Allergy tests

Definition

Allergy tests evaluate levels of allergic sensitivity to commonly encountered allergens, which may be foods, pollen, chemicals, or other substances in the environment.

Purpose

When recurring symptoms in children indicate sensitivity to certain substances in the environment, allergy testing can be used to identify the particular allergens that my be triggering reactions. Using special testing techniques, the child will be exposed to small amounts of specific allergens to determine which of these might provoke a reaction or a "positive" result. Laboratory tests may also be conducted to identify allergens that react with allergy-related substances in the child's blood serum. Positive results from any allergy test may be used to narrow candidates for the allergen responsible for the reaction. Identification of the allergen may help parents avoid exposing their child to the substance and thereby reduce allergic reactions. In addition, allergy testing may be done on children with asthma , eczema, or skin rashes to determine if an allergy is causing the condition or making another condition worse. Allergy tests may also be done before allergen desensitization treatments to ensure the safety of additional exposure.

Description

Allergy is the reaction of the immune system to substances foreign to the body. It is normal for the immune system to respond to foreign microorganisms and particles, like pollen or dust, by producing antibodies against those substances. Antibodies are specific proteins the immune system manufactures to bind to corresponding molecules (antigens) on the cell surfaces of foreign organisms in an attempt to render them harmless. This antigen/antibody reaction is the body's way of protecting itself from invasion by harmful substances and the allergic responses or possible illness that may follow. In some sensitive individuals, excessive antibody production can be triggered by seemingly harmless, everyday substances in the environment. This reactive condition is commonly known as allergy, and the offending substance is called an allergen. Allergic disease arises in the sensitive child from either acute or chronic exposure to certain allergens by inhaling, ingesting, or touching them. Allergic reactions may be dose dependent; that is, longer exposure or exposure to larger amounts of the offending allergen may cause a greater response of the immune system and result in a stronger reaction. Common inhaled allergens include pollen, dust, cat dander, and insect parts from tiny house mites. Common food allergens, all protein-based, include nuts, shellfish, and milk. Allergic reactions can also be triggered by insect bites , molds and fungi, certain prescription drugs, plants such as poison ivy and poison oak , and irritating or toxic substances released into the air.

Allergic reactions involve a special set of cells in the immune system known as mast cells. Mast cells serve as guards in the tissues where the body meets the outside world: the skin; the mucous membranes of the eyes (conjunctiva), nose and throat (nasal and oral mucosa); and the linings of the respiratory and digestive (gastrointestinal) systems. Mast cells produce a special class of antibody, immunoglobulin E (IgE), that coats cell surfaces. Inside the mast cells are reactive chemicals in small packets or granules. When the antibodies encounter allergens, mast cells release granules, which spill out their chemicals onto the cells of nearby tissues, including blood vessels and nerves. Histamine is the most notable of these chemicals, binding quickly to histamine receptors on cell surfaces. Interaction of histamine with receptors on blood vessel, nerve, and tissue cells causes inflammation and the accumulation of intracellular fluid released by the cells. The characteristic swelling and redness that accompanies allergies are the result, seen especially in an irritated nose and throat, a runny nose, and red, irritated eyes. Histamine also stimulates pain receptors, causing the itchy, scratchy nose, eyes, and throat common in allergic rhinitis .

Allergy tests may be performed on the skin or using blood serum in a test tube. During skin tests, potential allergens are placed on the skin and the reaction is observed. In radio-allergosorbent allergy testing (RAST), blood serum is combined with a specific concentration of potential allergens in a test tube, and the mixture is tested for antibody/antigen reactions. Provocation testing involves direct exposure to a likely allergen, either through inhalation or ingestion. It is sometimes performed to determine if symptoms develop on exposure to allergens identified in skin or RAST tests.

The range of allergens used for allergy testing is chosen to reflect possible sources in the environment and may include the following:

• pollen from a variety of trees, common grasses, and weeds
• mold and fungus spores
• house dust
• house mites
• animal skin cells (dander) and saliva
• food extracts
• antibiotics
• insect venoms

Skin testing is the most common type of allergy test. There are two forms of skin tests: percutaneous and intradermal. In percutaneous or prick testing, a drop of each allergen to be tested is placed on the skin, usually on the forearm or the back. A typical battery of tests may involve two dozen allergen drops, including a drop of saline solution that should never provoke a reaction (negative control) and a drop of histamine that should always provoke a reaction (positive control). A small needle is inserted through the drop to prick the skin below. A new needle is used for each prick. The sites are examined over the next 20 minutes for evidence of swelling and redness, indicating a positive reaction. In some instances, a tracing of the set of reactions may be made by placing paper over the tested area. Scratch testing, in which the skin is scratched instead of punctured, is used less often, but the principle is the same.

Intradermal testing involves directly injecting allergen solutions into the skin. Separate injections are made for each allergen tested. Observations are made over the next 20 minutes. As in percutaneous tests, a reddened, swollen spot develops at the injection site for each substance to which the child is sensitive. Skin reactivity can be seen for allergens whether they usually affect the skin. In other words, airborne and food allergens that are inhaled or ingested are capable of causing skin reactions when contact is made with mast cells.

