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16 Feb 2017

Understanding the mechanism of allergy

Understanding the mechanism of allergy Understanding the mechanism of allergy

Allergy or allergic diseases are the names for conditions which can manifest in a variety of ways and are triggered by the high sensitivity of a person’s immune system to certain food products, materials, components of the air, parts of plants, and so on that in the majority of people do not cause any negative reaction. Allergies manifest in a variety of forms: runny or stuffy nose, skin rash, swelling, short wind, headaches, and so on.


The term "allergy" was first used by the Austrian doctor Clemens von Pirquet in 1906. He came up with the idea of a standalone condition upon noticing that some of his patients were showing inadequate response to usually harmless things such as pollen, dust, or certain foods. The doctor called the condition “allergy” based on the Ancient Greek word “allos” which means “other”. Based on the Pirquet theory, all forms of hypersensitivity have been started to be considered allergic reactions. It was though back then that all of them are triggered by an inadequate reaction of the immune system. However, later upon the studies of the matter, it had been discovered that there is a range of mechanisms that are responsible for a certain allergic reaction.

A new classification pattern was created in 1963 by Philip Gell and Robin Coombs. The new scheme included 4 kinds of allergic reactions also called type 1, 2, 3, and type 4 hypersensitivity. In the new classification, the term allergic reaction remained valid only for hypersensitivity type 1 which is also known as immediate hypersensitivity for which an immediate or quickly developing reaction is typical. The other types are currently referred to as atopic allergy or an inclination towards developing certain allergic reactions upon the contact with an allergen. Such allergies can be inherited but the contact with the allergen still has to occur before the allergic reaction develops in order to be sure that the atopy exists in a patient.

The major landmark event was the understanding of allergy mechanisms of action in 1966-1967. The find was made at the same time by two groups of scientists, one from Colorado and the second from Sweden.

Statistics and epidemiology of allergic diseases

Allergy is a common condition. According to the recent study, in the developed countries, around 20% of population is affected by allergic rhinitis; around 20% currently have or have had a history of atopic dermatitis, and around 6% of the population has at least one food allergy. In different countries, the amount of people who suffers from asthma which is also considered an allergic reaction is from 1 to 18%. In the USA, around 3% of the population suffers from asthma which makes almost 10 million of people.

The recent decades are marked by a pronounced increase in the frequency of allergies and atopies. Though it is considered that for atopic diseases genetics play the most important role, the growth of atopy that developed in such short period of time can be hardly explained by genetics. Therefore, ambient factors are considered the major ones. There are hypotheses that the increased spread of atopy is due to rising exposure to allergens while the baby is still in the womb. The advocates of this theory say that housing changes, decreased time spent outdoors, and improved overall hygiene can be causing inappropriate reaction of the immune system to pollution and natural substances such as pollen and certain food products. They also believe that the immune reaction changes and fails due to the large amounts of processed food and lack of exercise.

As for the statistics for allergic rhinitis and asthma, they are especially increasing in the developed countries over the last 2-3 decades. Researchers believe that this tendency is related to the high level of industrialization of such countries because in the developing world the numbers are much lower.
However, there are also other theories to explain this phenomenon:

A theory of hygiene involvement proposed in 1989 by David P. Strachan suggests that the increased hygiene in the second half of the 20th century prevents body contact with many antigens that cause a lack of loading to the immune system (especially in children). As a result, as our bodies are designed to fight a certain level of threats, the immune system starts to negatively react to harmless antigens. The theory was based on the fact that children from large families much less frequently suffered from allergic rhinitis and eczema than children who do not have siblings.

The epidemiologic data confirm this theory. The research shows that various immunological and autoimmune conditions are much rarer in people who live in the third world countries and that the emigrants from those countries who move to the developed countries start suffering from immune system disorders much more often the more time has passed since the date of immigration.

Long-term research in the developing countries also shows the increase of the immune system disorders as welfare and cleanness of the country growths. They also confirm that the administration of antibiotics in children during their first year of life, cesarean section, and the use of antibacterial cleaning products is correlated with the frequency of asthma development and other allergic reactions. However, we should note that these studies show only a correlation between these factors and not a cause and effect relationship.

Increasing consumption of chemical industry products. Other theory suggests that the increasing consumption of chemical products can also contribute to the increasing rates of allergies among population of the developed countries. Many chemical products can themselves be allergens or create conditions for the development of allergic reactions through the negative impact on the nervous and endocrine systems. However, despite many attempts to explain the sharp rise in allergic diseases influenced by man-made environment, it still has not been given reasonable explanation why the same factors have such an impact on some people and do not have the same effect on others. There wasn’t discovered any correlation between the general health of an individual and predisposition to allergic reactions.

