Journal Citation
Joneja JMV. Comment on Skin Testing 2004
Janice M. Joneja, Ph.D., RD
2004
In the preliminary diagnosis of allergy, skin tests are commonly performed to demonstrate the existence of atopy, and to identify the probable allergens responsible for a patient’s symptoms. However, although skin testing is still the only in vivo test that is universally employed in clinical practice, its potential hazards have not been adequately investigated. It is well known that many agents can be effectively delivered to the body via the skin. Hormones, vaccines, antitoxins and proteins are efficiently introduced into the body via this route, circumventing the digestive tract and powerfully targeting the effector system for which they are designed. There is no reason to suppose that allergens delivered through the skin by absorption (in a patch), by injection (intradermally) or by pricking or scratching, should not induce allergen-specific IgE in a similar manner.
Examples of Primary Sensitization to Allergens Through the Skin
There are several reports that demonstrate that primary sensitization occurred through the skin, especially in food handlers (Saloga and Knop 2000). Allergen exposure and sensitization through inflamed skin has been demonstrated in a number of studies, especially to peanut in children with eczema (Lack et al 2003). Many
allergists will not skin test their atopic patients with highly allergenic foods, such as peanuts and nuts, because they are aware that antigen delivered via this route can trigger an anaphylactic reaction. It is only logical to assume that primary sensitization can occur by this route also. After all, vaccination using antigen delivered on skin patches is proving very effective (Partidos et al 2002).
Latex allergy is another example of epicutaneous sensitization to an allergen. The primary route for sensitization to latex allergens is through the skin, and occasionally by inhalation. The initial immunological process of sensitization is generally thought to be a type IV hypersensitivity (contact) allergy, which results in local dermatitis, usually on the hands in contact with latex gloves. Subsequent exposure to the allergens through the abraded skin leads to IgE-mediated Type I hypersensitivity, which in extreme cases has been reported to proceed to a life-threatening anaphylactic reaction. Evidence of the skin as a primary route for sensitization has been provided by recent research studies on laboratory animals in which topical application of the allergen to the skin resulted in the development of IgE-mediated Type I hypersensitivity (Lehto et al 2003). In addition to the possibility of anaphylaxis as a consequence of exposure to latex allergens, or the consumption of foods containing the same antigens (latex-associated food allergy), anaphylaxis has been reported in patients undergoing skin tests for latex allergy (Reunala et al 2004), which demonstrates an additional risk associated with skin testing.
Research on the Safety of Skin Tests
There are no published research studies to prove either the danger or the safety of skin testing. Any invasive technique requires extensive research before it is approved for use. Research on animals is followed by human studies, and only when the technique is proven to be safe and effective is it employed in clinical medical practice. No such studies have been carried out on skin testing, although thousands of skin tests are performed every day in medical offices and clinics throughout the world. Because the techniques of skin testing – prick, scratch, intradermal and patch delivery of the allergen – have been employed for decades, little thought has been given to the immunological processes involved in the tests. And because the technique is being performed through the skin, it has been assumed to be non-invasive and harmless. This is patently wrong! The very fact that the wheal and flare reaction is the observed result of a positive test demonstrates that triggering of an immunological response has occurred.
An immunological response is not trivial, especially when the response might involve seroconversion – that is, the change from the immune system not producing antibody against the antigen, to a profound response that produces antigen-specific antibodies together with memory cells that ensure continued production of those antibodies for the long-term, if not for life. This is the process involved in vaccination, and as everyone is aware, no vaccine is approved for use without extensive testing on both animals and humans. Vaccines are delivered by injection, and more recently via skin patch – similar to the techniques used in skin testing. Likewise, other agents that are designed to evoke a response in the body are delivered via the skin, for example, hormones such as oestrogen, and metabolites such as nicotine are routinely delivered by patch application. Quite clearly, allergens are not inert and have the potential to provoke an equally effective response in the body when delivered via the skin. In the case of immunological sensitisation during skin testing, the result is not restricted to the technique itself – the results will remain for a long time – if not for life. The allergic person might be put at risk of a life-time of allergen avoidance, which, as any allergy sufferer knows to their cost, can range from annoying, debilitating, to the extreme of life-threatening;
Alternatives to Skin Tests
Skin tests are not the only diagnostic tools for allergy available to the practitioner: Blood tests that involve the withdrawal of blood, and therefore no delivery of antigen to the body, produce evidence of sensitization to the allergen with an accuracy equal to that of skin tests. Radioallergosorbent tests (RAST) and enzyme-linked immunosorbent assays (ELISA) have the potential for providing information that in most cases is as accurate as any skin test. The cost and need for laboratory facilities might limit their use for the present, but refinement of the technique should make them more economical and universally available in the near future. Awareness by clinicians of the potential for primary sensitization to allergens through skin testing will undoubtedly stimulate the speedy development of safe in vitro tests.