Radio-allergosorbent testing (RAST) is a laboratory test performed on those who may be too sensitive to risk exposure to allergens through skin testing or when medications or skin conditions make testing unreliable. RAST testing involves obtaining a blood sample, usually venous blood from a vein in the arm. The sample will be centrifuged in the laboratory to separate the antibody-containing serum from the blood cells. The serum is then exposed to allergens bound to a solid-phase medium. If antibodies against a particular allergen are present, those antibodies will bind to the solid medium and remain attached after being rinsed. The antigen/antibody complex can be detected in the laboratory by adding specific immunoglobulins that are linked with a radioactive dye. The test is read by locating radioactive spots on the solid-phase medium, and a positive result is reported in each test in which reactive allergens are found.

Testing for food allergies is usually done through diet by a process of elimination, that is, by removing the suspect food from the diet for two weeks and then eating a single portion of the suspect food, followed by careful monitoring for symptoms. A slightly different method is to eat a simple, bland, prescribed diet for a period of two weeks, removing all possible food allergens. Suspect foods are then added to the diet one at a time and the individual is observed for reactions.

Provocation testing is done in some cases to confirm associations between exposure to certain allergens and the subsequent development of symptoms when skin testing or RAST tests have indicated possible sensitivity. In provocation challenges, the skin, nasal and oral mucosa, and lining of the lungs and gastrointestinal tract are exposed to suspected allergens. A purified preparation of the allergen is inhaled or ingested in increasing concentrations to determine if it will provoke symptoms. Oral food challenges with foods are more tedious than inhalation testing, since full passage through thedigestive system may take a day or more. The test involves gradual ingestion of increasing amounts of the suspect food, usually at timed intervals. The test is discontinued with a particular food when either gastrointestinal symptoms occur or it becomes clear that the food is tolerated. In bronchial provocation challenges, the individual inhales increasingly concentrated solutions of a particular allergen prepared in a nebulizer. Each inhalation is followed by measuring the exhalation capacity with a measuring tool called a spirometer. Only one allergen is tested per day. Because provocation tests may actually provoke an allergic reaction in sensitized individuals, treatment medications such as antihistamines are typically available during and following the tests, for administration as needed.

Precautions

While allergy tests are quite safe for most people, the testing involves additional exposure to allergens. The possibility of causing an exaggerated allergic response, a dangerous condition known as anaphylaxis , does exist. Anaphylaxis can result in difficulty breathing and a sharp drop in blood pressure. Individuals who have had prior anaphylactic episodes should inform the testing clinician. Skin tests should never include a substance to which the individual has had severe allergic reactions or that has previously caused anaphylaxis.

Provocation tests may provoke an allergic reaction by exposing the individual to reactive allergens. Treatment medications such as injectable antihistamines should, therefore, be available during and following the tests, to be administered if needed.

Preparation

Skin testing is preceded by a brief examination of the skin. The patient should refrain from using anti-allergy drugs for at least 48 hours before testing. Prior to inhalation testing, children with asthma who can tolerate it may be asked to stop asthma medications. Testing for food allergies usually requires the child to avoid all suspect food for at least two weeks before testing.

The RAST test will usually require that a venous blood sample be drawn to obtain sufficient serum for the test. Parents can explain the procedure briefly to the child ahead of time to help reduce fears and encourage cooperation.

Aftercare

Skin testing does not usually require any aftercare. A generalized redness and swelling may occur in the test area, but it will usually resolve within a day or two.

Inhalation tests may cause delayed asthma attacks, even if the antigen administered in the test initially produces no response. Severe initial reactions may justify close professional observation for at least 12 hours after testing.

If a blood sample has been drawn for RAST testing, a bandage may be applied to the venipuncture site to help keep it clean and to stop slight bleeding that may occur. Unusual bleeding or bruising of the site should be reported to the pediatrician.

Children should be observed closely for signs of allergic reactions after allergy testing using skin tests, inhalation tests, or provocation tests.

Risks

Intradermal testing may inadvertently result in the injection of the allergen into the circulation, with an increased risk of adverse reactions. Inhalation tests may provoke an asthma attack. Exposure to new or unsuspected allergens in any test carries the risk of anaphylaxis. Because patients are monitored following allergy testing, an anaphylactic reaction is usually recognized and treated promptly to reverse the condition. Occasionally, a delayed anaphylactic response can occur that requires immediate care. It is critical that physicians provide education about how to recognize anaphylaxis and tell patients what to do if it occurs at home.

Normal results

Lack of redness or swelling on a skin test indicates no allergic response. In an inhalation test, the exhalation capacity should remain unchanged. In a food challenge, no symptoms should occur.

Abnormal results

Presence of redness or swelling, especially over 5 mm (0.25 inch) in diameter, indicates an allergic response. This reaction does not mean the substance actually causes the child's symptoms, however, since he or she may have no regular exposure to the allergen. In fact, the actual allergen may not have been included in the test array.

Following allergen inhalation, reduction in exhalation capacity of more than 20 percent, and for at least 10 to 20 minutes, indicates a positive reaction to the allergen and the sensitivity of the individual being tested.

Gastrointestinal symptoms within 24 hours following the ingestion of a suspected food allergen indicates a positive response and sensitivity to that food allergen.

