Positive Negatives

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: Some patients develop a wheal (positive reaction) to the negative control used in skin-prick allergy testing.

##############

About 5% to 15% of the population reacts with a raised wheal to the negative control in allergy skin-prick testing.

Such a reaction is generally considered to be evidence of dermographism (also called dermatographism or dermatographic urticaria). This is a condition where a person will get a histamine response and wheal from any poke, scratch or pressure on the skin.

Dermographism is considered a contraindication to skin-prick allergy testing. It makes the results difficult if not impossible to interpret.

However, a positive reaction to the negative control is not necessarily indicative of dermographism. The control and/or the carrier used in allergy testing often contains glycerine--a substance known to cause hypersensitivity in some individuals.

Most allergen extracts are in a base of 50% saline and 50% glycerine.

There are documented cases of reactions to both glycerine and the preservatives (especially thimerosol) in saline solution. Several studies have found that a glycerine-containing control has a different rate of positive reactions than saline alone. Glycerin seems to be a comparatively common cause of allergic reactions.

Glycerine is made from oils derived from substances such as corn, coconut, soy, beef, pork, seaweed, and petroleum. Coconut, corn and soy are particularly common sources of vegetable glycerine. Corn, in particular, is notorious for having a higher degree of false negatives with skin testing than many other substances. This would make sense if the glycerine in the control and carrier often contains corn derivatives.

Strangely enough, I could find little if any mention of trying to differentiate between sources of glycerine when an allergic reaction is confirmed. Saying someone is "allergic to glycerine" without looking at the food from which the glycerine is derived is like saying someone is "allergic to oil" because they had a reaction to peanut oil.

Another potential allergen often found in both the saline control and the allergen extracts is phenol. Both phenol and glycerine can cause either true allergic reactions or false positives due to simple irritant reactions (phenol in particular is a highly corrosive and toxic substance, at least in higher than trace amounts).

If a person was reactive to a substance used both in the control and in the allergen extract bases, skin testing would of course be virtually useless. The patient would show raised wheals in response to every allergen unless some of the extracts were prepared differently than others.

Most sources agree that any positive reaction to the negative control makes interpreting test results difficult if not impossible. Yet a common standard is "3 mm larger than the negative control" for a positive result. Many allergists don't take into account that the control should be at or very close to 0 for results to be reliable.

I had a positive result of 3/9 to the control, which meant that none of my 5/7 or 4/10 welts "counted" as positive results--despite a clinical history of adverse reactions to those foods which meant I hadn't consumed some of them for a year or more.

I was told that I wasn't allergic to any foods because none of my welts reached 6/12. My allergist gave no indication that my response to the negative control was in any way unusual or that it could affect the reliability of the results.

My reaction to the control was clearly not the result of dermographism, because other allergens tested showed no wheal or a smaller wheal than the saline control.

There is no standard protocol in place among allergists for distinguishing between dermographism, a false positive for other reasons, and an actual allergic reaction to the negative control in allergy skin testing.

Dermographism is extremely easy and inexpensive to test for. If the patient has dermographism they will get a raised welt from having their skin pressed with a blunt instrument, or from a prick with a bare needle. So why isn't it standard procedure to test for dermographism when a patient shows a positive reaction to the saline/glycerine control?

Apparently there is some precedence in the scientific community for using the smallest wheal as the control if the saline or glycerine control has a larger wheal than one or more of the allergens being tested. The study linked above noted: "If the wheal reaction to the glycerin control was greater than the wheal diameter of the allergen reaction, the wheal size for that allergen was set to zero."

In my case that would have changed the results of my tests, giving me a number of positive reactions instead of all "negative" results as my allergist claimed.