Food allergies

A food allergy is an adverse immune response to a food protein. Food allergy is distinct from other adverse responses to food, such as food intolerance, pharmacologic reactions, and toxin-mediated reactions. The food protein triggering the allergic response is termed a food allergen. It is estimated that up to 12 million Americans have food allergies, and the prevalence is rising. Six to eight percent of children under the age of three have food allergies and nearly four percent of adults have them. Food allergy causes roughly 30,000 emergency room visits and 100 to 200 deaths per year in the United States. The most common food allergies in adults are shellfish, peanuts, tree nuts, fish, and eggs, and the most common food allergies in children are milk, eggs, peanuts, and tree nuts.

Treatment consists of avoidance diets, in which the allergic person avoids all forms of the food to which they are allergic. 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. 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. Persons diagnosed with a food allergy may carry an autoinjector 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.

Signs and symptoms
Classic immunoglobulin-E (IgE)-mediated food allergies are classified as type-I immediate hypersensitivity reactions. These allergic reactions have an acute onset (from seconds to one hour) and may include:
 * Angioedema: soft tissue swelling, usually involving the eyelids, face, lips, and tongue. Angioedema may result in severe swelling of the tongue as well as the larynx (voice box) and trachea, resulting in upper airway obstruction and difficulty breathing.
 * Hives
 * Itching of the mouth, throat, eyes, skin
 * Nausea, vomiting, diarrhea, stomach cramps, and/or abdominal pain. This group of symptoms is termed gastrointestinal hypersensitivity or anaphylaxis.
 * Rhinorrhea, nasal congestion
 * Wheezing, scratchy throat, shortness of breath, or difficulty swallowing
 * Anaphylaxis: a severe, whole-body allergic reaction that can result in death (see below)

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.

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. 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):
 * Type-I immediate hypersensitivity reaction (symptoms described above)
 * Oral allergy syndrome

2. IgE and/or non-IgE-mediated:
 * Allergic eosinophilic esophagitis
 * Allergic eosinophilic gastritis
 * Allergic eosinophilic gastroenteritis

3. Non-IgE mediated:
 * Food protein-induced Enterocolitis syndrome (FPIES)
 * Food protein proctocolitis/proctitis
 * Food protein-induced enteropathy. An important example is Coeliac 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.

The Big Eight
The most common food allergies are:
 * Dairy allergy
 * Egg allergy
 * Peanut allergy
 * Tree nut allergy
 * Seafood allergy
 * Shellfish allergy
 * Soy allergy
 * Wheat allergy

These are often referred to as "the big eight." They account for over 90% of the food allergies in the United States.

The top allergens vary somewhat from country to country but milk, eggs, peanuts, treenuts, fish, shellfish, soy, wheat and sesame tend to be in the top 10 in many countries. Allergies to seeds - especially sesame - seem to be increasing in many countries.

More Rare Food Allergies
Likelihood of allergy can increase with exposure. For example, rice allergy is more common in East Asia where rice forms a large part of the diet.

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

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. There appears to be a possible association between localised reaction to tick bite and the development of red meat allergy.

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.

Diagnosis
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. 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. Currently, predictive values are available for the following foods: 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.


 * Blood testing methodologies currently available that can measure antibodies of IgG are not acceptable as a method of allergy evaluation. IgG-type anitbodies are not implicated in a food allergy reactions [reference does not support claim ]. The significance of IgG anti-allergen antibodies was reviewed by the American Academy of Allergy and Immunology and found to be lacking . Although a number of commercial labs sell tests that reportedly measure IgG antibodies against common allergens there is no clinical significance of such findings . It is not established that these commercial assays actually measure the IgG antibodies that they report. Also, even if the assays are measuring IgG anti- allergen antibodies, the clinical significance of such antibodies is certainly not established. The significance of IgG anti-food antibodies is particularly questionable since the sera of many children with such antibodies in their serum tolerate the foods in question perfectly well . There was one study that showed a hypothetical possibility, in rheumatoid arthritis diarrhea, and constipation, among others.


 * 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.

Important differential diagnoses are:
 * Lactose intolerance; this generally develops later in life but can present in young patients in severe cases. This is due to an enzyme deficiency (lactase) and not allergy. It occurs in many non-Western people.
 * Celiac disease; this is an autoimmune disorder triggered by gluten proteins such as gliadin (present in wheat, rye and barley). It is a non-IgE mediated food allergy by definition.
 * Irritable bowel syndrome (IBS)
 * C1 esterase inhibitor deficiency (hereditary angioedema); this rare disease generally causes attacks of angioedema, but can present solely with abdominal pain and occasional diarrhea.

Pathophysiology
Generally, introduction of allergens through the digestive tract is thought to induce immune tolerance. In individuals who are predisposed to developing allergies (atopic syndrome), the immune system produces IgE antibodies against protein epitopes on non-pathogenic substances, including dietary components. The IgE molecules are coated onto mast cells, which inhabit the mucosal lining of the digestive tract.

Upon ingesting an allergen, the IgE reacts with its protein epitopes and release (degranulate) a number of chemicals (including histamine), which lead to oedema of the intestinal wall, loss of fluid and altered motility. The product is diarrhea.