Parental concerns

Parents who are already confronted with their child's allergies may be reluctant to have the child undergo testing. Physicians and medical personnel can assure parents that careful observation is involved in testing procedures and that allergens to which the child may have had severe reactions will be avoided. Appropriate medications will be available to treat the child immediately if a reaction is provoked by testing. It is important for parents to tell the child how the tests will be done so that the child is not anxious or apprehensive, which in some cases may increase the likelihood of false positive reactions.

KEY TERMS

Allergen —A foreign substance that provokes an immune reaction or allergic response in some sensitive people but not in most others.

Anaphylaxis —Also called anaphylactic shock; a severe allergic reaction characterized by airway constriction, tissue swelling, and lowered blood pressure.

Antibody —A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Antigen —A substance (usually a protein) identified as foreign by the body's immune system, triggering the release of antibodies as part of the body's immune response.

Antihistamine —A drug used to treat allergic conditions that blocks the effects of histamine, a substance in the body that causes itching, vascular changes, and mucus secretion when released by cells.

Histamine —A substance released by immune system cells in response to the presence of an allergen. It stimulates widening of blood vessels and increased porousness of blood vessel walls so that fluid and protein leak out from the blood into the surrounding tissue, causing localised inflammation of the tissue.

Immunoglobulin G (IgG) —Immunoglobulin type gamma, the most common type found in the blood and tissue fluids.

Intradermal —An injection into a deep layer of skin.

Mast cells —A type of immune system cell that is found in the lining of the nasal passages and eyelids. It displays a type of antibody called immunoglobulin type E (IgE) on its cell surface and participates in the allergic response by releasing histamine from intracellular granules.

See also Asthma; Allergic rhinitis; Drug allergies/sensitivities.

Resources

BOOKS

Gordon, Susan, et al. Allergy Methods and Protocols. Totowa, NJ: Humana Press, 2004.

Kemp, Stephen F., and Richard F. Lockey, eds. Diagnostic Testing of Allergic Disease. NY: Marcel Dekker Inc., 2000.

WEB SITES

"Allergies." Harvard Medical School Consumer Information. Available online at <http://www.intelihealth.com> (accessed October 10, 2004).

"ImmunoCAP Specific IgE Blood Test." Quest Diagnostics. Available online at <www.questdiagnostics.com/hcp/topics/immunocap/immunocap.html> (accessed October 10, 2004).

L. Lee Culvert
Richard Robinson

Allergy Tests

Definition

Allergy tests may be of two general types. In vivo tests that measure the immune response to an agent called an allergen that induces an allergic (atopic) reaction, and in vitro tests that measure the antibodies that mediate an allergic response. Such antibodies are those of the immunoglobulin E class (IgE) which have epsilon heavy chains which attach to mast cells.

Purpose

Allergy tests are performed to determine the cause of a person's allergic reaction. An allergic reaction is caused by the production of specific IgE antibodies against one or more antigens. Those antigens that elicit IgE production are termed allergens and are usually harmless substances. Some common allergens are described below.

• house dust mites and their waste
• hair, dander, and saliva of animals with fur or feathers
• cockroaches and their waste
• weed, grass, and tree pollens
• mold and mildew spores
• stinging insects such as bees, wasps, yellow jackets, hornets, and fire ants
• drugs such as penicillin and sulfa drugs
• foods such as eggs, milk, nuts, and seafood
• ingredients found in dyes, cosmetics, and latex

Precautions

While allergy tests are safe for most people, there is always a possibility that the subject will experience a severe allergic reaction to an allergen used for in vivo testing. For this reason, the subject should be exposed to the lowest dose of allergen in the first phase of testing. In vitroblood tests are particularly appropriate for persons who have a history of severe allergy. In vitro testing may also be more appropriate for persons taking antihistamines, neuroleptics, or antidepressants, and for those with skin conditions all of which may interfere with skin test results.

Description

An allergic reaction is caused when a person's immune system produces IgE antibodies in response to a foreign antigen (allergen). IgE molecules are tightly bound to the surface of mast cells (and basophils in blood). These cells contain granules that have a high concentration of histamine and other substances that are responsible for the allergic reaction. Upon subsequent exposure to the same antigen, an immediate (type 1) hypersensitivity reaction called the atopic or allergic reaction ensues. The allergen binds to the IgE and the crosslinking of antigen and antibody molecules causes the mast cell to degranulate. The histamine and other allergic mediators are released and cause local swelling (edema ) and redness (vasodilation). These reactions occur immediately and may be sufficient in intensity to cause constriction of the bronchi and shock. Such a systemic response to an allergen is called an anaphylactic reaction. Allergens most often responsible for anaphylactic reactions are insect bites and penicillin in persons who are allergic to these agents.

Allergies may be seasonal or chronic depending upon the exposure to the allergen. An allergy may be influenced by factors such as emotional stress, fatigue, infection, air pollution, and weather changes that can cause day to day variation in the severity of symptoms. These triggering factors add to what doctors call the "allergic load," the amount of allergens the body can tolerate at any given time without the occurrence of symptoms.

Allergies can manifest themselves in several ways. Conditions commonly caused by allergies include rhinitis, asthma, contact dermatitis, allergic gastritis, urticaria (hives ), and conjunctivitis. Allergy tests are used to identify the allergen(s) responsible for the allergy. Once the allergen is known, avoidance and desensitization (subcutaneous injection of allergen extract) can be added to the treatment modality.