Genetic predisposition

During the years of allergic disorders studies, it has been discovered that the chance of developing a disease highly rises if you have a history of certain allergies in your family. For example, children of allergic parents are much more likely to suffer from an allergy themselves and are the manifestations of the disease in them is likely to be more severe than in children of non-allergic parents. However, it doesn’t mean that they will have an allergy for the same product or environmental factor as their parents.

Statistically, if one of the identical twins suffers from a certain allergy, there is a 70% chance that the other twin will have the same allergy. The number is 40% for non-identical twins.

It is considered that children are more susceptible to severe allergy manifestations. The severity and frequency of allergic reactions usually drops between the ages of 10 and 30. For example, peak manifestations of allergic rhinitis usually occur in children and young adults and the first diagnosis of asthma usually is made in children less than 10 years of age.

In general, statistically, boys are more likely to develop allergies than girls, except asthma which occurs more frequently in females.

Classification of allergies by cause

Different people based on the genetic characteristics of the immune system have different reactivity with respect to different groups of allergens. There are identified the following groups of most common allergens:

- Dust and dust mites
- Foreign proteins contained in the donor plasma and vaccines
- Pollen (hay fever)
- Moulds
- Medications (most frequent allergens: Penicillin, Sulfonamide, Salicylates, local anesthetics)
- Food allergens
- Insects bites
- Animal products: animal dander, cockroaches, discharges of domestic mite, etc.

Most common allergens

A lot of people have food allergies but in 90% cases they are caused by these products: cow's milk, soy products, wheat, honey, chicken eggs, peanuts, various tree nuts, fish, and shellfish. Other food allergies occur in 1 individual in 10,000 and are considered rare.

In the USA, although peanut allergies are notorious for their severity, the most common food allergy is to crustacean (shrimp, crabs, lobsters, crayfish, krill, woodlice, and barnacles).

It is believed that the life-threatening manifestations of food allergies often occur if an individual also suffers from asthma and in much less degree if he or she has only the food allergy.

Some of the food allergies, for instance, peanut or chicken eggs allergies, can be overaged by the age of 5.

It is important to understand the difference between food allergy to milk and dairy products and lactose intolerance. Though these conditions manifest in a similar way, usually, irritation of the intestines and diarrhea, allergy is caused by the reactions caused by immunoglobulin E, a type of antibody that is in the basis of type I hypersensitivity or allergy. Lactose intolerance is caused by another factor – the lack of an enzyme responsible for lactose metabolism in the digestive tract. People who suffer from the condition can eat beef without any trouble while people with allergy to cow’s milk may develop also hypersensitivity to beef.

People who are allergic to one tree nut, for example, a walnut, may also be allergic to other nuts such as pistachios, hazelnuts, pecans, pine nuts. They also can have allergic reactions when eating sesame and poppy seeds.

Signs and symptoms

Allergy is characterized by general or local inflammatory response in exposure to allergens. The local symptoms include:

- Nose: swelling of the nasal mucosa (allergic rhinitis)
- Eyes: redness and pain in the conjunctiva (allergic conjunctivitis)
- Upper respiratory tract: bronchospasm, wheezing, shortness of breath, asthma attacks.
- Ears: stuffy sensation, ache and possible hearing loss due to the reduction of the eustachian tube drainage.
- Skin: various rashes eczema, contact dermatitis, and so on. The typical localizations of the allergy manifestations to food allergens are elbows (symmetrically), abdomen and groin.
- Mouth: aphthous stomatitis (damaged oral mucosa).
- Head: headache that occurs in some types of allergies.
- Cardiovascular system: allergic acute coronary syndrome (Kounis syndrome).

A systematic allergic response is called anaphylaxis. Depending on the level of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma and even death.

Stages of response to allergens

There are two types of responses to allergens based on the time that passes between the exposure to an allergen and the occurrence of allergic reaction:
- Acute or immediate response is caused by the excessive secretion of IgE plasmocytes and results in secretion of mucus, irritation of the nerve endings, contraction of the smooth muscle in the walls of blood vessels and internal organs. This is manifested in the form of a runny nose, itching, shortness of breath, anaphylaxis, as well as the formation of an inflammatory focus in the area of penetration of the allergen.

- Late response phase occurs when the action of inflammation mediators stops. It is caused by the migration of various types of leukocytes to the inflammatory focus which gradually substitute affected tissues with connective tissue. Usually, the late response phase develops 4-6 hours after the initial reaction and can last up to 1-2 days.

Complications of allergies

One of the most dangerous complications of allergy is anaphylaxis. It is manifested in a sudden occurrence of itching, then difficulty breathing, and a shock caused by the sharp drop in the blood pressure. The other symptoms of such manifestation of allergy are a weak thready pulse, excessive sweating and pale skin.

