What Are Common Cross-reactivities with Other Allergens?

Patient Presentation
A 3-month old came to clinic for blood in his stools. He was breastfeeding and his mother had already stopped using dairy products in her diet. He was now having obvious blood for the last 2-3 stools. He was otherwise acting well and had no changes to his skin or problems swallowing or breathing, The past medical history was positive for previous blood in his stools around 3-4 weeks of age. He also had mild infantile atopic dermatitis that was controlled with emollients. The family history was positive for an older sibling with allergy to cow’s milk protein and soy causing gastrointestinal symptoms. His father also had asthma and a tree nut allergy where he had orpharyngeal swelling and wheezing. His father carried epinephrine with him for his allergies. The review of systems was otherwise negative.

The pertinent physical exam showed a healthy infant with normal vital signs and growth parameters in the 25-75%. His skin was slightly dry on his face, trunk and legs, but not with significant inflammation. HEENT, lungs, heart and abdomen were negative. His anus had a small amount of obvious blood around it that tested positive for blood.

The diagnosis of increasing problems with probable cow’s milk protein allergy was made. The mother was well-educated about the problem and after discussion about potential options wanted to stop breastfeeding and use a formula. “I don’t want to stop breastfeeding but I think it will be the clearest option to make sure he doesn’t get more cow’s milk by accident,” she stated. “The recommendations are to use an elemental formula which I would highly recommend in your family, especially as his brother already has a soy allergy,” the pediatrician stated. “I’d also like to see a pediatric allergist. There’s just so many allergies in the family and I’d like to talk with them and their nurses directly. I think I would feel better about what I can do to continue to avoid the foods and what to do if things get worse. We don’t have a problem with peanuts but what if that happens too,” the mother requested. The pediatrician agreed with the consultation and referred the family.

Discussion
The most common allergic foods are cow’s milk (most common), egg, peanut, tree nut, soy, wheat, fish and shellfish. Egg, milk, soy and wheat tend to occur in young children and these are more likely to be outgrown over time. Peanut, tree nut, shellfish, and fish occur at all ages and are less likely to be outgrown. Peanut and tree nut allergies also tend to be more severe than other foods. Ninety percent of food fatalities were attributed to tree nuts and peanuts. In a study of anaphylaxis in schools, food was the most likely trigger (54%) with nuts and fruits being the most commonly identified foods. Co-factors of food-induced anaphylaxis include asthma, exercise, non-steroidal anti-inflammatory drugs, infections and alcohol.

Treatment for food allergy is strict avoidance of the food(s), management and avoidance of potential co-factors, and immediate management of reactions. Immunotherapy is one option for some allergens and a review of its indications can be found here.

Cross-reactivities within a plant group are common. For example the Rosacae family has many agriculturally important trees and plants and cross-reactivities between the them is common. Cross-reactivity syndromes do occur. Oral allergy syndrome or pollen food allergy syndrome is caused by shared homology between pollens, fruits, vegetables and tree nuts. Patients usually are sensitized to an environmental pollen and then have reactions with oral ingestion of various foods. Symptoms are usually localized to the oropharynx (i.e. tinging, itching, mild swelling). Systemic reactions are less common and anaphylaxis is rare. Latex fruit syndrome is again caused by shared homology. People who are allergic to latex may have reactions include apples, avocado, chestnuts, banana, kiwi, tomato, bell pepper and carrot. Ficus trees have some cross-reactivity too. Reactions can be severe. A review of latex allergy can be found here.

Learning Point
Common allergens and their cross-reactivities with other allergens are listed below.
Note: The examples given are common but not necessarily a comprehensive listing of all cross-reactivities.