Types of allergy tests

IN VIVO TESTING. Known as a skin or scratch test, this method is most commonly performed by pricking the skin at multiple sites. Each site is tested by scratching the skin surface with a sterile needle laden with an allergen extract or placing allergen extract on the skin and then pricking the skin with a needle.

The advantages of this testing method include speed (results are immediately available), cost-effectiveness, and a high degree of sensitivity. The disadvantages of this method include patient discomfort, a high incidence of false positives, interference from antihistamines, other drugs and skin conditions.

IN VITRO TESTING. Immunoassays that measure total and specific IgE antibodies are used for in vitro allergy testing. The most commonly used method for specific IgE testing is called the RAST test (radioallergosorbent test). This test is a variation of an indirect antiglobulin test. The allergen is bound to a solid phase such as a plastic test tube or disc. Serum is added and incubated with the allergen. If IgE antibodies specific for the allergen are present, these bind to the tube or disc. The tube is washed, and anti-human IgE tagged with radioactive iodide is added. This attaches to the allergen-antibody complexes. After incubation, the tube is washed again, and its radioactivity is measured. The amount of radioactivity is directly proportional to the IgE concentration. This can be quantified by comparing the radioactivity of the test to standards. Standards consist of a specific IgE of known concentration (e.g., anti-birch) that is reacted with the respective purified allergen (birch extract). The RAST test can be prepared as a screening test by combining groups of allergens onto a single disc. Results are compared to a low-level IgE standard which serves as a positive cutpoint. Radioactivity above the standard indicates a positive test for allergy, and subsequent tests are performed using the individual allergens to determine the cause of a positive screen.

The immunoassay most commonly used for measuring total IgE is called the PRIST test (paper radioimmunosorbent test). This test is a double antibody sandwich type radioimmunoassay in which the IgE is the antigen. Total IgE in serum can also be determined by immunoassay methods. A positive test for total IgE indicates a diagnosis of allergy when allergic symptoms are present. However, serum IgE levels may be increased in persons with parasitic infections and malignant diseases in the absence of allergy.

In vitro tests have the advantage of being sensitive and specific although they are somewhat less sensitive than skin tests. The reagent quality is highly consistent from lot to lot. The methods are more reproducible and accuracy can be monitored with quality control. In vitro methods can be used for persons who are being treated with antihistamines and other medications. One venipuncture replaces multiple skin scratches that are painful and not well tolerated by young children. Disadvantages of in vitro tests are higher costs and longer turnaround time than skin tests(specific IgE tests require 1-2 days before results are available because of long incubation times).

OTHER TESTING. Provocation testing may be performed to positively identify suspected allergens after preliminary skin testing. A purified preparation of the allergen is inhaled or ingested in increasing concentrations to determine if it will provoke a response.

Inhalation testing is performed only after a patient's lung capacity and response to the medium used to dilute the allergen has been determined. Once this has been determined, the patient inhales increasingly concentrated samples of a particular allergen, followed each time by measurement of the exhalation capacity. Only one allergen is tested per day.

Provocation testing with food is more tedious than inhalation testing. First the suspect food is removed from the patient's diet for two weeks; then the patient eats a single portion of the suspect food and is monitored for a reaction.

A double-blind food challenge may also be used for diagnosis of food allergy. During this test, various foods, some of which are suspected of inducing an allergic reaction, are each placed in individual capsules; the patient swallows a capsule and is then watched to see if a reaction occurs. Persons with a history of severe allergic food reactions cannot be tested this way.

Preparation

Skin testing is preceded by a brief examination of the skin. The patient should refrain from using allergy medications for at least 48 hours before testing.

Immunoassay and RAST tests require a sample of blood, which is obtained via venipuncture by a nurse or phlebotomist followng standard precautions for the prevention of transmission of bloodborne pathogens.

Aftercare

Patients receiving skin tests should be monitored for 30 minutes following testing, and treated promptly should they develop signs of a severe allergic reaction. Occasionally, a delayed anaphylactic response may occur that will require immediate care; therefore, patient education regarding how to recognize delayed anaphylaxis is vital. The generalized redness and swelling that may occur in the skin test area will usually resolve within a day or two. More severe reactions may require topical or antihistamine therapy.

Inhalation tests may cause delayed asthma attacks, even if the antigen administered in the test initially produced no response. Severe initial reactions may justify close professional observation for at least 12 hours after testing.

Complications

Intradermal testing may inadvertently result in the injection of the allergen into the circulation, with an increased risk of adverse reactions. Inhalation tests may provoke an asthma attack. Exposure to new or unsuspected allergens in any test carries the risk of anaphylaxis.

Results

Skin testing

Lack of redness or swelling on a skin test indicates no allergic response. A wheal (an area of redness and swelling) exceeding 7 mm in diameter or larger than the histamine control, has a higher diagnostic value than smaller wheals.

Immunoassay testing

SPECIFIC IGE. Quantitative specific IgE cutoffs are the lowest radioactivity levels encountered in the highest dilution of standard used. The IgE level may be reported in RAST units, or as positive, equivocal, or negative.

