The behavior of allergies varies considerably from one individual to the next. There is no exact formula for predicting how skin prick reactions or antibody levels will translate to allergy symptoms. This can make diagnosing allergies complicated and leave much room for uncertainty in the interpretation of test results. For my last post in this series on food allergies, I will discuss identification and therapy options currently available along with their limitations.

Before I proceed, the obvious should be noted; I am not a doctor. Your diagnosis and treatment plan should be reviewed with your medical provider. The purpose of this post is simply to supply information on some of the routes available.

Can’t I just diagnose my own allergy?

Many people take it upon themselves to diagnose their own allergies. While this may work in cases where severe reactions can be linked easily to certain foods, it’s generally not a reliable method and can lead to unnecessary dietary restrictions. Even for practitioners with years of experience, establishing an allergy can be tricky.

Sensitization gets mentioned a lot with allergy tests. Is it the same thing as an allergy?

Sensitization is not synonymous with allergy. Sensitization means the body has created defensive proteins (antibodies) to a particular substance it has deemed a potential threat. Sensitization may be asymptomatic, but symptoms must be present with an allergy. All allergies require sensitization; not all sensitizations become allergies.

How is an allergy diagnosed?

Diagnosing an allergy is a multi-step process. First, the clinical history of the patient should be assessed including family background and range of symptoms. The second step is typically a skin prick test. Additionally, an IgE serum analysis may be performed. After all that, a double-blind, placebo-controlled food challenge test may be conducted. The food challenge test is the gold standard for allergy identification and is the only way to conclusively determine the presence of an allergy and its level of reactivity.

What exactly does a skin prick test measure?

The skin prick test is often one of the first tools utilized to diagnose a food allergy. It is used to ascertain IgE sensitization to certain foods. For this test, the skin is lightly punctured in the presence of an allergen. This puncturing is done to allow mast cells in the skin to associate with the allergen. If IgE antibodies are present and cause mast cells to degranulate, histamine will be released, and a welt will form. This signifies a possible sensitization.

Why isn’t a skin prick test enough?

Skin prick tests are very accurate (90%) in proving someone is not allergic to a food, but they are much less successful in proving they are allergic. False positives are so common only 50% of reactions actually coincide with an allergy. Therefore, a skin prick test is not enough to verify an allergy to a given food. However, a history of reacting to a food and a positive skin prick test together are much more conclusive than a skin prick test alone. It should be noted, skin prick tests are only relevant for hypersensitivity reactions mediated by IgE. Delayed reactions like those facilitated by T cells cannot be detected via this method. As one final caution, you should pay no heed to the size of the welts created during this test. Although it may seem logical, bigger welts do not correlate with worse allergies.

If skin prick tests are regularly inaccurate, why are they performed so often?

The skin prick test does have many drawbacks, but it generally takes less than 15 minutes and only causes marginal irritation to the patient. Hence, its popularity.

What about IgE serum tests?

IgE serum assessments like fluorescent enzyme immunoassay and radioallergosorbent tests ascertain the presence of IgE antibodies in the blood to specific allergens. These tests only require a blood draw, which makes them particularly appealing. Unfortunately, they also have sizeable disadvantages.

Skin prick and IgE serum tests share some downsides. Both only detect sensitization, and they don’t detect it that well. Like a positive skin prick test, even if you have IgE antibodies to a particular food, it does not automatically follow that the food will cause allergy symptoms. Further, quantities of IgE do not correlate with severity of reactions. You could have a large amount of IgE in your blood for a specific allergen and tolerate it, or you could have a slightly positive test result for a food that elicits horrible reactions.

If skin prick and serum tests aren’t enough, what then?

Only those patients that have had a severe systemic reaction after ingesting a food and have a positive skin prick test need no further confirmation of their allergy. For everyone else, verification requires a double-blind, placebo-controlled food challenge.

A double-blind, placebo-controlled food challenge (DBPCFC), also called an oral challenge test, is the best way to diagnose a food allergy. Due to the chance of a severe reaction, this test is usually done at a hospital under medical supervision. The challenge starts with the patient consuming an amount of the suspected food so miniscule it’s not likely to cause a reaction or an identical amount of a placebo. The dose taken is doubled again and again until a normal amount of the food is being consumed. If a reaction occurs, the test is halted as needed.

Why the placebo control for the oral challenge test?

Patients may have anxiety about the possibility of having a reaction. This concern may lead them to believe they are having a reaction when they are not. The placebo control rules out these anxiety-driven false outcomes.

What about patch testing?

