Skin Testing in the Diagnosis of Food Allergy

Skin Testing in the Diagnosis of Food Allergy: Limitations and Risks

Janice M. Joneja, Ph.D., RD 2004 are aware that antigen delivered via this route can trigger an anaphylactic In the preliminary diagnosis of allergy, reaction. It is only logical to assume that skin tests are commonly performed to primary sensitization can occur by this demonstrate the existence of atopy, and route also. After all, vaccination using to identify the probable allergens antigen delivered on skin patches is responsible for a patient’s symptoms. proving very effective (Partidos et al However, although skin testing is still 2002). the only in vivo test that is universally Latex allergy is another example employed in clinical practice, its of epicutaneous sensitization to an potential hazards have not been allergen. The primary route for adequately investigated. It is well sensitization to latex allergens is through known that many agents can be the skin, and occasionally by inhalation. effectively delivered to the body via the The initial immunological process of skin. Hormones, vaccines, antitoxins and sensitization is generally thought to be a proteins are efficiently introduced into type IV hypersensitivity (contact) the body via this route, circumventing allergy, which results in local dermatitis, the digestive tract and powerfully usually on the hands in contact with targeting the effector system for which latex gloves. Subsequent exposure to they are designed. There is no reason to the allergens through the abraded skin suppose that allergens delivered through leads to IgE-mediated Type I the skin by absorption (in a patch), by hypersensitivity, which in extreme cases injection (intradermally) or by pricking has been reported to proceed to a life- or scratching, should not induce threatening anaphylactic reaction. allergen-specific IgE in a similar Evidence of the skin as a primary route manner. for sensitization has been provided by recent research studies on laboratory Examples of Primary Sensitization to animals in which topical application of Allergens Through the Skin the allergen to the skin resulted in the development of IgE-mediated Type I There are several reports that hypersensitivity (Lehto et al 2003). In demonstrate that primary sensitization addition to the possibility of anaphylaxis occurred through the skin, especially in as a consequence of exposure to latex food handlers (Saloga and Knop 2000). allergens, or the consumption of foods Allergen exposure and sensitization containing the same antigens (latex- through inflamed skin has been associated food allergy), anaphylaxis has demonstrated in a number of studies, been reported in patients undergoing especially to peanut in children with skin tests for latex allergy (Reunala et al eczema (Lack et al 2003). Many 2004), which demonstrates an additional allergists will not skin test their atopic risk associated with skin testing. patients with highly allergenic foods, such as peanuts and nuts, because they

 Janice M. Joneja, Ph.D., RD 2004 1 Research on the Safety of Skin Tests Likewise, other agents that are designed to evoke a response in the body There are no published research studies are delivered via the skin, for example, to prove either the danger or the safety hormones such as oestrogen, and of skin testing. Any invasive technique metabolites such as nicotine are requires extensive research before it is routinely delivered by patch application. approved for use. Research on animals Quite clearly, allergens are not inert and is followed by human studies, and only have the potential to provoke an equally when the technique is proven to be safe effective response in the body when and effective is it employed in clinical delivered via the skin. In the case of medical practice. No such studies have immunological sensitisation during skin been carried out on skin testing, testing, the result is not restricted to the although thousands of skin tests are technique itself – the results will remain performed every day in medical offices for a long time – if not for life. The and clinics throughout the world. allergic person might be put at risk of a Because the techniques of skin testing - life-time of allergen avoidance, which, prick, scratch, intradermal and patch as any allergy sufferer knows to their delivery of the allergen – have been cost, can range from annoying, employed for decades, little thought has debilitating, to the extreme of life- been given to the immunological threatening; processes involved in the tests. And because the technique is being Alternatives to Skin Tests performed through the skin, it has been assumed to be non-invasive and Skin tests are not the only diagnostic harmless. This is patently wrong! The tools for allergy available to the very fact that the wheal and flare practitioner: Blood tests that involve the reaction is the observed result of a withdrawal of blood, and therefore no positive test demonstrates that triggering delivery of antigen to the body, produce of an immunological response has evidence of sensitization to the allergen occurred. with an accuracy equal to that of skin An immunological response is tests. Radioallergosorbent tests (RAST) not trivial, especially when the response and enzyme-linked immunosorbent might involve seroconversion – that is, assays (ELISA) have the potential for the change from the immune system not providing information that in most cases producing antibody against the antigen, is as accurate as any skin test. The cost to a profound response that produces and need for laboratory facilities might antigen-specific antibodies together with limit their use for the present, but memory cells that ensure continued refinement of the technique should make production of those antibodies for the them more economical and universally long-term, if not for life. This is the available in the near future. Awareness process involved in vaccination, and as by clinicians of the potential for primary everyone is aware, no vaccine is sensitization to allergens through skin approved for use without extensive testing will undoubtedly stimulate the testing on both animals and humans. speedy development of safe in vitro Vaccines are delivered by injection, and tests. more recently via skin patch – similar to the techniques used in skin testing.

