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Effective management of allergic diseases relies on the ability to make an accurate diagnosis. Allergy testing can help confirm or rule out allergies. Correct diagnosis, counseling, and avoidance advice based on valid allergy test results reduces the incidence of symptoms and need for medications, and improves quality of life. To assess the presence of allergen-specific IgE antibodies, two different methods can be used: a skin prick test, or an allergy blood test. Both methods are recommended, and they have similar diagnostic value.
Skin prick tests and blood tests are equally cost-effective, and health economic evidence shows that both tests were cost-effective compared with no test. Also, early and more accurate diagnoses save cost due to reduced consultations, referrals to secondary care, misdiagnosis, and emergency admissions.
Allergy undergoes dynamic changes over time. Regular allergy testing of relevant allergens provides information on if and how patient management can be changed, in order to improve health and quality of life. Annual testing is often the practice for determining whether allergy to milk, egg, soy, and wheat have been outgrown, and the testing interval is extended to 2–3 years for allergy to peanut, tree nuts, fish, and crustacean shellfish. Results of follow-up testing can guide decision-making regarding whether and when it is safe to introduce or re-introduce allergenic food into the diet.
An allergy blood test is quick and simple, and can be ordered by a licensed health care provider ("e.g.", an allergy specialist), GP, or PED. Unlike skin-prick testing, a blood test can be performed irrespective of age, skin condition, medication, symptom, disease activity, and pregnancy. Adults and children of any age can take an allergy blood test. For babies and very young children, a single needle stick for allergy blood testing is often more gentle than several skin tests.
An allergy blood test is available through most laboratories. A sample of the patient's blood is sent to a laboratory for analysis, and the results are sent back a few days later. Multiple allergens can be detected with a single blood sample. Allergy blood tests are very safe, since the person is not exposed to any allergens during the testing procedure.
The test measures the concentration of specific IgE antibodies in the blood. Quantitative IgE test results increase the possibility of ranking how different substances may affect symptoms. A rule of thumb is that the higher the IgE antibody value, the greater the likelihood of symptoms. Allergens found at low levels that today do not result in symptoms can nevertheless help predict future symptom development. The quantitative allergy blood result can help determine what a patient is allergic to, help predict and follow the disease development, estimate the risk of a severe reaction, and explain cross-reactivity.
A low total IgE level is not adequate to rule out sensitization to commonly inhaled allergens. Statistical methods, such as ROC curves, predictive value calculations, and likelihood ratios have been used to examine the relationship of various testing methods to each other. These methods have shown that patients with a high total IgE have a high probability of allergic sensitization, but further investigation with allergy tests for specific IgE antibodies for a carefully chosen of allergens is often warranted.
Laboratory methods to measure specific IgE antibodies for allergy testing include enzyme-linked immunosorbent assay (ELISA, or EIA), radioallergosorbent test (RAST) and fluorescent enzyme immunoassay (FEIA).
Skin prick tests can be used to confirm specific food allergies. Skin prick tests are designed to identify specific IgE bound to cutaneous mast cells. During the test, a glycerinated allergen extract drop is placed on the patient's skin. The patient's skin is then pricked through the drop. This procedure is repeated with two controls: a histamine drop designed to elicit an allergic response, and a saline drop designed to elicit no allergic response. The wheal that develops from the glycerinated extract drop is compared against the saline control. A positive allergic test is one in which the extract wheal is 3mm larger than the saline wheal. A positive skin prick test is about 50% accurate, so a positive skin prick test alone is not diagnostic of food allergies.
There are three main classifications of anaphylaxis. Anaphylactic shock is associated with systemic vasodilation that causes low blood pressure which is by definition 30% lower than the person's baseline or below standard values. Biphasic anaphylaxis is the recurrence of symptoms within 1–72 hours with no further exposure to the allergen. Reports of incidence vary, with some studies claiming as many as 20% of cases. The recurrence typically occurs within 8 hours. It is managed in the same manner as anaphylaxis. Pseudoanaphylaxis or anaphylactoid reactions are a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation. Non-immune anaphylaxis is the current term used by the World Allergy Organization with some recommending that the old terminology no longer be used.
Peanut allergies tend to resolve in childhood less often than allergies to soy, milk, egg, and wheat. Accordingly, re-evaluation of peanut allergy is recommended on a yearly basis for young children with favorable previous test results, and every few years or longer for older children and adults.
Skin prick testing is a common way of testing for an allergy. Other ways to test for allergies can be challenge testing, which consists in feeding a very small and measured amount of the allergen to the patient and monitor the reaction (O'Neil, Zanovec and Nickla). This should only be done by a doctor under surveillance.
Allergy testing may help in determining the trigger. Skin allergy testing is available for certain foods and venoms. Blood testing for specific IgE can be useful to confirm milk, egg, peanut, tree nut and fish allergies.