TOTAL IGE. The upper limit of normal for total IgE is highly age dependent for children. The upper limit increases over the first 10 years, then levels off. The cutoff for adults varies with the test methodology. For the PRIST test the cutoff is approximately 25 kU/L IgE when the standard used is traceable to the 2nd International Reference Preparation of the World Health Organization.

Inhalation testing

In an inhalation test, the exhalation capacity should remain unchanged. Following allergen inhalation, reduction in exhalation capacity of more than 20%, and for at least 10-20 minutes, indicates a positive reaction to the allergen.

KEY TERMS

Allergen— A substance that provokes an allergic response.

Anaphylaxis— Increased sensitivity caused by previous exposure to an allergen that can result in blood vessel dilation (swelling) and smooth muscle contraction. Anaphylaxis can result in shock caused by a sharp fall in blood pressure.

Antibody— A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.

Antigen— A foreign protein to which the body reacts by making antibodies.

Histamine— A chemical released by mast cells that causes vasodilation and bronchial constriction.

Mast cells— A tissue analog of the blood basophil, mast cells are prevalent near small blood vessels in the skin, membranes, and bone marrow. Mast cells bind a type of antibody called immunoglobulin E (IgE) on their surface, and participate in the allergic response by releasing histamine from intracellular granules.

Food testing

In a food challenge, no symptoms should occur. Gastrointestinal symptoms within 24 hours following the ingestion of a suspected food allergen indicates a positive response.

Health care team roles

Allergy tests are ordered by a physician. Skin tests and inhalation tests are performed in a doctor's office by a nurse or healthcare worker specially trained to administer the test. A physician, nurse, or physician assistant should monitor patient for signs of anaphylaxis for 30 minutes after testing.

In vitro allergy tests are performed by clinical laboratory scientists CLS(NCA)/medical technologists MT(ASCP). Results are interpreted by a physician usually a specialist in immunologic and allergic diseases.

Resources

BOOKS

Chernecky, Cynthia C, and Barbara J. Berger. Laboratory Tests and Diagnostic Procedures, 3rd ed. Philadelphia, PA: W. B. Saunders Company, 2001.

Lawlor, G.J., Jr., T.J. Fischer, and D.C. Adelman. Manual of Allergy and Immunology. Boston: Little, Brown and Co., 1995.

PERIODICALS

Parker-Pope, Tara. "Little-Used Simple Blood Test Can Help Screen for Allergies." The Wall Street Journal (September 15, 2000).

"The Use of In Vitro Tests for IgE Antibody in the Specific Diagnosis of Ige-Mediated Disorders and in the Formulation of Allergy Immunotherapy." The Journal of Allergy and Clinical Immunology 90, no. 2 (August 1992): 263-267.

OTHER

Allergy, Asthma & Immunology Online. 〈http://www.allergy.mcg.edu〉.

American Academy of Allergy, Asthma and Immunology. 〈http://www.aaai.org〉.

Allergy Tests

Definition

Allergy tests indicate a person's allergic sensitivity to commonly encountered environmental substances.

Purpose

Allergy is a reaction of the immune system. Normally, the immune system responds to foreign microorganisms and particles, like pollen or dust, by producing specific proteins called antibodies that are capable of binding to identifying molecules, or antigens, on the foreign organisms. This reaction between antibody and antigen sets off a series of reactions designed to protect the body from infection. Sometimes, this same series of reactions is triggered by harmless, everyday substances. This is the condition known as allergy, and the offending substance is called an allergen. Common inhaled allergens include pollen, dust, and insect parts from tiny house mites. Common food allergens include nuts, fish, and milk.

Allergic reactions involve a special set of cells in the immune system known as mast cells. Mast cells serve as guards in the tissues where the body meets the outside world: the skin, the mucous membranes of the eyes and other areas, and the linings of the respiratory and digestive systems. Mast cells display a special type of antibody, called immunoglobulin type E (IgE), on their surface. Inside, mast cells store reactive chemicals in small packets, called granules. When the antibodies encounter allergens, they trigger the release of granules, which spill out their chemicals onto neighboring cells, including blood vessels and nerve cells. One of these chemicals, histamine, binds to the surfaces of these other cells, through special proteins called histamine receptors. Interaction of histamine with receptors on blood vessels causes neighboring cells to become leaky, leading to the fluid collection, swelling, and increased redness characteristic of a runny nose and red, irritated eyes. Histamine also stimulates pain receptors, causing the itchy, scratchy nose, eyes, and throat common in allergic rhinitis.

The particular allergens to which a person is sensitive can be determined through allergy testing. Allergy tests may be performed on the skin or using blood serum in a test tube. During skin tests, potential allergens are placed on the skin and the reaction is observed. In radio-allergosorbent allergy testing (RAST), a patient's blood serum is combined with allergen in a test tube to determine if serum anti-bodies react with the allergen. Provocation testing involves direct exposure to a likely allergen, either through inhalation or ingestion. Positive reactions from any of these tests may be used to narrow the candidates for the actual allergen causing the allergy.

Identification of the allergenic substance may allow the patient to avoid the substance and reduce allergic reactions. In addition, allergy testing may be done in those with asthma that is difficult to manage, eczema, or skin rashes to determine if an allergy is causing the condition or making it worse. Allergy tests may also be done before allergen desensitization to ensure the safety of more extensive exposure.

