Food allergy is an exaggerated immune response to dietary components, usually proteins. Manifestations vary widely and can include atopic dermatitis, gastrointestinal or respiratory symptoms, and anaphylaxis. Diagnosis is by history and sometimes allergen-specific serum IgE testing, skin testing, and/or elimination diets. Treatment is with elimination of the food that triggers the reaction and sometimes oral cromolyn.
(See also Overview of Allergic and Atopic Disorders.)
Food allergy should be distinguished from nonimmune reactions to food (eg, lactose intolerance, irritable bowel syndrome, infectious gastroenteritis) and reactions to additives (eg, monosodium glutamate, metabisulfite, tartrazine) or food contaminants (eg, latex dust in food handled by workers wearing latex gloves). Prevalence of true food allergy ranges from < 1 to 3% and varies by geography and method of ascertainment; patients tend to confuse intolerance with allergy (1).
Довідковий матеріал загального характеру
1. Warren CM, Sehgal S, Sicherer SH, Gupta RS. Epidemiology and the Growing Epidemic of Food Allergy in Children and Adults Across the Globe. Curr Allergy Asthma Rep 24(3):95-106, 2024. doi:10.1007/s11882-023-01120-y
Etiology of Food Allergy
Almost any food or food additive can cause an allergic reaction, but the most common triggers include
In infants and young children: Milk, soy, eggs, peanuts, and wheat
In older children and adults: Nuts and seafood
Cross-reactivity between food and nonfood allergens exists, and sensitization may occur nonenterally. For example, patients with oral allergies (typically, pruritus, erythema, and edema of the mouth when fruits and vegetables are eaten) may have been sensitized by exposure to pollens that are antigenically similar to food antigens. Children with peanut allergy may have been sensitized by topical creams containing peanut oil used to treat rashes. Many patients who are allergic to latex are also allergic to bananas, kiwis, avocados, or a combination.
Food allergies are more common among children whose parents have food allergies, allergic rhinitis, or allergic asthma.
In general, food allergy is mediated by IgE, T cells, or both:
IgE-mediated allergy (eg, urticaria, asthma, anaphylaxis) is acute in onset, usually develops during infancy, and occurs most often in people with a strong family history of atopy.
T-cell–mediated allergy (eg, dietary protein gastroenteropathies, celiac disease) manifests gradually and is chronic; it is most common among infants and children.
Allergies mediated by both IgE and T cells (eg, atopic dermatitis, eosinophilic gastroenteropathy) tend to be delayed in onset or chronic.
Оральний алергічний синдром (синдром харчової алергії на пилок)
Oral allergy syndrome (pollen food allergy syndrome) is caused by proteins in pollens and foods that cross-react (frequently raw fruits and vegetables and nuts). When patients are allergic to a particular pollen protein, the immune system reacts to a similar protein in the food and generates an allergic response. Patients can usually tolerate the food if it is cooked or heated because the food protein is denatured, altering the structure of the proteins that cross-react.
The following pollens and foods are commonly associated:
Birch pollen: Apples, almonds, carrots, celery, cherries, hazelnuts, kiwi, peaches, pears, and plums
Grass pollen: Celery, melons, oranges, peaches, and tomatoes
Ragweed pollen: Bananas, cucumbers, melons, sunflower seeds, and zucchini
Typical symptoms include itching of the mouth and throat when the causative food is eaten. Although anaphylaxis is not common, it can occur (1).
Diagnosis of oral allergy syndrome is usually made clinically but can be confirmed by skin prick testing.
Treatment of oral allergy syndrome involves avoiding the food, thoroughly cooking the food to denature the protein, and carrying a prefilled, self-injecting epinephrine syringe in case of an anaphylactic reaction.
Еозинофільна гастроентеропатія
This unusual disorder causes pain, cramps, and diarrhea with blood eosinophilia, eosinophilic infiltrates in the gut, and protein-losing enteropathy; patients have a history of atopic disorders.
Eosinophilic esophagitis may accompany eosinophilic gastroenteropathy or occur in isolation. Eosinophilic esophagitis is characterized by chronic inflammation of the esophagus and may cause dysphagia, nonacid-related dyspepsia, and dysmotility or, in children, feeding intolerance and abdominal pain. Eosinophilic esophagitis may cause strictures; diagnosis is by endoscopic biopsy.
Синдром альфа-гал
Alpha-gal syndrome refers to a recently discovered form of allergy to red meat (2). Alpha-gal is a sugar molecule (galactose-alpha-1,3-galactose) that occurs in most mammals except for primates (including humans). Also, alpha-gal does not occur in fish, birds, or reptiles.
