Allergic and non-allergic hypersensitivity to food

Allergic and non-allergic hypersensitivity to food

Hypersensitivity to food can be divided into: allergic hypersensitivity and non-allergic hypersensitivity (also known as intolerance).
Examples of allergic hypersensitivity are food allergy and gluten intolerance (celiac disease) Examples of non-allergic hypersensitivity are lactose intolerance and intolerance to the food additive sulfite (sulphite).

Allergic Food Hypersensitivity

What is food allergy?
Our immune system protects our bodies from infections by producing molecules, called antibodies that specifically recognise the germs that cause infections. We produce a number of different types of antibodies (for example, IgE, IgG and IgM) that differ in their specific roles in the immune system. The antibody type, which may cause an allergic reaction, is called IgE. We produce IgE molecules to fight infections caused by parasites, like worms or those that cause malaria. We do not understand why, but the immune system of some people mistakenly produces IgE to harmless things like pollen or dust mites, giving rise to hay fever and asthma, and to some foods, giving rise to food allergies.

Food allergens (the specific components of food responsible for an allergic reaction) are usually proteins, and there are generally several kinds of allergens in each food. It is not yet clear what makes some proteins food allergens, and not others.

The development of an allergy occurs in two stages:

Sensitisation: when the allergic individual first encounters the allergen and is programmed to produce IgE which arms the immune system.
Reaction: upon any subsequent contact with the allergen, the now armed immune system is triggered to rapidly respond with inflammation, which leads to the allergy symptoms.

Sensitisation
When a person eats a food, the food may trigger immune cells to produce large amounts of IgE that specifically recognises that food. Sometimes the immune cells can even be triggered to produce IgE when a person breathes in tiny food particles, for example, dust from sunflower seeds when they are used to feed birds. The IgE circulates in the blood and attaches to the surface of specialized inflammatory cells called mast cells. These cells occur in all body tissues but are especially common in areas of the body that are typical sites of allergic reactions such as the skin and linings of the nose, lungs and gut. The person is then sensitized to the food and primed to produce an allergic reaction. However, it is possible to be sensitized to an allergen without developing symptoms.

Reaction
On any subsequent occasion when the person eats the same food, the food allergens interact with the specific IgE on the surface of the mast cells. In response, the activated mast cells rapidly release powerful inflammatory chemicals such as histamine (which is why anti-histamines are used to relieve allergy symptoms). Depending upon the tissue in which they are released, these chemicals will cause a person to have various symptoms of food allergy.

Non-IgE-mediated Allergies
Although IgE is normally involved in allergic reactions, the immune system is very complex and other immune pathways can sometimes be involved. An example is gluten intolerance (discussed later).

The allergy march
Various forms of allergic reactions often develop depending on age and contacts with different allergens, and these reactions tend to occur in succession. This is called ‘the allergy march’. Allergic reactions to food, such as gastrointestinal and skin symptoms, are often in the foreground in infants. Young children tend to have eczema, whereas problems in the airways, such as asthma, often become prominent between four and seven years of age. Hay fever occurs more often during puberty, although hay fever is also being diagnosed increasingly often in young children.

How common are food allergies?
This is a question that is very difficult to answer because different studies give different results. Many studies do not discriminate between food allergy and food intolerances. If people are randomly asked in surveys if they have food allergies, 3 - 35% answer that they do. If those people that suspect they have food allergy are challenged with the food that they think causes their allergy, only 1 - 11% have their food allergy confirmed. So there is a large gap between the frequency of perceived allergy by the general public and the true, clinically proven incidence.
It is also difficult to compare different studies because they use different ways of carrying out the study. Even studies from different countries using the same design show a large variation in how many people suspect they have food allergies, which suggests that there are true regional differences.

The EU project EuroPrevall will study the frequency of food allergy in different countries using the same methods and thereby get information on food allergy frequencies.

Foods that may cause allergy
More than 120 foods have been described as causing food allergies. However, the foods that most commonly causing serious allergic reactions on a worldwide basis are: Cereals containing gluten, milk, egg, tree nuts, peanuts, soybeans, fish, and shellfish. Several studies indicate that most allergic reactions among children are due to a limited number of foods, namely egg, peanut, milk, fish and tree nuts. Egg and milk allergy are often outgrown during the first years of life. Fruits, vegetables, tree nuts and peanuts are responsible for most allergic reactions to foods among adults. The foods that are common causes of allergic reactions, differ between geographical areas, as a result of dietary preferences.

