Allergy Diagnosis and Controversial Tests

Allergies Clinics of London

"Controversial" Allergy Tests

We review tests ranging from those that have been scientifically validated but are not readily available, to those of a less scientific nature that have not yet subjected to any large clinical studies or validation.

The more "controversial" tests have not been subjected to any large scientifically reviewed clinical trials by their manufacturers, who tend to site the expense as a deterrent to such studies. Their validity as tests are often based on anecdotal reports of diagnostic efficacy and hearsay.

We will include those Allergy Tests that are in the process of being validated and have impressive initial diagnostic reports through to those that are frankly ridiculous and have no logical basis. The Histamine Release test and Cellular Allergen Stimulation Test are in the process of being evaluated and to date have in some studies shown excellent diagnostic accuracy. They are however not commercially available for routine use as yet. The Leucocytotoxic test has been around for many years and numerous trials have failed to show any diagnostic accuracy. Then tests such as Applied Kinesiology, VEGA, Provocation-neutralisation testing, Hair analysis and Pulse tests have been submitted to a few trials. They seem to have no scientific basis and results have not been shown to be reproducible or detect allergies at all.

The criteria for an allergy test

An Allergy Test should reliably identify one or more agents to which the patient reacts on each exposure. These allergens must be the cause of the patient’s immune-mediated allergic symptoms. This reaction need not necessarily be IgE mediated, but may involve a T-cell Delayed hypersensitivity reaction or direct Histamine release from Mast Cells and Basophils. The test should be reproducible and identify the implicated allergen on each occasion the test is done. The allergy should be specific to that allergen with minimal false positive test results (when the test is positive in someone with no allergy), or false negative test results (where the test is negative in a person who is known to be allergic to that allergen). Abnormal (Positive) results should always be associated with clinical allergic disease.

Three tests are undergoing evaluation for allergy diagnosis and results of preliminary studies are very encouraging.

Histamine Release Test

Histamine is the chemical that drives the initial acute allergic reaction causing itching, swelling and congestion. Sometimes in allergy, histamine is released from Basophils and Mast Cells by non-IgE controlled mechanisms and our conventional IgE measuring allergy tests are of no diagnostic use. It would therefore be ideal to directly measure histamine released in an allergic reaction. A method to measure histamine released from Mast Cells and Basphils has now been developed. The Histamine Release test can directly measure Histamine release from Basophils in "In Vitro". Hence we can measure allergy to any number of agents by mixing these agents with the patients blood Basophils in the laboratory. The resultant Histamine released will accurately and positively identify if the patient is allergic to that allergen by using a Radio-immune Assay (RIA) which measures the amount of Histamine released. The test only requires a small amount of blood for each allergen. Unfortunately the blood must be freshly drawn, the test is expensive and not widely available yet. Occasionally other histamine like substances (vaso-active amines) may cross-react in the blood specimen, resulting in a false positive test. As a result this test is still undergoing evaluation and is not yet commercially available.

CAST Test (Cellular Allergen Stimulation Test)

The Cellular Allergen Stimulation Test (CAST, FAST or FLOW-CAST) test is another new test undergoing evaluation. In this test, we measure other allergy mediators known as Sulphido-leukotrienes, which promote the allergic reaction and resultant inflammation. This test can be used in Non-IgE mediated allergy but measuring mediator release when the patients white blood cells are mixed with the offending allergens. The antigen causes the white blood cells in the test-tube to release sulphido-leukotrienes which as then measured. A test is considered Positive if over 400pg/ml of Leukotriene is liberated in the supernatant. The CAST test has very good diagnostic accuracy with a wide number of allergens, particularly for diagnosing allergy to drugs, bee and wasp venom, food additives and colourants. This is very much an experimental test that is being tried out at a number of allergy centres but is not yet widely available. The CAST test is also undergoing extensive evaluation by the developers Buhlmann Laboratories (a Swiss based company) and marketed in the UK by Diagenics Ltd. Again, the test requires freshly drawn blood and is at present still very expensive and not readily available. However the prospect of using CAST in diagnosing allergy to additives, insect venom and drugs, which to date cannot readily be diagnosed, is an exciting development.

