Allergies A Wikipedia Guide

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Articles

Overview 1 Allergy 1 Allergen 17 Aeroallergen 23 Allergic inflammation 26 Anaphylaxis 28

Food Allergies 37 Food allergy 37 Corn allergy 48 Egg allergy 49 Milk allergy 53 Fruit allergy 56 Peanut allergy 58 Seafood allergy 64 Soy allergy 65 Tree nut allergy 67 Wheat allergy 69 Gluten sensitivity 75

Other Allergies 88 Allergic contact dermatitis 88 Drug allergy 92 Latex allergy 93 Insect sting allergy 96 Cat allergy 97 Perfume allergy 100

Testing 102 Skin allergy test 102 Patch test 105 RAST test 111

Treatment & Prevention 114 Elimination diet 114 Feingold diet 119 Allergen immunotherapy 130 Sublingual immunotherapy 137 References Article Sources and Contributors 141 Image Sources, Licenses and Contributors 144 Article Licenses License 145 1

Overview

Allergy

Allergy Classification and external resources

Hives are a common allergic symptom.

[1] ICD-10 T78.4

[2] ICD-9 995.3

[3] DiseasesDB 33481

[4] MedlinePlus 000812

[5] eMedicine med/1101

[6] MeSH D006967

An allergy is a hypersensitivity disorder of the immune system.[7] Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid. Allergy is one of four forms of hypersensitivity and is formally called type I (or immediate) hypersensitivity. Allergic reactions are distinctive because of excessive activation of certain white blood cells called mast cells and basophils by a type of antibody called Immunoglobulin E (IgE). This reaction results in an inflammatory response which can range from uncomfortable to dangerous. Mild allergies like hay fever are very common in the human population and cause symptoms such as red eyes, itchiness, and runny nose, eczema, hives, or an asthma attack. Allergies can play a major role in conditions such as asthma. In some people, severe allergies to environmental or dietary allergens or to medication may result in life-threatening reactions called anaphylaxis. Food allergies, and reactions to the venom of stinging insects such as wasps and bees are often associated with these severe reactions.[8] A variety of tests exist to diagnose allergic conditions. These include placing possible allergens on the skin and looking for a reaction such as swelling. Blood tests can also be done to look for an allergen-specific IgE. Allergy 2

Treatments for allergies include avoiding known allergens, use of medications such as anti-histamines that specifically prevent allergic reactions, steroids that modify the immune system in general, and medications such as decongestants that reduce the symptoms. Many of these medications are taken by mouth, though epinephrine, which is used to treat anaphylactic reactions, is injected. Immunotherapy uses injected allergens to desensitize the body's response.

Signs and symptoms

Common symptoms

Affected organ Symptom Nose swelling of the nasal mucosa (allergic rhinitis) Sinuses allergic sinusitis Eyes redness and itching of the conjunctiva (allergic conjunctivitis) Airways Sneezing, coughing, bronchoconstriction, wheezing and dyspnea, sometimes outright attacks of asthma, in severe cases the airway constricts due to swelling known as laryngeal edema Ears feeling of fullness, possibly pain, and impaired hearing due to the lack of eustachian tube drainage. Skin rashes, such as eczema and hives (urticaria) Gastrointestinal abdominal pain, bloating, vomiting, diarrhea tract

Many allergens such as dust or pollen are airborne particles. In these cases, symptoms arise in areas in contact with air, such as eyes, nose, and lungs. For instance, allergic rhinitis, also known as hay fever, causes irritation of the nose, sneezing, itching, and redness of the eyes.[9] Inhaled allergens can also lead to asthmatic symptoms, caused by narrowing of the airways (bronchoconstriction) and increased production of mucus in the lungs, shortness of breath (dyspnea), coughing and wheezing.[10] Aside from these ambient allergens, allergic reactions can result from foods, insect stings, and reactions to medications like aspirin and antibiotics such as penicillin. Symptoms of food allergy include abdominal pain, bloating, vomiting, diarrhea, itchy skin, and swelling of the skin during hives. Food allergies rarely cause respiratory (asthmatic) reactions, or rhinitis.[11] Insect stings, antibiotics, and certain medicines produce a systemic allergic response that is also called anaphylaxis; multiple organ systems can be affected, including the digestive system, the respiratory system, and the circulatory system.[12][13][14] Depending on the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma, and even death. This type of reaction can be triggered suddenly, or the onset can be delayed. The severity of this type of allergic response often requires injections of epinephrine, sometimes through a device known as the EpiPen or Twinject auto-injector. The nature of anaphylaxis is such that the reaction can seem to be subsiding, but may recur throughout a prolonged period of time.[14] Substances that come into contact with the skin, such as latex, are also common causes of allergic reactions, known as contact dermatitis or eczema.[15] Skin allergies frequently cause rashes, or swelling and inflammation within the skin, in what is known as a "wheal and flare" reaction characteristic of hives and angioedema.[16] Allergy 3

Cause Risk factors for allergy can be placed in two general categories, namely host and environmental factors.[17] Host factors include heredity, gender, race, and age, with heredity being by far the most significant. However, there have been recent increases in the incidence of allergic disorders that cannot be explained by genetic factors alone. Four major environmental candidates are alterations in exposure to infectious diseases during early childhood, environmental pollution, allergen levels, and dietary changes.[18]

Foods One of the most common food allergies is a sensitivity to peanuts. Peanut allergies may be extremely severe, but can sometimes be outgrown by children school-age.[19] Tree nuts, including pecans, pistachios, pine nuts, and walnuts, are another common allergen. Sufferers may be sensitive to one, or many, tree nuts.[20] Also seeds, including sesame seeds and poppy seeds, contain oils where protein is present, which may elicit an allergic reaction.[20] Egg allergies affect one to two percent of children but are outgrown by about two-thirds of children by the age of 5.[21] The sensitivity is usually to proteins in the white rather than the yolk.[20] 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. Lactose intolerance, a common reaction to milk, is not in fact a form of allergy. A 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.[22] Other foods containing allergenic proteins include soy, wheat, fish, shellfish, fruits, vegetables, spices, synthetic and natural colors, chicken, and chemical additives.

Non-food proteins Latex can trigger an IgE-mediated cutaneous, respiratory, and systemic reaction. The prevalence of latex allergy in the general population is believed to be less than one percent. In a hospital study, one in 800 surgical patients (0.125 percent) report latex sensitivity, although the sensitivity among healthcare workers is higher, between seven and ten percent. Researchers attribute this higher level to the exposure of healthcare workers to areas with significant airborne latex allergens, such as operating rooms, intensive-care units, and dental suites. These latex-rich environments may sensitize healthcare workers who regularly inhale allergenic proteins.[23] The most prevalent response to latex is an allergic contact dermatitis, a delayed hypersensitive reaction appearing as dry, crusted lesions. This reaction usually lasts 48 to 96 hours. Sweating or rubbing the area under the glove aggravates the lesions, possibly leading to ulcerations.[23] Anaphylactic reactions occur most often in sensitive patients, who have been exposed to the surgeon's latex gloves during abdominal surgery, but other mucosal exposures, such as dental procedures, can also produce systemic reactions.[23] Latex and banana sensitivity may cross-react; furthermore, patients with latex allergy may also have sensitivities to avocado, kiwifruit, and chestnut.[24] These patients often have perioral itching and local urticaria. Only occasionally have these food-induced allergies induced systemic responses. Researchers suspect that the cross-reactivity of latex with banana, avocado, kiwifruit, and chestnut occurs because latex proteins are structurally homologous with some plant proteins.[23]

Toxins interacting with proteins Another non-food protein reaction, urushiol-induced contact dermatitis, originates after contact with poison ivy, eastern poison oak, western poison oak, or poison sumac. Urushiol, which is not itself a protein, acts as a hapten and chemically reacts with, binds to, and changes the shape of integral membrane proteins on exposed skin cells. The immune system does not recognize the affected cells as normal parts of the body, causing a T-cell-mediated immune response.[25] Of these poisonous plants, sumac is the most virulent.[26] The resulting dermatological response to the Allergy 4

reaction between urushiol and membrane proteins includes redness, swelling, papules, vesicles, blisters, and streaking.[27] Estimates vary on the percentage of the population that will have an immune system response. Approximately 25 percent of the population will have a strong allergic response to urushiol. In general, approximately 80 percent to 90 percent of adults will develop a rash if they are exposed to .0050 milligrams (expected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operatorexpected operator×10−5 gr) of purified urushiol, but some people are so sensitive that it takes only a molecular trace on the skin to initiate an allergic reaction.[28]

Genetic basis Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins.[29] Allergic parents are more likely to have allergic children,[30] and their allergies are likely to be more severe than those from non-allergic parents. Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may have children who are allergic to ragweed. It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not.[30] The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk.[31] Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.[31] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.[32] Overall, boys have a higher risk of developing allergy than girls,[30] although for some diseases, namely asthma in young adults, females are more likely to be affected.[33] Sex differences tend to decrease in adulthood.[30] Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to migration.[30] It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins.[34]

Hygiene hypothesis Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the TH1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease.[35] In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens and thus normally benign microbial objects — like pollen — will trigger an immune response.[36] The hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents. Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that Allergy 5

immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.[37] Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.[38] The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[39] The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth.[40][41]

Other environmental factors International differences have been associated with the number of individuals within a population that suffer from allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.[42] Exposure to allergens, especially in early life, is an important risk factor for allergy. Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy.[18] Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood.[43] Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.[44] Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies.[45] Recent research has shown that some common parasites, such as intestinal worms (e.g., hookworms), secrete chemicals into the gut wall (and, hence, the bloodstream) that suppress the immune system and prevent the body from attacking the parasite.[46] This gives rise to a new slant on the hygiene hypothesis theory — that co-evolution of man and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive.[47] In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants.[48] However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms.[42] Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies.[49] It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.[49] For more information on this topic, see Helminthic therapy.

Pathophysiology

This is a summary diagram that explains how allergy develops. Tissues affected in allergic inflammation. Allergy 6

In the early stages of allergy, a type I hypersensitivity reaction against an allergen encountered for the first time and presented by a professional Antigen-Presenting Cell causes a response in a type of immune cell called a T 2 lymphocyte, which belongs to a subset of T H cells that produce a cytokine called interleukin-4 (IL-4). These T 2 H cells interact with other lymphocytes called B cells, whose role is 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 Degranulation process in allergy. Second exposure to allergen.1 - antigen; 2 - IgE antibody; receptor called FcεRI) on the surface of other kinds of immune cells 3 - FcεRI receptor; 4 - preformed mediators called mast cells and basophils, which are both involved in the acute (histamine, proteases, chemokines, heparine); 5 - inflammatory response. The IgE-coated cells, at this stage are granules; 6 - mast cell; 7 - newly formed sensitized to the allergen.[18] mediators (prostaglandins, leukotrienes, thromboxanes, PAF) 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, allergen, and 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.[18]

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.[50] 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 T 2 cells.[51] H Allergy 7

Diagnosis

Before a diagnosis of allergic disease can be confirmed, the other possible causes of the presenting symptoms should be carefully considered.[52] Vasomotor rhinitis, for example, is one of many maladies that shares symptoms with allergic rhinitis, underscoring the need for professional differential diagnosis.[53] Once a diagnosis of asthma, rhinitis, anaphylaxis, or other allergic disease has been made, there are several methods for discovering the causative agent of that allergy.

Effective management of allergic diseases relies on the ability to make an accurate diagnosis.[54] Allergy testing can help confirm/rule out allergies and consequently reduce adverse reactions and limit unnecessary avoidance and medications.[55][56] Correct diagnosis, counseling and avoidance advice based on valid allergy test results will help reduce the incidence of symptoms, medications and improve quality of life.[55] For assessing the presence of allergen-specific IgE antibodies, you can use two different methods—a skin prick test or an allergy blood test. Both methods are recommended by the NIH An allergy testing machine being operated in the diagnostic immunology lab at Lackland Air Force guidelines and have similar diagnostic value in terms of sensitivity and Base specificity.[56][57]

A healthcare provider can use the test results to identify the specific allergic triggers that may be contributing to the symptoms. Using this information, along with a physical examination and case history, the doctor can diagnose the cause of the symptoms and tailor treatments that will help the patient feel better. A negative result can help the doctor rule out allergies in order to consider other possible. NIH Guidelines state that: “sIgE tests are useful for identifying foods potentially provoking IgE-mediated food-induced allergic reactions, and specified ‘‘cutoff’’ levels, defined as 95% predictive values, may be more predictive than skin prick tests of clinical reactivity in certain populations.” It further states, “sIgE tests are very useful for detecting the presence of sIgE antibodies, which indicates the presence of allergic sensitization. Fluorescence-labeled antibody assays have comparable sensitivity to that of skin prick tests, and the absolute levels of sIgE antibodies may directly correlate with the likelihood of clinical reactivity when compared with oral food challenges for the identification of foods provoking IgE mediated FA.”[58] According to NICE Guidelines, skin prick tests and blood tests are equally cost-effective and health economic evidence show that both the IgE antibody test and the skin prick test were cost effective compared with no test.[55] Also, earlier and more accurate diagnoses save cost due to reduced GP consultations, referrals to secondary care, misdiagnosis and emergency admissions.[59] Allergy undergoes dynamic changes over time. Regular allergy testing of relevant allergens provides information on if and how patient management can be changed, in order to improve health and quality of life. Annual testing is often the practice for determining whether allergy to milk, egg, soy, and wheat have been outgrown and the testing interval is extended to 2 to 3 years for allergy to peanut, tree nuts, fish, and crustacean shellfish.[56] Results of follow-up testing can guide decision-making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet.[58] Allergy 8

Skin testing

Skin testing is also known as "puncture testing" and "prick testing" due to the series of tiny puncture or pricks made into the patient's skin. Small amounts of suspected allergens and/or their extracts (pollen, grass, mite proteins, peanut extract, etc.) are introduced to sites on the skin marked with pen or dye (the ink/dye should be carefully selected, lest it cause an allergic response itself). A small plastic or metal device is used to puncture or prick the skin. Sometimes, the allergens are injected "intradermally" into the patient's skin, with a needle and syringe. Common areas for testing include the inside forearm and the back. If the patient is allergic to the substance, then a visible Skin testing on arm inflammatory reaction will usually occur within 30 minutes. This response will range from slight reddening of the skin to a full-blown hive (called "wheal and flare") in more sensitive patients similar to a mosquito bite. Interpretation of the results of the skin prick test is normally done by allergists on a scale of severity, with +/- meaning borderline reactivity, and 4+ being a large reaction. Increasingly, allergists are measuring and recording the diameter of the wheal and flare reaction. Interpretation by well-trained allergists is often guided by relevant literature.[60] Some patients may believe they have determined their own allergic sensitivity from observation, but a skin Skin testing on back test has been shown to be much better than patient observation to detect allergy.[61]

If a serious life threatening anaphylactic reaction has brought a patient in for evaluation, some allergists will prefer an initial blood test prior to performing the skin prick test. Skin tests may not be an option if the patient has widespread skin disease or has taken antihistamines sometime the last several days.

Blood testing An allergy blood test is quick and simple and can be ordered by a licensed health care provider e.g. an allergy specialist, GP or PED. Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity and pregnancy. Adults and children of any age can take an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often more gentle than several skin tests. An allergy blood test is available through most laboratories, and a sample of the patient’s blood is sent to a laboratory for analysis and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. Allergy blood tests are very safe, since you are not exposed to any allergens during the testing procedure. How does the test work? The test measures the concentration of specific IgE antibodies in the blood. Quantitative IgE test results increases the possibility of ranking how different substances may affect your symptoms. A general rule of thumb is that the higher the IgE antibody value, the greater the likelihood of symptoms. Allergens found at low levels that today do not result in symptoms can nevertheless help predict future symptom development. The quantitative allergy blood result can help determine what a patient is allergic to, help predict and follow the disease development, estimate the risk of a severe reaction and explain cross-reactivity.[62][63] Allergy 9

A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens.[64] Statistical methods, such as ROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with allergy tests for specific IgE antibodies for a carefully chosen of allergens is often warranted. History Radiometric assays include the radioallergosorbent test (RAST) test method, which uses IgE-binding (anti-IgE) antibodies labeled with radioactive isotopes for quantifying the levels of IgE antibody in the blood.[65] Other newer methods use colorimetric or fluorescence-labeled technology in the place of radioactive isotopes. The market-leading RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronym RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which uses the newer fluorescence-labeled technology. American College of Allergy Asthma and Immunology (ACAAI) and the American Academy of Allergy Asthma and Immunology (AAAAI) issued the Joint Task Force Report “Pearls and pitfalls of allergy diagnostic testing” in 2008, and is firm in its statement that the term RAST is now obsolete: “The term RAST became a colloquialism for all varieties of (in vitro allergy) tests. This is unfortunate because it is well recognized that there are well-performing tests and some that do not perform so well, yet they are all called RASTs, making it difficult to distinguish which is which. For these reasons, it is now recommended that use of RAST as a generic descriptor of these tests be abandoned.”[66] The new version, the ImmunoCAP Specific IgE blood test, is the only specific IgE assay to receive FDA approval to quantitatively report to its detection limit of 0.1kU/l.

Other Challenge testing: Challenge testing is when small amounts of a suspected allergen are introduced to the body orally, through inhalation, or other routes. Except for testing food and medication allergies, challenges are rarely performed. When this type of testing is chosen, it must be closely supervised by an allergist. Elimination/Challenge tests: This testing method is utilized most often with foods or medicines. A patient with a particular suspected allergen is instructed to modify his/her diet to totally avoid that allergen for determined period of time. If the patient experiences significant improvement, he/she may then be “challenged” by reintroducing the allergen to see if symptoms can be reproduced. Patch testing: Patch testing is used to help ascertain the cause of skin contact allergy, or contact dermatitis. Adhesive patches, usually treated with a number of different commonly allergic chemicals or skin sensitizers, are applied to the back. The skin is then examined for possible local reactions at least twice, usually at 48 hours after application of the patch, and again two or three days later. Some "screening" test methods are intended to provide qualitative test results, giving a "yes" or "no" answer in patients with suspected allergic sensitization. One such method has a sensitivity of about 70.8% and a positive predictive value of 72.6% according to a large study.[67] Unreliable tests: There are other types of allergy testing methods that the American Academy of Allergy, Asthma, and Immunology considers to be unacceptable. These unreliable allergy testing methods are: Applied kinesiology (allergy testing through muscle relaxation), Cytotoxicity testing, Urine autoinjection, Skin titration (Rinkel method), and Provocative and neutralization (subcutaneous) testing or sublingual provocation[68] Allergy 10

Management In recent times, there have been enormous improvements in the medical practices used to treat allergic conditions. With respect to anaphylaxis and hypersensitivity reactions to foods, drugs, and insects and in allergic skin diseases, advances have included the identification of food proteins to which IgE binding is associated with severe reactions and development of low-allergen foods, improvements in skin prick test predictions; evaluation of the atopy patch test; in wasp sting outcomes predictions and a rapidly disintegrating epinephrine tablet, and anti-IL-5 for eosinophilic diseases.[69] Traditional treatment and management of allergies consisted simply of avoiding the allergen in question or otherwise reducing exposure. For instance, people with cat allergies were encouraged to avoid them. However, while avoidance of allergens may reduce symptoms and avoid life-threatening anaphylaxis, it is difficult to achieve for those with pollen or similar air-borne allergies. Nonetheless, strict avoidance of allergens is still considered a useful treatment method, and is often used in managing food allergies. New technology approaches to decreasing IgE overproduction, and regulating histimine release in allergic individuals have demonstrated statisitically significant reduction on Total Nasel Symptom Scores.[70][71]

Medication Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, glucocorticoids, epinephrine (adrenaline), theophylline and cromolyn sodium. Anti-leukotrienes, such as Montelukast (Singulair) or Zafirlukast (Accolate), are FDA approved for treatment of allergic diseases. Anti-cholinergics, decongestants, mast cell stabilizers, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. These drugs help to alleviate the symptoms of allergy, and are imperative in the recovery of acute anaphylaxis, but play little role in chronic treatment of allergic disorders.

Immunotherapy

Desensitization or hyposensitization is a treatment in which the person is gradually vaccinated with progressively larger doses of the allergen in question. This can either reduce the severity or eliminate hypersensitivity altogether. It relies on the progressive skewing of IgG antibody production, to block excessive IgE production seen in atopys. In a sense, the person builds up immunity to increasing amounts of the allergen in question. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the development of new allergy.[72] Meta-analyses have also confirmed Anti-allergy immunotherapy efficacy of the treatment in allergic rhinitis in children[73] and in asthma.[74] A review by the Mayo Clinic in Rochester confirmed the safety and efficacy of allergen immunotherapy for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insect based on numerous well-designed scientific studies.[75] In addition, national and international guidelines confirm the clinical efficacy of injection immunotherapy in rhinitis and asthma, as well as the safety, provided that recommendations are followed.[76]

A second form of immunotherapy involves the intravenous injection of monoclonal anti-IgE antibodies. These bind to free and B-cell associated IgE; signalling their destruction. They do not bind to IgE already bound to the Fc receptor on basophils and mast cells, as this would stimulate the allergic inflammatory response. The first agent of this class is Omalizumab. While this form of immunotherapy is very effective in treating several types of atopy, it should not be used in treating the majority of people with food allergies. Allergy 11

A third type, Sublingual immunotherapy, is an orally-administered therapy that takes advantage of oral immune tolerance to non-pathogenic antigens such as foods and resident bacteria. This therapy currently accounts for 40 percent of allergy treatment in Europe. In the United States, sublingual immunotherapy is gaining support among traditional allergists and is endorsed by doctors treating allergy.[77] Allergy shot treatment is the closest thing to a ‘cure’ for allergic symptoms. This therapy requires a long-term commitment.

Other An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective.[78] EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favouring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases but is not approved by the U.S. Food and Drug Administration or of proven effectiveness.[78] Systematic literature searches conducted by the Mayo Clinic through 2006, involving hundreds of articles studying multiple conditions, including asthma and upper respiratory tract infection, showed no effectiveness of homeopathic treatments and no difference compared with placebo. The authors concluded that, based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.[79]

Epidemiology Many diseases related to inflammation such as type 1 diabetes, rheumatoid arthritis, and allergic diseases — hay fever and asthma — have increased in the Western world over the past 2-3 decades.[80] Rapid increases in allergic asthma and other atopic disorders in industrialized nations, it is estimated, began in the 1960s and 1970s, with further increases occurring during the 1980s and 1990s,[81] although some suggest that a steady rise in sensitization has been occurring since the 1920s.[82] The incidence of atopy in developing countries has, in general, remained much lower.[81]

Allergic conditions: Statistics and Epidemiology

[83] Allergy type United States United Kingdom

[84] [85] Allergic rhinitis 35.9 million (about 11% of the population ) 3.3 million (about 5.5% of the [86] population )

Asthma 10 million suffer from allergic asthma (about 3% of the 5.7 million (about 9.4%). In six and seven population). The prevalence of asthma increased 75% year olds asthma increased from 18.4% to from 1980-1994. Asthma prevalence is 39% higher in 20.9% over five years, during the same time [87] African Americans than in Europeans. the rate decreased from 31% to 24.7% in 13 to 14 year olds.

Atopic eczema About 9% of the population. Between 1960 and 1990 5.8 million (about 1% severe). prevalence has increased from 3% to 10% in [88] children.

Anaphylaxis At least 40 deaths per year due to insect venom. About Between 1999 and 2006, 48 deaths occurred 400 deaths due to penicillin anaphylaxis. About 220 in people ranging from five months to 85 cases of anaphylaxis and 3 deaths per year are due to years old. [89] latex allergy. An estimated 150 people die annually [90] from anaphylaxis due to food allergy. Allergy 12

Insect venom Around 15% of adults have mild, localized allergic Unknown reactions. Systemic reactions occur in 3% of adults and [91] less than 1% of children. Drug allergies Anaphylactic reactions to penicillin cause 400 deaths per Unknown year.

Food allergies About 6% of US children under age 3 and 3.5-4% of the 5-7% of infants and 1-2% of adults. A overall US population. Peanut and/or tree nut (e.g. 117.3% increase in peanut allergies was walnut) allergy affects about three million Americans, or observed from 2001 to 2005, an estimated [90] 1.1% of the population. 25,700 people in England are affected.

Multiple allergies Unknown 2.3 million (about 3.7%), prevalence has (Asthma, eczema and increased by 48.9% between 2001 and [92] allergic rhinitis together) 2005.

Although genetic factors fundamentally govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes.[81] Several hypotheses have been identified to explain this increased prevalence; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise.[80] The hygiene hypothesis maintains[93] that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from T 1 type responses, leading to unrestrained H T 2 responses that allow for an increase in allergy.[47][94] H Changes in rates and types of infection alone however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, Toxoplasma gondii, and Helicobacter pylori (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%,[95] and an increased prevalence of parasitic infections has been associated with a decreased prevalence of asthma.[96] It is speculated that these infections exert their effect by critically altering T 1/T 2 H H regulation.[97] Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.[97]

History The concept of "allergy" was originally introduced in 1906 by the Viennese pediatrician Clemens von Pirquet, after he noted that some of his patients were hypersensitive to normally innocuous entities such as dust, pollen, or certain foods.[98] Pirquet called this phenomenon "allergy" from the Ancient Greek words ἄλλος allos meaning "other" and ἔργον ergon meaning "work".[99] All forms of hypersensitivity used to be classified as allergies, and all were thought to be caused by an improper activation of the immune system. Later, it became clear that several different disease mechanisms were implicated, with the common link to a disordered activation of the immune system. In 1963, a new classification scheme was designed by Philip Gell and Robin Coombs that described four types of hypersensitivity reactions, known as Type I to Type IV hypersensitivity.[100] With this new classification, the word "allergy" was restricted to type I hypersensitivities (also called immediate hypersensitivity), which are characterized as rapidly developing reactions. A major breakthrough in understanding the mechanisms of allergy was the discovery of the antibody class labeled immunoglobulin E (IgE) - Kimishige Ishizaka and co-workers were the first to isolate and describe IgE in the 1960s.[101] Allergy 13

Medical specialty An allergist is a physician specially trained to manage and treat allergies, asthma and the other allergic diseases. In the United States physicians holding certification by the American Board of Allergy and Immunology (ABAI) have successfully completed an accredited educational program and an evaluation process, including a secure, proctored examination to demonstrate the knowledge, skills, and experience to the provision of patient care in allergy and immunology.[102] Becoming an allergist/immunologist requires completion of at least nine years of training. After completing medical school and graduating with a medical degree, a physician will then undergo three years of training in internal medicine (to become an internist) or pediatrics (to become a pediatrician). Once physicians have finished training in one of these specialties, they must pass the exam of either the American Board of Pediatrics (ABP) or the American Board of Internal Medicine (ABIM). Internists or pediatricians wishing to focus on the sub-specialty of allergy-immunology then complete at least an additional two years of study, called a fellowship, in an allergy/immunology training program. Allergist/immunologists listed as ABAI-certified have successfully passed the certifying examination of the American Board of Allergy and Immunology (ABAI), following their fellowship.[103] In the United Kingdom, allergy is a subspecialty of general medicine or pediatrics. After obtaining postgraduate exams (MRCP or MRCPCH respectively), a doctor works for several years as a specialist registrar before qualifying for the General Medical Council specialist register. Allergy services may also be delivered by immunologists. A 2003 Royal College of Physicians report presented a case for improvement of what were felt to be inadequate allergy services in the UK.[104] In 2006, the House of Lords convened a subcommittee that reported in 2007. It concluded likewise that allergy services were insufficient to deal with what the Lords referred to as an "allergy epidemic" and its social cost; it made several other recommendations.[105]

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version (http:/ / www. rcplondon. ac. uk/ pubs/ contents/ 81e384d6-0328-4653-9cc2-2aa7baa3c56a. pdf)PDF (1.03 MB) [105] House of Lords - Science and Technology Committee (2007). Allergy - HL 166-I, 6th Report of Session 2006-07 - Volume 1: Report (http:/

/ www. publications. parliament. uk/ pa/ ld200607/ ldselect/ ldsctech/ 166/ 16602. htm). London, UK: TSO (The Stationery Office). ISBN 978-0-10-401149-2. . Allergy 17

External links

• American Academy of Allergy, Asthma & Immunology (http:/ / www. aaaai. org)

Allergen

An allergen is any substance that can cause an allergy. In technical terms, an allergen is an antigen capable of stimulating a type-I hypersensitivity reaction in atopic individuals through Immunoglobulin E (IgE) responses.[1]. Most humans mount significant Immunoglobulin E responses only as a defense against parasitic infections. However, some individuals may respond to many common environmental antigens. This hereditary predisposition is called atopy. In atopic individuals, non-parasitic antigens stimulate inappropriate IgE production, leading to type I hypersensitivity. Sensitivities vary widely from one person (or other animal) to another. A very broad range of substances can be allergens to sensitive individuals.

Types of allergies Allergens can be found in a variety of sources, such as dust mite excretion, pollen, pet dander or even royal jelly.[2] Food allergies are not as common as food sensitivity, but some foods such as peanuts (a legume), nuts, seafood and shellfish are the cause of serious allergies in many people. Officially, the United States Food and Drug Administration does recognize eight foods as being common for allergic reactions in a large segment of the sensitive population. These include peanuts, tree nuts, eggs, milk, shellfish, fish, wheat and their derivatives, and soy and their derivatives, as well as sulfites (chemical based, often found in flavors and colors in foods) at 10ppm and over. See the FDA website for complete details. It should be noted that other countries, in view of the differences in the genetic profiles of their citizens and different levels of exposure to specific foods due to different dietary habits, the "official" allergen list will change. Canada recognizes all eight of the allergens recognized by the US, and also recognizes sesame seeds,[3] and mustard.[4] The European Union additionally recognizes celery. Another type of allergen is urushiol, a resin produced by poison ivy and poison oak. It causes the skin rash condition known as urushiol-induced contact dermatitis by changing a skin cell's configuration so that it is no longer recognized by the immune system as part of the body. A little over half of North Americans are known to be allergic to urushiol and repeated exposure can increase one's sensitivity to the allergen. An allergic reaction can be caused by any form of direct contact with the allergen—consuming food or drink one is sensitive to (ingestion), breathing in pollen, perfume or pet dander (inhalation), or brushing a body part against an allergy-causing plant (direct contact, generally resulting in hives). Other common causes of serious allergy are wasp, fire ant and bee stings, penicillin, and latex. An extremely serious form of an allergic reaction is called anaphylaxis. One form of treatment is the administration of sterile epinephrine to the person experiencing anaphylaxis, which suppresses the body's overreaction to the allergen, and allows for the patient to be transported to a medical facility.

Fungal allergens In 1952 basidiospores were described as being possible airborne allergens[5] and were linked to asthma in 1969.[6] Basidiospores are the dominant airborne fungal allergens. Fungal allergies are associated with seasonal asthma.[7][8] They are considered to be a major source of airborne allergens.[9] The basidospore family include mushrooms, rusts, smuts, brackets, and puffballs. The airborne spores from mushrooms reach levels comparable to those of mold and pollens. The levels of mushroom respiratory allergy are as high as 30 percent of those with allergic disorder, but it is believed to be less than 1 percent of food allergies.[10][11] Heavy rainfall (which increases fungal spore release) is associated with increased hospital admissions of children with asthma.[12] A study in New Zealand found that 22 Allergen 18

percent of patients with respiratory allergic disorders tested positive for basidiospores allergies.[13] Mushroom spore allergies can cause either immediate allergic symptomatology or delayed allergic reactions. Those with asthma are more likely to have immediate allergic reactions and those with allergic rhinitis are more likely to have delayed allergic responses.[14] A study found that 27 percent of patients were allergic to basidiomycete mycelia extracts and 32 percent were allergic to basidiospore extracts, thus demonstrating the high incidence of fungal sensitisation in individuals with suspected allergies.[15] It has been found that of basidiomycete cap, mycelia, and spore extracts that spore extracts are the most reliable extract for diagnosing basidiomycete allergy.[16][17] In Canada, 8% of children attending allergy clinics were found to be allergic to Ganoderma, a basidiospore.[18] Pleurotus ostreatus,[19] cladosporium,[20] and calvatia cyathiformis are significant airborne spores.[9] Other significant fungal allergens include aspergillus and alternaria-penicillin families.[21] In India fomes pectinatis is a predominant air-borne allergen affecting up to 22 percent of patients with respiratory allergies.[22] Some fungal air-bourne allergens such as coprinus comatus are associated with worsening of eczematous skin lesions.[23] Children who are born during autumn months (during fungal spore season) are more likely to develop asthmatic symptoms later in life.[24]

Common allergens

In addition to foreign proteins found in foreign serum (from blood transfusions) and vaccines, common allergens include: • Animal products • Fel d 1 (cat allergy) • fur and dander • cockroach calyx • wool • dust mite excretion • Drugs • penicillin

• sulfonamides SEM of miscellaneous plant pollens. Pollens are very common • salicylates (also found naturally in numerous allergens. fruits) • Foods • celery and celeriac [25] • corn or maize • eggs (typically albumen, the white) • fruit • pumpkin • legumes • beans • peas • peanuts • soybeans • milk The house dust mite, its feces and chitin are common allergens • seafood around the home • sesame • soy Allergen 19

• tree nuts • pecans • almonds • wheat • Insect stings • bee sting venom • wasp sting venom • mosquito stings • Mold spores • Other • latex • metal • Plant pollens (hay fever) • grass — ryegrass, timothy-grass • weeds — ragweed, plantago, nettle, artemisia vulgaris, chenopodium album, sorrel • trees — birch, alder, hazel, hornbeam, aesculus, willow, poplar, platanus, tilia, olea, Ashe juniper

Seasonal allergies Seasonal allergy symptoms are commonly experienced part of the year, usually during spring, summer or fall when certain trees or grasses pollinate. This depends on the kind of tree or grass. For instance, some trees such as oak, elm, and maple pollinate in the spring, while grasses such as Bermuda, timothy and orchard pollinate in the summer. Grass allergy is generally linked to hay fever because their symptoms and causes are somehow similar to each other. Symptoms include rhinitis, which causes sneezing and a runny nose, as well as allergic conjunctivitis, which includes watering and itchy eyes.[26] Also an initial tickle on the roof of the mouth or in the back of the throat may be experienced. Also, depending on the season, the symptoms may be more severe and people may experience coughing, wheezing, and irritability. A few people even become depressed, lose their appetite, or have problems sleeping. Moreover, since the sinuses may also become congested, some people experience headaches.[27] If both parents suffered from allergies in the past, there is a 66% chance for the individual to suffer from seasonal allergies, and the risk lowers to 60% if just one parent had suffered from allergies. The immune system also has strong influence on seasonal allergies, since it reacts differently to diverse allergens like pollen. When an allergen enters the body of an individual that is predisposed to allergies, it triggers an immune reaction and the production of antibodies. These allergen antibodies migrate to mast cells lining the nose, eyes and lungs. When an allergen drifts into the nose more than once, mast cells release a slew of chemicals or histamines that irritate and inflame the moist membranes lining the nose and produce the symptoms of an allergic reaction: scratchy throat, itching, sneezing and watery eyes. Some symptoms that differentiate allergies from a cold include[28]: • No fever or muscle ache. • Mucous secretions are runny and clear. • Sneezes occurring in rapid and several sequences. • Itchy throat, ears and nose. • These symptoms usually last longer than 7–10 days. Among seasonal allergies, there are some allergens that fuse together and produce a new type of allergy. For instance, grass pollen allergens cross-react with food allergy proteins in vegetables such as onion, lettuce, carrots, celery and corn. Besides, the cousins of birch pollen allergens, like apples, grapes, peaches, celery and apricots, produce severe itching in the ears and throat. The cypress pollen allergy brings a cross reactivity between diverse Allergen 20

species like olive, privet, ash and Russian olive tree pollen allergens. In some rural areas there is another form of seasonal grass allergy, combining airborne particles of pollen mixed with mold.[29] Recent research has suggested that humans might develop allergies as a defense to fight off parasites. According to Yale University Immunologist Dr Ruslan Medzhitov, protease allergens cleave the same sensor proteins that evolved to detect proteases produced by the parasitic worms.[30] Additionally, a new report on seasonal allergies called “Extreme allergies and Global Warming”, have found that many allergy triggers are worsening due to climate change. 16 states in the United States were named as “Allergen Hotspots” for large increases in allergenic tree pollen if global warming pollution keeps increasing. Therefore, researchers on this report claimed that global warming is bad news for millions of asthmatics in the United States whose asthma attacks are triggered by seasonal allergies.[31] Indeed, seasonal allergies are one of the main triggers for asthma, along with colds or flu, cigarette smoke and exercise. In Canada, for example, up to 75% of asthmatics also have seasonal allergies.[32]

Seasonal Allergy Diagnosis Based on the symptoms seen on the patient, the answers given in terms of symptom evaluation and a physical exam, doctors can make a diagnosis to identify if the patient has a seasonal allergy. After performing the diagnosis, the doctor is able to tell the main cause of the allergic reaction and recommend the treatment to follow. 2 tests have to be done in order to determine the cause: a blood test and a skin test. Allergists do skin tests in one of two ways: either dropping some purified liquid of the allergen onto the skin and pricking the area with a small needle; or injecting a small amount of allergen under the skin.[33] Alternative tools are available to identify seasonal allergies, such as laboratory tests, imaging tests and nasal endoscopy. In the laboratory tests, the doctor will take a nasal smear and it will be examined microscopically for factors that may indicate a cause: increased numbers of eosinophils (white blood cells), which indicates an allergic condition. If there is a high count of eosinophils, an allergic condition might be present. Another laboratory test is the blood test for IgE (immunoglobulin production), such as the radioallergosorbent Test (RAST), implemented to detect high levels of allergen-specific IgE in response to particular allergens. Although blood tests are less accurate than the skin tests, they can be performed on patients unable to undergo skin testing. Imaging tests can be useful to detect sinusitis in people suffering from chronic rhinitis, and they can work when other test results are ambiguous. There is also nasal endoscopy, wherein a tube is inserted through the nose with a small camera to view the passageways and examine any irregularities in the nose structure. Endoscopy can be used for some cases of chronic or unresponsive seasonal rhinitis.[34]

Treatment Treatment includes over-the-counter medications, antihistamines, nasal decongestants, allergy shots, and alternative medicine. In the case of nasal symptoms, antihistamines are normally the first option. They may be taken together with pseudoephedrine to help relieve a stuffy nose and they can stop the itching and sneezing. Some over-the-counter options are Benadryl and Tavist. However, these antihistamines may cause extreme drowsiness, therefore, people are advised to not operate heavy machinery or drive while taking this kind of medication. Other side effects include dry mouth, blurred vision, constipation, difficulty with urination, confusion, and light-headedness.[35] There is also a newer second generation of antihistamines that are generally classified as the "non-sedating antihistamines" or anti-drowsy, which include cetirizine, loratadine, and fexofenadine.[36] An example of nasal decongestants is pseudoephedrine and its side-effects include insomnia, restlessness, and difficulty urinating. Some other nasal sprays are available by prescription, including Azelastine and Ipratropium. Some of their side-effects include drowsiness. For eye symptoms, it is important to first bath the eyes with plain eyewashes to reduce the irritation. People should not wear contact lenses during episodes of conjunctivitis. Allergy shots, also called immunotherapy, are also available and are especially recommended for people who cannot tolerate allergy medications or who severe symptoms, and also for those who develop asthma during pollen season. Allergen 21

Immunotherapy contains a small amount of the substance that triggers the allergic reactions [37] and it should start after the pollen season to get prepared for the next season. Natural remedies are another option that patients look to for relief. One of the most popular recently is the European herb butterbur (Petasites hybridus). The British Medical Journal published a study in which Swiss researchers proved how one tablet of butterbur four times daily was as effective as an antihistamine in controlling symptoms of hay fever. On a second study, a group of British researchers gave their approval to butterbur's effectiveness in battling symptoms of grass allergy. Other herbal supplements that function as remedies include freeze-dried nettles (Urtica) and a tonic made from the goldenseal herb (Hydrastis candiensis), which doctors recommend in addition to saline nasal spray (another natural remedy).[38]

Links • General information on allergy and allergens [39] • Allermatch - Sequence comparison to allergenic proteins [40] • SDAP - Structural database of allergenic proteins [41] • Allergome Database [42] • Allergen Nomenclature [43]

References [1] Goldsby, Richard A., et al.,Immunology. 5th ed. New York: W.H. Freeman [2] Rosmilah, M; et al. (December 2008). "Characterization of major allergens of royal jelly Apis mellifera". Trop Biomed 25 (3): 243–51. PMID 19287364.

[3] "Health Canada: Food Allergies" (http:/ / www. hc-sc. gc. ca/ fn-an/ securit/ allerg/ index_e. html). . Retrieved 2007-06-09. [4] "CFIA: Revised Labelling Regulations for Food Allergens, Gluten Sources and Sulphites (Amendments to the Food and Drug Regulations)"

(http:/ / www. inspection. gc. ca/ english/ fssa/ labeti/ allerg/ 20110216inde. shtml). . Retrieved 2011-02-28. [5] GREGORY, PH.; HIRST, JM. (Sep 1952). "Possible role of basidiospores as air-borne allergens". Nature 170 (4323): 414–414. doi:10.1038/170414a0. PMID 12993181. [6] Herxheimer, H.; Hyde, HA.; Williams, DA. (Jul 1969). "Allergic asthma caused by basidiospores". Lancet 2 (7612): 131–3. PMID 4183245. [7] Hasnain, SM.; Wilson, JD.; Newhook, FJ. (May 1985). "Fungal allergy and respiratory disease". N Z Med J 98 (778): 342–6. PMID 3858721. [8] Levetin, E. (Apr 1989). "Basidiospore identification". Ann Allergy 62 (4): 306–10. PMID 2705657. [9] Horner, WE.; Lopez, M.; Salvaggio, JE.; Lehrer, SB. (1991). "Basidiomycete allergy: identification and characterization of an important allergen from Calvatia cyathiformis". Int Arch Allergy Appl Immunol 94 (1–4): 359–361. doi:10.1159/000235403. PMID 1937899. [10] Sprenger, JD.; Altman, LC.; O'Neil, CE.; Ayars, GH.; Butcher, BT.; Lehrer, SB. (Dec 1988). "Prevalence of basidiospore allergy in the Pacific Northwest". J Allergy Clin Immunol 82 (6): 1076–1080. doi:10.1016/0091-6749(88)90146-7. PMID 3204251. [11] Koivikko, A.; Savolainen, J. (Jan 1988). "Mushroom allergy". Allergy 43 (1): 1–10. doi:10.1111/j.1398-9995.1988.tb02037.x. PMID 3278649. [12] Khot, A.; Burn, R.; Evans, N.; Lenney, W.; Storr, J. (Jul 1988). "Biometeorological triggers in childhood asthma". Clin Allergy 18 (4): 351–358. doi:10.1111/j.1365-2222.1988.tb02882.x. PMID 3416418. [13] Hasnain, SM.; Wilson, JD.; Newhook, FJ.; Segedin, BP. (May 1985). "Allergy to basidiospores: immunologic studies". N Z Med J 98 (779): 393–6. PMID 3857522. [14] Santilli, J.; Rockwell, WJ.; Collins, RP. (Sep 1985). "The significance of the spores of the Basidiomycetes (mushrooms and their allies) in bronchial asthma and allergic rhinitis". Ann Allergy 55 (3): 469–71. PMID 4037433. [15] Lehrer, SB.; Lopez, M.; Butcher, BT.; Olson, J.; Reed, M.; Salvaggio, JE. (Sep 1986). "Basidiomycete mycelia and spore-allergen extracts: skin test reactivity in adults with symptoms of respiratory allergy". J Allergy Clin Immunol 78 (3 Pt 1): 478–485. doi:10.1016/0091-6749(86)90036-9. PMID 3760405. [16] Weissman, DN.; Halmepuro, L.; Salvaggio, JE.; Lehrer, SB. (1987). "Antigenic/allergenic analysis of basidiomycete cap, mycelia, and spore extracts". Int Arch Allergy Appl Immunol 84 (1): 56–61. doi:10.1159/000234398. PMID 3623711. [17] Liengswangwong, V.; Salvaggio, JE.; Lyon, FL.; Lehrer, SB. (May 1987). "Basidiospore allergens: determination of optimal extraction methods". Clin Allergy 17 (3): 191–198. doi:10.1111/j.1365-2222.1987.tb02003.x. PMID 3608137. [18] Tarlo, SM.; Bell, B.; Srinivasan, J.; Dolovich, J.; Hargreave, FE. (Jul 1979). "Human sensitization to Ganoderma antigen". J Allergy Clin Immunol 64 (1): 43–49. doi:10.1016/0091-6749(79)90082-4. PMID 447950. [19] Lopez, M.; Butcher, BT.; Salvaggio, JE.; Olson, JA.; Reed, MA.; McCants, ML.; Lehrer, SB. (1985). "Basidiomycete allergy: what is the best source of antigen?". Int Arch Allergy Appl Immunol 77 (1–2): 169–170. doi:10.1159/000233775. PMID 4008070. Allergen 22

[20] Stephen, E.; Raftery, AE.; Dowding, P. (Aug 1990). "Forecasting spore concentrations: a time series approach". Int J Biometeorol 34 (2): 87–89. doi:10.1007/BF01093452. PMID 2228299. [21] Dhillon, M. (May 1991). "Current status of mold immunotherapy". Ann Allergy 66 (5): 385–92. PMID 2035901. [22] Gupta, SK.; Pereira, BM.; Singh, AB. (Mar 1999). "Fomes pectinatis: an aeroallergen in India". Asian Pac J Allergy Immunol 17 (1): 1–7. PMID 10403002. [23] Fischer, B.; Yawalkar, N.; Brander, KA.; Pichler, WJ.; Helbling, A. (Oct 1999). "Coprinus comatus (shaggy cap) is a potential source of aeroallergen that may provoke atopic dermatitis". J Allergy Clin Immunol 104 (4 Pt 1): 836–841. doi:10.1016/S0091-6749(99)70295-2. PMID 10518829. [24] Harley, KG.; Macher, JM.; Lipsett, M.; Duramad, P.; Holland, NT.; Prager, SS.; Ferber, J.; Bradman, A. et al (Apr 2009). "Fungi and pollen exposure in the first months of life and risk of early childhood wheezing". Thorax 64 (4): 353–358. doi:10.1136/thx.2007.090241. PMID 19240083. [25] Bublin M; Radauer C; Wilson IBH; Kraft D; Scheiner O; Breiteneder H; Hoffmann-Sommergruber K (2003). "Cross-reactive N-glycans of Api g 5, a high molecular weight glycoprotein allergen from celery, are required for immunoglobulin E binding and activation of effector cells

from allergic patients" (http:/ / www. fasebj. org/ cgi/ content/ full/ 17/ 12/ 1697). FASEB 17 (12): 1697–1699. doi:10.1096/fj.02-0872fje. PMID 12958180.

[26] "Seasonal Allergy - What to Know" (http:/ / seasonalallergies. us/ ). . Retrieved 2010-04-09.

[27] "Seasonal Allergies" (http:/ / www. merck. com/ mmhe/ sec16/ ch185/ ch185b. html). . Retrieved 2010-04-09.