At least one species of tick (lone star tick) has alpha-gal in its saliva. Evidence suggests that the bite (particularly multiple bites) from such ticks may sensitize a person to alpha-gal. Because alpha-gal is present in many red meats (eg, pork, beef, lamb, venison) and in food products derived from mammals (eg, dairy products, gelatin), affected people may develop an IgE-mediated allergic response to these food products.
The allergic reactions can include an itchy rash, indigestion, constipation, nausea, and anaphylactic reactions. Unlike those of other food allergies, symptoms of alpha-gal syndrome frequently do not occur until 3 to 8 hours after eating.
Довідкові матеріали щодо етіології
1. Skypala IJ: Can patients with oral allergy syndrome be at risk of anaphylaxis? Curr Opin Allergy Clin Immunol 2020 20 (5):459–464, 2020. doi: 10.1097/ACI.0000000000000679
2. Hashizume H, Fujiyama T, Umayahara T, et al: Repeated Amblyomma testudinarium tick bites are associated with increased galactose-α-1,3-galactose carbohydrate IgE antibody levels: A retrospective cohort study in a single institution. J Am Acad Dermatol 78 (6):1135–1141.e3, 2018. doi: 10.1016/j.jaad.2017.12.028 Epub 2017 Dec 19.
Symptoms and Signs of Food Allergy
Symptoms and signs of food allergies vary by allergen, mechanism, and patient age.
The most common manifestation in infants is atopic dermatitis alone or with gastrointestinal (GI) symptoms (eg, nausea, vomiting, diarrhea). Children usually outgrow these manifestations and react increasingly to inhaled allergens, with symptoms of asthma and rhinitis; this progression is called atopic march. By age 10 years, patients rarely have respiratory symptoms after the allergenic food is eaten, even though skin tests remain positive. If atopic dermatitis persists or appears in older children or adults, its activity seems largely independent of IgE-mediated allergy with a dominance of T-cell–mediated reactions, even though patients who have atopy and extensive dermatitis have much higher serum IgE levels than patients with atopy who are free of dermatitis.
When food allergy persists in older children and adults, the reactions tend to be more severe (eg, explosive urticaria, angioedema, even anaphylaxis). In a few patients, food (especially wheat and shrimp) triggers anaphylaxis only if they exercise soon afterward; mechanism is unknown. Food may also trigger nonspecific symptoms (eg, light-headedness, syncope). Occasionally, cheilitis, aphthous ulcers, pylorospasm, spastic constipation, pruritus ani, and perianal eczema are attributed to food allergy.
T-cell–mediated reactions tend to involve the GI tract, causing symptoms such as subacute or chronic abdominal pain, nausea, cramping, and diarrhea.
Цінні поради та підводні камені
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Diagnosis of Food Allergy
Allergen-specific serum IgE testing
Skin testing
Trial elimination diet (alone or after skin testing or allergen-specific serum IgE testing)
Severe food allergy is usually obvious in adults. When it is not or when it occurs in children (the most commonly affected age group), diagnosis may be difficult, and the disorder must be differentiated from other GI problems. Diagnosis of celiac disease is discussed elsewhere.
Testing (eg, allergen-specific serum IgE testing, skin testing) and elimination diets are most useful in diagnosing IgE-mediated reactions. Patients should keep a food diary, meticulously listing everything they consume and any adverse effects they have (particularly timing in relation to food consumption), to help guide decisions regarding elimination of suspect foods.
It is recommended to test only to foods that have resulted in a clinical response. Broad panel testing to multiple foods or food groups is highly discouraged due to the risk of unneeded removal of foods from the diet.
If a food reaction is suspected, one of the following is done:
In either case, a positive test does not confirm a clinically relevant allergy. Both tests can have false-positive or false-negative results. Skin testing is generally more sensitive than the allergen-specific serum IgE test but is more likely to have to false-positive results. The skin test provides a result within 15 to 20 minutes, much more quickly than the allergen-specific serum IgE test.
If either test is positive, the tested food is eliminated from the diet. If eliminating the food relieves symptoms, the patient is reexposed to the food (preferably in a double-blind test) to see whether symptoms recur (oral challenge testing). (See also the National Institute of Allergy and Infectious Diseases (NIAID) medical position statement: Guidelines for the diagnosis and management of food allergy in the United States.)
If skin testing is not available to confirm food allergy or results are inconclusive, the next options may include one or both of the following:
Eliminating foods the patient suspects of causing symptoms based on the patient's food diary, then evaluating symptom resolution
Prescribing a diet that consists of relatively nonallergenic foods and that eliminates common food allergens (see table Allowable Foods in Representative Elimination Diets)
For the latter diet, no foods or fluids may be consumed other than those specified. Pure products must always be used. Many commercially prepared products and meals contain an undesired food in large amounts (eg, commercial rye bread contains wheat flour) or in traces as flavoring or thickeners, and determining whether an undesired food is present may be difficult.
A discussion with the patient and observations from the patient's food diary can help with the choice of the initial elimination diet. If no improvement occurs after 1 week of the initial diet, another diet should be tried; however, T-cell–mediated reactions may take weeks to resolve. If symptoms are relieved and if patients have less severe symptoms, one new food is added and eaten in large amounts for > 24 hours or until symptoms recur. But if patients have particularly severe symptoms, small amounts of the food to be tested are eaten in the clinician’s presence, and the patient’s reactions observed.
Aggravation or recrudescence of symptoms after addition of a new food is the best evidence of allergy.
Допустимі продукти в репрезентативних елімінаційних дієтах*
Food | Diet No. 1 (No beef, pork, fowl, milk, rye, or corn) | Diet No. 2 (No beef, lamb, milk, or rice) | Diet No. 3 (No lamb, fowl, rye, rice, corn, or milk) |
|---|---|---|---|
Cereal | Rice products | Corn products | None |
Vegetables | Artichokes, beets, carrots, lettuce, spinach | Asparagus, corn, peas, squash, string beans, tomatoes | Beets, lima beans, potatoes (white and sweet), string beans, tomatoes |
Meats | Lamb | Bacon, chicken | Bacon, beef |
Flour (bread or biscuits) | Rice | Corn, 100% rye (ordinary rye bread contains wheat) | Lima bean, potato, soybean |
Fruits | Grapefruit, lemons, pears | Apricots, peaches, pineapple, prunes | Apricots, grapefruit, lemons, peaches |
Fat | Cottonseed oil, olive oil | Corn oil, cottonseed oil | Cottonseed oil, olive oil |
Beverages | Coffee (black), lemonade, tea | Coffee (black), lemonade, tea | Coffee (black), lemonade, juice from approved fruit, tea |
Miscellaneous | Cane sugar, gelatin, maple sugar, olives, salt, tapioca pudding | Cane sugar, corn syrup, gelatin, salt | Cane sugar, gelatin, maple sugar, olives, salt, tapioca pudding |
* Diet No. 4: If symptoms persist when patients are following any of the above 3 elimination diets and diet is still suspected, daily diet may be restricted to an elemental diet (using extensively hydrolyzed or amino acid–based formulas). | |||
Treatment of Food Allergy
Food elimination
Sometimes oral cromolyn
Sometimes corticosteroids for eosinophilic enteropathy
Oral or sublingual immunotherapy for desensitization
Monoclonal antibodies (omalizumab, dupilumab)
Treatment of food allergies consists of eliminating the food that triggers the allergic reaction. Thus, diagnosis and treatment overlap. When assessing an elimination diet’s effect, clinicians must consider that food sensitivities may disappear spontaneously.
Patients with severe food allergies should be advised to carry antihistamines to take immediately if a reaction starts and a prefilled, self-injecting syringe of epinephrine to use when needed for severe reactions. Antihistamines have little value except for acute reactions causing urticaria and angioedema.
Oral cromolyn appears to effectively lessen the allergic reaction to food.
Long-term corticosteroid treatment is useful for symptomatic eosinophilic enteropathy. Oral budesonide suspension has efficacy for treating eosinophilic esophagitis in adults and pediatric patients age 11 and older.
For patients with eosinophilic esophagitis, an elemental diet or an empiric, 6-food elimination diet may be used (1, 2).
Omalizumab may be used to help prevent severe IgE mediated allergic reactions to foods.
Імунотерапія та денсибілізація
Oral immunotherapy for desensitization to peanuts uses defatted peanut (Arachis hypogaea) allergen powder; it is available for treatment of people who are 4 to 17 years old and are allergic to peanuts. Oral desensitization involves escalating daily doses every 2 weeks over several months up to 300 mg. Desensitization can be carried out at home between escalations, which are carried out in a health care setting.
After patients successfully tolerate the 300-mg dose in a health care setting, they must take the 300-mg daily dose indefinitely to maintain desensitization. Also, they still need to maintain a strict peanut-free diet but benefit from a reduced risk of severe allergic reactions (including anaphylaxis) to inadvertently consumed peanut.
Oral desensitization protocols to various other foods are being investigated (3).