Skin testing is available to confirm penicillin allergies, but is not available for other medications. Non-immune forms of anaphylaxis can only be determined by history or exposure to the allergen in question, and not by skin or blood testing.
Diagnosis is usually based on a medical history, elimination diet, skin prick test, blood tests for food-specific IgE antibodies, or oral food challenge.
- For skin-prick tests, a tiny board with protruding needles is used. The allergens are placed either on the board or directly on the skin. The board is then placed on the skin, to puncture the skin and for the allergens to enter the body. If a hive appears, the person is considered positive for the allergy. This test only works for IgE antibodies. Allergic reactions caused by other antibodies cannot be detected through skin-prick tests.
Skin-prick testing is easy to do and results are available in minutes. Different allergists may use different devices for testing. Some use a "bifurcated needle", which looks like a fork with two prongs. Others use a "multitest", which may look like a small board with several pins sticking out of it. In these tests, a tiny amount of the suspected allergen is put onto the skin or into a testing device, and the device is placed on the skin to prick, or break through, the top layer of skin. This puts a small amount of the allergen under the skin. A hive will form at any spot where the person is allergic. This test generally yields a positive or negative result. It is good for quickly learning if a person is allergic to a particular food or not, because it detects IgE. Skin tests cannot predict if a reaction would occur or what kind of reaction might occur if a person ingests that particular allergen. They can, however, confirm an allergy in light of a patient's history of reactions to a particular food. Non-IgE-mediated allergies cannot be detected by this method.
- Patch testing is used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed food reactions.
- Blood testing is another way to test for allergies; however, it poses the same disadvantage and only detects IgE allergens and does not work for every possible allergen. Radioallergosorbent testing (RAST) is used to detect IgE antibodies present to a certain allergen. The score taken from the RAST is compared to predictive values, taken from a specific type of RAST. If the score is higher than the predictive values, a great chance the allergy is present in the person exists. One advantage of this test is that it can test many allergens at one time.
A CAP-RAST has greater specificity than RAST; it can show the amount of IgE present to each allergen. Researchers have been able to determine "predictive values" for certain foods, which can be compared to the RAST results. If a person's RAST score is higher than the predictive value for that food, over a 95% chance exists that patients will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food. Currently, predictive values are available for milk, egg, peanut, fish, soy, and wheat. Blood tests allow for hundreds of allergens to be screened from a single sample, and cover food allergies as well as inhalants. However, non-IgE-mediated allergies cannot be detected by this method. Other widely promoted tests such as the antigen leukocyte cellular antibody test and the food allergy profile are considered unproven methods, the use of which is not advised.
- Food challenges test for allergens other than those caused by IgE allergens. The allergen is given to the person in the form of a pill, so the person can ingest the allergen directly. The person is watched for signs and symptoms. The problem with food challenges is that they must be performed in the hospital under careful watch, due to the possibility of anaphylaxis.
Food challenges, especially double-blind, placebo-controlled food challenges, are the gold standard for diagnosis of food allergies, including most non-IgE-mediated reactions. Blind food challenges involve packaging the suspected allergen into a capsule, giving it to the patient, and observing the patient for signs or symptoms of an allergic reaction.
The best method for diagnosing food allergy is to be assessed by an allergist. The allergist will review the patient's history and the symptoms or reactions that have been noted after food ingestion. If the allergist feels the symptoms or reactions are consistent with food allergy, he/she will perform allergy tests. Additional diagnostic tools for evaluation of eosinophilic or non-IgE mediated reactions include endoscopy, colonoscopy, and biopsy.
The majority of children outgrow egg allergy. One review reported that 70% of children will outgrow this allergy by 16 years. In subsequently published longitudinal studies, one reported that for 140 infants who had challenge-confirmed egg allergy, 44% had resolved by two years. A second reported that for 203 infants with confirmed IgE-mediated egg allergy, 45% resolved by two years of age, 66% by four years, and 71% by six years. Children will be able to tolerate eggs as an ingredient in baked goods and well-cooked eggs sooner than under-cooked eggs. Resolution was more likely if baseline serum IgE was lower, and if the baseline symptoms did not include anaphylaxis.
Testing is available to help identify any environmental or food allergies. Caregivers and clinicians can assess the child for the development of an allergy by noting the presence of signs and symptoms and history of exposure.
Urinary cystyl-leukotriene or urinary LTE4 can be used after a supervised challenge with aspirin. In aspirin sensitivity, no change in N-methylhistamine is observed; while LTE4 levels are increased. This test however lacks sensitivity and has a 25 percent false negative rate among affected persons.