[28] Seasonal allergies: Something to sneeze at (http:/ / www. cbc. ca/ health/ story/ 2010/ 03/ 19/ f-seasonal-allergies-symptoms. html/ ) CBS News. Retrieved on 2010-08-31

[29] Seasonal Allergies: What to know (http:/ / www. seasonalallergies. us/ ) Seasonal Allergy. Retrieved on 2010-08-31

[30] Parasites behind seasonal allergies (http:/ / www. abc. net. au/ science/ articles/ 2010/ 04/ 12/ 2870397. htm/ ) ABC Science. Retrieved on 2010-08-31

[31] Weinmann, Aileo (2010-04-14) Seasonal allergies getting worse from Climate Change (http:/ / www. nwf. org/ News-and-Magazines/

Media-Center/ News-by-Topic/ Global-Warming/ 2010/ 04-14-10-Seasonal-Allergies-Getting-Worse-From-Climate-Change. aspx/ ) National Wildlife Federation. Media Center. Retrieved on 2010-08-31

[32] Asthma and Allergies: The Symptoms (http:/ / www. asthma. ca/ allergies/ asthmaandallergiessymptoms. html/ ) Asthma & Allergies. Retrieved on 2010-08-31

[33] Seasonal Allergies (http:/ / kidshealth. org/ parent/ medical/ allergies/ seasonal_allergies. html/ ) Kids Health. Retrieved on 2010-08-31

[34] Allergic Rhinitis (http:/ / health. nytimes. com/ health/ guides/ disease/ allergic-rhinitis/ diagnosis. html/ ) New York Times Health Guide. Retrieved on 2010-08-31

[35] "Seasonal Allergies" (http:/ / www. pdrhealth. com/ disease/ disease-mono. aspx?contentFileName=BHG01AL10. xml&

contentName=Seasonal+ allergies& contentId=134& sectionMonograph=ht4). . Retrieved 2010-04-09.

[36] "Non-Sedating or Anti-Drowsy Antihistamine Tablets" (http:/ / www. hayfeverpharmacy. co. nz/ products/ antihistamine-tablets). . Retrieved 2010-04-09.

[37] "Allergy shots" (http:/ / www. mayoclinic. com/ health/ allergy-shots/ MY01158). . Retrieved 2010-04-09.

[38] Relieve Allergies the Natural Way (http:/ / www. webmd. com/ allergies/ guide/ relieve-allergies-natural-way) Web MD. Retrieved on 2010-08-31

[39] http:/ / www. hon. ch/ Library/ Theme/ Allergy/ Glossary/ allergy. html

[40] http:/ / www. allermatch. org

[41] http:/ / fermi. utmb. edu/ SDAP/

[42] http:/ / www. allergome. org/ script/ about. php

[43] http:/ / www. allergen. org Aeroallergen 23 Aeroallergen

An Aeroallergen (pronounced aer·o·al·ler·gen) is any airborne substance, such as pollen or spores, which triggers an allergic reaction.

Pollens Aeroallergens include the pollens of specific seasonal plants is commonly known as "hay fever", because it is most prevalent during haying season, from late May to the end of June in the Northern Hemisphere; but it is possible to suffer from hay fever throughout the year. The pollen which causes hay fever varies from person to person and from region to region; generally speaking, the tiny, hardly visible pollens of wind-pollinated plants are the predominant cause. Pollens of insect-pollinated plants are too large to remain airborne and pose no risk. Examples of plant pollen commonly responsible for hay fever include: • Trees: such as birch (Betula), alder (Alnus), cedar (Cedrus), hazel (Corylus), hornbeam (Carpinus), horse chestnut (Aesculus), willow (Salix), poplar (Populus), plane (Platanus), linden/lime (Tilia) and olive (Olea). In northern latitudes birch is considered to be the most important allergenic tree pollen, with an estimated 15–20% of hay fever sufferers sensitive to birch pollen grains. Olive pollen is most predominant in Mediterranean regions. • Grasses (Family Poaceae): especially ryegrass (Lolium sp.) and timothy (Phleum pratense). An estimated 90% of hay fever sufferers are allergic to grass pollen. • Weeds: ragweed (Ambrosia), plantain (Plantago), nettle/parietaria (Urticaceae), mugwort (Artemisia), Fat hen (Chenopodium) and sorrel/dock (Rumex) The time of year at which hay fever symptoms manifest themselves varies greatly depending on the types of pollen to which an allergic reaction is produced. The pollen count, in general, is highest from mid-spring to early summer. As most pollens are produced at fixed periods in the year, a long-term hay fever sufferer may also be able to anticipate when the symptoms are most likely to begin and end, although this may be complicated by an allergy to dust particles.

Spores In fungi, both asexual and sexual spores or sporangiospores of many fungal species are actively dispersed by forcible ejection from their reproductive structures, which travel through the air over long distances. Many fungi thereby possess specialized mechanical and physiological mechanisms as well as spore-surface structures, such as hydrophobins, for spore ejection. These mechanisms include, for example, forcible discharge of ascospores enabled by the structure of the ascus and accumulation of osmolytes in the fluids of the ascus that lead to explosive discharge of the ascospores into the air.[1] The forcible discharge of single spores termed ballistospores involves formation of a small drop of water (Buller's drop), which upon contact with the spore leads to its projectile release with an initial acceleration of more than 10,000 g.[2] Other fungi rely on alternative mechanisms for spore release, such as external mechanical forces, exemplified by puffballs. Aeroallergen 24

Foodstuffs It is thought that peanuts and other allergic foodstuffs may become airborne, thus triggering allergic reactions in susceptible individuals, especially children.[3][4][5] However, one report notes: Recently concern has been raised that peanut protein in the air will trigger a full-blown anaphylaxis since respiratory exposure can occur in the school setting as food proteins aerosolize into vapors during cooking at high temperatures, even in well-ventilated cafeterias. When airborne peanut protein exposure and reactions of children with known peanut allergies were explored, no allergic symptoms or anaphylaxis were observed when peanut allergic children were not aware of the airborne exposure. Interestingly, when aware of the exposure, symptoms of itchy eyes, sneezing, and runny nose resulted. In a research article by Perry, et al. (2004), no peanut allergen was detected in the air after subjects consumed peanut butter, shelled peanuts, and unshelled peanuts. As Dr. Michael Young notes in his 2006 book, The Peanut Allergy Answer Book, predicting who will have a life-threatening anaphylactic response to airborne allergy is very unpredictable and the likelihood of it is very, very small. ... There remains no evidence that exposure to airborne peanut protein worsens allergy or results in anaphylaxis for the majority of peanut allergic individuals. There always remains the possibility that someone who is exceptionally sensitive will experience a severe reaction, however, protecting them from all possible exposures to peanut protein is extremely difficult. —NetWellness website[6]

Eosinophilic gastroenteritis Eosinophilic gastroenteritis (EG) is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic infiltration of gastrointestinal (GI) tissue, first described by Kaijser in 1937 [7] .[8] Aeroallergens can cause EG.[9][10] The stomach is the organ most commonly affected, followed by the small intestine and the colon .[11][12] As a part of host defense mechanism, eosinophil is normally present in gastrointestinal mucosa, though finding in deeper tissue is almost always pathologic .[13] What triggers such dense infiltration in EG is not clear. It is possible that different pathogenetic mechanisms of disease is involved in several subgroups of patients. Food allergy and variable IgE response to food substances has been observed in some patients which implies role of hypersensitive response in pathogenesis. Many patients indeed have history of other atopic conditions like eczema, asthma etc. Eosinophil recruitment into inflammatory tissue is a complex process, regulated by a number of inflammatory cytokines. In EG cytokines IL-3, IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF) may be behind the recruitement and activation. They have been observed immunohistochemically in diseased intestinal wall .[14] In addition eotaxin has been shown to have an integral role in regulating the homing of eosinophils into the lamina propria of stomach and small intestine .[10] In the allergic subtype of disease, it is thought that food allergens cross the intestinal mucosa and trigger an inflammatory response that includes mast cell degranulation and recruitment of eosinophils.[9] EG is "managed" (treated) with corticosteroids, with a 90% response rate in some studies. Various steroid sparing agents e.g. sodium cromoglycate (a stabilizer of mast cell membranes), ketotifen (an antihistamine), and montelukast (a selective, competitive leukotriene receptor antagonist) have been proposed, centering around an allergic hypothesis, with mixed results.[9][15] An elimination diet may be successful if a limited number of food allergies are identified.[16] Aeroallergen 25

References [1] Trail F. (2007). "Fungal cannons: explosive spore discharge in the Ascomycota". FEMS Microbiology Letterrs 276 (1): 12–8. doi:10.1111/j.1574-6968.2007.00900.x. PMID 17784861. [2] Pringle A, Patek SN, Fischer M, Stolze J, Money NP. (2005). "The captured launch of a ballistospore". Mycologia 97 (4): 866–71. doi:10.3852/mycologia.97.4.866. PMID 16457355. [3] The Michael C. Young, M.D., "Common Beliefs About Peanut Allergy: Fact or Fiction?" (reprinted with permission of the Food Allergy &

Anaphylaxis Network, in Anaphylaxis Canada, September newsletter) found at allergysafecommunities.ca (http:/ / www.

allergysafecommunities. ca/ assets/ common_beliefs_faan_2003. pdf). (.pdf) Accessed March 19, 2009. [4] "Passengers with the condition, which can be deadly, can try to ensure a peanut-free flight. But even the best plans sometimes don't work." See "Out of the Blue: Peanut allergies are a little-known danger." Elliott Hester, St. Petersburg Times, December 30, 2001, St. Petersburg

Times (http:/ / www. sptimes. com/ News/ 123001/ Travel/ Out_of_the_Blue__Pean. shtml). Accessed March 19, 2009. [5] Constance Hays, "Ideas & Trends: Airborne Allergies; A New Fear of Flying: Peanuts," New York Times, Sunday, May 10, 1998, found at

NY Times archives (http:/ / query. nytimes. com/ gst/ fullpage. html?sec=health& res=9E03E2D61031F933A25756C0A96E958260). Accessed March 19, 2009. [6] Jill F. Kilanowski & Ann Stalter (College of Nursing, The Ohio State University), "Children's Health: Peanut Allergy in the School

Environment: Myths and Facts: Part 1 of a 2-Part Series," at NetWellness website (http:/ / www. netwellness. org/ healthtopics/ ch/ peanut1. cfm), citing Perry, T., Conover-Walker, M., Pomes, A., Chapman, M., & Wood, R. (2004). "Distribution of peanut allergen in the environment." Journal of Allergy and Clinical Immunology, 113, 973-976. Accessed March 19, 2009. [7] Kaijser R. Zur Kenntnis der allergischen Affektionen des Verdauugskanals vom Standpunkt des Chirurgen aus. Arch Klin Chir 1937; 188:36–64. [8] Whitaker I, Gulati A, McDaid J, Bugajska-Carr U, Arends M (2004). "Eosinophilic gastroenteritis presenting as obstructive jaundice". European journal of gastroenterology & hepatology 16 (4): 407–9. doi:10.1097/00042737-200404000-00007. PMID 15028974. [9] Pérez-Millán A, Martín-Lorente J, López-Morante A, Yuguero L, Sáez-Royuela F (1997). "Subserosal eosinophilic gastroenteritis treated efficaciously with sodium cromoglycate". Dig. Dis. Sci. 42 (2): 342–4. doi:10.1023/A:1018818003002. PMID 9052516. [10] Mishra A, Hogan S, Brandt E, Rothenberg M (2001). "An etiological role for aeroallergens and eosinophils in experimental esophagitis". J. Clin. Invest. 107 (1): 83–90. doi:10.1172/JCI10224. PMC 198543. PMID 11134183. [11] Naylor A (1990). "Eosinophilic gastroenteritis". Scottish medical journal 35 (6): 163–5. PMID 2077646. [12] Jimenez-Saenz M, Villar-Rodriguez J, Torres Y, Carmona I, Salas-Herrero E, Gonzalez-Vilches J, Herrerias-Gutierrez J (2003). "Biliary tract disease: a rare manifestation of eosinophilic gastroenteritis". Dig. Dis. Sci. 48 (3): 624–7. doi:10.1023/A:1022521707420. PMID 12757181. [13] Blackshaw A, Levison D (1986). "Eosinophilic infiltrates of the gastrointestinal tract". J. Clin. Pathol. 39 (1): 1–7. doi:10.1136/jcp.39.1.1. PMC 499605. PMID 2869055. [14] Desreumaux P, Bloget F, Seguy D, Capron M, Cortot A, Colombel J, Janin A (1996). "Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis". Gastroenterology 110 (3): 768–74. doi:10.1053/gast.1996.v110.pm8608886. PMID 8608886. [15] Barbie D, Mangi A, Lauwers G (2004). "Eosinophilic gastroenteritis associated with systemic lupus erythematosus". J. Clin. Gastroenterol. 38 (10): 883–6. doi:10.1097/00004836-200411000-00010. PMID 15492606. [16] Katz A, Twarog F, Zeiger R, Falchuk Z (1984). "Milk-sensitive and eosinophilic gastroenteropathy: similar clinical features with contrasting mechanisms and clinical course". J. Allergy Clin. Immunol. 74 (1): 72–8. doi:10.1016/0091-6749(84)90090-3. PMID 6547462. Allergic inflammation 26 Allergic inflammation

Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including allergic asthma, atopic dermatitis, allergic rhinitis and several ocular allergic diseases. Allergic reactions may generally be divided into two components; the early phase reaction, and the late phase reaction. While the contribution to the development of symptoms from each of the phases varies greatly between diseases, both are usually present and provide us a framework for understanding allergic disease [1][2][3][4]. Tissues affected in allergic inflammation. The early phase of the allergic reaction typically occurs within minutes, or even seconds, following allergen exposure and is also commonly referred to as the immediate allergic reaction or as a Type I allergic reaction [5]. The reaction is caused by the release of histamine and mast cell granule proteins by a process called degranulation, as well as the production of leukotrienes, prostaglandins and cytokines, by mast cells following the cross-linking of allergen specific IgE molecules bound to mast cell FcεRI receptors [3]. These mediators affect nerve cells causing itching [6], smooth muscle cells causing contraction (leading to the airway narrowing seen in allergic asthma) [4], goblet cells causing mucus production [1], and endothelial cells causing vasodilatation and edema [6].

The late phase of a Type 1 reaction (which develops 8-12 hours and is mediated by mast cells)[5] should not be confused with delayed hypersensitivity Type IV allergic reaction (which takes 48-72 hours to develop and is mediated by T cells)[7]. The products of the early phase reaction include chemokines and molecules that act on endothelial cells and cause them to express Intercellular adhesion molecule (such as vascular cell adhesion molecule and selectins), which together result in the recruitment and activation of leukocytes from the blood into the site of the allergic reaction [3]. Typically, the infiltrating cells observed in allergic reactions contain a high proportion of lymphocytes, and especially, of eosinophils. The recruited eosinophils will degranulate releasing a number of cytotoxic molecules (including Major Basic Protein and eosinophil peroxidase) as well as produce a number of cytokines such as IL-5 [8]. The recruited T-cells are typically of the Th2 variety and the cytokines they produce lead to further recruitment of mast cells and eosinophils, and in plasma cell isotype switching to IgE which will bind to the mast cell FcεRI receptors and prime the individual for further allergic responses. Allergic inflammation 27

References

[1] Fireman P (2003). "Understanding asthma pathophysiology" (http:/ / openurl. ingenta. com/ content/ nlm?genre=article& issn=1088-5412&

volume=24& issue=2& spage=79& aulast=Fireman). Allergy Asthma Proc 24 (2): 79–83. PMID 12776439. .

[2] Leung DY (1998). "Molecular basis of allergic diseases" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S1096-7192(98)92682-8). Mol. Genet. Metab. 63 (3): 157–67. doi:10.1006/mgme.1998.2682. PMID 9608537. .

[3] Hansen I, Klimek L, Mösges R, Hörmann K (2004). "Mediators of inflammation in the early and the late phase of allergic rhinitis" (http:/ /

meta. wkhealth. com/ pt/ pt-core/ template-journal/ lwwgateway/ media/ landingpage. htm?issn=1528-4050& volume=4& issue=3& spage=159). Curr Opin Allergy Clin Immunol 4 (3): 159–63. doi:10.1097/00130832-200406000-00004. PMID 15126935. . [4] Katelaris CH (2003). "Ocular allergy: implications for the clinical immunologist". Ann. Allergy Asthma Immunol. 90 (6 Suppl 3): 23–7. doi:10.1016/S1081-1206(10)61656-0. PMID 12839109. [5] Janeway, Charles (2001). Immunobiology: the immune system in health and disease (5th ed.). New York: Garland. ISBN 0-8153-3642-X.

[6] Trocme SD, Sra KK (2002). "Spectrum of ocular allergy" (http:/ / meta. wkhealth. com/ pt/ pt-core/ template-journal/ lwwgateway/ media/

landingpage. htm?issn=1528-4050& volume=2& issue=5& spage=423). Curr Opin Allergy Clin Immunol 2 (5): 423–7. doi:10.1097/00130832-200210000-00010. PMID 12582327. .

[7] Hinshaw WD, Neyman GP, Olmstead SM. "Hypersensitivity Reactions, Delayed" (http:/ / emedicine. medscape. com/ article/ 136118-overview). eMedicine. .

[8] Rothenberg ME; Rothenberg, Marc E. (1998). "Eosinophilia" (http:/ / content. nejm. org/ cgi/ pmidlookup?view=short& pmid=9603798& promo=ONFLNS19). N. Engl. J. Med. 338 (22): 1592–600. doi:10.1056/NEJM199805283382206. PMID 9603798. . Anaphylaxis 28 Anaphylaxis

Anaphylaxis Classification and external resources

Angioedema of the face such that the boy is unable to open his eyes. This reaction was due to an allergen exposure.

[1] ICD-10 T78.2

[2] ICD-9 995.0

[3] DiseasesDB 29153

[4] MedlinePlus 000844

[5] eMedicine med/128

[6] MeSH D000707

Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death".[7] It typically results in a number of symptoms including an itchy rash, throat swelling, and low blood pressure. Common causes include insect bites, foods, and medications. On a pathophysiologic level, anaphylaxis is due to the release of mediators from certain types of white blood cells triggered either by immunologic or non-immunologic mechanisms. It is diagnosed based on the presenting symptoms and signs. The primary treatment is injection of epinephrine, with other measures being complementary. Worldwide 0.05–2% of people are estimated to have anaphylaxis at some point in their life and rates appear to be increasing. The term comes from the Greek words ἀνά ana, against, and φύλαξις phylaxis, protection. Anaphylaxis 29

Signs and symptoms

Anaphylaxis typically presents with many different symptoms over minutes or hours[8][9] with an average onset of 5 to 30 minutes if exposure is intravenous and 2 hours for foods.[10] The most common areas affected include: skin (80–90%), respiratory (70%), gastrointestinal (30–45%), heart and vasculature (10–45%), and central nervous system (10–15%)[9] with usually two or more being involved.[11]

Signs and symptoms of anaphylaxis.

Skin

Symptoms typically include generalized hives, itchiness, flushing or swelling of the lips.[12] Those with swelling or angioedema may describe a burning sensation of the skin rather than itchiness.[10] Swelling of the tongue or throat occurs in up to about 20% of cases.[13] Other features may include a runny nose and swelling of the conjunctiva.[14] The skin may also be blue tinged due to a lack of oxygen.[14]

Respiratory Hives and flushing on the back of a person with anaphylaxis Respiratory symptoms and signs that may be present, including shortness of breath, wheezes or stridor.[12] The wheezing is typically due to spasms of the bronchial muscles[15] while stridor is related to upper airway obstruction secondary to swelling.[14] Hoarseness, pain with swallowing, or a cough may also occur.[10]

Cardiac Coronary artery spasm may occur with subsequent myocardial infarction, dysrhythmia, or cardiac arrest.[9][11] Those with underlying coronary disease are at greater risk of cardiac effects from anaphylaxis.[15] The coronary spasm is related to the presence of histamine-releasing cells in the heart.[15] While a fast heart rate due to low blood pressure is more common,[14] a Bezold–Jarisch reflex has been described in 10% of cases, where a slow heart rate is associated with low blood pressure.[16] A drop in blood pressure or shock (either distributive or cardiogenic) may result in the feeling of lightheadedness or loss of consciousness.[15] Rarely very low blood pressure may be the only sign of anaphylaxis.[13] Anaphylaxis 30

Other Gastrointestinal symptoms may include crampy abdominal pain, diarrhea, and vomiting.[12] There may be confusion, a loss of bladder control or pelvic pain similar to that of uterine cramps.[12][14] Dilation of blood vessels around the brain may cause headaches.[10] A feeling of anxiety or of "impending doom" has also be described.[11]

Causes Anaphylaxis can occur in response to almost any foreign substance.[17] Common triggers include venom from insect bites or stings, foods, and medication.[16][18] Foods are the most common trigger in children and young adults while medications and insect bites and stings are more common in older adults.[11] Less common causes include: physical factors, biological agents such as semen, latex, hormonal changes, food additives such as monosodium glutamate and food colors, and topical medications.[14] Physical factors such as exercise (known as exercise-induced anaphylaxis) or temperature (either hot or cold) may also act as triggers through their direct effects on mast cells.[11][19] Exercise induced events are frequently associated with the ingestion of certain foods.[10] During anesthesia, neuromuscular blocking agents, antibiotics, and latex are the most common causes.[20] The cause remains unknown in 32-50% of cases, referred to as "idiopathic anaphylaxis".[21]

Food Many foods can trigger anaphylaxis; this may occur upon the first known ingestion.[16] Common triggering foods vary around the world. In Western cultures, ingestion of or exposure to peanuts, wheat, tree nuts, shellfish, fish, milk, and eggs are the most prevalent causes.[9][11] Sesame is common in the Middle East, while rice and chickpea are frequently encountered as sources of anaphylaxis in Asia.[11] Severe cases are usually the result of ingesting the allergen,[16] but some people experience a severe reaction upon contact. Children can outgrow their allergies. By age 16, 80% of children with anaphylaxis to milk or eggs and 20% who experience isolated anaphylaxis to peanuts are able to tolerate these foods.[17]

Medication Any medication may potentially trigger anaphylaxis. The most common are β-lactam antibiotics (such as penicillin) followed by aspirin and NSAIDs.[9][22] Other antibiotics are implicated less frequently and the reactions to NSAIDs are agent specific meaning that if one is allergic to one NSAID they can typically tolerate a different one.[22] Other relatively common causes include chemotherapy, vaccines, protamine and herbal preparations.[11][22] Some medications (vancomycin, morphine, x-ray contrast among others) cause anaphylaxis by directly triggering mast cell degranulation.[16] The frequency of a reaction to an agent partly depends on the frequency of its use and partly on its intrinsic properties.[23] Anaphylaxis to penicillins or cephalosporins only occurs after they bind to proteins inside the body with some agents binding more easily than other.[10] Anaphylaxis to penicillin occurs once in every 2,000 to 10,000 courses of treatment, with death occurring in less than one in every 50,000 courses of treatment.[10] Anaphylaxis to aspirin and NSAIDs occurs in about one in every 50,000 persons.[10] If someone has a reaction to penicillins their risk of a reaction to cephalosporins is greater but still less than one in 1000.[10] The old radiocontrast agents caused reactions in 1% of cases while the newer lower osmolar agents cause reactions in 0.04% of cases.[23] Anaphylaxis 31

Venom Venom from stinging or biting insects such as Hymenoptera (bees and wasps) or Triatominae (kissing bugs) may induce anaphylaxis in susceptible people.[9][24] Previous systemic reactions, which are anything more than a local reaction around the site of the sting, are a risk factor for future anaphylaxis;[25][26] however, half of fatalities have had no previous systemic reaction.[27]

Risk factors People with atopic diseases such as asthma, eczema, or allergic rhinitis are at high risk of anaphylaxis from food, latex, and radiocontrast but not injectable medications or stings.[11][16] One study in children found that 60% had a history of previous atopic diseases, and of those who die from anaphylaxis more than 90% have asthma.[16] Those with mastocytosis or of a higher socioeconomic status are at increased risk.[11][16] The longer the time since the last exposure to the agent in question the lower the risk.[10]

Pathophysiology Anaphylaxis is a severe allergic reaction of rapid onset affecting many body systems.[7][28] It is due to the release of inflammatory mediators and cytokines from mast cells and basophils, typically due to an immunologic reaction but sometimes non-immunologic mechanism.[28]

Immunologic In the immunologic mechanism, immunoglobulin E (IgE) binds to the antigen (the foreign material that provokes the allergic reaction). Antigen-bound IgE then activates FcεRI receptors on mast cells and basophils. This leads to release of inflammatory mediators such as histamine. These mediators subsequently increase the contraction of bronchial smooth muscles, trigger vasodilation, increase the leakage of fluid from blood vessels, and cause heart muscle depression.[10][28] There is also an immunologic mechanism that does not rely on IgE, but it is not known if this occurs in humans.[28]

Non-immunologic Non-immunologic mechanisms involved substances that directly cause the degranulation of mast cells and basophils. These include agents such as contrast medium, opioids, temperature (hot or cold), and vibration.[19][28]

Diagnosis Anaphylaxis is diagnosed based on clinical criteria.[11] When any one of the following three occurs within minutes/hours of exposure to an allergen there is a high likelihood of anaphylaxis:[11] 1. Involvement of the skin or mucosal tissue plus either respiratory difficulty or a low blood pressure 2. Two or more of the following symptoms:- a. Involvement of the skin or mucosa b. Respiratory difficulties c. Low blood pressure d. Gastrointestinal symptoms 3. Low blood pressure after exposure to a known allergen During an attack, blood tests for tryptase or histamine (released from mast cells) might be useful in diagnosing anaphylaxis due to insect stings or medications. However these tests are of limited utility if the cause is food or if the person has a normal blood pressure,[11] and they are not specific for the diagnosis.[17] Anaphylaxis 32

Classification There are three main classifications of anaphylaxis. Anaphylactic shock is associated with systemic vasodilation that results in low blood pressure which is by definition 30% lower than the person's baseline or below standard values.[13] Biphasic anaphylaxis is the recurrence of symptoms within 1–72 hours with no further exposure to the allergen.[11] Reports of incidence vary, with some studies claiming as many as 20% of cases.[29] The recurrence typically occurs within 8 hours.[16] It is managed in the same manner as anaphylaxis.[9] Pseudoanaphylaxis or anaphylactoid reactions are a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation.[16][30] Non-immune anaphylaxis is the current term use by the World Allergy Organization[30] with some recommending that the old terminology no longer be used.[16]

Allergy testing

Allergy testing may help in determining the trigger. Skin allergy testing (such as patch testing) is available for certain foods and venoms.[17] Blood testing for specific IgE can be useful to confirm milk, egg, peanut, tree nut and fish allergies.[17] Skin testing is available to confirm penicillin allergies but is not available for other medications.[17] Non-immune forms of anaphylaxis can only be determined by history or exposure to the allergen in question, and not by skin or blood testing.[30]

Skin allergy testing being carried out on the right Differential diagnosis arm It can sometimes be difficult to distinguish anaphylaxis from asthma, syncopy, and panic attacks.[11] Asthma however typically does not have itching or gastrointestinal symptoms, syncope presents with pallor rather than a rash, and a panic attack may have flushing but does not have hives.[11] Other conditions that may present similarly include: scrombroidosis and anisakiasis.[16]

Post-mortem findings In a person who died from anaphylaxis, autopsy may show an "empty heart" attributed to reduced venous return from vasodilation and redistribution of intravascular volume from the central to the peripheral compartment.[31] Other signs are laryngeal edema, eosinophilia in lungs, heart and tissues, and evidence of myocardial hypoperfusion.[32] Laboratory findings could detect increased levels of serum tryptase, increase in total and specific IgE serum levels.[32]

Prevention Avoidance of the trigger of anaphylaxis is recommended. In cases where this may not be possible, desensitization may be an option. Immunotherapy with Hymenoptera venoms is effective at desensitizing 80–90% of adults and 98% of children against allergies to bees, wasps, hornets, yellowjackets, and fire ants. Oral immunotherapy may be effective at desensitizing some people to certain food including milk, eggs, nuts and peanuts; however adverse effects are common. Desensitization is also possible for many medications, however it is advised that most people simply avoid the agent in question. In those who react to latex it may be important to avoid cross-reactive foods such as avocados, bananas, and potatoes among others.[11] Anaphylaxis 33

Management Anaphylaxis is a medical emergency that may require resuscitation measures such as airway management, supplemental oxygen, large volumes of intravenous fluids, and close monitoring.[9] Administration of epinephrine is the treatment of choice with antihistamines and steroids often used as adjuncts.[11] A period of in hospital observation for between 2 and 24 hours is recommended for people once they have returned to normal due to concerns of biphasic anaphylaxis.[16][29][33][10]

Epinephrine

Epinephrine (adrenaline) is the primary treatment for anaphylaxis with no absolute contraindication to its use.[9] It is recommended that an epinephrine solution be given intramuscularly into the mid

anterolaterial thigh as soon as the diagnosis is suspected. The injection An old version of an EpiPen auto-injector may be repeated every 5 to 15 minutes if there is insufficient response.[11] A second dose is needed in 16 to 35% of episodes[16] with more than two doses rarely required.[11] The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption.[34] Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations.[11]

People on β-blockers may be resistant to the effects of epinephrine.[16] In this situation if epinephrine is not effective intravenous glucagon can be administered which has a mechanism of action independent of β-receptors.[16] If necessary, it can also be given intravenously using a dilute epinephrine solution. Intravenous epinephrine however has been associated both with dysrhythmia and myocardial infarction.[35] Epinephrine autoinjector used for self-administration typically in two doses, one for adults or children who weight more than 25 kg and one for children who weigh 10 to 25 kg.[36]

Adjuncts Antihistamines (both H1 and H2), while commonly used and assumed effective based on theoretical reasoning, are poorly supported by evidence. A 2007 Cochrane review did not find any good-quality studies upon which to base recommendations[37] and they are not believed to have an effect on airway edema or spasm.[16] Corticosteroids are unlikely to make a difference in the current episode of anaphylaxis, but may be used in the hope of decreasing the risk of biphasic anaphylaxis. Their prophylactic effectiveness in these situations is uncertain.[29] Nebulized salbutamol may be effective for bronchospasm that does not resolve with epinephrine.[16] Methylene blue has been used in those not responsive to other measures due to its presumed effect of relaxing smooth muscle.[16]

Preparedness People prone to anaphylaxis are advised to have an "allergy action plan", and parents are advised to inform schools of their children's allergies and what to do in case of an anaphylactic emergency.[38] The action plan usually includes use of epinephrine auto-injectors, the recommendation to wear a medical alert bracelet, and counseling on avoidance of triggers.[38] Immunotherapy is available for certain triggers to prevent future episodes of anaphylaxis. A multi-year course of subcutaneous desensitization has been found effective against stinging insects, while oral desensitization is effective for many foods.[9] Anaphylaxis 34

Prognosis In those in whom the cause is known and prompt treatment is available, the prognosis is good.[39] Even if the cause is unknown, if appropriate preventative medication is available, the prognosis is generally good.[10] If death occurs, it is usually due to either respiratory (typically asphyxia) or cardiovascular causes (shock),[16][28] with 0.7–20% of cases resulting in death.[10][15] There have been cases of death occurring within minutes.[11] Outcomes in those with exercise-induced anaphylaxis are typically good, with fewer and less severe episodes as people get older.[40]

Epidemiology The incidence of anaphylaxis is 4–5 per 100,000 persons per year,[16] with a lifetime risk of 0.5–2%.[11] Rates appear to be increasing: incidence in the 1980s was approximately 20 per 100,000 per year, while in the 1990s it was 50 per 100,000 per year.[9] The increase appears to be primarily for food-induced anaphylaxis.[41] The risk is greatest in young people and females.[9][16] Currently, anaphylaxis leads to 500–1,000 deaths per year (2.4 per million) in the United States, 20 deaths per year in the United Kingdom (0.33 per million), and 15 deaths per year in Australia (0.64 per million).[16] Mortality rates have decreased between the 1970s and 2000s.[42] In Australia, death from food-induced anaphylaxis occur primarily in women while deaths due to insect bites primarily occur in males.[16] Death from anaphylaxis is most commonly triggered by medications.[16]

History The term "aphylaxis" was coined by Charles Richet in 1902 and later changed to "anaphylaxis" due to its nicer quality of speech.[17] He was subsequently awarded the Nobel Prize in Medicine and Physiology for his work on anaphylaxis in 1913.[10] The phenomenon itself however has been described since ancient times.[30] The term comes from the Greek words ἀνά ana, against, and φύλαξις phylaxis, protection.[43]

Research There are ongoing efforts to develop sublingual epinephrine to treat anaphylaxis.[16] Subcutaneous injection of the anti-IgE antibody omalizumab is being studied as a method of preventing recurrence, but it is not yet recommended.[11][44]

References

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[6] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D000707 [7] Tintinalli, Judith E. (2010). Emergency Medicine: A Comprehensive Study Guide (Emergency Medicine (Tintinalli)). New York: McGraw-Hill Companies. pp. 177–182. ISBN 0-07-148480-9. [8] Oswalt ML, Kemp SF (May 2007). "Anaphylaxis: office management and prevention". Immunol Allergy Clin North Am 27 (2): 177–91, vi. doi:10.1016/j.iac.2007.03.004. PMID 17493497. "Clinically, anaphylaxis is considered likely to be present if any one of three criteria is satisfied within minutes to hours"

[9] Simons FE (October 2009). "Anaphylaxis: Recent advances in assessment and treatment" (https:/ / secure. muhealth. org/ ~ed/ students/

articles/ JAClinImmun_124_p0625. pdf). J. Allergy Clin. Immunol. 124 (4): 625–36; quiz 637–8. doi:10.1016/j.jaci.2009.08.025. PMID 19815109. . [10] Marx, John (2010). Rosen's emergency medicine: concepts and clinical practice 7th edition. Philadelphia, PA: Mosby/Elsevier. p. 15111528. ISBN 978-0-323-05472-0. [11] Simons, FE; World Allergy, Organization (2010 May). "World Allergy Organization survey on global availability of essentials for the

assessment and management of anaphylaxis by allergy-immunology specialists in health care settings." (http:/ / www. csaci. ca/ include/ files/ Anaphylaxis 35

WAO_Anaphylaxis_Guidelines_2011. pdf). Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 104 (5): 405–12. PMID 20486330. . [12] Sampson HA, Muñoz-Furlong A, Campbell RL, et al. (February 2006). "Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium". J. Allergy Clin. Immunol. 117 (2): 391–7. doi:10.1016/j.jaci.2005.12.1303. PMID 16461139. [13] Limsuwan, T; Demoly, P (2010 Jul). "Acute symptoms of drug hypersensitivity (urticaria, angioedema, anaphylaxis, anaphylactic shock)."

(http:/ / smschile. cl/ documentos/ cursos2010/ MedicalClinicsNorthAmerica/ Acute Symptoms of Drug Hypersensitivity (Urticaria,

Angioedema, Anaphylaxis, Anaphylactic Shock). pdf). The Medical clinics of North America 94 (4): 691–710, x. PMID 20609858. . [14] Brown, SG; Mullins, RJ, Gold, MS (2006 Sep 4). "Anaphylaxis: diagnosis and management.". The Medical journal of Australia 185 (5): 283–9. PMID 16948628.

[15] Triggiani, M; Patella, V, Staiano, RI, Granata, F, Marone, G (2008 Sep). "Allergy and the cardiovascular system." (http:/ / www. ncbi. nlm.

nih. gov/ pmc/ articles/ PMC2515352/ ?tool=pubmed). Clinical and experimental immunology 153 Suppl 1: 7–11. PMC 2515352. PMID 18721322. . [16] Lee, JK; Vadas, P (2011 Jul). "Anaphylaxis: mechanisms and management.". Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 41 (7): 923–38. PMID 21668816. [17] Boden, SR; Wesley Burks, A (2011 Jul). "Anaphylaxis: a history with emphasis on food allergy.". Immunological reviews 242 (1): 247–57. PMID 21682750. [18] Worm, M (2010). "Epidemiology of anaphylaxis.". Chemical immunology and allergy 95: 12–21. PMID 20519879.

[19] editors, Marianne Gausche-Hill, Susan Fuchs, Loren Yamamoto, (2007). The pediatric emergency medicine resource (http:/ / books. google.

ca/ books?id=lLVfDC2dh54C& pg=PA69) (Rev. 4. ed. ed.). Sudbury, Mass.: Jones & Bartlett. pp. 69. ISBN 978-0-7637-4414-4. . [20] Dewachter, P; Mouton-Faivre, C, Emala, CW (2009 Nov). "Anaphylaxis and anesthesia: controversies and new insights.". Anesthesiology 111 (5): 1141–50. doi:10.1097/ALN.0b013e3181bbd443. PMID 19858877.

[21] editor, Mariana C. Castells, (2010). Anaphylaxis and hypersensitivity reactions (http:/ / books. google. ca/ books?id=bEvnfm7V-LIC& pg=PA223). New York: Humana Press. pp. 223. ISBN 978-1-60327-950-5. .

[22] Volcheck, Gerald W. (2009). Clinical allergy : diagnosis and management (http:/ / books. google. ca/ books?id=pWZLkZB7EW8C& pg=PA442). Totowa, N.J.: Humana Press. pp. 442. ISBN 978-1-58829-616-0. . [23] Drain, KL; Volcheck, GW (2001). "Preventing and managing drug-induced anaphylaxis.". Drug safety : an international journal of medical toxicology and drug experience 24 (11): 843–53. PMID 11665871. [24] Klotz, JH; Dorn, PL, Logan, JL, Stevens, L, Pinnas, JL, Schmidt, JO, Klotz, SA (2010 Jun 15). ""Kissing bugs": potential disease vectors and cause of anaphylaxis.". Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 50 (12): 1629–34. PMID 20462351. [25] Bilò, MB (2011 Jul). "Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment.". Allergy 66 Suppl 95: 35–7. PMID 21668850. [26] Cox, L; Larenas-Linnemann, D, Lockey, RF, Passalacqua, G (2010 Mar). "Speaking the same language: The World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System.". The Journal of allergy and clinical immunology 125 (3): 569–74, 574.e1-574.e7. PMID 20144472. [27] Bilò, BM; Bonifazi, F (2008 Aug). "Epidemiology of insect-venom anaphylaxis.". Current opinion in allergy and clinical immunology 8 (4): 330–7. PMID 18596590. [28] Khan, BQ; Kemp, SF (2011 Aug). "Pathophysiology of anaphylaxis.". Current opinion in allergy and clinical immunology 11 (4): 319–25. PMID 21659865. [29] Lieberman P (September 2005). "Biphasic anaphylactic reactions". Ann. Allergy Asthma Immunol. 95 (3): 217–26; quiz 226, 258. doi:10.1016/S1081-1206(10)61217-3. PMID 16200811.

[30] Ring, J; Behrendt, H, de Weck, A (2010). "History and classification of anaphylaxis." (http:/ / media. wiley. com/ product_data/ excerpt/ 42/

04708611/ 0470861142. pdf). Chemical immunology and allergy 95: 1–11. PMID 20519878. .

[31] Anaphylaxis, Author: Stephen F Kemp, MD, FACP; Chief Editor: Michael A Kaliner, MD;http:/ / emedicine. medscape. com/ article/ 135065-overview#showall [32] Da Broi, U; Moreschi, C (2011 Jan 30). "Post-mortem diagnosis of anaphylaxis: A difficult task in forensic medicine.". Forensic science international 204 (1-3): 1–5. PMID 20684869.

[33] "Emergency treatment of anaphylactic reactions – Guidelines for healthcare providers" (http:/ / www. resus. org. uk/ pages/ reaction. pdf) (PDF). Resuscitation Council (UK). January 2008. . Retrieved 2008-04-22. [34] Simons, KJ; Simons, FE (2010 Aug). "Epinephrine and its use in anaphylaxis: current issues.". Current opinion in allergy and clinical immunology 10 (4): 354–61. PMID 20543673. [35] Mueller, UR (2007 Aug). "Cardiovascular disease and anaphylaxis.". Current opinion in allergy and clinical immunology 7 (4): 337–41. PMID 17620826. [36] Sicherer, SH; Simons, FE, Section on Allergy and Immunology, American Academy of, Pediatrics (2007 Mar). "Self-injectable epinephrine for first-aid management of anaphylaxis.". Pediatrics 119 (3): 638–46. PMID 17332221. [37] Sheikh A, Ten Broek V, Brown SG, Simons FE (August 2007). "H1-antihistamines for the treatment of anaphylaxis: Cochrane systematic review". Allergy 62 (8): 830–7. doi:10.1111/j.1398-9995.2007.01435.x. PMID 17620060. Anaphylaxis 36

[38] Martelli, A; Ghiglioni, D, Sarratud, T, Calcinai, E, Veehof, S, Terracciano, L, Fiocchi, A (2008 Aug). "Anaphylaxis in the emergency department: a paediatric perspective.". Current opinion in allergy and clinical immunology 8 (4): 321–9. PMID 18596589.

[39] Harris, edited by Jeffrey; Weisman, Micheal S. (2007). Head and neck manifestations of systemic disease (http:/ / books. google. ca/

books?id=31yUl-V90XoC& pg=PA325). London: Informa Healthcare. pp. 325. ISBN 978-0-8493-4050-5. .

[40] editor, Mariana C. Castells, (2010). Anaphylaxis and hypersensitivity reactions (http:/ / books. google. ca/ books?id=bEvnfm7V-LIC& pg=PA223). New York: Humana Press. pp. 223. ISBN 978-1-60327-950-5. . [41] Koplin, JJ; Martin, PE, Allen, KJ (2011 Oct). "An update on epidemiology of anaphylaxis in children and adults.". Current opinion in allergy and clinical immunology 11 (5): 492–6. PMID 21760501. [42] Demain, JG; Minaei, AA, Tracy, JM (2010 Aug). "Anaphylaxis and insect allergy.". Current opinion in allergy and clinical immunology 10 (4): 318–22. PMID 20543675.

[43] "anaphylaxis" (http:/ / www. merriam-webster. com/ dictionary/ anaphylaxis). merriam-webster.com. . Retrieved 2009-11-21. [44] Vichyanond, P (2011 Sep). "Omalizumab in allergic diseases, a recent review.". Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 29 (3): 209–19. PMID 22053590.

External links

• Anaphylaxis (http:/ / www. dmoz. org/ Health/ Conditions_and_Diseases/ Allergies/ Anaphylaxis/ / ) at the Open Directory Project 37

Food Allergies

Food allergy

Food allergy Classification and external resources

[1] ICD-10 T78.0

[2] [3] ICD-9 V15.01 -V15.05

[4] OMIM 147050

[5] MedlinePlus 000817

[6] eMedicine med/806

[7] MeSH D005512

A food allergy is an adverse immune response to a food protein.[8][9] They are distinct from other adverse responses to food, such as food intolerance, pharmacological reactions, and toxin-mediated reactions. The 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 anaphylactic responses as biphasic anaphylaxis and vasodilation; these require immediate emergency intervention. 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 wear some form of medical alert jewelry, or develop an emergency action plan, in accordance with their doctor. The scope of problem, particularly for young people, is a significant public health issue. Food allergy 38

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.[10] 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 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.

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:[11] • Hives[11] • Itching of mouth, lips, tongue, throat, eyes, skin, or else areas[11] • Swelling (angioedema) of lips, tongue, eyelids, or the whole face[11] • Difficulty swallowing[11] • Runny or congested nose[11] [11] • Hoarse voice Hives on the back are a common allergy [11] • Wheezing and/or shortness of breath symptom.

• Nausea[11] • Vomiting[11] • Abdominal pain and/or stomach cramps[11] • Lightheadedness[11] • Fainting[11] Symptoms of allergies vary from person to person. The amount of food needed to trigger a reaction also varies from person to person. Food allergy 39

Cardiopulmonary Serious danger regarding allergies can begin when the respiratory tract or blood circulation is affected. The latter can be indicated through wheezing and cyanosis. Poor blood circulation leads to a weak pulse, pale skin, and fainting.[12] 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 affected and show symptoms.[13] This occurs because no nutrients are circulated throughout the body, causing the widening of blood vessels. This vasodilation causes blood pressure to decrease, 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.[14]

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.[15] Tree nuts, including pecans, pistachios, pine nuts, and walnuts, are also common allergens. Sufferers may be sensitive to one particular tree nut or to many different tree nuts.[16] Also seeds, including sesame seeds and poppy seeds, contain oils where protein is present, which may elicit an allergic reaction.[16] Egg allergies affect about one in fifty children but are frequently outgrown by children when they reach age five.[17] Typically the sensitivity is to proteins in the white, rather than the yolk.[16] Milk, from cows, goats or sheep, is another common food allergen, 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.[18] 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.[19] These are often referred to as "the big eight."[20] Allergies to seeds — especially sesame — seem to be increasing in many countries.[21] 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.[22]

Cross reactivity Some children who are allergic to cow's milk protein also show a cross sensitivity to soy-based products.[23] 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.[24] Food allergy 40

Pathophysiology

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 A histamine, the structure shown, is what causes a person to feel itchy during an allergic reaction. on the surface of the protein, creating a tag, just as a virus or parasite A common medication to stop this is an becomes tagged. It is not entirely clear why some proteins do not antihistamine, which fights the histamines in the denature and subsequently trigger allergic reactions and person's system. hypersensitivity while others do not.[25]

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.[26] 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.[27]

Acute response

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 T 2 lymphocyte, which belongs to a subset of H T cells that produce a cytokine called interleukin-4 (IL-4). These T 2 H 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 Degranulation process in allergy. 1 — antigen called mast cells and basophils, which are both involved in the acute 2 — IgE antibody inflammatory response. The IgE-coated cells, at this stage are 3 — FcεRI receptor sensitized to the allergen.[28] 4 — preformed mediators (histamine, proteases, chemokines, heparine) If later exposure to the same allergen occurs, the allergen can bind to 5 — granules the IgE molecules held on the surface of the mast cells or basophils. 6 — mast cell 7 — newly formed mediators (prostaglandins, Cross-linking of the IgE and Fc receptors occurs when more than one leukotrienes, thromboxanes, PAF) 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 Food allergy 41

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.[28]

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.[29] 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 T 2 cells.[30] H

Protein structure and organization Proteins are composed of amino acid monomers linked by peptide bonds.[31] 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.[32] 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.[31] 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 [33] Quaternary structure is the overall combination of polypeptide subunits to form the functional unit.

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. Food allergy 42

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. • 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.[34] • Blood testing is another way to test for allergies; however, it poses the same disadvantage and only detects IgE allergens and does not Skin testing on arm is a common way for work for every possible allergen. RAST, RadioAllergoSorbent Test, detecting an allergy, however, it is not as is used to detect IgE antibodies present to a certain allergen. The effective as other tests. 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.[35]

• 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.[36] 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.[37] 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.[38][39][40] 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 43

Food Allergy Profile are considered unproven methods, the use of which is not advised.[41] • 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.

Differential diagnosis 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.

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."[42] 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.[43] 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.