Any food allergy has the potential to cause a fatal reaction.

Causes
The immune system's eosinophils, once activated in a histamine reaction, will register any foreign proteins they see. One theory regarding the causes of food allergies focuses on proteins presented in the blood along with vaccines, which are designed to provoke an immune response. Influenza vaccines and the Yellow Fever vaccine are still egg-based, but the Measles-Mumps-Rubella vaccine stopped using eggs in 1994. However large scientific studies do not support this theory, especially as it applies to autoimmune disease.

Another theory focuses on whether an infant's immune system is ready for complex proteins in a new food when it is first introduced.

One hypothesis at this time is the Hygiene hypothesis. While there is no proof for the hygiene hypothesis, people speculate that in modern, industrialized nations, such as the United States, food allergies are more common due to the lack of early exposure to dirt and germs, in part due to the over use of antibiotics and antibiotic cleansers. This hypothesis is based partly on studies showing less allergy in third world countries. Some research suggests that the body, with less dirt and germs to fight off, turns on itself and attacks food proteins as if they were foreign invaders.

Antibiotics have also been implicated in Leaky Gut Syndrome which is another possible cause of food allergies.

A lower incidence of food allergies in the developing world could also be due to differences in diet from the West and less exposure to food allergens.

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."

Treatment
The mainstay of treatment for food allergy is avoidance of the foods that have been identified as allergens.

If the food is accidentally ingested and a systemic reaction occurs, then epinephrine (best delivered with an autoinjector of epinephrine such as an Epipen or Twinject) should be used. It is possible that a second dose of epinephrine may be required for severe reactions. The patient should also seek medical care immediately.

At this time, there is no cure for food allergies. There are no allergy desensitization or allergy "shots" available for food allergies. Some doctors feel they do not work in food allergies because even minute amounts of the food in question or even food extracts (as in the case of allergy shots) can cause an allergic response in many sufferers.

According to experts at the BA Festival of Science in Norwich, England, 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.

Statistics
For reasons that are not entirely understood, the diagnosis of food allergies has apparently become more common in Western nations in recent times. 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. There is a similar prevalence in Canada.

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.

Differing views
Various medical practitioners have a differing views on food allergies. Irritable Bowel Syndrome (IBS) patients have been studied with regards to food allergies. Some studies have reported on the role of food allergy in IBS; only one epidemiological study on functional dyspepsia and food allergy has been published. However, since 2005 several studies have demonstrated strong correlation between IgG and/or IgE food allergy and IBS symptoms  The mechanisms by which food activates mucosal immune system are incompletely understood, but food specific IgE and IgG4 appeared to mediate the hypersensitivity reaction in a subgroup of IBS patients. Specific chemicals and receptors have been demonstrated to be critical in food allergy development in murine models. Exclusion diets based on skin prick test, RAST for IgE or IgG4, hypoallergic diet and clinical trials with oral disodium cromoglycate have been conducted, and some success has been reported in a subset of IBS patients.

Studies comparing skin prick testing and ELISA blood testing have found that the results of skin prick testing correlate poorly with symptoms of irritable bowel syndrome that correlate with food allergies demonstrated through ELISA testing and dietary challenge.

Extensive clinical experience has demonstrated significant improvement of patients with IBS whose ELISA-based food allergy testing is positive and where treatment includes a careful exclusion diet.

In addition, many practitioners of alternative medicine ascribe symptoms to food allergy where other doctors do not. The causal relationships between some of these conditions and food allergies have not been studied extensively enough to provide sufficient evidence to become authoritative. The interaction of histamine with the nervous system receptors has been demonstrated, but more study is needed. Other immune response effects are commonly known (swelling, irritation, etc.), but their relationships to some conditions has not been extensively studied. Examples are arthritis, fatigue, headaches, and hyperactivity. Nevertheless, hypoallergenic diets reportedly can be of benefit in these conditions, indicating that the current medical views on food allergy may be too narrow. Holford and Brady (2005) suggest three levels of response; classical immediate-onset allergy (IgE), delayed-onset allergy (giving a positive response on an ELISA IgG test but rarely on an IgE skin prick test), and food intolerance (non-allergic), and claim the last two to be more common. It is important to note that IgG is present in the body and is known to respond to foods. So some medical practitioners, especially allergists, claim that there is no predictive value to these types of tests, despite the studies cited above.

In children
Milk and soy allergies in children can often go undiagnosed for many months, causing much worry for parents and health risks for infants and children. Many infants with milk and soy allergies can show signs of colic, blood in the stool, mucous in the stool, reflux, rashes and other harmful medical conditions. These conditions are often misdiagnosed as viruses or colic.

Some children who are allergic to cow's milk protein also show a cross sensitivity to soy-based products. 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.

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.

Peanut and tree nut allergies are less likely to be outgrown, although evidence now shows that about 20% of those with peanut allergies and 9% of those with tree nut allergies will outgrow their allergies. In such a case, they need to consume nuts in some regular fashion to maintain the non-allergic status. This should be discussed with a doctor.

Those with other food allergies may or may not outgrow their allergies.

Labeling laws
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.

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 are responsible enough to list allergens in a statement separate from the ingredient statement.