Cross-allergies
Sometimes the immune system cannot differentiate between different proteins because they strongly resemble each other. For instance, individuals with pollen or latex allergy often experience allergic symptoms when they eat certain fruits, vegetables or nuts. This “cross-reactivity” occurs because the body cannot distinguish between the allergens in pollen or latex and related proteins in food and may react to both. In fact, up to 70% of food allergies can be connected to sensitisation to pollen. The most common symptom here is a tingling or irritation of the mouth, throat, and eyes. This is called Oral Allergy Syndrome (O.A.S.).

Examples of cross-reacting allergens are:

Birch – apple, hazelnut, carrot, celery, cherry, peer, walnut, peach, plum, apricot, Brazil nut, peanut
Mugwort - celery, carrot, fennel, parsley, mustard
Grass – orange, melon, tomato, peanut
Cow’s milk – goat's milk, sheep milk, beef (very seldom)
Peanut – soy beans, green beans, peas, lentils, lupine
Lentil – soy, peanut
Latex – banana, avocado, kiwi, chestnut, papaya, figs

Symptoms of food allergies
Symptoms of food allergies vary between different individuals, although an individual will tend to have the same reaction each time they consume an offending food. The symptoms of food allergies range from mild discomfort to severe, life-threatening reactions that require immediate medical intervention.

Allergic reactions to foods generally occur within a few minutes to one hour after eating the offending food. Symptoms can last for minutes through to days or even weeks. The symptoms generally arise every time the offending food is. However, if you are allergic to a food that cross-reacts with pollen you may only experience symptoms in the pollen season.

The specific symptoms and severity of an allergic reaction are affected by the amount of the allergen consumed, by the preparation of the food, and by the sensitivity of the allergic person. Some people can, for instance, better tolerate cooked than raw fruit and vegetables.

After inadvertently eating an offending food, the first symptom is often itching and perhaps swelling of the lips, mouth, and throat. Later symptoms may arise in the eyes, nose, lungs, gastrointestinal tract and skin.

Mouth
The most frequent symptoms of food allergies are itching and/or swelling of the mouth. Oral itching (known as Oral Allergy Syndrome) can be an initial symptom in any kind of food allergy. Oral itching is, however, a well known symptom in food allergy induced by cross-reaction with pollen, such as for instance by apple, kiwifruit, hazelnuts, walnuts, celery, carrot, tomato, cherry and melon. Most of the allergens in cross-reacting foods will be destroyed by digestion in the gastrointestinal tract. This explains why the symptoms are frequently mild and limited to the mouth. Most of the allergens in the cross-reactive foods will also be destroyed if the food is cooked. This explains, for example, why many birch pollen allergic people cannot eat raw apples without experiencing symptoms, but stewed apples and apple juice might not be a problem.

Eyes and nose
The eyes and nose may show hay fever-like symptoms. The eyes may swell, itch, and become red. Sneezing and an itchy and runny (or stuffed) nose may be experienced.

Lungs
Asthmatic symptoms such as wheezing, breathlessness and coughing may arise from the lungs.

The Gut
Symptoms from the gut include pain, bloating, sickness (nausea), vomiting, and diarrhoea.

Skin
On the skin, acute urticaria (often called hives or nettle rash) with itchy, well-defined white or pale red swellings can appear. This rash is generally short-lived, disappearing within a few days. Chronic nettle rash is rarely associated with food allergy.

Longer lasting, chronic skin reactions in the form of eczema are associated with food allergy, especially in children.

Anaphylactic shock
Anaphylactic shock is an uncommon, acute, potentially life-threatening and sometimes fatal allergic reaction involving the whole body.

A person who has this type of reaction will typically experience the following symptoms. First, itching of the skin or tingling in the mouth and throat followed quickly by feeling unwell and dizzy with an accelerated heart rate and nausea. At the same time, there may be a nettle rash or skin flushness, hay fever and asthma. Blood pressure may drop dangerously and the person may faint. Untreated anaphylactic shock can rapidly result in death.

An unusual form of this condition can be triggered by eating problem foods within 2-3 hours of vigorous exercising and is called exercise-induced anaphylaxis.

In Europe and the US, peanut and nuts are the foods most commonly reported to cause anaphylactic shock. Prompt administration of adrenaline after eating suspected problem foods has helped minimise life-threatening episodes, and applicators to administer adrenaline (Epipen or Anapen) can be carried by people who are aware that they are at risk of anaphylaxis.

