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Food allergy

Food allergy
Classification and external resources
ICD-10 T78.0
ICD-9 V15.01-V15.05
OMIM 147050
MedlinePlus 000817
eMedicine med/806
MeSH D005512

A food allergy is an adverse immune response to a food protein.[1][2] They are distinct from other adverse responses to food, such as food intolerance, pharmacological reactions, and toxin-mediated reactions.

A protein in the food is the most common allergic component. These kinds of allergies occur when the body's immune system mistakenly identifies a protein as harmful. Some proteins or fragments of proteins are resistant to digestion and those that are not broken down in the digestive process are tagged by the Immunoglobulin E (IgE). These tags fool the immune system into thinking that the protein is harmful. The immune system, thinking the organism (the individual) is under attack, triggers an allergic reaction. These reactions can range from mild to severe. Allergic responses include dermatitis, gastrointestinal and respiratory distress, including such life-threatening anaphylaxic responses as biphasic anaphylaxis and vasodilation; these require immediate emergency intervention. Non-food protein allergies include latex sensitivity. Individuals with protein allergies commonly avoid contact with the problematic protein. Some medications may prevent, minimize or treat protein allergy reactions.

Treatment consists of either immunotherapy (desensitisation) or avoidance, in which the allergic person avoids all forms of contact with the food to which they are allergic. Areas of research include anti-IgE antibody (omalizumab, or Xolair) and specific oral tolerance induction (SOTI), which have shown some promise for treatment of certain food allergies. People diagnosed with a food allergy may carry an injectable form of epinephrine such as an EpiPen or Twinject, wear some form of medical alert jewelry, or develop an emergency action plan, in accordance with their doctor.


[edit] Classification

Food allergy is thought to develop more easily in patients with the atopic syndrome, a very common combination of diseases: allergic rhinitis and conjunctivitis, eczema and asthma.[3] The syndrome has a strong inherited component; a family history of allergic diseases can be indicative of the atopic syndrome.

Conditions caused by food allergies are classified into 3 groups according to the mechanism of the allergic response:

1. IgE-mediated (classic):

2. IgE and/or non-IgE-mediated:

3. Non-IgE mediated:

  • Food protein-induced Enterocolitis syndrome (FPIES)
  • Food protein proctocolitis/proctitis
  • Food protein-induced enteropathy. An important example is Celiac disease, which is an adverse immune response to the protein gluten.
  • Milk-soy protein intolerance (MSPI) is a non-medical term used to describe a non-IgE mediated allergic response to milk and/or soy protein during infancy and early childhood. Symptoms of MSPI are usually attributable to food protein proctocolitis or FPIES.
  • Heiner syndrome - lung disease due to formation of milk protein/IgG antibody immune complexes (milk precipitins) in the blood stream after it is absorbed from the GI tract. The lung disease commonly causes bleeding into the lungs and results in pulmonary hemosiderosis.
food allergy pharmacologic toxins intolerance
adverse immune response to a food protein caffeine tremors, cheese/wine (tyramine) migraine, scombroid (histamine) fish poisoning bacterial food poisoning, staphylotoxin lactose intolerance (lactase deficiency)

The reaction may progress to anaphylactic shock: A systemic reaction involving several different bodily systems including hypotension (low blood pressure),loss of consciousness, and possibly death. Allergens most frequently associated with this type of reaction are peanuts, nuts, milk, egg, and seafood, though many food allergens have been reported as triggers for anaphylaxis.

[edit] Signs and symptoms

Classic immunoglobulin-E (IgE)-mediated food allergies are classified as type-I immediate Hypersensitivity reaction. These allergic reactions have an acute onset (from seconds to one hour) and may include:[4]

Symptoms of allergies vary from person to person. The amount of food needed to trigger a reaction also varies from person to person. Symptoms vary depending on the severity of the allergy, and they can appear in as little as a few minutes or may take up to an hour. Symptoms affect the skin, gastrointestinal tract, and in severe cases, the respiratory tract and blood circulation.

[edit] Dermal

A common skin symptom is hives. Hives appear as red, itchy bumps. Edema, another common symptom, is the swelling of the skin. Swelling of the eyes and swelling of the lips are also common during an allergic reaction. A less severe symptom is eczema, a dry and bumpy rash, also known as atopic dermatitis. Eczema is a type of skin rash that is inherited and triggered by an irritant, mainly food allergies.