Important differential diagnoses are:
- Lactose intolerance generally develops later in life, but can present in young patients in severe cases. It is due to an enzyme deficiency (lactase) and not allergy, and occurs in many non-Western people.
- Celiac disease is an autoimmune disorder triggered by gluten proteins such as gliadin (present in wheat, rye, and barley). It is a non-IgE-mediated food allergy by definition.
- Irritable bowel syndrome
- C1 Esterase inhibitor deficiency (hereditary angioedema), a rare disease, generally causes attacks of angioedema, but can present solely with abdominal pain and occasional diarrhea.
Diagnosis of egg allergy is based on the person's history of allergic reactions, skin prick test (SPT), patch test and measurement of egg-specific serum immunoglobulin E (IgE or sIgE). Confirmation is by double-blind, placebo-controlled food challenges. SPT and sIgE have sensitivity greater than 90% but specificity in the 50-60% range, meaning these tests will detect an egg sensitivity, but will also be positive for other allergens. For young children, attempts have been made to identify SPT and sIgE responses strong enough to avoid the need for a confirming oral food challenge.
To confirm OAS, the suspected food is consumed in a normal way. The period of observation after ingestion and symptoms are recorded. If other co factors like combined foods are required, this is also replicated in the test. For example, if the individual always develops symptoms after eating followed by exercise, then this is replicated in the laboratory.
Milk allergy typically presents in the first year of life. The majority of children outgrow milk allergy by the age of ten years. One large clinical trial reported resolutions of 19% by age 4 years, 42% by age 8 years, 64% by age 12 years, and 79% by 16 years. Children are be able to tolerate milk as an ingredient in baked goods relative to liquid milk. Resolution was more likely if baseline serum IgE was lower, or if IgE-mediated allergy was absent so that all that was present was cell-mediated, non-IgE allergy.
People with confirmed cow's milk allergy may also demonstrate an allergic response to beef, moreso to rare beef versus well-cooked beef. The offending protein appears to be bovine serum albumin. This is not the same beef allergy that is seen primarily in the southeastern United States, triggered by being bitten by a Lone Star tick.
Milk allergy has consequences. In a U.S. government diet and health surveys conducted in 2007-2010, 6,189 children ages 2-17 years were assessed. For those classified as cow's milk allergic at the time of the survey, mean weight, height and body-mass index were significantly lower than their non-allergic peers. This was not true for children with other food allergies. Diet assessment showed a significant 23% reduction of calcium intake and near-significant trends for lower vitamin D and total calorie intake.
Allergy testing may reveal the specific allergens to which an individual is sensitive. Skin testing is the most common method of allergy testing. This may include a patch test to determine if a particular substance is causing the rhinitis, or an intradermal, scratch, or other test. Less commonly, the suspected allergen is dissolved and dropped onto the lower eyelid as a means of testing for allergies. This test should be done only by a physician, since it can be harmful if done improperly. In some individuals not able to undergo skin testing (as determined by the doctor), the RAST blood test may be helpful in determining specific allergen sensitivity. Peripheral eosinophilia can be seen in differential leukocyte count.
Allergy testing can either show allergies that are not actually causing symptoms or miss allergies that do cause symptoms. The intradermal allergy test is more sensitive than the skin prick test but is more often positive in people that do not have symptoms to that allergen.
Even if a person has negative skin-prick, intradermal and blood tests for allergies, he/she may still have allergic rhinitis, from a local allergy in the nose. This is called local allergic rhinitis. Specialized testing is necessary to diagnose local allergic rhinitis.
Unlike most food allergies, it may be possible for the alpha-gal allergy to recede with time, as long as the person is not bitten by another tick. The recovery period can take anywhere from eight months to five years. This recovery potential is not confirmed. More research needs to be conducted to determine why some patients seem to recover and some do not.
Many people have no idea that they have OAS. However, if swelling, tingling or pain develops while eating certain foods, then it is wise to see an allergy specialist. Before a diagnosis can be made, keep a food diary. This is important as the physician can then perform an allergy test. Before testing is started, a comprehensive history is obtained so that random testing is avoided. The diagnosis of OAS may involve skin prick tests, blood tests, patch tests or oral challenges. When OAS is suspected, the oral challenge test is ideal.
A traditional skin prick allergy test for allergy to meat may give a false negative answer. Blood tests for IgE response indicating alpha-gal allergy have not been approved by the U.S. Food and Drug Administration (FDA), and must usually be purchased by private individuals, but are available and are in use. Determination of specific IgE to alpha-gal testing is commercially available. The highest sensitivity is observed with skin and basophil activation tests with cetuximab which is, however, limited by its high costs.