Diagnosis
The aim of diagnosing food allergy is to determine if food is causing the symptoms and, if so, to identify specific causal food(s). Once correctly diagnosed, an allergy sufferer can then be provided with the relevant information on how to avoid the offending food(s). This may be more challenging than initially realised by the allergic patient, since some food allergens, such as egg, milk and wheat, are used widely in processed foods. However, equally as important, a proper clinical diagnosis can prevent unnecessary dietary restrictions by people who incorrectly assume that they have food allergies (a common occurrence).
The diagnosis of food allergy starts with a combination of an investigation into the patient's clinical history, a clinical examination and a test for the detection of IgE antibodies.

The first test is usually a test for the detection of food-specific IgE antibodies. Skin prick testing and blood tests are the main tests used for this purpose. However, the presence of specific IgE does not necessarily mean that a person will experience symptoms. Test results therefore need to be interpreted in view of clinical history and examination. Clear negative results demonstrate that there is no IgE-mediated allergy. However, either skin prick tests or blood tests for specific IgE are definitive tests for the disease. Rather tests for sensitization.

The reliability of results of specific IgE tests are dependent on the quality and stability of the food allergen extracts used. In some cases the test result is negative, but a patient may still have symptoms when consuming a food. Generally, test used by physicians are sensitive and efficient in ruling out allergy to a food when giving negative results. For optimal results it is important to use evaluated and well-documented tests and allergen extracts.

Both skin prick- and blood tests are suitable at any age of the patients. Even babies under one year of age are tested.

If possible, a so called blind provocation or challenge test with the suspect food should be performed. This involves introducing the food to the patient in gradually increasing amounts and is today seen as the reference method in diagnosing food allergic patients. These tests are performed under controlled conditions in hospitals.

Food allergy tests

Blood test for specific IgE
Several types of blood tests are available to test for food allergies. A blood sample has to be taken from the patient and analysed in a well-equipped laboratory. Therefore the results of the blood tests are not available immediately. Unlike for skin prick tests, antihistamines do not interfere with blood tests, which means that the blood tests can be used in patients with severe allergic symptoms from e.g. the skin without stopping the intake of antihistamines. With one blood sample it is possible to measure sensitization to many several allergens.

If the patients are allergic to the suspected food they will have specific IgE antibodies in their blood that will bind to the food allergens that are available in the test system.
One advantage with most blood tests is that results are reported in quantitative values. There is a relationship between the amount of specific IgE and presence of symptoms, strongly positive results are more associated with clinical reactivity than very low results and completely negative results are more associated with clinical tolerance than the low results. Thus, more information is obtained when using a test reporting quantitative values with a high precision compared to test reporting only results as positive and negative.

Skin prick testing
A tiny prick is made with a lancet through a drop of allergen placed on the skin, usually on the forearm. One prick for each allergen tested.
Itching within a few minutes will indicate a positive reaction. The site where the allergen was introduced then becomes red and swollen, with a raised weal in the centre that looks like a nettle sting. The weal enlarges and reaches its maximum size within 15-20 minutes, when the measurements of the weal are recorded. The reaction fades within an hour. The procedure and interpretation of results require experience.

Once the range of possible allergens has been narrowed down, challenge testing can then be used to confirm or exclude allergy.

The prick-prick test
This test is identical to the skin prick test, but instead of using a prepared allergen extract, the tester first pricks the lancet into a fresh food product and then, with the same lancet, pricks the skin. See skin prick test for further information.

Challenge testing
A challenge test involves giving the patient increasing doses of the suspected allergenic food, allowing ample time between doses for a response to occur. A medical specialist with a high degree of knowledge about food allergy must always supervise the performance of the challenge test. The challenge must be conducted within a medical facility with equipment and staff to deal with possible life-threatening reactions. A patient who has had a genuinely life-threatening allergic reaction, like anaphylaxis, should not be challenged with the food that caused it unless the challenge starts with extremely low dose.

Before oral food challenges, patients must avoid the suspected food(s) for at least 2 weeks. Regular antihistamine medication is also withdrawn. When performing the test the doses should be increased very gradually until a normal serving of the foods has been eaten. A negative challenge is valid only if no symptoms are observed following exposure to the problem food in a dose equivalent to a normal serving. The medical team will observe the patient for symptoms for up to several hours after the challenge.

For infants/small children an open challenge is the standard procedure.

For older children and adults, challenges are normally conducted in a double-blind manner with a placebo control (double-blind, placebo-controlled, food challenge, DBPCFC). In this test, neither the patient, nor the investigator knows whether the food preparation being given contains the specific allergen or a placebo. The suspected allergen or placebo will be hidden in a food matrix (recipe) consisting of foods normally tolerated by the patient.

