Food Allergies and Cross-Reactivity

On this page:

What is cross-reactivity?
Cross-reactivity and false positive allergy tests
Cross-reactivity between cow’s milk and milk from other mammals
Cross-reactivity between foods in the same animal group
Cross-reactivity between peanuts and other legumes (soy and beans)
Cross-reactivity between peanuts and tree nuts or seeds
Cross-reactivity between tree nuts
Cross-reactivity between fish
Cross-reactivity between shellfish
Cross-reactivity between shellfish and dust mites
Cross-reactivity between pollen and foods (pollen-food syndrome or oral allergy syndrome)
Cross-reactivity between latex and foods
A final word

What is Cross-Reactivity?

The most common type of food allergy is when the immune system makes a type of antibody called IgE to proteins in a particular food. This is an IgE-mediated food allergy. In persons who make IgE against a food, when exposure to that food occurs, symptoms start quickly because the body is geared up to attack and defend against this trigger. Symptoms include any or several of the following: skin itching, hives, swelling of the skin, nausea, vomiting, diarrhea, breathing difficulty (wheezing, repeated throat clearing, cough, throat tightness), or anaphylaxis.

Anaphylaxis is a severe allergic reaction that is rapid in onset and progressive. Symptoms of anaphylaxis involve more than one organ system from the above list. They can also include dizziness or loss of consciousness (from a drop in blood pressure) and other serious, potentially life-threatening complications. Anaphylaxis can occur with any IgE-mediated food allergy.

The most common food allergens are milk, egg, peanut, tree nuts, fish, shellfish, wheat, soy, and sesame.

Cross-reactivity occurs when the proteins in one substance are similar to proteins in another. As a result, there is enough common between the two proteins that the immune system sees them as the same. Sometimes, this does not cause any problem, but other times it has the chance of resulting in an allergic reaction.  Cross-reactivity can also happen between pollens, between foods, between pollens and foods, and latex and foods.

Cross-Reactivity and False Positive Allergy Tests

Because of cross-reactivity, testing and diagnosis of food allergies can be challenging. This is just one reason why your allergist does not want to run a panel of tests—it can be hard to interpret the results when there is a chance of cross-reactivity. The tests sometimes are not “smart” enough to help determine if something is cross-reactive, or a primary danger. Think of a test as giving you a “yes/no” answer to if the body recognizes a certain protein. A negative test means “no, it does not”.  A positive test means “yes it does”. But…there is more to diagnosis than just protein recognition, and not all recognition means it will make someone sick. A lot of times this is actually harmless.

Take the case of a person with tree (birch) pollen allergy. This person, just because their immune system recognizes birch, may also recognize a other tree pollens and plant-based foods that are in the birch family (even far removed), such as fruits and tree nuts. At some level, these foods all have some protein in it that is similar to birch, and that part of the item can be recognized, causing a test to be “positive”. A birch allergic person may test positive to any tree nut, and multiple different fruits because of such cross-reactivity.

Most of this cross-reactivity does not result in the person having symptoms, because this cross-reactive part is not the same protein as the part known to cause allergy in people. With standard allergy tests, this is easy to confuse because it becomes positive with any part of the allergen being recognized, not just the “danger” parts. This explains a lot of cases of multiple positive tests to different tree nuts, shellfish, fish, or other allergens where certain parts of the protein are just common among lesser related species.

This is why allergists take such a careful history, importantly asking what has been eaten that causes symptoms, and what has been tolerated. It is also why no test by itself can diagnose an allergy. In the case where the food has been tested but not eaten before, this becomes very tricky and is best solved by an oral food challenge, where this can be safely tested.

The main point is to realize that not all positive tests mean there is an allergy, especially in the case of a positive test in a person who can eat that food without reacting (false positive) or when a food to which a person has never eaten is tested and that is positive (a test without meaning, no matter the size, until the food is eaten and we see what happens). However, because tests are placed for different reasons, and can be read differently, many people may end up being tested to foods without good reason and then told to avoid certain foods because of positive tests. They may have been eating that food before without any problems and unnecessarily remove the food from their diet based on the test result.

While most cross-reactivity is not a reason for concern, there are a few special cases where there is a chance that two foods will not only have testing that cross-reacts, but the person may have an allergic reaction if either food is eaten.