Hives on the back are a common symptom caused from allergic reactions.

[edit] Gastrointestinal

These symptoms include: itchy mouth with bumps, stomachache, nausea, vomiting, diarrhea, bloody stool in infants and children, and a taste of metal that lingers in the mouth.

[edit] Cardiopulmonary

Serious danger regarding allergies can begin when the respiratory tract or blood circulation is infected. Less serious symptoms are runny nose, coughing, and constant clearing of the throat. These are signs that more serious symptoms may be seen. These serious symptoms are closing of the windpipe, which leads to trouble swallowing and problems breathing. These can be indicated through wheezing and a blue coloring of the lips and skin. Poor blood circulation leads to a weak pulse, pale skin, and fainting.[5]

A severe case of an allergic reaction, caused by symptoms affecting the respiratory tract and blood circulation, is called anaphylaxis. When symptoms are shown where breathing is impaired and circulation is affected, 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 infected and show symptoms.[6] This occurs because no nutrients are circulated throughout the body, causing the widening of blood vessels. The blood vessels widen, and blood pressure decreases, which leads to the loss of consciousness. Those with asthma or an allergy to peanuts, tree nuts, or seafood are at greater risk for anaphylaxis.[7]

[edit] Cause

One of the most common food allergies is a sensitivity to peanuts, a member of the bean family. Peanut allergies may be severe, but children with peanut allergies sometimes outgrow them.[8] Tree nuts, including pecans, pistachios, pine nuts, and walnuts, are also common allergens. Sufferers may be sensitive to one, or many, tree nuts.[9] Also seeds, including sesame seeds and poppy seeds, contain oils where protein is present, which may elicit an allergic reaction.[9]

Egg allergies affect about one in fifty children but are frequently outgrown by children when they reach age five.[10] Typically the sensitivity is to proteins in the yolk, rather than the white.[9]

Milk, from cows, goats or sheep, is another common allergy causing food, and many sufferers are also unable to tolerate dairy products such as cheese. A very small portion of children with a milk allergy, roughly ten percent, will have a reaction to beef. Beef contains a small amount of protein that is present in cow's milk.[11]

Other foods containing allergenic proteins include soy, wheat, fish, shellfish, fruits, vegetables, spices, synthetic and natural colors, and chemical additives.

Although sensitivity levels vary by country, the most common food allergies are allergies to milk, eggs, peanuts, tree nuts, seafood, shellfish, soy and wheat.[12][clarification needed] These are often referred to as "the big eight."[13] They account for over 90% of the food allergies in the United States.[14] Allergies to seeds - especially sesame - seem to be increasing in many countries.[15] An example of allergies more common to a particular region is the surplus rice allergies in East Asia where rice forms a large part of the diet.[16]

[edit] Cross reactivity

Some children who are allergic to cow's milk protein also show a cross sensitivity to soy-based products.[17] There are infant formulas in which the milk and soy proteins are degraded so when taken by an infant, their immune system does not recognize the allergen and they can safely consume the product. Hypoallergenic infant formulas can be based on hydrolyzed proteins, which are proteins partially predigested in a less antigenic form. Other formulas, based on free amino acids, are the least antigenic and provide complete nutrition support in severe forms of milk allergy.

People with latex allergy often also develop allergies to bananas, kiwi, avocados, and some other foods.[18]

[edit] Pathophysiology

A histamine, the structure shown, is what causes a person to feel itchy during an allergic reaction. A common medication to stop this is an antihistamine, which fights the histamines in the person's system.

Allergic reactions are hyperactive responses of the immune system to generally innocuous substances. 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 on the surface of the protein, creating a tag, just as a virus or parasite becomes tagged. It is not entirely clear why some proteins do not denature and subsequently trigger allergic reactions and hypersensitivity while others do not.[19]

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. There are four types of Hypersensitivity reaction: Type 1, Immediate IgE-mediated, Type 2, Cytotoxic, Type 3, Immune complex-mediated, and Type 4, Delayed cell-mediated.[20] 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 the tertiary and quaternary structure which prevent degradation during digestion. Many theoretically allergenic proteins cannot survive the destructive environment of the digestive tract and thus don't trigger hypersensitive reactions.[21]

[edit] Acute response

Degranulation process in allergy.1 - antigen; 2 - IgE antibody; 3 - FcîµRI receptor; 4 - preformed mediators (histamine, proteases, chemokines, heparine); 5 - granules; 6 - mast cell; 7 - 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 ofFc receptor called FcîµRI) 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.[22]

