On the Topic of Allergies

When I was six months old, I experienced my first full-blown anaphylactic reaction. The cause- a handful of seemingly harmless rice cereal. An allergy test following this incident revealed a whole slew of allergies, the most significant of which included milk, peanut and tree nuts. This discovery marked the beginning of a new life, filled with unpredictable danger. However, as I quickly realized, I was not alone in my diagnosis.

A Rising Predicament
IgE-mediated food allergies affect a significant proportion of the population, with estimates as high as 10% in western societies. While some food allergies such as milk, egg and soy are generally outgrown by the age of 5, many allergies like peanut, tree nuts and shellfish persist into adulthood. Due to this, food allergies are considerably more common in young children than adults, but exact measurements of those affected are hindered by the inaccuracies of self-diagnosis and reporting. What is clear however, is that the incidence of food allergies is on the rise. In a report released in 2013 by the CDC, it was shown that the proportion of the US population affected by allergies nearly doubled from 1997 to 2011.

Simply put, a food allergy is an adverse immune reaction to a normally harmless food protein. An allergic reaction occurs when allergen-specific IgE antibodies bound to the surface of mast cells and basophils recognize an epitope on the allergen and crosslink. This results in degranulation of the effector cells, the contents of which go on to affect multiple organ systems causing increased vascular permeability and the recruitment of other inflammatory cell subsets. The symptoms of an allergic reaction can range in severity from mild to potentially fatal depending on a variety of factors including the sensitivity of the individual’s immune system and amount of allergen ingested.

There is considerable debate in the scientific community regarding the exact cause of food allergies. Due to the complex nature of this disease, both genetic and environmental factors undoubtedly play a role in its manifestation.

A Complex Diagnosis
Food allergy diagnosis is largely based on patient history. Allergy testing is usually done to confirm or refute a suspected allergen. The most common allergy test is the skin prick test (SPT), where a small amount of soluble, purified allergen is introduced to the patient via a light scratch on the skin. The SPT often includes the allergens in question in addition to a few other common allergens, as patients frequently misattribute the cause of their symptoms. The SPT also includes a positive and negative control, most commonly histamine and saline respectively. After 15-30 minutes, the skin is checked for red bumps (wheal and flare) which would thus indicate an allergy. However, the size of the bump is not necessarily indicative of the severity of the allergy. The SPT is a quick, cost effective and relatively safe method for diagnosis, although in some extremely sensitive individuals, there is a slight risk of a serious reaction. Although the SPT is generally good for ruling out sources of allergy, 50-60% of tests tend to yield false positive results due to cross reactivity and lack of antigen processing that normally occurs during digestion. Additionally, SPT results can easily be affected by the presence of antihistamines.

It is apparent that all allergy tests currently being used for diagnosis … cannot predict with 100% certainty the presence of an allergy, or the severity of a reaction without risking the patient’s health unnecessarily.”

Another common test that can be done in concert with the SPT is the measurement of allergen-specific IgE antibodies in blood. This test has no risk of reaction, is not affected by the presence of allergy medications and can be done on patients with skin conditions, where the SPT is unreliable. While presence of allergen-specific IgE indicates sensitization to an allergen, this may not be representative of clinical outcome. Since it is possible for individuals to be sensitized to an allergen and have specific-IgE but no clinical symptoms, the threshold for a definitive allergy – which requires a clinical outcome and symptoms – is difficult to establish.

Another less common method of allergy identification is the Basophil Activation Test (BAT), where basophils in blood samples of potentially allergic individuals are observed for markers of activation following allergen exposure. This test is not yet used for diagnostic purposes in Canada, but positive tests have been shown to be predictive of clinical symptoms.

