this supplement, may also help to determine whether any dietary manipulations are likely to be helpful. The type and scope of the elimination diet depends on the problem and the age of the child. In young infants who are being exclusively breastfed or who are consuming an infant formula, a brief trial of an extensively hydrolyzed milk formula, ie, “hypoallergenic” formula such as Alimentum or Nutramigen, may be useful to clarify the potential role of food allergy. For example, most children with milk allergy-induced skin symptoms will respond to a change to a soy-based or hypoallergenic formula, whereas a higher proportion of children with complex gastrointestinal problems may require an amino acid-based formula, eg, EleCare or Neocate. In nursing mothers whose infants are consuming some solid foods, both the mother’s diet and the infant’s diet may need to be altered. If symptoms resolve, then referral to a specialist is appropriate to determine the type of allergy, IgE or non–IgE-mediated, and whether other adverse food reactions are identifiable. Infants with IgE-mediated food allergy are at high risk for developing other food allergies, respiratory allergy, and asthma, as discussed in this supplement. If symptoms do not resolve and food allergy is suspected, then referral is appropriate for additional evaluation.
In older children, eliminating 1 or 2 suspected foods may be appropriate. Frequently, however, a child will present to the pediatrician with a diet that has already been limited by the parents, who have seen no improvement in symptoms. The question then becomes whether additional dietary elimination will be helpful or whether the problem is related to food allergy. Elimination of large numbers of foods before evaluation can lead to unnecessarily broad restrictions and subsequent nutritional deficiencies. As discussed below, a few specific laboratory tests may be ordered to help clarify the situation, or referral to a specialist may be appropriate. When the history and laboratory studies fail to identify potential food allergens, oligoantigenic diets (diets that contain a very limited number of “less allergenic” foods) may be recommended by the specialist. A number of diets have been published in the literature, and 1 example is presented in Table 3. The principle approach is to use an oligoantigenic diet that eliminates most of the foods ingested daily by the child. If the symptom occurs daily, then use of the diet for up to 2 weeks (but not longer because of nutritional inadequacy) should provide a strong indication of whether the symptoms in question are improving. If not, then it is not likely that the elimination diet contains the solution to the problem. If the symptoms improve on the diet, then it is more likely that there is “a needle in the haystack.” This opinion may be reinforced in children without anaphylactic symptoms by placing the child back on a normal diet and finding that the symptoms return. There are a few situations in which 2 weeks is simply not long enough to show that the diet contains an offending food. However, these situations are uncommon and would need to be referred for intensive evaluation in a tertiary center.12
Skin testing remains a useful tool in the practice of allergy. Perhaps that it is a bioassay has saved it from the laboratory dustbin. As allergen extract materials have improved over the years, the proper use and interpretation of skin testing has also improved. Now there is a clear understanding of the role of skin testing in food allergy evaluations and how to interpret skin testing in children of various ages.1,2,13–16 At present, it is recommended that skin testing remain the purview of the allergist. It is hoped that the following discussion will help to clarify skin testing, principles, techniques, and interpretation.
Several techniques are used for allergy skin testing, but research studies indicate that the prick/puncture skin test (PST) is the most useful technique with the most predictable results. True scratch tests (in which a scratch is made on the skin and then the extract is applied) are rarely used any longer. Intradermal skin tests using various concentrations of extract are widely used for inhalant allergy skin testing but are not recommended for use in clinical food allergy because of their high degree of false-positive results and poor positive predictive accuracy.
The PST is performed by placing a drop of the allergen extract, eg, egg white protein, being evaluated on the skin. One of several available devices is used to puncture the skin through the drop, and results are read in 15 to 20 minutes. Several different scoring systems are used to record the skin test results. However, the critical piece of information is whether the PST is positive or negative. We currently consider a wheal of 3 mm or larger compared with the diluent (negative) control to be immunologically significant (ie, it has detected the presence of antibody).
In children older than 1 year, negative skin tests for major food allergens have high negative predictive accuracies, virtually excluding IgE-mediated food allergy in most cases. The positive predictive accuracy is lower, 50% or less, and a positive skin test with a vague history often indicates the need for a food challenge. Overall, only ∼40% of patients with a positive PST will experience allergic symptoms if they ingest the food.
In children younger than 1 to 1.5 years, the negative predictive accuracy of the skin test is lower, probably 80% to 85%, because cutaneous mast cell numbers and the degree of sensitization may be too low to detect a response in the skin. In this age group, Hill and colleagues17,18 have reported that larger skin tests (mean wheal ≥8 mm) are highly predictive of clinical reactivity and may be used to avoid performing food challenges. However, additional studies in more varied populations will be needed to confirm these results. In younger children, positive skin test results may be used to guide the composition of an elimination diet used to determine whether symptoms of concern can be ameliorated. It is important not to discount histories of strongly suspected foods for which the skin test is negative.
