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Allergies are hypersensitivities, overreactions of the immune system to substances that do not cause reactions in most people. Hypersensitivities are grouped into four types, I through IV. These classifications are based, to some extent, on what parts of the immune system are activated and how long it takes for a reaction to occur.

The two types of hypersensitivities commonly associated with the term “allergies” are type I immediate hypersensitivities, in which antigens (allergens, foreign substances) combine with specific IgE (immunoglobulin E) antibodies to cause local and sometimes systemic reactions, usually within minutes; and type IV delayed hypersensitivities, reactions caused by the interactions of antigens with specific sensitized T lymphocytes instead of antibodies.

According to the American Academy of Allergy Asthma and Immunology (AAAAI), as many as 50 million people in the United States have some type of allergy and the number appears to be increasing. While anyone can develop an allergy, those with affected family members are at an increased risk. A person who is “predisposed” may not, however, react to the same substances as his parents and siblings. It depends upon what antigens he is exposed to and his immune system’s response.

Type I hypersensitivities primarily affect the respiratory and gastrointestinal systems and the skin. The first time a predisposed person is exposed to a potential allergen, they will not have a major reaction; instead, they will begin producing a specific IgE antibody and become “sensitized.” Once someone is sensitized, subsequent exposures can result in severe reactions.

The IgE antibody produced attaches itself to mast cells, specialized cells in the tissues, and basophils in the bloodstream. This action primes the immune system. During subsequent exposures to the allergen, the specific bound IgE identifies the intruder, attaches to it, and triggers the release of chemicals, including histamine, causing allergic symptoms that start in the mouth, nose, or on the skin, wherever the allergen has been introduced.

Type IV hypersensitivities usually involve the skin and are defined as “delayed” hypersensitivities since the reaction typically appears about 48-72 hours after exposure. These reactions occur when an antigen interacts with specific sensitized T lymphocytes. The lymphocytes release inflammatory and toxic substances, which attract other white blood cells to the exposure site, resulting in tissue injury. No immune system “priming” is necessary; people can have a type IV reaction with the first exposure. A common example of this type of allergy is the reaction to poison ivy.

What is not an allergy?
There are other reactions that can cause allergy-like symptoms but are not caused by an activation of the immune system. They range from toxic reactions that affect anyone who has sufficient exposure, such as food poisoning caused by bacterial toxins, to genetic conditions, such as intolerances caused by the lack of an enzyme – for example, the inability to digest milk sugar, resulting in lactose intolerance, and sensitivities to things like gluten (in Celiac disease). Symptoms can also be caused by medications such as aspirin and ampicillin, food dyes, MSG (monosodium glutamate – a food flavor additive), and by some psychological triggers. While these diseases and conditions may need to be investigated by a physician, they are not allergies and will not be identified during allergy testing.

Symptoms
On the skin, an acute type I allergic reaction causes hives, dermatitis, and itching, while chronically, the allergy may cause atopic dermatitis and eczema. In the respiratory tract, an acute allergic reaction causes coughing, nasal congestion, sneezing, throat tightness, and, chronically, asthma. It can also cause red itchy eyes. Acute allergic reactions in the gastrointestinal system start in the mouth with tingling, itching, a metallic taste, and swelling of the tongue and throat, followed by abdominal pain, muscle spasms, vomiting and diarrhea, chronically leading to a variety of gastrointestinal problems.

Any severe acute allergic reaction has the potential to be life threatening, causing anaphylaxis, a multi-organ reaction that can start with agitation, a feeling of “impending doom,” pale skin due to low blood pressure, and/or a loss of consciousness (fainting). Anaphylaxis can be fatal without the rapid administration of an epinephrine (adrenaline) injection. Type I allergic reactions can be variable in severity, one time causing hives, the next time anaphylaxis.

Type I allergies can be in response to a variety of substances including but not limited to: foods, plants (pollens, weeds, grasses, etc), insect venoms, animal dander and saliva (such as cat and dog), dust mites, mold spores, occupational substances (latex), and drugs (such as penicillin). There can also be cross-reactions, where someone allergic to ragweed, for instance, may also react to melons (watermelon or cantaloupe) and banana. The most common food-related causes of severe anaphylactic reactions are peanuts, tree nuts such as walnuts, and shellfish.

Type IV delayed hypersensitivity reactions are most often skin reactions. A common example is the reaction to nickel in metal jewelry. Type IV hypersensitivity may cause redness, swelling, hardening of the skin, rash, and dermatitis at the exposure site hours to days after exposure.

Tests
The diagnosis of type I hypersensitivities starts with a careful review of the person’s symptoms, family history, and personal history, including: the age of onset, seasonal symptoms, and those that appear after exposure to animals, hay, or dust, or that develop in specific environments, such as home and work. Other environmental and life style factors such as exposure to pollutants, smoking, exercise, alcohol, drugs, and stress may worsen symptoms and should be taken into consideration. Once the list of possible allergens has been narrowed, specific testing can be done.