Diagnosis of soy allergy is based on the person's history of allergic reactions, skin prick test (SPT), patch test and measurement of soy protein specific serum immunoglobulin E (IgE or sIgE). A negative IgE test does not rule out non-IgE mediated allergy, also described as cell-mediated allergy. SPT and sIgE have sensitivities of 55% and 83% respectively, and specificities of 68% and 38%. These numbers mean that either test may miss diagnosing an existing soy allergy, and that both can also be positive for other food allergens. Confirmation is by double-blind, placebo-controlled food challenges, conducted by an allergy specialist.
Diagnosis of milk allergy is based on the person's history of allergic reactions, skin prick test (SPT), patch test and measurement of milk protein specific serum immunoglobulin E (IgE or sIgE). A negative IgE test does not rule out non-IgE mediated allergy, also described as cell-mediated allergy. Confirmation is by double-blind, placebo-controlled food challenges, conducted by an allergy specialist. SPT and sIgE have sensitivity around 88% but specificity of 68% and 48%, respectively, meaning these tests will probably detect a milk sensitivity but will also be positive for other allergens.
Attempts have been made to identify SPT and sIgE responses accurate enough to avoid the need for a confirming oral food challenge. A systematic review stated that for children younger than two years, cut-offs for specific IgE or SPT seem to be more homogeneous and may be proposed. For older children the tests were less consistent. It concluded "None of the cut-offs proposed in the literature can be used to definitely confirm cow's milk allergy diagnosis, either to fresh pasteurized or to baked milk."
An allergy is different from an intolerance. Food allergies and food intolerances should not be confused because they do not contain the same risks and are not diagnosed the same way. Allergies can be fatal after only a small consumption, while intolerance, although uncomfortable, are not as deadly. An intolerance may lead to a nutrient deficiency which could cause death if untreated but the intolerance itself is not enough to cause rapid death. Allergies, with their varying symptoms, could cause instantaneous death if there is inflammation in the throat and causes suffocation.
Diagnosis of alcohol-induced respiratory symptoms can be strongly suggested on the bases of survey questionnaires. Questionnaires can be devised to determine the specific types of alcoholic beverages eliciting reactions; reactions evoked by one or only a few but not other types of alcoholic beverage, particularly when the offending beverage(s) is wine and/or beer, suggest that the reactions are due to classical allergic reaction to allergens in the beverage; reactions to all or most types of alcoholic beverages favors a genetic (i.e. acetaldehyde-induce) basis. Further differentiation between these two causes can be tested under medical supervision be determining if ingestion of a water-diluted pure ethanol solution elicits reactions or if an offending alcoholic beverage but not the same beverage without ethanol elicits reactions. Either result would favor an acetaldehyde-induced genetic basis for the reaction.
Diagnosis of alcohol sensitivity due to the accumulation of acetaldehyde in individuals bearing the glu487lys ALDH2 allele can be made by measuring the diameter of the erythema (i.e. red) area developing under a 15 millimeter skin patch plaster soaked in 70% ethanol and applied for 48 hours (ethanol patch test); erythema of 15 millimeters is considered positive with a false positive ratio ([100 x {number of individuals with a positive patch test}]/{number of individuals with a normal ALDH2 genotype}) of 5.9% and a false negative ratio ([100 x {number of individuals with a negative patch test}]/{number of individuals with a glu487lys ALDH2 allele}) of 0%. To resolve ambiguities in or replace the ethanol patch test for other reasons, a polymerase chain reaction using special primers and conditions can be used to directly detect the glu487lys ALDH2 genes. For other causes of acetaldehyde-induced alcohol sensitivities, the ethanol patch test will need to be tested for verification of its acetaldehyde basis and appropriate polymerase chain reactions will likewise be needed to verify a genetic basis for symptoms.
Diagnosis of alcohol sensitivity due to allergic reactivity to the allergens in alcoholic beverages can be confirmed by standard skin prick tests, skin patch tests, blood tests, challenge tests, and challenge/elimination tests as conducted for determining the allergen causing other classical allergic reactions (see allergy and Skin allergy tests.)
There are no laboratory or skin testing methods for testing salicylate sensitivity. Provocative challenge is one method of obtaining reliable diagnosis. Provocative challenge is intended to induce a controlled reaction as a means of confirming diagnosis. During provocative challenge, the person is given incrementally higher doses of salicylates, usually aspirin, under medical supervision, until either symptoms appear or the likelihood of symptoms appearing is ruled out.
A detailed history allows physicians to determine whether the presenting symptoms are due to an allergen or another source. Diagnostic tests such as conjunctival scrapings to look for eosinophils are helpful in determining the cause of the allergic response. Antihistamines, medication that stabilizes mast cells, and NSAIDs are safe and usually effective. Corticosteroids are reserved for more severe cases of ocular allergy disease, and their use should be monitored by an eye care physician due to possible side-effects. When an allergen is identified, the person should avoid the allergen as much as possible.