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; asthma is localized to the respiratory system and eczema is localized to the dermis.[22]

[edit] Late-phase response

After the chemical mediators of the acute response subside, late phase responses can often occur. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils, and macrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction.[23] Cytokines from mast cells may also play a role in the persistence of long-term effects. Late phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils, and are still dependent on activity of TH2 cells.[24]

[edit] Protein structure and organization

Proteins are composed of amino acid monomers linked by peptide bonds.[25] The higher order structure of a protein depends on the sequence of amino acids which form its primary sequence, as various non-covalent interactions between these amino acids ensure proper protein folding. Proteins have specific amino acid sequences, which all identical proteins share.[26]

A protein's secondary structure is created by hydrogen-bond interactions between the amide and carboxyl groups of the amino acid backbone. Secondary structure includes the formation of alpha helices and beta sheets.[25] The tertiary structure is the overall shape of the protein, and is usually driven by the protein's tendency to orient hydrophobic amino acid side chains internally, although hydrogen bonding, ionic interactions and disulfide bonds also help to stabilize proteins in the tertiary state [27] Quaternary structure is the overall combination of polypeptide subunits to form the functional unit.

[edit] Protein function

Protein folding is essential to the overall function of the individual protein; some protein structures allow them to resist degradation in the acidic environment of the digestive tract.Polypeptide chains are often very long and flexible, which leads to a wide variety of ways for a protein to fold. Non-covalent interactions control the shape and structure of the nascent protein. A protein's proper amino acid sequence is absolutely required to induce proper folding into the quaternary structure. Two common folding patterns seen in proteins are the alpha helix and beta sheets.

[edit] Diagnosis

There are three common types of allergy testing: skin prick test, blood test, and food challenges. An allergist can perform these tests, and they can also go into further depth depending on the results.

Skin testing on arm is a common way for detecting an allergy, however, it is not as effective as other tests.
  • For skin prick tests, a tiny board with protruding needles is used. The allergens are placed either on the board or directly on the skin. The board is then placed on the skin, in order to puncture the skin and for the allergens to enter the body. If a hive appears, the person will be considered positive for the allergy. This test only works for IgE antibodies. Allergic reactions caused by other antibodies cannot be detected through skin prick tests.[28]
  • 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. RAST, RadioAllergoSorbent Test, is used to detect IgE antibodies present to a certain allergen. The score taken from the RAST test is compared to predictive values, taken from a specific type of RAST test. If the score is higher than the predictive values, there is a great chance the allergy is present in the person. One advantage of this test is that it can test many allergens at one time.[29]
  • 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. The problem with food challenges is that they must be performed in the hospital under careful watch, due to the possibility of anaphylaxis.[30]

The best method for diagnosing food allergy is to be assessed by an allergist. The allergist will review the patient's history and the symptoms or reactions that have been noted after food ingestion. If the allergist feels the symptoms or reactions are consistent with food allergy, he/she will perform allergy tests.

Examples of allergy testing include:

  • Skin prick testing is easy to do and results are available in minutes. Different allergists may use different devices for skin prick testing. Some use a "bifurcated needle", which looks like a fork with 2 prongs. Others use a "multi-test", which may look like a small board with several pins sticking out of it. In these tests, a tiny amount of the suspected allergen is put onto the skin or into a testing device, and the device is placed on the skin to prick, or break through, the top layer of skin. This puts a small amount of the allergen under the skin. A hive will form at any spot where the person is allergic. This test generally yields a positive or negative result. It is good for quickly learning if a person is allergic to a particular food or not, because it detects allergic antibodies known as IgE. Skin tests cannot predict if a reaction would occur or what kind of reaction might occur if a person ingests that particular allergen. They can however confirm an allergy in light of a patient's history of reactions to a particular food. Non-IgE mediated allergies cannot be detected by this method.
  • Blood tests are another useful diagnostic tool for evaluating IgE-mediated food allergies. For example, the RAST (RadioAllergoSorbent Test) detects the presence of IgE antibodies to a particular allergen. A CAP-RAST test is a specific type of RAST test with greater specificity: it can show the amount of IgE present to each allergen.[31] Researchers have been able to determine "predictive values" for certain foods. These predictive values can be compared to the RAST blood test results. If a persons RAST score is higher than the predictive value for that food, then there is over a 95% chance the person will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food.[citation needed] Currently, predictive values are available for the following foods: milk, egg, peanut, fish, soy, and wheat.[32][33][34] 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 (ALCAT) and the Food Allergy Profile are considered unproven methods, the use of which is not advised.[35]
  • Food challenges, especially double-blind placebo-controlled food challenges (DBPCFC), are the gold standard for diagnosis of food allergies, including most non-IgE mediated reactions. Blind food challenges involve packaging the suspected allergen into a capsule, giving it to the patient, and observing the patient for signs or symptoms of an allergic reaction. Due to the risk of anaphylaxis, food challenges are usually conducted in a hospital environment in the presence of a doctor.
  • Additional diagnostic tools for evaluation of eosinophilic or non-IgE mediated reactions include endoscopy, colonoscopy, and biopsy.