 Janice M. Joneja, Ph.D., RD 2004 2 Role of Skin Tests in the Diagnosis of than skin-prick testing. The difficulty in Food Allergy the interpretation of the results, the pain of intradermal injections, and the risk of Another question to be considered in the anaphylaxis mean that intradermal debate about the unavoidability of skin testing has no place in the routine testing in the diagnosis of food allergy is investigation of IgE-mediated allergic the fact that skin testing has a very low reactions or food intolerances in correlation with the clinical expression childhood” (David 1993 p 250). (For the of allergy. Many false positive and false information of the reader, Dr. David negative reactions associated with the defines “food intolerance” as test make it invalid as a diagnostic tool encompassing food allergy, enzyme without the corroborating evidence of defect, pharmacological reactions, elimination and challenge. No single irritant reactions, effects of drugs, and test will definitively identify the specific toxic reactions (David 1993 p 5)). food component responsible for allergy, since factors in addition to the mere presence of IgE seem to play an Anecdotal Reports of Sensitization important role in triggering symptoms. Following Skin Tests

Several practitioners have stated My concern regarding the risks of skin in print that skin tests in the diagnosis of testing arose from anecdotal reports food allergy are without merit and from patients whom I assisted in the should be discontinued. For example, the management of their food allergies in late Dr. Keith Eaton found in his practice my role as Head of the Allergy Nutrition that skin prick testing for determining a Clinic in Vancouver General Hospital in patient’s allergenic foods had an British Columbia, Canada. A surprising accuracy of only 28% when confirmed number claimed that they had no known by elimination and challenge. He wrote, reaction to a certain food until they had “It is therefore suggested that the use of been tested. The explanation from the skin prick tests in the diagnosis of physician performing the test was that ingestant responses to foods should be they had simply been unaware of the discontinued.” (Eaton 2004). Dr reaction until they became focused on T.J.David, a noted British Paediatrician their food allergies as a result of the states in his book, “Food and Food diagnostic procedures. I realised then Additive Intolerance in Childhood”, that very little research has ever been “Skin prick testing still has its undertaken in the field of immunological enthusiasts. They tend to be based in the sensitisation as a result of skin testing, specialty of allergy, where there may be but sadly, I lacked the resources to carry a perceived need to demonstrate “allergy out the research myself. My greatest expertise” or where the performance of hope is that as a result of this tests is associated with a fee for service. commentary, appropriate research will Although skin-prick testing has a place be performed in order to ensure that no- in research studies, it is difficult to see a one, especially a child, is ever put at risk place for skin testing in the general of life-long misery as a result of a diagnosis or management of intolerance relatively unnecessary diagnostic to food or food additives” (David 1993 p procedure. I have been felt extremely 251). Regarding intradermal testing, Dr. uncomfortable in advising my patients to David states, “The number of false undergo skin tests, especially when the positive reactions makes the patient is an atopic child, because of the interpretation of the results of risk of inducing IgE via this route. In intradermal testing even more difficult good conscience I could never condone  Janice M. Joneja, Ph.D., RD 2004 3 any action that might result, in an the potential benefits of skin tests do not extreme case, in a life-threatening justify the possible risks, until and unless anaphylactic reaction. Even milder these can be proven to be negligible. reactions can result in a life-time of misery. Until I see well-conducted Another requirement for ethical scientific research that proves that there health care states that the patient must be is no possibility of immunological provided with the information that will sensitization via the skin, I shall tend to enable them to make an informed discourage my patients from undergoing decision as to their willingness to face this method of allergy testing. the risks of a procedure in the interests of a beneficial outcome. However, it would be difficult for patients to be fully Methods for Demonstrating the Safety informed about the safety or risks of skin of Skin Tests testing when these are unknown, even to the administrator of the test him- or The research that is needed to prove the herself, at the present time. The required safety or risk of skin testing is fairly research has not been carried out, and straightforward: Blood is drawn from the potential for harm has not been the subject and analysed by RAST or examined. ELISA for the presence of allergen- specific antibody to the foods or other The attitude of many allergists allergens being tested. The subject is that "this is the way we've always done then skin tested using the prick, scratch, it" is not good enough when we have no intradermal or patch technique. After proof, apart from the anecdotal reports defined intervals of time – possibly each of the practitioners themselves, that a day for fourteen days, or possibly longer procedure is totally without risk. Since to allow seroconversion – the blood is blood tests such as RAST and ELISA again drawn and tested for the presence provide results that have been of antigen-specific antibody. If none is demonstrated to be as accurate as those detected, one can assume the test to be obtained from skin tests, they should be safe. If seroconversion occurs, we have utilized in food allergy diagnosis in demonstrated that the test is indeed place of skin tests until appropriate hazardous. Usually this procedure research has unequivocally demonstrated would be carried out first on animals – the safety of the latter. It behoves every for example the mouse and/or rat – and practitioner, in whatever field of health only when safe on animals would the care to ensure, to the utmost of their research be done on humans. ability, that whatever procedure they use, the health and safety of the patient Responsibilities of the Health Care entrusted to their care is paramount. Professional