Selection of which skin test extract to use should be based on the individual patient history. Use of large numbers of food skin tests applied indiscriminately often leads to more confusion than clarification. If the history does not suggest any likely culprits but the pattern of symptoms suggests a food hypersensitivity, then it may be useful to use the data from a study by Burks et al19 and perform a very limited panel of skin tests to establish the probability that food allergy is present. The major foods for which skin testing has been found to be most helpful when it is negative (high negative predictive accuracy) include egg, milk, wheat, peanut, tree nuts, fish, and shellfish. A negative soy skin test is usually helpful but has been found to be somewhat more variable that the others listed.
Recently, another test that is being investigated is the “atopy patch test.” This test is used in combination with the PST to augment the results of the PST and to attempt to increase the accuracy of the diagnosis in children with atopic dermatitis. Although the test has gained popularity in Europe, most US centers have not yet used this procedure routinely. It is still seeking its place in the evaluation of food hypersensitivity.20–23 Also being used in Europe is the labial test for food allergy wherein a drop of the food extract is placed on the inner side of the lip and the area is observed for the appearance of local signs. This, too, is a test seeking its place in our usual evaluation program.24
IN VITRO TESTING
The major form of in vitro testing for food hypersensitivity has involved some type of immunoassay that detects the presence of circulating IgE antibody. Variations of the radioallergosorbent test or enzyme-linked immunosorbent assays have been used for this purpose. Until recently, these tests have been no more accurate than properly performed skin tests, and in the past they were shown to be slightly less sensitive than skin testing. In the past few years, Sampson25,26 has shown that, for a few select foods, the quantitative CAP fluorescent enzyme immunoassay (FEIA) may provide more useful positive and negative predictive values. This procedure may now be used to eliminate the need for food challenges when the measured antibodies exceed certain levels for egg, milk, peanut, soy, wheat, and fish (Table 4). These values predict that there is a >95% probability that the food challenge will be positive and therefore need not be performed until the level is lower. Conversely, Sampson has suggested that low levels may be used to decide that a challenge is likely to be negative and should be performed with proper supervision. Slightly different “cutoff” levels have been found for young children (≤2 years) with cow milk27 and egg allergy.28 Proper performance of in vitro tests are not accomplished in every laboratory, and quality control of these tests is critical, especially when the results are used to determine whether challenges should be performed. Like any laboratory tests, the CAP-FEIA must be interpreted in context with the patient history, physical examination, and other laboratory studies. However, they may be used to determine whether a child has evidence of an IgE-mediated disease and requires additional evaluation by an allergist. In the primary care setting, the patient’s history may be used to determine whether in vitro testing is likely to be helpful. Ordering CAP-FEIA tests to those foods for which there are adequate data on the positive and negative accuracies (egg, milk, peanut, and fish) may be useful. The results may be compared with the tables and predictive graphs created by Sampson.26 A positive result should prompt referral to an allergist, who can determine whether a challenge test is needed to clarify the diagnosis, provide proper education about allergen elimination (see sections on dietary measures and management) and management of allergic reactions, and monitor for tolerance development.
Families often inquire about “blood tests” for allergy. It is also crucial to note that there are other blood tests for food allergy that have not been validated. Several laboratories throughout the United States will perform food-specific IgG blood testing for food or some combination of IgE and IgG enzyme-linked immunosorbent assay testing. Families often present at the pediatrician’s office with a child who is on a very restricted diet on the basis of these tests, leading to significant parental and patient frustration. These tests are often used in situations in which the problem of concern is behavioral or some other subjective symptoms. Unfortunately, use of these tests is fairly widespread, they are expensive, and they yield more confusion than clarification. Occasionally, diets are so restrictive and rigorously applied that they lead to malnutrition and/or eating disorders.
The food challenge is currently the most effective means to determine whether an individual truly reacts to the food under consideration. These studies are generally labor intensive and carry some risk to the patient. Anyone who performs such challenges on children with suspected food allergies must have the background and equipment to treat anaphylactic reactions. For the most part, the purpose of this section is to assist the pediatrician in understanding the food challenge techniques that are available and which ones might be used when they refer a patient for food allergy evaluation. It should also aid the primary care provider in helping families understand what may be done when they visit allergists who perform food challenges (Table 5). For research purposes, the double-blind placebo-controlled food challenge (DBPCFC) is the gold standard against which other diagnostic tests are compared.1,2,29–32 Food allergy diagnosis has become 1 of the most precise aspects of allergic disease because of this method for determining with high certainty whether a food reaction is occurring, especially if the symptoms being examined occur promptly after the food is ingested (within minutes to 1–2 hours). The precision of the challenge will vary depending on the circumstances, the history, and the setting.
