Journal Citation
Joneja,J.M. Food Allergy Testing: Problems in Identification of Allergenic Foods. Canadian Journal of Dietetic Practice and Research 1999 60(4):222-226
Article
Abstract
The greatest challenge in the management of food allergy or intolerance is the identification of the food that is responsible for the symptoms. The medical model of a diagnosis based on tests appropriate to the symptoms, which dictates the usual most effective treatment strategy does not work well in the management of adverse reactions to foods. A single test could not identify the specific trigger for the wide array of symptoms that can result from food sensitivity because the immunological, physiological and biochemical reactions that mediate food sensitivity are so diverse. Skin tests, blood tests for food antigen-specific antibodies, and other in vitro tests can not provide the same information as well-controlled elimination and challenge. Once the reactive foods have been identified, management of the condition may be effectively achieved by a diet that avoids the culprit food components and supplies complete balanced nutrition from alternative sources. A suitably qualified dietitian/nutritionist is the most appropriate health care practitioner to inform and supervise the food-sensitive person in the identification and avoidance of the specific food components that are responsible for their symptoms, and in obtaining complete nutrition from an appropriately selected diet.
Introduction
The primary function of the professional dietitian/nutritionist is to provide the information that will allow every person to consume a diet that ensures their optimal health. In cases of food allergy and food intolerance, when food itself is the cause of disease, the challenge is to ensure that the client avoids the foods that make them sick, while still obtaining optimal nutrition from their diet. In theory this should be a fairly straight-forward process: Identify the culprit foods, and substitute with nutritionally equivalent ones. In practice, it is a very difficult endeavour because there is no reliable test that will identify the specific foods and food additives that are responsible for the various symptoms of food sensitivity. Many tests have been developed in an effort to determine the reactive foods. The traditional skin tests of the allergist; the blood tests of the immunologist; biochemical analysis of hair, urine, and other body products; and a variety of “new age tests” utilizing energy waves (Vega test), muscle response (biokinesiology) and other more unorthodox tests, have proven unreliable in identifying the food component responsible for clinical symptoms (1, 2). As a result, the many different test modalities used by traditional and non-traditional medical practitioners often indicate that a person is reacting adversely to a bewildering array of foods. The more professionals the food-sensitive person consults, the longer the list of foods they must avoid. The immense confusion and distress caused by the process of “food allergy diagnosis” itself may become a debilitating condition (3).
Food phobia, and eating disorders such as anorexia, are not uncommon as a result of perceiving food to be the cause of disease (3). Many food-sensitive people are at risk of nutritional deficiency as a result of trying to obtain symptomatic relief by avoiding all the foods suspected to be the cause of their distress on the basis of unreliable tests. Although many of the in vivo and in vitro tests are useful as indicators that a person is atopic (that is, has the potential to develop allergies), a physician cannot predict with great accuracy whether a person will have a reaction following the ingestion of a food, or the specific type of adverse reaction the person will experience (4). This can only be done by careful elimination of the suspect foods and systematic and carefully monitored challenge with individual food components that will provide the maximum amount of information on the way in which the food-sensitive person reacts adversely. This review examines the methods and potential pitfalls in the detection of the culprit foods and provision of a nutritionally complete diet for the food-sensitive individual, based on the experience obtained in a clinic and research program specifically designed to exclusively manage adverse reactions to foods.
The Allergy Nutrition Program in British Columbia
The Allergy Nutrition Research Program was inaugurated in September 1991 as a unique outpatient clinic and resource centre solely devoted to the management of adverse reactions caused by allergy or intolerance to food. The Program is based in the Vancouver Hospital and Health Sciences Centre and serves the province of British Columbia . However, I am frequently requested to present lectures and workshops and to share my research and experiences with personnel in health care centres throughout Canada , as well as internationally. The management strategies that have proved so successful in the Program have been published in the form of a comprehensive manual (5), and a reference book (6). Physicians, dietitians, public health nurses, and clients regularly contact the Allergy Nutrition Program for advice on the dietary management of a diverse variety of food allergies and intolerances.
The outpatient clinic takes clients on referral from physicians. We counsel clients of all ages, from pregnancy and birth to advanced age, and have developed strategies for management of their adverse reactions to foods that pose the least possible risk to the client. The “culprit food components” are identified by initial elimination of the suspect foods, always accompanied by substitution with alternative nutrient sources. The “substitution diet”, which normally continues for four weeks, is followed by reintroduction of individual food components using a sequential incremental dose protocol designed to identify the specific symptom triggers (5).