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Allergen How Common Overall? Cross-reacts with (examples) Avoidance Pattern Other
Cow’s Milk Most common food allergy – 2.0 – 3.5% for children, 1.94% in adults Goat’s milk – 92%, Cooked beef – 10%, Soy 14-70% Cow’s milk can be avoided, Cooked beef is recommended not to be avoided Often outgrown as child ages, Baked/cooked milk is often tolerated
Egg 1.3 – 3.2% in children and 0.51% in adults Egg can be avoided Often outgrown as child ages, Some proteins are less allergenic if cooked/baked, Influenza vaccine is recommended for those with documented egg allergy
Peanut 0.6 – 1.3% in children 5% between legumes (ex. peas, lentils, beans and soy), Peanut cross-reactivity is unknown, but within atopic individuals is reported as between 23-50% All peanuts should be avoided, Soy can be avoided Tends not to be outgrown, Fatal reactions are more common, Roasting peanuts can increase allergenicity
Tree nuts 0.2 – 0.5% in children and 0.87% in adults 37% within the tree nuts (ex. almond, brazil nuts, cashew, almond, hazelnut, pecan, pistachio, etc.), Peanut cross-reactivity is unknown, but within atopic individuals is reported as between 23-50% Avoid tree nuts, see notes about cross-reactivity with peanuts above or to left Fatal reactions are more common
Wheat 20% between grains (ex. barley, rye) Avoid only the wheat, not other grains unless specific testing shows reactions Often develops in childhood and then outgrown by adulthood
Shellfish 0.87% in children and 2.04% in adults Cross-reactivity within shellfish is 75%. Occurs in different crustaceans and also insects such as cockroach, dust mite and grasshopper Avoid all shellfish, There is not specific cross-reactivity between shellfish and fish, There is not specific cross-reactivity with iodine allergy or radiocontrast reactions. Usually develops during childhood and not outgrown
Fish 0.4 – 0.6% in children Cross-reactivity between fish is 50% (ex. swordfish, sole), There is not specific cross-reactivity between shellfish and fish Avoid all fish unless specific food testing shows tolerance for specific fish type
Pollen (Birch, Ragweed, etc.) 55% with other fruits/vegetables (ex. apple, peaches, honeydew) Ragweed often cross-reacts with bananas, melons, cucumbers and tomatoes, Grasses cross-react with kiwi, melons, peaches and tomato
Peach 55% with other Rosacae family such as apple, plum, cherry, pear Avoid specific fruits
Melon 92% with other fruits, avocado, banana, watermelon Avoid specific fruits
Latex Fruits, avocado, banana, kiwi If allergic to latex fruits are 35% cross-reactivity, if allergic to the fruit, the cross-reactivity to latex is 11%, avoid specific fruits

Questions for Further Discussion
1. What are recipes for introducing peanut foods for potentially high-risk infants? A review can be found here.
2. What proteins cause cow’s milk protein allergy? A review can be found here.

Related Cases

    Symptom/Presentation: Bloody Stool

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, the National Guideline Clearinghouse 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.

Host A, Halken S. Cow’s milk allergy: where have we come from and where are we going? Endocr Metab Immune Disord Drug Targets. 2014 Mar;14(1):2-8.

Isok S, Arıkan-Ayyıldız Z, Caglayan-Sozmen S, Fırıncı F, Tuncel T, Karaman O, Uzuner N. Cross-reactivity syndromes: presentation of two cases and review of the literature. Turk J Pediatr. 2014 May-Jun;56(3):291-4.

Patel BY, Volcheck GW. Food Allergy: Common Causes, Diagnosis, and Treatment. Mayo Clin Proc. 2015 Oct;90(10):1411-9. doi: 10.1016/j.mayocp.2015.07.012.

Radlovic N, Lekovic Z, Radlovic V, Simic D, Ristic D, Vuletic B. Food allergy in children. Srp Arh Celok Lek. 2016 Jan-Feb;144(1-2):99-103.

White MV, Silvia S, Muniz R, Herrem C, Hogue SL.
Prevalence and triggers of anaphylactic events in schools. Allergy Asthma Proc. 2017 Jul 1;38(4):286-293.

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