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. 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. Food allergy 44

Epinephrine

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. EpiPens are portable epinephrine-dispensing Epinephrine is produced naturally in the body. It is produced during devices which can be used to alleviate the "flight-or-fight" response. When a person is presented with a symptoms of severe, acute allergies. 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.[44]

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.[45]

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.[46]

Desensitisation Desensitisation may be a cure for food allergies.[47] 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.[48]

Epidemiology 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.[49] The most common food allergies in adults are shellfish, peanuts, tree nuts, fish, and egg.[50] The most common food allergies in children are milk, eggs, peanuts, and tree nuts.[50] Six to eight percent of children under the age of three have food allergies and nearly four percent of adults have food allergies.[50] For reasons that are not entirely understood, the diagnosis of food allergies has apparently become more common in Western nations in recent times.[51] In the United States, food allergy affects as many as 5% of infants less than three years of age[52] and 3% to 4% of adults.[53] There is a similar prevalence in Canada.[54] Food allergy 45

Seventy-five percent of children who have allergies to milk protein are able to tolerate baked-in milk products, i.e., muffins, cookies, cake. About 50% of children with allergies to milk, egg, soy, and wheat will outgrow their allergy by the age of 6. Those that are still allergic by the age of 12 or so have less than an 8% chance of outgrowing the allergy.[55] Peanut and tree nut allergies are less likely to be outgrown, although evidence now shows[56] that about 20% of those with peanut allergies and 9% of those with tree nut allergies will outgrow them.[57] In Central Europe, celery allergy is more common. In Japan, allergy to buckwheat flour, used for soba noodles, is more common. Meat allergy is extremely rare in the general population, but a geographic cluster of people allergic to meat has been observed in Sydney, Australia.[58] There appears to be a possible association between localised reaction to tick bite and the development of meat allergy. Fruit allergies exist, such as to apples, peaches, pears, jackfruit, strawberries, etc. 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.[59] Protein allergies or intolerance of seeds, nuts, meat, and milk are especially common among children.[60]

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.

Footnotes

[1] http:/ / apps. who. int/ classifications/ icd10/ browse/ 2010/ en#/ T78. 0

[2] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=V15. 01

[3] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=V15. 05

[4] http:/ / omim. org/ entry/ 147050

[5] http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 000817. htm

[6] http:/ / www. emedicine. com/ med/ topic806. htm

[7] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D005512

[8] "Frequently Asked Questions" (http:/ / www. foodallergy. org/ questions. html). Food Allergy & Anaphylaxis Network. .

[9] "Allergy Glossary of Terms" (http:/ / www. revolutionhealth. com/ conditions/ asthma-allergies/ hay-fever-seasonal-allergies/ introduction/ allergy-glossary). Revolution Health. .

[10] "Other atopic dermatitis and related conditions" (http:/ / www. icd9data. com/ 2007/ Volume1/ 680-709/ 690-698/ 691/ 691. 8. htm). ICD9. .

[11] MedlinePlus Encyclopedia Food allergy (http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 000817. htm) [12] van Ree 1 [13] Sicherer 2006, p. 12

[14] Food Allergies (http:/ / www. foodallergyinitiative. org). Food Allergy Initiative. 2009. Accessed 27 Mar 2010. [15] Sicherer 2006, p. 62 [16] Sicherer 2006, p. 63

[17] Savage JH, Matsui EC, Skripak JM, Wood RA (December 2007). "The natural history of egg allergy" (http:/ / linkinghub. elsevier. com/

retrieve/ pii/ S0091-6749(07)01834-9). J Allergy Clin Immunol 120 (6): 1413–7. doi:10.1016/j.jaci.2007.09.040. PMID 18073126. . [18] Sicherer 2006, p. 64

[19] "Food Allergy Facts & Figures" (http:/ / www. aafa. org/ display. cfm?id=9& sub=30). Asthma and Allergy Foundation of Americs. March 28, 2007. .

[20] "Food allergy and intolerance" (http:/ / www. faia. org. uk/ html/ food_sensitivity. php). Allergy & Intolerance. Food Additives and Ingredients Association. . Retrieved 2010-06-08.

[21] "About Food Allergies" (http:/ / www. faiusa. org/ ?page=aboutFoodAllergies). Food Allergy Initiative. 2008. . Retrieved 2008-12-08.

[22] "Rice Allergy" (http:/ / allergy. healthcentersonline. com/ foodallergyintolerance/ riceallergy2. cfm). HealthCentersOnline. 2006. pp. 2. . Retrieved 2006-10-26.

[23] "Policy Statement: Hypoallergenic Infant Formulas" (http:/ / aappolicy. aappublications. org/ cgi/ content/ full/ pediatrics;106/ 2/ 346). American Academy of Pediatrics. August 2, 2000. . Food allergy 46

[24] "Other Common Allergens" (http:/ / www. foodallergy. org/ page/ other). The Food Allergy & Anaphylaxis Network. .

[25] Food Reactions. Allergies (http:/ / www. foodreactions. org/ allergy/ ). Foodreactions.org. Kent, England. 2005. Accessed 27 Apr 2010. [26] Nester 2009, p. 414

[27] Mayo Clinic. Causes of Food Allergies. (http:/ / www. mayoclinic. com/ health/ food-allergy/ AN00179) April 2010.

[28] Janeway, Charles; Paul Travers, Mark Walport, and Mark Shlomchik (2001). Immunobiology; Fifth Edition (http:/ / www. ncbi. nlm. nih.

gov/ books/ bv. fcgi?call=bv. View. . ShowTOC& rid=imm. TOC& depth=10). New York and London: Garland Science. pp. e-book. ISBN 0-8153-4101-6. .. [29] Grimbaldeston MA, Metz M, Yu M, Tsai M, Galli SJ (2006). "Effector and potential immunoregulatory roles of mast cells in IgE-associated acquired immune responses". Curr. Opin. Immunol. 18 (6): 751–60. doi:10.1016/j.coi.2006.09.011. PMID 17011762. [30] Holt PG, Sly PD (2007). "Th2 cytokines in the asthma late-phase response". Lancet 370 (9596): 1396–8. doi:10.1016/S0140-6736(07)61587-6. PMID 17950849. [31] Freeman 2008, p. 53 [32] Alberts 2010, p. 121 [33] Freeman 2008, p. 54 [34] Sicherer 2006, p. 185 [35] Sicherer 2006, pp. 187–8 [36] Sicherer 2006, p. 189

[37] "What is a RAST test ? What is a CAP-RAST test?" (http:/ / www. kidswithfoodallergies. org/ resourcespre. php?id=48& title=What is a RAST test ? What is a CAP-RAST test?). kidswithfoodallergies.org. . [38] Sampson, HA; Ho DG (October 1997). "Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents". J Allergy Clin Immunol 100 (4): 444–51. doi:10.1016/S0091-6749(97)70133-7. PMID 9338535. [39] Sampson, HA (May 2001). "Utility of food-specific IgE concentrations in predicting symptomatic food allergy". J Allergy Clin Immunol 107 (5): 891–6. doi:10.1067/mai.2001.114708. PMID 11344358. [40] Garcia-Ara, C; Boyano-Martinez T, Diaz-Pena JM, et al. (January 2001). "Specific IgE levels in the diagnosis of immediate hypersensitivity to cows' milk protein in the infant". Allergy Clin Immunol 107 (1): 185–90. doi:10.1067/mai.2001.111592. PMID 11150010. [41] Wüthrich B (2005). "Unproven techniques in allergy diagnosis". J Investig Allergol Clin Immunol 15 (2): 86–90. PMID 16047707. [42] Greer, F. R.; Sicherer, SH; Burks, AW; American Academy of Pediatrics Committee on Nutrition; American Academy of Pediatrics Section on Allergy and Immunology (2008). "Effects of early nutritional interventions on the development of atopic disease in infants and children:

the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas" (http:/ /

pediatrics. aappublications. org/ cgi/ content/ full/ 121/ 1/ 183?submit. y=5& submit. x=110& submit=sendit& gca=121/ 1/ 183& ). Pediatrics (American Academy of Pediatrics) 121 (1): 183. doi:10.1542/peds.2007-3022. PMID 18166574. . Retrieved 2008-01-09. [43] Sicherer 2006, pp. 151–8 [44] Sicherer 2006, p. 133 [45] Sicherer 2006, p. 131 [46] Sicherer 2006, p. 134

[47] "Studies Show Children Can Complete Treatment for Peanut Allergies and Achieve Long-Term Tolerance" (http:/ / www. dukehealth. org/

HealthLibrary/ News/ studies_show_children_can_complete_treatment_for_peanut_allergies_and_achieve_long_term_tolerance). Duke University Medicine News and Communications. 2009-03-15. . Retrieved Mar. 15, 2009.

[48] "Food allergies 'gone in 10 years'" (http:/ / news. bbc. co. uk/ 2/ hi/ health/ 5329572. stm). BBC News. 2006-09-09. . Retrieved 2006-09-09.

[49] "About Food Allergies" (http:/ / www. faiusa. org/ ?fuseaction=home. viewpage& page_id=5556A2E8-E081-2F43-D4153C0689F035F6). Food Allergy Initiative. . Retrieved 2010-08-06.

[50] National Institute of Allergy and Infectious Diseases (July 2004). "Food Allergy: An Overview" (http:/ / www. niaid. nih. gov/ publications/

pdf/ foodallergy. pdf) (PDF). National Institutes of Health. pp. 35. .

[51] Kagan RS (February 2003). "Food allergy: an overview" (http:/ / www. ehponline. org/ members/ 2003/ 5702/ 5702. html). Environ Health Perspect 111 (2): 223–5. doi:10.1289/ehp.5702. PMC 1241355. PMID 12573910. .

[52] Sampson H (2004). "Update on food allergy" (http:/ / www. jacionline. org/ article/ PIIS0091674904011455/ fulltext). J Allergy Clin Immunol 113 (5): 805–819. doi:10.1016/j.jaci.2004.03.014. PMID 15131561. . [53] Sicherer S, Sampson H (2006). "9. Food allergy". J Allergy Clin Immunol 117 (2 Suppl Mini–Primer): S470–5. doi:10.1016/j.jaci.2005.05.048. PMID 16455349.

[54] "Food Allergies and Intolerance" (http:/ / www. hc-sc. gc. ca/ fn-an/ securit/ allerg/ index_e. html). Health Canada. December 6, 2007. .

[55] "What Are Food Allergies? Food Allergy Summary" (http:/ / www. aafa. org/ display. cfm?id=9& sub=15& cont=78). Asthma and Allergy Foundation of America. March 28, 2007. .

[56] "Outgrowing food allergies" (http:/ / www. childrensmemorial. org/ depts/ allergy/ outgrow. asp). Children's Memorial Hospital. . [57] Fleischer DM, Conover-Walker MK, Matsui EC, Wood RA (November 2005). "The natural history of tree nut allergy". J Allergy Clin Immunol 116 (5): 1087–93. doi:10.1016/j.jaci.2005.09.002. PMID 16275381.

[58] "One tick red meat could do without" (http:/ / www. theaustralian. news. com. au/ story/ 0,25197,23667445-23289,00. html). The Australian. . [59] Parker, Cherry (February 1980). "Food Allergies". The American Journal of Nursing (Lippincott Williams &) 80 (2): 262–5. doi:10.2307/3470059. JSTOR 3470059. PMID 6898386. Food allergy 47

[60] Sicherer, Scott H. M.D., Understanding and Managing Your Child's Food Allergy. Baltimore: The Johns Hopkins University Press, 2006.

References • Alberts, Bruce; Bray, Dennis; Hopkin, Karen; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter (2010). "Protein Structure and Function". Essential Cell Biology (3rd ed.). New York: Garland Science, Taylor and Francis Group. pp. 120–170. • Fernández de Corres L, Moneo I, Muñoz D, Bernaola G, Fernández E, Audicana M, Urrutia I (January 1993). "Sensitization from chestnuts and bananas in patients with urticaria and anaphylaxis from contact with latex". Ann Allergy 70 (1): 35–9. PMID 7678724. • Frankel, Edward (1991). Poison Ivy, Poison Oak, Poison Sumac and Their Relatives; Pistachios, Mangoes and Cashews. Pacific Grove CA: Boxwood Press. ISBN 0-940168-18-9. • Freeman, Scott (2008). "Protein Structure and Function". Biological Science (3rd ed.). San Francisco CA: Pearson Education. pp. 43–65.

• Food Allergy and Anaphylaxis Network. Network (http:/ / foodallergy. org). 2008. Accessed 25 Mar 2010.

• Hogan, C.Michael. Western poison-oak: Toxicodendron diversilobum (http:/ / globaltwitcher. auderis. se/

artspec_information. asp?thingid=82914). GlobalTwitcher, ed. Nicklas Stromberg. 2008. Accessed 30 April 2010. • Keeler, Harriet L. Our Native Trees and How to Identify Them. New York: Charles Scriber's Sons. 1900.

• Medic Alert Foundation. Medic Alert (http:/ / medicalert. org). California. 2010. Accessed 25 Mar 2010.

• American Academy of Allergy, Asthma and Immunology. Allergies (http:/ / www. aaaai. org). 2010. Accessed 25 Mar 2010.

• Food and Drug Administration. USFDA: Allergies (http:/ / www. cfsan. fda. gov). United States Department of Health and Human Services. 2010. Accessed 27 Mar 2010.

• Food Allergies (http:/ / www. foodallergyinitiative. org). Food Allergy Initiative. 2009. Accessed 27 Mar 2010.

• Food Reactions. Allergies (http:/ / www. foodreactions. org/ allergy/ ). foodreactions.org Kent, England. 2005. Accessed 27 Apr 2010.

• Mayo Clinic Food Allergy (http:/ / www. mayoclinic. com/ health/ food-allergy/ AN00179). 2010. Accessed 27 Apr 2010.

• High Protein foods. Foods (http:/ / www. highproteinfoods. net). High Protein Foods.net, 2004. Accessed 21 Mar 2010.

• Mount Sinai School of Medicine. Food allergy (http:/ / www. mssm. edu/ jaffe_food_allergy). 2010. Accessed 25 Mar 2010. • Nester, Eugene W.; Anderson, Denise G.; Roberts, Jr, C. Evans; Nester, Martha T. (2009). "Immunologic Disorders". Microbiology: A Human Perspective (6th ed.). New York: McGraw-Hill. pp. 414–428. • Sicherer, Scott H. (2006). Understanding and Managing Your Child's Food Allergy. Baltimore: Johns Hopkins University Press. • Zuidmeer L, van Ree R (June 2007). "Lipid transfer protein allergy: primary food allergy or pollen/food

syndrome in some cases" (http:/ / meta. wkhealth. com/ pt/ pt-core/ template-journal/ lwwgateway/ media/

landingpage. htm?issn=1528-4050& volume=7& issue=3& spage=269). Curr Opin Allergy Clin Immunol 7 (3): 269–73. doi:10.1097/ACI.0b013e32814a5401. PMID 17489047. Food allergy 48

Further reading

• "Food Allergies and Intolerances Resource List for Consumers" (http:/ / www. nal. usda. gov/ fnic/ pubs/ bibs/

allergy. pdf). Food and Nutrition Information Center, National Agricultural Library. December 2010. - a collection of resources on the topic of food allergies and intolerances • Weissman, Susan, Feeding Eden: The Trials and Triumphs of a Food Allergy Family, New York : Sterling Publishing Co., Inc., March 6, 2012. ISBN 978-1-4027-8122-3

External links

• Why Risk It (http:/ / www. whyriskit. ca) - support for Canadian teenagers suffering from anaphylaxis

• The Anaphylaxis Campaign (http:/ / www. anaphylaxis. org. uk) — UK support charity

• The Food Allergy & Anaphylaxis Network (http:/ / www. foodallergy. org) - US

• x20051103230534239900 (http:/ / www. gpnotebook. co. uk/ simplepage. cfm?ID=x20051103230534239900) at GPnotebook General Practice Notebook

• 16-182d. (http:/ / www. merck. com/ mmhe/ sec16/ ch182/ ch182d. html) at Merck Manual of Diagnosis and Therapy Home Edition

Corn allergy

Corn/Maize allergy is a type of food allergy. It can be a difficult allergy to manage, particularly in the United States, due to the high number of food products which contain various forms of corn, such as corn starch, citric acid, modified food starch, vinegar, and vanilla, among many others. [1] However, it is an allergy that often goes unrecognized.[2]

Symptoms As a result of a possible IgE allergy to corn, symptoms can resemble that of any other recognized allergy, including anaphylaxis. Reactions to corn derivatives, such as corn syrup, are also possible.

Notes [1] "Food Allergies", The American Journal of Nursing, Vol. 80, No. 2 (Feb., 1980), pp. 262-265 [2] "Allergy to Corn Often Remains Unrecognized", Science News 89:331 May 7, 1966 24 Egg allergy 49 Egg allergy

Egg allergy Classification and external resources

Fried chicken egg

[1] ICD-9 V15.03

[2] MeSH D021181

Egg allergy is a type of food allergy. It is a hypersensitivity to dietary substances from the yolk or whites of eggs, causing an overreaction of the immune system which may lead to severe physical symptoms for millions of people around the world.[3] Egg allergy appears mainly, but not exclusively, in children. In fact, it is the second most common food allergy in children.[4] (The most common is cows' milk allergy.) It is usually treated with an exclusion diet and vigilant avoidance of foods that may be contaminated with egg. The most severe food allergy reaction is called anaphylaxis[5] and is an emergency situation requiring immediate attention and treatment with epinephrine. The Asthma and Allergy Foundation of America estimates that most children outgrow egg allergy by the age of five, but some people remain allergic for a lifetime.[6]

Antigens Most people who are allergic to hen's eggs have antibodies which react to one of four proteins in the egg white:[7] ovomucoid, ovalbumin, ovotransferrin, and lysozyme; ovomucoid, also called Gal d 1, is the most common target of immune system attack.[7] The egg yolk contains several potential antigens: livetin, apovitillin, and vosvetin. A person who reacts only to a protein in the egg yolk may be able to easily tolerate egg whites, and vice versa. Some people will be allergic to proteins in both the egg white and the egg yolk. Egg yolk allergies may be somewhat more common in adults.[7] A small number of people who are allergic to eggs will develop an allergy to chicken or other poultry meats.[7] Egg allergy 50

Diagnosis Diagnosis is generally made through a combination of skin prick testing or blood testing and detailed records of all foods and drink the person regularly intakes.

Treatment There is currently no cure for egg allergy. Most people who are allergic to eggs avoid eating any form of egg or egg component. For people with a more serious allergic reaction to eggs, urticaria (hives) and inflammation can occur and as such, doctors suggest that the person carries around an EpiPen.

Prognosis In a study presented at the 2007 American Academy of Allergy, Asthma, and Immunology (AAAAI) meeting, 50% of patients outgrew egg allergy by age 17. Of those patients who outgrew it, 45% did so by age 5. Children who outgrew the allergy tended to have peak IgE levels at around age one, which then decline.[8]

Vaccine hazard The flu vaccine is typically made using chicken embryo, and as a result the final vaccine does contain egg proteins. Egg-allergic individuals may react to egg protein(s) in the vaccine (or to gelatin or neomycin if they are allergic to that). If an individual is unable to take the vaccine, vaccinating all other members of their family can help protect them from the flu. Different brands and even individual batches of flu vaccine do vary in their egg protein content. Allergist formerly used skin testing with flu vaccine to predict if receiving the flu shot might be safe, but the results of this type of testing are totally unpredictive and this type of testing should be abandoned. Instead, the age-appropriate immunization material containing the lowest amount of egg proteins should be chosen, then a 1/10 dose should be given followed by a 30 minute observation period in a medical setting fully equipped to treat any possible reaction. Ovalbumin is usually used as a marker for the egg proteins. Vaccines available as recently as 2010 in the US contained up to 21 mcg of ovalbumin per 0.5 mL dose. In 2011 the ovalbumin content varies from less than 5.0 mcg/dose down to less than 0.05 mcg/dose, depending on the brand. One study done on 83 egg allergic patients resulted in a lack of serious reactions at doses of ovalbumin ranging from 0.10 mcg to 0.60 mcg. Thus so some brands available in the US in 2011 are probably safe for most egg allergic patients (administered with caution), but others may not be. For reference modern MMR vaccine (which is generally accepted now to be well tolerated by egg allergic patients, but which is still given with caution) was shown in a 2009 study reported in the BMJ to contain 0.0005 to 0.0010 mcg/dose [0.5 to 1.0 ng/dose). REFERENCE: June 2011 UPTODATE.com monograph on "influenza vaccine and egg allergy" and the NIH Expert Panel Report on Food Allergy, December 2010. Egg proteins can also be found in yellow fever vaccine and MMR vaccine.[9] The quantity of egg protein in a dose of MMR vaccine is approximately 40 picograms (much lower than in influenza vaccine, which contains approximately 0.02-1.0 micrograms), and this is believed to be associated with a much lower risk.[10]

Cooking without eggs In cooking, eggs are multifunctional: they may act as an emulsifier to reduce oil/water separation (mayonnaise), a binder (water binding and particle adhesion, as in meatloaf), or an aerator (cakes, especially angel food). Some commercial egg replacers can substitute for particular functions (potato starch and tapioca for water binding, whey protein for aeration or particle binding, or soy lecithin for emulsification). For home use, one-half cup of applesauce can replace one egg in some baking recipes. Most people find it necessary to strictly avoid any item containing eggs, including:[11] Egg allergy 51

• Albumin • Apovitellin • Cholesterol-free egg substitute (e.g. Eggbeaters) • Dried egg solids, dried egg • Egg, egg white, egg yolk • Egg wash • Eggnog • Fat substitutes (some) • Globulin • Livetin • Lysozyme • Mayonnaise • Meringue or meringue powder • Ovalbumin • Ovoglobulin • Ovomucin • Ovomucoid • Ovotransferrin • Ovovitelia • Ovovitellin • Powdered eggs • Silici albuminate • Simplesse • Trailblazer • Vitellin • Whole egg Ingredients that sometimes include egg are: • Artificial flavoring • Lecithin • Natural flavoring • Nougat

Egg white intolerance Egg whites, which are potent histamine liberators, also provoke a nonallergic response in some people. In this situation, proteins in egg white directly trigger the release of histamine from mast cells on contact.[12][13] Because this mechanism is classified as a pharmacological reaction, or "pseudoallergy",[12] the condition is considered a food intolerance instead of a true IgE-based allergic reaction. The response is usually localized, typically in the gastrointestinal tract.[12] Symptoms may include abdominal pain, diarrhea, or any symptoms of histamine release. It can result in an anaphylactoid reaction, which is clinically indistinguishable from true anaphylaxis, if sufficiently strong.[13] Some people with this condition tolerate small quantities of egg whites.[14] They are more often able to tolerate well-cooked eggs, such as found in cake or dried egg-based pasta, than loosely cooked eggs, such as fried eggs or meringues, or uncooked eggs.[14] Egg allergy 52

Notable people allergic to eggs Famous people allergic to eggs include: • Elizabeth Bird, wife of Alfred Bird, who invented the famous egg-free Bird's Custard, the original version of what is known generically as custard powder today. • NFL player Drew Brees [15]

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=V15. 03

[2] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D021181

[3] National Institutes of Health, NIAID Allergy Statistics 2005 http:/ / www. niaid. nih. gov/ factsheets/ allergystat. htm

[4] "Egg Allergy" (http:/ / www. faiusa. org/ ?page=egg). Food Allergy Initiative. 2008. . Retrieved 12-11-2008.

[5] National Report of the Expert Panel on Food Allergy Research, NIH-NIAID 2003 http:/ / www3. niaid. nih. gov/ about/ organization/ dait/

PDF/ june30_2003. pdf

[6] “Egg Allergy Facts” (http:/ / www. aafa. org/ display. cfm?id=9& sub=20& cont=523) Asthma and Allergy Foundation of America [7] Thomas Platts-Mills; Ring, Johannes (2005). Allergy in Practice. Berlin: Springer. p. 106. ISBN 3-540-00219-7.

[8] The Natural History of Egg Allergy by J. H. Rabe, E. C. Matsui, K. E. Mudd, J. M. Skripak, R. A. Wood; http:/ / www. abstractsonline. com/

viewer/ viewAbstract. asp?CKey={DD35189B-AC3C-4320-AAD4-6A60AB84247B}&

MKey={ADB9F23F-599E-4E3C-8BFE-532DF96F148F}& AKey={3B788255-C10D-411E-A96E-F2E03408D278}& SKey={2DF953E8-793B-4112-8FE0-58A9F4495EC0} [9] Romero GL, Kumar S (December 2006). "Case 1: The case of the cookie, the rash and the flu vaccine". Paediatr Child Health 11 (10): 675–7. PMC 2528595. PMID 19030254.

[10] "Egg Allergies : Vaccine Education Center - Children's Hospital of Philadelphia" (http:/ / www. chop. edu/ consumer/ jsp/ division/ generic. jsp?id=75811). .

[11] "Egg Avoidance List" (http:/ / www. kidswithfoodallergies. org/ resourcespre. php?id=36& title=Egg_allergy_avoidance_list). . [12] Arnaldo Cantani (2008). Pediatric Allergy, Asthma and Immunology. Berlin: Springer. pp. 710–713. ISBN 3-540-20768-6. [13] Joris, Isabelle; Majno, Guido (2004). Cells, tissues, and disease: principles of general pathology. Oxford [Oxfordshire]: Oxford University Press. pp. 538. ISBN 0-19-514090-7. [14] Carina Venter; Isabel Skypala (2009). Food Hypersensitivity: Diagnosing and Managing Food Allergies and Intolerance. Wiley-Blackwell. pp. 129–131. ISBN 1-4051-7036-0.

[15] "NFL Workout: Strapped In A system designed by a Navy SEAL got the Saints' Drew Brees in shape to succeed" (http:/ / sportsillustrated.

cnn. com/ 2007/ players/ 01/ 09/ nfl. workout0115/ index. html). CNN. 2007-01-09. . Retrieved 2008-10-01. Milk allergy 53 Milk allergy

Milk allergy Classification and external resources

A glass of pasteurized cow milk.

[2] [1] ICD-9 995.3 , V15.02

A milk allergy is a food allergy, an adverse immune reaction to one or more of the constituents of milk from any animal (most commonly alpha S1-casein, a protein in cow's milk). This milk-induced allergic reaction can involve anaphylaxis, a potentially life-threatening condition. It is important to note that a milk allergy is a separate and distinct condition from lactose intolerance.

Allergen A person with milk allergy can be reactive to one of dozens of the proteins within milk. The most common one is alpha S1-casein.[2] Alpha S1-caseins differ between species. This explains why someone with an allergic reaction to sheep's milk cannot drink goat's milk but can drink breast milk without an allergic reaction.[3]

Symptoms The principal symptoms are gastrointestinal, dermatological and respiratory. These can translate to: skin rash, hives, vomiting, and gastric distress such as diarrhea, constipation, stomach pain or flatulence. The clinical spectrum extends to diverse disorders: anaphylactic reactions, atopic dermatitis, wheeze, infantile colic, gastroesophageal reflux (GER), oesophagitis, allergic colitis, headache/migraine, oral irritation, and constipation. The symptoms may occur within a few minutes after exposure in immediate reactions, or after hours (and in some cases after several days) in delayed reactions. Milk allergy 54

Difference between milk allergy and lactose intolerance Milk allergy is a food allergy, an adverse immune reaction to a food protein that is normally harmless to the non-allergic individual. Lactose intolerance is a non-allergic food sensitivity, and comes from a lack of production of the enzyme lactase, required to digest the predominant sugar in milk. Adverse effects of lactose intolerance generally occur after much higher levels of milk consumption than do adverse effects of milk allergy. (Lactose intolerance is considered the normal state for most adults on a worldwide scale and is not typically considered to be a disease condition.[4])

Difference from milk protein intolerance Milk protein intolerance (MPI) is delayed reaction to a food protein that is normally harmless to the non-allergic, non-intolerant individual. Milk protein intolerance produces a non-IgE antibody and is not detected by allergy blood tests. Milk protein intolerance produces a range of symptoms very similar to milk allergy symptoms, but can also include blood and/or mucus in the stool. Treatment for milk protein intolerance is the same as for milk allergy. Milk protein intolerance is also referred to as milk soy protein intolerance (MSPI).[5] It is commonplace for milk or milk derivatives to be included in processed foods such as bread, crackers, cookies, cakes, prepared meats, "soy cheese", soups, gravies, crisps, margarine, and products labeled "non-dairy", such as whipped topping and creamer (non-dairy simply means less than 0.5% milk by weight[6]). It is also commonplace for milk derivatives, like casamino acid, to be in vaccines. In some cases, heating the dairy product to force an exothermic chemical reaction can denature the proteins, (i.e. baking bread, or other baked goods). Only the ingredients that are chemically reacting will denature. It is important to note that many processed foods that do not contain milk may be processed on equipment contaminated with dairy foods, which may cause an allergic reaction in some sensitive individuals.

Milk avoidance and replacement for infants Since milk protein may be transferred from a breastfeeding mother [7] to an allergic infant, lactating mothers of allergic infants can simply be put on a dairy elimination diet.[8] For formula fed infants, milk substitute formulas are used to provide a complete source of nutrition. Milk substitutes include soy based formulas, hypoallergenic formulas based on partially or extensively hydrolyzed protein, and free amino acid-based formulas. Non-milk derived amino acid-based formulas, known as amino acid formulas or elemental formulas, are considered the gold standard in the treatment of cows milk allergy when the mother is unable to breastfeed. Hydrolyzed formulas come in partially hydrolyzed and extensively hydrolyzed varieties. Partially hydrolyzed formulas (PHFs) are characterized by a larger proportion of long chain peptides and are considered more palatable. However, they are intended for milder cases and are not considered suitable for treatment of moderate to severe milk allergy or intolerance. Extensively hydrolyzed formulas (EHFs) are composed of proteins that have been largely broken down into free amino acids and short peptides. Casein and whey are the most commonly used sources of protein in hydrolyzed formulas because of their high nutritional quality and their amino acid composition. Soy based formula may or may not pose a risk of allergic sensitivity, as some infants who are allergic to milk may also be allergic to soy. Also soy based formula are not recommended for infants under 6 months. However, for infants with multiple allergies there are rice milk or oat milk based formulas available. Milk allergy 55

Milk substitution for children and adults There are many commercially available replacements for milk for children and adults. Rice milk, soy milk, oat milk, coconut milk and almond milk are sometimes used as milk substitutes but are not suitable nutrition for infants. However, special infant formula based on soy, rice, almonds or carob seeds is commercially available. On an avoidance diet, it may be possible to reduce the longer-term risk of calcium deficiency and osteoporosis by incorporating other sources of calcium, although the effect of calcium and vitamin D supplementation on osteoporosis is not always clear. There are fruit juices supplemented with calcium, sesame seeds, hemp seeds and some kinds of tofu. They may, however, have other effects on health.

Accidental exposure Treatment for accidental ingestion of milk products by allergic individuals varies depending on the sensitivity of the allergic person. Frequently medications such as an Epinephrine pen or an Antihistamine such as Diphenhydramine (Benadryl) are prescribed by an allergist in case of accidental ingestion. Milk allergy can cause anaphylaxis, a severe, life threatening allergic reaction. Milk allergies are common in infants but are usually outgrown within the first 2–3 years of life.

Statistics Milk allergy is the most common food allergy in early childhood. It affects somewhere between 2% and 3% of infants in developed countries, but approximately 85–90% of affected children lose clinical reactivity to milk once they surpass 3 years of age.[9] Between 13% and 20% of children allergic to milk are also allergic to beef.[10]

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=V15. 02

[2] http:/ / www. dynamicchiropractic. com/ mpacms/ dc/ article. php?id=38646

[3] http:/ / foodallergens. ifr. ac. uk/ biochemical. lasso?selected_food=5000& allergenID=1041

[4] http:/ / kidshealth. org/ parent/ medical/ allergies/ milk_allergy. html

[5] MSPI Overview (http:/ / mspikids. info/ )

[6] Go Dairy Free | Dairy Ingredient List (http:/ / www. godairyfree. org/ Food-to-Eat/ Food-Label-Info/ Dairy-Ingredient-List. html)

[7] http:/ / www. fussybaby. ca/ breastfeedingdairy. html

[8] Brill H (September 2008). "Approach to milk protein allergy in infants" (http:/ / www. cfp. ca/ cgi/ pmidlookup?view=long& pmid=18791102). Can Fam Physician 54 (9): 1258–64. PMC 2553152. PMID 18791102. . [9] Høst A (December 2002). "Frequency of cow's milk allergy in childhood". Ann. Allergy Asthma Immunol. 89 (6 Suppl 1): 33–7. doi:10.1016/S1081-1206(10)62120-5. PMID 12487202. [10] Martelli A, De Chiara A, Corvo M, Restani P, Fiocchi A (December 2002). "Beef allergy in children with cow's milk allergy; cow's milk allergy in children with beef allergy". Ann. Allergy Asthma Immunol. 89 (6 Suppl 1): 38–43. doi:10.1016/S1081-1206(10)62121-7. PMID 12487203. Milk allergy 56

External links

• A muffin a day could keep milk allergy at bay (http:/ / www. aboutkidshealth. ca/ En/ News/ NewsAndFeatures/

Pages/ muffins-milk-allergy. aspx)

• Eating without Casein (http:/ / web. mit. edu/ kevles/ www/ nomilk. html) Practical guide to milk-free eating

• Milk Allergy (http:/ / www. faiusa. org/ ?page=milk) at Food Allergy Initiative

• Milk Allergy Symptoms (http:/ / milkallergy. info/ )

Fruit allergy

Fruit allergy is a food allergy. Fruit allergies make up about 10 percent of all food related allergies[1]

Symptoms Allergic reactions to fruit and vegetables are usually mild and often just affect the mouth, causing itching, a rash, or blisters where the food touches the lips and mouth. This is called oral allergy syndrome. (A number of people who react in this way to fruit or vegetables will also react to pollen from some trees and weeds. So, for example, people who are allergic to birch pollen are also likely to be allergic to apples.[2]) Another symptom may include slight swelling in the throat, making it feel like it is closing. The ability to breathe is still present though, so it is not fatal.

Other Symptoms due to Hypersensitivity The symptoms may vary upon the person and the severity of the allergy and also the type of fruit, for example mango allergy was shown that they may go from symptoms such as hoarseness, dyspnoea and bronchitic rales (asthma) (Sareen and Shah). The length of the appearance of the symptoms tested by Saree and Shah were variable and ranged from 4 h [11] to 7 days [12]. The appearance of symptoms may appear within a few minutes.

Different Allergic Fruits There are many different types of fruits that people have been shown to react allergically such as mangoes and bananas. some foods are clearly more allergenic than others. In adults, peanuts, tree nuts, finned fish, crustaceans, fruit, and vegetables account for 85% of the food-allergic reactions(O'Neil, Zanovec and Nickla). People suffering from allergies may suffer from a hypersensitivity to the allergic food, which is what causes the allergic reaction. Most fruit allergies are oral syndrome allergies because they are consumed but may also be an external allergy if the fruit touches the skin.

Diagnostic Skin prick testing is a common way of testing for an allergy. Other ways to test for allergies can be challenge testing, which consists in feeding a very small and measured amount of the allergen to the patient and monitor the reaction (O'Neil, Zanovec and Nickla). This should only be done by a doctor under surveillance.

Allergy or Intolerance An allergy is different from an intolerance. Food allergies and food intolerances should not be confused because they do not contain the same risks and are not diagnosed the same way. Allergies can be fatal after only a small consumption, while intolerance, although uncomfortable, are not as deadly. An intolerance may lead to a nutrient deficiency which could cause death if untreated but the intolerance itself is not enough to cause rapid death. Allergies, with their varying symptoms, could cause instantaneous death if there is inflammation in the throat and Fruit allergy 57

causes suffocation.

Mitigation For those allergic to fruits, cooking may help reduce or eliminate the reaction to some fruits.[2] People with this allergy might not necessarily be allergic to citrus fruits.

References

[1] Asthma and Allergy Foundation of America - Information About Asthma, Allergies, Food Allergies and More! (http:/ / www. aafa. org/

display. cfm?id=9& sub=20& cont=286)

[2] Food Standards Agency - Eat well, be well - Fruit and vegetable allergy (http:/ / www. eatwell. gov. uk/ healthissues/ foodintolerance/

foodintolerancetypes/ fruitandveg/ ) Sareen and Shah. (2011). Hypersensitivity manifestations to the fruit mango. Asia Pacific Allergy. (44-49).

Retrieved from http:/ / www-ncbi-nlm-nih-gov. login. ezproxy. library. ualberta. ca/ pmc/ articles/ PMC3206236/

pdf/ apa-1-43. pdf O'Neil, Zanovec and Nicklas. (2010). A Review of Food Allergy and Nutritional Considerations in the Food-Allergic

Adult. American Journal of Lifestyle Medicine. (49-62). Retrieved from http:/ / ajl. sagepub. com. login. ezproxy.

library. ualberta. ca/ content/ 5/ 1/ 49. full. pdf+ html

External links

• Asthma and Allergy Foundation of America (http:/ / www. aafa. org) Peanut allergy 58 Peanut allergy

Peanut allergy Classification and external resources

A peanut allergy warning

[1] ICD-10 T78.4

[1] [2] ICD-9 995.61 , V15.01

[2] DiseasesDB 29154

[3] MeSH D021183

Peanut allergy is a type of food allergy distinct from nut allergies. It is a type 1 hypersensitivity reaction to dietary substances from peanuts causing an overreaction of the immune system which in a small percentage of people may lead to severe physical symptoms. It is estimated to affect 0.4-0.6% of the population.[4] In England, an estimated 4,000 people are newly diagnosed with peanut allergy per year (11 per day); 25,700 having been diagnosed with peanut allergy by a clinician at some point in their lives.[5] The most severe allergies in general can result in anaphylaxis,[6] an emergency situation requiring immediate attention and treatment with epinephrine. It is usually treated with an exclusion diet and vigilant avoidance of foods that may contain whole peanuts or peanut particles and/or oils.

Symptoms Symptoms of peanut allergy are related to the action of Immunoglobulin E (IgE) and other anaphylatoxins, which act to release histamine and other mediator substances from mast cells (degranulation). In addition to other effects, histamine induces vasodilation of arterioles and constriction of bronchioles in the lungs, also known as bronchospasm (constriction of the airways). Symptoms can include the following:[7] • vomiting • diarrhea • urticaria (hives) • angioedema (swelling of the lips, face, throat and skin) • acute abdominal pain • exacerbation of atopic eczema Peanut allergy 59

• asthma • anaphylactic shock The British Dietetic Association warns that: "If untreated, anaphylactic shock can result in death due to obstruction of the upper or lower airway (bronchospasm) or hypotension and heart failure. This happens within minutes to hours of eating the peanuts. The first symptoms may include sneezing and a tingling sensation on the lips, tongue and throat followed by pallor, feeling unwell, warm and light headed. Severe reactions may return after an apparent resolution of 1–6 hours. Asthmatics with peanut sensitivity are more likely to develop life threatening reactions".[7]

Causes The exact cause of someone developing a peanut allergy is unknown. A 2003 study found no link to maternal exposure to peanuts during pregnancy or during breast-feeding,[8] though the data show a linkage to the amount of time a child is breastfed. The same study indicated that exposure to soy milk or soy products was correlated with peanut allergies. However, an analysis of a larger group in Australia found no linkage to consumption of soy milk, and that the appearance of linkage is likely due to preference to using soy milk among families with known milk allergies.[9][10] It's possible that exposure to peanut oils in lotions may be implicated with development of the allergy.[11][12] Another hypothesis for the increase in peanut allergies (and other immune and auto-immune disorders) in recent decades is the hygiene hypothesis. Comparative studies have found that delaying introduction of peanut products significantly increases the risks of development of peanut allergies,[13][14] and the American Academy of Pediatrics, in response to ongoing studies that showed no reduction in risk of atopic disease, rescinded their recommendation to delay exposure to peanuts along with other foods. They also found no reason to avoid peanuts during pregnancy or while breastfeeding.[15] A study conducted jointly in Israel and United Kingdom in 8600 children noted a nearly 10 fold increase in incidence of peanut allergy among U.K. children compared to Israeli children. It was found that Israeli children were given peanut at a much younger age than those in the U.K. following recommendation of pediatricians in the U.K.[16] Pediatric Associations in Britain and Australia recommend delaying introduction until age 3 and have not changed their recommendations as of March 2009.

Prevalence The Asthma and Allergy Foundation of America estimates that peanut allergy is one of the most common causes of food-related death.[17] However, there is an increasing body of medical opinion that, while there definitely are food sensitivities, the dramatic uptake in frequency of nut allergies and more particularly the measures taken in response to the threat show elements of mass psychogenic illness, hysterical reactions grossly out of proportion to the level of danger:[18] "Dr. Christakis points out that about 3.3 million Americans are allergic to nuts, and even more — 6.9 million — are allergic to seafood. But of 30 million hospitalizations each year, just 2,000 are due to food allergies, and about 150 people die annually from serious allergic food reactions. That’s the same number of people killed by bee stings and lightning strikes combined. About 10,000 children are hospitalized annually with traumatic brain injuries from sports, 2,000 children drown each year, and about 1,300 die in gun accidents, he writes." Media sensationalism has also been blamed.[19] Prevalence among adults and children is similar—around 1%—but at least one study shows it to be on the rise in children in the United States.[20] The number of young children affected doubled between 1997 and 2002.[21] 25% of children with a peanut allergy outgrow it.[22] In America, about 10 people per year die from peanut allergies.[23] One study has shown that peanut allergies also correlate with ethnicity; in particular, Native Americans are less prone to be allergic to peanuts.[24] Peanut allergy 60

Routes of Exposure While the most obvious and dangerous route for an allergic individual is unintentional ingestion, some reactions are possible through external exposure. However some of these are controversial, exaggerated, or have been discredited through empirical testing. Common beliefs are that anaphylaxis can be triggered by touching peanuts or products, smelling the odor of peanuts, and simple proximity to peanut products. Many of these beliefs have resulted in controversial bans on all peanut products from entire facilities such as schools and medical facilities. Harvard pediatrician Dr. Michael C. Young notes in his book The Peanut Allergy Answer Book that while such secondary contact might pose a risk to an allergic individual, the occurrence of a reaction is rare and limited to minor symptoms.[25] Some reactions have been noted to be psychogenic in nature, the result of conditioning and belief rather than a true chemical reaction. Blinded, placebo-controlled studies by Sicherer et al. were unable to produce any reactions using the odor of peanut butter or its mere proximity.[25] That said, some activities such as cooking or large-scale shelling or crushing of peanuts (such as in a farming or factory production environment) can cause particles to become airborne, and can have respiratory effects to allergic individuals who are nearby. Similarly, residue on surfaces has been known to cause minor skin rashes, though not anaphylaxis.[25]

Treatments Currently there is no confirmed treatment to prevent or cure allergic reactions to peanuts; however some children have been recently participating in a method of treating the allergy to peanuts. This method consists of feeding the children minuscule peanut traces which gradually become larger and larger in order to desensitize the immune system to the peanut allergens.[21] Strict avoidance of peanuts is the only way to avoid an allergic reaction. Children and adults are advised to carry epinephrine injectors to treat anaphylaxis. In order to diagnose allergies one must be prepared to first tell their doctor about their symptoms. These symptoms should include any time intervals between the ingestion of the product and the time that the symptoms began. A person should also include the exact type of symptoms and any other history of the symptoms that may have also occurred from this same product. The time interval from the person's last reaction will also be helpful to the doctor to determine the specific allergy or medical issue. One of the first and easiest ways a doctor is able to diagnose the food allergy is by means of something called a Food Challenge. During this challenge, the patient will be asked to eliminate the peanut allergen completely from their diet for a time span from 10 to 14 days from start to finish. This type of elimination food challenge time span if for the IgE mediated allergy. There will be a time span as long as 8 weeks for the reaction called the cell mediated allergic reaction. By running these Food Challenges, doctors are able to determine whether or not the suspicion of the peanut allergy is accurate. The doctor will look at the results after the given time and if the symptoms have not changed, even after the peanuts have been eliminated completely for such a long period of time, that the allergy is probably not the likely cause. If the symptoms go away after the challenge then the allergy is probably the cause of the symptoms. While several companies have developed promising drugs to counteract peanut allergies, trials have been mired in legal battles.[26] Peanut allergy 61

Injected peanut desensitization An early and successful trial of injecting escalating doses of peanut allergen was conducted in 1996. However, one participant died seconds later from laryngospasm due to a pharmacy error in calculating the dose. The tragic incident itself abruptly ended one of the only studies on injected allergen desensitization to peanut allergies.[27][28][29]

Oral desensitization A desensitization study at Duke University was done with escalating doses of peanut protein. Eight children with known peanut allergy were given escalating doses of peanut protein in the form of a ground flour mixed into apple sauce or other food. To enter the study peanut IgE level > 7 kU/L and a positive skin prick test. The first day, they are given 0.1 mg of peanut protein, then the amount of peanut is increased gradually to 50 mg, if tolerated, over that first day. About ½ of the kids tolerated 50 mg dose by the end of the day, while the others were able to reach 12.5 mg or 25 mg. The children continued taking daily doses of peanut at home, returning to the hospital every two weeks for dose increases until they reached 300 mg peanut protein a day, or the equivalent of a single peanut. The maintenance phase follows lasted up to 18 months, depending on how much peanut protein the child tolerated. Seven children completed the study. These children were given a "food challenge" to peanut flour, exposing them to up to nearly 8 grams, or the equivalent of more than 13 peanuts. Five of the seven children tolerated the equivalent of 13 peanuts at the food challenge at the end of the study.[30] The children’s immunologic findings were similar to those seen with other types of immunotherapy—an initial rise followed by a decline in peanut-specific IgE and IgG. They also had a rise in peanut-specific IgG4 throughout the study, which is thought to be a marker of protection in other forms of immunotherapy.[31] In February 2009 a successful desensitization study was announced by Addenbrooke's Hospital in Cambridge, England.[32] An example of the oral rush immunotherapy protocol is the administration of diluted peanut at a dose of 0.1 mg (1 mL of a 1 gram/10L solution), and escalating by 10 fold every 30 minutes. Once a maximum dose of 50 mg is reached (1 mL of a 5 gram/100 mL solution), or when systemic or local reaction occurs, the escalation is stopped.[27][33] The patient is maintained on this maximum day one dose daily and the dose is escalated by a less rapid twofold increase each week, or each month, depending on tolerance or protocol used. Reactions are treated with antihistamines, and if needed anaphylactic drugs. Standard protocols are being developed by several clinical trials being conducted in the United States.[34] Pre- and post-study serum anti-peanut IgE levels are measured, and varying doses and escalation schedules are being compared to placebo in blinded study protocols. Actual desensitization treatments are being carried out in the community using modified protocols.[35] Success has been reported in both rapid (short duration of weeks) to slow rush protocol (spread over months) with minimal systemic reactions. The first day of the protocol often required inpatient hospital admission, or observation in a physician's office equipped with resuscitative drugs and with IV access). Frequent follow up is required during the desensitization trials to treat reactions and modify the protocol if needed.[36] Because of the relative safety of oral rush immunotherapy, some in the medical community have questioned if desensitization is better than living with peanut allergy.[37]

Allergen-free peanuts On July 20, 2007, the North Carolina Agricultural and Technical State University announced that one of its scientists, Dr. Mohamed Ahmedna, had developed a process to make allergen-free peanuts. Initial testing showed a 100 percent deactivation of peanut allergens in whole roasted kernels, and human serums from severely allergic individuals showed no reaction when exposed to the processed peanuts. Food companies have expressed an interest in licensing the process, which purportedly does not degrade the taste or quality of treated peanuts, and even results in easier processing to use as an ingredient in food products.[38] Peanut allergy 62

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=995. 61

[2] http:/ / www. diseasesdatabase. com/ ddb29154. htm

[3] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D021183

[4] National Institutes of Health, NIAID Allergy Statistics 2005 (http:/ / www3. niaid. nih. gov/ topics/ foodAllergy/ understanding/ quickFacts. htm) [5] Kotz D, Simpson CR, Sheikh A (2011). "Incidence, prevalence, and trends of general practitioner-recorded diagnosis of peanut allergy in England, 2001-5". Journal of Allergy and Clinical Immunology 127 (3): 623–630.e1. doi:10.1016/j.jaci.2010.11.021. PMID 21236479.