Open Food Challenge
The open food challenge is very useful for ruling-out suspected food allergies. It is most commonly used in situations in which the history suggests that a reaction to a putative food is very unlikely. For example, a child has been on a diet free of eggs but has been eating foods that contain eggs in sufficient quantities to make the reaction during challenge very unlikely. The school-aged child who eats pancakes or French toast probably does not have egg allergy. Another example is the child who has been avoiding nuts but has been consuming cereal that contains almonds. Again, an open challenge is exceedingly likely to be negative and to eliminate almond from the list of potential offenders.
Single-Blind Food Challenge
Single-blind food challenge techniques are useful in office practice. The use of blinding in the practice setting offers the opportunity to give children foods about which they and/or their parents may have concerns. Usually the physician who provides the challenge and especially the nurse are able to administer the challenge without “telegraphing” which dose is active and which is placebo. If objective symptoms are expected or if it is likely that the challenge will be negative, if not influenced, by the patient/parent beliefs, then the single-blind approach will often yield the correct answer with relative ease. These challenges are administered in a vehicle that completely obscures the nature of the food being challenged or at least masks it enough to render the doses difficult to identify. The vehicle chosen will often depend on the child’s age, the circumstances, and the expected outcome. Nuts are often hidden in chocolate pudding. Nonfat dry milk may be mixed into formulas, soy milk, or rice milk. Elemental formulas are also a reasonable hiding place (hydrolyzed protein formulas, amino acid formulas). Mashed potatoes may be used for larger quantities. The list of potential vehicles is relatively endless.
The DBPCFC remains the gold standard for both clinical and research purposes.1,2,29–32 Its importance in research is obvious. However, there are also circumstances in clinical practice when complete blinding of subject, parent, and medical personnel becomes crucial. Subjective symptoms must be challenged in this manner to eliminate the biases of everyone involved. Even with complete blinding, it is often difficult to eliminate some strongly held beliefs that families may possess. Issues about diet and behavior fall into this category. If it is unlikely that the belief will be abolished by the results of the food challenge, then it may be unwise to do the challenge. However, in situations in which families have been convinced that the doctor’s bias has been eliminated, the results may be more acceptable. (Unfortunately, the elimination of 1 belief, may lead to the substitution of another.) Open challenges and even single-blind challenges are relatively easy to arrange and to administer. However, the DBPCFC is probably the purview of the specialist.
The DBPCFC requires the use of placeboes, of which there are 2 major categories. The first is using another food, which is not a suspect, or in some situations, the vehicle itself may serve as the placebo. The second is using dextrose that may be purchased in granular or powdered from. In older studies of food hypersensitivity, the dextrose placebo was important because it was placed in capsules and often resembled the active challenge food that was also in capsules.13,14,29–32
Although the details are not crucial to this discussion, it is important for pediatricians to be aware that numerous precautions are taken before and during food challenges to be certain that they are safe.30,32,33 Families are educated about the nature of the procedure and the reason for doing the challenge. The vast majority of families are anxious to have the information provided by food challenges. The results help them to limit their child’s diet appropriately. Foods that are no longer causing problems (or may have been mistakenly identified) may be returned to the diet, making the family’s lives easier.
Whenever possible, food challenges are performed with children having discontinued all medication before the initiation of the challenge. This is not always possible because severe asthma must be stable for challenges to be performed, and some children with asthma cannot stop their maintenance medications. In a few instances, challenges have been performed with children continuing their antihistamines. Challenges in these circumstances have yielded some very helpful observations. Despite taking asthma medication and antihistamines, children have had positive challenges. This indicates that these mediations are not sufficient to prevent allergic reactions to foods. Although the dose of food at which the reaction occurs might be higher on the medication, this point is not certain and it seems unwise to tell parents that giving their children antihistamines or bronchodilators before a possible food ingestion would diminish the severity of the reaction.
When confronted with a child with possible food allergy, what is the pediatrician to do? Applying some of the following suggestions will depend on individual circumstances and the availability of pediatric allergists or a major medical center in the community. One must bear in mind that food allergy in an infant is often the harbinger of future allergic disorders, especially atopic dermatitis, asthma, other food allergies, and respiratory allergies. A very important step is to develop a partnership with an allergist who is interested in helping in the evaluation of children with food allergy and knowledgeable about various prophylactic strategies. One of the most important goals is to identify children who are at risk for severe reactions and to be sure that they are educated and equipped to prevent a potential tragic outcome. The following steps offer 1 approach that may be of assistance in many situations.
First and foremost, a detailed relevant history should be obtained. If there is a need for additional detail, then it may be helpful to have the parents take home a list of questions for each food under suspicion. The questions include a description of symptoms (for each suspected food), timing from ingestion to symptom onset, the number of occasions on which symptoms have occurred, the approximate quantity of food observed to produce symptoms, and associated factors such as exercise (Table 2).