Rarely, anaphylaxis is aggravated with the swelling of the brain and lungs which can cause death.

Diagnosis of allergy

Diagnosis of the allergy must identify not only that a patient indeed has an allergic reaction but also the substance that causes the allergy.
The most popular allergy testing is skin puncture testing. The method implies multiple small punctures on a chosen area of skin, usually on the back, to which different types of the most common allergens are applied. The method allows seeing if a patient is allergic to a certain substance within 30 minutes based on the inflammation of the area to which a certain allergen was applied. The doctor then assesses the response to all allergens checked and gives a patient a list of the allergens with the level of danger they have based on the scale of severity for this particular individual. In case a serious life-threatening anaphylaxis can be suspected based on the previous manifestations of an allergy, before the test is made, doctors can decide to perform a preliminary blood test.

A patch test is another diagnosis method. It implies the application of patches with samples of the most common allergens to the selected area of the skin, also, usually on the back. The test takes more time to show results. Usually, the skin is checked for allergic reactions not earlier than 48 hours after the procedure and the second time 3 days after the procedure.

Blood testing is the most convenient test for allergy as it does not imply the application of possible allergens to the skin of the patient. The blood is taken from the vein, and then it is tested in a laboratory for the concentration of specific IgE antibodies responsible for certain allergies. The results are usually available within a couple of days.

Another method is a differential diagnosis. It is made to exclude allergens through the testing for other diseases and disorders that may look like an allergy. For example, a vasomotor rhinitis has the same symptoms as allergic rhinitis but requires a different treatment. In this case, a doctor should perform patient’s survey and examination in order to exclude the condition before sending the patient for taking allergens probes.

Other methods are considered ineffective and can be also life-threatening though some doctors decide on them if they think that there is a very low chance for a patient to receive any serious damage while being diagnosed in such a way. For example, one of such methods is called an Elimination/Challenge test. If a doctor suspects that a patient has an allergy to a certain food or medication, he or she can give them the instruction to completely exclude that substance from their diet. If a patient shows significant improvement of symptoms, the suspected allergen is then re-introduced and the symptoms are checked. If the patient starts experiencing the same symptoms again, the doctor can then make the diagnosis about the allergy presence to a certain product or substance.

Prevention of allergy

Currently, doctors consider that early exposure to potential allergens can prevent further development of an allergy. For example, previous guidelines for infants’ diet advised not to give any food that contains peanuts to children below the age of 3 but the latest update says it is better to incorporate peanut pasta in small amounts once an infant starts eating other solid food.

Current studies also prove that there is a link between the use of antacid medications and proton pump inhibitors during pregnancy and a chance of the baby to develop asthma. It is also not recommended to eat celery, citrus fruits, margarine, raw pepper, and vegetable oil in large amounts during pregnancy because they can increase the risk of future diagnosis of eczema in the baby.

To minimize the risk of allergy development in a baby, it is advised to consume antioxidants, zinc, selenium additives, and probiotic supplements during pregnancy.

For the people who already have an allergy, the prevention measures are aimed at reducing the exposure to allergens. For example, for people allergic to pollen they include:

- During the blossoming season, do not open windows unless they are covered with fine mesh or even better with a coal window filter.
- Do not dry clothes outdoors or on an open balcony.
- Try staying indoors between 11 AM and 6 PM, especially in dry and windy weather.
- When you are outdoors, put on sunglasses and a hat to ensure that the minimum amount of pollen can reach your mucosa.
- Once you get home, take a shower and wash your hair to get rid of all of the pollen residues.
- Rinse your nose several times a day with salty water.
- Do wet cleaning daily.
- Get an air filtering device, preferably with coal filter and make sure to replace cartridges regularly.

People who are allergic to dust mites are recommended to:

- Use pillows made from hypoallergenic fabrics.
- Wash bedclothes weekly in hot water.
- Eliminate all stuff that collects dust, especially in your bedroom, i.e. stuffed animals, a massive carpet, decorative pillows, and so on.
People who are allergic to mold are advised to keep their houses dry. For this purpose, it is advised not to have any home plants, fix all water leakages once noticed, do not stock vegetables such as potato in large amounts as when it spoils it develops mold.

Management with medications

Understanding the mechanism of allergy

The main treatment of any allergy is to avoid exposure to allergy triggers. If it is impossible, a person who suffers from it can use medications to suppress allergic reactions such as antihistamines, glucocorticoids, epinephrine (adrenaline), mast cell stabilizers, and antileukotriene agents.
Another way to prevent allergy attacks is to start immune therapy though it is believed not to be effective for food allergies. There are two main methods - Hyposensitisation and desensitization. They imply treatment in which the patient is gradually vaccinated with accruing doses of specific antigens. This can lead to the reduction in severity and the complete elimination of hypersensitivity.

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