[6] National Report of the Expert Panel on Food Allergy Research, NIH-NIAID 2003 (http:/ / www3. niaid. nih. gov/ about/ organization/ dait/

PDF/ june30_2003. pdf)

[7] The British Dietetic Association. Peanut Allergy Information for Dietitians. 1999 (http:/ / www. bda. uk. com/ Downloads/ peanutallergy. pdf)

[8] "Interesting causes for peanut allergy identified" (http:/ / www. cincinnatichildrens. org/ svc/ alpha/ e/ eosinophilic/ doctors_comment1. htm). Cincinnatichildrens.org. 2007-09-26. . Retrieved 2010-07-08.

[9] Soy milk allergy myth debunked (http:/ / www. smh. com. au/ news/ health/ soy-milk-allergy-myth-debunked/ 2008/ 06/ 18/ 1213770721239. html), Sydney Morning Herald, June 18, 2008

[10] Soy milk study results (http:/ / scienceinpublic. com/ sciencenow/ 2008/ jennifer_koplin. htm)

[11] "Factors Associated with the Development of Peanut Allergy in Childhood" (http:/ / content. nejm. org/ cgi/ content/ short/ 348/ 11/ 977). NEJM. 2003-07-17. doi:10.1056/NEJMoa013536. . Retrieved 2010-07-08.

[12] "Peanut allergy may be linked to peanut oil skin preparations and soy milk consumption" (http:/ / www. highbeam. com/ doc/

1P3-340612661. html). Community Practitioner. 2003-05-01. . Retrieved 2010-07-08.

[13] Food allergy advice may be peanuts (http:/ / www. sciencenews. org/ view/ generic/ id/ 38370/ title/ Food_allergy_advice_may_be_peanuts), Science News magazine, Dec 6 2008

[14] Høst A, Halken S, Muraro A, et al'.' (February 2008). "Dietary prevention of allergic diseases in infants and small children" (http:/ / www3.

interscience. wiley. com/ resolve/ openurl?genre=article& sid=nlm:pubmed& issn=0905-6157& date=2008& volume=19& issue=1& spage=1). Pediatr Allergy Immunol 19 (1): 1–4. doi:10.1111/j.1399-3038.2007.00680.x. PMID 18199086. . [15] Greer FR, Sicherer SH, Burks AW (January 2008). "Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas"

(http:/ / pediatrics. aappublications. org/ cgi/ content/ full/ 121/ 1/ 183). Pediatrics 121 (1): 183–91. doi:10.1542/peds.2007-3022. PMID 18166574. . [16] Du Toit, G. et.al. The Journal of Allergy and Clinical Immunology. November 2008, Volume 122, Pages 978-985 "Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy"

[17] "Allergy Facts and Figures", Asthma and Allergy Foundation of America http:/ / www. aafa. org/ display. cfm?id=9& sub=20& cont=517

[18] http:/ / well. blogs. nytimes. com/ 2008/ 12/ 15/ are-nut-bans-promoting-hysteria/

[19] Colver A (September 2006). "Are the dangers of childhood food allergy exaggerated?" (http:/ / www. bmj. com/ cgi/ content/ full/ 333/

7566/ 494#TBL1). BMJ 333 (7566): 494–6. doi:10.1136/bmj.333.7566.494. PMC 1557974. PMID 16946341. . [20] Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: A 5-year

follow-up study http:/ / www. allerg. qc. ca/ peanutallergy. htm#pressreldec903

[21] "Expert sees peanut allergy solution within 5 years" (http:/ / www. reuters. com/ article/ latestCrisis/ idUSN01401804). Reuters. 2008-05-01. . Retrieved 2008-10-30.

[22] http:/ / www. ich. ucl. ac. uk/ factsheets/ families/ F000279/

[23] http:/ / www. aaaai. org/ patients/ advocate/ 2003/ fall/ reactions. stm

[24] "peanut allergy" (http:/ / www. allerg. qc. ca/ peanutallergy. htm). Allerg.qc.ca. . Retrieved 2010-07-08. [25] Young, Michael C.. The Peanut Allergy Answer Book: 2nd Edition. Fair Winds Press. ISBN 1-59233-233-1.

[26] "Trials of an allergy drug Remedy against peanuts is mired in legal battles" (http:/ / www. nytimes. com/ 2003/ 03/ 13/ business/

wrangling-may-delay-peanut-allergy-drug. html). International Herald Tribune. 2003-03-14. . Retrieved 2010-07-08.

[27] Robert A. Wood, MD. "Peanut Allergy: Presentations and Prospects for a Cure" (http:/ / www. childrensnational. org/ files/ PDF/

ForDoctors/ cme/ GrandRounds/ Wood-_Peanut_Allergy_DC_Childrens. pdf) (PDF). . Retrieved 2010-07-08.

[28] "Answers from Dr. Greene | Allergy Care Guide" (http:/ / www. pennmedicine. org/ health_info/ allergy/ 000067. html). Pennmedicine.org. 2007-10-07. . Retrieved 2010-07-08. [29] Nelson HS, Lahr J, Rule R, Bock A, Leung D (June 1997). "Treatment of anaphylactic sensitivity to peanuts by immunotherapy with

injections of aqueous peanut extract" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S0091674997001528). J. Allergy Clin. Immunol. 99 (6 Pt 1): 744–51. doi:10.1016/S0091-6749(97)80006-1. PMID 9215240. .

[30] "Progress Against Peanut Allergies" (http:/ / www. webmd. com/ allergies/ news/ 20070226/ progress-against-peanut-allergies). Webmd.com. . Retrieved 2010-07-08.

[31] Terry Murray (2007-03-20). "AAAAI: Peanut desensitization program for kids shows promise" (http:/ / www. medicalpost. com/ medicine/

meeting/ article. jsp?content=20070321_101113_6224). Medicalpost.com. . Retrieved 2010-07-08. Peanut allergy 63

[32] "News from Cambridge UK" (http:/ / www. cambridgenetwork. co. uk/ news/ article/ default. aspx?objid=56692). Cambridgenetwork.co.uk. . Retrieved 2010-07-08. [33] Clark AT, Islam S, King Y, Deighton J, Anagnostou K, Ewan PW (August 2009). "Successful oral tolerance induction in severe peanut

allergy" (http:/ / www3. interscience. wiley. com/ resolve/ openurl?genre=article& sid=nlm:pubmed& issn=0105-4538& date=2009&

volume=64& issue=8& spage=1218). Allergy 64 (8): 1218–20. doi:10.1111/j.1398-9995.2009.01982.x. PMID 19226304. .

[34] "Peanut Sublingual Immunotherapy" (http:/ / clinicaltrials. gov/ ct2/ show/ NCT00580606). ClinicalTrials.gov. . Retrieved 2010-07-08.

[35] "Dallas Allergy" (http:/ / dallasallergy. net/ ). Dallas Allergy. . Retrieved 2010-07-08.

[36] Beyer K, Wahn U (December 2008). "Oral immunotherapy for food allergy in children" (http:/ / meta. wkhealth. com/ pt/ pt-core/

template-journal/ lwwgateway/ media/ landingpage. htm?issn=1528-4050& volume=8& issue=6& spage=553). Curr Opin Allergy Clin Immunol 8 (6): 553–6. doi:10.1097/ACI.0b013e32831952c8. PMID 18978471. . [37] Brown HM (February 2007). "Would oral desensitization for peanut allergy be safer than avoidance?". Ann. Allergy Asthma Immunol. 98 (2): 203. doi:10.1016/S1081-1206(10)60701-6. PMID 17304895. [38] North Carolina A & T State University Press Release, July 23, 2007

External links

• The "Peanut Patch": The future of peanut allergy treatments? (http:/ / www. aboutkidshealth. ca/ En/ News/

NewsAndFeatures/ Pages/ Peanut-patch-future-of-peanut-allergy-treatments. aspx)

• "Are Nut Bans Promoting Hysteria?" (http:/ / well. blogs. nytimes. com/ 2008/ 12/ 15/

are-nut-bans-promoting-hysteria/ ) by Tara Parker-Pope at The New York Times (15 Dec 2008)

• This allergies hysteria is just nuts (http:/ / christakis. med. harvard. edu/ pdf/ publications/ misc/ 023. pdf) by Nicholas A. Christakis (British Medical Journal, December 2008)

• Peanut Allergy (http:/ / peanut. dy. fi) (Finnish) Allergy Aware.org. "Peanut Allergy". 2009. Web, 20 July 2011. Goodman, Brenda. WebMD Health News. "Food Allergies in Kids More Common Than Thought." 20 June 2011. Web 2 July 2011. . Laino, Charlene. Web MD. "New Therapy May Knock Out Peanut Allergy". 16 March 2009. Web 31 July 2011. . Seafood allergy 64 Seafood allergy

Seafood allergy Classification and external resources

[1] ICD-9 V15.04

Seafood allergy is a type of food allergy. It is a hypersensitivity to dietary substances from shellfish, scaly fish or crustaceans, causing an overreaction of the immune system, which may lead to severe physical symptoms for millions of people.[2] The Asthma and Allergy Foundation of America estimates that the majority of pediatric and adult food allergy patients have a seafood allergy.[3] It occurs mainly (but not exclusively) in adults. Allergic reactions may result when the susceptible person is not consuming the allergenic substance, by exposure to vapours resulting from cooking of seafood or even preparation or handling.[4]

Treatment Seafood allergies are usually treated with an exclusion diet and vigilant avoidance of foods that may be contaminated with shellfish or fish ingredients and/or oils. The most severe seafood allergy reaction is called anaphylaxis,[5] which is an emergency, requiring immediate attention. It is treated with Epinephrine, which can be administered with an EpiPen.

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=V15. 04

[2] National Institutes of Health, NIAID Allergy Statistics 2005 http:/ / www. niaid. nih. gov/ factsheets/ allergystat. htm

[3] “Allergy Facts and Figures,” Asthma and Allergy Foundation of America http:/ / www. aafa. org/ display. cfm?id=9& sub=20& cont=518

[4] "Seafood* (Fish, Crustaceans and Shellfish) - One of the nine most common food allergens" (http:/ / www. inspection. gc. ca/ english/ fssa/

labeti/ allerg/ fispoie. shtml). Canadian Food Inspection Agency. 2009-06-12. . Retrieved 2009-06-21.

[5] National Report of the Expert Panel on Food Allergy Research, NIH-NIAID 2003 http:/ / www3. niaid. nih. gov/ about/ organization/ dait/

PDF/ june30_2003. pdf

External links

• Asthma and Allergy Foundation of America (http:/ / www. aafa. org)

• The National Institutes of Health (http:/ / www. nih. gov)

• Shellfish Allergy (http:/ / www. faiusa. org/ ?page=shellfish) at Food Allergy Initiative

• Fish Allergy (http:/ / www. faiusa. org/ ?page=fish) at Food Allergy Initiative Soy allergy 65 Soy allergy

Soy allergy is a type of food allergy. It is a hypersensitivity to dietary substances from soy causing an overreaction of the immune system which may lead to severe physical symptoms for millions of people.[1] The Asthma and Allergy Foundation of America estimates soy is among the nine most common food allergens for pediatric and adult food allergy patients.[2] It is usually treated with an exclusion diet and vigilant avoidance of foods that may be contaminated with soy ingredients. The most severe food allergy reaction is called anaphylaxis[3] and is a medical emergency requiring immediate attention and treatment with Epinephrine.

Reactions and treatment Some people who are allergic to soy protein may have an extreme allergic reaction and go into anaphylactic shock (anaphylaxis). In cases of anaphylaxis, emergency medical personnel typically administer epinephrine (available as an autoinjector, such as EpiPen) and an antihistamine such as Benadryl (diphenhydramine). In event of an allergic reaction, the victim should see a physician or immediately go to the emergency room, as anaphylaxis can be fatal if not treated immediately.

Food sources of soy protein Many fast-food restaurants commonly use soy protein in hamburger buns (soy flour) hamburger meat (soy protein) and hydrolyzed vegetable protein (HVP) in sauces. On their respective websites, McDonald's and Burger King list soy flour as an ingredient in their hamburger buns.[4][5] U.S. Nutrition Information Multi-grain breads, doughnuts, doughnut mix and pancake mix commonly contain soy flour. Nearly all bread products available in the US now contain soy. Soy can now be found in nearly all types of foods, from meat to ice cream, to cheese, to french fries. Many foods are contaminated with soy due to being cooked in soy oil. At the Jack in the Box fast food chain for example, everything fried is cooked in a soy oil. At Baskin Robbins, over half of all ice creams offered contain soy. Canned tuna may contain vegetable broth which contains soy protein. Some products [for reasons having to do with national regulation of soy products] don't list soy protein or soy flour on their ingredients labels, yet they still contain soy. There are still many latent issues resolving how soy should be regulated, as well as its long term effects on human health. Unilever Holland use soy bean oil in their peanut butter among other foods, which they state on their website concerning allergies contains no soy bean. People will have allergy reactions but the reaction may be put on peanuts rather than soy oil. Products containing soy protein include: • edamame • miso • natto • shoyu sauce • soy (soy albumin, soy fiber, soy flour, soy grits, soy milk, soy nuts, soy sprouts) • soya • soybean (curd, granules) • soybean butter • soy protein (concentrate, isolate) • soy milk • soy sauce, tamari • tempeh • textured vegetable protein (TVP) • tofu Soy allergy 66

The following food additives may contain soy protein: • chocolate • hydrolyzed vegetable protein (HVP) • flavoring (including natural and artificial) • canned chicken broth • vegetable broth, gum, protein, and starch • bouillon cubes (beef, chicken, vegetable, etc.) • lecithin • caramel color • vegetable • vegetable oil • methylcellulose • vegetable fat • vegetable oil • mono- and di-glycerides

Dosage tolerance Many people with soy allergy can not tolerate small or moderate amounts of soy protein: the typical dose needed to induce an allergic response is about 100 times lower than for many other food allergens, with 90% of sufferers being unable to tolerate doses up to 400 mg.[6] As a result, not all of those allergic to soy need to avoid very minor sources of soy protein such as soy oil or soy lecithin.

References

[1] National Institutes of Health, NIAID Allergy Statistics 2005 http:/ / www. niaid. nih. gov/ factsheets/ allergystat. htm

[2] “Allergy Facts and Figures,” Asthma and Allergy Foundation of America http:/ / www. aafa. org/ display. cfm?id=9& sub=20& cont=518

[3] National Report of the Expert Panel on Food Allergy Research, NIH-NIAID 2003 http:/ / www3. niaid. nih. gov/ about/ organization/ dait/

PDF/ june30_2003. pdf

[4] "McDonald's Nutrition Information and Ingredients" (http:/ / www. mcdonalds. com/ app_controller. nutrition. categories. ingredients. index. html), August 26, 2006, retrieved September 7, 2006

[5] Burger King USA (http:/ / www. bk. com/ Nutrition/ PDFs/ ingredients. pdf) (11 page PDF file) "Burger King Nutrition and Ingredients" Burger King Brands Inc. USA, August, 2006, retrieved September 7, 2006

[6] Christopher T. Cordle (1 May 2004). "Soy Protein Allergy: Incidence and Relative Severity" (http:/ / jn. nutrition. org/ cgi/ content/ full/ 134/

5/ 1213S). Journal of Nutrition 134 (5): 1213S–1219S. PMID 15113974. .

External links

• Soy Allergy (http:/ / www. aafa. org/ display. cfm?id=9& sub=20& cont=522) information page. Asthma and Allergy Foundation of America

• Soy Allergy (http:/ / www. faiusa. org/ ?page=soy) at Food Allergy Initiative

• Soy - One of the nine most common food allergens (http:/ / www. hc-sc. gc. ca/ fn-an/ securit/ allerg/ fa-aa/

allergen_soy-soja-eng. php) Health Canada Tree nut allergy 67 Tree nut allergy

Tree nut allergy Classification and external resources

Hazelnuts

[1] [3] ICD-9 995.64 , V15.05

[2] MeSH D021184

Tree nut allergy is a common type of food allergy, affecting millions of people worldwide. It is a hypersensitivity to dietary substances from tree nuts causing an overreaction of the immune system, which may lead to severe physical symptoms[3]. Tree nuts include almonds, Brazil nuts, cashews, chestnuts, filberts/hazelnuts, macadamia nuts, coconut, pecans, pine nuts (pignolia nuts), pistachios, and walnuts. People with tree nut allergy are seldom allergic to just one type of nut, and are therefore usually advised to avoid all tree nuts, even though an individual may not be allergic to all varieties of tree nuts. Someone allergic to walnuts or pecans may not have an allergy to cashews or pistachios, even though close biological relatives often share related allergenic proteins. The severity of the allergy varies from person to person, and exposure can increase sensitization. For those with a milder form of the allergy, the raw nut protein usually causes a more severe reaction than the oil, and extra roasting or processing can reduce the allergic reaction. Those diagnosed with anaphylaxis will have a more immediate mast cell reaction and be required to avoid all exposure to any allergen-containing products or byproducts, regardless of processing, as they are prone to even greater sensitivity. An allergy test or food challenge may be performed at an allergy clinic to determine the exact allergens. New immunotherapy treatments are being developed for tree nut allergy. Tree nut allergy is distinct from peanut allergy, as peanuts are considered legumes, whereas a tree nut is a hard-shelled fruit of certain plants. This allergy tends to be life-long; recent studies have shown that only about 9% of children outgrow their tree nut allergy[3]. Hazelnut has been used as a model tree nut in the study of tree nut allergies.[4]

Prevention and treatment In the United States, the federal Food Allergen Labeling and Consumer Protection Act (FALCPA) requires that any packaged food product that contains tree nuts as an ingredient must list the specific tree nut on the label[3]. Foods that almost always contain tree nuts include pesto, marzipan, Nutella, baklava, pralines, nougat, gianduja, and turrón. Other common foods that may contain tree nuts include cereals, crackers, cookies, baked goods, candy, chocolates, energy/granola bars, flavored coffee, frozen desserts, marinades, barbecue sauces, and some cold cuts, such as Tree nut allergy 68

mortadella. Tree nut oils (especially shea nut) are also sometimes used in lotions and soaps. Asian and African restaurants, ice cream parlors, and bakeries are considered high-risk for people with tree nut allergy due to the common use of nuts and the possibility of cross contamination. Treatment usually involves an exclusion diet and vigilant avoidance of foods that may be contaminated with tree nuts, nut particles, or oils. The most severe nut allergy reaction is anaphylaxis,[5] an emergency situation requiring immediate attention and treatment with epinephrine.

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=995. 64

[2] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D021184

[3] National Institutes of Health, NIAID Allergy Statistics http:/ / www3. niaid. nih. gov/ topics/ foodAllergy/ understanding/ quickFacts. htm [4] Birmingham NP, Parvataneni S, Hassan HM, et al. (2007). "An adjuvant-free mouse model of tree nut allergy using hazelnut as a model tree

nut" (http:/ / content. karger. com/ produktedb/ produkte. asp?typ=fulltext& file=000103993). Int. Arch. Allergy Immunol. 144 (3): 203–10. doi:10.1159/000103993. PMID 17570928. .

[5] National Report of the Expert Panel on Food Allergy Research, NIH-NIAID 2003 http:/ / www3. niaid. nih. gov/ about/ organization/ dait/

PDF/ june30_2003. pdf

External links

• Tree nut allergy (http:/ / www. faiusa. org/ ?page=treenuts) at Food Allergy Initiative

• "Are Nut Bans Promoting Hysteria?" (http:/ / well. blogs. nytimes. com/ 2008/ 12/ 15/

are-nut-bans-promoting-hysteria/ ) by Tana Parker-Pope at The New York Times (15 Dec 2008) Wheat allergy 69 Wheat allergy

Wheat allergy Classification and external resources

Wheat

[1] MeSH D021182

Wheat allergy is a food allergy, but can also be a contact allergy resulting from occupational exposure. Like all allergies wheat allergy involves IgE and mast cell response. Typically the allergy is limited to the seed storage proteins of wheat, some reactions are restricted to wheat proteins, while others can react across many varieties of seeds and other plant tissues. Wheat allergy may be a misnomer since there are many allergenic components in wheat, for example serine protease inhibitors, glutelins and prolamins and different responses are often attributed to different proteins. Twenty-seven potential wheat allergens have been successfully identified.[2] The most severe response is exercise/aspirin induced anaphylaxis attributed to one omega gliadin that is a relative of the protein that causes celiac disease.[3] Other more common symptoms include nausea, urticaria, atopy.[4]

Types of allergens There are four major classes of seed storage proteins: albumins, globulins, prolamins and glutelins. Within wheat, prolamins are called gliadins and glutelins are called glutenins. These two protein groups form the classic glutens. While gluten is a causative agent of Coeliac disease (CD), coeliac disease can be contrasted to gluten allergy by the involvement of different immune cells and antibody types (See Comparative pathophysiology of gluten sensitivities), and because the list of allergens extend beyond the classic gluten category of proteins. Wheat allergy 70

Gluten allergy

Prolamin allergies Prolamins and the closely related glutelins, a recent study in Japan found that glutinins are a more frequent allergen, however gliadins are associated with the most severe disease. A proteomics based study found a γ-gliadin isoform gene.[3] Wheat dependent exercise induced anaphylaxis (WDEIA) is primarily mediated by ω-5 gliadin which is encoded by the Gli-1B gene derived from the Aegilops speltoides B genome within wheat.

Glutelin allergies Glutenin (wheat glutelin) is a predominant allergen in wheat.[3] Nine subunits of LMW-glutinen have been linked in connection with wheat allergies.

Albumin and globulin allergy At present many of the allergens of wheat have not been characterized; however, the early studies found many to be in the albumin class.[5] A recent study in Europe confirmed the increased presence of allergies to amylase/trypsin inhibitors (serpins)[3][6] and lipid transfer protein (LPT),[7] but less reactivity to the globulin fraction.[8] The allergies tend to differ between populations (Italian, Japanese, Danish or Swiss), indicating a potential genetic component to these reactivities.

Other allergies

Wheat pollen and grass allergies Respiratory allergies are an occupational disease that develop in food service workers. Previous studies detected 40 allergens from wheat; some cross-reacted with rye proteins and a few cross-reacted with grass pollens.[9] A later study showed that baker's allergy extend over a broad range of cereal grasses (wheat, durum wheat, triticale, cereal rye, barley, rye grass, oats, canary grass, rice, maize, sorghum and Johnson grass) though the greatest similarities were seen between wheat and rye,[10] and that these allergies show cross reactivity between seed proteins and pollen proteins,[11] including a prominent crossreactivity between the common environment rye pollen and wheat gluten.[12][13]

Derivative allergies Proteins are made of a chain of dehydrated amino acids. When enzymes cut proteins into pieces they add water back to the site at which they cut, called enzymatic hydrolysis, for proteins it is called proteolysis. The initial products of this hydrolysis are polypeptides, and smaller products are called simply peptides; these are called wheat protein hydrolysates. These hydrolysates can create allergens out of wheat proteins that previously did not exist by the exposure of buried antigenic sites in the proteins. When proteins are cut into polypeptides, buried regions are exposed to the surface, and these buried regions may possibly be antigenic. Such hydrolyzed wheat protein is used as an additive in foods and cosmetics. The peptides are often 1 kD in size (9 amino acid residues in length) and may increase the allergic response.[14] These wheat polypeptides can cause immediate contact urticaria in susceptible people.[15] Wheat allergy 71

Signs and Symptoms Wheat allergies are not altogether different from other food allergies or respiratory allergies. However two conditions, exercise/aspirin induced anaphylaxis and urticaria occur more frequently with wheat allergies. Common symptoms of a wheat allergy include sacroiliitis, eczema (atopic dermatitis), hives (urticaria), asthma, "Hay fever" (allergic rhinitis), angioedema (tissue swelling due to fluid leakage from blood vessels), abdominal cramps, nausea, and vomiting.[16] Rarer symptoms include anaphylactic shock, arthritis, bloated stomach, chest pains, depression or mood swings, diarrhea, dizziness, headache, joint and muscle aches and pains (may be associated with progressive arthritis), palpitations, psoriasis, irritable bowel syndrome (IBS), swollen throat or tongue, tiredness and lethargy, and unexplained cough. Reactions may become more severe with repeated exposure.

Asthma, Anaphylaxis, Nasal Allergies

Exercise-induced anaphylaxis Wheat gliadins and potentially oat avenins are associated with another disease, known as wheat-dependent exercise Induced Anaphylaxis (WDEIA) which is similar to Baker's Allergy as both are mediated by IgE responses.[17] In WDEIA, however, the ω-gliadins[18] or a high molecular weight glutenin subunit, and similar proteins in other Triticeae genera enter the blood stream during exercise where they cause acute asthmatic or allergic reaction.[19] One recent study of ω-gliadins demonstrated these gliadins are more similar to the bulk of oat avenins than α/β or γ gliadins but, so far, oat avenins have not been linked to WDEIA. Wheat may specifically induce WDEIA and certain chronic urticaria because the anti-gliadin IgE detects ω -gliadins expressed by most of the Gli-B1 alleles but almost 5 no responses prolamins extracted from rye or wheat/rye translocates. The Gli-B1 gene in wheat, Triticum aestivum comes from one of three progenitor species, Aegilops speltoides, indicating that nascent mutations on the B genome of wheat or from a small number of cultivated triticeae species.[20]

Aspirin sensitivity and wheat allergy Recent study of WDEIA shows that both aspirin and exercise increase the presence of gliadin in the blood stream[21] and the chronic induced behavior may extend to NSAIDs, MSG, Benzoate and other synthetic chemical food additives.

Baker's Allergy Baker's allergy has a ω-gliadin component and thioredoxin hB component.[22] In addition, a gluten-extrinsic allergen has been identified as aspergillus amylase, added to flour to increase its baking properties. Wheat allergy 72

Urticaria, Atopy, Eczema

Contact Sensitivity,[23] Atopic Dermatitis,[24] Eczema, and Urticaria appear to be related phenomena the cause of which is generally believed to be the hydrophobic prolamin components of certain Triticeae, Aveneae cultivars, in wheat one of these proteins is ω-gliadin (Gli-B1 gene product). A study of mothers and infants on an allergen-free diet demonstrated that these conditions can be avoided if wheat sensitive cohort in the population avoid wheat in the first year of life.[25] As with exercise induced anaphylaxis aspirin (also: tartrazine, sodium benzoate, sodium glutamate (MSG), sodium metabisulfite, tyramine) may be sensitizing factors for reactivity.[26] Studies of the wheat-dependent exercise induced anaphylaxis demonstrate that atopy and EIA can be triggered from the ingestion of that aspirin and probably

NSAIDs allow the entry of wheat proteins into the blood, where IgE reacts Allergic urticaria on the shin within allergens in the dermal tissues. Some individuals may be so sensitive that low dose aspirin therapy can increase risk for both atopy and WDEIA.

Wheat allergies were also common with contact dermatitis. A primary cause was the donning agent used for latex gloves prior to the 1990s, however most gloves now use protein free starch as donning agents.

Autoimmune (Rheumatoid) arthritis There appears to be an association of autoimmune rheumatoid arthritis (ARA) both with GSE and gluten allergies.[27] ARA in GSE/CD may be secondary to tTG autoimmunity. In a recent study in Turkey, 8 of 20 ARA patients had wheat reactivities on the RAST tests. When this allergic food and all other patient specific RAST+ foods were removed half of the patients had improved ARA by serological markers. In patients with wheat allergies, rye was effectively substituted.[28] This may indicate that some proportion of RA in GSE/CD is due to downstream effects of allergic responses. In addition, cross-reactive anti-beef-collagen antibodies (IgG) may explain some rheumatoid arthritis (RA) incidences.[29]

Neuropathies Migraines. In the late 70s it was reported that people with migraines had reactions to food allergens, like ARA, the most common reaction was to wheat (78%), orange, eggs, tea, coffee, chocolate, milk, beef, corn, cane sugar, and yeast. When 10 foods causing the most reactions were removed migraines fell precipitously, hypertension declined.[30] Some specific instances are attributed to wheat.[31] Autism. Parents of children with autism often ascribe the children's gastrointestinal symptoms to allergies to wheat and other foods. The published data on this approach are sparse, with the only double-blind study reporting negative results.[32]

Diagnosis Diagnoses of wheat allergy may deserve special consideration. Omega-5 gliadin, the most potent wheat allergen, cannot be detected in whole wheat preparations, it must be extracted and partially digested (similar to how it degrades in the intestine) to reach full activity. Other studies show that digestion of wheat proteins to about 10 amino acids can increase the allergic response 10 fold. Certain allergy test may not be suitable to detect all wheat allergies, resulting in cryptic allergies. Because many of the symptoms associated with wheat allergies, such as sacroiliitis, eczema and asthma, may be related or unrelated to a wheat allergy, medical deduction can be an effective way of determining the cause. Wheat proteins can take months to fully metabolize so removing these foods from one's diet Wheat allergy 73

could be difficult to do as a method of diagnosis. If symptoms are alleviated by immunosuppressant drugs, such as Prednisone, an allergy related cause is likely. If multiple symptoms associated with wheat allergies are present in the absence of immunosuppressants then a wheat allergy is probable.[18]

Treatment Wheat allergies differ from gluten-diet exclusion in that some types of allergens do not create species crossreactive responses, an individual may be able to consume barley and rye safely, although more than likely they will be allergic to other wheat such as spelt and Kamut. Wheat is often a cryptic contaminant of many foods; more obvious items are bread crumbs, maltodextrin, bran, cereal extract, couscous, cracker meal, enriched flour, gluten, high-gluten flour, high-protein flour, seitan, semolina wheat, vital gluten, wheat bran, wheat germ, wheat gluten, wheat malt, wheat starch or whole wheat flour. Less obvious sources of wheat could be gelatinized starch, hydrolyzed vegetable protein, modified food starch, modified starch, natural flavoring, soy sauce, soy bean paste, hoisin sauce, starch, vegetable gum, specifically Beta-glucan, vegetable starch. People with wheat allergy who are gluten sensitive may also need to avoid related cereals, rye and barley, which have similar glutinous proteins.

Alternative cereals Triticeae gluten-free oats (free of wheat, rye or barley) may be a useful source of cereal fiber. Some wheat allergies allow the use of rye bread as a substitute. Rice flour is a commonly used alternative for those allergic to wheat. Wheat-free millet flour, buckwheat, flax seed meal, corn meal, quinoa flour, chia seed flour, tapioca starch or flour, and others can be used a substitutes. Spelt and khorasan wheat are grains related to common wheat, but are usually a suitable substitute for people with wheat allergies or that are gluten intolerant. Spelt and khorasan wheat are not options for those with Coeliac disease.

References

[1] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D021182 [2] Sotkovský P, Sklenář J, Halada P, Cinová J, Setinová I, Kainarová A, Goliáš J, Pavlásková K, Honzová S, Tučková L.,"A new approach to the isolation and characterization of wheat flour allergens.", Clin Exp Allergy. 2011 Jul;41(7):1031-43 [3] Akagawa M, Handoyo T, Ishii T, Kumazawa S, Morita N, Suyama K (2007). "Proteomic analysis of wheat flour allergens". J. Agric. Food Chem. 55 (17): 6863–70. doi:10.1021/jf070843a. PMID 17655322. [4] Perr HA (2006). "Novel foods to treat food allergy and gastrointestinal infection". Current allergy and asthma reports 6 (2): 153–9. doi:10.1007/s11882-006-0054-z. PMID 16566866. [5] Sutton R, Hill DJ, Baldo BA, Wrigley CW (1982). "Immunoglobulin E antibodies to ingested cereal flour components: studies with sera from subjects with asthma and eczema". Clin. Allergy 12 (1): 63–74. doi:10.1111/j.1365-2222.1982.tb03127.x. PMID 7067068. [6] Armentia A, Sanchez-Monge R, Gomez L, Barber D, Salcedo G (1993). "In vivo allergenic activities of eleven purified members of a major allergen family from wheat and barley flour". Clin. Exp. Allergy 23 (5): 410–5. doi:10.1111/j.1365-2222.1993.tb00347.x. PMID 8334538. [7] Pastorello EA, Farioli L, Conti A et al (2007). "Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors, lipid transfer proteins and low-molecular-weight glutenins. Allergenic molecules recognized by double-blind, placebo-controlled food challenge". Int. Arch. Allergy Immunol. 144 (1): 10–22. doi:10.1159/000102609. PMID 17496422. [8] Walsh BJ, Wrigley CW, Musk AW, Baldo BA (1985). "A comparison of the binding of IgE in the sera of patients with bakers' asthma to soluble and insoluble wheat-grain proteins". J. Allergy Clin. Immunol. 76 (1): 23–8. doi:10.1016/0091-6749(85)90799-7. PMID 3839248. [9] Blands J, Diamant B, Kallós P, Kallós-Deffner L, Lowenstein H (1976). "Flour allergy in bakers. I. Identification of allergenic fractions in flour and comparison of diagnostic methods". Int. Arch. Allergy Appl. Immunol. 52 (1–4): 392–406. PMID 65335. [10] Baldo BA, Krilis S, Wrigley CW (1980). "Hypersensitivity to inhaled flour allergens. Comparison between cereals". Allergy 35 (1): 45–56. doi:10.1111/j.1398-9995.1980.tb01716.x. PMID 6154431. [11] Valero Santiago A, Amat Par P, Sanosa Valls J, Sierra Martínez P, Malet Casajuana A, García Calderón PA (1988). "Hypersensitivity to wheat flour in bakers". Allergologia et immunopathologia 16 (5): 309–14. PMID 3228051. [12] Donovan GR, Baldo BA (1990). "Crossreactivity of IgE antibodies from sera of subjects allergic to both ryegrass pollen and wheat endosperm proteins: evidence for common allergenic determinants". Clin. Exp. Allergy 20 (5): 501–9. doi:10.1111/j.1365-2222.1990.tb03142.x. PMID 2253081. [13] Yazicioglu M, Oner N, Celtik C, Okutan O, Pala O (2004). "Sensitization to common allergens, especially pollens, among children with respiratory allergy in the Trakya region of Turkey". Asian Pac. J. Allergy Immunol. 22 (4): 183–90. PMID 15783130.. Wheat allergy 74

[14] Akiyama H, Sakata K, Yoshioka Y et al (2006). "Profile analysis and immunoglobulin E reactivity of wheat protein hydrolysates". Int. Arch. Allergy Immunol. 140 (1): 36–42. doi:10.1159/000092000. PMID 16534217. [15] Laurière M, Pecquet C, Bouchez-Mahiout I et al (2006). "Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities". Contact Derm. 54 (5): 283–9. doi:10.1111/j.0105-1873.2006.00830.x. PMID 16689814.

[16] "Allergy Society of South Africa - Wheat Allergy" (http:/ / web. archive. org/ web/ 20080424072330/ http:/ / www. allergysa. org/ wheat.

htm). Archived from the original (http:/ / www. allergysa. org/ wheat. htm) on 2008-04-24. . Retrieved 2008-10-20. [17] Mittag D, Niggemann B, Sander I, Reese I, Fiedler EM, Worm M, Vieths S, Reese G. (2004). "Immunoglobulin E-reactivity of wheat-allergic subjects (baker's asthma, food allergy, wheat-dependent, exercise-induced anaphylaxis) to wheat protein fractions with different solubility and digestibility". Mol Nutr Food Res. 48 (5): 380–389. doi:10.1002/mnfr.200400016. PMID 15672478. [18] Matsuo H, Morita E, Tatham AS, Morimoto K, Horikawa T, Osuna H, Ikezawa Z, Kaneko S, Kohno K, and Dekio S. (2004). "Identification of the IgE-binding epitope in omega-5 gliadin, a major allergen in wheat-dependent exercise-induced anaphylaxis". J Biol Chem. 279 (13): 12135–12140. doi:10.1074/jbc.M311340200. PMID 14699123. [19] Matsuo H, Morimoto K, Akaki T, Kaneko S, Kusatake K, Kuroda T, Niihara H, Hide M, and Morita E. (2005). "Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis". Clin Exp Allergy. 35 (4): 461–466. doi:10.1111/j.1365-2222.2005.02213.x. PMID 15836754. [20] Denery-Papini S, Lauriére M, Branlard G et al (2007). "Influence of the allelic variants encoded at the Gli-B1 locus, responsible for a major allergen of wheat, on IgE reactivity for patients suffering from food allergy to wheat". J. Agric. Food Chem. 55 (3): 799–805. doi:10.1021/jf062749k. PMID 17263477. [21] Morita E, Kunie K, Matsuo H (2007). "Food-dependent exercise-induced anaphylaxis". J. Dermatol. Sci. 47 (2): 109–17. doi:10.1016/j.jdermsci.2007.03.004. PMID 17507204. [22] Weichel M, Glaser AG, Ballmer-Weber BK, Schmid-Grendelmeier P, Crameri R (2006). "Wheat and maize thioredoxins: a novel cross-reactive cereal allergen family related to baker's asthma". J. Allergy Clin. Immunol. 117 (3): 676–81. doi:10.1016/j.jaci.2005.11.040. PMID 16522470. [23] Langeland T, Nyrud M (1982). "Contact urticaria to wheat bran bath: a case report". Acta Derm. Venereol. 62 (1): 82–3. PMID 6175150. [24] Barnetson RS, Wright AL, Benton EC (1989). "IgE-mediated allergy in adults with severe atopic eczema". Clin. Exp. Allergy 19 (3): 321–5. doi:10.1111/j.1365-2222.1989.tb02390.x. PMID 2736432. [25] Zeiger RS, Heller S, Mellon MH et al (1989). "Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study". J. Allergy Clin. Immunol. 84 (1): 72–89. doi:10.1016/0091-6749(89)90181-4. PMID 2754147. [26] Van Bever HP, Docx M, Stevens WJ (1989). "Food and food additives in severe atopic dermatitis". Allergy 44 (8): 588–94. doi:10.1111/j.1398-9995.1989.tb04205.x. PMID 2610332. [27] Hvatum M, Kanerud L, Hällgren R, Brandtzaeg P (2006). "The gut–joint axis: cross reactive food antibodies in rheumatoid arthritis". Gut 55 (9): 1240–7. doi:10.1136/gut.2005.076901. PMC 1860040. PMID 16484508. [28] Karatay S, Erdem T, Kiziltunc A et al (2006). "General or personal diet: the individualized model for diet challenges in patients with rheumatoid arthritis". Rheumatol. Int. 26 (6): 556–60. doi:10.1007/s00296-005-0018-y. PMID 16025333. [29] Dieterich W, Esslinger B, Trapp D, Hahn E, Huff T, Seilmeier W, Wieser H, and Schuppan D. (2006). "Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease". Gut. 55 (4): 478–84. doi:10.1136/gut.2005.069385. PMC 1856150. PMID 16188922. [30] Grant EC (1979). "Food allergies and migraine". Lancet 1 (8123): 966–9. doi:10.1016/S0140-6736(79)91735-5. PMID 87628. [31] Pascual J, Leno C (2005). "A woman with daily headaches". The journal of headache and pain : official journal of the Italian Society for the Study of Headaches 6 (2): 91–2. doi:10.1007/s10194-005-0158-1. PMID 16362649. [32] Elder JH (2008). "The gluten-free, casein-free diet in autism: an overview with clinical implications". Nutr Clin Pract 23 (6): 583–8. doi:10.1177/0884533608326061. PMID 19033217. Gluten sensitivity 75 Gluten sensitivity

Gluten sensitivity (also gluten intolerance) is a spectrum of disorders, including celiac disease and wheat allergy, in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in celiac disease or wheat allergy (other conditions which fall under the gluten-related disorders spectrum). Gluten sensitivity is thought to affect roughly 10% of the general population.[1] Symptoms of gluten sensitivity include bloating, abdominal discomfort, pain or diarrhea; or it may present with a variety of extraintestinal symptoms including headaches and migraines, lethargy and tiredness, attention-deficit disorder and hyperactivity, schizophrenia, muscular disturbances as well as bone and joint pain.[2][3][4][5] Until recently, the terms gluten sensitivity and celiac disease were used interchangeably in literature. However, emerging research is beginning to identify the differences that exist between celiac disease and gluten sensitivity. If the medical history of a patient, along with clinical tests, rule out celiac disease and wheat allergy, a diagnosis of gluten sensitivity can be considered. However, certain criteria need to be met before a diagnosis of gluten sensitivity can be confirmed (see diagnosis section). Treatment for all three conditions is a gluten-free diet; the difference being that with wheat allergy the interruption is temporary and drugs may be administered; in the case of celiac disease the diet is lifelong and even ingesting very small amounts of gluten-containing food could damage their health and, in the case of gluten sensitivity the withdrawal of gluten from the diet may only be temporary. Gluten is a protein composite found in foods processed from wheat and related species, including barley and rye. It gives elasticity to dough helping it to rise and to keep its shape. It is found in many staple foods in the Western diet. Gluten is composed of a gliadin fraction (alcohol soluble) and a glutenin fraction (only soluble in dilute acids or alkali).

Symptoms Symptoms of gluten sensitivity may include bloating, abdominal discomfort, pain, or diarrhea; or it may present with a variety of extraintestinal symptoms including headaches and migraines, lethargy and tiredness, attention-deficit disorder and hyperactivity, muscular disturbances as well as bone and joint pain.[4][5][6]

Diagnosis If the medical history of a patient, along with clinical tests, rule out celiac disease and wheat allergy, a diagnosis of gluten sensitivity can be considered. However, before a diagnosis of gluten sensitivity can be confirmed the following criteria need to be met: • Wheat allergy excluded (anti IgE antibody negative) • Celiac disease excluded (negative serological results of tTG/EMA/dAGA and IgA deficiency) • Not HLA restricted- the absence of HLA DQ2/8 heterodimers makes it possible to practically rule out celiac disease, however, it is also important to note that the presence of HLA DQ 2 or DQ8 does not always mean celiac disease • Intestinal biopsy shows no villous atrophy (Marsh III classification) but there may be minimal changes to the lining of the gut (Marsh 0-I classification) • Possible presence of serum anti-gliadin antibodies (AGA) IgA and/or IgG investigated • If the patient reports alleviation of symptoms on a gluten-free diet If the above criteria are met then the person can be classed as ‘gluten sensitive’ and it can be treated with a gluten-free diet for a period of time. This should lead to symptom resolution. Gluten sensitivity 76

Difference between gluten sensitivity and celiac disease While the research surrounding gluten sensitivity is still very much emerging, celiac disease is a well-defined condition. It is a lifelong autoimmune condition characterised by the chronic inflammation of the intestine. In genetically predisposed children and adults the intake of foods containing gluten leads to an immune response in the small intestine. This results in the flattening of the intestinal villi and in reduced absorption of nutrients from food which can lead to nutritional deficiencies and associated long-term complications such as osteoporosis. It is believed celiac disease affects 1% of the general population in the Western world. In comparison, in a recent clinical paper, gluten sensitivity was defined as ‘one or more of a variety of immunological, morphological or symptomatic manifestations that may also be shared by celiac disease and irritable bowel syndrome (IBS).[7] In cases where there is reactivity to gluten, yet celiac disease and wheat allergy are eliminated as possibilities, gluten sensitivity may be considered. Whilst the general clinical picture for gluten sensitivity is similar to celiac disease in particular, it is usually less severe and neither anti-tissue transglutaminase antibodies nor autoimmune comorbidities are found. It is believed that approximately 40-50% of gluten sensitivity patients may have IgG or IgA anti-gliadin antibodies (AGA)[8][9] There is also a study identifying approximately 50% of gluten sensitivity patients, few more than the general population, carry either HLA DQ 2 or 8 [10] On closer inspection, it has also been found that gluten-sensitive subjects do not develop full histological lesions; their lesions, if any, are limited to types 0-1 of the Marsh classification. In addition, it has been found that they have normal intestinal permeability and an increased expression of Toll Like receptors 2 (TLR2) but no change in the cytokines involved in adaptive immune responses Th1 and Th17 such as IL-6, IL-17 A, IL 21, which are increased only in patients with celiac disease. The knowledge of the response in gluten sensitivity to date suggests that only the innate immune system is involved, whereas celiac disease is an adaptive immune response (autoimmunity). Gluten sensitivity should have a defined cause, although not apparent always with first examination, affected individuals should eventually fall into GSE or wheat allergy. Only rarely should gluten sensitivity be idiopathic. Idiopathic gluten sensitivity (IGS) arises spontaneously or from an obscure or unknown cause and may involve neuropathy, myopathy, dermal, or intestinal abnormalities. Anti-gliadin antibodies are the primary link between gluten and idiopathic sensitivity in instances "in which enteropathy or allergy are not clearly involved".[11] This form of gluten sensitivity is controversial at the moment but there is a growing body of research to support the concept of gluten sensitivity that is different from celiac disease and wheat allergy.

Etiology Gluten sensitivity can develop at any point in life, and symptomatic disease may appear years after disease develops. When enteropathy develops in early childhood symptomatic disease is more rapidly evident. A survey of geriatrics with celiac disease in Finland[12] revealed that the incidence of disease was much higher than the general population. Allergic disease may rise or fall with age; however, certain evidence points to the increased or daily use of non-steroidal anti-inflammatory factors (aspirin, ibuprofen) as an increased risk factor for urticaria or anaphylaxis, and the sensitizing dose may include low-dose aspirin therapy used in the treatment of heart disease. Idiopathic disease appears largely late onset. Gluten-sensitive enteropathy develops as a consequence of genetic and environmental factors. Other than the involvement of certain HLA-DQ isoforms (antigen presenting proteins in humans) and certain wheat proteins, there is no clarity in the involvement of other genes or other environmental factors (see risk modifiers). Strong genetic factors such as seen in GSE have not been seen in gluten allergy, and with idiopathic gluten-sensitivity the HLA-DQ associations are weak. Researchers reported extreme fatigue and pain in patients without celiac disease, with gliadin antibodies. They called this a “non-celiac gluten intolerance” for which there is no explanation as to the mechanisms involved.[13] Gluten sensitivity 77

Causes of gluten sensitivity

Underlying conditions The normal intestine

Illustration of the brush border membrane of small intestinal villi

Wheat proteins interact with the immune system by means of DQ2-mediated programmed cell death (apoptosis) of the gut in sensitive individuals. New research is finding that the celiac gut may be predisposed to sensitivity in the absence of HLA genetic factors.

How diet proteins reach the blood

The fate of digestible protein in the small intestine

In the normal gut, proteins are digested to peptides by pepsin (stomach), trypsin and chymotrypsin (derived from the pancreas and activated in the gut). Peptides are further digested when they enter the villi, where brush border peptidase break proteins into amino acids. Over much of the small intestine only small solutes, like water, can cross the tight junctions, however some regions of the intestine peptides as large as 500 daltons (4 amino-acids residues in length can cross).

The gluten sensitive gut Gluten sensitivity 78

The fate of gluten in celiac disease or EIA

There is a growing body of evidence that the gluten-sensitive intestine differs from the normal gut. Several gluten peptides can infiltrate the region behind the cells lining the small intestine. The "33mer" of α-2 gliadin is a magnitude larger than the maximum size allowable by the barrier around the cell, the tight junctions. Omega-5 gliadin peptides have been found in the blood stream of people with exercise-induced anaphylaxis, aided by salicylates. And the innate "25mer" is capable of reaching mononuclear cells in celiac gut, but in normal gut is broken down by brush border peptidases. It may be a lower peptidase activity that explains the presence of these peptides behind the brush border membrane. Recently, it was found that an α-9 gliadin peptide was capable of binding the "CXCR3" receptor, increasing zonulin production and weakening tight junctions, this may explain how, generally, larger peptides can enter the gluten-sensitive gut.