KEY TERMS

Allergen— A substance that provokes an allergic response.

Anaphylaxis— Increased sensitivity caused by previous exposure to an allergen that can result in blood vessel dilation (swelling) and smooth muscle contraction. Anaphylaxis can result in sharp blood pressure drops and difficulty breathing.

Antibody— A specific protein produced by the immune system in response to a specific foreign protein or particle called an antigen.

Antigen— A foreign protein to which the body reacts by making antibodies.

Histamine— A chemical released by mast cells that activates pain receptors and causes cells to become leaky.

Mast cells— A type of immune system cell that is found in the lining of the nasal passages and eyelids, displays a type of antibody called immunoglobulin type E (IgE) on its cell surface, and participates in the allergic response by releasing histamine from intracellular granules.

Skin testing is the most common type of allergy test. There are two forms: percutaneous and intradermal. In percutaneous or prick testing, allergen solutions are placed on the skin, and the skin is then pricked with a needle, allowing the allergen to enter the skin and become exposed to mast cells. Scratch testing, in which the skin is scratched instead of punctured, is used less often. Intradermal testing involves directly injecting allergen solutions into the skin. In both tests, a reddened, swollen spot develops at the injection site for each substance to which the person is sensitive. Skin reactivity is seen for allergens regardless of whether they usually affect the skin. In other words, airborne and food allergens cause skin reactions equally well.

The range of allergens used for testing is chosen to reflect possible sources in the environment and may include the following:

• pollen from a variety of trees, common grasses, and weeds
• mold and fungus spores
• house dust
• house mites
• animal skin cells (dander) and saliva
• food extracts
• antibiotics
• insect venoms

Radio-allergosorbent testing (RAST) is a laboratory test performed when a person may be too sensitive to risk skin testing or when medications or skin conditions prevent it.

Provocation testing is done to positively identify suspected allergens after preliminary skin testing. A purified preparation of the allergen is inhaled or ingested in increasing concentrations to determine if it will provoke a response. In 2004, scientists introduced an optical method to continuously measure the changes in nasal mucosa (lining) changes with an infrared light to help improve the accuracy of provocation testing. Food testing is much more tedious than inhalation testing, since full passage through the digestive system may take a day or more.

Precautions

While allergy tests are quite safe for most people, the possibility of a condition known as anaphylaxis exists. Anaphylaxis is a potentially dangerous condition that can result in difficulty breathing and a sharp drop in blood pressure. People with a known history of anaphylaxis should inform the testing clinician. Skin tests should never include a substance known to cause anaphylaxis in the person being tested.

Provocation tests may cause an allergic reaction. Therefore, treatment medications should be available following the tests, to be administered, if needed.

Description

In prick testing, a drop of each allergen to be tested is placed on the skin, usually on the forearm or the back. A typical battery of tests may involve two dozen allergen drops, including a drop of saline solution that should not provoke a reaction (negative control) and a drop of histamine that should provoke a reaction (positive control). A small needle is inserted through the drop, and used to prick the skin below. A new needle is used for each prick. The sites are examined over the next 20 minutes for evidence of swelling and redness, indicating a positive reaction. In some instances, a tracing of the set of reactions may be made by placing paper over the tested area. Similarly, in intradermal testing, separate injections are made for each allergen tested. Observations are made over the next 20 minutes.

In RAST testing, a blood sample is taken for use in the laboratory, where the antibody- containing serum is separated from the blood cells. The serum is then exposed to allergens bound to a solid medium. If a person has antibodies to a particular allergen, those antibodies will bind to the solid medium and remain behind after a rinse. Location of allergen-antibody combinations is done by adding antibody-reactive antibodies, so called anti-antibodies, that are chemically linked with a radioactive dye. By locating radioactive spots on the solid medium, the reactive allergens are discovered.

Provocation testing may be performed to identify airborne or food allergens. Inhalation testing is performed only after a patient's lung capacity and response to the medium used to dilute the allergen has been determined. Once this has been determined, the patient inhales increasingly concentrated samples of a particular allergen, followed each time by measurement of the exhalation capacity. Only one allergen is tested per day. Testing for food allergies is usually done by removing the suspect food from the diet for two weeks, followed by eating a single portion of the suspect food and follow-up monitoring.

Preparation

Skin testing is preceded by a brief examination of the skin. The patient should refrain from using antiallergy drugs for at least 48 hours before testing. Prior to inhalation testing, patients with asthma who can tolerate it may be asked to stop any asthma medications. Testing for food allergies requires the person to avoid all suspect food for at least two weeks before testing.

Aftercare

Skin testing does not usually require any aftercare. A generalized redness and swelling may occur in the test area, but it will usually resolve within a day or two.

Inhalation tests may cause delayed asthma attacks, even if the antigen administered in the test initially produced no response. Severe initial reactions may justify close professional observation for at least 12 hours after testing.

Risks

Intradermal testing may inadvertently result in the injection of the allergen into the circulation, with an increased risk of adverse reactions. Inhalation tests may provoke an asthma attack. Exposure to new or unsuspected allergens in any test carries the risk of anaphylaxis. Because patients are monitored following allergy testing, an anaphylactic reaction is usually recognized and treated promptly. Occasionally, a delayed anaphylactic response can occur that will require immediate care. Proper patient education regarding how to recognize anaphylaxis is vital.