Cross-Reactivity Between Cow’s Milk and Milk from Other Mammals

There is a high degree of cross-reactivity between cow’s milk and the milk from other mammals such as goat and sheep. In studies, the risk of allergy (resulting in symptoms) to goat’s milk or sheep’s milk in a person with cow’s milk allergy is about 90%. The risk is much lower, about 5%, for allergy to mare’s milk (or donkey’s milk) which is less cross-reactive with cow’s milk. Plant-based milks or special formula without any milk-based proteins are the safest alternatives in these cases.

Cross-Reactivity Between Foods in the Same Animal Group

Cross-reactivity is uncommon between foods in the same animal group. For example, most people with an allergy to cow’s milk can eat beef and most people with an allergy to egg can eat chicken without any symptoms to the respective meats. It is exceptionally rare for it to be necessary to avoid these foods based on a risk of cross-reactivity.

However, in the special case of alpha-gal, an allergy to a carbohydrate in mammalian meat, there is risk of cross-reactivity between beef and pork, including derivative products such as gelatin, or medications. This can occur among different beef or among different pork products, and between beef and pork. For more on alpha-gal, we recommend this link: https://aafa.org/allergies/types-of-allergies/insect-allergy/alpha-gal-syndrome/ 

Cross-Reactivity Between Peanuts and Other Legumes (Soy and Beans)

Peanuts and soybean are in the legume family, which includes beans and lentils. A common question that comes up for people with an allergy to peanut is whether they can eat soy-based foods or other beans. More than half of individuals with a peanut allergy will have a positive skin test or blood allergy test to another legume (soy, other beans) but it turns out that almost all of them (95%) can tolerate and eat the cross-reactive legumes. For this reason, testing for other legume allergy in peanut allergic persons is not recommended. The link between soy and peanut allergy was debunked around 2006.

Other legumes may also cross-react on testing, but across legumes, these are unlikely to cause reaction. One exception may be lentil—there are multiple different types of lentil, and most individuals with lentil allergy are advised to avoid all lentils as opposed to just the particular type of lentil to which they have reacted.

Cross-Reactivity Between Peanuts and Tree Nuts or Seeds

As noted above, peanuts are legumes and are not related to tree nuts (almonds, walnuts, cashews, etc.) or seeds (sesame, sunflower, etc.). However, these all grow out of the ground, and carry proteins common to birch, as well as common proteins that help plants grow in the wild and survive. Old data, based on co-positive testing, once stated that about 1 out of 3 toddlers with peanut allergy in the U.S. have or will develop a tree nut allergy. However, this is not necessarily accurate based on two things:

• Much of this is based on co-positive tests in someone that has never actually eaten the tree nut. Well-intended advice that was common years ago to “avoid” these nuts and test children with peanut allergy for tree nut allergy and vice versa is not recommended anymore.
• It is now known that many cases of peanut allergic children who later developed tree nut allergy may have done so because of delayed food introduction (based on the positive tests or hesitancy to introduce) rather than having the allergy originally.

Still, it is possible to have both peanut and tree nut allergy. It is just not as common for someone to “cross-react”, and with more data and acceptance of oral food challenges, many people with peanut allergy are learning that they can tolerate eating tree nuts.

Cross-Reactivity Between Tree Nuts

People with tree nut allergies are very likely to test positive to other tree nuts, both within and across tree nut families. People who test positive within the tree nut family are at a higher risk of having true reactions. For example, very few cashew allergic persons tolerate pistachio, and vice versa, and are advised to avoid both.  Walnut allergic persons are generally advised to avoid pecan and hazelnut. However, while not absent, the risk of a cashew allergic person reacting to walnut is low, and to almond even lower.

Screening for tree nut allergy (in either someone allergic to peanut or allergic to one tree nut), e.g., testing someone before they’ve eaten the food, is not accurate for all the reasons described earlier.

Young children (and some adults) may have a hard time identifying a tree nut from a peanut, or a tree nut from another tree nut.  This safety concern means that in certain instances, doctors may recommend that some individuals avoid all tree nuts.

Cross-Reactivity Between Fish

There are two major proteins in the muscles of most fish: tropomyosin and enolase. This sets up a similar situation where allergy to one fish likely results in co-positive tests to other fish, but not always a risk of a reaction. While there certainly is some risk of cross-reactivity resulting in symptoms, generally, through oral food challenges, it is possible to find other safe fish to eat. There can be cross-reactivity among different species of fish including fresh and saltwater fish.