Even though the DBPCFC test is the gold standard in food allergy diagnosis, the test may produce false negative results. The challenge procedure usually cannot reproduce the exact circumstances under which the patient experienced the adverse reaction.

Unproven diagnostic methods
Different Internet pages advertise many alternative diagnostic methods. Examples include measurement of food specific IgG antibodies, hair-analysis, cytotoxic tests, kinesiology, iridology, and electrodermal testing. The usefulness of these methods for food allergy diagnosis has not been proven by properly performed scientific studies. Hence, scientists and clinicians cannot recommend the use of these methods in the diagnosis of food allergy.

How to live with food allergy

Treatment
When treating a food allergy, the food product that causes reactions must be removed from the diet. This is often difficult and a risk remains that there will be accidental contact with the food allergen. For individuals at risk of severe allergic reactions, added measures such as the carrying of adrenaline may be necessary.

Diet
It is always necessary for individuals who have food allergy to follow a diet. This diet will sometimes need to be adapted because certain allergies can disappear, decrease and/or new allergies can occur after a time. Medical supervision is necessary and it is helpful to get advise from a dietician.

For young infants with food allergy, the most effective strategy to avoid reactions is to be breast-fed for four to six months (quite seldom, a child may react to food residues in the mothers milk). Additional food is often recommended from the age of 6 months and is introduced in a special order.

For older children and adults it is generally quite complicated to adhere to a diet. Supervision by a dietician is strongly advised to maintain as healthy and varied a diet as possible. Also adequate training to read food labeling is essential to prevent reactions to processed and prepared foods.

With food allergies, it is very important to avoid cross-contamination during food preparation, storage and serving. By this we mean “contamination” of food through spilling, spatters, crumbs, not separating the diet food well, and dirty hands, plates, or silverware. These can cause unintentional ingestion of the allergens and cause reactions.

Medication
Antihistamines reduce the symptoms that result from the release of histamines by mast cells. This medication can be used to suppress acute allergic symptoms during an allergic reaction. In general, antihistamines are only prescribed for patients over the age of one year.

In cases of a fast, life-threatening reaction (anaphylactic shock), an auto-injector should be prescribed (Epipen or Anapen). This is an injector filled with adrenaline that was specifically developed to be used by the medically untrained. This type of medication can be carried by people who know that they are at risk of anaphylactic reactions.

Prevention
If its family has a predisposition for allergies, there is a real risk that a baby will also develop allergic complaints.
Preventative measures can help prevent the child from developing allergic complaints in the long term.

Primary preventative guidelines for food allergies are:

Do not smoke during pregnancy.
During pregnancy, a special diet is not necessary. Just eat normal amounts of dairy products and eat as varied a diet as possible.
Do not smoke after the birth or in the environment of the child.
Breast-feed for at least 4 months, preferably for 6.
A special diet while breast-feeding has not been proven to be effective. Find out if a special diet is advisable during breast-feeding for your own particular situation. If this is the case, do it under the supervision of a dietician to ensure proper nutrition.
If breast-feeding is not possible, get advice on the best baby formula to use. Additional foods should be used after 6 months under the supervision of a doctor or dietician.

Gluten intolerance (Celiac disease)
Gluten intolerance also called celiac disease is a non-IgE-mediated food allergy. It is a disease of the small intestine triggered by ingestion of gluten. Gluten is a type of protein found in wheat, barley and rye. When a person with celiac disease ingests gluten an immunological reaction in the small intestine leads to flattening of the mucosa (villous atrophy). Normally we absorb most nutrients, vitamins and minerals in the small intestine. A flattened mucosa is not able to absorb nutrients, vitamins, and minerals very well leading to many of the symptoms of celiac disease.

It is estimated that about 1% of the population have antibodies connected to celiac disease. Celiac disease is thus an important public health issue. Because of the role of gluten in celiac disease, the Codex Alimentarius Commission Committee on Food Labelling has listed wheat and other gluten-containing cereals on their list of the foods and ingredients known to cause hypersensitivity.

Wheat can also trigger IgE-mediated food allergy, though this is not as common as celiac disease.

Symptoms
Celiac disease was for many years mainly diagnosed in small children. Within months of starting a gluten-containing diet, susceptible children would present with chronic diarrhoea or loose stools, vomiting, a distended abdomen and failure to thrive. Similarly, diarrhoea, weight loss, and general weakness are the most common symptoms in adults.