Normal results

Lack of redness or swelling on a skin test indicates no allergic response. In an inhalation test, the exhalation capacity should remain unchanged. In a food challenge, no symptoms should occur.

Abnormal results

Presence of redness or swelling, especially over 5 mm (1/4 inch) in diameter, indicates an allergic response. This does not mean the substance actually causes the patient's symptoms, however, since he or she may have no regular exposure to the allergen. In fact, the actual allergen may not have been included in the test array.

Following allergen inhalation, reduction in exhalation capacity of more than 20%, and for at least 10-20 minutes, indicates a positive reaction to the allergen.

Gastrointestinal symptoms within 24 hours following the ingestion of a suspected food allergen indicates a positive response.

Resources

PERIODICALS

Hampel, U., et al. "Optical Measurements of Nasal Swellings." IEEE Transactions on Biomedical Engineering (September 2004): 1673-1680.

Allergy tests

Definition

Allergy tests are performed to confirm whether allergy signs and symptoms are indeed caused by allergies and to identify allergy-causing substances.

Description

Allergies are immune responses to a substance which is not necessarily harmful in itself, but results in a reaction that causes symptoms and disease in a predisposed person. People who have allergies produce an antibody called immunoglobulin E (IgE), responsible for the allergic reaction. When the IgE come into contact with an allergy-causing substance (allergen), the mast cells of the body release chemical substances, such as histamine, that cause allergy symptoms such as sneezing and other reactions. When a person experiences symptoms indicative of an allergic response, it becomes important to know which allergen can trigger a response in that person. Allergy tests have been developed to diagnose allergies. These tests expose the skin or the blood to suspected allergen(s) and the exposure site is then observed for signs of an allergic reaction.

Because of changing world demographics, it is estimated that an ever-growing proportion of allergy patients will be from the elderly population. Health practitioners are acknowledging that it will become increasingly important to test for allergies in this patient group, especially in patients with rather mild symptoms such as rhinitis.

Purpose

The purpose of allergy tests is to confirm that experienced symptoms, most commonly hives, contact dermatitis , runny nose, watery eyes, chest congestion or wheezing, are indeed caused by an allergy, and not by another condition with similar symptoms. For in-stance, food intolerance reactions, often called “pseudo—allergic reactions”, are not allergic reactions. The tests are also used to identify the allergen. They provide specific information about what precisely a person is allergic to and conversely, what he or she is not allergic to. Once the specific allergen is identified, the health practitioner can develop a treatment plan aimed at controlling or eliminating the allergy symptoms and the patient can limit exposure to known allergens.

Operation

Allergy tests are available for various allergies. They expose a person to specific allergen extracts and the response of the person, either positive or negative, is recorded. Extracts are available to test for allergies with symptoms affecting the nose and eyes, such as hay fever or other seasonal allergies, or allergy to various pollens, or to pet dander, dust mite droppings, stinging-insect or snake venom, food and medication allergies (e.g. penicillin or local anesthetics) and to latex. They are performed as follows:

• Prick test: This technique pricks the skin to introduce a small amount of allergen extracts into the skin. If the person is allergic to the extract, signs of an allergic response will occur. The procedure allows testing for several allergens, because only the spots pricked by a specific allergen to which the person is allergic to will show the allergic response, usually redness and swelling.
• Intradermal test: This test is more sensitive than a prick test and involves injecting the allergen extracts under the skin with a syringe.
• Skin patch test: For a skin patch test, the allergen extract is placed on a pad that is taped to the skin for 24 to 72 hours. This test is commonly used for contact dermatitis to various chemicals.
• Blood IgE test: This is a blood test that can detect the amount of IgE, present in the blood. It can be performed using various methods such as the RAST (radioallergosorbent), or ELISA (enzyme-linked immunosorbent assay), or CAP-FEIA (fluorenzy-meimmunoassay) tests.
• Elimination diet: An elimination diet tests suspected foods by having the patient avoid them for several weeks and then by gradually re%#x2014;introducing them one at a time in the diet. The person is monnitored for signs of an allergic reaction.
• Provocation test: This type of test is performed only under close medical supervision and involves exposing a person to a suspected allergen under controlled circumstances. The allergen is applied under the tongue, or by intradermal injection. Increasing test doses are given until a wheal appears on the skin (provocation dose). The dose is then decreased until the wheal disappears (neutralisation dose). This neutralising dose is used to treat the allergy and desensitise the patient to the allergen.

If a person is not allergic to suspected allergens, allergy tests will be negative, meaning that there is no allergic response to the allergen. If however, the person is allergic to one or several allergens, the tests will be positive, meaning that the person is allergic to the allergen(s) that produced the positive result.

Maintenance

In the United States, the Food and Drug Administration (FDA) regulates the biological extracts used in allergy tests and shots. The extracts are used both to treat and to test individuals to determine exactly what causes their allergic reactions. The FDA is also working to standardize allergenic extracts to improve the medical management of allergies and lessen the risk of an adverse reaction to a test.

KEY TERMS

Allergen —Any substance that causes an allergic response. Allergens contain protein, and almost anything can be an allergen for someone.