Cross-Reactivity Between Shellfish

Shellfish follows most of the same logic as discussed above. First, shellfish come in two species—crustacean (soft, molten shell) and mollusk (hard shell). There is a high degree of cross-recognition based on testing among the crustacean shellfish (shrimp, lobster, crab, crawfish) and within mollusk. Many individuals may tolerate mollusk if crustacean allergic, and vice versa.

If you are allergic to one type of crustacean (like shrimp), it is possible for some increase risk of cross-reactivity to another crustacean (like lobster). But also, through oral food challenge, it is possible you may find out you tolerate the other crustacean. The same applies to mollusks.

Cross-Reactivity Between Shellfish and Dust Mites

There is cross-reactivity between chitins (a component of exoskeleton of shellfish and insects) in dust mites and crustacean shellfish. This is because one evolved from the other at some point in history. This can result in “false positive” testing for shellfish without any clinical symptoms. This was nicely demonstrated in the early 2000s at Mt. Sinai, where investigators tested individuals who kept kosher, and noted that despite no history of eating shellfish, these persons tested positive to crustacean shellfish. It was shown, through laboratory analysis, that these persons were simply allergic to dust mites, and that was the reason for the positive shellfish testing.

An allergy to dust mite may cause an allergy test to shellfish to falsely show a positive result.

Cross-Reactivity Between Pollen and Foods (Pollen-Food Syndrome or Oral Allergy Syndrome)

Going back to the earlier discussion about birch pollen and how birch protein residues are in a lot of foods brings us to a common “cross-reactivity” issue. Some individuals with pollen allergies (allergic rhinitis or hay fever) can develop symptoms around and in the mouth and throat immediately after eating raw fresh fruits, vegetables, nuts or seeds that contain proteins cross-reactive to the pollens. This is known as oral allergy syndrome or pollen-food syndrome.

For example, people with birch pollen allergy may experience symptoms after eating raw apples, peaches, pitted fruits, carrot, and even peanut and hazelnut among others. Likewise, ragweed allergic individuals experience symptoms with melons among other foods. Symptoms can include itching or tingling of the lips, tongue, and roof of the mouth or throat. In addition, there may be hives around the mouth area where the food came into contact with the skin or swelling of the lips, tongue, and throat tightness. In less than 3% of these reactions, symptoms may become systemic (beyond the mouth or throat) or result in anaphylaxis with primarily GI symptoms.

Cooked forms of the foods are usually tolerated because the food proteins which are pollen cross-reactive are fragile and are broken down when subjected to heat, physical force (grinding or macerating) or stomach acids. So, for example, raw apples can cause symptoms but an apple pie can be eaten without any symptoms. Not all people with pollen allergies have oral allergy syndrome (OAS), but many do. And, for those who do have oral allergy syndrome, they may experience symptoms with some but not all foods cross-reactive to a particular pollen to which they are allergic.

Importantly, pollen food allergy syndrome is NOT A FOOD ALLERGY.  It is a pollen allergy, and, while yes the symptoms result from eating food, the issue is not the food itself, and is the pollen in the food to which the body temporarily reacts. It is not recommended that such patients need epinephrine. Much of how this is treated is recognition, careful planning, or acceptance of the generally mild symptoms that may result.

Cross-Reactivity Between Latex and Foods

Latex is a natural product that is derived from the milky substance extracted from a rubber tree. Common natural rubber latex products include latex gloves and balloons. Latex can cause several types of allergic or non-allergic (irritant) reactions. The most concerning type is an IgE-mediated allergic reaction to latex that results in immediate reactions such hives, swelling, wheezing, and anaphylaxis.

About 30 to 50% of people with IgE-mediated allergies to latex can experience symptoms with any or several fruits cross-reactive to latex including most commonly banana, avocado, kiwi, and chestnut. This is similar to what happens with pollen food allergy syndrome to an extent. However, the overall prevalence of IgE-mediated reactions to latex is rare and decreasing as latex is not commonly used like it once was. Most reported reactions are due to contact sensitivity, resulting in a rash, and this is a different form of allergy than an IgE-mediated allergy.

A Final Word

Individual reactions vary when it comes to food allergies and cross-reactivity. And, because of the additional challenges in diagnostic testing posed by allergen cross-reactivity, it is important to talk with your allergist-immunologist (allergist) about your symptoms with foods. For example, people with birch or grass pollen allergy may have a positive skin test to peanut as well.

Your allergist has expertise in the area of allergen cross-reactivity and can help in making an accurate diagnosis and providing guidance as to whether a cross-reactive food needs to be eliminated or not.