The gold-standard allergy test, and the only definitive approach to diagnosing an allergy is the oral food challenge (OFC). In this test, the patient is given increasing doses of the suspected allergen until a threshold of tolerance is met or the allergy is disproved. However, this test is very labour and resource intensive as well as potentially very dangerous to the patient. Thus, the other allergy tests are much more commonly used. Due to the potential for an anaphylactic reaction, OFC and SPT must be done in a clinical setting with a board-certified allergist that is prepared to treat a systemic reaction. It is apparent that all allergy tests currently being used for diagnosis have many pros and cons; most cannot predict with 100% certainty the presence of an allergy, or the severity of a reaction without risking the patient’s health unnecessarily. Due to this, new methods of allergy testing must be developed.

The Elusive Treatment
Currently, there is no approved treatment or cure for food allergy. Management is limited to avoidance of the offensive allergen and emergency interventions upon accidental exposure. In the case of allergen ingestion, the first-line of treatment for an anaphylactic reaction is a shot of epinephrine (adrenaline). As such, people with serious food allergies must always carry epinephrine on them just in case. Additionally, the presence of any atopic disease greatly increases the chances of another. Therefore, many people with allergies must also cope with asthma, eczema and/or rhinitis.

On the bright side, advancements in this field are expanding. The ground-breaking LEAP (Learning Early About Peanut Allergy) and LEAP-ON (Persistence of Oral Tolerance to Peanut) studies published in The New England Journal of Medicine in 2015 and 2016 respectively, were instrumental in changing the way we understand the development of food allergies. These studies showed that early exposure to peanuts in infants with a high-risk of developing peanut allergy (determined by the presence of egg allergy and/or severe eczema) dramatically reduced the acquisition of the allergy in comparison to those that avoided peanuts. It was also shown that early exposure maintained tolerance to peanuts in the majority of infants after one year of peanut avoidance. Due to these studies, the National Institute of Allergy and Infectious Diseases (NIAID) recently released new guidelines for introducing peanut to infants, now favoring early exposure over avoidance. This is a dramatic shift compared to the guidelines released by the American Academy of Pediatrics in 2000, which suggested avoiding peanut exposure in high-risk infants until the age of 3.

In the same vein, many treatments for food allergy are currently undergoing clinical trials. This includes testing the use of pre-existing drugs such as Omalizumab (anti-IgE antibody, commercially sold as Xolair), a drug currently used to control severe allergic asthma. Additionally, there are many studies focusing on oral immunotherapy for milk and egg allergies using increasing doses of baked goods (heat-denatured protein) to stimulate desensitization. Indeed, there are also many clinical trials exploring preventative immunotherapy using various routes of exposure. Due to this, a standard treatment for allergies should be expected in the near future.

From the perspective of an immunologist, I must say I find my allergies exceedingly fascinating. They give me a unique connection to my research which, coincidentally, is in the field of allergy. Of course, the constant looming danger of literal death by chocolate can dampen a person’s outlook on life. But in recent years, food allergies are becoming an increasingly common issue, and people are truly starting to take notice. If you don’t already know someone with allergies, your children might have them or you may even develop them later in life. It is important now more than ever to increase awareness about this condition, for your sake and mine.

References

1. Benede S et al. The rise of food allergy: Environmental factors and emerging treatments. EBioMedicine, 7:27-34 (2016).
2. Boyce JA et al. Guidelines for Diagnosis and Managment of Food Allergy in the United States. J Allergy Clin Immunol, 126(60):S1-58 (2014).
3. Lieberman JA & Chehade M. Use of omalizumab in the treatment of food allergy and anaphylaxis. Curr Allergy Asthma Rep, 13(1):78-84 (2013).
4. Prescott SL et al. A global survey of changing patterns of food allergy burden in children. World Allergy Organ J, 6(1):21 (2013).
5. Savage J & Johns CB. Food Allergy: Epidemiology and Natural History. Immunol Allergy Clin North Am, 35(1):45-59 (2016).

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Lisa Hung

Lisa is an M.Sc. student at the University of Toronto in the Department of Immunology. She is currently doing research on the mechanisms of food allergy and anaphylaxis. In her spare time, she enjoys knitting, baking and listening to podcasts.

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