Antigen Induced T-Cell Proliferation Test

Another new test under evaluation is the Antigen Induced T-Cell Proliferation (or Lymphocyte Transformation)test, a test for Delayed Allergic Hypersensitivity reactions. These include those allergic reactions that take over 24 hours to manifest, and in which it is very difficult to detect the offending allergen due to this delay. The patient’s blood T Cells are incubated with the allergen for 5 days and then chemical cytokines, which mediate the allergy, are measured in the supernatant. The problem is that the cytokines measured are not as yet reliable indicators of allergy and we see positive results in both allergic and non-allergic people. This test therefore is not recommended at present and is undergoing further evaluation.

There are some test that have been around for quite some time which have been shown to be unreliable in allergy diagnosis. Every few years they are re-marketed under a new brand name usually with a lot of media hype and interest. The Leukocytotoxic (Bryan’s) test and ELISA test are two such tests.

The Leucocytotoxic Test (Bryan’s Test)

Bryan’s Leukocytotoxic test was originally developed in 1956 by a Dr Black, and further elucidated by Bryan in 1960. The basis of the test is that if the patient’s white blood cells are mixed with the offending allergen, they swell. The test then measures any swelling of the Leukocytes (white blood Cells) and if a certain threshold of swelling is measured., using a Coulter Counter – a Positive result is recorded. Studies to date have shown poor correlation between this test and clinical allergy. The marketers, who rely on anecdotal evidence of efficacy, do not mention these disappointing clinical studies. A large number of allergens are tested for and patients are usually positive to a number of foods, additives and other agents. Katelaris in Australia and Steinman in South Africa both conducted studies on the ALCAT test and found no diagnostic accuracy. At present the test is marketed in the UK under the name "Nutron". Despite claims to the contrary, no large studies have ever shown the test to be accurate despite it being available for 44 years.

The original protagonists of the ALCAT test (which includes the Leucocytotoxic test and Nutron Test) could only site a few non-peer reviewed congress abstracts as evidence that it had worked. While the antagonists (some of the leading opinion leaders in the allergy of field including Bindslev-Jensen, Potter and Katelaris) have substantial data on record to show a poor diagnostic accuracy. The lack of medical support for these tests, is often blamed on a conspiracy by the larger Multinational Diagnostic companies to try and remove the "smaller" opposition from the market. This perception is not a true evaluation of the situation.

The IgG ELISA Allergy Test

Another allergy test of questionable accuracy is IgG ELISA test. This test measures IgG antibodies to the various foods. This should not be confused with IgE antibody testing in conventional RAST and UniCAP testing. Although a patient may develop IgG antibodies to food, this is a non-specific reaction and there is no evidence to suggest that this test has any diagnostic value. Until scientific evidence is available to validate this test, we cannot recommend its use for allergy diagnosis.There is some evidence that IgG antibodies may even protect against the development of food allergy!

The following tests are not validated and play no role in allergy diagnosis. They are still widely used but mainly by Complementary Medical Practitioners

Applied Kinesiology

Applied Kinesiology was developed in the USA by Goodheart in 1964 and relies on energy fields within the body to diagnose allergy and intolerance. It is popular with Chiropractic practitioners in the USA. In this test, the practitioner tests the patients muscle strength when the allergen is placed in a vial in front of them. The shoulder strength (Deltoid muscle) is usually tested for weakness. The patient holds out their arm and the practitioner applies a counter pressure – if the patient is unable to resist the counter pressure, the test is considered positive to that allergen. The antidote to the allergy is then also held in front of the patient and if the weakness is reversed that is the correct antidote. There are a number of variations to the technique of muscle testing and many practitioners complement the test by holding a magnet in front of the patient. There is no convincing evidence that this test has any useful role to play in allergy diagnosis.