Laboratory tests:

Allergen specific IgE testing: Immunoassay and RAST (radioallergosorbent) are blood tests that are used to screen for type I allergen-specific IgE antibodies. Allergen-specific IgE antibody testing involves taking a blood sample and checking for each allergensuspected. Allergens may be selected one at a time or by choosing panels such as food panels, which contain the most common adult or child food allergens, and regional weed and grass panels, which contain the most common airborne allergens in the location where the person lives. Individual selections are very specific; for example: bumble bee versus honeybee, egg white versus egg yolk, common ragweed versus western ragweed. The doctor will select the most appropriate allergens; usually someone will only be truly allergic to a few substances (4 or less).

If a specific IgE test is negative, then chances are that the person tested is not allergic to that substance, but a positive test must be evaluated in the context of the person’s clinical history. Someone can have a low level and still have a severe reaction to actual exposure to the allergen or an elevated level and never experience a reaction. Children who outgrow a food allergy may continue to have positive IgE test results for many years.

Total IgE testing is sometimes done to look for an ongoing allergic process. It is a blood test that detects the presence of IgE protein (including allergy antibodies) but does not identify specific allergens. Conditions besides allergies can also cause it to rise.

Other tests:

Skin prick or scratch tests are done in an allergist’s or dermatologist’s office and must be done by a trained professional. They are often used to detect airborne allergies such as pollens, dust, and molds. Because of the potential for a severe reaction, skin prick tests are not usually used for food allergies. The person being tested must not have significant eczema or be taking antihistamines or certain antidepressants for several days before the skin prick test. False positives can arise with even a non-allergic person if the dosage of the allergen is high enough.

Intradermal allergy skin tests, using injections that form a bubble under the skin, may be done but they are not widely accepted because of a high false positive rate.

Patch testing. Delayed hypersensitivity skin and patch tests are the easiest methods of testing for type IV delayed hypersensitivity. A concentration of the suspected allergen is applied to the skin

under a nonabsorbent adhesive patch and left for 48 hours. If burning or itching develops more rapidly, the patch is removed. A positive test consists of redness with some hardening and swellin

g of the skin, and, sometimes, vesicle (blister-like) formation. Some reactions will not appear until after the patches are removed, so the test sites are also checked at 72 and 96 hours.

Oral food challenges are considered the “gold standard” for diagnosing food allergies. They are labor-intensive and require close medical supervision because reactions can be severe, including life-threatening anaphylaxis. Food challenges involve giving a person small amounts of unmarked potential food allergens in capsule or intravenous form and watching for allergic reactions. Negatives are confirmed with larger meal-sized portions of food.

Elimination is another way to test for food allergies: eliminating all suspected foods from the diet, then reintroducing them one at a time to find out which one(s) are causing the problem.

Other tests not widely accepted as useful include:

Immunoglobulin G4 (IgG4) antibody

Provocation-neutralization

Cytotoxic testing

Applied kinesiology

Sublingual provocation

Neutralization testing

Food immune complex assay

Dark field video analysis of peripheral blood

Miniscribe infra-red analysis

Treatment
Prevention. There is some evidence that children who were breast-fed have fewer type I and type IV hypersensitivities. It is also thought that too restricted and “hygienic” an environment may play a role in increasing allergies. Some studies have shown that infants raised on farms tend to have fewer allergies than those raised in a more allergen-free environment.

Avoidance and Elimination. Once an allergy has developed, the best way to prevent a reaction is to prevent exposure wherever possible. In the case of food, this may mean a lifetime elimination of that

substance from the diet and vigilance in watching for hidden ingredients in processed and restaurant food. For example, a spatula that has touched peanut butter cookies before touching chocolate chip cookies may be contaminated enough to provoke a reaction in a peanut-sensitive person.

In the case of insects and animals, avoidance is best. In the case of airborne pollens, such as regional weeds and grasses, limiting time outside can help but may not prevent the problem. Some people try moving to another area to avoid certain local allergens; this may not be effective since people with allergies often develop new allergies to pollens or grasses in the region to which they move.

Desensitization (immunotherapy, specific immune therapy, “allergy shots”) is sometimes recommended if the allergen cannot be avoided. It includes regular injections of the allergen, given in increasing doses that may “acclimatize” the body to the allergen. The shots decrease the amount of IgE antibodies in the blood and cause the body to make a protective antibody, another of the immunoglobulins,

IgG. Because it moves across the placental barrier, IgG is important in producing immunity in an infant before birth. Immunotherapy shots can cause side effects, like hives and rashes, and can trigger anaphylaxis. Desensitization is most effective for those with hay fever symptoms and severe insect sting allergies. Many with hay fever may have a significant reduction in their symptoms within 12 months, and it is effective in about two-thirds of those who try it. People may continue their shots for 3 years, then consider stopping. Some will have long-term relief; others will see a resumption of their symptoms. Immunotherapy is not recommended for food allergens.

Short-term symptomatic treatment is used for the relief of symptoms. For example, with respiratory symptoms, treatment may include antihistamines, topical nasal steroids, oral steroids, or decongestants.

In the case of anaphylaxis, epinephrine injections are required. Those who have severe reactions must carry a kit that contains an emergency injection of epinephrine with them at all times. Anyone who has a reaction and uses epinephrine should seek medical treatment, as follow-up treatment is often needed


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