Triticeae and the potential role of selective evolution in gluten sensitivities The fruiting bodies of plants contain genes as well as reserves of nutrients that allow seedlings to grow. The enrichment of nutrients is an attractant to herbivores and omnivores. For annual grasses that release seeds during a brief period each year there is a need to protect seeds during maturation from insects or animals, which might stock seeds for year round usage. For wheat, alpha-gliadins are seed-storage proteins, but also act as inhibitors of alpha-amylase activity in some animals, particularly in insects.[14] It is also known that wheat gliadins create intestinal disease when fed to very young rodents.[15] One recent publication even raises the question 'is wheat safe for anyone to eat?'.[16] Critically, pathology in insects or artificially fed rodents does not reflect what causes disease in humans, but it is interesting that toxicological effects of wheat are being uncovered that do have the potential to cause pathology in humans. One interesting consequence of these studies is that there may be a general gluten sensitivity that underlies various pathological manifestations, such as celiac disease, urticaria and idiopathic sensitivity. The rise of gluten sensitivity (particularly in adults) may reflect the convergence of many phenomena. An aging population, genetic risks associated with westernization, excesses in the diet, sensitizing chemicals (e.g.NSAIDs), and allergy-enhancing chemical treatment of foods (e.g. enzymatic deamidation of gluten) may act together with natural defensive agents in foods to cross the threshold between normality and pathology.

Gluten toxicity

Further information: Innate immunity of gluten An increasing number of studies on gliadin indicate gluten has a direct Illustration of 2 alpha gliadins showing 2 and modifying effect on the cells of the small intestine. Two different proteolytically resistant sites, Top shows 6 lines of research show that different gliadins can increase permeability T-cells sites in 33mer, and bottom shows innate immune peptide and two CXCR3 binding sites of the epithelial cells (outermost cells of the villus) allowing food proteins to enter. One study examined the effect of ω-5 gliadin, the primary cause of Wheat Dependent exercise/aspirin induced anaphylaxis, and found increased permeability of intestinal cells caused by this gliadin and another wheat albumin.[17]

Another line of research shows gliadin binds a chemoattractant receptor and causes increases of a factor that destroys tight junctions.[18] These junctions prevent leakage around the cells that line the small intestine, resulting in the Gluten sensitivity 79

leaking of food proteins into the body.[19] These toxicities of gluten that are not part of the adaptive immune response may be the link between wheat and gluten sensitivity, and possibly type 1 diabetes.

Immunochemistry of glutens Triticeae glutens are important factors in several inflammatory diseases. The immunochemistry can be subdivided into innate responses (direct stimulation of immune system), class II mediated presentation (HLA DQ), class I mediated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In enteropathy, there are at least 3 types of recognition, innate immunity (a form of cellular immunity priming), HLA-DQ and antibody recognition of gliadin and transglutaminase.[20] The three dominant sequences responsible for the antibody reaction have been identified.[21][22] With idiopathic disease only antibody recognition to gliadin has been resolved. In wheat allergy, there appears to be an innate components and the response pathways are mediated through IgE against gliadin and other wheat proteins.[23][24][25]

Separating forms of gluten sensitivity Only rarely should gluten sensitivity be without cause. Generally the sensitivity can be split between celiac disease, gluten sensitivity and wheat allergy. Since individuals with celiac disease can also have wheat allergy, a finding of wheat allergy does not eliminate the possibility of enteropathy. Individuals highly suspect of celiac disease may be tested for anti-transglutaminase antibodies followed by duodenal biopsy, this will confirm or refute active celiac disease.[26] The study that recommends this, however, has a number of ATA positive/biopsy-negative individuals, this could result from patchy villous atrophy or subclinical pathology.[27][28] One current study recommended at biopsy samples running distally from the duodenum to avoid the risk of false negatives. Eliminating the possibility of celiac disease can generally be done by adding HLA-DQ typing, in which DQ2 and DQ8 are found in enteropathy 98% of the time in caucasians, DQ7.5 the remaining 1.6% and 0.4% not found with either of these 3. Without ATA or HLA-DQ2/8 positivity, celiac disease is not likely the cause of the sensitivity. In either case, other avenues of diagnostics, such as allergy testing are available.[29] Rarely gluten sensitivity may be idiopathic, a potential that wheat proteins play a role in other disease, in these instances DQ1 may be associated with sensitivity. There is research showing that in certain patients with gluten ataxia early diagnosis and treatment with a GFD can improve ataxia and prevent its progression.[30]

Gluten-sensitive enteropathy (GSE)

Celiac disease as the classically defined gluten-sensitivity and dermatitis herpetiformis was appended to a broadening definition of gluten sensitivity. The diagnostic "gold standard" of celiac disease is the villus atrophy detected in duodenal biopsies. However, it is now recognized that inflammation of the epithelial tissue of the Schematic of the Marsh classification of upper jejunal pathology in celiac disease. small intestine precedes atrophy. Early in the disease, gluten elicits T-lymphocyte recognition of gluten hydrolysates (polypeptides of gluten) and gluten peptides bind to mammalian tissue transglutaminase (tTG).

This second interaction results in the production of "self" antibodies to tTG. This increases lymphocytes within the epithelia of the small intestine (Marsh grade 1 and 2) and antibody-tTG complexes seen as deposits. This usually Gluten sensitivity 80

progresses to celiac disease (Marsh grade 3 and 4). The dietary cause of GSE is not limited to wheat gluten; 'glutens' from all known edible cultivars of Triticeae can induce GSE in susceptible individuals (see: Gluten immunochemistry). There are a large number of medical conditions that result from GSE that can occur prior to the development of celiac disease and might be gluten responsive. While the level of villus atrophy in some cases of GSE may not reach clinical celiac disease recognition, the elevation of cellular immunity is capable of producing disorders more frequently found in celiac disease. Conditions secondary to GSE are important diagnostic criteria for gluten sensitivity when there may be no obvious intestinal abnormality.

Frequencies of phenotypes in Celiac disease, Normal Americans, Odds ratios

DQ haplotypes -Celiac Disease

DQ hap 2.5 2.2 7.5 8.0 Other

2.5 34 22 4.0 2.0 22

2.2 1.1 4.0 1.1 2.9

7.5 0.3 0.0 1.3

8.1 2.9 2.0

other 0.4

DQ haplotypes -Normal Population

DQ hap 2.5 2.2 7.5 8.1 Other

2.5 1.7 2.9 2.9 1.8 15.1

2.2 1.2 2.4 1.6 12.8

7.5 1.2 1.5 1.3

8.1 0.5 8.0

other 33.4

Odds ratios

DQ hap 2.5 2.2 7.5 8.1 Other

2.5 20:11 8:12 1.4:16 1.1:1 1.5:15

2.2 1:1.1 1.6:14 1:1.3 1:5

7.5 1:4 0 1:10

8.1 6:13 1:4

other 1:100

DQ Types by allele numbers (e.g. 0501) can be found here

Presentation of GSE is often the result of initial recognition of the secondary condition which in followup testing (ATA test, AGA test, HLA-DQ typing, and/or biopsy) recognizes the primary condition. The secondary conditions associated with GSE tend to make late onset celiac disease a systemic phenomena. Gluten sensitivity 81

Idiopathic gluten sensitivity Idiopathic diseases are proposed as an expansion of the gluten-sensitivity. By the definition of idiopathic disease, the cause is not well defined. One hundred years ago, before gluten was discovered as the cause of celiac disease, celiac disease in adults was called adult idiopathic steatorrhoea, non-tropical sprue, sprue nostras, and many other names. The debate over this subset stems from the fact that identification of all grades of GSE and allergies is not uniformly approached. Most cases of early GSE go undetected, particularly before 2005. There appears to be a small fraction of non-GSE gluten-sensitive individuals that show neither gluten-allergies but do have elevated anti-gliadin IgA or IgG. Common symptoms are peripheral neuropathies and cerebellar ataxia. Within the GSE set these may be explained by calcification of brain channels and avitaminosis. Within the remaining 'DQ2 and DQ8'less cohort. Given that this cohort of GS is idiopathic, the role of allergies, other sensitivities (e.g. aspirin), or other factors in IGS is also unresolved. Further information: Anti-gliadin antibodies Silent Disease. Depending on testing somewhere between 3 and 15% of the normal population have anti-gliadin antibodies (AGA). Studies using anti-gliadin antibodies (AGA) reveal that in undiagnosed or untreated individuals with AGA, with increasing risk for lymphoid cancers and decreased risk for other associated with affluence.[31] Though it is unknown in these studies the percentage that are early stage GSE.

Other conditions Antibodies to α-gliadin have been significantly increased in non-celiacs individuals with oral ulceration.[32] Anti-α-gliadin antibodies are frequently found in celiac disease(CD), to a lesser degree subclinical CD, but are also found in a subset who do not have the disease. The 1991 reference comes from a period when testing for subclinical CD was undeveloped. Of people with pseudo-exfoliation syndrome, 25% showed increased levels of anti-gliadin IgA.[33] One fourth of people with Sjögren's syndrome had responses to gluten, of 5 that had positive response to gluten, only one could be confirmed as CD and another was potentially GSE, the remaining 3 appear to be gluten-sensitive. All were HLA-DQ2 and/or DQ8-positive.[34] Treatment to produce remission of Crohns disease(CrD) symptoms on elimination diet indicated the most important foods provoking symptoms were wheat and dairy.[35] A later paper showed little IgE mediated response except to the dairy,[36] while another paper showed no significant anti-food IgE association.[37] Crohn's disease (CrD) may have a link to wheat that is independent of gluten. CrD appears to be associated with high anti-yeast antibodies (ASCA - yeast antigens that are found in bread and other cereal derived products) and affected individuals lack lectin binding proteins such that the mannins in yeast, the antibodies that bind them and aggravate inflammatory colitis. One concern of the above studies is the high prevalence of markers for gluten-sensitive enteropathy, one has to question how idiopathic these conditions are if close examination for GSE has not been undertaken.

Gluten-allergy related sensitivities Why treat gluten allergies as sensitivities? Over the last 10 years it has become apparent that allergies to certain substances do not behave in predictable ways. One clear example of this is exercise induced anaphylaxis and asthma, WDEIA (Wheat Dependent Exercise Induced Anaphylaxis) is now believed to be induced by ingested gluten that finds a way into the blood stream. This pathway is now believed responsible for some forms of eczema. Recent studies on two wheat allergens show that they possess the capability of bypassing the gut/blood barrier. The most active of these is ω-5 gliadin, a gluten component that is a strong allergen and causes WDEIA. Allergy tests may not reveal allergies to gluten because the unfractionated allergens are 'hidden' from these tests, and most currently available tests cannot detect these new allergens. Finally, allergies typically involve IgE, but some studies indicate there are several classes of responses, for example IgG1,IgG2, IgG4 that are associated with IgE.[38] Gluten allergy may be a cause of some idiopathic gluten sensitivity and gluten allergy can be a secondary consequence of Gluten sensitivity 82

gluten-sensitive enteropathy.

Comparative pathophysiology

Comparison of different forms of gluten sensitivity

Gluten-sensitive enteropathy Wheat allergy Gluten-sensitive idiopathic neuropathy Typical symptoms steatorrhoea, malnutrition, diarrhea, eczema, asthma ataxia, peripheral lactose intolerance, food allergies neuropathies Primary tissue epithelia of small intestine (epi) dermis, bronchi, intestines CNS, Peripheral nerves targets Atypical other autoimmune diseases, chronic arthritis, migraines, anaphylaxis unknown pathologies constipation, neuropathies, cancer (exercise or aspirin induced) (lymphoid) Secondary targets blood (chemistry), bowel, nervous connective tissue, CNS, vascular (common) system, autoantigens Immunoglobin IgA, IgG IgE, IgG, IgA IgG, IgA isotype Antibody α/β,γ-gliadin (AGA), transglutaminase albumins, globulins, prolamins α/β-gliadin recognition (ATA) (ω-gliadin)(AGA), glutelins (LMW)(AGA) HLA associations DQ2.5, DQ8, DQ2.2/DQ7.5 unknown DQ2, DQ8?, DQ1? Cellular immunity T-cells, Eosinophils, Monocytes Mast cells, Eosinophils unknown Innate responses (α-gliadin) immune, increased (ω-5 gliadin)- increased permeability unknown permeability Background & Celiac disease, GSEA conditions Wheat allergy IGS Neuropathies references

Notes on table. Features of idiopathic neuropathy assume that all GSE cohort has been removed, assuming there is a gluten-sensitive, but not GSE contingent. Anti-gliadin antibodies covers all immunoglobulin isotypes and all gliadin isoforms. T-cell, Killer cell, and other gluten recognitions are covered in Gluten immunochemistry.

Gluten sources Politics of Gluten-Free and Oats Current guidelinesAs a consequence, the current international standard for the "Gluten-free" designation, drafted in 1981 and agreed on in 1983[39] within the Codex Alimentarius (CA), states: For the purpose of this standard, gluten is defined as those proteins, commonly found in wheat, triticale, rye, barley or oats to which some persons are intolerant.[40] The American Dietetic Association’s Nutrition Care Manual position on the use of oats in a medically necessitated gluten-free diet is: However, commercially available oats in the United States may be contaminated with small amounts of wheat, barley, or rye. For this reason, if you are newly diagnosed with celiac disease, you should not eat oats. Once your intestine heals, you may want to discuss the use of oats with your dietitian and physician.[41] Gluten sensitivity 83

indicating the need for a separate standard of purity for people with gluten sensitivity. New standards in developmentCodex Alimentarius is undergoing revision and a revised standard will be presented at the meeting of the Codex Alimentarius Commission at the end of June 2008.[42] The proposed standard limits the amount of contaminant in product that would qualify that product as gluten-free: Gluten-free foods are dietary foods a) consisting of or made only from one or more ingredients which do not contain wheat (i.e., all Triticum species, such as durum wheat, spelt, and kamut), rye, barley, oats1 or their crossbred varieties, and the gluten level does not exceed 20 mg/kg in total, based on the food as sold or distributed to the consumer, and/or b) consisting of one or more ingredients from wheat (i.e., all Triticum species, such as durum wheat, spelt, and kamut), rye, barley, oats1 or their crossbred varieties, which have been specially processed to remove gluten, and the gluten level does not exceed 20 mg/kg in total, based on the food as sold or distributed to the consumer.[43] 1 The Committee agreed to specify that the allowance of oats that are not contaminated with wheat, rye or barley in foods covered by the standard may be determined at national level."[43] In realizing the benefit of whole oats in a gluten free diet, the Canadian Celiac Association sought to assure oats and oat products fulfill the gluten-free standards set by the Canadian Food Inspection Agency and Health Canada: in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats.[44] From the perspective of gluten sensitivity there is no single definition of gluten that concisely defines all potentially pathogenic glutens. With wheat allergies, there can be a wide spectrum of species that may trigger allergies with similar proteins, the omega-gliadin proteins have similar proteins found in oats at high frequency, but omega-gliadin allergy is not a predictor of oat allergy or intolerance.[45] A person can have an allergy to wheat, but not rye.[46] Glutelins have not been characterized over broad taxa. With idiopathic gluten sensitivity, the antibodies that correlate with disease are anti-gliadin antibodies. Whether these antibodies are pathogenic or are simply indicators of circulating gliadin is unknown. For gluten-sensitive enteropathy, gliadin and homologous proteins from rye and barley cause disease. T-cell epitopes implicated in disease have been found in glutinous protein genes in all species sequenced within the tribe Triticeae.[47] Also, since barley is distantly related to wheat, but carries pathogenic epitopes it can be assumed that all members of Triticeae should carry T-cell sites capable of sustaining disease (see also Genetics of Triticeae). While often not explicitly stated in some standards, pathogenic glutens found in wheat are also found in Spelt and Kamut (both types of wheat), Triticale (a trans-species Triticeae hybrid).

The oat controversy

Oats are a species within the grass tribe Aveneae, which is in the Pooideae subfamily along with Triticeae (contains wheat, rye, barley and many other genera). Oats are the most closely related cereal species to Triticeae cereals. Some, but not all, cultivars of oat contain the pathogenic proteins that provoke a response in gluten sensitive individuals and those with celiac disease.[48] Alternatively, oat seeds appear similar to seeds of wheat, barley and rye; cross-contamination between these grains is difficult to resolve.

Further information: Oat-sensitive celiac disease

Oat grains in their husks Gluten sensitivity 84

Origin of controversy After World War II, wheat was suspected as the cause of celiac disease, and the gluten from wheat was identified as a cause soon after. At the time, duodenal biopsy—the current "gold standard" of diagnosis—had not yet been developed;[49] indirect measures of disease were used. In two studies, three children were fed 75 to 150 grams of oats per day and developed symptoms. In three concurrent studies, 10 children and two adults were allowed to eat 28 to 60 grams of oats and developed no symptoms.[50] Since wheat, barley and sometimes rye are common contaminants in oats,[41][51] until this was investigated, oats were considered to be toxic to celiacs. Further information: History of celiac disease

Current findings While the problem of contamination has been known for several years, scientists' understanding of how oats and gluten are related continues to evolve. A study published in February 2011 uncovered differing levels of toxicity amongst different varieties of oat, indicating that cross-contamination is not the only reason why some oats provoke reactions in some people with a gluten intolerance.[48] A study published in June 2008 found that of 109 sources of oats screened, 85 had unacceptable levels of gluten from wheat, barley or rye.[52] Triticeae contaminated oats in the study came from many countries indicating that most sources of oats are unacceptable for GS based on contamination.

Tolerable levels of gluten In summary of recent developments, oats can be tolerated in a gluten-free diet, but oat products should be limited in contamination from Triticeae derived gluten to 20 PPM (20 mg per kg). US states are free to deny the GF-label standard for oat products, if warranted (see Politics of Gluten-Free and oats).[53]

Gluten-free testing As of February 2011, G12, the newest monoclonal antibody (moAb) available, is the only one proven to detect both cross-contamination in oats and also the inherent gluten / avenin that is only found in some varieties of oat.[48] Alternative methods of detection, while currently accepted by many gluten-free certification organizations, are not in fact able to detect this second form of gluten in oats. This may partially explain why some celiacs react to oats and others do not. A barley-sensitive ELISA called the R5 sandwich assay does not detect gluten in any of 25 pure oat varieties, but it does detect barley, wheat and rye.[52] Disease-sensitive farming practices, antibody testing and species specific genetic testing are capable of producing pure oats.[52] In the United States, 3 domestic GF-brands are available and one brand imported from Ireland 'reckons' to be 99.95% pure oats.[54][55] Two brands in the United States use the R5 antibody test and claim to be below 20 PPM in defined gluten.[54][56] However, the R5 antibody test has not been proven to be as sensitive as the G12 test. Further information: Antibody testing for gluten-free foods

Diets Gluten-free oats in a gluten-free diet. Gluten-free oats can provide a valuable source of fiber, vitamin B, iron, zinc and complex carbohydrates.[57] Recent studies show that gluten-sensitive individuals on a gluten-free diet often get too much simple starch, too little fibre and vitamin B. Currently most guidelines do not include oats in a gluten-free diet. While this is likely to change, oats are not recommended within a year of diagnosis because of the oat-sensitive enteropathy (ASE) risk, the desire to establish a clinical baseline and complexity of the contamination issue.[58] Consuming oats when anti-gliadin antibodies or gliadin are present increases anti-avenin antibodies, and may promote ASE. Duodenal biopsy may be recommended after oat consumption is initiated. The DQ phenotype of all 3 Gluten sensitivity 85

ASE individuals studied so far indicated DQ2 homozygotes are at risk for ASE. Preferably, newly diagnosed celiacs seek the help of a dietician. However, guidelines are also available for the introduction of pure, uncontaminated oats into the gluten-free diet.[58] Further information: Oat sensitivity

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[21] http:/ / www. livescience. com/ health/ celiac-disease-gluten-peptides-100721. html [22] Tye-Din JA, Stewart JA, Dromey JA, Beissbarth T, van Heel DA, Tatham A, Henderson K, Mannering SI, Gianfrani C, Jewell DP, Hill AV, McCluskey J, Rossjohn J, Anderson RP (2010). "Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease". Sci Transl Med 2 (41): 41ra51. doi:10.1126/scitranslmed.3001012. PMID 20650871. [23] Bittner C, Grassau B, Frenzel K, Baur X (March 2008). "Identification of wheat gliadins as an allergen family related to baker's asthma". J. Allergy Clin. Immunol. 121 (3): 744–9. doi:10.1016/j.jaci.2007.09.051. PMID 18036646. [24] Matsuo H, Dahlström J, Tanaka A, et al. (February 2008). "Sensitivity and specificity of recombinant omega-5 gliadin-specific IgE measurement for the diagnosis of wheat-dependent exercise-induced anaphylaxis". Allergy 63 (2): 233–6. Gluten sensitivity 86

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1983 REPORT OF THE 13TH SESSION OF THE CODEX COMMITTEE ON FOODS FOR SPECIAL DIETARY USES (http:/ / www.

codexalimentarius. net/ download/ report/ 241/ al83_26e. pdf) Bonn-Bad Godesberg, 20–24 September 1982

[40] "Codex standard for "GLUTEN-FREE FOODS", CODEX STAN 118-19811 (http:/ / www. codexalimentarius. net/ download/ standards/

291/ CXS_118e. pdf). Codex alimentaris, Food and Agricultural Organization of the United Nations

[41] American Dietetic Association. Nutrition Care Manual: Celiac Disease. Available at: http:/ / www. nutritioncaremanual. org. Accessed December 15, 2004. [42] "CODEX ALIMENTARIUS COMMISSION - Thirty first Session - Geneva, Switzerland, 30 June - 5 July 2008". From Title page. Committee on Nutrition and Foods for Special Dietary Uses. JOINT FAO/WHO FOOD STANDARDS PROGRAMME CODEX ALIMENTARIUS COMMISSION. Thirty-first Session Geneva, Switzerland, 30 June – 4 July 2008, Codex Alimentarius Commission REPORT OF THE 29th SESSION OF THE CODEX COMMITTEE ON NUTRITION AND FOODS FOR SPECIAL DIETARY USES

(http:/ / www. codexalimentarius. net/ download/ report/ 687/ al08_26e. pdf) [43] "Draft Revised Standard for Foods for Special Dietary Use for Persons intolerant to Gluten (at Step 8)". page 50-51. Committee on Nutrition and Foods for Special Dietary Uses. JOINT FAO/WHO FOOD STANDARDS PROGRAMME CODEX ALIMENTARIUS COMMISSION. Thirty-first Session Geneva, Switzerland, 30 June – 4 July 2008, Codex Alimentarius Commission REPORT OF THE 29th

SESSION OF THE CODEX COMMITTEE ON NUTRITION AND FOODS FOR SPECIAL DIETARY USES (http:/ / www.

codexalimentarius. net/ download/ report/ 687/ al08_26e. pdf) [44] Rashid M, Butzner D, Burrows V, et al. (October 2007). "Consumption of pure oats by individuals with celiac disease: A position statement by the Canadian Celiac Association". Can. J. Gastroenterol. 21 (10): 649–51. PMC 2658132. PMID 17948135. [45] Baldo BA, Krilis S, Wrigley CW (1980). "Hypersensitivity to inhaled flour allergens. Comparison between cereals". Allergy 35 (1): 45–56. doi:10.1111/j.1398-9995.1980.tb01716.x. PMID 6154431. [46] Karatay S, Erdem T, Kiziltunc A, et al. (2006). "General or personal diet: the individualized model for diet challenges in patients with rheumatoid arthritis". Rheumatol. Int. 26 (6): 556–60. doi:10.1007/s00296-005-0018-y. PMID 16025333. [47] Kupper C (2005). "Dietary guidelines and implementation for celiac disease". Gastroenterology 128 (4 Suppl 1): S121–7. doi:10.1053/j.gastro.2005.02.024. PMID 15825119. [48] Comino, Isabel; Ana Real, Laura de Lorenzo, Hugh Cornell, Miguel Ángel López-Casado, Francisco Barro, Pedro Lorite, Ma Isabel Torres, Ángel Cebolla, Carolina Sousa (12). "Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in

coeliac disease" (http:/ / gut. bmj. com/ content/ early/ 2011/ 02/ 11/ gut. 2010. 225268. abstract). Gut 60 (First Online): 915–22. doi:10.1136/gut.2010.225268. PMC 3112367. PMID 21317420. . Retrieved 12 March 2011. Gluten sensitivity 87

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[54] Cleaning/Inspection Process Gluten Free Oats (http:/ / www. glutenfreeoats. com/ cleaning. aspx)

[55] "Are McCann's Oat products gluten free?". URL: FAQ - Frequently asked questions (http:/ / www. mccanns. ie/ faq. html)

[56] GLUTEN FREE ROLLED OATS Bob's Red Mill Natural Foods (http:/ / www. bobsredmill. com/ catalog/ index. php?action=showdetails& product_ID=680) [57] Størsrud S, Hulthén LR, Lenner RA (July 2003). "Beneficial effects of oats in the gluten-free diet of adults with special reference to nutrient status, symptoms and subjective experiences". Br. J. Nutr. 90 (1): 101–7. doi:10.1079/BJN2003872. PMID 12844381.

[58] Rashid, Mohsin (2007-06-08). "Guidelines for Consumption of Pure and Uncontaminated Oats by Individuals with Celiac Disease" (http:/ /

www. celiac. ca/ Articles/ PABoatsguidelines2007June. html). Professional Advisory Board of Canadian Celiac Association. . Retrieved 2008-08-14. 88

Other Allergies

Allergic contact dermatitis

Allergic contact dermatitis Classification and external resources

[1] ICD-10 L23

[2] ICD-9 692

[3] MeSH D017449

Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD). Although less common than ICD, ACD is accepted to be the most prevalent form of immunotoxicity found in humans.[4] By its allergic nature, this form of contact dermatitis is a hypersensitive reaction that is atypical within the population. The mechanisms by which these reactions occur are complex, with many levels of fine control. Their immunology centres around the interaction of immunoregulatory cytokines and discrete subpopulations of T lymphocytes.

Pathophysiology ACD arises as a result of two essential stages: an induction phase, which primes and sensitizes the immune system for an allergic response, and an elicitation phase, in which this response is triggered (Kimble et al. 2002). As such, ACD is termed a Type IV delayed hypersensitivity reaction involving a cell-mediated allergic response. Contact allergens are essentially soluble haptens (low in molecular weight) and, as such, have the physico-chemical properties that allow them to cross the stratum corneum of the skin. They can only cause their response as part of a complete antigen, involving their association with epidermal proteins forming hapten-protein conjugates. This, in turn, requires them to be protein-reactive. The conjugate formed is then recognized as a foreign body by the Langerhans cells (LCs) (and in some cases other Dendritic cells (DCs)), which then internalize the protein; transport it via the lymphatic system to the regional lymph nodes; and present the antigen to T-lymphocytes. This process is controlled by cytokines and chemokines - with tumor necrosis factor alpha (TNF-α) and certain members of the interleukin family (1, 13 and 18) - and their action serves either to promote or to inhibit the mobilization and migration of these LCs. (Kimble et al. 2002) As the LCs are transported to the lymph nodes, they become differentiated and transform into DCs, which are immunostimulatory in nature. Once within the lymph glands, the differentiated DCs present the allergenic epitope associated with the allergen to T lymphocytes. These T cells then divide and differentiate, clonally multiplying so that if the allergen is experienced again by the individual, these T cells will respond more quickly and more aggressively. White et al. have suggested that there appears to be a threshold to the mechanisms of allergic sensitisation by ACD-associated allergens (1986).[5] This is thought to be linked to the level at which the toxin induces the up-regulation of the required mandatory cytokines and chemokines. It has also been proposed that the vehicle in which the allergen reaches the skin could take some responsibility in the sensitisation of the epidermis by both Allergic contact dermatitis 89

assisting the percutaneous penetration and causing some form of trauma and mobilization of cytokines itself.

Allergens Common allergens implicated include the following: • Nickel (nickel sulfate hexahydrate) - metal frequently encountered in jewelry and clasps or buttons on clothing • Gold (gold sodium thiosulfate) - precious metal often found in jewelry and dental materials • Balsam of Peru (Myroxylon pereirae) - a fragrance used in perfumes and skin lotions, derived from tree resin (see also Tolu balsam). It may also be a component of artificial vanilla and/or cinnamon flavorings. • Chromium - used in the tanning of leather. Also a component of uncured cement/mortar, facial cosmetics and some bar soaps. • Oily coating from plants of the Toxicodendron genus: poison ivy, poison oak, and poison sumac. • Thimerosal - a mercury compound used in local antiseptics and in vaccines • Neomycin - a topical antibiotic common in first aid creams and ointments, cosmetics, deodorant, soap and pet food. Found by itself, or in Polysporin or Triple Antibiotic • Fragrance mix - a group of the eight most common fragrance allergens found in foods, cosmetic products, insecticides, antiseptics, soaps, perfumes and dental products [6] • Formaldehyde - a preservative with multiple uses, e.g., in paper products, paints, medications, household cleaners, cosmetic products and fabric finishes. Often released into products by the use of formaldehyde releasers such as imidazolidinyl urea, diazolidinyl urea, Quaternium-15, DMDM Hydantoin and 2-bromo-2-nitropropane-1,3-diol. • Cobalt chloride - metal found in medical products; hair dye; antiperspirant; metal-plated objects such as snaps, buttons or tools; and in cobalt blue pigment • Bacitracin - a topical antibiotic found by itself, or as Polysporin or Triple Antibiotic • Quaternium-15 - preservative in cosmetic products (self-tanners, shampoo, nail polish, sunscreen) and in industrial products (polishes, paints and waxes).[7] • Colophony (Rosin) - Rosin, sap or sawdust typically from spruce or fir trees • Topical steroid - see steroid allergy • Photographic developers, especially those containing metol • Topical anesthetics such as pramoxine or diphenhydramine, after prolonged use • Methylchloroisothiazolinone/Methylisothiazolinone is a preservative used in wash-off products such as shampoos/conditioners.

Symptoms The symptoms of allergic contact dermatitis are very similar to the ones caused by irritant contact dermatitis, which makes the first even harder to diagnose. The first sign of allergic contact dermatitis is the presence of the rash or skin lesion at the site of exposure.[8] Depending on the type of allergen causing it, the rash can ooze, drain or crust and it can become raw, scaled or thickened. Also, it is possible that the skin lesion does not take the form of a rash but it may include papules, blisters, vesicles or even a simple red area. The main difference between the rash caused by allergic contact dermatitis and the one caused by irritant contact dermatitis is that the first one tends to be confined to the area where the trigger touched the skin, whereas in the second case, the rash is more likely to be more widespread on the skin.[9] Another characteristic of the allergic contact dermatitis rash is that it usually appears after a day or two after exposure to the allergen, unlike irritant contact dermatitis that appears immediately after the contact with the trigger. Other symptoms may include itching, skin redness or inflammation, localized swelling and the area may become more tender or warmer. If left untreated, the skin may darken and become leathery and cracked.[10] Pain can also be present. Allergic contact dermatitis 90

The symptoms of allergic contact may persist for as long as one month before resolving completely. Once an individual has developed a skin reaction to a certain substance it is most likely that he will have it for the rest of the life, and the symptoms will reappear when in contact with the allergen.

Treatment The main treatment to cure allergic contact dermatitis consists of avoiding the allergen. Persons who develop the rash and the other symptoms from a certain trigger are most likely to have it for the rest of their lives and detecting and avoiding the allergen is mandatory in treating the condition and resolving its symptoms. The first step in treating the condition is applying a damp cloth shortly after the skin problem first shows to make sure that all of the irritant has been removed from the area.[11] In some cases, the best treatment is to do nothing to the area.[8] In mild to moderate cases, patients may use skin creams containing corticosteroids to reduce the inflammation. These creams should be used carefully and according to the instructions they come with because when overused over longer periods of time they can cause serious skin conditions. Also, calamine lotion and cool oatmeal baths may relieve itching.[12]. Over the counter diphenhydramine by mouth is helpful for night time itching. Usually, severe cases are treated with systemic corticosteroids which may be tapered gradually, with various dosing schedules ranging from a total of 12 - 20 days to prevent the recurrence of the rash as well as a topical corticosteroid.[8] Tacrolimus ointment or pimecrolimus cream can also be used additionally to the corticosteroid creams or instead of these. Oral antihistamines such as diphenhydramine or hydroxyzine may also be used in more severe cases to relieve the intense itching. Topical antihistamines are not advised as there might be a second skin reactions from the lotion itself. The other symptoms caused by allergic contact dermatitis are generally eased with wet dressings and drying lotions to stop the itching. In most cases however, medication or actual treatment is not required as long as the trigger has been identified and avoided. The discomfort caused by the symptoms may be relieved by wearing smooth-textured clothing to avoid more skin irritation or by avoiding soaps with perfumes and dyes. Commonly, the symptoms may resolve without treatment in 2 to 4 weeks but specific medication may hasten the healing as long as the trigger is avoided. Also, the condition might become chronic if the allergen is not detected and therefore it is not avoided.

Diagnosis Diagnosing allergic contact dermatitis is primarily based on physical exam and medical history. In some cases doctors can establish an accurate diagnosis based on the symptoms that the patient experiences and on the rash's appearance. In the case of a single episode of allergic contact dermatitis, this is all that is necessary. Chronic and/or intermittent rashes which are not readily explained by history and physical exam often will benefit from further testing. A patch test (contact delayed hypersensitivity allergy test)[13] is a commonly used examination to determine the exact cause of an allergic contact dermatitis. According to the American Academy of Allergy, Asthma, and Immunology, "patch testing is the gold standard for contact allergen identification".[8] The patch test consists in applying small quantities of potential allergens to small patches and which are then placed on the skin.[14] After two days, they are removed and if a skin reaction occurred to one of the substances applied, a raised bump will be noticeable underneath the patch. The tests are again read at 72 or 96 hours after application. Patch testing is used for patients who have chronic, recurring contact dermatitis.[8] Other tests that may be used to diagnose contact dermatitis and rule out other potential causes of the symptoms include a skin biopsy and culture of the skin lesion. Allergic contact dermatitis 91

References

[1] http:/ / apps. who. int/ classifications/ icd10/ browse/ 2010/ en#/ L23

[2] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=692

[3] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D017449

[4] Kimber I, Basketter DA, Gerberick GF, Dearman RJ (2002). "Allergic contact dermatitis" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S1567-5769(01)00173-4). Int. Immunopharmacol. 2 (2–3): 201–11. doi:10.1016/S1567-5769(01)00173-4. PMID 11811925. . [5] White SI, Friedmann PS, Moss C, Simpson JM (1986). "The effect of altering area of application and dose per unit area on sensitization by DNCB". Br. J. Dermatol. 115 (6): 663–8. doi:10.1111/j.1365-2133.1986.tb06646.x. PMID 3801307.

[6] Allergy to fragrance mix at DermNetNZ, http:/ / dermnetnz. org/ dermatitis/ fragrance-allergy. html

[7] Mayo Clinic study, http:/ / www. mayoclinic. org/ news2006-rst/ 3268. html

[8] "Contact dermatitis" (http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 000869. htm). . Retrieved 2010-06-16.

[9] "Contact Dermatitis Symptoms" (http:/ / www. emedicinehealth. com/ contact_dermatitis/ page3_em. htm#Contact Dermatitis Symptoms). . Retrieved 2010-06-16.

[10] "Allergic Contact Dermatitis" (http:/ / www. aocd. org/ skin/ dermatologic_diseases/ allergic_contact_d. html). . Retrieved 2010-06-16.

[11] "Allergic Dermatitis Symptoms and Treatment" (http:/ / www. allergicdermatitis. org/ ). . Retrieved 2010-06-16.

[12] "Self-Care at Home" (http:/ / www. emedicinehealth. com/ contact_dermatitis/ page7_em. htm#Self-Care at Home). . Retrieved 2010-06-16.

[13] "Contact dermatitis" (http:/ / www. mayoclinic. com/ health/ contact-dermatitis/ DS00985/ DSECTION=tests-and-diagnosis). . Retrieved 2010-06-16.

[14] "Tests and diagnosis" (http:/ / www. mayoclinic. com/ health/ contact-dermatitis/ DS00985/ DSECTION=tests-and-diagnosis). . Retrieved 2010-06-16.

Further reading • A list of common allergens is shown in Table III in: Kucenic MJ, Belsito DV (2002). "Occupational allergic

contact dermatitis is more prevalent than irritant contact dermatitis: a 5-year study" (http:/ / linkinghub. elsevier.

com/ retrieve/ pii/ S0190962202083366). J. Am. Acad. Dermatol. 46 (5): 695–9. doi:10.1067/mjd.2002.118561. PMID 12004309. Drug allergy 92 Drug allergy

Drug allergy Classification and external resources

ICD-10 T88.7

[1] ICD-9 995.27

A drug allergy is an allergy to a drug, most commonly a medication. Medical attention should be sought immediately if an allergic reaction is suspected. An allergic reaction will not occur on the first exposure to a substance. The first exposure allows the body to create antibodies and memory lymphocyte cells for the antigen. However, drugs often contain many different substances, including dyes, which could cause allergic reactions. This can cause an allergic reaction on the first administration of a drug. For example, a person who developed an allergy to a red dye will be allergic to any new drug which contains that red dye. A drug allergy is different from an intolerance. A drug intolerance, which is often a milder, non-immune-mediated reaction, does not depend on prior exposure. Most people who believe they are allergic to aspirin are actually suffering from a drug intolerance.

Risk factors A drug allergy is more likely to develop with large doses and extended exposure.

Common drug allergens When a medication causes an allergic reaction, it is called an allergen. The following is a short list of the most common drug allergens[2]: • Antibiotics • Penicillin • Sulfa drugs • Tetracycline • Analgesics • Codeine • Non-steroidal anti-inflammatory drugs (NSAIDs) • Antiseizure • Phenytoin • Carbamazepine

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=995. 27

[2] "eMedicine" (http:/ / www. emedicinehealth. com/ drug_allergy/ page2_em. htm). . Retrieved 2007-06-08. Latex allergy 93 Latex allergy

Latex allergy Classification and external resources

Latex medical glove

[1] ICD-9 V15.07

[2] MeSH D020315

Latex allergy is a medical term encompassing a range of allergic reactions to natural rubber latex.

Types Latex is known to cause 2 of the 4 (or 5) types of hypersensitivity.

Type I The most serious and rare form, type I is an immediate and potentially life-threatening reaction, not unlike the severe reaction some people have to bee stings. Such reactions account for a significant proportion of perioperative anaphylactic reaction, especially in children with myelomeningocele.[3] [4] Testing for type I natural rubber latex allergy is through blood testing, such as RAST (radioallergosorbent test) identifies what types of IgE proteins trigger allergic reactions. While the standard for allergen testing is the skin prick test, there is no approved skin testing reagent for latex in the United States, though some other countries do have approved skin testing reagents. Type I natural rubber latex allergy is caused from IgE (immune) mediated reactions to proteins found in the Hevea brasiliensis tree, a type of rubber tree. Some people who are allergic to latex are also allergic to clothes, shoes, and other things that contain natural rubber latex—for example elastic bands, rubber gloves, condoms, pacifiers and baby-bottle nipples, balloons, cars, and clothing containing natural rubber based elastic. A Type I reaction can be triggered by exposure to airborne particles resulting from the inflation of balloons even if the person is not present while the balloons are being inflated. Latex allergy 94

Type IV (allergic contact dermatitis) Also known as allergic contact dermatitis. This involves a delayed skin rash that is similar to poison ivy with blistering and oozing of the skin (see urushiol-induced contact dermatitis). This type is caused by a naturally occurring latex protein. Type IV reactions are caused by the chemicals used to process the rubber. Patch testing needs to be done to verify which type of chemical triggers the reaction. Once the chemical is identified, then the person can choose products that are not processed with that chemical.

Irritant contact dermatitis It can also cause irritant contact dermatitis:[5] The most common type of reaction. This causes dry, itchy, irritated areas on the skin, most often on the hands. It can be caused by the irritation of using gloves, or it can also be caused by exposure to other workplace products. Frequent washing of the hands, incomplete drying, exposure to hand sanitizers, and the talc-like powder coatings (zinc oxide, etc.) used with gloves can aggravate symptoms. Irritant contact dermatitis is not a true allergy.

Those at greatest risk • Children with Spina bifida. About 68% will have a reaction.[6] • Industrial rubber workers, exposed for long periods to high amounts of latex. About 10% have an allergic reaction. • Health care providers. Given the ubiquitous use of latex products in health care settings, management of latex allergy presents significant health organizational problems. Healthcare workers who frequently use latex gloves and other latex-containing medical supplies such as physicians, nurses, aides, dentists, dental hygienists, operating room employees, laboratory technicians, and hospital housekeeping personnel are at risk for developing latex allergy.[7] Between about 4% to 17% of healthcare workers have a reaction, this usually presents as Irritant Contact Dermatitis, and can develop through allergic sensitivity to a status of full anaphylaxis shock; with health workers losing their vocation.[8] In the surgical setting, however, the risk of a potentially life-threatening allergic reaction by a patient has been deemed by Johns Hopkins Hospital to be sufficiently high to replace all latex surgical gloves with synthetic alternatives.[9] • People who have had multiple surgical procedures, especially in childhood.[5] Estimates of latex sensitivity in the general population range from 0.8% to 8.2%,[10] although not all will ever develop a noticeable allergic reaction. Synthetic latex compounds can be chemically identical to latex, producing the same allergic reactions. They also contain many of the same or similar accelerators. These synthetics do not have to be labeled as such.

Latex and foods Some people who have latex allergy may also have an allergic response to any of a number of plant products, usually fruits. This is known as the latex-fruit syndrome.[11] Fruits (and seeds) involved in this syndrome include banana, pineapple, avocado, chestnut, kiwi fruit, mango, passionfruit, strawberry and soy. Some but not all of these fruits contain a form of latex. The Asthma and Allergy Foundation of America estimates that nearly 6 percent of the United States population have some type of food allergy and up to 4 percent have an allergy to latex.[12] It can also cause reactions from foods touched by latex products in the most severe cases. Some individuals who are highly allergic to latex have had allergic reactions to foods that were handled or prepared by people wearing latex gloves. Latex allergy 95

Alternatives • Synthetic elastic such as elastane or neoprene do not contain the proteins from the Hevea brasiliensis tree that trigger type I reactions. • Products made from guayule natural rubber emulsions also do not contain the proteins from the Hevea rubber tree,[6] and have only trace amounts of other proteins, indicating a very low potential for causing sensitization to this material. • Chemical treatment to reduce the amount of antigenic proteins in Hevea latex has yielded alternative materials, such as Vytex, which reduce exposure to latex allergens while otherwise retaining the properties of natural rubber. • Some patients' sensitivity is so extreme that replacement of Latex products with non-latex products may still result in a reaction if the products are manufactured in the same facility as the Latex-containing products.

Latex allergens Hevein-like protein domains[13] are a possible cause for allergen cross-reactivity between latex and banana[14] or fruits in general (latex-fruit syndrome).[15] Natural rubber latex contains several conformational epitopes located on several enzymes like Hev b 1[16], Hev b 2[17], Hev b 4[18], Hev b 5[19] and Hev b 6.02.[20][21] FITkit is a latex allergen testing method for quantification of the major natural rubber latex (NRL) specific allergens: Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02.[22]

References

[1] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=V15. 07

[2] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D020315 [3] Rendeli C, Nucera E, Ausili E, Tabacco F, Roncallo C, Pollastrini E, Scorzoni M, Schiavino D, Caldarelli M, Pietrini D, Patriarca G. (Jan 2006). "Latex sensitisation and allergy in children with myelomeningocele.". Childs Nerv Syst 22 (1): 28–32. doi:10.1007/s00381-004-1110-4. PMID 15703967. [4] Banta JV, Bonanni C, Prebluda J. (Jun 1993). "Latex anaphylaxis during spinal surgery in children with myelomeningocele". Dev Med Child Neurol 235 (6): 543–8. PMID 8504897.

[5] "Latex Allergy" (http:/ / www. aafp. org/ afp/ 980101ap/ reddy. html). . Retrieved 2009-08-08.

[6] "Plant Biologists And Immunochemists Develop Hypoallergenic Alternative To Latex" (http:/ / www. sciencedaily. com/ videos/ 2008/

1206-protect_yourself_from_latex_allergies. htm). ScienceDaily. December 1, 2008. . Retrieved 2010-02-13.

[7] "NIOSH Alert:Preventing Allergic Reactions to Natural Rubber Latex in the Workplace" (http:/ / www. cdc. gov/ niosh/ latexalt. html). United States National Institute for Occupational Safety and Health. . Retrieved 2008-01-20.

[8] Latex Allergy (http:/ / www. latexallergy. ndo. co. uk/ )

[9] WJZ 13 (CBS) (2008-01-15). "Hopkins ceases use of latex gloves during surgery" (http:/ / wjz. com/ local/ johns. hopkins. hospital. 2.

629922. html). Baltimore. . Retrieved 2009-07-30. [10] Grzybowski M, Ownby DR, Rivers EP, Ander D, Nowak RM (October 2002). "The prevalence of latex-specific IgE in patients presenting to an urban emergency department". Ann Emerg Med 40 (4): 411–9. doi:10.1016/S0196-0644(02)00063-X. PMID 12239498. [11] Brehler R, Theissen U, Mohr C, Luger T (April 1997). ""Latex-fruit syndrome": frequency of cross-reacting IgE antibodies". Allergy 52 (4): 404–10. doi:10.1111/j.1398-9995.1997.tb01019.x. PMID 9188921.

[12] “Allergy Facts and Figures,” Asthma and Allergy Foundation of America http:/ / www. aafa. org/ display. cfm?id=9& sub=30 [13] Dìaz-Perales, A; Sánchez-Monge, R; Blanco, C; Lombardero, M; Carillo, T; Salcedo, G (2002). "What is the role of the hevein-like domain of fruit class I chitinases in their allergenic capacity?". Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 32 (3): 448–54. doi:10.1046/j.1365-2222.2002.01306.x. PMID 11940077. [14] Mikkola JH, Alenius H, Kalkkinen N, Turjanmaa K, Palosuo T, Reunala T (December 1998). "Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana". J. Allergy Clin. Immunol. 102 (6 Pt 1): 1005–12. doi:10.1016/S0091-6749(98)70339-2. PMID 9847442. [15] Wagner, S; Breiteneder, H (2002). "The latex-fruit syndrome". Biochemical Society transactions 30 (Pt 6): 935–40. PMID 12440950. [16] Chen, Zhiping; Cremer, Reinhold; Posch, Anton; Raulf-Heimsoth, Monika; Rihs, Hans-Peter; Baur, Xaver (1997). "On the allergenicity of Hev b 1 among health care workers and patients with spina bifida allergic to natural rubber latex". Journal of Allergy and Clinical Immunology 100 (5): 684–93. doi:10.1016/S0091-6749(97)70174-X. PMID 9389300. Latex allergy 96

[17] Barre, Annick; Culerrier, Raphaël; Granier, Claude; Selman, Laetitia; Peumans, Willy J.; Van Damme, Els J.M.; Bienvenu, Françoise; Bienvenu, Jacques et al (2009). "Mapping of IgE-binding epitopes on the major latex allergen Hev b 2 and the cross-reacting 1,3β-glucanase fruit allergens as a molecular basis for the latex-fruit syndrome". Molecular Immunology 46 (8–9): 1595–604. doi:10.1016/j.molimm.2008.12.007. PMID 19185347. [18] Kolarich, Daniel; Altmann, Friedrich; Sunderasan, Elumalai (2006). "Structural analysis of the glycoprotein allergen Hev b 4 from natural rubber latex by mass spectrometry". Biochimica et Biophysica Acta (BBA) - General Subjects 1760 (4): 715. doi:10.1016/j.bbagen.2005.11.012. [19] Beezhold, Donald H.; Hickey, Vicky L.; Slater, Jay E.; Sussman, Gordon L. (1999). "Human IgE-binding epitopes of the latex allergen Hev b 5". Journal of Allergy and Clinical Immunology 103 (6): 1166–72. doi:10.1016/S0091-6749(99)70194-6. PMID 10359901. [20] Reyes-López, CA; Hernández-Santoyo, A; Pedraza-Escalona, M; Mendoza, G; Hernández-Arana, A; Rodríguez-Romero, A (2004). "Insights into a conformational epitope of Hev b 6.02 (hevein)". Biochemical and biophysical research communications 314 (1): 123–30. PMID 14715255. [21] Pedraza-Escalona, Martha; Becerril-Luján, Baltazar; Agundis, Concepción; Domínguez-Ramírez, Lenin; Pereyra, Ali; Riaño-Umbarila, Lidia; Rodríguez-Romero, Adela (2009). "Analysis of B-cell epitopes from the allergen Hev b 6.02 revealed by using blocking antibodies". Molecular Immunology 46 (4): 668–76. doi:10.1016/j.molimm.2008.08.282. PMID 18930549. [22] Koh D, Ng V, Leow YH, Goh CL. (2005). "A study of natural rubber latex allergens in gloves used by healthcare workers in Singapore". Br. J. Dermatol. 153 (5): 954–59. doi:10.1111/j.1365-2133.2005.06820.x. PMID 16225605.