VEGA Testing (Electrodermal Test)

This test was developed by German physician Dr Reinhold Voll in 1958. The VEGA Test (or Electrodermal Test) involves measuring electromagnetic conductivity in the body using a Wheatstone bridge Galvanometer. The patient has one electrode placed over acupuncture points and the other is applied to a battery of allergens and chemicals in a metallic honeycomb. A fall in the electromagnetic conductivity or a "disordered reading" measured indicates an allergy or intolerance to that allergen. Newer transistorised/computerised versions of the original VEGA or Voll test are called Dermatron, BEST, Quantum and LISTEN Systems which have a similar application and give more rapid results. Some proclaim to test for 3500 allergens in 3 minutes! Katelaris et al and Holgate performed independant double blind testing comparing VEGA testing with conventional testing in known allergy sufferers, and the VEGA Tests had no reproducibility or diagnostic accuracy at all.

Hair Analysis Testing in Allergy

Hair is analysed for allergies in two ways. First of all, the hair is tested for toxic levels of heavy metals such as Lead, Mercury and Cadmium or low levels of Selenium, Zinc, Chromium, Manganese and Magnesium. There is no scientific evidence to support the hypothesis that these heavy metals have any bearing on allergic diseases. Hair samples are usually sent away for analysis and numerous studies have failed to find any accuracy in hair analysis diagnosing allergies. Another hair test is called Dowsing. The dowser swings a pendulum over the hair and an allergy is diagnosed if an altered swing is noted.

Auriculo-cardiac reflex

Suspected allergens are placed in filter papers over the skin of the forearm. A bright light is shone through the ear lobe or back of hand. At the same time the pulse is assessed. If the filter paper contains an allergen to which the patient is allergic, the pulse increases by 12 or more beats per minute. To date, no scientific data is available to validate this test.

Provocation-Neutralisation Tests

The allergen is applied sublingually, or by intradermal injection. Increasing test doses are given until a wheal appears on the skin (Provocation Dose), as the dose is then decreased until the wheal disappears. This is the Neutralisation Dose. This neutralising dose is used to treat the allergy and "desensitise" the patient. This test has also not been validated by studies and has no diagnostic reliability in allergy diagnosis and treatment.

Nampudripad's Allergy Elimination Technique (NAET)

NAET has to be the most unsubstantiated allergy treatment proposed to date. It consists of combination of discredited methods of diagnosing and treating allergy such as kinesiology, Vega testing and acupuncture. It was proposed in 1983 by American chiropractor Devi Nampudripad, hence Nampudripad’s Allergy Elimination Technique (NAET). The premise is that allergy contrary to our current understanding, is due to some form of internal energy blockage triggered by abnormal energy fields in the brain and Nampudripad proposed that after 20 or so treatments she can reprogram the brain and body energy flow and eradicate all allergies and many other diseases affecting mankind. However the whole issue of energy flow and electrical fields in the body being the cause of allergies has not ever been proven.

Beware of anecdotal and unsubstantiated allergy tests

These tests are often promoted as "wonder" diagnoses and anecdotal stories of lifelong allergies finally being diagnosed abound. It is naïve for medical practitioners to accept these individual anecdotal reports of diagnostic efficacy without any scientifically validated studies to prove their worth. We often read about similar tests in the media and unsuspecting patient’s flock to part with their hard-earned money. Often conventional medical practitioners are accused of bias against these simple and "cheap" tests and feel pressurised to try them out. On the other hand, a convincing practitioner armed with an impressive allergy-diagnosing "contraption" can talk even the most sensible patient into believing their pseudo-scientific explanations and anecdotal reports of allergy cures. Once the patient realises that they have been incorrectly diagnosed, they feel embarrassed, put the matter down to bad experience and hardly ever complain about the treatment or costs involved. For more information on these dubious tests visit the Quackwatch website at www.quackwatch.com

Written by Dr Adrian Morris Click here for the Surrey Allergy Clinic.

September 2006

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