Patch testing involves the application of suspected allergens to the skin for two days. Each allergen solution is contained in a disc that is held in place with hypoallergenic tape. Often, a large panel of substances is screened at the same time, which can uncomfortably take up all the space on someone’s back. I think my doctor packed about 90 compounds on mine. Patch testing is performed to ascertain delayed-type reactions, such as those mediated by T cells instead of IgE. These include nickel and fragrance allergies. And yes, you can react to those substances in your food. Patch testing can also be useful when investigating possible causes for eosinophilic esophagitis, an allergic condition that triggers inflammation in the esophagus.

How does a food diary fit in?

A food diary can be helpful when investigating dietary issues of any sort whether they be allergies or other adverse reactions. It can be particularly valuable in uncovering routines of reaction and obscure problem ingredients. In a food diary, everything consumed is recorded from drinks to cough drops.

What about unconventional means of allergy diagnosis?

Those that suffer from allergies or have children that do can be taken advantage of by purveyors of diagnostic methods that lack scientific credibility. These unproven procedures include hair analysis, IgG testing, electroacupuncture, and muscle testing. While it is possible that some of these analyses will have enough research behind them to validate their use at some point, that is not the case today. Don’t be exploited in your eagerness for answers.

Are there treatments for allergies beyond avoidance?

While avoidance is the only treatment for allergies that is completely successful, other approaches like immunotherapy have merit in many cases.

The goal of immunotherapy is to switch the body’s attitude to a food from allergy to tolerance. Immunotherapy involves eating daily doses of the allergen that slowly increase over time. This regular exposure in growing concentrations can lead to desensitization, which means reactions will be less acute and greater quantities of the allergen will be necessary to elicit them. Unfortunately, immunotherapy requires many doctor visits, often causes mild to moderate reactions throughout, and has the potential to cause severe reactions. Further, the most advantageous dosing amounts and periods are still being debated. Yet, this approach will likely become more common in the future since it has been shown to discontinue reactions in 50% of patients, which is called sustained unresponsiveness. Immunotherapy can be particularly helpful in removing some of the anxiety of inadvertent exposure. A doctor can talk you through the risks and benefits of this treatment and determine if it might be a good option in your particular situation.

But isn’t it better to just avoid everything I’m allergic to?

While avoidance does prevent symptoms, in some cases it may not be the best course of action as it can increase the severity of an allergy. Intake of an allergy-inducing food over time can lead to tolerance by increasing the formation of IgG antibodies, which block IgE. Therefore, regular consumption may protect against anaphylaxis. However, complete avoidance is still the best course of action in many acute cases. Your exact circumstances should be discussed with your doctor.

How exactly do IgG fit in?

IgG are our most prolific antibody defenders. They are found throughout the body and fight diligently against bacteria and viruses. In the intestines, they form for individual proteins when these proteins penetrate the intestinal lining. This most often happens when there is inflammation present, and the lining is compromised. Unlike IgE, significant amounts of IgG specific to food ingredients are normal in all individuals, and IgG antibodies are not associated with hypersensitivity reactions. In fact, they are essential to developing tolerance to food allergens. Since their presence is ordinary and not correlated with allergies, IgG tests should not be used to diagnose allergies. Interestingly, although IgG are largely beneficial, some studies have indicated surplus levels may be associated with chronic intestinal inflammation.

What is an elimination diet?

An elimination diet can be used to evaluate if a certain food or foods is causing or worsening a condition like atopic dermatitis. These diets may make getting nutrients difficult and are often only prescribed temporarily.

What about medications?

Drugs are available that may have an impact on food allergies. These include antihistamines, steroids, anti-IgE compounds, and antileukotrienes. From basic Benadryl to prescription medications like Omalizumab, which binds to IgE, you’ve got some options.

What will the future bring?

While the testing and treatment routes presently available for food allergies are perhaps less than ideal, the future may be more inspiring. More accurate testing methods are in their early stages. For instance, research has shown the basophil activation test (BAT) can differentiate between allergies and tolerances in sensitized foods. Additionally, allergy vaccines are being researched and developed. Vaccines work by inducing the creation of IgG antibodies specific to particular food allergens, which leads to tolerance. These could potentially be administered to pregnant women or at-risk infants. Scientists have also been undertaking the challenging task of designing processing and genetic manipulation to decrease the allergenicity of food. As an example, enzyme treatment has successfully been used to diminish the allergenicity of proteins such as gluten.

Like figuring out what triggers tantrums in two-year-olds, understanding more about what’s behind your body’s overblown reactions can help you manage them better. I wish you the greatest success in deciphering and dealing with the hypersensitive. May your IgE antibodies take up knitting or yoga instead of taking to drama.

References:

1. Anvari et al. (2018). The Nuts and Bolts of Food Immunotherapy: The Future of Food Allergy. Children, 5, 47.

2. Begin et al. (2013). Diagnosis of Food Allergy. Pediatric Annals, 1, 42(6), 102-109.

3. Gocki and Bartuzi. (2016). Role of Immunoglobulin G Antibodies in Diagnosis of Food Allergy. Advances in Dermatology and Allergology.

