What is the Allergen Cross-Reactivity Rate of Legumes?

Patient Presentation
A 6-month-old female came to clinic for her health supervision visit. The mother was worried about food allergies. The mother had tried to feed the infant jarred peas for the first time and the infant had a rash around her mouth and face within a few hours. The rash resolved but recurred the next 2 days when fed peas and the rash seemed to come on quicker and was spreading down her neck. The mother wasn’t sure if she was itching but she did not have any problems with breathing or swallowing. The infant had been receiving only breast milk and other foods such as cereals, carrots and sweet potatoes which she had not had any reactions to in the past. The mother reported eating a general diet. The father had some seasonal allergic rhinitis and the older brother did not have any problems with food. He enjoyed eating peanut butter. There was no history of eczema or asthma in the family.

The pertinent physical exam showed a healthy female with normal growth patterns in the 75-90%.She had a minor diaper dermatitis but no other rashes. Her examination was normal.

The diagnosis of a healthy female with possible pea sensitivity or allergy was made. The pediatrician counseled, “I don’t know the exact percentage of children with pea allergy but it does happen. Usually around now we also recommend starting peanut butter containing foods and both peas and peanuts are legumes and therefore may have some cross-reactivity. She didn’t have any breathing or swallowing problems and no one else in the family has any food allergies and they also don’t have eczema or asthma. I also bet she’s been exposed to peanut butter because of her brother eating it too. Usually the allergy doctors tell us to take precautions but also use reasonable judgment because we know that being exposed to some of these foods actually decreases the allergies long-term. I wouldn’t give her any more peas, but I do think you can start to give her peanut containing foods. I’ll give you detailed instructions about how to do this and signs to watch her closely for. I’m also going to give you an Epi-pen® to have in case there is a problem, and if she has problems you are going to call 911. I would rather you give her the peanut food now and watch her, than she gets it by accident later and she has a reaction when you aren’t expecting it.” The patient’s clinical course showed at her 9-month appointment she didn’t have any reactions to peanut or soy foods.

Discussion
There are 8 common foods which compromise 90% of food allergens with those being peanuts, soybeans, cow’s milk, eggs, fish, crustacean/shellfish, wheat and tree nuts. Some people believe that lupin (a legume) is 9th.

Legumes belong to the Fabaceae family. They provide protein, fat, vitamins other essential nutrients and therefore are used in the human diet throughout the world.

“[A]llergenicity due to consumption of legumes in decreasing order may be peanut, soybean, lentil, chickpea, pea, mung bean and red gram.” Other common legumes include alfalfa, clovers, beans, lupins, mesquite, carob, and red kidney bean. Different legumes are consumed in different countries and therefore the prevalence of allergenicity to those legumes will be different. For example, legumes have a higher sensitization rate in Spain (5th most common reason for allergies) and India. Lupin is grown in Mediterranean countries and has a high rate of allergens in this area particularly Italy. Lupin seeds are eaten as a snack or it is ground and used as flour. It is becoming more commonly consumed in other Western European countries and in the same geographical areas there are also an increase of people with these allergies. In India, allergies to lentils, chickpeas, red gram and moong are more common.

The allergenicity of legumes is IgE mediated. The protein allergens are characterized into 4 main groupings including storage proteins (i.e. seed storage), profilins or other proteins. There is cross reactivity among the legumes themselves. There is also cross-reactivities with legume proteins and other botanicals including legume seed storage proteins cross-reacting with some tree and groundnuts. Cooking changes the allergenicity. For example, boiling or frying peanuts decreases the allergenicity whereas roasting increases it. Boiled legumes such as lentils, peas, and chickpeas can be decreased but it also depends on the length of time.

Legume allergy symptoms are similar for all legumes and range from mild to life threatening including urticaria, rhinorrhea, asthma exacerbation, angioedema, and anaphylaxis. Oral consumption is the main exposure to legume allergens but inhalation from flour, powder or vapor can also cause problems. People who are allergies have to be careful of hidden allergens. Not only because there might be contact with the production and processing of the foods, but because other ingredients may be included but not be required to be listed on food labels. These include lupin and pea, as well as celery, mustard, colorings, preservatives and spices. For example, fenugreek is a legume that is often part of spice mixtures.

Learning Point
“Although extensive serological IgE cross-reactivity among legume species has been found using in vitro methods, the rate of clinically relevant cross-reactivity to multiple legumes has been reported to be low.” For peanuts (the most common legume studied), the rates of cross-reactivity with another legume was 5-7.9%. Cross-reactivity between certain legumes also appear to be more clinically relevant.
Peas have cross-reactivity especially to lentils and chickpeas as they have similar allergens within them from the cupin superfamily of allergens.

Chickpea allergy is almost never seen alone but is associated with other allergies particularly lentil allergy.

Peanuts are associated with lentil, chickpea, pea and soy allergies. Lupin (44%) and fenugreek have high cross-reactivity with peanut. Lupin has a 44% cross-reactivity with peanut.

Cross-reactivities with other common allergens can be found here.

Questions for Further Discussion
1. What are risk factors for latex allergy? A review can be found here
2. What are common food allergies in your location?
3. How do you instruct families to introduce peanut containing foods? A review can be found here

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: Food Allergy

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Verma AK, Kumar S, Das M, Dwivedi PD. A comprehensive review of legume allergy. Clin Rev Allergy Immunol. 2013;45(1):30-46. doi:10.1007/s12016-012-8310-6

Bar-El Dadon S, Pascual CY, Reifen R. Food allergy and cross-reactivity-chickpea as a test case. Food Chem. 2014;165:483-488. doi:10.1016/j.foodchem.2014.05.138

Cabanillas B, Jappe U, Novak N. Allergy to Peanut, Soybean, and Other Legumes: Recent Advances in Allergen Characterization, Stability to Processing and IgE Cross-Reactivity. Mol Nutr Food Res. 2018;62(1). doi:10.1002/mnfr.201700446

Skypala IJ. Food-Induced Anaphylaxis: Role of Hidden Allergens and Cofactors. Front Immunol. 2019;10:673. doi:10.3389/fimmu.2019.00673

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa