Food allergy

Food allergy symptoms occur within minutes to hours after exposure and may include: • Rash • Hives • Itching of mouth, lips, tongue, throat, eyes, skin, or other areas • Swelling (angioedema) of lips, tongue, eyelids, or the whole face • Difficulty swallowing • Runny or congested nose • Hoarse voice • Wheezing and/or shortness of breath • Diarrhea, abdominal pain, and/or stomach cramps • Lightheadedness • Fainting • Nausea • Vomiting Symptoms can vary. The amount of food needed to trigger a reaction also varies. A severe case of an allergic reaction, caused by symptoms affecting the respiratory tract and blood circulation, is called anaphylaxis. When symptoms are related to a drop in blood pressure, the person is said to be in anaphylactic shock. Anaphylaxis occurs when IgE antibodies are involved, and areas of the body that are not in direct contact with the food become affected and show symptoms. Those with asthma or an allergy to peanuts, tree nuts, or seafood are at greater risk for anaphylaxis. ==Causes==

Common food allergies The most common food allergies are those to milk, egg, peanuts, tree nuts, fish, shellfish, soy, and wheat, which are referred to as "the big eight", and are required by US law to be on labels of foods that contain those foods. In April 2021, President Biden signed the FASTER Act into law. This recognized sesame as the ninth US mandatory food label allergen. Peanuts, a member of the legume family, are one of the most common food allergens that induce reactions in both children and adults. Affecting about 2% of the Western population, peanut allergies tend to cause more severe reactions and anaphylaxis than other food allergies. Tree nuts, including almonds, brazil nuts, cashews, coconuts, hazelnuts, macadamia nuts, pecans, pistachios, pine nuts, and walnuts, are also common allergens. Affected individuals may be sensitive to one particular tree nut or many different ones. Peanuts and seeds, including sesame seeds and poppy seeds, can be processed to extract oils, but trace amounts of protein may also elicit an allergic reaction. Egg allergies affect about one in 50 children but are frequently outgrown when children reach age five. Affected individuals can be sensitive to proteins both in the egg white and egg yolk, but most children are allergic to those in the white while most adults are allergic to those in the yolk. Cow's milk is the most common food allergen in infants and young children, yet many adults are also sensitized to cow's milk. Many affected individuals cannot tolerate dairy products such as cheese and yogurt. A small portion of children with milk allergy, roughly 10%, have a reaction to beef because it contains small amounts of protein that are also present in cow's milk. People may be allergic to other types of seafood, such as fish. Fish allergies were found to be more common in countries that have high fish consumption compared to those with lower consumption. Other common food allergens include soy and wheat. Those allergic to wheat may be sensitized to any protein in the wheat kernel. To a lesser frequency, people may be mildly allergic to raw fruits and vegetables, a disease known as oral allergy syndrome. and chemical additives. Balsam of Peru, which is in various foods, is in the top five allergens most commonly causing patch test reactions in people referred to dermatology clinics. Routes of exposure Exposure to certain food proteins may trigger the production of antigen-specific immunoglobulin E (IgE) antibodies, which, if unaccompanied by allergic symptoms, is known as allergic sensitization. Oral ingestion is the main sensitization route for most food allergy cases, but other routes of exposure include inhalation and skin contact. Furthermore, peanut allergies are much more common in adults who had oozing and crusted skin rashes as infants, suggesting that impaired skin may be a risk factor for sensitization. An estimated 28.5 million people worldwide are engaged in the seafood industry, which includes fishing, aquaculture, processing and industrial cooking. In these occupational settings, individuals with fish and shellfish allergies are at high risk of exposure to allergenic proteins via aerosolization. Previous studies detected 40 allergens from wheat, some cross-reacted with rye proteins and a few cross-reacted with grass pollens. Allergic sensitization can occur via skin antigen exposure, which usually manifests as hives. The skin has been suggested to be a critical sensitization route for peanut-allergic individuals. Atopy Food allergies develop more easily in people with atopic syndrome, a very common combination of diseases: allergic rhinitis and conjunctivitis, eczema, and asthma. The syndrome has a strong inherited component; a family history of allergic diseases can be indicative of atopic syndrome. Cross-reactivity Some children who are allergic to cow's milk protein also show a cross-sensitivity to soy-based products. Some infant formulas have their milk and soy proteins hydrolyzed, so when taken by infants, their immune systems do not recognize the allergen and they can safely consume the product. Hypoallergenic infant formulas can be based on proteins partially predigested to a less antigenic form. Other formulas, based on free amino acids, are the least antigenic and provide complete nutritional support in severe forms of milk allergy. Crustaceans (shrimp, crab, lobster, etc.) and molluscs (mussel, oyster, scallop, squid, octopus, snail, etc.) are different invertebrate classes, but the allergenic protein tropomyosin is present and responsible for cross-reactivity. People with latex allergy often also develop allergies to bananas, kiwifruit, avocados, and some other foods. In some cases, allergic symptoms may occur upon first ingestion of a particular food due to IgE cross-reactivity: prior sensitization to structurally similar proteins from other sources leads the immune system to recognize homologous proteins in the newly consumed food as allergens. ==Pathophysiology==

Conditions caused by food allergies are classified into three groups according to the mechanism of the allergic response: • IgE-mediated (classic): the most common type, occurs shortly after eating and may involve anaphylaxis. • Non-IgE mediated: characterized by an immune response not involving immunoglobulin E; may occur some hours after eating, complicating diagnosis. • IgE and/or non-IgE-mediated: a hybrid of the above two types. Allergic reactions are abnormal immune responses to certain substances that are normally harmless. When immune cells encounter the allergenic protein, IgE antibodies are produced; this is similar to the immune system's reaction to foreign pathogens. The IgE antibodies identify the allergenic proteins as harmful and initiate the allergic reaction. The harmful proteins are those that do not break down due to the strong bonds of the protein. IgE antibodies bind to a receptor on the surface of the protein, creating a tag, just as a virus or parasite becomes tagged. Why some proteins do not denature and subsequently trigger allergic reactions and hypersensitivity while others do is not entirely clear. Hypersensitivities are categorized according to the parts of the immune system that are attacked and the amount of time it takes for the response to occur. The four types of hypersensitivity reaction are: type 1, immediate IgE-mediated; type 2, cytotoxic; type 3, immune complex-mediated; and type 4, delayed cell-mediated. The pathophysiology of allergic responses can be divided into two phases. The first is an acute response that occurs immediately after exposure to an allergen. This phase can either subside or progress into a "late-phase reaction" which can substantially prolong the symptoms of a response, and result in tissue damage. Many food allergies are caused by hypersensitivities to particular proteins in different foods. Proteins have unique properties that allow them to become allergens, such as stabilizing forces in their tertiary and quaternary structures which prevent degradation during digestion. Many theoretically allergenic proteins cannot survive the destructive environment of the digestive tract, thus do not trigger hypersensitive reactions. Acute response 6 — mast cell7 — newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF) In the early stages of allergy, a type I hypersensitivity reaction against an allergen, encountered for the first time, causes a response in a type of immune cell called a TH2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These TH2 cells interact with other lymphocytes called B cells, whose role is the production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of Fc receptor called FcεRI) on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage, are sensitized to the allergen. If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule and activates the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation, and smooth-muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, the allergen, and the mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems. Cytokines from mast cells may also play a role in the persistence of long-term effects. == Diagnosis ==

Diagnosis is usually based on a medical history, elimination diet, skin prick test, blood tests for food-specific IgE antibodies, or oral food challenge. • Blood testing is another way to test for allergies; however, it poses the same disadvantage and only detects IgE allergens and does not work for every possible allergen. Radioallergosorbent testing (RAST) is used to detect IgE antibodies present to a certain allergen. The score taken from the RAST is compared to predictive values, taken from a specific type of RAST. If the score is higher than the predictive values, a great chance the allergy is present in the person exists. One advantage of this test is that it can test many allergens at one time. Researchers have been able to determine "predictive values" for certain foods, which can be compared to the RAST results. If a person's RAST score is higher than the predictive value for that food, over a 95% chance exists that patients will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food. Currently, predictive values are available for milk, egg, peanut, fish, soy, and wheat. Blood tests allow for hundreds of allergens to be screened from a single sample, and cover food allergies as well as inhalants. However, non-IgE-mediated allergies cannot be detected by this method. Other widely promoted tests such as the antigen leukocyte cellular antibody test and the food allergy profile are considered unproven methods, the use of which is not advised. • Food challenges test for allergens other than those caused by IgE allergens. The allergen is given to the person in the form of a pill, so the person can ingest the allergen directly. The person is watched for signs and symptoms. Double-blind, placebo-controlled food challenges, are the gold standard for diagnosis of food allergies, including most non-IgE-mediated reactions, but they are rarely performed. They must be performed in the hospital under careful watch, due to the possibility of anaphylaxis. • Irritable bowel syndrome • C1 Esterase inhibitor deficiency (hereditary angioedema), a rare disease, generally causes attacks of angioedema, but can present solely with abdominal pain and occasional diarrhea, and thus may be confused with allergy-triggered angioedema. == Prevention ==

Breastfeeding for more than four months may prevent atopic dermatitis, cow's milk allergy, and wheezing in early childhood. Early exposure to potential allergens may be protective. The former guidelines, advising delaying the introduction of peanuts, are now thought to have contributed to the increase in peanut allergy seen recently. To avoid an allergic reaction, a strict diet can be followed. It is difficult to determine the amount of allergenic food required to elicit a reaction, so complete avoidance should be attempted. In some cases, hypersensitive reactions can be triggered by exposures to allergens through skin contact, inhalation, kissing, participation in sports, blood transfusions, cosmetics, and alcohol. Inhalation exposure Allergic reactions to airborne particles or vapors of known food allergens have been reported as an occupational consequence of people working in the food industry, but can also take place in home situations, restaurants, or confined spaces such as airplanes. According to two reviews, respiratory symptoms are common, but in some cases there has been progression to anaphylaxis. The most frequent reported cases of reactions by inhalation of allergenic foods were due to peanut, seafood, legumes, tree nut, and cow's milk. One review mentioned case study examples of allergic responses to inhalation of other foods, including examples in which oral consumption of the food is tolerated. == Treatment ==

The mainstay of treatment for food allergy is total avoidance of the foods identified as allergens. An allergen can enter the body by consuming a portion of food containing the allergen, and can also be ingested by touching any surfaces that may have come into contact with the allergen, then touching the eyes or nose. For people who are extremely sensitive, avoidance includes avoiding touching or inhaling problematic food. Total avoidance is complicated because the declaration of the presence of trace amounts of allergens in foods is not mandatory (see regulation of labelling). If the food is accidentally ingested and a systemic reaction (anaphylaxis) occurs, then epinephrine should be used. A second dose of epinephrine may be required for severe reactions. The person should then be transported to the emergency room, where additional treatment can be given. Other treatments include antihistamines and steroids. Epinephrine Epinephrine (adrenaline) is the first-line treatment for severe allergic reactions (anaphylaxis). If administered in a timely manner, epinephrine can reverse its effects. Epinephrine relieves airway swelling and obstruction, and improves blood circulation; blood vessels are tightened and heart rate is increased, improving circulation to body organs. Epinephrine is available by prescription in an autoinjector. Omalizumab Omalizumab, an injectable asthma treatment drug sold under the brand name Xolair, was approved in the United States in February 2024 to reduce severe reactions to accidental exposure to food allergens. It is a genetically engineered monoclonal antibody which specifically binds to immunoglobulin E (IgE) to reduce the severity of an immune response. Successful results were reported for wheat, eggs, milk and baked products containing wheat and milk. ==Epidemiology==

Food allergies affect up to 10% of the worldwide population, and they are currently more prevalent in children (~8%) than adults (~5) in western nations. Children are most commonly allergic to cow's milk, chicken eggs, peanuts, and tree nuts. An estimated 15 million people currently have food allergies in the United States. In 1997, 0.4% children in the United States were reported to have peanut allergy, yet this number markedly rose to 1.4% in 2008. In Australia, hospital admission rates for food-induced anaphylaxis increased by an average of 13.2% from 1994–2005. Also, shellfish allergy is the most common cause of anaphylaxis in adults and adolescents particularly in East Asian countries like Hong Kong, Taiwan, Singapore, and Thailand. Another example is that, out of nine European countries, egg allergy was found to be most prevalent in the UK and least prevalent in Greece. Special population: children About 75% of children who have allergies to milk protein are able to tolerate baked-in milk products, i.e., muffins, cookies, cake, and hydrolyzed formulas. About 50% of children with allergies to milk, egg, soy, peanuts, tree nuts, and wheat will outgrow their allergy by the age of 6. Those who are still allergic by the age of 12 or so have less than an 8% chance of outgrowing the allergy. United States In the United States, food allergy affects as many as 5% of infants less than three years of age and 3% to 4% of adults. The prevalence of food allergies is rising. Food allergies cause roughly 30,000 emergency room visits and 150 deaths per year. ==Regulation==

Whether rates of food allergy are increasing or not, food allergy awareness has definitely increased, with impacts on the quality of life for children, their parents and their caregivers. In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 causes people to be reminded of allergy problems every time they handle a food package, and restaurants have added allergen warnings to menus. The Culinary Institute of America, a premier school for chef training, has courses in allergen-free cooking and a separate teaching kitchen. School systems have protocols about what foods can be brought into the school. Despite all these precautions, people with serious allergies are aware that accidental exposure can easily occur at other peoples' houses, at school or in restaurants. Regulation of labelling In response to the risk that certain foods pose to those with food allergies, some countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain priority allergens or byproducts of major allergens among the ingredients intentionally added to foods. The priority allergens vary by country. There are no labeling laws mandating declaration of the presence of trace amounts in the final product as a consequence of cross-contamination, except in Brazil. The European Union requires listing for those eight major allergens plus molluscs, celery, mustard, lupin, sesame and sulfites. A decision was reached in November 2020 that food manufacturers voluntarily declare that when powdered sesame seeds are used as a previously unspecified spice or flavor, the label be changed to "spice (sesame)" or "flavor (sesame)." Congress and the President passed a law in April 2021, the "FASTER Act", stipulating that labeling be mandatory, to be effect January 1, 2023, making it the ninth required food ingredient label. The Food Allergen Labeling and Consumer Protection Act of 2004 applies to packaged foods regulated by the FDA, which does not include poultry, most meats, certain egg products, and most alcoholic beverages. The EU Food Information for Consumers Regulation 1169/2011 – requires food businesses to provide allergy information on food sold unpackaged, for example, in catering outlets, deli counters, bakeries and sandwich bars. In the United States, there is no federal mandate to address the presence of allergens in drug products, medicines, or cosmetics. Trace amounts as a result of cross-contamination The value of allergen labeling other than for intentional ingredients is controversial. This concerns labeling for ingredients present unintentionally as a consequence of cross-contact or cross-contamination at any point along the food chain (during raw material transportation, storage or handling, due to shared equipment for processing and packaging, etc.). Experts in this field propose that if allergen labeling is to be useful to consumers, and healthcare professionals who advise and treat those consumers, ideally there should be agreement on which foods require labeling, threshold quantities below which labeling may be of no purpose, and validation of allergen detection methods to test and potentially recall foods that were deliberately or inadvertently contaminated. Labeling regulations have been modified to provide for mandatory labeling of ingredients plus voluntary labeling, termed precautionary allergen labeling, also known as "may contain" statements, for possible, inadvertent, trace amount, cross-contamination during production. Precautionary allergen labeling can be confusing to consumers, especially as there can be many variations on the wording of the warning. Precautionary allergen labeling is optional in the United States. , precautionary allergen labeling is regulated only in Switzerland, Japan, Argentina, and South Africa. Argentina decided to prohibit precautionary allergen labeling since 2010 and instead puts the onus on the manufacturer to control the manufacturing process and label only those allergenic ingredients known to be in the products. South Africa does not permit the use of precautionary allergen labeling, except when manufacturers demonstrate the potential presence of allergen due to cross-contact through a documented risk assessment and despite adherence to good manufacturing practice. VITAL 2.0 was developed by the Allergen Bureau, a food industry sponsored, non-government organization. The European Union has initiated a process to create labeling regulations for unintentional contamination but is not expected to publish such before 2024. In Brazil, since April 2016, the declaration of the possibility of cross-contamination is mandatory when the product does not intentionally add any allergenic food or its derivatives, but the good manufacturing practices and allergen control measures adopted are not sufficient to prevent the presence of accidental trace amounts. These allergens include wheat, rye, barley, oats and their hybrids, crustaceans, eggs, fish, peanuts, soybean, milk of all species of mammalians, almonds, hazelnuts, cashew nuts, Brazil nuts, macadamia nuts, walnuts, pecan nuts, pistachios, pine nuts, and chestnuts. and a 2016 U.S. National Academy of Sciences report concluded that there is no relationship between consumption of genetically modified foods and the increase in prevalence of food allergies. One concern is that genetic engineering could make an allergy-provoking food more allergic, meaning that smaller portions would suffice to set off a reaction. There are requirements in some countries and recommendations in others that all foods containing genetically modified ingredients be so labeled, and that there be a post-launch monitoring system to report adverse effects (similar to the requirements in some countries for drug and dietary supplement reporting). Diagnosing issues There exists both over-reporting and under-reporting of the prevalence of food allergies. Self-diagnosed perceptions of food allergy are greater than the rates of true food allergy because people confuse non-allergic intolerance with allergy, and also attribute non-allergy symptoms to an allergic response. Conversely, healthcare professionals treating allergic reactions on an out-patient or even hospitalized basis may not report all cases. Recent increases in reported cases may reflect a real change in incidence or an increased awareness on the part of healthcare professionals. ==Social impact==