Today we know that celiac disease is a complex disorder with symptoms not only occurring in the gastrointestinal tract. Many symptoms and diseases are associated with celiac disease. For example, the villous atrophy caused by celiac disease leads to malabsorption of nutrients in the intestine. Poor absorption of iron can lead to anaemia, poor absorption of vitamin B12 can lead to dementia, and poor absorption of vitamin D and calcium can affect our bones and teeth. Celiac disease is also often found in connection with other immunological diseases such as diabetes and rheumatoid arthritis.

Diagnose
The accepted way to diagnose celiac disease in Europe is to see the flattened mucosa in a biopsy from the small intestine, and to observe that the symptoms disappear on a gluten-free diet.

People with celiac disease have an increased amount of certain antibodies when they eat gluten. These antibodies can be measured in a blood test. Measurement of antibodies cannot be used as positive proof for the disease. A blood test can, however, help decide whether to take a biopsy from the small intestine.

Treatment
A life-long gluten-free diet is the only treatment available for celiac disease. Products with wheat, rye and barley must be avoided. Most patients tolerate products with oat as long as they are free from contamination with other cereals containing gluten. Once on a gluten-free diet the flattened mucosa in the small intestine of celiac patients heals and the symptoms disappear.

Systemic contact dermatitis
Nickel
Persons with contact allergy to nickel may get skin symptoms if they eat food with high nickel content such as beans, chocolate, peanut and nuts. Electrical kettles with a heating element of copper plated with nickel or chromium may release amounts of nickel into the water high enough to induce symptoms. It is only a minority of nickel allergic persons that develop symptoms in this way.

Perfume
Although rare, persons with contact allergy to perfume may get skin symptoms when they eat spicy or aromatic foods.

Non-Allergic Food Hypersensitivity

What is non-allergic hypersensitivity?
Non-allergic hypersensitivity (also known as intolerance) does not directly involve the immune system and cannot be measured by allergy tests. Lactose intolerance is also a non-allergic hypersensitivity and reactions to food additives are mostly non-allergic.

How often does non-allergic hypersensitivity occur?
At this point in time, there is no data on the number of people suffering from non-allergic hypersensitivity.

Symptoms caused by non-allergic hypersensitivity
With non-allergic hypersensitivity, small amounts of a food can often be tolerated, while normal portions can cause symptoms. The body can tolerate one cookie which contains milk, for example, but three cookies or a glass of milk are too much, causing a stomach ache.
The level which causes complaints varies per person.
The symptoms of allergic and non-allergic hypersensitivity resemble each other. In general, the symptoms of non-allergic hypersensitivity are milder and there are rarely serious reactions.

Lactose intolerance
Lactose intolerance is a hypersensitivity to the lactic sugar (lactose) in milk. It is different from cow’s-milk allergy which is a reaction to the proteins in milk. Lactose intolerance is caused by a deficiency of the digestive enzyme, lactase. This causes lactose to be insufficiently absorbed through the intestines. When the lactose is not absorbed in the small intestine it is broken down by bacteria in the large bowel leading to stomach ache, gassiness, or (foaming) diarrhea after ingestion of normal portions of dairy products. Small portions of lactose rarely cause symptoms.

Lactose intolerance may be inborn (rare) but mostly appears during adolescence or early adulthood.

It is the normal condition in 75% of the human population, but is relatively rare in northern Europeans probably occurring in 3-6%.
Lactose intolerance may be transient in connection with intestinal infections.

Lactose in different diary products
1 glass of milk (2 dl): 9.4 g lactose
2 dl yoghurt: 5.0 g lactose
50 g feta cheese: 0.3 g lactose
1 slice of hard cheese (20 g): traces of lactose

Food additives
Food additives are a large and varied group of substances added to food to, for example, prevent growth of microorganisms, give colour or flavour, improve texture or prevent browning. There are few scientific investigations concerning food additives and hypersensitivity probably because it is a difficult subject to investigate. This is because there are many different food additives and relatively few people who react to any individual substances. This means that most descriptions of food additive hypersensitivity are based on very few patients. The one exception is sulfites. Sulfites are used as preservative and anti-browning agent and may be present in many different foods such as wine, beer, dried fruit and vegetables; white vegetables e.g. horse radish and sauerkraut, biscuits, crustaceans and mussels.

Hypersensitivity to sulfites is relatively well described especially in people with asthma and may also trigger skin reactions such as hives (urticaria).