External links

• The American Latex Allergy Association (http:/ / www. latexallergyresources. org/ )

• UK Latex Allergy Support Group (http:/ / www. lasg. org. uk/ )

• NIOSH Latex Allergy Alert (http:/ / www. cdc. gov/ niosh/ latexalt. html) from the U.S. Centers for Disease Control and Prevention

• Asthma and Allergy Foundation of America (http:/ / aafa. org/ display. cfm?id=9& sub=21/ )

Insect sting allergy

Insect sting allergy is the term commonly given to the allergic response of an animal in response to the bite or sting of an insect. Typically, insects which generate allergic responses are either stinging insects (wasps, bees, hornets and ants) or biting insects (mosquitoes, ticks). Stinging insects inject venom into their victims, whilst biting insects normally introduce anti-coagulants into their victims. The great majority of insect allergic animals just have a simple allergic response - a reaction local to the sting site which appears as just a swelling arising from the release of histamine and other chemicals from the body tissues near to the sting site. The swelling, if allergic, can be helped by the provision of an anti-histamine ointment as well as an ice pack. This is the typical response for all biting insects and many people have this common reaction to one extreme or another. Mosquito allergy may result in a collection of symptoms called Skeeter Syndrome that occur after a bite. This syndrome may be mistaken for an infection such as cellulitis. In anaphylactic patients the response is more aggressive leading to a systemic reaction where the response progresses from the sting site around the whole body. This is potentially something very serious and can lead to anaphylaxis which is potentially life threatening. Venom Immunotherapy [1] is a course of treatment which is now well established in North America and Europe and offers patients with a systemic allergic response a considerable reduction in the level of their allergic response. Insect sting allergy 97

Epidemiology of Stinging Insect Reactions The majority of individuals who receive a sting from an insect experience local reactions. It is estimated that 5-10% of individuals will experience a generalized systemic reaction that can involve symptoms ranging from hives to wheezing and even anaphylaxis. In the United States approximately 40 people die each year from anaphylaxis due to stinging insect allergy. Potentially life-threating reaction occur in 3% of adults and 0.4-0.8% of children.[2]

References

[1] http:/ / www. insectstings. co. uk/ immunotherapy. shtml [2] Golden DBK. Epidemiology of allergy to insect venoms and stings. Allergy Proc 1989;10:103-7 • Golden DBK. Epidemiology of allergy to insect venoms and stings. Allergy Proc 1989;10:103-7

Cat allergy

Cat allergy in humans is an allergic reaction to one or more of the five known allergens produced by cats. The most common of these are the glycoprotein Fel d 1, secreted by the cat's sebaceous glands and Fel d 4, which is expressed in saliva. An allergic reaction is a histamine reaction that is usually characterized by coughing, wheezing, chest tightening, itching, nasal congestion, rash, watering eyes, sneezing, chapped lips, and similar symptoms.

Cat allergens Five cat allergens have been described in medical literature. The two major allergens are Fel d 1 (a secretoglobin) and Fel d 4 (a lipocalin). The minor allergens include Fel d 2 (an albumin), Fel d 3 (a cystatin), and cat IgA.[1] Fel d 4 is the product of the cat major urinary protein gene. It is primarily expressed in the submandibular salivary gland and is deposited onto dander as the cat grooms itself. A study found that 63% of cat allergic people have antibodies against Fel d 4.[2]

Symptoms Symptoms of an allergic reaction to cats include: swollen, red, itchy, watery eyes; nasal congestion, itchy nose, sneezing, chronic sore throat or itchy throat, coughing, wheezing, asthma, hay fever[3], hives or rash on the face or chest, or itchy skin. If a cat has scratched, licked, or bitten someone who is allergic to cats, redness will occur.[4] Symptoms are often confused with a common cold.[5]

Coping with allergies Allergic reaction to cats can be lessened most successfully by minimizing exposure to the animals. That is not always a practical solution, and there are a number of other strategies that may aid an allergy sufferer.

Lower exposure Allergens are airborne and survive for months or even years by themselves, hence removing anything that can trap and hold the allergens (carpet, rugs, pillows) and cleaning regularly and thoroughly with HEPA filters and Air purifier systems reduces risk. Frequent hand washing, especially after handling the cat, and washing hands prior to touching eyes, nose, or mouth, and limiting the cat to the outdoors or barring the animal from certain rooms, such as the bedroom or other rooms where much time is spent, may also reduce allergic reactions. Cat allergy 98

Medications Cat allergies can often be controlled with over the counter or prescription medications. Antihistamines and decongestants may provide allergy relief.[6]

Allergy shots Some allergy sufferers find relief in immunotherapy, a periodic injection therapy designed to stimulate the body's natural immune responses to the cat allergens.[7][8]

Synthetic epitope vaccine The Synthetic epitope vaccine is an in-development vaccine to provide a long term vaccine for allergies.[9]

Cat Bathing Regularly bathing the cat may remove significant amounts of allergens from the fur.[10] Furthermore, regularly brushing the cat will reduce the amount of loose fur (and its attached saliva) in the air. Feeding the cat a high quality diet with plenty of Omega-3 fatty acids will help keep the coat healthy and minimize dander.[11]

Hypoallergenic cats A hypoallergenic cat is a cat which is less likely to provoke an allergic reaction in humans; Although the topic is controversial, with many studies showing statistically significant results,[12] owner's experience and recent clinical studies suggest that Siberian cats, Russian Blue cats, Devon Rex and Cornish Rex cats, Abyssinian cats, and several other breeds, especially females are likely to have low levels of Fel d 1, the main allergenic protein.[13] In 2006, the Allerca company announced the successful breeding of a line of hypoallergenic cats. However, no peer-reviewed studies have been done to confirm their claims and many scientists and consumers are skeptical of the company's assertions.[14] The company has announced that on January 1, 2010 they will cease their breeding activities.[15] Another company, Felix Pets, also claims to be developing a breed of hypoallergenic cat.[16]

Cat gender and color Female cats produce a lower level of allergens than males, and neutered males produce a lower level of allergens than unaltered males.[17] In 2000, researchers at the Long Island College Hospital found that cat owners with dark-colored cats were more likely to report allergy symptoms than those with light-colored cats.[18][19][20] A later study by the Wellington Asthma Research Group found that hair color had no effect on how much allergen a cat produced.[21][22]

References

[1] Adédoyin J, et. al. "Cat IgA, representative of new carbohydrate cross-reactive allergens" (http:/ / download. journals. elsevierhealth. com/

pdfs/ journals/ 0091-6749/ PIIS0091674906030284. pdf) The Journal of Allergy and Clinical Immunology, 2007-3. Retrieved on 2009-8-1. [2] Smith W, Butler AJ, Hazell LA, Chapman MD, Pomés A, Nickels DG et al (2004). "Fel d 4, a cat lipocalin allergen". Clin Exp Allergy 34 (11): 1732–8. doi:10.1111/j.1365-2222.2004.02090.x. PMID 15544598.

[3] "Allergy to pets and animals" (http:/ / www. allergyclinic. co. uk/ animals. htm). allergyclinic.co.uk. . Retrieved 9 November 2011.

[4] "WebMD - Cat Allergies" (http:/ / www. webmd. com/ allergies/ cat-allergies). WebMD, LLC.. . Retrieved 9 November 2011.

[5] "Human Allergies to Cats" (http:/ / www. peteducation. com/ article. cfm?c=0+ 1278& aid=144). Foster & Smith, Inc.. . Retrieved 9 November 2011.

[6] Cat Allergies, WebMD, http:/ / www. webmd. com/ allergies/ cat-allergies

[7] Clinical efficacy of specific immunotherapy to cat dander: a double-blind placebo-controlled trial http:/ / www. jacionline. org/ medline/

record/ ivp_09547894_27_860. Accessed 08 Jan 2011. Cat allergy 99

[8] Immunotherapy with cat- and dog-dander extracts. V. Effects of 3 years of treatment. http:/ / www. jacionline. org/ medline/ record/

ivp_00916749_87_955. Accessed 08 Jan 2011. [9] Larché, M.; Akdis, C.; Valenta, R. (2006). "Immunological mechanisms of allergen-specific immunotherapy.". Nature reviews. Immunology 6 (10): 761–771. doi:10.1038/nri1934. PMID 16998509.

[10] Evaluation of different techniques for washing cats: Quantitation of allergen removed from the cat and the effect on airborne Fel d 1 http:/ /

www. jacionline. org/ article/ S0091-6749(97)70242-2/ fulltext. Retrieved 10 Jan 2011.

[11] Human Allergies to Cats. http:/ / www. peteducation. com/ article. cfm?c=0+ 1278& aid=144

[12] Hypoallergenic Cats - Do They Exist? http:/ / www. cat-world. com. au/ hypoallergenic-cats-do-they-exist Accessed 10 Jan 2011.

[13] http:/ / www. siberianresearch. com/ index. php?option=com_content& view=article& id=125:siberian-allergen-levels&

catid=45:allergens& Itemid=75

[14] Felis Enigmaticus (http:/ / www. the-scientist. com/ 2007/ 1/ 1/ 32/ 1/ )

[15] "Lifestyle Pets" (http:/ / www. webcitation. org/ query?url=http:/ / www. allerca. com/ html/ aboutallerca. html& date=2009-11-01). Allerca.

Archived from the original (http:/ / www. allerca. com/ html/ aboutallerca. html) on 2009-11-01. . Retrieved 2009-11-01.

[16] Pepling, Racheal. (9 June 2006). "Hypoallergenic" Cats For Sale, U.S. Firm Announces. (http:/ / news. nationalgeographic. com/ news/

2006/ 06/ 060609-allergies-cats_2. html) National Geographic News. Accessed 13 March 2010.

[17] Sex difference in Fel d 1 allergen production. http:/ / www. jacionline. org/ article/ S0091-6749(96)70238-5/ fulltext . Accessed 11 Jan 2011.

[18] preliminary results (http:/ / www. prevention. com/ article/ 0,5778,s1-1-51-288-756-1,00. html), cited in Prevention (magazine)

[19] full study (http:/ / jama. ama-assn. org/ cgi/ content/ extract/ 284/ 24/ 3115-a), cited in the Journal of the American Medical Association [20] Hussain S, Bassett C, Kaplan S, Schneider A, Silverman B. (2000). "Correlation between the color of cat hair and severity of allergic

symptoms in patients with allergic rhinitis" (http:/ / download. journals. elsevierhealth. com/ pdfs/ journals/ 0091-6749/

PIIS0091674900904433. pdf). Journal of Allergy and Clinical Immunology. 105(1 Part 2):S5.

[21] cited by Allergy New Zealand (http:/ / www. allergy. org. nz/ newsMedia/ news/ snippets/ cats. php)

[22] This citation will be automatically completed in the next few minutes. You can jump the queue or expand by hand (http:/ / en. wikipedia.

org/ wiki/ Template:cite_doi/ _10. 1067. 2fmai. 2001. 118788?preload=Template:Cite_doi/ preload& editintro=Template:Cite_doi/ editintro& action=edit)

External links

• Allergen-free cats – a breed apart? (http:/ / www. newscientist. com/ article. ns?id=dn9313& feedId=online-news_rss20) - article from New Scientist.

• Cat Choo (http:/ / www. accessexcellence. org/ WN/ SUA02/ cat-choo. html) - News on immunisation

• Coping with Allergies (http:/ / www. allergyfiles. com/ cat-allergies-how-to-cope-18) - Pet Allergy Information Perfume allergy 100 Perfume allergy

The most common allergic reactions to perfume or fragrance added to products is contact allergy,[1][2] although other symptoms may occur, including allergic conjunctivitis.[3] As with all allergies, it is important to note the difference between hypersensitivity and true allergy. Many claiming to be allergic to perfumes are not allergic but hypersensitive towards perfumes. True allergy is an immunological overreaction which is specific at a molecular level to a certain substance. A perfume contains thousands of different substances. It is not likely that anyone has true allergy towards all perfumes, unless it is towards a common ingredient. Hypersensitivity is usually a feeling of obnoxiousness towards solvents involving sore feeling and itching in nose, mouth, and throat and hypersecretion of snot and saliva. Immunological mechanisms may or may not be involved, but is not detectable by current methods. The nose and sense of smell is evolutionary very important to all living beings. How smell interacts with other cerebral function in higher animals is not fully understood. For certain, complex psychosomatic mechanisms not fully understood is involved in perfume hypersensitivity. Household products such as soaps and detergents, perfume products, cosmetics, and other consumer goods are estimated to use 2500 different fragrance ingredients. Of those, approximately 100 different substances are known to elicit allergic responses in at least some individuals. It is estimated that 1.7-4.1% of the general population shows a contact allergic response to a mix of common perfume ingredients. [4] Although products can be labeled "fragrance-free", many still contain lesser-known fragrance chemicals that consumers may not recognize.[5]

Fragrance allergens • cinnamic aldehyde[6][7]

References

[1] http:/ / etd. ohiolink. edu/ send-pdf. cgi/ SAIYASOMBATI%20PENPAN. pdf?ucin1061561348

[2] https:/ / depts. washington. edu/ exposure/ article_faqs. html

[3] http:/ / www. mckinley. illinois. edu/ handouts/ allergies. htm

[4] "Fragrance Contact Allergy: A Clinical Review" (http:/ / www. ingentaconnect. com/ content/ adis/ derm/ 2003/ 00000004/ 00000011/ art00006). American Journal of Clinical Dermatology. . Retrieved 11 Feb 2012. "Fragrance ingredients are also one of the most frequent causes of contact allergic reactions. The diagnosis is made by patch testing with a mixture of fragrance ingredients, the fragrance mix. This gives a positive patch-test reaction in about 10% of tested patients with eczema, and the most recent estimates show that 1.7–4.1% of the general population are sensitized to ingredients of the fragrance mix." [5] . PMID 11753900.

[6] http:/ / www. emeraldmaterials. com/ epm/ kalama/ micms_doc_admin. display?p_customer=FISKALAMA&

p_name=PRODBULL-CINNAMICALDEHYDE. PDF

[7] http:/ / etd. ohiolink. edu/ send-pdf. cgi/ SAIYASOMBATI%20PENPAN. pdf?ucin1061561348

Further reading • Elberling J, Linneberg A, Dirksen A, Johansen JD, Frølund L, Madsen F, et al. Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity. Clin Exp Allergy 2005 • Kumar P, Caradonna-Graham VM, Gupta S, Cai X, Rao PN, Thompson J. Inhalation challenge effects of perfume scent strips in patients with asthma. Ann Allergy Asthma Immunol 1995 Perfume allergy 101

External links

• Allergy to Perfume in the Air (http:/ / www. users. globalnet. co. uk/ ~aair/ perfume_corr. htm)

• Fragranced Products Information Network (http:/ / www. fpinva. org) 102

Testing

Skin allergy test

Skin allergy testing is a method for medical diagnosis of allergies that attempts to provoke a small, controlled, allergic response.

A patient receiving a skin allergy test

Process

A microscopic amount of an allergen is introduced to a patient's skin by various means: • Prick test or scratch test: pricking the skin with a needle or pin containing a small amount of the allergen. • Patch test: applying a patch to the skin, where the patch contains the allergen If an immuno-response is seen in the form of a rash, urticaria (hives), Skin testing on arm or (worse) anaphylaxis it can be concluded that the patient has a hypersensitivity (or allergy) to that allergen. Further testing can be done to identify the particular allergen. The "scratch test" as it's called, is still very commonly used as an allergen test. A similar test involving injecting the allergen is also used, but is not quite as common due to increased likelihood of infection and general ineffectiveness by comparison. There are other methods available to test for allergy. Some allergies are identified in a few minutes but others may take several days. In all cases where the test is positive, the skin will become raised, red and appear itchy. The results are recorded- larger Skin testing on back wheals indicating that the subject is more sensitive to that particular allergen. A negative test does not mean that the subject is not allergic; simply that either the right concentration was not used or the body failed to elicit a response. Skin allergy test 103

Prick test In the prick (scratch) test, a few drops of the purified allergen are gently pricked on to the skin surface, usually the forearm. This test is usually done in order to identify allergies to pet dander, dust, pollen, foods or dust mites. Intradermal injections are done by injecting a small amount of allergen just beneath the skin surface. The test is done to assess allergies to drugs like penicillin or bee venom. To ensure that the skin is reacting in the way it is supposed to, all skin allergy tests are also performed with proven allergens like histamine or glycerin. The majority of people do react to histamine and do not react to glycerin. If the skin does not react appropriately to these allergens then it most likely will not react to the other allergens. These results are interpreted as falsely negative.[1]

Patch test The patch test simply uses a large patch which has different allergens on it. The patch is applied onto the skin, usually on the back. The allergens on the patch include latex, medications, preservatives, hair dyes, fragrances, resins and various metals. When a patch is applied the subject should avoid bathing or exercise for at least 48 hours.

Skin end point titration Also called an intra dermal test, this skin end point titration (SET) uses intradermal injection of allergens at increasing concentrations to measure allergic response.[2] To prevent a severe allergic reaction, the test is started with a very dilute solution. After 10 minutes, the injection site is measured to look for growth of wheal, a small swelling of the skin. Two millimeters of growth in 10 minutes is considered positive. If 2 mm of growth is noted, then a second injection at a higher concentration is given to confirm the response. The end point is the concentration of antigen that causes an increase in the size of the wheal followed by confirmatory whealing. If the wheal grows larger than 13 mm, then no further injection are given since this is considered a major reaction.

Preparation There are no major preparations required for skin testing. At the first consult, the subject's medical history is obtained and physical examination is performed. All consumers should bring a list of their medications because some may interfere with the testing. Other medications may increase the chance of a severe allergic reaction. Medications that commonly interfere with skin testing include the following: • Histamine antagonists like Allegra, Claritin, Benadryl, Zyrtec • Antidepressants like Amitriptyline, Doxepin • Antacid like Tagamet or Zantac Consumers who undergo skin testing should know that anaphylaxis can occur anytime. So if any of the following symptoms are experienced, a physician consultation is recommended immediately: • Low grade Fever • Lightheadedness or dizziness • Wheezing or Shortness of breath • Extensive skin rash • Swelling of face, lips or mouth • Difficulty swallowing or speaking Skin allergy test 104

Contraindications Even though skin testing may sound like a benign procedure it does have some risks which include swollen red bumps (hives) may occur after the test. The hives usually disappear in a few hours after the test. In rare cases they can persist for a day or two. These hives may be itchy and are best treated by applying an over the counter hydrocortisone cream.[3] In very rare cases one may develop a full blown allergic reaction. Physicians who perform skin test always have equipment and medications available in case an anaphylaxis reaction occurs. This is the main reason why consumers should not get skin testing performed at corner stores or by people who have no medical training.[4] Skin testing can be done on individuals of all ages. However, there are times when a skin test should not be done. Individuals who take medications for depression, gastric acidity or antihistamines should not undergo this test. In such cases, stopping the medications for a skin test may not be worthwhile as one may develop symptoms from the untreated medical disorders. Individuals who have severe, generalized skin disease or an acute skin infection should not undergo skin testing. One needs uninvolved skin for testing. There are some individuals who are highly sensitive to even the smallest amount of allergen and in such scenarios, allergic testing is not recommended. Whenever the chances of an anaphylactic shock are high, the test is best avoided.[5] Besides skin tests, there are blood tests which measure a specific antibody in the blood. The IgE antibody plays a vital role in allergies but its levels in blood do not always correlate with the allergic reaction.[6] There are many alternative health care practitioners who perform a variety of provocation neutralization tests, but the vast majority of these tests have no validity and have never been proven to work scientifically.

Notes

[1] American Academy of Allergy Asthma & Immunology: What is Allergy Testing? (http:/ / www. aaaai. org/ patients/ publicedmat/ tips/

whatisallergytesting. stm), Retrieved on 2010-01-20.

[2] MeSH Skin Test End-Point Titration (http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?mode=& term=Skin+ Test+ End-Point+ Titration)

[3] Skin Testing and Allergy Injection Treatment for Allergies and Asthma - The University of Arizona Health Sciences Center (http:/ / allergy.

peds. arizona. edu/ southwest/ skintesting. html), Retrieved on 2010-01-20.

[4] Allergy Testing - August 15,2002 - American Family Physician (http:/ / www. aafp. org/ afp/ 2002/ 0815/ p621. html), Retrieved on 2010-01-20.

[5] Skin test for Allergy (http:/ / www. medicinenet. com/ skin_test_for_allergy/ article. htm), Retrieved on 2010-01-20.

[6] Skin Testing Basic Information (http:/ / www. skintesting. net/ ), Retrieved on 2010-01-20.

References

External links

• The British Institute for Allergies (http:/ / www. allergy. org. uk/ )

• About.com - allergy tests (http:/ / allergies. about. com/ od/ allergies101/ a/ allergytest. htm)

• Skin Patches (Allergy Testing) (http:/ / www. dermnetnz. org/ procedures/ patch-tests. html) Patch test 105 Patch test

Patch test (medicine) Intervention

Patch test

[1] MeSH D010328

A patch test is a method used to determine if a specific substance causes allergic inflammation of the skin. Any individual with eczema suspected of having allergic contact dermatitis and/or atopic dermatitis needs patch testing. Patch testing helps identify which substances may be causing a reaction in a patient. It is intended to produce a local allergic reaction on a small area of your back where the diluted chemicals were planted. The chemicals included in the patch test kit are the offenders in approximately 85-90 percent of contact allergic eczema and include chemicals present in metals (e.g. nickel), rubber, leather, hair dyes, formaldehyde, lanolin, fragrance, preservative and other additives.

Mechanism A patch test relies on the principle of a type IV hypersensitivity reaction. The first step in becoming allergic is sensitization. When the skin is exposed to an allergen, the antigen presenting cells (APCs) - also known as Langerhans cell or Dermal Dendritic Cell - eat up substance (phagocytoze) and break it into smaller pieces. This is where a substance is recognized by immune cells in the skin. They then put parts of the substance onto their surface (technically holds the part of the molecule on the surface in the major histocompatibility complex type two (MHC-II). Once this is done the APC moves down the lymphatic system to a lymph node where it presents this part of the substance (what we now call an antigen) to a particular immune cell called a CD4+ T-cell or T-helper cell. The T-cell, if it recognizes the substance as dangerous, expands in number and sends out more of itself to the skin, at the site of antigen exposure. When the skin is again exposed to the antigen, the memory t-cells in the skin recognize the antigen and produce cytokines (chemical signals) which cause more T-cells to migrate from blood vessels. This starts a complex immune cascade leading to skin inflammation, itching and the typical rash of contact dermatitis. In general, it takes 2 to 4 days for a response in patch testing to develop. The patch test is really just induction of a contact dermatitis in a small area. Interestingly, the size of the molecule necessary to be picked up and recognized is ten times the size of the largest molecule that can pass through the skin. Therefore, it is likely that an antigen (like nickel) when it has passed through the skin, combines with something else before it is recognized. Patch test 106

Setting up a service Setting up a patch testing service is a time consuming process (see below) and takes up three clinic spaces a week for each patient. It is useful to know how many patients are likely to be seen and how useful the testing will be to pick up positive results. Studies have shown that the optimum number of patients to be tested is 1 in 700 of a population.[2] So in a population of 70,000, 100 patients should be tested annually to detect contact allergy. Coupled with this, differences exist between the rates of positive reactions to the patients tested in different centers. Effectively, the greater the proportion of the population tested for contact allergy, the lower the proportion of positive outcomes identified.[3] When setting up a service, it is important to know what impact it will have on the population. The British Association of Dermatology has set guidelines for patch testing within the UK which state that a patch test service needs: • A named lead dermatologist for the unit who has received training for at least 6 months at a recognized contact dermatitis investigation unit or who can demonstrate comparable experience. • That the contact dermatitis investigation unit conforms to best practice guidelines. The unit and the staff should • Have a dedicated investigation clinic which should include an area for storage (refrigerator) and preparation of allergens. • Record investigation results on an electronic database with a minimum data set: site of onset of dermatitis and duration; gender, occupational, atopy, hand dermatitis, leg dermatitis, face dermatitis and age index; details of occupation and leisure activities; patch test results including type (allergic/irritant) and severity of reaction; relevance of positive tests, occupational or otherwise; and final diagnosis. • Participate in regular audit of data and ‘benchmarks’ results with nationally pooled data. This is evolving and will be reviewed periodically. • The lead dermatologist demonstrates regular attendance at CME-approved update meetings on contact dermatitis (at least every 2 years). • The unit should have up-to-date reference textbooks on contact dermatitis including occupational dermatitis and relevant journals.[4]

Process Prior to testing, avoid taking oral prednisone or other immunosuppressive medications for at least a week prior to testing. Steroid inhalers are OK to use. Avoid sunlight/sunburn for at least a week on the back as this may suppress positive reactions. Antihistamines such as diphenhydramine (Benadryl) or cetirizine (Zyrtec) are permissible prior to and during testing. Application of the patch tests will take about half an hour, though many times the overall appointment time will be longer as your provider will take an extensive history. Tiny quantities of 25 to ~150 materials (allergens) in individual square plastic or round aluminium chambers are applied to the upper back. They are kept in place with special hypoallergenic adhesive tape. The patches stay in place undisturbed for at least 48 hours. Getting the back wet during patch testing should be avoided (no shower). Vigorous exercise or stretching may disrupt the tests. At the second appointment, usually 48 hours later, the patches will be removed. Sometimes further patches are applied. The back is marked with an indelible black felt tip pen or other suitable marker to identify the test sites and a preliminary reading is done. These marks must be visible at the third appointment, usually 24–48 hours later (72–96 hours after application). The back should be checked and if necessary re-marked on several occasions between the 2nd and 3rd appointments. In some cases, a reading at 7 days may be requested, especially if a special metal series is tested. Patch test 107

Interpretation of the results The dermatologist or allergist will complete a record form at the second and third appointments (usually 48 and 72/96 hour readings). The result for each test site is recorded. One system used is as follows: • Negative (-) • Irritant reaction (IR) • Equivocal / uncertain (+/-) • Weak positive (+) Patch test 108

• Strong positive (++)

• Extreme reaction (+++) Irritant reactions include miliaria (sweat rash), follicular pustules and burn-like reactions. Uncertain reactions refer to a pink area under the test chamber. Weak positives are slightly elevated pink or red plaques, usually with mild vesiculation. Strong positives are ‘papulovesicles’ and extreme reactions have spreading redness, severe itching and blisters or ulcers. Relevance is determined by exposure to the positive allergen(s) and is rated as definite, probable, possible, past or unknown. For an allergen to have definite relevance, the product the patient is exposed to must be tested and also be positive in addition to the test allergen. Probable would be used to describe a positive allergen ingredient which is in a product the patient uses (i.e. quaternium-15 listed in a moisturizing cream used on the sites of dermatitis). The interpretation of the results requires considerable experience and training. A positive patch test(s), might not explain the present skin problem since the test only indicates that the individual became allergic during the encounters with that chemical(s) at some point in their life. Relevance, therefore, has to be established by determining the casual relationship between the positive test(s) and the eczema. The confirmation of relevance will occur after the patient has avoided exposure to the chemical(s) and after they have noticed that the improvement or clearance of your dermatitis is directly related to this avoidance. This outcome usually occurs within four to six weeks after stopping the exposure to the chemical(s). If all patch tests are negative, the eczema is probably not due to an allergic reaction to a contactant. It is possible, however, that you were not tested to other chemical(s) that can produce allergic reactions on the rare occasions. If the suspicion is high in spite of negative patch testing, further investigation might be required. This can be discussed during the final evaluation of the patch test procedure. Patch test 109

Common allergens The most frequent allergen that was recorded in many research studies all around the world is Nickel. Nickel allergy is more prevalent in young women and it is especially associated with ear piercing or any nickel-containing watch, belt, zipper or jewelry. Other common allergens are surveyed in North America by the North American Contact Dermatitis Group (NACDG)[5]. The latest update of top allergens from 2005-2006 were: Nickel sulfate (19.0%), Myroxylon pereirae (balsam of Peru, 11.9%), fragrance mix I (11.5%), quaternium-15 (10.3%), neomycin (10.0%), bacitracin (9.2%), formaldehyde (9.0%), cobalt chloride (8.4%), methyldibromoglutaronitrile/phenoxyethanol (5.8%), p-phenylenediamine (5.0%), potassium dichromate (4.8%), carba mix (3.9%), thiuram mix (3.9%), diazolidinyl urea (3.7%), and 2-bromo-2-nitropropane-1,3-diol (3.4%)

Food allergy There is often an assumption that certain foods can cause or worsen skin complaints like eczema. However, there is very little evidence that cutting out foods such as milk and eggs actually improves eczema. Dermatologists may refer patients with suspected food allergies for patch testing. Sometimes this is justified as certain food additives and flavorings can cause dermatitis around the mouth, around the anus and vagina as food allergens pass out of the body or cause a widespread rash on the skin. While this is controversial, allergens such as nickel, Balsam of Peru, parabens, sodium benzoate or cinnamic aldehyde may worsen or cause skin rashes. However, the foods that cause urticaria (hives) or anaphylaxis (such as peanuts) cause a type I hypersensitivity reaction whereby the part of the food molecule is directly recognized by cells close to the skin called mast cells. Mast cells have antibodies on their surface called immunoglobulin E (IgE). These act as receptors and if they recognize the allergen, they release their contents, causing an immediate allergic reaction. Type I reactions like anaphylaxis are immediate and do not take 2 to 4 days to appear. In a recent study of patients with chronic hives who were patch tested, those who were found allergic and avoided all contact with their allergen, including dietary intake, stopped having hives. Those who started eating their allergen again had recurrence of their hives.[6] Often, patch testing for food allergies is not necessary, but in selected individuals it may be helpful.

References

[1] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D010328 [2] Bhushan M. Beck, MH. An audit to identify the optimum referral rate to a contact dermatitis investigation unit. British Journal of Dermatology, 1999 141(3) P570-572 [3] Statham B, Mughal A, Bodger O. The relationship between the proportion of the population tested annually and the rate of patients with positive patch test reactions. Contact Dermatitis. 2011 64(1) P54-57 [4] J. Bourke, I. Coulson and J. English Guidelines for the management of contact dermatitis: British Journal of Dermatology 2009 160 P946-954. [5] Zug KA, Warshaw EM, Fowler JF Jr, Maibach HI, Belsito DL, Pratt MD, Sasseville D, Storrs FJ, Taylor JS, Mathias CG, Deleo VA, Rietschel RL, Marks J. Patch-test results of the North American Contact Dermatitis Group 2005-2006. Dermatitis. 2009 May-Jun;20(3):149-60. [6] Guerra L, Rogkakou A, Massacane P, Gamalero C, Compalati E, Zanella C, Scordamaglia A, Canonica WG, Passalacqua G. Role of contact sensitization in chronic urticaria. J Am Acad Dermatol 2007; 56:88-90. Patch test 110

External links

• MeSH Patch tests (http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?mode=& term=patch+ tests)

• DermNet NZ: Patch tests (contact allergy testing) (http:/ / dermnetnz. org/ procedures/ patch-tests. html)

• Netdoctor: Patch testing for skin allergies (http:/ / www. netdoctor. co. uk/ health_advice/ examinations/

patchtesting. htm)

• American Contact Dermatitis Society (http:/ / www. contactderm. org) RAST test 111 RAST test

RAST test Diagnostics

[1] MeSH D011852

A RAST test (short for radioallergosorbent test) is a blood test used to determine to what substances a person is allergic. This is different from a skin allergy test, which determines allergy by the reaction of a person's skin to different substances. Because there are other tests that help with confirmation, results are best interpreted by a doctor.

History The market-leading RAST methodology was invented and marketed in 1974 by Pharmacia Diagnostics AB, Uppsala, Sweden, and the acronym RAST is actually a brand name. In 1989, Pharmacia Diagnostics AB replaced it with a superior test named the ImmunoCAP Specific IgE blood test, which literature may also describe as: CAP RAST, CAP FEIA (fluorenzymeimmunoassay), and Pharmacia CAP. A review of applicable quality assessment programs shows that this new test has replaced the original RAST in approximately 80% of the world's commercial clinical laboratories, where specific IgE testing is performed. The newest version, the ImmunoCAP Specific IgE 0-100, is the only specific IgE assay to receive FDA approval to quantitatively report to its detection limit of 0.1kU/l. This clearance is based on the CLSI/NCCLS-17A Limits of Detection and Limits of Quantitation, October 2004 guideline. The guidelines for diagnosis and management of food allergy issues by the National Institute of Health state that: "sIgE levels were originally measured using the radioallergosorbent test (RAST), but this test has been replaced by more sensitive fluorescence enzyme-labeled assays and the term RAST should be abandoned"[2]

Indication The two most commonly used methods of confirming allergen sensitization are skin testing and allergy blood testing. Both methods are recommended by the NIH guidelines and have similar diagnostic value in terms of sensitivity and specificity.[3][4] Advantages of the allergy blood test range from: excellent reproducibility across the full measuring range of the calibration curve, it has very high specificity as it binds to allergen specific IgE, and extremely sensitive too, when compared with skin prick testing. In general, this method of blood testing (in-vitro, out of body) vs skin-prick testing (in-vivo, in body) has a major advantage: it is not always necessary to remove the patient from an anthihistamine medication regimen, and if the skin conditions (such as eczema) are so widespread that allergy skin testing cannot be done. Allergy blood tests, such as ImmunoCAP, are performed without procedure variations, and the results are of excellent standardization[5]. Adults and children of any age can take an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often more gentle than several skin tests. In the NIH food guidelines issued in December 2010 it was stated that “The predictive values associated with clinical evidence of allergy for ImmunoCAP cannot be applied to to other test methods.”[6] With over 4000 scientific articles using ImmunoCAP and showing its clinical value, ImmunoCAP is perceived as “Gold standard” for in vitro IgE testing[7][8] RAST test 112

Method The RAST test is a radioimmunoassay test to detect specific IgE antibodies to suspected or known allergens. IgE is the antibody associated with Type I allergic response: for example, if a person exhibits a high level of IgE directed against pollen, the test may indicate the person is allergic to pollen (or pollen-like) proteins. A person who has outgrown an allergy may still have a positive IgE years after exposure. The suspected allergen is bound to an insoluble material and the patient's serum is added. If the serum contains antibodies to the allergen, those antibodies will bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material. The unbound anti-human IgE antibodies are washed away. The amount of radioactivity is proportional to the serum IgE for the allergen.[9] RAST are often used to test for allergies when: • a physician advises against the discontinuation of medications that can interfere with test results or cause medical complications; • a patient suffers from severe skin conditions such as widespread eczema or psoriasis; or • a patient has such a high sensitivity level to suspected allergens that any administration of those allergens might result in potentially serious side effects.

Scale The RAST test is scored on a scale from 0 to 6:

RAST rating IgE level (KU/L) comment

0 < 0.35 ABSENT OR UNDETECTABLE ALLERGEN SPECIFIC IgE

1 0.35 - 0.69 LOW LEVEL OF ALLERGEN SPECIFIC IgE

2 0.70 - 3.49 MODERATE LEVEL OF ALLERGEN SPECIFIC IgE

3 3.50 - 17.49 HIGH LEVEL OF ALLERGEN SPECIFIC IgE

4 17.50 - 49.99 VERY HIGH LEVEL OF ALLERGEN SPECIFIC IgE

5 50.0 - 100.00 VERY HIGH LEVEL OF ALLERGEN SPECIFIC IgE

6 > 100.00 EXTREMELY HIGH LEVEL OF ALLERGEN SPECIFIC IgE

References

[1] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?field=uid& term=D011852 [2] NIH Guidelines for the Diagnosis and Management of Food Allergy in the United States. Report of the NIAID- Sponsored Expert Panel, 2010, NIH Publication no. 11-7700. [3] NIH Guidelines for the Diagnosis and Management of Food Allergy in the United States. Report of the NIAID- Sponsored Expert Panel, 2010, NIH Publication no. 11-7700. [4] Cox, L. Overview of Serological-Specific IgE Antibody Testing in Children. Pediatric Allergy and Immunology. 2011. [5] Hamilton R et al. Proficiency Survey-Based Evaluation of Clinical Total and Allergen-Specific IgE Assay Performance. Arch Pathol Lab Med. 2010; 134: 975–982 [6] Boyce J et al. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of [7] Wood R et al. Accuracy of IgE antibody laboratory results. Ann Allergy Asthma Immunol. 2007; 99: 34–41. [8] Wang J, et al. J Allergy Clin Immunol. 2008;121(5):1219-1224

[9] WebMD > Medical Dictionary > radioallergosorbent test (RAST) (http:/ / dictionary. webmd. com/ terms/ radioallergosorbent-test(rast)) Citing: Stedman’s Medical Dictionary 28th Edition. Copyright 2006 RAST test 113

External links • A discussion by world renowned experts on the relative value of RAST testing from the American Academy of Allergy, Asthma and Immunology (AAAAI), the largest professional medical specialty organization representing allergists, clinical immunologists, allied health professionals, and other physicians with a special interest in allergy

• http:/ / www. aaaai. org/ aadmc/ ate/ category. asp?cat=1137 • ImmunoCAP articles, disease management data, product info from the manufacturer that markets this product:

• http:/ / isitallergy. com/

• http:/ / www. phadia. us/ • Short FAQ's: How a RAST test is performed, results, when ordered:

• http:/ / www. healthatoz. com/ healthatoz/ Atoz/ dc/ tp/ tprast. jsp

• http:/ / www. labtestsonline. org/ understanding/ analytes/ allergy/ test. html • A glossary of allergy testing information regarding RAST

• http:/ / www. acaai. org/ public/ background/ testing. htm

• MeSH Radioallergosorbent+Test (http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2011/ MB_cgi?mode=&

term=Radioallergosorbent+ Test) 114

Treatment & Prevention

Elimination diet

An elimination diet is a method of identifying foods that an individual cannot consume without adverse effects.[1] Adverse effects may be due to food allergy, food intolerance, other physiological mechanisms (such as metabolic or toxins),[2] or a combination of these. Elimination diets typically involve entirely removing a suspected food from the diet for a period of time from two weeks to two months, and waiting to determine whether symptoms resolve during that time period. In rare cases, a health professional may wish to use an oligoantigenic diet to relieve a patient of symptoms they are experiencing.[3] Common reasons for undertaking an elimination diet include suspected food allergies and suspected food intolerances. An elimination diet might remove one or more common foods, such as eggs or milk, or it might remove one or more minor or non-nutritive substances, such as artificial food colorings. An elimination diet relies on trial and error to identify specific allergies and intolerances. Typically, if symptoms resolve after the removal of a food from the diet, then the food is reintroduced to see whether the symptoms reappear. This challenge-dechallenge-rechallenge approach is particularly useful in cases with intermittent or vague symptoms.[4] The terms exclusion diet and elimination diet are often used interchangeably in the literature, and there is no standardised terminology. The exclusion diet can be a diagnostic tool or method used temporarily to determine whether a patient’s symptoms are food-related. The term elimination diet is also used to describe a "treatment diet", which eliminates certain foods for a patient.[2] [5][6] Adverse reactions to food can be due to several mechanisms. Correct identification of the type of reaction in an individual is important, as different approaches to management may be required. The area of food allergies and intolerances has been controversial and is currently a topic that is heavily researched. It has been characterised in the past by lack of universal acceptance of definitions, diagnosis and treatment.[2][7]

History The concept of the elimination diet was first proposed by Dr. Albert Rowe in 1926 and expounded upon in his book, Elimination Diets and the Patient's Allergies, published in 1941.[8] In 1978 Australian researchers published details of an 'exclusion diet' to exclude specific food chemicals from the diet of patients. This provided a basis for challenge with these additives and natural chemicals. Using this approach, the role played by dietary chemical factors in the pathogenesis of chronic idiopathic urticaria (CIU) was first established and set the stage for futute DBPCT trials of such substances in food intolerance studies.[9][10] Elimination diet 115

Definitions 'Food hypersensitivity' is an umbrella term which includes food allergy and food intolerance. [11] [12] [13] Food allergy is defined as an immunological hypersensitivity which occurs most commonly to food proteins such as egg, milk, seafood, shellfish, tree nuts, soya, wheat and peanuts. Its biological response mechanism is characterized by an increased production of IgE (immunoglobulin E) antibodies.[14] A food intolerance on the other hand does not activate the individual's immune response system. A food intolerance differs from a food allergy or chemical sensitivity because it generally requires a normal serving size to produce symptoms similar to an IgE immunologic response. While food intolerances may be mistaken for a food allergy, they are thought to originate in the gastrointestinal system. Food intolerances are usually caused by the individual’s inability to digest or absorb foods or food components in the intestinal tract.[14] One common example of food intolerance is lactose intolerance. • Metabolic food reactions are due to an inborn or acquired errors of metabolism of nutrients such as in diabetes melitus, lactase deficiency, phenylketonuria and favism. Toxic food reactions are caused by the direct action of a food or additive without immune involvement.[15] • Pharmacological reactions are generally to low molecular weight chemicals which occur either as natural compounds such as salicylates, amines, or to artificially added substances such as preservatives, coloring, emulsifiers and taste enhancers including glutamate (MSG).[16] These chemicals are capable of causing drug-like (biochemical) side effects in susceptible individuals. • Toxins may either be present naturally in food or released by bacteria or from contamination of food products.[17][18] • Psychological reactions involve manifestation of clinical symptoms caused not by the food but by emotions associated with the food. The symptoms do not occur when the food is given in an unrecognizable form.[19] Although an individual may have an adverse reaction to a food, this is not considered a food intolerance. Elimination diets are useful to assist in the diagnosis of food allergy and pharmacological food intolerance. Metabolic, toxic and psychological reactions should be diagnosed by other means.[2][20][21]

Diagnosis Food allergy is principally diagnosed by careful history and examination. When reactions occur immediately after certain food ingestion then diagnosis is straight forward and can be documented by using carefully performed tests such as the skin prick test (SPT) and the radioallergosorbent test RAST to detect specific IgE antibodies to specific food proteins and aero-allergens. However false positive results occur when using the SPT when diagnosis of a particular food allergen is hard to determine. This can be confirmed by exclusion of the suspected food or allergen from the patient's diet. It is then followed by an appropriately timed challenge under careful medical supervision. If there is no change of symptoms after 2 to 4 weeks of avoidance of the protein then food allergy is unlikely to be the cause and other causes such as food intolerance should be investigated.[21][22][23] This method of exclusion-challenge testing is the premise by which the Elimination Diet is built upon, as explained in the sections below. Vega testing, a bioelectric test, is a controversial method that attempt to measure allergies or food or environmental intolerances. Currently this test has not been shown to be an effective measure of an allergy or intolerance.[24][25] Food intolerance due to pharmacological reaction is more common than food allergy and has been estimated to occur in 10% of the population. Unlike a food allergy, a food intolerance can occur in non-atopic individuals. Food intolerances are more difficult to diagnose since individual food chemicals are widespread and can occur across a range of foods. Elimination of these foods one at a time would be unhelpful in diagnosing the sensitiveity. Natural chemicals such as benzoates and salicylates found in food are identical to artificial additives in food processing and can provoke the same response. Since a specific component is not readily known and the reactions are often delayed Elimination diet 116

up to 48 hours after ingestion, it can be difficult to identify suspect foods. In addition, chemicals often exhibit dose-response relationships and so the food may not trigger the same response each time. There is currently no skin or blood test available to identify the offending chemical(s), and consequently, elimination diets aimed at identifying food intolerances need to be carefully designed. All patients with suspected food intolerance should consult a physician first to eliminate other possible causes.[2][20]

Elimination diet The elimination diet must be comprehensive and should contain only those foods unlikely to provoke a reaction in a patient. They also need to be able to provide complete nutrition and energy for the weeks it will be conducted. Professional nutritional advice from a dietitian or nutritionist is strongly recommended. Thorough education about the elimination diet is essential to ensure patients and the parents of children with suspected food intolerance understand the importance of complete adherence to the diet, as inadvertent consumption of an offending chemical can prevent resolution of symptoms and render challenge results useless. While on the elimination diet, records are kept of all foods eaten, medications taken, and symptoms that the patient may be experiencing. Patients are advised that withdrawal symptoms can occur in the first weeks on the elimination diet and some patients may experience symptoms that are worse initially before settling down. While on the diet some patients become sensitive to fumes and odours, which may also cause symptoms. They are advised to avoid such exposures as this can complicate the elimination and challenge procedures. Petroleum products, paints, cleaning agents, perfumes, smoke and pressure pack sprays are particular chemicals to avoid when participating in an elimination diet. Once the procedure is complete this sensitivity becomes less of a problem. Clinical improvement usually occurs over a 2 to 4 week period; if there is no change after a strict adherence to the elimination diet and precipitating factors, then food intolerance is unlikely to be the cause. A normal diet can then be resumed by gradually introducing suspected and eliminated foods or chemical group of foods one at a time. Gradually increasing the amount up to high doses over 3 to 7 days to see if exacerbated reactions are provoked before permanently reintroducing that food to the diet. A strict elimination diet is not usually recommended during pregnancy, although a reduction in suspected foods that reduce symptoms can be helpful.[2] Reasons for undertaking an elimination diet may vary from patient to patient, as some types of elimination diets are not out of medical necessity but completely by choice. Some of the most common elimination diets include • Veganism, where an individual removes all animal products from the diet, including meat, dairy, fish, eggs, and even honey. Many will refuse to use any item that has been produced by an animal, like leather or fur clothing. • Vegetarianism, which tends to be a less extreme version of veganism, with options ranging from an ovo-lacto vegetarian, a person who will consume no meat, but will consume dairy products and eggs, a Pescetarian that consumes no meat products except fish and shellfish, or even a flexitarian who will consume a mostly vegan diet, but eats meat and other animal products on occasion. • Gluten-free, a diet where all grains that contain gluten are eliminated from the diet, including wheat, kamut, spelt, barley, rye, and potentially oats, though there is some controversy on this grain. This is the only medically accepted treatment for patients who have Celiac disease and has some inconclusive studies linked to decreasing symptoms of autism.