[edit] Differential diagnosis

Important differential diagnoses are:

[edit] Prevention

According to a report issued by the American Academy of Pediatrics, "There is evidence that breastfeeding for at least 4 months, compared with feeding infants formula made with intact cow milk protein, prevents or delays the occurrence of atopic dermatitis, cow milk allergy, and wheezing in early childhood."[36] There is also a study going on in which they are introducing peanuts to low-allergenic patients, and they gradually give amounts to the patient to try to make their body immune to reactions from the peanuts. Only patients with low RAST on peanuts should be enrolled. Anything above 0.35 on a RAST test is positive.

In order 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 unless otherwise suggested by a qualified medical professional. In some cases, hypersensitive reactions can be triggered by exposures to allergens though skin contact, inhalation, kissing, participation in sports, blood transfusions, cosmetics, and alcohol.[37]

When avoiding certain foods in order to lessen the risk of reaction, it can be hard to maintain the proper amounts of nutrients. Some allergens are also common sources of vitamins and minerals, as well as macronutrients such as fat and protein; healthcare providers will often suggest alternate food sources of essential vitamins and minerals which are less allergenic.

[edit] Treatment

The mainstay of treatment for food allergy is avoidance of the foods that have been identified as allergens. For people who are extremely sensitive, this may involve the total avoidance of any exposure with the allergen, including touching or inhaling the problematic food as well as touching any surfaces that may have come into contact with it.

If the food is accidentally ingested and a systemic reaction (anaphylaxis) occurs, then epinephrine should be used. It is possible that a second dose of epinephrine may be required for severe reactions.[citation needed]

There are treatments for an allergic reaction. Among the first time the reaction occurs, it is most beneficial to take the person to the emergency room, where proper action may be taken. Other treatments include: epinephrine, antihistamines, and steroids.

[edit] Epinephrine

EpiPens are portable epinephrine-dispensing devices which can be used to alleviate the symptoms of severe, acute allergies.

Epinephrine, also known as adrenaline, is a common medication used to treat allergic reactions. Epinephrine reverses the allergic reaction by improving blood circulation. This is done by tightening blood vessels in order to increase the heart beat and circulation to bodily organs. Epinephrine is produced naturally in the body. It is produced during "flight-or-fight" response. When a person is presented with a dangerous situation, the adrenal gland is triggered to release adrenaline; this gives the person an increased heart rate and more energy to try to fight off the danger being imposed on the individual. Epinephrine is also prescribed by a physician in a form that is self-injectable. This is what is called an epi-pen.[38]

[edit] Antihistamines

Antihistamines are also used to treat allergic reactions. Antihistamines block the action of histamine, which causes blood vessels to dilate and become leaky to plasma proteins. Histamine also causes itchiness by acting on sensory nerve terminals. The most common antihistamine given for food allergies is diphenhydramine, also known as Benedryl. Antihistamines relieve symptoms. When it comes to dealing with anaphylaxis, however, they do not completely improve the dangerous symptoms that affect breathing.[39]

[edit] Steroids

Steroids are used to calm down the immune system cells that are attacked by the chemicals released during an allergic reaction. This form of treatment in the form of a nasal spray should not be used to treat anaphylaxis, for it only relieves symptoms in the area in which the steroid is in contact. Another reason steroids should not be used to treat anaphylaxis is due to the long amount of time it takes to reduce inflammation and start to work. Steroids can also be taken orally or through injection. By taking a steroid in these manners, every part of the body can be reached and treated, but a long time is usually needed for these to take effect.[40]

[edit] Desensitisation

Desensitisation may be a cure for food allergies.[41] If the major precipitating allergen is a pollen then this is targeted by current protocols for desensitisation, not the food analogue allergen. Injections are used, as sublingual drops are not suitable for sufferers of oral allergy.