Sublingual immunotherapy for IgE-mediated food allergies involves placing drops of glycerinated allergen extracts under the tongue once a day. Allergens that have been studied include peanuts (mainly), hazelnuts, peaches, apples, and milk. Early results in phase II clinical trials have been promising although further studies are needed before such treatment is broadly recommended in practice (4).
Моноклональні антитіла
Omalizumab (a humanized recombinant monoclonal anti-IgE antibody) and other anti-IgE monoclonal antibodies have been used to treat people who have had severe anaphylactic reactions to food. In one study of children who had a peanut allergy, omalizumab resulted in a higher peanut tolerability threshold in children who took the medication (5).
Treatment using other monoclonal antibodies, such as dupilumab (an anti-IL4R antibody), is under study (6).
Довідкові матеріали щодо лікування
1. Hirano I, Chan ES, Rank MA, et al: AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis. Gastroenterology 158(6):1776–1786, 2020. doi:10.1053/j.gastro.2020.02.038
2. Kliewer KL, Gonsalves N, Dellon ES, et al: One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial. Lancet Gastroenterol Hepatol 8(5):408–421, 2023. doi:10.1016/S2468-1253(23)00012-2
3. Anderson B, Wong L, Adlou B, et al: Oral immunotherapy in children: Clinical considerations and practical management. J Asthma Allergy 14:1497–1510, 2021. doi: 10.2147/JAA.S282696 eCollection 2021
4. Schworer SA, Edwin H Kim EH: Sublingual immunotherapy for food allergy and its future directions. Immunotherapy 12 (12):921–931, 2020. doi: 10.2217/imt-2020-0123
5. Sampson HA, Leung DY, Burks AW, et al: A phase II, randomized, double‑blind, parallel‑group, placebo‑controlled oral food challenge trial of Xolair (omalizumab) in peanut allergy. J Allergy Clin Immunol 127 (5):1309–1310.e1, 2011. doi: 10.1016/j.jaci.2011.01.051
6. Sindher SB, Hillier C, Anderson B, Long A, Chinthrajah RS: Treatment of food allergy: Oral immunotherapy, biologics, and beyond. Ann Allergy Asthma Immunol 131(1):29–36, 2023. doi:10.1016/j.anai.2023.04.02
Prevention of Food Allergy
For many years, avoiding feeding young infants allergenic foods (eg, peanuts) has been recommended as a way to prevent food allergies. However, one study (1) showed that early introduction and regular consumption of food that contains peanuts can prevent peanut allergy in infants at high risk of developing this allergy (eg, infants with egg allergy or eczema). Thus, more clinicians are moving away from infant food restrictions based on allergy concerns and permitting or encouraging consumption of such foods. Current guidelines recommend not delaying the introduction of more foods—more than what is usually recommended for all infants—into the diet of infants, including high-risk infants. Thus, most recommendations are to introduce foods such as egg and peanuts at about age 4 to 6 months (2).
Довідкові матеріали щодо профілактики
1. Du Toit G, Roberts G, Sayre PH, et al: Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 372 (9):803–813, 2015. doi: 10.1056/NEJMoa1414850
2. Fleischer DM, Sicherer S, Greenhawt M, et al: Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants. Pediatr Dermatol 33 (1):103–106, 2016. doi: 10.1111/pde.12685
Ключові моменти
Food allergy is commonly mediated by IgE (typically resulting in acute systemic allergic reactions) or T cells (typically resulting in chronic gastrointestinal symptoms).
Distinguish food allergy from nonimmune reactions to food (eg, lactose intolerance, irritable bowel syndrome, infectious gastroenteritis) and reactions to additives (eg, monosodium glutamate, metabisulfite, tartrazine) or food contaminants.
If the diagnosis is not clinically obvious in adults or if children are being evaluated, do skin tests, an allergen-specific serum IgE test, or an elimination diet.
Make sure patients understand that in an elimination diet, they can eat only foods on the list and only pure foods (which excludes many commercially prepared foods).
Other treatments include cromolyn, immunotherapy for desensitization and monoclonal antibodies.
Додаткова інформація
The following English-language resource may be helpful. Please note that THE MANUAL is not responsible for the content of this resource.
National Institute of Allergy and Infectious Diseases (NIAID): Guidelines for the diagnosis and management of food allergy in the United States.
Sampson HA, Aceves S, Bock SA, et al. Food allergy: a practice parameter update-2014. J Allergy Clin Immunol 134(5):1016-25.e43, 2014. doi:10.1016/j.jaci.2014.05.013