Challenge testing Challenge testing is not carried out until all symptoms have cleared or improved significantly for five days after a minimum period of two weeks on the elimination diet. The restrictions of the elimination diet is maintained throughout the challenge period. Open food challenges on wheat and milk can be carried out first, then followed by challenge periods with natural food chemicals, then with food additives. Challenges can take the form of purified food chemicals or with foods grouped according to food chemical. Purified food chemicals are used in double blind Elimination diet 117

placebo controlled testing, and food challenges involve foods containing only one suspect food chemical eaten several times a day over 3 to 7 days. If a reaction occurs patients must wait until all symptoms subside completely and then wait a further 3 days (to overcome a refractory period) before recommencing challenges. Patients with a history of asthma, laryngeal oedema or anaphylaxis may be hospitalised as inpatients or attended in specialist clinics where resuscitation facilities are available for the testing. If any results are doubtful the testing is repeated, only when all tests are completed is a treatment diet determined for the patient. The diet restricts only those compounds to which the patient has reacted and over time liberalisation is attempted. In some patients food allergy and food intolerance can coexist, with symptoms such as asthma, eczema and rhinitis. In such cases the elimination diet for food intolerance is used for dietary investigation. Any foods identified by SPT or RAST as suspect should not be included in the elimination diet.[2][7][20][21][22][23][26][27][28][29][30]

Tax Credit Some countries offer a tax credit available to a patient if they are on a specific elimination diet. More commonly a tax credit will be issued to an individual suffering from Celiac Disease who is required to maintain a gluten free diet for life. Countries involved in this type of medical tax credit include Canada[31] and the U.S.[32]

References

[1] "Allergies: Elimination Diet and Food Challenge Test" (http:/ / www. webmd. com/ allergies/ allergies-elimination-diet). WebMD. . Retrieved 2009-04-01. [2] Clarke L, McQueen J, Samild A, Swain AR (1996). "Dietitians Association of Australia review paper. The dietary management of food

allergy and food intolerance in children and adults" (http:/ / www. fedupwithfoodadditives. info/ information/ Clarke et al 1996. pdf) (PDF). Aust J Nutr Dietetics 53 (3): 89–98. ISSN 1032-1322. OCLC 20142084. . [3] Is migraine food allergy? A double-blind controlled trial of oligoantigenic diet treatment. PMID 6137694. [4] Minford, A M; MacDonald, A; Littlewood, J M (October 1982). "Food intolerance and food allergy in children: a review of 68 cases". Arch Dis Child 57 (10): 742–7. doi:10.1136/adc.57.10.742. PMC 1627921. PMID 7138062.

[5] Laitinen K, Isolauri E (2007). "Allergic infants: growth and implications while on exclusion diets" (http:/ / content. karger. com/ produktedb/

produkte. asp?doi=10. 1159/ 0000106367& typ=pdf). Nestle Nutr Workshop Ser Pediatr Program 60: 157–67; discussion 167–9. doi:10.1159/0000106367. PMID 17664903. . [6] Barbi E, Berti I, Longo G (2008). "Food allergy: from the of loss of tolerance induced by exclusion diets to specific oral tolerance induction"

(http:/ / www. bentham-direct. org/ pages/ content. php?IAD/ 2008/ 00000002/ 00000003/ 0007IAD. SGM). Recent Pat Inflamm Allergy Drug Discov 2 (3): 212–4. doi:10.2174/187221308786241875. PMID 19076011. . [7] Allen DH, Van Nunen S, Loblay R, Clarke L, Swain A (1984). "Adverse reactions to foods". Med J Aust 141 (5 Suppl): S37–42. PMID 6482784. [8] Rowe, A. Elimination Diets and the Patient's Allergies. 2nd Edition. Lea & Febiger, Philadelphia, PA: 1944 [9] Gibson AR, Clancy RL (March 1978). "An Australian exclusion diet". Med. J. Aust. 1 (5): 290–2. PMID 661687. [10] Gibson A, Clancy R (November 1980). "Management of chronic idiopathic urticaria by the identification and exclusion of dietary factors". Clin. Allergy 10 (6): 699–704. doi:10.1111/j.1365-2222.1980.tb02154.x. PMID 7460264. [11] Gerth van Wijk R, van Cauwenberge PB, Johansson SG (August 2003). "[Revised terminology for allergies and related conditions]" (in Dutch; Flemish). Ned Tijdschr Tandheelkd 110 (8): 328–31. PMID 12953386. [12] Johansson SG, Bieber T, Dahl R, et al. (May 2004). "Revised nomenclature for allergy for global use: Report of the Nomenclature Review

Committee of the World Allergy Organization, October 2003" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S0091674904009303). J. Allergy Clin. Immunol. 113 (5): 832–6. doi:10.1016/j.jaci.2003.12.591. PMID 15131563. . [13] Johansson SG, Hourihane JO, Bousquet J, et al. (September 2001). "A revised nomenclature for allergy. An EAACI position statement from

the EAACI nomenclature task force" (http:/ / www3. interscience. wiley. com/ resolve/ openurl?genre=article& sid=nlm:pubmed&

issn=0105-4538& date=2001& volume=56& issue=9& spage=813). Allergy 56 (9): 813–24. doi:10.1034/j.1398-9995.2001.t01-1-00001.x. PMID 11551246. .

[14] "Food Allergies and Intolerances" (http:/ / www. hc-sc. gc. ca/ fn-an/ securit/ allerg/ index-eng. php). Health Canada. . Retrieved 2010-12-01.

[15] "UNL Food: Food Allergies: General information on food allergies and sensitivities" (http:/ / food. unl. edu/ web/ allergy/ allergy-sensitivity#metabolic). University of Nebraska-Lincoln. . Retrieved 2010-12-01.

[16] Asero R, Bottazzi G (2007). "Chronic rhinitis with nasal polyposis associated with sodium glutamate intolerance" (http:/ / content. karger.

com/ produktedb/ produkte. asp?typ=fulltext& file=000103229). Int. Arch. Allergy Immunol. 144 (2): 159–61. doi:10.1159/000103229. Elimination diet 118

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[17] "Marine Toxins" (http:/ / www. cdc. gov/ ncidod/ dbmd/ diseaseinfo/ marinetoxins_g. htm). Centers for Disease Control and Prevention. . Retrieved 2010-12-01.

[18] "Protecting Against Foodborne Illnesses" (http:/ / www. nsf. org/ consumer/ food_safety/ fsafety_illness. asp). NSF: The Public Health and Safety Company. . Retrieved 2010-12-01.

[19] "Food allergy or food intolerance" (http:/ / www. umm. edu/ careguides/ 000013. htm). University of Maryland: Medical Center. . Retrieved 2010-12-01. [20] Ortolani C, Pastorello EA (2006). "Food allergies and food intolerances". Best practice & research. Clinical gastroenterology 20 (3): 467–83. doi:10.1016/j.bpg.2005.11.010. PMID 16782524. [21] Pastar Z, Lipozencić J (2006). "Adverse reactions to food and clinical expressions of food allergy". Skinmed 5 (3): 119–25; quiz 126–7. doi:10.1111/j.1540-9740.2006.04913.x. PMID 16687980. [22] Schnyder B, Pichler WJ (1999). "[Food intolerance and food allergy]" (in German). Schweizerische medizinische Wochenschrift 129 (24): 928–33. PMID 10413828. [23] Kitts D, Yuan Y, Joneja J, et al. (1997). "Adverse reactions to food constituents: allergy, intolerance, and autoimmunity". Can. J. Physiol. Pharmacol. 75 (4): 241–54. doi:10.1139/cjpp-75-4-241. PMID 9196849.

[24] "Vegatest – High Tech Pseudoscience" (http:/ / www. theness. com/ neurologicablog/ ?p=2177). Neurologica. . Retrieved 2010-12-01.

[25] "Vega Machine" (http:/ / en. wikipedia. org/ wiki/ Vega_machine). Wikipedia. . Retrieved 2010-12-01. [26] Sullivan PB (1999). "Food allergy and food intolerance in childhood". Indian journal of pediatrics 66 (1 Suppl): S37–45. PMID 11132467. [27] Vanderhoof JA (1998). "Food hypersensitivity in children". Current opinion in clinical nutrition and metabolic care 1 (5): 419–22. doi:10.1097/00075197-199809000-00009. PMID 10565387. [28] Liu Z, Li N, Neu J (2005). "Tight junctions, leaky intestines, and pediatric diseases". Acta Paediatr 94 (4): 386–93. doi:10.1111/j.1651-2227.2005.tb01904.x. PMID 16092447. [29] MacDermott RP (2007). "Treatment of irritable bowel syndrome in outpatients with inflammatory bowel disease using a food and beverage intolerance, food and beverage avoidance diet". Inflamm Bowel Dis 13 (1): 91–6. doi:10.1002/ibd.20048. PMID 17206644. [30] Carroccio A, Di Prima L, Iacono G, et al. (2006). "Multiple food hypersensitivity as a cause of refractory chronic constipation in adults". Scand J Gastroenterol 41 (4): 498–504. doi:10.1080/00365520500367400. PMID 16635922.

[31] "Celiac disease - Medical expenses" (http:/ / www. cra-arc. gc. ca/ tx/ ndvdls/ tpcs/ clc-eng. html). Canada Revenue Agency. . Retrieved 2010-12-02.

[32] "Medical and Dental expenses (Including the Health Coverage Tax Credit) Publication 502" (http:/ / www. irs. gov/ pub/ irs-pdf/ p502. pdf). Internal Revenue Service. . Retrieved 2010-12-02. Feingold diet 119 Feingold diet

The Feingold diet is a food elimination program developed by Ben F. Feingold, MD to treat hyperactivity. It eliminates a number of artificial colors and artificial flavors, aspartame, three petroleum-based preservatives, and (at least initially) certain salicylates. There has been much debate about the efficacy of this program. The mainstream medical establishment dismissed it as an "outmoded approach" lacking evidence and efficacy,[1] however some medical practitioners, as well as many people living with ADHD and parents of children with ADHD, claim that it is effective in the management of ADHD as well as a number of other behavioral, physical and neurological conditions including salicylate sensitivity. The debate has continued for more than 30 years, involving not only consumers and physicians, but scientists, politicians, and the pharmaceutical and food industries.

The Feingold Program The Feingold Program eliminates three groups of synthetic food additives and one class of synthetic sweeteners: • synthetic colors (FD&C and D&C colors) • synthetic flavors (several thousand different chemicals) • synthetic preservatives (BHA, BHT, and TBHQ) • artificial sweeteners (Aspartame, Neotame, and Alitame) The above-listed colorings and preservatives are made from petroleum.[2][3] The word "synthetic" is used instead of "artificial" because not all artificial colorings are eliminated by the program. For example, titanium dioxide and coloring made from iron oxides are acceptable, posing no problem for most people. Only FD&C and D&C colorings are eliminated. There are thousands of synthetic flavorings, from a variety of sources, most of which are not specified in ingredient lists. Due to the "de minimis" principle,[4] safety and neurotoxicity studies are not required for these chemicals. Aspartame and its related chemicals have recently been eliminated from the Feingold Program because of evidence that they may be harmful to the nervous system.[5] During the initial weeks of the program, certain foods containing salicylates are removed and may later be reintroduced and tested for tolerance, one at a time. Most of the problematic salicylate-rich foods are common temperate-zone fruits, as well as a few vegetables, spices, and one tree nut. During this early period, foods like pears, cashews and bananas are used instead of foods like apples, almonds and grapes. Contrary to popular misconception, soft drinks, chocolate and sugar have never been eliminated on the Feingold Program, although moderation is encouraged when consuming such items. Families can often continue to eat the types of food to which they are accustomed, including desserts. It is a matter of picking brands free of the unwanted additives. Most of the acceptable foods are easily available at supermarkets.

History Dr. Feingold was a pediatrician and allergist, and was considered a pioneer in the fields of allergy and immunology.[6] He served as Chief of Pediatrics, Cedars of Lebanon Hospital, Los Angeles, CA; later he established a number of allergy centers for Kaiser Permanente of Northern California, and served as Chief of Allergy at the Kaiser Permanente Medical Center in San Francisco.

First recorded case Since the 1940s, researchers worldwide had discussed cross-reactions of aspirin (a common salicylate) and Tartrazine (FD&C Yellow #5).[7] Dr. Stephen Lockey[8] at the Mayo Clinic and later Dr. Feingold at Kaiser, found that eliminating both salicylates and synthetic food additives from patients' diets not only eliminated allergic-type reactions, but also induced behavioral changes in some of their patients. Feingold diet 120

The first clear case for Dr. Feingold was an adult patient referred to him for treatment of her severe hives in 1965.[9] Typical treatments had not worked for her. Dr. Feingold placed her on a low-salicylate diet with no synthetic coloring or flavoring. Soon her hives were gone, and the patient was happy. Ten days later, however, her psychiatrist called Dr. Feingold to ask, "What did you do to my patient?" She had been receiving treatment for a personality disorder for years, but in less than two weeks on the diet, her behavior had noticeably improved. Both doctors were puzzled. Dr. Feingold asked his staff to watch for other patients who did not respond to standard treatments. He suggested the diet regimen to them, and sometimes it worked. As more reports of behavioral improvement came in, he began to use the diet for people - especially children - with behavioral problems as well as allergy, and eventually found the diet often worked for children with behavioral problems even without allergy symptoms. He named the diet the K-P Diet for Kaiser-Permanente (and he liked the pun of "K-P" as Kitchen Police).[10] Later, as this diet became more well-known for helping hyperactive and learning disabled children, the media dubbed it the "Feingold diet."

Early use of the K-P / Feingold diet In his early work with children (and adults) who suffered from what was then called "minimal brain dysfunction" (MBD), Hyperkinesis, or Hyperkinesis-Learning Disability (H-LD), Dr. Feingold found that response was variable, depending on the age of the child and the presence or absence of a history suggestive of neurological damage. In 1976, he reported that in five separate programs, totalling 360 children managed with the K-P diet, 30% to 50% of them showed favorable responses and could be removed from medication.[11][12] In 1977, Dr. Arnold Brenner published a study he had begun with the intention of disproving Dr. Feingold's claims. Of 32 children who had been under various medication treatments for years with poor success, and who were now put on the K-P diet, 11 (about 33%) were "markedly improved." Surprised, Dr. Brenner wrote that "the startling changes in patients who had been followed for years with other forms of therapy suggest strongly that this improvement was genuine."[13] Although 33% does not appear to be a high rate of success, these were children who had already tried everything else - they were what is called "medication failures." In the beginning, Dr. Feingold did not eliminate the preservatives BHA or BHT. By 1979, he reported having treated over 600 children with the diet, and that his success rate had risen to 60-70% once he had begun eliminating the preservatives as well.[14] At that time TBHQ and aspartame, which are eliminated today, did not yet exist.

Initial controversy In late 1972, Dr. Feingold was invited to present his findings at the annual conference of the American Medical Association in June 1973, which he did.[15][16] Before that time, he had been treating children and adults with allergy symptoms as well as behavioral symptoms, but by 1972 he had arranged for a group of 25 children with a primary complaint of behavioral problems to be managed by the K-P diet. Dramatic improvement in behavior was repeated in this group as well. Dr. Feingold was again invited to participate in the June 1974 AMA conference, where he reported on 169 children in five separate samples that had experienced a success rate of 30 to 50 percent, depending on the age of the child and the sample. (Note, this was also before the diet eliminated preservatives.) This led to the first controlled double-blind crossover study, at the University of Pittsburgh, which was funded by the National Institute of Education. It was directed by Dr. C. Keith Connors, with Dr. Feingold as consultant, and the favorable results were published in the August 1976 issue of Pediatrics, the official publication of the American Academy of Pediatrics.[17] Meanwhile, in 1974, the food industry became involved via its industry-supported organization called the "Nutrition Foundation of New York."[16] This is an organization whose members included Dow Chemical, Coca Cola, and several companies who make, use, and distribute the food additives removed from the K-P diet.[18] In December, 1974, the Nutrition Foundation issued a "proposal for the study of dietary relationship to hyperkenesis" which Feingold diet 121

promised, in its final paragraph, that "no publicity will be given to the findings until the committee has approved the report for release." A two-week long conference, by invitation only, was arranged in January, 1975, in Glen Cove, Long Island. There, they created what they called the National Advisory Committee, which was not government-related in any way. One week later - and certainly long before any of the planned studies had been done, let alone published - this committee widely published its preliminary report concluding that "no controlled studies have demonstrated that hyperkinesis is related to the ingestion of food additives."[16] This conclusion is still quoted today, more than 30 years later.[19][20] Adding to the confusion is the assumption that the National Advisory Committee is a governmental agency rather than an arm of industry. Over the next few years, the Nutrition Foundation funded and designed several small studies, each concluding that the diet produced little effect.[21][22] Although the studies were conducted at universities, which would normally have lent them credibility, Congressman Ben Rosenthal of New York complained, "Despite the compelling need for experts who can examine the food industry with a critical eye, nutrition and food science communities have fallen under the $200 billion industry's influence. At our more prominent universities, eminent nutritionists have traded their independence for food companies' favors."[16] A review of the early studies published by M.A. Lipton in 1983[23] concluded that possibly 2% of children respond adversely to food additives, and that "even the 2% are questionable." Dr. Lipton further asserted that there "is no need for high-priority research or for changes in public policy regarding the use and labeling of foods containing additives." It should be noted that Dr. Lipton chaired the National Advisory Committee set up by the food industry's Nutrition Foundation discussed above.[16] However, when toxicologist Bernard Weiss[24] and autism expert Bernard Rimland[22] analyzed these same studies, they found that they actually did support the positive effects of the Feingold diet. Meanwhile, the media had begun calling the K-P Diet the "Feingold Diet," but because of the confusion with weight-loss diets, and because more than just food is involved in the management of ADHD suggested by the Feingold Association, the "Feingold Diet" was renamed the "Feingold Program."

Research findings Many studies show that 70% or more of hyperactive children respond positively to the removal of synthetic additives, especially when salicylates or allergens are removed.[25][26] There is controversy, however, over what happens when researchers take children whose behavior has improved on a diet that eliminates several thousand additives, and then challenge them with one or a few additives, usually synthetic colors. Especially in the early studies, if such a challenge did not produce a change in behavior, researchers often concluded that the diet had not directly caused the initial improvement in behavior. Rather, the assumption was that the improvement had been due to a placebo effect. There are other possible reasons for the failure of a challenge to evoke a response, however. For example, the amount of additive used as a challenge might have been too small to cause an effect.[22] Rowe & Rowe in 1994 found a dose-related effect; the higher the amount of coloring he used for his double-blind challenge, the stronger (and longer) the reaction of the children.[25] The following chart lists the amount of coloring used in various studies along with the rate of response: Feingold diet 122

Name of Researcher and Amount of Food Dye Challenge Used Percent of Children w/Behavioral Reactions to Food Dye Challenge Year Published in Study

[27] Levy 1978 4 mg in cookies w/1 mg each 0% of 8 children 1 child was dropped from study when behavior deteriorated on challenge

[27] Levy 1978 5 mg in cookies w/1 mg each testing 0% of 12 children done day AFTER challenge

[28] Wilson 1989 17 mg 5% of 19 children

[29] Weiss 1980 35.26 mg 9% of 22 children (not ADHD)

[30] Williams 1978 26 mg 11% of 26 children

[31] Goyette 1978 (a) 26 mg 19% of 16 children showed visual tracking problem; Behavior of all the children was worse after eating food dye, but not significantly so

[31] Goyette 1978 (b) 26 mg, using younger children This is a 100% of 8 children were impaired by food dye higher dose in a younger child

[32] Rowe 1988 50 mg 25% of 8 children

[25] Rowe 1994 50 mg 64.7% of 34 children

[26] Boris 1994 100 mg or 5 g other provoking food 81% of 16 children

[33] Swanson 1980 100 & 150 mg 85% of 20 children

[34] Pollock 1989 125 mg 89.5% of 19 children

[35] Egger 1985 150 mg 79% of 34 children

Considering that in 1976 an FDA scientist estimated that children may be consuming up to 315 mg food dye per day,[36] all the above studies appear to be overly conservative in their choice of challenge amounts. In addition, the effect of an additive might only be seen in synergy with other additives or foods,[5] or the additive used for the challenge may simply not be among those causing the original effect.[36]

Early studies As with many new developments, the first reports of improvement of behavior via diet were anecdotal. This was followed by clinical trials and eventually by larger, double-blind placebo-controlled studies. In 1976, a double-blind crossover diet trial found that both parents and teachers saw fewer hyperkinetic symptoms on the K-P diet as compared to the pretreatment baseline.[37] A 1978 double-blind crossover study using cookies with 13 mg food dye each combined with either medication or placebo found, "The results of this study offer data that a diet free of artificial flavors and colors results in a reduction of symptoms in some hyperactive children."[38] In 1980, forty children were put on a diet free of artificial food dyes and other additives for five days. They then performed the usual double-blind placebo-controlled test but used 100 mg or 150 mg of the food dye mix. They found that the food dyes impaired the performance of the 20 hyperactive children on paired-associate learning tests. The dyes did not hurt the performance of the 20 non-hyperactive children. The study states: "Our data suggest that a large dose of food dye blend decreases attention span in hyperactive children as reflected by performance on the learning test."[39] Seven small studies adding up to a total of 190 children were published starting in the late 1970s. Some of them were elaborate double-blind diet studies using a Feingold-type diet. In some of these studies, the children were taken off their medication, while in others, they continued on stimulant medications including artificial colorants, in spite of the interference that this would create with the diet. Feingold diet 123

One of the studies in 1978,[40] for example, used 36 children between 6 and 12, and 10 children between 3 and 5. The teachers of the school-aged children did not record any improvement, but 63% of the mothers reported improved behavior, as well as 100% of the mothers of the preschoolers; however, since the improvement was reported by the parents of the children rather than teachers, and locomotor activity tests were unaffected, it was reported that there was "no diet effect." In 1980 the Nutrition Foundation set up a review team to review studies related to the Feingold diet.[41] They published a report that stated that there was no response at all to the diet. In 1983, the review team's co-chairman and a colleague reviewed a variety of studies and concluded that no more than 2% of children respond adversely to dye additives.[23] An influential comparative diet study was conducted in 1987 by Gross et al.[42] This was a study of 39 children, of whom 18 were hyperactive, and the balance had other learning disorders. Of those 18, all but one were on behavior-modifying medications during the entire study. The researchers provided a Feingold-type diet for a single week that was, by their own description, unpalatable. They particularly noted that the children missed mustard and ketchup; however, mustard is not eliminated by the Feingold diet, and no reason was given for its exclusion. This diet week was followed by an additive-rich diet the next week. Although the study reported that the camp director and all teachers felt that the children were noisier and more active during the second, additive-rich week, they discounted these observations in favor of filmed 4-minute sequences made during meals. These films were intended to measure reaction to additives in the meals in spite of the fact that any such reaction would not be expected to occur for some time after eating. During the course of the study, three children were dropped: one who was not on stimulant medication, whose behavior became worse during the second week; one who refused to behave altogether; and one whose dose of Cylert became "inadequate" and whose behavior worsened when additives were allowed during the second week. They concluded that the "Feingold diet has no beneficial effect on most children with learning disorders" and moreover that the diet was "distasteful to the typical American child."

Later studies A number of studies conducted since 1980 using diets similar to the Feingold Program report greater than 70% of children responding positively to the diets. Others that eliminated synthetic colors and flavors, but included salicylates still reported greater than 50% positive response.[25][26][32][33] [35][43][44][45][46] In the biggest such study ever performed, published in 1986, the performance of over a million children in 803 New York City public schools was studied for seven years. The children's average standardized test scores rose 8.1% when levels of sucrose (normal table sugar) were restricted to 11 percent along with the removal of two synthetic food colors; when the remaining food colors and all artificial flavors were removed the next academic year, performance rose another 3.8%; when no further changes were made the following academic year, test performance also remained stable; finally, when the petroleum-based preservatives BHT and BHA were removed from the menu in the next academic year, performance improved another 3.7% for an overall improvement of 15.7% in mean national percentile rankings (from 39.2% to 54.9%).[47] Although it appears that improvement increases as the diet approaches the guidelines of the Feingold Program, the researchers suggest that by removing sugar and additives - thereby removing empty calories and processed foods - malnutrition is reduced. It is not clear what portion of the effects can be contributed to limiting sugar intake or the foods containing BHT and BHA (the related preservative TBHQ did not exist at that time) and what portion can be attributed to the removal of the artificial colorants themselves. A most important and often overlooked detail in this study is that all the children did not improve equally. There was a dramatic decline in learning disabled and repeat-failure children. In 1979, 12.4% of the million children were performing two or more grades below their proper level. By the end of the study in 1983, the percent of children two or more grades below proper level had dropped to 4.9%. Moreover, before the dietary changes, the more school food Feingold diet 124

that was consumed, the worse the children did academically. After the changes, however, the more school food the children ate, the better they did academically.[48] In 1997, an association between brain electrical activity and intake of provoking foods was shown in children with food-induced ADHD. (Picture [49]) [50] Another study showed that an oligoantigenic diet can work as well as Ritalin for conduct-disordered children.[51] Other research demonstrated the positive effect of treating young criminals with dietary intervention and correction of mineral imbalances,[52][53] and that toddlers show both significant reductions in hyperactive behaviour when additives are removed from their diet, as well as increased hyperactivity when exposed to a very small (20 mg) amount of food coloring and a benzoate preservative. This effect was observed by parents whether or not the child was hyperactive or atopic.[54] A 2007 British study at the University of Southampton[55] has pointed to food additives as a health hazard for all children, whether they have ADHD or not. The study concluded that artificial colors or a sodium benzoate preservative (or both) in the diet result in increased hyperactivity in 3-year-old and 8/9-year-old children in the general population. In response to this study and a massive media and grass-roots campaign, the major supermarket chains in the UK have removed additives from their house brands. Several American-based candy companies have done the same with the candies they sell in the UK. In response to that study, which had been financed by Britain’s Food Standards Agency and published online by the British medical journal The Lancet, the American Academy of Pediatrics concluded that a low-additive diet is a valid intervention for children with ADHD. It released the following statement in the February 2008 issue of its publication, AAP Grand Rounds: “Although quite complicated, this was a carefully conducted study in which the investigators went to great lengths to eliminate bias and to rigorously measure outcomes. The results are hard to follow and somewhat inconsistent. For many of the assessments there were small but statistically significant differences of measured behaviors in children who consumed the food additives compared with those who did not. In each case increased hyperactive behaviors were associated with consuming the additives. For those comparisons in which no statistically significant differences were found, there was a trend for more hyperactive behaviors associated with the food additive drink in virtually every assessment. Thus, the overall findings of the study are clear and require that even we skeptics, who have long doubted parental claims of the effects of various foods on the behavior of their children, admit we might have been wrong.” Anne Swain, of the Allergy Unit at Royal Prince Alfred Hospital in Sydney Australia, measured amounts (but not type) of salicylate in 333 foods in 1985,[56] and has done other research based on the Feingold Diet.[57]

Criticism of Feingold diet Over the years, a number of criticisms of the Feingold Program have been presented. Many of these center on the difficulty in avoiding synthetic additives, especially in processed or fast food or while eating out, or with social or emotional side-effects the diet may cause. Others center on the range of symptoms claimed to be improved by the Feingold Program.

Food- and diet-related issues Some critics say that the Feingold Program requires a significant change in family lifestyle and eating patterns because families are limited to a narrow selection of foods, and that such foods are often expensive, and must be prepared "from scratch", greatly increasing the amount of time and effort a family must put into preparing a meal.[19] However, the Feingold Association publishes a Foodlist & Shopping Guide that provides thousands of acceptable brand-name items to choose from, including many convenience foods available in local supermarkets. The Foodlist books are organized by region (seven regions in the U.S., one encompassing Canada). They also provide a Fast Food Feingold diet 125

& Restaurant Guide as well as other help. Like any change in diet, the Feingold Program does require that patients make changes in the food that they eat. However, these changes do not usually require significant changes in the types or cost of food a family may choose or the way a family chooses to prepare them. Such choices can be more difficult when little is known about the exact ingredients used in a product, such as at a restaurant or when purchasing food from a vending machine. This requires that a family identify restaurants or products that are not likely to create a problem. Questionable choices can also be avoided by bringing appropriate food when necessary, such as bringing a lunch to school. Parents are encouraged to keep treats available at home and school, so that the children never need feel deprived or left out.[] Nutritionally, the Feingold Program is little different from a normal diet. While some fruits and a few vegetables are eliminated in the first weeks of the Program, they are replaced by others. Often, some or all of these items can be returned to the diet, once the level of tolerance is determined. Studies have found that children on the Feingold Program actually ate better than those eating a "usual" diet, and were more likely to achieve the Recommended Dietary Allowance (RDA) of various nutrients.[58][59]

Psychological or behavioral issues Other critics express concerns about social or emotional effects of putting children on a specific diet. These include that their self esteem may be undermined by implanting notions that they are unhealthy and fragile, or that children may experience situations in which the children's eating behavior or "fear of chemicals" are regarded as peculiar by other children. No clinical evidence supports these speculations, although the attitude of the parents may be important. The issues that a child on the Feingold Program faces are very similar to the issues that a child with an allergy to a common product such as eggs or peanuts must deal with, or a medical condition such as diabetes. Compared to these situations, the Feingold Program could be seen as relatively liberal, as it includes sugary foods, junk foods and even fast food.

Treating multiple symptoms Some feel that it is absurd to think that one intervention could improve symptoms as diverse as asthma, allergies, bedwetting, chronic ear infections, headaches, and insomnia all at once. Critics point to the fact that effectiveness against a wide range of unrelated symptoms is frequently a hallmark of treatments that work via the placebo effect. The diet was originally designed as a diagnostic elimination diet to improve food-related asthma and allergic reactions and was only later found to also be effective in treating behavioral issues. In addition, many children with ADHD suffer from multiple comorbid symptoms. It has been found that there is a profile of the child most likely to benefit from the diet. [60] The child may not have all of these symptoms: some may have few symptoms and others seem to have all of them. While the underlying physiological reason is not understood, when a patient eliminates the additives to which they are sensitive, many or even most of the symptoms contained within the profile are improved. Research supports dietary intervention for each of the symptoms in turn.[5][25][44][61][62][63][64][65][66][67][68][69][70][71] Feingold diet 126

Support for parents Dr. Feingold wrote a book directed to parents, entitled Why Your Child is Hyperactive,[72] as well as The Feingold Cookbook,[73] written in collaboration with his wife, Helene. In addition, more up-to-date books have also been published. As parents began using this diet for their children, many saw dramatic success and formed grass roots support groups. When they gathered in 1976 to form a non-profit national organization, they chose the name "Feingold Association" to honor Dr. Feingold. As time passed, due to the increasing number of double-income families, fewer mothers were available to run these local "kitchen table" support groups, and today the Feingold Association of the United States provides member support services. Recently, some support has been added for Canadian members, and there is some information on the website suitable for people in other countries, as well. The Feingold Association provides information and support for those starting the Program. Members can purchase comprehensive materials[74] including a book listing thousands of brand name foods that have been researched by the Association and are free of the eliminated additives. Newsletters, updates, and phone and email support are also provided. Acceptable products — food, toiletries, cleaning supplies — are included in the Foodlist and Shopping Guide, the Mail Order Guide, the Supplements Guide and the Fast Food Guide. A good introduction to the Feingold Program, as well as 400 pages of compiled wisdom from over 30 years of working with families using the diet, is provided by the book Why Can't My Child Behave?[75]

References [1] Turka, L.A. and Caplan, A. (2011 July 1). "What is the evidence for our standards of care?". Journal of Clinical Investigation 121: 2530-2530. doi:10.1172/JCI59185.

[2] Dale Blumenthal. "U.S. Food & Drug Administration, Red No. 3 and Other Colorful Controversies" (http:/ / web. archive. org/ web/

20080223165547/ http:/ / www. fda. gov/ bbs/ topics/ CONSUMER/ CON00063. html). Archived from the original (http:/ / www. fda. gov/

bbs/ topics/ CONSUMER/ CON00063. html) on 2008-02-23. . Retrieved 2008-03-15. "Approved color additives were divided into two groups: those requiring FDA's certification (synthetic dyes made mostly from coal tar and petroleum derivatives) and those exempt from FDA's certification (substances derived from vegetable, animal or mineral products)."

[3] "Food Additives" (http:/ / www. imadrugpat. org/ foodadditives. htm). . Retrieved 2008-03-15. "E319 Tert-ButylHydroQuinone (TBHQ) Petroleum based... E320 Butylated hydroxy-anisole (BHA) Petroleum derivative ... E321 Butylated hydroxy-toluene (BHT) Petroleum derivate."

[4] "Threshold of toxicological concern (TTC) in food safety assessment." (http:/ / www. feingold. org/ Research/ dye. html#Kroes2002). . [5] Lau, K. and McLean, W.G. and Williams, D.P. and Howard, C.V. (March 2006). "Synergistic interactions between commonly used food additives in a developmental neurotoxicity test". Toxocological Sciences 90 (1): 178–187. doi:10.1093/toxsci/kfj073. PMID 16352620. [6] Allan Magaziner, Linda Bonvie, Anthony Zolezzi (2003). Chemical-Free Kids: How to Safeguard Your Child's Diet and Environment (pp.62). Kensington Books. ISBN 0-7582-0369-1.

[7] "National Health Museum" (http:/ / www. accessexcellence. org/ HHQ/ qow/ qow05/ qow051031. html). . Retrieved 2008-03-31. [8] Lockey, SD (1959 September–October). "Allergic reactions due to F D and C Yellow No. 5, tartrazine, an aniline dye used as a coloring and

identifying agent in various steroids" (http:/ / www. feingold. org/ Research/ lockey1959. html). Annals of Allergy 17: 719–21. PMID 14417794. . [9] Feingold, B.F. (1985). Why Your Child is Hyperactive (pp.1-2). Random House. ISBN 0-394-73426-2. [10] Feingold, B.F. (1985). Why Your Child is Hyperactive (p.37). Random House. ISBN 0-394-73426-2. [11] Feingold, Ben F. (November 1976). "Hyperkinesis and learning disabilities linked to the ingestion of artificial food colors and flavors"

(http:/ / www. feingold. org/ Research/ PDFstudies/ Feingold76. pdf) (PDF). Journal of Learning Disabilities 9 (9): 551–559. doi:10.1177/002221947600900902. .

[12] Feingold, Ben F. (May 1975). "Hyperkinesis and learning disabilities linked to artificial food colors and flavors" (http:/ / www. feingold.

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[16] Feingold, Ben F. (June 8, 1977). "A View of the Press From the Other Side" (http:/ / www. feingold. org/ Research/ PDFstudies/

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[18] Feingold Association website: Who is the Nutrition Foundation? (http:/ / www. feingold. org/ nut. html)

[19] Quackwatch website page (http:/ / www. quackwatch. org/ 01QuackeryRelatedTopics/ feingold. html)

[20] Elisabeth Schafer, Iowa State University Professor, quoted in National Network for Child Care website (http:/ / www. nncc. org/ Nutrition/

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[21] Weiss, Bernard (March 1982). "Food Additives and Environmental Chemicals as Sources of Childhood Behavior Disorders" (http:/ / www.

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double-blind challenge study" (http:/ / www. feingold. org/ Research/ adhd. html#Goyette). Psychopharmacol Bull 14 (2): 39–40. PMID 652927. . [32] Rowe KS (1988). "Synthetic food colourings and "hyperactivity': A double-blind crossover study". Australian Pediatrics 24 (2): 143–147. PMID 3395307. [33] Swanson, J. and Kinsbourne, M. (March 1980). "Food Dyes Impair Performance of Hyperactive Children on a Laboratory Learning Test". Science 207 (4438): 1485–1487. doi:10.1126/science.7361102. PMID 7361102. [34] Pollock, I. and Warner, J.O. (January 1990). "Effect of artificial food colours on childhood behaviour". Arch Dis Child 65 (1): 74–77. doi:10.1136/adc.65.1.74. PMC 1792406. PMID 2301986. [35] Egger, J. and Carter, C.M. and Soothill, J.F. and Wilson, J. (January 1989). "Oligoantigenic diet treatment of children with epilepsy and migraine". Journal of Pediatrics 114 (1): 51–58. doi:10.1016/S0022-3476(89)80600-6. PMID 2909707.

[36] Center for Science in the Public Interest, Quarter-Century Review, pg.11 (http:/ / www. cspinet. org/ new/ adhd_resch_bk02. pdf) [37] Conners CK, Goyette CH, Southwick DA, Lees JM, Andrulonis PA. (August 1976). "Food additives and hyperkinesis: a controlled double-blind experiment". Pediatrics 58 (2): 154–66. PMID 781610. [38] Williams JI, Cram DM, Tausig FT, Webster E. (June 1978). "Relative effects of drugs and diet on hyperactive behaviors: an experimental study". Pediatrics 61 (6): 811–7. PMID 353680. [39] Swanson JM, Kinsbourne M. (March 1980). "Food dyes impair performance of hyperactive children on a laboratory learning test". Science 207 (4438): 1485–7. doi:10.1126/science.7361102. PMID 7361102. [40] Harley, J.P. and Ray, R.S. and Tomasi, L. and Eichman, P.L. and Matthews, C.G. and Chun, R. and Cleeland, C.S. and Traisman, E. (June 1978). "Hyperkinesis and food additives: testing the Feingold hypothesis". Pediatrics 61 (6): 818–828. PMID 353681. [41] Wender EH, Lipton MA. The National Advisory Committee Report on Hyperkinesis and Food Additives -- Final Report to the Nutrition Foundation. Washington D.C: The Nutrition Foundation, 1980. [42] Gross, M.D. and Tofanelli, R.A. and Butzirus, S.M. and Snodgrass, E.W. (January 1987). "The effect of diets rich in and free from additives

on the behavior of children with hyperkinetic and learning disorders" (http:/ / www. feingold. org/ Research/ PDFstudies/ Gross87. pdf) (PDF). Journal of the American Academy of Child and Adolescent Psychiatry 26 (1): 53–55. doi:10.1097/00004583-198701000-00011. PMID 3584001. . Feingold diet 128

[43] Egger J, Carter CM, Graham PJ, Gumley D, Soothill JF (1985). "Controlled trial of oligoantigenic treatment in the hyperkinetic syndrome". Lancet 1 (8428): 540–5. doi:10.1016/S0140-6736(85)91206-1. PMID 2857900. [44] Kaplan BJ, McNicol J, Conte RA, Moghadam HK (1989). "Dietary replacement in preschool-aged hyperactive boys". Pediatrics 83 (1): 7–17. PMID 2909977. [45] Egger J, Carter CH, Soothill JF, Wilson J. (1992). "Effect of diet treatment on enuresis in children with migraine or hyperkinetic behavior". Clinical Pediatrics. 31 (5): 302–7. doi:10.1177/000992289203100508. PMID 1582098. [46] Carter CM, Urbanowicz M, Hemsley R, Mantilla L, Strobel S, Graham PJ, Taylor E. (1993). "Effects of a few food diet in attention deficit disorder". Archives of Disease in Childhood. 69 (5): 564–8.. doi:10.1136/adc.69.5.564. PMC 1029619. PMID 8257176. [47] Schoenthaler SJ, Doraz WE, Wakefield JA. (1986). "The Impact of a Low Food Additive and Sucrose Diet on Academic Performance in

803 New York City Public Schools" (http:/ / www. feingold. org/ Research/ research_school. html). International Journal of Biosocial Research 8 (2): 185–195. . [48] Schoenthaler SJ, Doraz WE, Wakefield J. (1986). "The Testing of Various Hypothesis as Explanations for the Gains in National Standardized Academic Test Scores in the 1978-1983 New York City Nutrition Policy Modification Project". The International Journal of Biosocial Research. 8 (2): 196–203..

[49] http:/ / www. feingold. org/ Research/ uhlig-pic. html [50] Uhlig T, Merkenschlager A, Brandmaier R, Egger J. (1997). "Topographic mapping of brain electrical activity in children with food-induced attention deficit hyperkinetic disorder". European Journal of Pediatrics. 156 (7): 557–61. doi:10.1007/s004310050662. PMID 9243241. [51] Schmidt MH, Mocks P, Lay B, Eisert HG, Fojkar R, Fritz-Sigmund D, Marcus A, Musaeus B. (1997). "Does oligoantigenic diet influence hyperactive/conduct-disordered children--a controlled trial". European Child & Adolescent Psychiatry. 6 (2): 88–95. PMID 9257090. [52] Peter C, Bennett W, Brostoff J. (1997). "The Health of Criminals Related to Behaviour, Food, Allergy and Nutrition: A Controlled Study of

100 Persistent Young Offenders" (http:/ / www. feingold. org/ Research/ PDFstudies/ Peter97. pdf) (PDF). Journal of Nutritional & Environmental Medicine. 7 (4): 359–366. doi:10.1080/13590849762493. . [53] Peter C, Bennett W, McEwen, LM, McEwen HC, ROSE, EL. (1997). "The Shipley project: Treating food allergy to prevent criminal

behavior in community settings" (http:/ / www. feingold. org/ Research/ PDFstudies/ Peter98. pdf) (PDF). Journal of Nutritional & Environmental Medicine. 8 (1): 77–8. . [54] Bateman B, Warner JO, Hutchinson E, Dean T, Rowlandson P, Gant C, Grundy J, Fitzgerald C, Stevenson J. (2004). "The effects of a double blind, placebo controlled, artificial food colourings and benzoate preservative challenge on hyperactivity in a general population sample of preschool children". Archives of Disease in Childhood. 89 (6): 506–11. doi:10.1136/adc.2003.031435. PMC 1719942. PMID 15155391. [55] McCann D, Barrett A, Cooper A, et al. (November 2007). "Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial". Lancet 370 (9598): 1560–7. doi:10.1016/S0140-6736(07)61306-3. PMID 17825405. [56] Swain AR, Dutton SP, Truswell AS (August 1985). "Salicylates in foods.". Journal of the American Dietetic Association. 85 (8): 950–60.. PMID 4019987.

[57] "Food Intolerance Network" (http:/ / www. fedupwithfoodadditives. info/ information/ Swain et al 1985. pdf) (PDF). . Retrieved 2008-03-31. [58] Dumbrell, S. and Woodhill, J.M. and Mackie, L. and Leelarthaepin, B. (December 1978). "Is the Australian version of the Feingold diet safe?". The Medical Journal of Australia 2 (12): 569–570. PMID 364258. [59] Harper, P.H. and Goyette, C.H. and Conners, C.K. (November 1978). "Nutrient intakes of children on the hyperkinesis diet". Journal of the American Dietetic Association 73 (5): 515–519. PMID 701681.

[60] The Feingold Association of the United States (2006). "Feingold Program - Symptoms" (http:/ / web. archive. org/ web/ 20061002063332/

http:/ / www. feingold. org/ symptom-pg. html). The Feingold Association website. The Feingold Association of the United States. Archived

from the original (http:/ / www. feingold. org/ symptom-pg. html) on 2006-10-02. . Retrieved 2006-08-21. [61] Schab DW, Trinh NH. (December 2004). "Do artificial food colors promote hyperactivity in children with hyperactive syndromes? A meta-analysis of double-blind placebo-controlled trials". Journal of Developmental and Behavioral Pediatrics 25 (6): 423–34. doi:10.1097/00004703-200412000-00007. PMID 15613992. [62] Jiménez-Aranda GS, Flores-Sandoval G, Gómez-Vera J, Orea-Solano M. (Nov-Dec 1996). "Prevalence of chronic urticaria following the ingestion of food additives in a third tier hospital". Revista Alergia Mexico 43 (6): 152–6. PMID 9053127. [63] Egger J, Carter CH, Soothill JF, Wilson J. (May 1992). "Effect of diet treatment on enuresis in children with migraine or hyperkinetic behavior". Clinical Pediatrics 31 (5): 302–7. doi:10.1177/000992289203100508. PMID 1582098. [64] Schmidt MH, Möcks P, Lay B, Eisert HG, Fojkar R, Fritz-Sigmund D, Marcus A, Musaeus B. (June 1997). "Does oligoantigenic diet influence hyperactive/conduct-disordered children--a controlled trial.". European Child & Adolescent Psychiatry 6 (2): 88–95. PMID 9257090. [65] Novembre E, Dini L, Bernardini R, Resti M, Vierucci A. (Jan-Feb 1992). "Unusual reactions to food additives". Medical and Surgical Pediatrics 14 (1): 39–42. PMID 1579515. [66] Wasowka-Królikowska K, Dynowski J, Godzisz J. (December 1998). "The way of nutrition and frequency of otitis media in hospitalized infants and 3-year-old children". Polski Merkuriusz Lekarski 5 (30): 333–4. PMID 10101517. [67] Moneret-Vautrin DA. (May 2003). "Allergic and pseudo-allergic reactions to foods in chronic urticaria". Annales de dermatologie et de vénéréologie 130 Spec No 1: 1S35–42. PMID 12843808. Feingold diet 129

[68] Feingold BF. (1979). "Dietary management of nystagmus". Journal of Neural Transmission 45 (2): 107–15. doi:10.1007/BF01250086. PMID 469522. [69] Inomata N, Osuna H, Fujita H, Ogawa T, Ikezawa Z. (June 2006). "Multiple chemical sensitivities following intolerance to azo dye in sweets in a 5-year-old girl". Allergology International 55 (2): 203–5. doi:10.2332/allergolint.55.203. PMID 17075259. [70] Spector SL, Wangaard CH, Farr RS. (December 1979). "Aspirin and concomitant idiosyncrasies in adult asthmatic patients". Journal of Allergy & Clinical Imunology 64 (6 Pt 1): 500–6. doi:10.1016/0091-6749(79)90059-9. PMID 512268. [71] Egger J, Carter CM, Soothill JF, Wilson J. (January 1989). "Oligoantigenic diet treatment of children with epilepsy and migraine". The Journal of Pediatrics 114 (1): 51–8. doi:10.1016/S0022-3476(89)80600-6. PMID 2909707. [72] Feingold, B.F. (1985). Why Your Child is Hyperactive. Random House. ISBN 0-394-73426-2. [73] Feingold, B.F. (1979). The Feingold Cookbook for Hyperactive Children. Random House. ISBN 0-394-73664-8.

[74] The Feingold Association of the United States (2006). "The Feingold Program" (http:/ / www. feingold. org/ materials-pg. html). The Feingold Association website. The Feingold Association of the United States. . Retrieved 2006-04-29.

[75] Hersey, Jane; Robert C. Lawlor (2006). Why Can't My Child Behave? (http:/ / www. feingold. org/ book. html) (4th printing ed.). Williamsburg, VA: Pear Tree Press. ISBN 0-9651105-0-8. .

