Inaccurate Testing

This is one of a series of several posts discussing issues that complicate the diagnosis of allergies. The summary and index of the series can be found here.

Problem: There is a common belief among doctors and others that IgE testing is the only accurate way to diagnose allergies. However, such tests are not always accurate.

[Edits in brackets]

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This issue is illustrated by a statement from The British Dietic Association that typifies a common attitude toward allergies and testing. It says, "The only reliable way to test for a true allergy is an IgE blood test, a skin prick test or a patch test."

That's a common misconception among doctors and even allergists. The scientific community largely agrees that none of those tests are really all that accurate.

Skin prick tests are the most commonly-relied-upon method of diagnosing allergies. As I discussed in another article, a significant portion of patients will show a positive reaction to the negative control, making accurate interpretation of such tests difficult or impossible.

Even with no reaction to the negative control, the statistics I've seen for reliability of skin prick testing range from about 50% to 90% accuracy, or sometimes as low as 15% in accuracy and specificity.

[Generally these tests are considered to be more accurate when negative than when positive. A negative result (no wheal and no flare) should be close to the high end of the accuracy range in IgE-regulated allergies, though a person can still have a food intolerance (not considered a true allergy, though it may have some similar symptoms) with a negative reaction. According to research, false positives are far more common than false negatives, although false negatives do happen.

With a large enough welt, skin prick testing approaches near-100% accuracy when it comes to avoiding false positives. What is unclear is exactly how large of a welt is required to get a reliable positive result. I've seen recommended protocols requiring a welt ranging from 2mm in size to 8mm in size before the result is considered a reliable positive.

The size of welt that accurately corresponds with observable clinical reactions to a food may vary according to the food, the method of testing and the individual being tested. Interpreting results that fall between no reaction at all and a very large wheal can be difficult.]

An article published by a Mayo Clinic Doctor in American Family Physician says, "In a study(7) where the gold standard for allergy was a double-blind food challenge to the suspected allergen (e.g., egg, milk, peanut, soy, wheat, or fish), the sensitivity of percutaneous tests was 76 to 98 percent, with specificity ranging from 29 to 57 percent, depending on the food extract used for testing."

Most sources agree that the other methods of testing (subcutaneous testing, blood assay testing, etc.) are even less accurate.

[However, combining several testing methods, particularly combining skin testing with either blood IgE testing such as RAST or ELISA testing, and/or a food challenge or elimination diet, gives a much better chance of getting accurate results, especially when combined with a careful clinical history.

If the results of the skin test match up well with the clinical history, then no further testing may be needed. However, if the patient strongly feels that they react to a food which tested negative or do not have problems with a food that tested positive, or if the skin test was rendered inaccurate by factors such as dermographism, following up with a food challenge and/or blood test is important.

Unfortunately, many allergists do not carry out any additional testing even when there are indications for doing so. This lack of follow-through can leave patients being advised to unecessarily restrict their diet, or to continue eating a food which clearly causes reactions.]

Variables such as the tools used, how the test is performed, medications taken by the patient, how recently the person has been exposed to the allergen, recent anaphylactic events, and even the age and quality of allergen extracts used can affect the reliability of testing.

Several studies have indicated that commercial allergen extracts are less effective and reliable in allergy skin-prick testing than a prick-to-prick method (poking the actual food and then the person's arm), especially with fruit.

Incidentally, some experts point out that "false positives" are not really false positives in that they do reliably indicate the presence of IgE antibodies to that substance. In some cases a person may have antibodies with no discernible clinical reaction; in others this could be an indication that the person may develop a more serious allergy with continued exposure to that item.

A severe allergic reaction can develop to any substance at any time, even if the patient has regularly consumed the food previously with no symptoms. [Conversely, some people, especially children, eventually grow out of or become desensitized to allergies with strict avoidance of the food. Sometimes this immunity lasts, and sometimes the allergy resurfaces later.]

Test results can provide useful information, but clinical symptoms trump testing.

An elimination diet (taking out a food to see if symptoms subside, and then reintroducing it to see if they return) can be used with some reliability to diagnose adverse food reactions, and is often used in conjunction with other testing to confirm results. [An elimination diet is best done under the direction of a doctor.]

The gold standard for diagnosing allergies is a double-blind oral challenge: giving the person something (when neither the doctor nor the patient knows whether it's the food or a placebo) and seeing how they react. If the person has an onset of symptoms consistent with allergies after consuming the food, they can be considered allergic no matter what another kind of test says. [If they have no adverse symptoms when consuming a food, even after eliminating it completely and then reintroducing it, then it is not usually necessary to avoid that food even with a positive test result.]

However, even an oral challenge may not be 100% accurate. A number of factors can affect the results of even this test.

If a patient has not eaten the offending food for some time, they may not react to the allergen the first time it is reintroduced.

Many people have delayed reactions or dose-specific reactions that build up over time. [Delayed-reaction allergies usually present with gastrointestinal symptoms or certain types of rashes such as eczema, although GI symptoms and rashes can also be caused by many things other than food allergies.]

A person might have adverse reactions to a food consumed every day while having no reaction to the same food consumed in moderate amounts every fourth day. Rotation diets are often helpful in such cases. [Eliminating the food completely may not be necessary.]

There is quite a bit of speculation about the existence of delayed-reaction allergies that are mediated by means other than IgE antibodies, such as reactions occurring on the cellular level or that attack a body system such as the digestive organs.

For example, some doctors are currently looking at the possibility that corn intolerance can cause a cell-mediated or possible autoimmune reaction. Many food allergies can cause changes directly in the cells of the esophagus [eosiniphilic esophagitis] and the digestive system, or can result in damage to the intestinal cilia (similar to the effect gluten has on celiacs). [Celiac disease is an example of an immune-system-regulated food reaction that is not actually an allergy. It is an autoimmune disease triggered by food, and has different symptoms, though the treatment--avoidance of the offending food--is the same.]

One thing that is often not taken into account in allergy testing and research is that, for many people, the total allergen load can greatly affect the reaction to any individual allergen. A person who is already under a heavy histamine load from one allergen may be pushed over the edge, so to speak, by exposure to another allergen that would not normally cause the body to release enough histamine to cause clinical symptoms.

Many people may have a reaction when exposed to multiple allergens at once, but not when a single allergen is introduced in isolation.

One example of this is in the case of cross-reactivity between foods and pollens. When there is a high level of a particular environmental allergen in the environment, the patient may have a serious adverse reaction to foods containing similar allergens. At another time, when the environmental allergen is not in season, the person may tolerate the food without problems.

Other factors can also influence the incidence of allergic reactions. For instance, exercise-induced anaphylaxis takes place only when both exposure to the allergen and vigorous physical activity are present.

Such uncertainties make it truly impossible to determine for certain that a person has never had or will never have an allergic reaction to a particular substance.

Severe anaphylaxis that is clearly the result of consuming a particular food usually requires no other testing. A skin prick or oral challenge in that case can be too dangerous. Blood testing can still be used to help confirm the diagnosis, but a negative blood test cannot conclusively rule out the allergy.

If a person has had a truly severe allergic reaction that can be strongly connected to a particular substance, they should avoid exposure to that substance no matter what any tests say.