Food fear has a significant impact on quality of life. The social impacts of food allergies can carry over into adulthood. ==Portrayal in media==

Media portrayals of food allergy in television and film are not accurate, often used for comedic effect or underplaying the potential severity of an allergic reaction. These tropes misinform the public and cause harm by minimizing the damage that allergies can cause. Some examples of the several different types of tropes are: • Characters who have food allergies which provides a weakness that can be used to sabotage them. In the movie Parasite a housekeeper is displaced by taking advantage of her peach allergy. • Food allergy is used for comedic effect, such as in the movies Hitch and in television, Kelso's egg allergy in ''That '70s Show.'' • Food allergies may be incorporated into characters who are also portrayed as annoying, weak and oversensitive, which can be taken as implying that their allergies are either not real or not potentially severe. For example Howard, in an episode of The Big Bang Theory, deliberately consumes a peanut-containing food bar, causing a serious reaction, just to delay another character from arriving at a surprise birthday party too early. • Any of these portrayals may underplay the potential severity of a food allergy, some showing that Benadryl or an EpiPen is sufficient. Viewing of humorous portrayals of food allergies has been shown to have a negative effect on related health policy support due to low perceived seriousness. ==Research==

Several theories have been suggested to explain why certain individuals develop allergic sensitization instead of oral tolerance to food allergens. One such theory is the dual allergen hypothesis, which states that ingesting food allergens early on promotes oral tolerance while skin exposure leads to sensitization. A number of desensitization techniques are being studied. Areas of research include specific oral tolerance induction (also known as oral immunotherapy), and sublingual immunotherapy. The benefits of allergen immunotherapy for food allergies is unclear, thus is not recommended . but the effects were not all sustained past 12 months. For infants, supplementing their diet with oils high in polyunsaturated fatty acids did not affect the risks of food allergies, eczema or asthma either as infants or into childhood. There is research on probiotics, prebiotics and the combination of the two (synbiotics) as a means of treating or preventing infant and child allergies. From reviews, there appears to be a treatment benefit for eczema, but not asthma, wheezing or rhinoconjunctivitis. The evidence was not consistent for preventing food allergies and this approach cannot yet be recommended. The Food Standards Agency, in the United Kingdom, are in charge of funding research into food allergies and intolerance. Since their founding in 1994 they have funded over 45 studies. In 2005 Europe created EuroPrevall, a multi-country project dedicated to research involving allergies. == See also ==