Skin Prick Testing as a Cause of Food Allergy?
Could skin prick tests cause the allergies that they are designed to diagnose? Dr Janice Joneja believes that they could.
See here for comment from allergist Dr Adam Fox.
The accurate diagnosis of food allergy and food intolerance is fraught with difficulties. No single test can definitively identify the food components responsible for the clinical expression of an immunological or non-immunological reaction to a food. In the end, elimination and challenge must be undertaken to determine the precise role of a food component in triggering symptoms.
Although skin testing is still the only in vivo test that is universally employed in clinical practice, its potential hazards have been greatly underestimated.
(Image of skin prick test being performed courtesy of the Medical Journal of Australia.)
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.
Tolerance versus sensitisation; the gut versus the skin
Our immune system is designed to protect the body from any foreign substance that enters. In this way we are protected from invading micro-organisms, toxins and other noxious agents that pose a threat to our health and survival. Of course, all food is entirely foreign to the body, and as such should logically be rejected by the immune system. So, how and why does this not occur?
It is all due to a process known as “oral tolerance”, which distinguishes between “foreign and a threat” and “foreign but safe”. Oral tolerance is achieved by a very complex series of reactions of immune cells lining the gastrointestinal (digestive) tract, directed by T-call lymphocytes. The molecules in the intestinal contents from food, beverages and other ingested material are sampled, analysed and responded to by the immune cells. If safe, the material is then allowed into the body. When the same material is ingested on future occasions, it is recognised as safe and no adverse immunological response occurs.
However, if tolerance to the substance does not occur, the immune system will reject it; in the case of food, this response results in allergy. When the food material enters the body via a route other than the digestive tract, it is assumed to be a threat unless previous tolerance has been established via the oral route. Exposure to food antigens through the skin is more likely to lead to allergy compared to early oral consumption, which is more likely to lead to tolerance. I have provided details about the processes of immunological tolerance and sensitisation in my books and articles on food allergy, and a good review of the topic can be found in reference Izadi 2015 below.
Allergen exposure via the skin
New research confirms this route to sensitisation
A recent research study at Northwestern University in Chicago demonstrated that in genetically predisposed mice, exposure to food and environmental allergens through the skin led to the development of allergic markers such as inflammation, inflammatory mediators and anaphylactic reactions after the mice were fed the allergenic food (Walker et al 2018). Interestingly, mice of allergic mothers were more likely to develop reactions to lower sensitising doses of the allergenic food.
Following publication of this research, the idea that human babies could be similarly predisposed to be at risk of allergic sensitisation was suggested. An article in the popular press warned parents that using baby wipes could initiate food allergy by facilitating the passage of the food through the skin (Bodkin 2018).
Scratch and prick tests
It is ironic that the authors should suggest baby wipes as a means of facilitating the introduction of the allergenic food to the immune system, while ignoring the most obvious mechanism of intradermal exposure, namely scratch and prick tests commonly used in an effort to diagnose allergy to a specific food.
In such tests, allergen extracts are placed on the skin, which is scarified with a lancet or pricked with a needle, to ensure that the allergen encounters immune cells beneath the surface. In intradermal testing, the allergen is actually injected into the skin, thus ensuring an even greater exposure to the immune system.
All of these tests are incredibly efficient methods of delivering the allergen to the immune cells, which are more than ready to respond, with rapid development of food-specific IgE that, in predisposed children can, and will, lead to food allergy, and in severe cases, anaphylaxis – as demonstrated by the 2018 article mentioned above.
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 sensitisation can occur by this route. After all, vaccination using antigen delivered on skin patches is proving very effective (Partidos et al 2002).
Have allergies been caused by these diagnostic methods?
I often wonder how many innocent children and their unwitting families have been sentenced to a life-time of dealing with the miseries of allergies as a result of the tests so commonly used in diagnosis. I have actively discouraged my patients, especially atopic children, from having skin tests performed 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 sensitisation through this route, I shall continue to dissuade my patients from undergoing this method of allergy testing.
Alternative methods diagnostic procedures
There are alternative in vitro methods for detecting allergen-specific IgE; RAST, FAST and ELISA tests have the potential for providing information that in most cases is as useful 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. The newer techniques of component resolved diagnosis (CRD) which are currently being developed may prove to be a concise method for allergen identification in the future. Hopefully, awareness by clinicians of the potential for primary sensitisation to allergens through the skin will stimulate the speedy development of more specific in vitro tests, and discontinuance of the risky practice of skin testing in all its forms.
Blyth T, Lack G. Are we generating peanut allergy? Asthma J 2002;7:120-122
Bodkin, Henry. Baby wet wipes 'cause food allergy', new study warns. Daily Telegraph April 7 2018
Izadi N, Luu M, Ong PY, Tam JS. The role of skin barrier in the pathogenesis of food allergy. Children 2015;2:382-402
Khakoo A, Lack G. Preventing food allergy. Current Allergy and Asthma Reports 2004 Jan;4(1):36-42
Lack G, Fox D, Northstone K, Golding J. Factors associated with the development of peanut allergy in childhood. New Eng J Med 2003;348:977-985
Matsuoko H, Maki N, Yoshida S, Arai M, Wang J, Oikawa Y, Ikeda T, Hirota
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
Radhakrishna N, Prickett S, Phan T, Rolland JM, Puy R, O'Hehir RE. Anaphylaxis to oats after cutaneous sensitization by oatmeal in skin products used for the treatment of atopic dermatitis. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):152-3.
Saloga J, Knop J. Does sensitization through the skin occur? Allergy 2000;55:<905-909
Voskamp AL, Zubrinich CM, Abramovitch JB, Rolland JM, O'Hehir RE. Goat's cheese anaphylaxis after cutaneous sensitization by moisturizer that contained goat's milk. J Allergy Clin Immunol Pract 2014 Sep-Oct; 2(5):629-30
Walker M, Green J, Ferrie R, Queener A, Kaplan MH, Cook-Mills JM. Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen co-stimulation. J Allergy Clin Immunol 2018 Feb 15;[Epub ahead of print]
Comment from Dr Adam Fox - May 2018
Dr Fox is consultant paediatric allergist at a leading London children's hospital. He is President Elect of the British Society of Allergy & Clinical Immunology and chairs their Paediatric committee. He is also trustee and Chair of the Advisory Board of Allergy UK, and member of the Anaphylaxis Campaign Clinical and Scientific Panel.
'Skin prick testing is internationally accepted as a safe method of allergy testing and is endorsed by organisations around the world as part of standard allergy practice eg NICE, European and American Allergy academies. Whilst there has been longstanding interest in the role of skin exposure to allergens as a way of developing sensitisation, this is quite distinct from skin prick testing and there is no published evidence at all to suggest that skin prick testing in anyway contributes to the development of allergies. '