More than two thousand clients have passed through the Clinic. Without exception, each one has increased our knowledge about the ways in which humans respond to food, to changes in their food intake, and the issues surrounding eating, from many different aspects (7). Although we derive a great deal of satisfaction, and immense gratification when the outcome of our strategies benefits our clients, there is a certain amount of frustration associated with the dietary practice of food allergy management. Perhaps the greatest cause of this is the lack of any definitive tests that can guide us in the selection of the foods that are causing adverse reactions. In the majority of cases, our clients share our frustration. In the most extreme cases, misunderstanding of the limitations of the commonly performed tests has led to overt harm.
Food Allergy Diagnosis:
Skin tests
The traditional practice of allergy in Western medicine, almost without exception involves diagnosis of the allergic reaction by skin tests. These may involve placing a drop of a commercial antigen on the skin, usually the patient`s arm or back, and scratching or pricking the skin surface (scratch or prick test) to allow the antigen to contact cells of the immune system under the epidermis. Alternatively, some practitioners favour injection of the antigen into the dermis through a hypodermic syringe (intradermal test). The resulting “wheal and flare” response (a flattened reddened area surrounding a central denser area) of a positive reaction is compared in size to a control. A wheal at least 3mm larger than the negative control is considered positive (8). Allergists rate the degree of reaction on a variety of scales. Some favour the 0 to 4 plus (++++) rating; others use a broader scale, 0 to 40+ or higher; others use a system measuring both the wheal and flare (for example, 8X12; 15X10). Quite often the allergist does not provide a rating, but gives a verbal report without documentation, because of the risk of the results being misinterpreted.
The value of skin tests in practice
The lack of correlation between skin tests for food allergy and symptoms has been commented on by many practitioners. Positive predictive accuracies for skin tests for foods rarely exceed 60% (8) and many practitioners would rate them even lower. This means that although a person may have produced anti-food IgE antibodies, their presence alone is not sufficient to produce an immediate hypersensitivity reaction (allergy) to the food. An American allergist, Dr.M.Mandell, states “…conventional skin tests for determining specific food allergies give results that are wrong more than 80 percent of the time” (9).
Several studies have indicated that skin tests for the highly allergenic foods such as egg, peanut, wheat, milk, fish and tree nuts have close to 100% negative predictive accuracy, while other allergens, notably soy, do not produce this degree of accuracy (8). What this means in practice is that if the skin test for these foods is negative, there is virtually no possibility of them causing a life-threatening anaphylactic reaction. However, this does not guarantee that they will not produce symptoms of a milder type when eaten, because the reaction may be produced by a mechanism other than an IgE-mediated Type I hypersensitivity.
The British paediatrician, Dr.T.J.David, (10, p.251) appraises the value of skin testing as a diagnosis of food allergy thus: “Skin-prick testing still has its enthusiasts. They tend to be based in the specialty of allergy, where there may be a perceived need to demonstrate `allergy expertise` or where the performance of tests is associated with a fee for service. Although skin-prick testing has a place in research studies, it is difficult to see a place for skin testing in the general diagnosis or management of intolerance to food or food additives”. A number of authorities concur that “Skin-prick tests for food allergy are especially unreliable because of the large number of false positive and false negative reactions” (10,p 250, 11,12,13,14,15,16). Furthermore, intradermal skin testing for food has not been shown to be useful (8). Bock (8 p 156) states, “Until additional studies are undertaken to show their utility, it appears that intradermal skin tests carry too high a risk of producing systemic reactions without enhancing the predictive accuracy of the test”.
Recently, a patient was referred to the Clinic, having been tested by three different allergists in the preceding few months. The first reported “very large reactions” and the patient was told that she was “very allergic”; the second reported that she was “not allergic”; the third reported “significant reactions to cats and grasses, with modest reactions to dust mite” and “…..significant reactions to yeast, pork, milk and eggs”. Another recent example of the confusion engendered by the results of skin tests involved a 37 year old client (Ms A.B.) with rhinitis, digestive tract symptoms and chronic fatigue. She was reported to be strongly skin test positive to many foods including milk, egg, wheat, corn, brewer`s yeast, soya, chocolate, peanut, pork, salmon, shrimp, as well as various air-borne allergens such as grass, tree and weed pollens, and mildly reactive to many more foods. After avoiding all of the skin test positive foods, Ms AB reported that her symptoms were “no different”. She undertook sequential incremental dose reintroduction of each restricted food component, and reported that she did not react to any of them adversely. These are only two recent examples of a phenomenon that we see quite often in the clinic – foods which cause a wheal and flare reaction when scratched or injected into the skin are tolerated without any problems when eaten. Some allergists explain this discrepancy as being due to “hidden food allergy” and advise avoidance of the skin test positive foods without any further evidence. It seems much more likely that the discrepancy is due to differences in reactivity of the mast cells that release the inflammatory mediators responsible for the reaction (17).