The most important directive in health care management in any area of practice is “do no harm”. If there is the slightest References risk of harm, the benefits of the procedure must be unequivocally Blyth T, Lack G. Are we generating demonstrated to outweigh the risks. peanut allergy? Asthma J 2002, 7:120- Given the possibility that allergic 122 sensitization can occur through the skin, and that skin tests have questionable value in the diagnosis of food allergy,  Janice M. Joneja, Ph.D., RD 2004 4 David TJ. Food and Food Additive Reunala T, Alenius H, Turjanmaa K, Intolerance in Childhood. Blackwell Palusuo T. Latex allergy and skin. Scientific Publications, Oxford. 1993 Current Opinion ion Allergy and Clinical Immunology 2004. 4:397-401 Eaton KK Accuracy of skin prick tests for ingestant hypersensitivity diagnosis. Saloga J, Knop J Does sensitization Journal of Nutritional and through the skin occur? Allergy 2000 Environmental Medicine (June 2004) 55:905-909 14(2): 79-82 Zhang XD, Murray DK, Lewis DM, Khakoo A and Lack G. Preventing food Siegel PD. Dose-response and time allergy. Current Allergy and Asthma course of specific IgE and IgG after Reports 2004 Jan;4(1):36-42 single and repeated topical skin exposure to dry trimellitic anhydride powder in a Lack G, Fox D, Northstone K, Golding Brown Norway rat model. Allergy 2002 J. Factors associated with the Jul;57(7):620-626 development of peanut allergy in childhood. New Eng J Med 2003, 348:977-985

Lehto M, Koivuluhta M, Wang G, Amghaiab I, Majuri ML, Savolainen K, Turjanmaa K, Wolff H, Reunala T, Lauerma A, Palosuo T, Alenius H. Epicutaneous natural rubber latex sensitization induces T helper 2-type dermatitis and strong prohevein-specific IgE response. J Invest Dermatol. 2003 Apr;120(4):633-640

Matsuoko H, Maki N, Yoshida S, Arai M, Wang J, Oikawa Y, Ikeda T, Hirota N, Nakagawa H, Ishii A. A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae. Allergy 2003 Feb;58(2):139-145

Partidos CD, Beignon AS, Brown F, Kramer E, Briand JP, Muller S. Applying peptide antigens onto bare skin: induction of humoral and cellular immune responses and potential for vaccination. J Control Release 2002 Dec 13;85(1-3):27-34

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