Prof. Dr. Ronald van Ree of The University of Amsterdam and The Academic Medical Center expects that vaccines can in theory be created using genetic engineering to cure allergies. If this can be done, food allergies could be eradicated in about ten years.[42]

[edit] Epidemiology

In the United States, it is estimated that up to twelve million people have food allergies.[43] The most common food allergens include peanuts, milk, eggs, tree nuts, fish, shellfish, soy, and wheat - these foods account for about 90% of all allergic reactions. [44] The most common food allergies in adults are shellfish, peanuts, tree nuts, fish, and egg.[45] The most common food allergies in children are milk, eggs, peanuts, and tree nuts.[45]

Six to eight percent of children under the age of three have food allergies and nearly four percent of adults have food allergies.[45] Food allergies cause roughly 30,000 emergency room visits and 100 to 200 deaths per year in the United States.[46] The prevalence is rising.[47]

For reasons that are not entirely understood, the diagnosis of food allergies has apparently become more common in Western nations in recent times.[47] In the United States food allergy affects as many as 5% of infants less than three years of age[48] and 3% to 4% of adults.[49] There is a similar prevalence in Canada.[50]

Seventy-five percent of children who have allergies to milk protein are able to tolerate baked-in milk products, i.e., muffins, cookies, cake.[citation needed]

About 50% of children with allergies to milk, egg, soy, and wheat will outgrow their allergy by the age of 6. Those that don't, and those that are still allergic by the age of 12 or so, have less than an 8% chance of outgrowing the allergy.[51]

Peanut and tree nut allergies are less likely to be outgrown, although evidence now shows[52] that about 20% of those with peanut allergies and 9% of those with tree nut allergies.[53]

In Central Europe, celery allergy is more common. In Japan, allergy to buckwheat flour, used for Soba noodles, is more common.[citation needed]

Red meat allergy is extremely rare in the general population, but a geographic cluster of people allergic to red meat has been observed in Sydney, Australia.[54] There appears to be a possible association between localised reaction to tick bite and the development of red meat allergy.

Fruit allergies exist, such as to apples, peaches, pears, jackfruit, strawberries, etc.[citation needed]

Corn allergy may also be prevalent in many populations, although it may be difficult to recognize in areas such as the United States and Canada where corn derivatives are common in the food supply.[55]

Protein allergies are a common intolerance, especially among children, that are caused by seeds, nuts, meat, and milk.[56][clarification needed]

[edit] Society and culture

In response to the risk that certain foods pose to those with food allergies, countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain major allergens or by-products of major allergens.

[edit] United States law

Under the Food Allergen Labeling and Consumer Protection Act of 2004 (Public Law 108-282), companies are required to disclose on the label whether the product contains a major food allergen in clear, plain language. The allergens have to clearly be called out in the ingredient statement. Most companies list allergens in a statement separate from the ingredient statement.[57]

In 2009, Governor Deval Patrick signed into Massachusetts law an Act Relative to Food Allergy Awareness in Restaurants. The allergy awareness act requires food protection managers to view a video about food allergens, a poster identifying the 8 most common food allergens and information about identifying and responding to food allergies posted for food service staff, and customers must be notified of their obligation to inform staff about any food allergies.[58]

[edit] See also

[edit] References

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  2. ^ "Allergy Glossary of Terms". Revolution Health. http://www.revolutionhealth.com/conditions/asthma-allergies/hay-fever-seasonal-allergies/introduction/allergy-glossary. 
  3. ^ "Other atopic dermatitis and related conditions". ICD9. http://www.icd9data.com/2007/Volume1/680-709/690-698/691/691.8.htm. 
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  6. ^ Sicherer 12
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  9. ^ a b c Sicherer 63
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  27. ^ Freeman 54
  28. ^ Sicherer 185
  29. ^ Sicherer 187-88
  30. ^ Sicherer 189
  31. ^ "What is a RAST test ? What is a CAP-RAST test?". kidswithfoodallergies.org. http://www.kidswithfoodallergies.org/resourcespre.php?id=48&title=What%20is%20a%20RAST%20test%20?%20%20What%20is%20a%20CAP-RAST%20test?. 
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