Discrepancies between skin test results and the appearance of symptoms
Adverse reactions to foods may or may not be caused by the “classical” allergic response of an IgE-mediated Type I hypersensitivity reaction. A number of other immune system mediated hypersensitivity reactions as well as responses to food components not mediated by the immune system can result in symptoms (8). Since skin tests are designed to detect reactions mediated by IgE, non-IgE mediated reactions can be expected to be negative (15). There is notoriously a poor correlation between the results of challenge tests of the food and skin prick tests. For example, in a 1977 study by Bock and his colleagues (11) of 31 children with a strongly positive skin prick test response to peanut, only 16 had any symptoms when peanuts were eaten. Conversely, false negative results are frequently reported in young infants and toddlers (14, 18). Data on the effect of age on skin reactivity to allergens are sadly lacking, and there are no age-related guidelines for what constitutes a positive reaction (10).
Mast cells and release of mediators of allergy
Mast cells in the mucosa of the digestive tract differ quite markedly from those in connective tissue such as the skin (17). Differences between mast cells include differences in their staining properties, in the types of inflammatory mediators contained in their intracellular granules, and the types of stimuli that induce release of those granules and the mediators they contain. In general, human skin mast cells are responsive to a wide range of stimuli which do not cause degranulation of intestinal mast cells (17). A positive reaction to a food by stimulated skin mast cells does not guarantee that the same antigen will cause degranulation of mast cells in the digestive mucosa. Clinically, it is likely that in many cases symptoms may not result from eating a skin test positive food because mucosal mast cells may not be degranulated by the food antigen that caused degranulation of mast cells in the skin.
False positive skin tests may be due to:
False negative skin tests may occur because:
David succinctly assesses the logic of skin testing for food allergy diagnosis thus (10 p 249): “The role for skin-prick tests in food intolerance, if any, is far from clear. The fact that skin tests are still in use reflects both the unscientific nature of allergy practice and the lack of reliable and simple tests”.
In vitro tests
Laboratory (in vitro) tests for the diagnosis of food allergy tend to be even less accurate than skin tests. Radioallergosorbent tests (RAST), enzyme-linked immunosorbent assay (ELISA) and similar tests are designed to detect antibodies to foods in blood serum. Because the presence of antibodies to viruses, bacteria, and other pathogenic microorganisms can be used successfully to diagnose infectious diseases, it was assumed that the presence of circulating anti-food antibodies would be an equally useful tool in the diagnosis of food allergy (4). Unfortunately, the presence of an anti-food antibody does not correlate well with clinical symptoms when the food is eaten. Anti-food antibodies of both IgE and IgG types can be detected in people who have no signs of ever having had adverse reactions to foods (22). David states that in vitro tests for specific IgE antibodies (for example RAST) are considered “..of little if any practical value in the management of food intolerance” (10 p 264) an opinion that is shared by other researchers (23). David further warns that “The clinical interpretation of in vitro IgE antibody tests is subject to the same caveats and pitfalls as the interpretation of skin-prick testing, so that, as with skin testing, tests to detect circulating IgE antibody are of very little use in the management of food intolerance” (10 p.265).
Unorthodox tests
Because the standard tests available to the clinical allergist are so unreliable in detecting the specific foods that are causing the patient grief, many people turn to alternative medical practitioners for help when they find that in spite of diligently avoiding all of their skin-test or RAST-positive foods, they still experience their usual symptoms. Clients sometimes spend thousands of dollars for a variety of unorthodox tests, such as the Vega test (electro-acupuncture), applied kinesiology (which tests a diminishing of muscle strength while the patient holds a vial containing the suspect food), lymphocyte cytotoxicity, urine therapy, hair analysis, radionics, oral or subcutaneous provocation and neutralisation (24), and really outrageous methods such as consulting crystals. The drawbacks of food allergy testing have been succinctly summarized by Dr.David (25), and include: “…diagnostic inaccuracy, therapeutic failure, false diagnosis of allergy or the creation of fictitious disease entities…, failure to recognize and treat genuine disease, and inappropriate and nutritionally inadequate diets and malnutrition”. The result is that patients and physicians alike are disenchanted with the whole field of food allergy. Some physicians have been known to dismiss the idea of food intolerance as fiction, neurosis, or hypochondriasis and to refer their food intolerant patients to a psychiatrist.