Role of Skin Tests in the Diagnosis of Food Allergy
Another question to be considered in the debate about the unavoidability of skin testing in the diagnosis of food allergy is the fact that skin testing has a very low correlation with the clinical expression of allergy. Many false positive and false negative reactions associated with the test make it invalid as a diagnostic tool without the corroborating evidence of elimination and challenge. No single test will definitively identify the specific food component responsible for allergy, since factors in addition to the mere presence of IgE seem to play an important role in triggering symptoms.
Several practitioners have stated in print that skin tests in the diagnosis of food allergy are without merit and should be discontinued. For example, the late Dr. Keith Eaton found in his practice that skin prick testing for determining a patient’s allergenic foods had an accuracy of only 28% when confirmed by elimination and challenge. He wrote, “It is therefore suggested that the use of skin prick tests in the diagnosis of ingestant responses to foods should be discontinued.” (Eaton 2004). Dr T.J.David, a noted British Paediatrician states in his book, “Food and Food Additive Intolerance in Childhood”, “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” (David 1993 p 251). Regarding intradermal testing, Dr. David states, “The number of false positive reactions makes the interpretation of the results of intradermal testing even more difficult than skin-prick testing. The difficulty in the interpretation of the results, the pain of intradermal injections, and the risk of anaphylaxis mean that intradermal testing has no place in the routine investigation of IgE-mediated allergic reactions or food intolerances in childhood” (David 1993 p 250). (For the information of the reader, Dr. David defines “food intolerance” as encompassing food allergy, enzyme defect, pharmacological reactions, irritant reactions, effects of drugs, and toxic reactions (David 1993 p 5)).
Anecdotal Reports of Sensitization Following Skin Tests
My concern regarding the risks of skin testing arose from anecdotal reports from patients whom I assisted in the management of their food allergies in my role as Head of the Allergy Nutrition Clinic in Vancouver General Hospital in British Columbia , Canada . A surprising number claimed that they had no known reaction to a certain food until they had been tested. The explanation from the physician performing the test was that they had simply been unaware of the reaction until they became focused on their food allergies as a result of the diagnostic procedures. I realised then that very little research has ever been undertaken in the field of immunological sensitisation as a result of skin testing, but sadly, I lacked the resources to carry out the research myself. My greatest hope is that as a result of this commentary, appropriate research will be performed in order to ensure that no-one, especially a child, is ever put at risk of life-long misery as a result of a relatively unnecessary diagnostic procedure. I have been felt extremely uncomfortable in advising my patients to undergo skin tests, especially when the patient is an atopic child, because of the risk of inducing IgE via this route. In good conscience I could never condone any action that might result, in an extreme case, in a life-threatening anaphylactic reaction. Even milder reactions can result in a life-time of misery. Until I see well-conducted scientific research that proves that there is no possibility of immunological sensitization via the skin, I shall tend to discourage my patients from undergoing this method of allergy testing.
Methods for Demonstrating the Safety of Skin Tests
The research that is needed to prove the safety or risk of skin testing is fairly straightforward: Blood is drawn from the subject and analysed by RAST or ELISA for the presence of allergen-specific antibody to the foods or other allergens being tested. The subject is then skin tested using the prick, scratch, intradermal or patch technique. After defined intervals of time – possibly each day for fourteen days, or possibly longer to allow seroconversion – the blood is again drawn and tested for the presence of antigen-specific antibody. If none is detected, one can assume the test to be safe. If seroconversion occurs, we have demonstrated that the test is indeed hazardous. Usually this procedure would be carried out first on animals – for example the mouse and/or rat – and only when safe on animals would the research be done on humans.
Responsibilities of the Health Care Professional
The most important directive in health care management in any area of practice is “do no harm”. If there is the slightest risk of harm, the benefits of the procedure must be unequivocally demonstrated to outweigh the risks. Given the possibility that allergic sensitization can occur through the skin, and that skin tests have questionable value in the diagnosis of food allergy, the potential benefits of skin tests do not justify the possible risks, until and unless these can be proven to be negligible.
Another requirement for ethical health care states that the patient must be provided with the information that will enable them to make an informed decision as to their willingness to face the risks of a procedure in the interests of a beneficial outcome. However, it would be difficult for patients to be fully informed about the safety or risks of skin testing when these are unknown, even to the administrator of the test him- or herself, at the present time. The required research has not been carried out, and the potential for harm has not been examined. The attitude of many allergists that “this is the way we`ve always done it” is not good enough when we have no proof, apart from the anecdotal reports of the practitioners themselves, that a procedure is totally without risk. Since blood tests such as RAST and ELISA provide results that have been demonstrated to be as accurate as those obtained from skin tests, they should be utilized in food allergy diagnosis in place of skin tests until appropriate research has unequivocally demonstrated the safety of the latter. It behoves every practitioner, in whatever field of health care to ensure, to the utmost of their ability, that whatever procedure they use, the health and safety of the patient entrusted to their care is paramount.
References
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