4. Manea et al. (2016). Overview of Food Allergy Diagnosis. Clujul Medical, 89(1), 5-10.

5. Masilamani et al. (2012). Determinants of Food Allergy. Immunology and Allergy Clinics of North America, 32(1), 11-33.

6. Mills and Shewry. (2004). Plant Food Allergens. Blackwell Publishing.

7. Thomsen. (2015). Epidemiology and Natural History of Atopic Diseases. European Clinical Respiratory Journal.

8. Valenta et al. (2015). Food Allergies: The Basics. Gastroenterology, 148(6), 1120-1131.

Though on the rise, food allergies are fairly rare. If you have one, particularly a serious one, you may wonder why you got so lucky. While I can’t answer for the grand plans of the universe, I can provide a few insights on the subject. In this post I will be discussing the factors that make some proteins more likely to cause allergies and some of us more susceptible to them.

Do all proteins cause allergies?

Proteins are necessary for living cells to survive. They are ubiquitous and diverse with nearly 13,000 different protein families. Despite all that variety, just 0.16% of those families cause 80% of food allergies. Clearly, there is more to being an allergen than just being a protein.

What factors influence the potential of a protein to cause an allergic reaction?

1. Characteristics and structure of the protein

2. Amount of exposure to the protein

3. Genetic susceptibility of the person exposed

What types of proteins are more likely to cause allergic reactions?

Proteins provide countless essential roles in living organisms from balancing fluids to orchestrating chemical reactions. A protein’s function impacts its allergenicity. The majority of food allergies are caused by proteins involved in protection or storage.

Why protection and storage?

Protection proteins do exactly that. They protect plants from invasion by pests or pathogens. They are usually found in higher concentrations in seeds and tubers. These proteins are tough since they are designed to function even in hostile environments. Their ability to withstand aggressive atmospheres makes them perfect candidates for resistance to cooking and digestion. Profilins and Bet v 1, the main allergen in birch, are among defense proteins.

Storage proteins are found in seeds such as grains, nuts, and legumes. Their main purpose is to supply the nutrients required for the sprouting and developing of seedlings. There are two primary issues with these proteins. They are highly concentrated in seeds leading to greater exposure, and many of them are not damaged by heat. For example, globulins, which comprise over 50% of the protein in some species of nuts, are stable up to 200 degrees Fahrenheit. Albumins, like those found in soybeans and peanuts, are another family of storage proteins implicated in a large number of allergic reactions.

Beyond function, are there other protein properties that enhance allergenicity?

In order for a protein to initiate an allergic response, the allergenic component must be at least 20-25 amino acid residues long. Otherwise, it will be too short to bind properly to antibodies and the IgE system won’t respond.

Allergenicity is also dependent on stability. Sensitization through the gut, which is typical of many allergens like those in nuts, requires the protein to survive a number of onslaughts. It has to withstand cooking temperatures. It has to remain intact through the acidic conditions of the stomach. Additionally, it has to endure many enzymes and bile salts bombarding it throughout the digestive process. Most proteins are not up to the task. Some manage all too adeptly though.

Proteins make 3D structures by folding in and crosslinking. These arrangements look a bit like noodle blobs. As Giada De Laurentiis would tell you, not all noodles are created equal. Some protein configurations hold up better to cooking and digestion. For instance, beta structures are more resilient than alpha helices. Other structural components like links between different regions through disulfide bonds increase a protein’s hardiness. Plus, size does matter; smaller proteins are more able to withstand the heat of cooking.

Are certain protein sources more likely to cause allergies?

Immune responses, including allergies, are based on the body’s ability to distinguish between self and non-self. If a food protein is similar to our own proteins, it’s less likely our immune system will recognize it as different. Animal proteins, particularly from mammals, are much less prone to trigger allergic reactions for this reason.

Remarkably, a protein’s source may matter in other ways. Soy allergens usually elicit much milder reactions at much higher doses than many other allergenic foods. Research has suggested this might be due to the anti-inflammatory phytochemicals present in soy dampening the immune response to this ingredient.

What traits make a person more likely to develop allergies?

Some scientific studies indicate the risk of developing allergies is about 80% due to genetics. Inherited programming causes some immune systems to be unnecessarily sensitive. A genetic predisposition for an overly reactive immune system is known as atopy. Atopic diseases include eczema, asthma, pollen allergies and food allergies. If you have one parent with atopic disease, you have a 25% chance of also developing one. Those odds jump to 50% if both your parents have atopy.

The inherited immune system anomalies associated with allergies may have broader impact too. Research has shown the same genetic factors that increase vulnerability to allergies augment susceptibility to inflammatory and autoimmune disorders like Crohn’s disease and psoriasis.