Potential harm due to food allergy tests
Traditional Western medicine relies on the “medical model” of evaluation of symptoms, followed by laboratory tests that indicate a diagnosis, which in turn dictates treatment with drugs or surgery. If the tests available are inadequate in making the diagnosis, the pivotal component in the sequence is missing. Consequently, if accurate diagnosis is not possible, appropriate treatment is not immediately evident. In the absence of definitive diagnostic test results, too many patients are dismissed without appropriate treatment, and are left with the thankless task of looking for answers on their own. A great deal of grief, time, and valuable health care funds could be spared if it were more widely recognized that there is no one test that could possibly diagnose all of the different ways in which food components can impact adversely on the body. It seems as illogical as expecting there to be a single test that could be used alone to diagnose the multiplicity of diseases that humankind is heir to.
So often the clients that are finally referred to the Allergy Nutrition Clinic are those who have been subjected to many and varied methods of diagnosis. They still experience distressing symptoms, and in many cases have lost a considerable amount of weight and may be suffering from overt malnutrition as a result of their extensive “elimination diets”. Some admit to “food phobia” as a result of being told that they risk a life-threatening anaphylactic reaction if they are merely exposed to the cooking odours of their allergenic foods. They are frequently angry and frustrated because of their perception of maltreatment by the “medical system” – and they are still looking for help. They know they must eat to stay alive, but they no longer know what is “healthy eating”, because so often what they eat seems to make them sick! Too often we end up as “the last resort clinic”, and this need not be the situation.
Except in the rare cases of anaphylactic reactions, adverse reactions to foods are not often life-threatening, and the issue becomes one of quality of life rather than a situation requiring acute medical intervention. Frequently, when the risk of life-threatening pathology has been ruled out, the patient is dismissed with the admonition that they “must learn to live with it”. Too often, that means living without the foods that have been deemed to be allergens based on skin tests, RAST, or other methods of in vitro diagnosis. A life sentence indeed!
Some time ago, a 35 year old RCMP officer came into the Allergy Nutrition Clinic in great distress. He had recently been referred to an allergist for a second set of allergy tests for foods, and had been told that on the basis of the size of the skin test reaction he had been “upgraded to anaphylactic”. He had never experienced an anaphylactic reaction, but based on the skin test alone, he felt that he had immediately been put under a sentence of death. Because of his distress, he had been distracted while driving home from his doctor`s office and for the first time in his career was involved in a car accident. The reality, of course, is that the size of the skin test has not been shown to correlate well with the probability of a positive food challenge (8), but clients are familiar with medical tests which provide a definitive diagnosis, and a patient will rarely question the reliability of any tests performed in a doctor`s office.
Researchers working in the field of food allergy tend to agree on one important aspect: all positive tests for food allergies, including skin tests or in vitro tests such as RAST and ELISA, should be confirmed by challenge with the suspect food before a person is condemned to a life-time of avoiding it. Furthermore, a positive reaction to one food in a botanic family rarely indicates a similar degree of reactivity to all members of that family: each needs to be challenged separately before being labelled “allergenic” for the atopic person (10).
No in vitro test available at present can replace a well-controlled challenge in the evaluation of food allergy (26). The ideal follow-up to skin tests and in vitro investigations for food allergy should be a double-blind placebo controlled food challenge. However, in practical terms this can be very expensive because of the time required for supervision by clinic personnel. In addition, it may result in false negative responses because the amount of food that can be properly disguised may be insufficient to elicit a reaction and the challenge may miss many dose-related responses.
Relevance to Practice – The role of dietitians and nutritionists
Dietitians and nutritionists have an obligation to their clients, and to their profession, to ensure that no-one is put at risk because of malnutrition as a result of unbalanced and nutritionally inadequate “elimination diets” based on unreliable tests. Each client must be assessed individually, and a diet formulated to ensure complete, balanced nutrition, while avoiding the foods responsible for adverse reactions, ideally based on well-defined challenge tests. There is ample information available now (5,6,8,27) to ensure that every food allergy test can be confirmed by elimination and challenge in vivo. If there is even a remote chance of the development of serious symptoms and anaphylaxis the challenge should be conducted only under medical supervision in appropriately equipped facilities. In the happy event that the substitution and challenge program establishes that food is not the cause of a client`s symptoms, the sufferer is freed from the constant fear that food will cause distress and can once again embrace it as a source of nurture and nourishment. This approach has worked well with our clients in the Allergy Nutrition Program, and there is no reason why everyone with access to a registered dietitian/nutritionist should not be provided with the resources to achieve this result.
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References
Goldberg BJ, Kaplan, MS. Controversial concepts and techniques in the diagnosis and management of food allergies. Immunology and Allergy Clinics of North America 1991;11(4):863-884
Bahna SL. Practical considerations in food challenge testing. Immunology and Allergy Clinics of North America11991;11:843-850