Second, the history should be used to try to classify the reactions by system and likely mechanism, ie, IgE or non–IgE-mediated (Table 1). Also, the potential severity of subsequent reactions should be considered. If the history suggests a severe allergic reaction, then prompt attention to a number of details must be arranged. These include the likelihood that the correct food has been identified, provision of injectable epinephrine, eg, EpiPen, with appropriate written instructions for its use, and arrangements for ongoing education in the early treatment of anaphylaxis and for accurate food avoidance. The potential severity of a reaction may also influence the physician’s assessment of how urgent dietary changes or testing may be needed. In unremitting atopic dermatitis that is moderately severe and does not respond well to treatment, there is approximately a 35% to 40% chance that food allergy is involved, and it should be evaluated. If a child has only a few areas of skin involvement and the parents have already undertaken dietary elimination and reintroduction without detecting a change in the condition, then additional dietary changes or laboratory testing may not be warranted. In general, the worse the eczema and the younger the child, the more likely that food allergy is playing a pathogenic role.
Third, on the basis of steps 1 and 2, it must be decided whether laboratory testing is likely to be helpful. The test that is generally most helpful and easily accessible is the CAP FEIA for a few selected foods. The test must be performed using the technology that yields quantitative results as noted in Table 4. In many circumstances, testing may be limited to egg, milk, and peanut, the most common food allergies in children. These are the 3 foods for which there are the most data and most experience in the hands of experts in this field. If the levels exceed those listed in Table 4, then it is highly probably that the child will react on challenge or accidental ingestion, and the food should be eliminated from the diet. A referral to an appropriate allergist should be considered, because food allergy is generally a marker for other allergic disease. If the levels are less than the “diagnostic values,” then a referral should also be made unless the pediatrician is planning to do challenges under observation in the office. If the levels are undetectable and the food is in the diet, then it is unlikely that eliminating that food will be helpful. However, if the food has been excluded from the diet, even if the level is undetectable, it is not acceptable to tell the parents to return home and put the food in the diet. The negative predictive accuracy of the CAP FEIA is not 100%, and there are circumstances in which reintroduction of the food may be accompanied by an allergic reaction, even a severe reaction. Therefore, these children should be referred to an allergist who will do the food challenge under observation in a setting appropriate to the situation.
Fourth, the physician may use the CAP immunoassay results to recommend an elimination diet. As noted above, pediatricians may use elimination diets in several ways. Specific foods identified by history and testing may be removed from the diet, recognizing that parents may need help to accomplish this goal (a dietitian who is knowledgeable in this area is extremely helpful). In young children, soy formula, hypoallergenic formulas, and amino acid formulas may prove diagnostic. In selected situations, the physician might decide to try an oligoantigenic diet for up to 2 weeks, but not longer. (If an allergist is nearby, then the child may be referred for this procedure.)
Fifth, once the foods to be eliminated have been identified, the education about avoidance and treatment of accidents must be supervised. Prescribing an elimination diet is no different from prescribing any medication. Although the process may have been initiated by an allergist, parents often do not follow-up with specialists. Therefore, it is crucial for the pediatrician to be certain that ongoing education is occurring and that patients/parents continue the education process. If self-injectable epinephrine is appropriate, then the pediatrician must ensure that their patients’ epinephrine injectors are up to date. The pediatrician will also need to be assured that arrangements are made and followed for appropriate food challenges and that parents are not reintroducing foods into the child’s diet at home.
Each of the sections in this monograph is concerned with specific conditions and present additional information that may be used to modify the foregoing suggestions.
The future holds much promise for the evaluation and treatment of food hypersensitivity. Over the last 30 years, both the diagnostic accuracy and the scientific basis of food hypersensitivity have increased immeasurably. Food challenges have made our observations solid, skin tests have found their place, and now in vitro testing is adding a new dimension to diagnosis. This process should continue. Several of the individuals who have written articles for this supplement are on the threshold of finding multiple treatment modalities, which have not existed previously. We can certainly be optimistic that over the course of the next decade, the increase in apparent food hypersensitivity throughout the world will be blunted by novel and effective treatments.
- ↵Behar D, Rapoport JL, Adams AJ, Berg CJ, Cornblath M. Sugar challenge testing with children considered behaviorally “sugar reactive.” Nutr Behav.1984;1 :277– 288
- ↵Eigenmann PA, Sicherer SH, Borkowski TA, Cohen BA, Sampson HA. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics.1998;101(3) . Available at: www.pediatrics.org/cgi/content/full/101/3/e8
- Copyright © 2003 by the American Academy of Pediatrics