That’s nature, but what about nurture?

Although genes clearly influence allergies, environment is decidedly also involved. Humankind’s genes haven’t changed in the last 50 years, but the incidence of atopic disease certainly has. In developed countries, the rates of asthma and allergies increased significantly in the last half of the 20^th century. For instance, in Australia, pollen allergies rose from 22.5% to 44% between 1982 and 1997.

One theory behind this surge is called the hygiene hypothesis. It speculates that modern environments have become too clean and our immune systems too sheltered from infections. Research has confirmed this hypothesis has merit, but no definitive conclusions can yet be made.

For my final part in this series, I will review how food allergies are diagnosed and treated. Come back to discover how to distinguish between an allergy that’s intolerable and an intolerance.

References:

1. Mills and Shewry. (2004). Plant Food Allergens. Blackwell Publishing.

2. Marenholz et al. (2017). Genome-Wide Association Study Identifies the SERPINB Gene Cluster as a Susceptibility Locus for Food Allergy. Nature Communications.

3. Masilamani et al. (2012). Determinants of Food Allergy. Immunology and Allergy Clinics of North America, 32(1), 11-33.

4. Thomsen. (2015). Epidemiology and Natural History of Atopic Diseases. European Clinical Respiratory Journal.

Cross-reactivity may sound like a description of your grandma’s irritation every time you walk through her pansies, but that’s not quite what it is.

As I mentioned in my previous post, 40% of those with pollen allergies have an associated plant food allergy due to cross-reactivity. Further, cross-reactivity is the predominant reason food allergies pop up in adulthood. While oral allergy syndrome is by far the most common way cross-reactivity presents, dangerous anaphylaxis can occur as well. Still, cross-reactivity perplexes both allergy sufferers and practitioners, which is why it will be the sole subject of this part in my allergies series.

What is cross-reactivity?

Cross-reactivity occurs when someone becomes sensitized to a particular allergen but then also reacts to separate species because of protein similarities.

Why do some proteins cause cross-reactivity reactions and others don’t?

As previously discussed, the bulk of food allergies are caused by proteins, and proteins are comprised of amino acids. One of the ways IgE antibodies recognize allergens is through amino acid sequences. If an unrelated protein has enough sequences in common with a substance we are allergic to, our IgE antibodies may flag it as an intruder as well. Yes, it may set our IgE Spidey sense and tongue tingling.

Why would two proteins be similar?

There are a couple reasons for likeness. Proteins from related species may share some components due to common genetics, but proteins from distinct species may also have commonalities because of similarities in function.

For instance, profilins are a group of proteins that are found in every plant part from fruit to nut. They perform essential functions like cell movement and, as they are present in almost every pollen, are a common pollen allergen. Roughly 10-30% of those with pollen allergies are sensitive to this family of proteins. Unfortunately, the uniformity between profilins from different plant sources is as high as 70-85%. What does this mean? Many people with pollen allergies will react when they encounter these proteins in food. Hence, profilins are involved in a high percentage of cross-reactivity cases.

Does the inhalant or food allergy come first?

Respiratory allergies are much more common than food allergies, impacting 10-30% of the world’s population. Therefore, in cases of cross-reactivity, the inhalant allergen is more often the primary sensitizer.

What are some of the common plants and foods that cause cross-reactivity reactions?

Which pollens and foods can cause cross-reactivity can be a bit confounding as the connections are not often obvious. Birch pollen and apple are the most frequently cross-reacting pollen and fruit pair. Birch pollen also causes cross-reactivity with carrots, pears, potatoes, and nuts.

Profilins, the protein family mentioned earlier, have been implicated in cross-reactivity with kiwis, apples, tomatoes, soybeans, celery, poppy seeds, and legumes. Fortunately, profilin allergy symptoms are typically mild involving a runny or stuffy nose in the case of pollens and oral allergy syndrome in the case of foods. On a side note, profilins are one of the allergens in birch pollen but are not the most common cause of birch allergies or cross-reactivity.

Many of those with a latex allergy will react to chestnuts, bananas, and avocados. This is because the protein involved in latex allergy, hevein, has 70% identical sequencing to proteins found in these fruits.

But cross-reactivity doesn’t stop with flora. People with a dust mite allergy can react to shrimp or other shellfish like mollusks.

Hopefully, how cross-reactivity connects the dissimilar is less confusing now. Next time, we will examine some of the properties of proteins and people that make allergies more likely to occur.

References:

1. Mills and Shewry. (2004). Plant Food Allergens. Blackwell Publishing.

2. Popescu. (2015). Cross-Reactivity Between Aeroallergens and Food Allergens. World Journal of Methodology, 5(2), 31–50.