External links

• The Feingold Association website (http:/ / www. feingold. org/ )

• NIH Consensus Statement on ADHD (http:/ / www. ajcn. org/ content/ 37/ 1/ 161. full. pdf) 1982

• Treatment alternatives for Attention-Deficit/Hyperactivity Disorder. (http:/ / www. feingold. org/ Research/

arnold. html) L.E. Arnold, Journal of Attention Disorders, Vol. 3, No. 1, April 1999, pp. 30-48

• American Academy of Pediatrics Guideline for Diagnosis and Evaluation of the Child With ADHD (http:/ / www.

pediatrics. org/ cgi/ content/ abstract/ 105/ 5/ 1158) 2000 • Psychopharmacological and Other Treatments in Preschool Children with ADHD: Current Evidence and Practice

(http:/ / www. ncbi. nlm. nih. gov/ pmc/ articles/ PMC2935821/ pdf/ cap. 2008. 022. pdf/ ) J.K. Ghuman et al, J of Child & Adolescent Psychopharmacology, Vol.18, No.5, 2008 Allergen immunotherapy 130 Allergen immunotherapy

Allergen immunotherapy Intervention

[1] ICD-10-PCS Z51.6

ICD-9-CM 99.12

[2] MeSH D003888

Allergen immunotherapy (also termed hyposensitization therapy, immunologic desensitization, hyposensibilization, or allergen-specific immunotherapy) is a form of immunotherapy for allergic disorders in which the patient is vaccinated with increasingly larger doses of an allergen (substances to which they are allergic) with the aim of inducing immunologic tolerance. Allergen specific immunotherapy is the only treatment strategy which treats the underlying cause of the allergic disorder. It is a highly cost-effective treatment strategy which results in an improved quality of life and a reduction in allergic- and allergen-related asthma, as well as a reduction in days off school/work.[3] Immunotherapy has been shown to produce long-term remission of allergic symptoms,[4] reduce severity of associated asthma, as well as reduce the chances of new sensitisations to allergens developing. This is achieved via immunotherapy modulating the immune system response to allergens.[5] Allergen immunotherapy can either reduce the need for medication, severity of symptoms or eliminate hypersensitivity altogether. Therapy can be administered under the tongue (sublingually) or by injections under the skin (subcutaneous). Allergen-specific immunotherapy is the only known treatment option that is known to modify the allergy disease process (with a possible chance of curing the disease), whereas other therapies merely suppress the symptoms.[6] Subcutaneous injection immunotherapy has been shown to be a highly efficient treatment for allergic disease, but due to a rare serious side effect of anaphylaxis, its use is restricted to specialist centers. As a result there has been growing interest in the sublingual immunotherapy which can be safely administered at home.[7]

Background Allergic rhinitis (an allergic inflammation of the nasal airways) is an extremely common disorder. For example in the UK 1 in 5 people have allergic rhinitis with approximately 50 percent of those with allergic rhinitis being allergic to grass pollen. Over half of people receiving symptom based treatments report that they benefit poorly or only partially from symptomatic based treatments. For these patients immunodesensitisation therapy can be recommended. Subcutaneous injection based immunotherapy is one effective route but is complicated by rare but serious side effects. As a result of these rare but serious side effects the sublingual route for allergen vaccination immunotherapy is gaining increasing popularity among allergy specialists due to its lack of serious side effects.[8] Immunotherapy administered through cutaneous injections or sublingually has substantial empirical support. Numerous research articles and several meta-analytic studies support its clinical effectiveness. Immunotherapy can lead to a substantial decline in allergen symptomatology leading to a significant improvement in quality of life for allergy sufferers. Repeated courses of immuno-desensitisation leads to further reduction in allergy disease severity. Immunotherapy is superior to antihistamines and topical steroids in reducing severity of allergy symptoms and has been found to be a cost effective treatment strategy. Immunotherapy results in less time taken off work compared to those who rely solely on symptomatic relieving medications.[9][10] In the case of grass allergy immunotherapy the pollen from the grass species used has strong cross reactivity between the various grass species thus meaning that treatment leads to desensitisation to all grass species.[5] Allergen immunotherapy 131

Sublingual specific immunotherapy has the benefit of allowing treatment to be carried out in the home environment and has been found to be a cost effective treatment strategy for allergic disorders.[11][12] Sublingual immunotherapy cost effectiveness is significantly increased due to the reduced number of medical visits compared to those receiving subcutaneous injection based immunotherapy. For example, those receiving subcutaneous injections make almost seven times more visits than those receiving home based sublingual immunotherapy, as those receiving subcutaneous injections require frequent visits to doctors to receive their regular injections. Furthermore the sublingual route appears to be as effective as the subcutaneous route in trials of grass allergy.[5]

Clinical experience and research Immunology is a relatively young science that originated in the 19th century. Grass pollens were identified for the first time as the likely trigger of seasonal hay fever in the 1870s. Skin allergy testing became an accepted assessment technique around 1910. IgE was identified in the 1960s. The first scholarly report of immunotherapy for allergy appeared in 1911 in the medical journal, The Lancet, but research lagged behind clinical practice. Whereas clinical lore in medicine generally supports the effectiveness of immunotherapy, sufficient research evidence on the effectiveness and mechanism of immunotherapy began to accumulate in the last 15 years of the 20th century.[13] Some limited research of sublingual immunotherapy in children has been conducted and shown promise as a generally well tolerated treatment strategy for allergic disorders in children.[14]

Benefits from immunotherapy Current pharmacotherapies (antihistamines) do not prevent allergic reaction, but instead block the action of histamine in the body, reducing allergic symptoms. Immunotherapy, in contrast, trains the immune system to tolerate allergic triggers by means of gradual exposure to increasing amounts of the offending allergen. The benefits of allergen specific immunotherapy are long lasting unlike symptomatic based treatments. Immunotherapy is most effective for pollen, dust, and animal dander allergies, and may help those with asthma.[15][16] Treatment started 10 – 14 weeks before the start of the grass pollen season results in a 34% reduction of rhinoconjunctivitis symptoms and a 54% increase in well days.[17] Continued treatment over 2 years in the case of grass allergy shows progressive immunological changes resulting in progressive desensitisation to the allergen with up to an 73 percent reduction in symptomatology.[18] About 3 in 4 patients with hay fever experience significant improvement with immunotherapy after one year of therapy. However, with continued therapy the number of people benefiting from specific immunotherapy appears to increase to over 4 in 5 people who benefit from specific immunotherapy by the end of the 2nd year of therapy. Sometimes symptoms are reduced rather than abolished. In that case immunotherapy may allow the patient to reduce the quantity of medication required for symptom relief.[5] Research in children aged from 5 years old to 16 years old shows similar effectiveness in the treatment of grass allergy as seen in adults. Like in adults allergen related asthma also decreases as well as allergic rhinitis symptoms.[19] Recent studies in children suggest that if immunotherapy is commenced soon after allergies first develop, it may actually reduce the risk of developing allergic reactions to other allergens, and even reduce the risk of later developing asthma. Immunotherapy is also an essential part of managing dangerous allergic reactions (anaphylaxis) to bee and wasp stings. In these cases, the protection against further dangerous allergic reactions to stinging insects is variously quoted at between 80 and 95%. Allergen immunotherapy 132

Mechanism of therapeutic action The immune system of allergy affected individuals, for reasons not fully understood, misinterprets a usually innocuous substance as a disease agent and begins producing a type of antibody against it, called immunoglobulin E (IgE). This is called the 'primary antibody response.' The IgE produced during this response binds to basophils in the bloodstream and to a similar type of cell called mast cells in the tissues. When the person again encounters the allergen, it binds to the IgE that has already attached to basophils and mast cells, causing release of histamine, prostaglandins, and leukotrienes, producing inflammation of the surrounding tissues, and bringing about the familiar allergic symptoms. Even the most allergic individual can tolerate minuscule amounts of an allergen without experiencing symptoms. Immunotherapy commences with the subcutaneous injection of a tiny amount of offending allergen, and gradually increases the dose until the individual's immune system is essentially 'retrained' to tolerate exposure without producing an allergic response. This process is also known as specific immunotherapy. Immunotherapy via repeated exposure to a specific allergen via either sublingual or subcutaneous route leads to a desensitisation to the allergen and thus a reduction in allergic symptomatology and use of symptomatic based treatments.[5] The exact mechanism is not fully understood but it is accepted that immunotherapy causes modification of the immune system. This modification leads to changes in IgE synthesis and the production of IgE blocking antibodies which thus reduces the immune systems allergic response to specific allergens. There is also an increase in conversion of Th2 to regulatory T cells.[5] At a molecular level, part of the therapeutic mechanism relies on the preferential induction of allergen-specific IgG to neutralize the allergen in place of allergen-specific IgE.[20] In bee or wasp venom immunotherapy, immunoglobulin subclass IgG4 has been considered to be particularly important, where IL-10 make the B cells to switch the produced immunoglobulin class from IgE to IgG4.[20][21][22] It has been revealed that the mechanism of this immunotherapy consists of some more other components. They include increased production of IL-10 which acts on Th2 or mast cells to become anergic and suppresses Th2 not to release cytokines and prevent histamine from being secreted.[23] It was indicated that osteopontin produced by CD14+ cells induced IL-12 in antigen presenting cells to activate Th1.[24] It was recently shown that a progressive expansion of circulating regulatory T cells was made during venom immunotherapy.[25]

Procedures For benefits to be felt from either sublingual or injection based allergen specific immunotherapy it needs to be started 2 – 4 months before the start of the allergen season in the case of seasonal allergies. The earlier it is started the better the level of allergy protection.[26] Subcutaneous immunotherapy (SCIT) Immunotherapy via the subcutaneous route involves the use of small hypodermic syringes which are used to inject commercial allergen extracts. Injections are normally given into the loose tissue over the back of the upper arm, half way between the shoulder and elbow. Injections are given under the skin ("subcutaneous"). This is the least painful place to inject allergen, as there are few nerve endings in the skin. When given correctly, the injections should be only slightly uncomfortable. They are not normally painful and are usually well tolerated by adults and teenagers. Some doctors may advise you to take an antihistamine a few hours before each injection to reduce the likelihood of local discomfort and other side-effects. Allergy injections are started at very low doses. The dose is gradually increased on a regular (and usually weekly) basis, until a "maintenance" dose is reached. This usually means four to six months of weekly injections to reach the maintenance dose. Once the maintenance dose is reached, the injections are administered less often (every two to four weeks), still on a regular basis. Maintenance injections are normally given once per month for a few years. Generally, the longer the treatment and the higher the dose, the greater the therapeutic benefit. Allergen immunotherapy 133

After successful completion of immunotherapy, long-term protection can be expected for a period of 3–5 years or more. Therapy can be repeated should symptoms begin to return or if the individual becomes exposed to new allergens that were not included in the previous treatment regimen. Because allergy vaccine injections have a strong evidence base for clinical effectiveness, this form of treatment is covered by the vast majority of insurance companies in the United States. Intralymphatic immunotherapy (ILIT) Intralymphatic delivery of immunotherapy is another modality which is effective in the treatment of allergic disorders.[27] Intralymphatic immunotherapy (ILIT) administers allergens directly into a subcutaneous lymph node;[28] A paper in 2009 found that studies on both animals and humans demonstrated that a direct injection into lymph nodes enhanced the immune responses to protein, peptide, and naked DNA vaccines and that this increased response meant that the overall allergen dosage and therapy duration could be reduced.[29] A study on mice found that intralymphatic immunisation induced a more than 10-fold higher IgG2a response with 100-fold lower allergen doses than subcutaneous immunisation; and that only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis.[30] ILIT is well tolerated and patients found it to be "practically painless" and easy to perform. Patient compliance with ILIT was improved as compared with SCIT.[29] Sublingual immunotherapy (SLIT) In some countries, particularly in Europe, there is a strong tradition of undertaking immunotherapy using oral vaccines or sublingual drops. While there has been some interesting research in this area in recent years, the effectiveness of this form of treatment is difficult to compare with standard injected immunotherapy. Double-blind, placebo-controlled studies in Europe using high-dose sublingual immunotherapy have shown benefit.[31] Some practitioners in the United States, particularly ENT physicians, offer sublingual immunotherapy as another immunotherapy option. Sublingual immunotherapy is a safe and effective alternative to injection based immunotherapy and can be administered in the home environment. Modest benefits have been demonstrated within the first season of therapy.[32] Treatment needs to be continued for at least 3 years to achieve maximum effectiveness in immune desensitisation to the allergen.[33] In the case of sublingual immunotherapy there is no need to do a titrated graduated updose and therapy is generally started at the usual clinical dose.[5] Transcutaneous immunotherapy (TCIT) / Epicutaneous immunotherapy (ELIT) This emerging therapy administers allergen by a skin patch. Though relatively new, clinical trials show that TCIT, EPIT is safe and comparably effective to conventional immunotherapy.[28] Allergen immunotherapy 134

Side effects and adverse reactions

Subcutaneous immuno-therapy (SCIT) While itchiness, swelling, and redness at the site of injection are expected, systemic reactions such as hives or anaphylaxis rarely occur. A July 2011 study following 773 patients that collectively received approximately 28,000 injections, the rate of systemic reaction to SCIT was about 4%.[34] As such, patients are advised or required to wait in the clinic for 20–30 minutes so that they can be treated immediately in the case that they develop a severe systemic reaction. However, a 2008 study found that just under 50% of reported systemic reactions occurred more than 30 minutes after the injection.[35]

Premedication with antihistamines or corticosteroids can reduce the risk of systemic reaction.[36] A relatively large but normative localized There is an established correlation between those receiving a Rushed reaction to an allergy injection on the upper arm Immunotherapy and higher rates of systemic reactions as compared to of a patient. This reaction would not cause concern, but larger reactions may require a that those receiving conventional SCIT. While it may seem attractive readjustment of the treatment regimen. to patients to rush SCIT, it seems as though it does lead to an increased risk to having a systemic reaction.[36] However, this may not be the same for allergic respiratory diseases.[37]

About 74% of systemic reactions to SCIT are mild reactions such as cutaneous or upper respiratory symptoms; about 23% are moderate reactions such as asthma with reduced lung function, and about 3% are severe, where life-threatening airway compromising or hypo-tension occurs.[38] Based on the highest reported symptoms of a systemic reaction, such as generalized itching, upper airway itchiness, coughs, or a shortness of breath should be reported immediately so they can be monitored or managed.[34] These are usually managed through the use of epinephrine. If such reactions occur, the allergy specialist will adjust the dosage to a safe level. The risk of a systemic reaction is reduced if the patient avoids exercising or overheating for a few hours before and after the procedure. Some heart and blood pressure medications such as beta-blockers are contraindicated as well. The physician should be consulted if the patient notices a worsening of allergy symptoms or if he or she is suffering from a cold or has been undergoing a different kind of vaccination procedure. Immunotherapy does not increase the risk of contracting a cold. Sublingual immuno-therapy (SLIT) The side effects of sublingual desensitisation therapy are generally mild and limited to local reactions. Common side effects include oral pruritus, edema mouth, ear pruritus, throat irritation, sneezing, mild itching and swelling of the mouth. Side effects which are less common or rare include headache, oral paraesthesia, eye pruritus, conjunctivitis, cough, asthma, pharyngitis, rhinorrhoea, nasal congestion, rhinitis, throat tightness, pruritus and fatigue. In most cases these side effects diminished minutes or hours after immunotherapy and disappeared 1 – 7 days after commencement of therapy. As a precautionary measure against rare but serious side effects e.g. asthma attacks it is recommended that the first sublingual tablet containing the specific allergen for immunotherapy is administrated whilst under the observation of a medical doctor and observed for 30 minutes for any signs of serious side effects.[5][39] Sublingual immunotherapy is contraindicated in patients who have systemic diseases of the immune system, inflammatory conditions of the oral cavity with associated severe symptoms e.g. oral lichen planus with ulcers or severe oral mycosis or individuals with severe and uncontrolled asthma. Immunotherapy tablets are also Allergen immunotherapy 135

contraindicated in individuals who are allergic to any of the addition constituents of the tablet.[5]

Insurance Issues Immunotherapy is one of the least-covered areas under most insurance plans. In the USA, sublingual immunotherapy is considered an "off-use" practice and is not approved by the FDA and therefore not covered by almost all insurers. Most insurers only cover immunotherapy if it is considered "medically necessary." The criteria for necessity generally require a history of allergic asthma, stinging insect allergy, and or severe reactivity. In the UK, injection immunotherapy is only covered for severe allergies and never for multiple allergies. For many government programs, including Healthy San Francisco, immunotherapy is not covered under any circumstances, including severe chronic asthma. Quality-of-life allergic rhinitis such as seasonal allergies, pet dander allergies often remain uncovered and undiagnosed.

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[27] Juillard, Guy. "Intralymphatic Injection of Immunogenic Material in Afferant Lymphatic Vessel: A Method of Choice" (http:/ / www.

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immunotherapy to treat seasonal allergic rhinitis" (http:/ / linkinghub. elsevier. com/ retrieve/ pii/ S0091674904022316). J. Allergy Clin. Immunol. 114 (4): 831–7. doi:10.1016/j.jaci.2004.06.058. PMID 15480323. . [32] Allison C, Fraser J (November 2007). "Grazax: an oral vaccine for the treatment of grass pollen allergy (hay fever)". Issues Emerg Health Technol (107): 1–4. PMID 18041171. [33] Svendsen UG (January 2008). "[Grazax—treatment for grass pollen hay fever]" (in Danish). Ugeskr. Laeg. 170 (3): 135–7. PMID 18208728. [34] Phillips JF, Lockey RF, Fox RW, Ledford DK, Glaum MC. (July 2011). "Systemic reactions to subcutaneous allergen immunotherapy and the response to epinephrine". Allergy and Asthma Proceedings 32 (4): 288–94. doi:10.2500/aap.2011.32.3446. PMID 21781404. [35] Rank MA, Oslie CL, Krogman JL, Park MA, Li JT (Jul-Aug 2008). "Allergen immunotherapy safety: characterizing systemic reactions and identifying risk factors". Allergy and Asthma Proceedings 29 (4): 400–5. doi:10.2500/aap.2008.29.3141. PMID 18702889. [36] Greineder DK (Dec 1996). "Risk management in allergen immunotherapy". Journal of Allergy and Clinical Immunology 98 (6 Part 3): S330–4. PMID 8977545. [37] Fernández-Távora L, Justicia JL, Moreno C, Tabar AI, Vidal C. (Jul 2011). "Safety evaluation of rapid build-up schedules with IR-standardized allergen extracts for subcutaneous immunotherapy of allergic respiratory diseases". Expert Opinion on Drug Safety [Epub ahead of print] 10 (6): 947–55. doi:10.1517/14740338.2011.603724. PMID 21770817. [38] Bernstein DI, Epstein T, Murphy-Berendts K, Liss GM (Jun 2010). "Surveillance of systemic reactions to subcutaneous immunotherapy injections: year 1 outcomes of the ACAAI and AAAAI collaborative study". Annals of Allergy, Asthma, and Immunology 104 (6): 530–5. doi:10.1016/j.anai.2010.04.008. PMID 20568387. [39] Dahl R, Kapp A, Colombo G et al (August 2006). "Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal

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External links

• "American Academy of Allergy, Asthma, and Immunology" (http:/ / www. aaaai. org/ patients. stm) information and articles of interest.

• "American College of Allergy, Asthma, and Immunology" (http:/ / www. acaai. org) information and articles of interest.

• "American Board of Allergy and Immunology" (http:/ / www. abai. org) American Board of Allergy and Immunology

• "Allergies" (http:/ / health. rutgers. edu/ brochures/ allergies. htm), from Rutgers.edu

• "Allergy shots, allergy immunotherapy" (http:/ / www. asthmahelpline. com/ allergy-shots. htm) FAQs on Allergy Immunotherapy. • D'Souza MF, Pepys J, Wells ID et al (June 1973). "Hyposensitization with Dermatophagoides pteronyssinus in house dust allergy: a controlled study of clinical and immunological effects". Clin. Allergy 3 (2): 177–93. doi:10.1111/j.1365-2222.1973.tb01320.x. PMID 4131252.

Sublingual immunotherapy

Sublingual Immunotherapy is method of allergy treatment that uses an allergen solution given under the tongue, which over the course of treatment, reduces sensitivity to allergens. Sublingual immunotherapy, or SLIT, has a very good safety profile and is given at home in adults and children.[1] As more patients are treated with SLIT, additional side effects are being studied. A serious anaphylactic reaction occurred in a patient being treated with multiple allergens prepared from commercially available US extracts.[2] The basis of sublingual immunotherapy is treatment of the underlying allergic sensitivity. Allergic symptoms improve as the allergic sensitivity improves. As a safe and effective method of treating the underlying disease, sublingual immunotherapy is capable of modifying the natural progression of allergic disease which can begin with allergic food sensitivities and eczema in young children and progress through allergic rhinitis and asthma in older children and adults. A recent study, published in Allergy 2007: 62: 943–948, showed that a 3-year course of Sub-cutaneous immunotherapy had long-term clinical effects, by significantly reducing the development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment. In a recent review of ALL studies on SLIT by the American Academy of Allergy, Asthma and Immunology published in Journal of Allergy and Clinical Immunology, 2007: 6: 1466-1468, 35% of studies resulted in significant reductions in medications and symptom scores but 38% of studies found no significant benefit from SLIT. When SLIT did work, it was typically less effective than with conventional subcutaneous injection immunotherapy and sometimes SLIT took two years to show significant clinical benefit. Sublingual immunotherapy 138

Mechanism Sublingual immunotherapy is taken as drops or tablets, placed under the tongue 3 or more times/week, containing a specific allergen which interacts with the immune system to decrease allergic sensitivity. Commonly the allergen is taken once a day. The antigen persists on the mucosal surface and is taken up by dendritic cells which interact with T lymphocytes (T-cells). Sublingual immunotherapy takes advantage of each individuals ability to develop immunologic tolerance to non-pathogenic antigens such as those in foods and in resident bacteria. Consider the vast number of antigens we are exposed to every day which do not elicit an allergic response. Dendritic cells in the oral mucosa act as antigen presenting cells (APC) to T-cells in the cervical lymph nodes. This system modulates the allergic response by creating immune tolerance to antigens. The sublingual mucosa also has pro-inflammatory cells, such as mast cells, which is the reason that SLIT sometimes results in local reactions. The dose progression used is critical to the relative safety margin of sublingual therapy. Early in treatment, sublingual dendritic cells secrete interleukin 10 (IL-10) which induces regulatory T cells to inhibit the inflammatory response.[3] Long term changes that occur with immunotherapy include a decrease in mast cell sensitivity and a decrease in IgE production by B-cells. With sublingual immunotherapy there is a decrease in the IgE/IgG4 and a decrease in the TH1/TH2 ratio. Allergic symptoms improve as the underlying basis of the allergic disease improves.

History Specific immunotherapy has been practiced for almost 100 years. Classical immunotherapy by subcutaneous injection was demonstrated by Noon[4] and Freeman in 1911. The oral route of immunotherapy was suggested earlier in 1900 [5]. Clinical attempts to determine the best dose and route for allergy therapy increased dramatically in the 1920s and 1930s.[6] Injection of allergen became the standard therapy based in part on many scientific trials showing the effectiveness of that method for pollen, mold, dust mite, stinging insect, cat, and dog allergies. Injection therapy for foods resulted in a number of deaths and was abandoned by mid-century. Clinical use of sublingual immunotherapy for foods was described in 1969 by David Morris[7]. Recent preliminary reports of success in inducing tolerance to peanuts and a few other foods are promising, but still investigational. SLIT was reintroduced in 1970 for inhalant allergens.[8] Although some patients treated for food, pollen, pet dander and mold allergy by sublingual immunotherapy appeared to improve, the ideal dose, degree of expected improvement, and the mechanism by which improvement occurred was not established, and few studies were published in peer reviewed journals until the 1990s. Controlled clinical trials first in Italy and later in England and throughout Europe have clearly shown the effectiveness of SLIT in the treatment of allergic rhinitis and asthma when due to one pollen. A few studies have been published in the US. The mechanisms involved have been studied, and the ideal dose range for some items (for example Timothy grass) have been established. In general SLIT is about 1/2 to 2/3 as effective as subcutaneous injection therapy, when optimal doses of a single pollen are used. Studies involving patients who require treatment with multiple pollens have shown less efficacy, and there is more concern about safety when multiple items are included in the treatment plan as well. The practice of sublingual immunotherapy has been more available in Europe than in the United States. Concerns regarding the risks of oral and injection immunotherapy have always included death from anaphylaxis[9]. Because of the higher risks of injection therapy in the 1980’s formal research into alternatives to injection therapy was supported in Europe. These studies demonstrated the relative safety and apparent effectiveness of sublingual immunotherapy, which resulted in widespread international acceptance of the method. In 1998 the World Health Organization concluded that sublingual immunotherapy was a viable alternative to the injection route and that its use in clinical practice is justified.[10] Public acceptance facilitated the publication of new research. Between 1990 and 2005 more Sublingual immunotherapy 139

than 40 controlled trials with non-injection routes were published in peer-reviewed journals.[11] Today in Europe, sublingual immunotherapy accounts for 40 percent of allergy treatment. In the United States, although sublingual immunotherapy is being tried by some practitioners of allergy it is considered an investigational therapy. There is no FDA approved product or protocol, and the procedure must be paid for directly by the patient because neither the safety nor the efficacy of the procedure is considered established. For example, current Medicare guidelines state "For antigens provided to patients on or after November 17, 1996, Medicare does not cover such antigens if they are to be administered sublingually, i.e., by placing drops under the patient’s tongue. This kind of allergy therapy has not been proven to be safe and effective. Antigens are covered only if they are administered by injection."[12] For more information on the current status of SLIT in the US visit AAAAI.ORG [13] or ACAAI.ORG [14].

Comparison to other allergy management regimens Options for managing allergy include avoiding what you're allergic to, such as not eating a food you have a known problem with, avoiding pets, etc. Many allergens are unavoidable due to the widespread nature of dust, molds, pollens, weeds, and various food elements in packaged and processed foods. A limitation of avoidance is that low levels of exposure to antigens allows the immune system to modulate the allergic sensitivity through T regulatory cells which are short lived. The allergic sensitivity persists much longer so that intermittent exposure is more problematic than frequent low level exposure. Symptomatic treatment options for allergies include over the counter medications such as antihistamines, prescription oral medication, nasal sprays and short-term prednisone. Biologics such as anti-IgE anti-bodies have been used in severe cases. While there is a role for all of these options, Allergy immunotherapy is the only treatment directed at resolving the underlying cause of allergy symptoms. Currently, immunotherapy is offered via allergy injections (allergy shots) for inhalation allergies although not for foods. Sublingual immunotherapy (allergy drops and tablets) is offered for inhalation allergies and foods. Like injection therapy, sublingual immunotherapy directly changes the body’s ability to react with allergens. Following successful treatment with immunotherapy, allergy symptoms are less apparent or at least less problematic.

Side Effects Because sublingual drops are used several times per week, it is necessary to take them at home. This is in contrast to injection therapy, which is usually taken in a medically supervised setting due to the risks of anaphylaxis (about 1/2000) and death (about 1/2,500,000). In the early years of SLIT local sensitivities were reported in many patients (oral itching, intestinal disturbances) but these could usually be managed by dose adjustments. Although as of July 2009 no deaths have been reported from SLIT (and many millions of doses have been taken), numerous cases of anaphylaxis have now been reported. In one study, for example, sixty patients who ranged in age from 6 to 50 years were treated over a 90-day period with a progressive dose of dust mite antigens via SLIT. In this small study alone there were seven systemic reactions (meaning, atopy, a reaction that occurs through the whole body, not just where the allergen is applied). All reactions were associated with wheezing or worsening nasal symptoms, and one patient had angioedema and urticaria.[15] Sublingual immunotherapy is safe during pregnancy, as has been reported for the first time in a recent study in Allergy (European Journal of Allergy and Clinical Immunology),[16] This study also showed safety when sublingual immunotherapy is initiated for the first time in a pregnant patient. Sublingual immunotherapy 140

References [1] Gidaro G, Marcucci F, Sensi L, Incorvaia C, Frati F, Ciprandi G (2005). "The safety of sublingual-swallow immunotherapy: an analysis of published studies". Clin Exp Allergy 35 (5): 565–71. doi:10.1111/j.1365-2222.2005.02240.x. PMID 15898976. [2] Dunsky EH; Goldstein, MF; Dvorin, DJ; Belecanech, GA (2006). "Anaphylaxis to sublingual immunotherapy". Allergy 61 (10): 1235. doi:10.1111/j.1398-9995.2006.01137.x. PMID 16942576. [3] Moingeon P, Batard T, Fadel R, Frati F, Sieber J, Van Overtvelt L (2006). "Immune mechanisms of allergen-specific sublingual immunotherapy". Allergy 61 (2): 151–65. doi:10.1111/j.1398-9995.2006.01002.x. PMID 16409190. [4] NOON L (1953). "Prophylactic inoculation against hay fever". Int Arch Allergy Appl Immunol 4 (4): 285–8. doi:10.1159/000228032. PMID 13096152. [5] Curtis HH. (1900) The immunizing cure of hayfever. Med News (NY);77:16-8. [6] Black JH. (1927) The oral administration of pollen. J Lab Clin Med;12:1156 [7] Morris D (1969). "Use of sublingual antigen in diagnosis and treatment of food allergy". Ann Allergy 27 (6): 289–94. PMID 5785921. [8] Morris D (1970). "Treatment of respiratory disease with ultra-small doses of antigens". Ann Allergy 28 (10): 494–500. PMID 5521180. [9] Reid M, Lockey R, Turkeltaub P, Platts-Mills T (1993). "Survey of fatalities from skin testing and immunotherapy 1985-1989". J Allergy Clin Immunol 92 (1 Pt 1): 6–15. doi:10.1016/0091-6749(93)90030-J. PMID 8335856.. [10] Bousquet J, Lockey R, Malling H (1998). "Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper". J Allergy Clin Immunol 102 (4 Pt 1): 558–62. doi:10.1016/S0091-6749(98)70271-4. PMID 9802362. [11] Canonica G, Passalacqua G (2003). "Noninjection routes for immunotherapy". J Allergy Clin Immunol 111 (3): 437–48; quiz 449. doi:10.1067/mai.2003.129. PMID 12642818. [12] Medicare National Coverage Determinations Manual; Chapter 1, Part 2 (Sections 90 – 160.25), Page 14. Coverage Determinations (Rev. 45, 12-06-05)110.9 – Antigens Prepared for Sublingual Administration (Rev. 1, 10-03-03)CIM 45-28

[13] http:/ / AAAAI. ORG

[14] http:/ / ACAAI. ORG [15] Rodriguez-Perez, et al. Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy. Annals of Allergy, Asthma and Immunology 2008; 101:304-310. [16] Shaikh WA, Shaikh SW. A prospective study on the safety of sublingual immunotherapy in pregnancy. Allergy 2012; 67 : 741-743.

External links

• The World Allergy Organization (http:/ / www. worldallergy. org)

• About.com Article on Sublingual Immunotherapy (http:/ / allergies. about. com/ od/ allergyshots/ a/ slit. htm)

• PubMed article (http:/ / www. ncbi. nlm. nih. gov/ pubmed/ 15575924?dopt=Abstract) Article Sources and Contributors 141 Article Sources and Contributors

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Fruit allergy Source: http://en.wikipedia.org/w/index.php?oldid=483567089 Contributors: Anna Frodesiak, Arcadian, Discospinster, Good Olfactory, GregorB, Hu12, Masamage, Ninjagecko, Nmacpherson, Sarahjdube, Scj0x, Snocrates, Steve2011, Wingsandsword, 10 anonymous edits

Peanut allergy Source: http://en.wikipedia.org/w/index.php?oldid=491538779 Contributors: AThing, Acalamari, Agamlen, Agateller, AlexHorovitz, Alisonnbecca, Allens, Allergy-mom, Allonym, Amruk, Andrewpmk, Antandrus, Apers0n, Arancaytar, Arcadian, Asbruckman, Bennetto, Bfmbomb, Biologos, Blake-, Bobby122, Bryan26, CSZero, Calmer Waters, Chezsruli, Cool3, Cplbeaudoin, Creavolution, Cyclopia, Danyak501, Daveswagon, DavidOaks, Deglr6328, DerHexer, Dr.booklovarrr, Dragon 280, Driftwoodzebulin, Eric Tittley, Farmerboy7311, Flamingspinach, ForestJay, Fullmetal2887, Gale Thurston, Gardsmyg, Gilliam, Good Olfactory, Gpr137, Grayshi, Grendlefuzz, Grover cleveland, Gusmovies, Hawesinsky, Headbomb, Hoyitsmykey, Hu12, Iepeulas, Iluvuzumaki, JHunterJ, Jeffrey.Rodriguez, Jesup, Jesuschex, Jfulgham, Jkister, Jredmond, Justintbassett, Jwoodger, Keilana, KelleyCook, Kinkyturnip, KristiJ, LafinJack, Legitimus, Libro0, Lilsnugg, Llenden, Londonsista, MER-C, MaccerTW, Mastrchf91, Matchups, Mdebets, Mentifisto, MichaelMaggs, Microcell, Mild Bill Hiccup, Misshappy123, Munblog, Mzinno, Nadyes, Nakon, Nerdonomics, NorthernThunder, Northerncedar, Nuttyvideo, PhilKnight, Phlegat, Picapicachu, Pmather, Predecess, Pseudomonas, Puffdaddy206, Pwoez, RDBrown, Radon210, Rjwilmsi, Ronhjones, Ronz, Rory096, Rreagan007, Sciencewatcher, Sebastian Goll, Sepeople, Shawje, Shogun 220, Shouriki, Skomorokh, Smiler jerg, Snocrates, Spinner2243, Stevegallery, Sudokyou, Tannline, Tarajo261, TastyPoutine, The Anome, Themfromspace, Thumperward, Tide rolls, Tomhubbard, Torontonian1, Tringm, Veinor, WhatamIdoing, White Trillium, Wikiabilly, Will Bradshaw, Xtcy3, 210 anonymous edits

Seafood allergy Source: http://en.wikipedia.org/w/index.php?oldid=486133659 Contributors: Aboutsellular, Acather96, Anna Frodesiak, Arcadian, Breakpoint, Circeus, Darth Panda, Digfarenough, Franamax, Good Olfactory, Hu12, Jmh649, Kb1, KristiJ, Nakon, Omer42, Reconsider the static, Relevantsus, Ronhjones, Ronz, Snocrates, Sudokyou, Tide rolls, Trevor Andersen, Tringm, Vincentanandraj, 32 anonymous edits

Soy allergy Source: http://en.wikipedia.org/w/index.php?oldid=481568685 Contributors: Ab762, Alan Joe Skarda, Anna Frodesiak, Apers0n, Arcadian, Asbruckman, CardinalDan, DO11.10, Davidruben, Delirium, Dr Zak, Eyreland, Fplay, Glesage, Good Olfactory, Greenwoodtree, Hildebrand the Editor, Hu12, Hunter1084, JamesBWatson, Jfdwolff, Keilana, Kelly2357, KristiJ, Mervyn, Mikeandjoedc, N. Harmonik, Nakon, No1lakersfan, Pearle, Rcmaster52, Rdrobertson, Rich Farmbrough, Rjwilmsi, Roger wilco, Ronz, Rufus843, Seooptimization, Snocrates, Sudokyou, Tgeairn, Veggieburgerfan, Veinor, WLU, Weird.Tesseract, Wmahan, 75 anonymous edits

Tree nut allergy Source: http://en.wikipedia.org/w/index.php?oldid=475264933 Contributors: Alan Liefting, Anna Frodesiak, Anna Lincoln, Arcadian, Asbruckman, Ashdenej, Chromancer, Circeus, Eric Tittley, Eric Yurken, Falcon8765, Flewis, Good Olfactory, Johngagon, Katalaveno, Loganberry, Mikeandjoedc, Nageh, Nerdonomics, Nuttyvideo, Penh, Rich Farmbrough, Themfromspace, Thumperward, Tide rolls, WhatamIdoing, 28 anonymous edits

Wheat allergy Source: http://en.wikipedia.org/w/index.php?oldid=492577285 Contributors: 2over0, Alan Liefting, Anna Frodesiak, Arcadian, Asbruckman, BD2412, Blahmos, Calaka, Capricorn42, Coccyx Bloccyx, CopperSquare, Creavolution, Csylcox, CuriousHumanoid, Dcfleck, Derecksuede, Discospinster, Drmies, Dweller, Echuck215, Edward, Elanaspantry, Elkman, Eubulides, Fan-1967, Ghedgepath, Good Olfactory, Hu12, Ian Glenn, InFairness, Iridescent, Jenmitch, Jim1138, Johner, Kitsunegami, KristiJ, KuroiShiroi, LilHelpa, Loren.wilton, Mdaa65, Michael Bailes, Mikeandjoedc, Miracle Pen, Nakon, Neeznoodle, Nimbex, Offshored2009, Omer42, Pdeitiker, Pearlshaynea, Prestonmcconkie, RainbowOfLight, Rhombus, Rich Farmbrough, Rjwilmsi, Rkielty, Ronz, SherlockEagleEyes, Shropman, Snocrates, Socrates2008, Spark010, Sudokyou, THEN WHO WAS PHONE?, TastyPoutine, Veinor, Wingman4l7, 95 anonymous edits

Gluten sensitivity Source: http://en.wikipedia.org/w/index.php?oldid=491932423 Contributors: ACEOREVIVED, AManWithNoPlan, Alan Liefting, Anna Frodesiak, Apostolos Margaritis, Arcadian, Balloonguy, BishopBandita, Black Falcon, BlackTerror, CailanMacLaren, Calliopejen1, Chowbok, Chrismarritt, Coachs, Colonies Chris, Cyfal, DBragagnolo, Dhfreedman, Dspradau, Edgar181, Elem1, Freestyle-69, Gabi S., Gaius Cornelius, Giftedlyarsenine, Glacialfox, GregorB, H Padleckas, Hassocks5489, Haymouse, Ibjoe, Imaglang, Isabel.hoffmann, Issaclofkrofski, Itub, Jesse Viviano, Jfdwolff, Johner, Johnnyblizzard, Kay Dekker, Keilana, Kslays, Kznf, LanguageMan, Laughs8, LilHelpa, Lt. penguin, Marwan soft, Meegs, Merehap, Michael Devore, Mind my edits, Nerdonomics, Nereocystis, Odoncaoa, Oolong, Orangemarlin, PamD, Pdeitiker, Phil Bridger, Ratel, Rich Farmbrough, Rknasc, RobinHood70, Ronz, SGGH, Scarian, Sciencewatcher, Siddhant, SilkTork, Skandha101, Socrates2008, Splitpeasoup, Susan118, Tide rolls, Tlabshier, TonyHagale, Tsjackso, Wai Hong, Wongcksimon, 299 anonymous edits

Allergic contact dermatitis Source: http://en.wikipedia.org/w/index.php?oldid=492407646 Contributors: Anna Frodesiak, Arcadian, Dermakarine, Epgui, Euchiasmus, Kjkolb, Mikael Häggström, My Core Competency is Competency, Svineviken, 7 anonymous edits

Drug allergy Source: http://en.wikipedia.org/w/index.php?oldid=423194553 Contributors: Arcadian, C6541, Cmcnicoll, Cyclonenim, Spitfire19, WhatamIdoing, 5 anonymous edits

Latex allergy Source: http://en.wikipedia.org/w/index.php?oldid=491781850 Contributors: Aboutsellular, Adamregan, Alex.tan, Anna Frodesiak, Arcadian, Bbrottlund, Beccles, Biosthmors, Brat32, Cburnett, Ceyockey, Chrisjw37, Denbyhunter, Dina, Druep, Edawgrules, Erich gasboy, Esuroon, Flowanda, Fortunecookie289, Gabbe, Gaius Cornelius, Hardin MD, Haz7po5, Imroy, Iridescent, Jag123, Jfdwolff, L Kensington, LOL, Leeatcookerly, MSTCrow, Matthieu.berthome, Mmoople, NotWith, Richard Arthur Norton (1958- ), Rjwilmsi, Sammka, SchuminWeb, Srich32977, TheVixenZozo, Tisdalepardi, Una Smith, Versageek, WhatamIdoing, Wikieditor06, Wossi, Wrighthere1710, 55 anonymous edits

Insect sting allergy Source: http://en.wikipedia.org/w/index.php?oldid=432593245 Contributors: Anna Frodesiak, [email protected], Ginkgo100, Jasefpotez, Komischn, Nazgul02, Skysmith, Stepp-Wulf, Unibusuk, 1 anonymous edits

Cat allergy Source: http://en.wikipedia.org/w/index.php?oldid=488920402 Contributors: Adrianhon, AgentPeppermint, Anna Frodesiak, Anthonyhcole, Bobo192, Booyabazooka, Bushcarrot, ChristineVH, Cluth, CopperSquare, Creavolution, Debhart, Djsasso, Dodo bird, Dr. Root, DrYak, Ekm02001, Emrklnd, Eostrom, Epbr123, FCYTravis, Foxj, Guesswhattt, Guswut, Haakon, Ifny, ItsWolfeh, Jmunroo, Jrcla2, Juhachi, Kaldari, Kilo-Lima, Kwiki, Lhagar, Luckas Blade, Mikael Häggström, Modden, MrArt, Paulh1221, Petclubuk, PhoenixMourning, Piano non troppo, Popoki, Quincunxcats, Ramdrake, Rhrad, Rjwilmsi, Rockpocket, RoyBoy, Runtime, Scarian, SiobhanHansa, Skycat, Spettro9, TastyPoutine, Tea with toast, Thue, Vicenarian, Woohookitty, Zachary crimsonwolf, Zero Serenity, 155 anonymous edits

Perfume allergy Source: http://en.wikipedia.org/w/index.php?oldid=490489701 Contributors: Anna Frodesiak, D6, EncMstr, Headbomb, Joneal122689, Martinor, Mikael Häggström, Nelson50, Passportguy, Trafford09, Wideangle, Xezbeth, 10 anonymous edits

Skin allergy test Source: http://en.wikipedia.org/w/index.php?oldid=483509136 Contributors: ADX99, Aaaai.official, Addere, Alltat, Anna Frodesiak, Anypodetos, Arcadian, Cmcnicoll, Frap, GeeJo, Gilbertryan, Hallows AG, Hu12, Iridescent, Jbrwilkinson, Jmh649, Kauczuk, Menue, Mikael Häggström, My Core Competency is Competency, Ophello, Pizik, Psycho katie, Purifiedwater, Rjparks, Shingra, Skysmith, SteveNenninger, Svineviken, Verbal, WhatamIdoing, William Avery, Zeeshan naseer, Zzzegan, 22 anonymous edits

Patch test Source: http://en.wikipedia.org/w/index.php?oldid=487185654 Contributors: Alexxandros, Anypodetos, Arcadian, Atompowered, Auntof6, CommonsDelinker, Cyclonenim, Freyr, Gaius Cornelius, Gorouhi, HenkvD, Ian Pitchford, Jan Polák, Jmath666, Jzm7aam, Pristino, SchreiberBike, Stevenfruitsmaak, Svineviken, Uncle Milty, 11 anonymous edits

RAST test Source: http://en.wikipedia.org/w/index.php?oldid=460937318 Contributors: Ahoerstemeier, Allmightyduck, Arcadian, Awr01, Baa, Bluemoose, Boing! said Zebedee, CXCV, Cheeseslice31, Chowbok, Cmcnicoll, Doctorsclinic, Jojo 1, Jonnyosgood, Kharker, Ldamico, Medic2008, Mikael Häggström, Nbrad01, Oddben, Remuel, Shingra, Sinamore, TechPurism, Tide rolls, Travis.Thurston, Tristanb, Verbal, Wickertu, Wouterstomp, 27 anonymous edits

Elimination diet Source: http://en.wikipedia.org/w/index.php?oldid=487522284 Contributors: 7mike5000, Aesopos, Asher196, BD2412, Cacycle, Crohnie, Deathlaser, Dennis Brown, Eloerc, Gaius Cornelius, Gsmckinney, Haafling, Imasleepviking, ImperfectlyInformed, Jagra, Ken634, Kfesko, LeadSongDog, Orangemarlin, Peerev, PigFlu Oink, Realkyhick, Rich Farmbrough, Ronz, Solace098, Tabletop, Una Smith, WhatamIdoing, 12 anonymous edits

Feingold diet Source: http://en.wikipedia.org/w/index.php?oldid=491784875 Contributors: A. B., Andiron, BD2412, Bender235, BradBeattie, BullRangifer, Chriswaterguy, Critical Chris, Deli nk, Deon Steyn, Drake144, Dyanega, Edgar181, Edward, Eyu100, Greswik, Harryboyles, Hordaland, Kamal006, Kilom691, LilHelpa, Matthewpcsmith, Melaen, Notbad, Oddharmonic, Pstrous, Qwertyas9, RDBrown, Random user 39849958, Rich Farmbrough, Rjwilmsi, Ronz, Sam Blacketer, Shulae, Slashme, Speace, That Guy, From That Show!, Thiseye, Tmassey, Txh190, WhatamIdoing, 26 anonymous edits

Allergen immunotherapy Source: http://en.wikipedia.org/w/index.php?oldid=491913766 Contributors: AManWithNoPlan, AaronM, Ageekgal, Ailinxu, Aminigh, Arakin, AySz88, BBerryhill, BayaniMills, Betacommand, Blagov, Blankfaze, Bongomatic, Clemdudu, Curious1i, DO11.10, DWizzy, Darkwind, Dawaegel, E rulez, Editor2020, Emperorbma, Esprit15d, Gaius Cornelius, Article Sources and Contributors 143

Gary Cziko, Gary0033, Gidip, Grick, Gurch, Hebrides, Hmwith, J04n, Jacosi, Jfdwolff, Jkbrat, Jusdafax, Kaszeta, Kenkoo1987, Kuplukjaya, Lectonar, Lennep, Literaturegeek, MarcoTolo, Mild Bill Hiccup, Minerva9, Mmpenland, NNemec, Nabokov, Nihiltres, Omer42, Pricebank, RDBrown, Rholton, Ronz, Russss, Sakkura, Shellac, Stevenfruitsmaak, SummerPhD, Tatsundo h, Tea with toast, Thue, Tideflat, Tossh eng, TotalFailure, Totsubo, Trevyn, Verbal, Woohookitty, 68 anonymous edits

Sublingual immunotherapy Source: http://en.wikipedia.org/w/index.php?oldid=492059614 Contributors: Ahendrickson, Atama, Belovedfreak, Bluedustmite, Carpetman2007, Causa sui, DO11.10, DanielRigal, Debresser, Doctorsclinic, Drwiqar, FironDraak, Flghtmstr1, Hbent, Hightowe, Jimthompson md, Kenkoo1987, Lyhan1000, Neon1000, NoSneezeZone, Pearle, Redrose64, Rfwilliam, Saylormd, Seeger7, Shablog, Sorcha niri, SunCreator, Thephotoman, Tim1357, Tmeyaart, Will Beback, Yobol, 57 anonymous edits Image Sources, Licenses and Contributors 144 Image Sources, Licenses and Contributors

File:Hives2010.JPG Source: http://en.wikipedia.org/w/index.php?title=File:Hives2010.JPG License: Creative Commons Attribution-Sharealike 3.0 Contributors: James Heilman, MD File:The Allergy Pathway.jpg Source: http://en.wikipedia.org/w/index.php?title=File:The_Allergy_Pathway.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: User:SariSabban File:Tissues Affected In Allergic Inflammation.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Tissues_Affected_In_Allergic_Inflammation.jpg License: Creative Commons Attribution-Sharealike 3.0 Contributors: User:SariSabban File:Allergy degranulation processes 01.svg Source: http://en.wikipedia.org/w/index.php?title=File:Allergy_degranulation_processes_01.svg License: Creative Commons Attribution-ShareAlike 3.0 Unported Contributors: Paweł Kuźniar (Jojo_1, Jojo) File:Allergy testing machine.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Allergy_testing_machine.jpg License: Public Domain Contributors: U.S. Air Force photo/Senior Airman Erin M. 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