Allergic reaction —Sensitivities to a specific allergen that is contacted through the skin, inhaled into the lungs, swallowed, or injected.

Allergy —Immune response of the body to a substance which is not necessarily harmful in itself, but results in a reaction that causes symptoms and disease in a predisposed person.

Antigen —Any foreign substance, usually a protein, that stimulates the body's immune system to produce antibodies.

Contact dermatitis —Itchy, blistering skin rash typically caused by an allergic reaction to direct contact of a substance with the skin.

Delayed hypersensitivity reaction —T cell responses that do not occur immediately upon exposure to an antigen, but over several days.

ELISA test —An ELISA (enzyme-linked immunosor-bent assay) test is used to detect IgE levels in the blood.

False negative result —A negative test result in a person known to be allergic to the tested allergen.

False positive result —A positive test result in a person with no allergy.

Food intolerance —An adverse food-induced reaction that does not involve the immune system.

Hay fever —A seasonal allergy to airborne particles characterized by itchy eyes, runny nose, nasal congestion, sneezing, itchy throat, and excess mucus.

Histamine —Substance released frommast cells during an allergic reaction. It causes itching, sneezing, increased mucous production, and nasal congestion.

Hives —A raised, itchy area of skin that is usually a sign of an allergic reaction.

Hypersensitivity —An exaggerated response by the immune system to a substance.

Immune response —The activity of the immune system to defend the body against antigens, involving primarily the production of antibodies and sensitized T-cells.

Immunoglobulin E (IgE) —Antibodies produced in the lungs, skin, and mucous membranes and responsible for allergic reactions.

Mast cells —A cell found in connective tissue that contains granules that release substances such as heparin and histamine during allergic reactions.

RAST test —A RAST (radioallergosorbent) test is used detect the amount of IgE in the blood.

Rhinitis —An inflammation of the nasal passageways, particularly with discharge.

Sensitivity —An exaggerated response by the immune system to a substance.

Allergy tests are required to reliably identify one or more allergens to which the patient reacts on each exposure. These allergens must be the cause of the patient's allergic symptoms. The reaction need not necessarily be IgE-associated, but may involve a T-cell delayed hypersensitivity reaction or direct histamine release from mast cells. Allergy tests are also required to be reproducible and identify the suspected allergen on each occasion the test is performed. The tests should also have minimal false positive results, meaning the return of a positive result in a person with no allergy, or false negative results, meaning the return of a negative result in a person known to be allergic to the allergen tested.

Training

Allergy tests are performed by allergists or immunologists, physicians specially trained to diagnose and treat allergies. Blood allergy tests are analyzed in laboratories by trained technicians. In the United States, a board certified allergist/immunologist is a physician who has fulfilled the requirements of and has received certification from the American Board of Internal Medicine (ABIM) and/or the American Board of Pediatrics (ABP) followed by additional certification by the American Board of Allergy and Immunology (ABAI), a conjoint board of the American Board of Internal Medicine and the American Board of Pediatrics.

Resources

BOOKS

Brostoff, Jonathan, and Linda Gamlin. Food Allergies and Food Intolerance: The Complete Guide to Their Identification and Treatment. Rochester, VT: Healing Arts Press, 2000.

Kwong, Frank. The Complete Allergy Book: Learn to Become Actively Involved in Your Own Care. Naperville, IL: Sourcebooks, Inc., 2002.

Miner, Margaret, and Stuart H. Young. Allergies: The Complete Guide to Diagnosis, Treatment, and Daily Management. New York, NY: Penguin Books, 1999.

Zellerbach, Merla. The Allergy Sourcebook. New York, NY: McGraw-Hill, 2000.

PERIODICALS

Bakos, N., et al. “Risk assessment in elderly for sensitization to food and respiratory allergens. “Immunology Letters 107, no. 1 (September 2006): 15–21.

Wöhrl, S., and G. Stingl. “Underestimation of allergies in elderly patients. “Lancet 363, no. 9404 (January 2004):249.

OTHER

Allergy skin tests: Identify the sources of your allergies. Mayo Clinic. Diagnostic Tests (March 30, 2008) http://www.mayoclinic.com/health/allergy-tests/AA00023

Allergy Testing. Lab Tests Online. (March 30, 2008) http://www.labtestsonline.org/understanding/analytes/allergy/test.html

What is allergy testing? AAAAI, Information Page. (March 30, 2008) http://www.aaaai.org/patients/publicedmat/tips/whatisallergytesting.stm

ORGANIZATIONS

American Academy of Allergy, Asthma & Immunology (AAAAI), 555 East Wells St., Milwaukee, WI, 53202-3823, (414) 272-6071, [email protected], http://www.aaaai.org.

Asthma and Allergy Foundation of America (AAFA), 1233 20th Street, NW, Suite 402, Washington, DC, 20036, (202) 466-7643, (800) 7-ASTHMA, [email protected], http://www.aafa.org/.

National Institute of Allergy and Infectious Diseases (NIAID), 6610 Rockledge Drive, MSC 6612, Bethesda, MD, 20892-6612, (301) 496-5717, (866) 284-4107, http://www3.niaid.nih.gov.

Monique Laberge Ph.D.