Fourteen year old Hanna was at the mall with friends when she discovered she was allergic to macadamia nut.  This fact became clear when she nearly died. She had only taken a few bites of the ice cream with macadamia nut from Cold Stone Creamery.  She had eaten a variety of nuts on numerous occasions without problems, her favorites being almond and hazelnut, but his was her  first time to try this macadamia nut.

By the time paramedics had arrived, she was covered in hives, felt dizzy, had vomited, and could not stand

Immediately her mouth began to burn and after a few minutes her face turned bright red.  She felt itchy all over, her eye lids and lips began to swell and she had a hard time breathing.  By the time paramedics had arrived, she was covered in hives, felt dizzy, had vomited, and could not stand.  The paramedics did not waist anytime:  A syringe filled with epinephrine was jabbed into her upper leg, an IV was started and connected to a larger bag of fluid and she was taken to the nearest hospital.  When she arrived at the emergency room she was feeling better, the hives were clearing and she could breath easier.   She was able to go home after several hours.

Trip to the Allergy Office

She was seen in our office the next week for allergy testing.  A small drop of macadamia nut extract was placed on the skin of her back and gently pricked. After 20 minutes the test was read by measuring the size of any swelling at the test site, the “wheal” as well as any redness or erythema.  The size of the test wheal is compared with a negative (saline) and a positive (histamine) control. A wheal that is 3-4 mm larger than the negative control is a positive test. Hanna’s macadamia test was over 20 mm!

For Hanna, the diagnosis of allergy to macadamia nut is clear.  She has a compelling history of typical allergy symptoms appearing within minutes of exposure and a strongly positive result on allergy skin testing to the allergen in question.  The recommendation is also clear.   No macadamia nuts…EVER. She will also need to carry an EpiPen in case of accidental exposure.  Having it nearby could be life saving.

Now let’s back up a notch.

Let’s suppose Hanna stayed home from the mall that day to study for a test and mom decided to make an appointment with an allergist to talk about Hanna’s itchy eyes and sneezing during the spring.   In this alternate universe, Hanna has never eaten macadamia nut.    During the visit mom mentioned that Hanna complained of itching of the mouth with almonds and hazelnuts when she was a child  but is now eating both nuts fairly regularly without problems.  She would like to check for tree nut allergy though, “just to be sure”.

Allergy testing is completed and the results show strongly positive reactions to spring tree and weed pollen.  Testing to the tree nuts showed an 8 mm reaction to almond, 6 mm reaction to Hazelnut, both moderately positive.  Macadamia nut showed a 20 mm skin test reaction.

What is the diagnosis?  Is Hanna allergic to almond and hazelnut?

To answer this important question, we need to start with how we define “allergy”.  The definition of allergy has two parts:

1. A history of  symptoms (rash, abdominal pain, breathing difficulty, etc.) on exposure to an allergen
2. A positive result to the suspected allergen on a skin or blood test for allergy

We like to have both to make a diagnosis of allergy. Even though Hanna’s allergy test is positive to almond and hazelnut, she has eaten both frequently without problems.  By definition therefore, she is not allergic to almond or hazelnut.

“Why are the almond and hazelnut allergy tests positive if  she is not allergic.”

There are a number of possibilities but it is most likely that the positive skin test reaction is the result of cross reaction between proteins in the tree nut and very similar proteins in the tree pollen that she is sensitive too. (To learn more about false positive allergy tests, go here.)

Although Hanna understands this explanation (“sort of”) she is still concerned about eating almond and hazelnut now that she knows that the allergy test was positive.  She asks if there is another test that will prove she is not allergic.

In fact, there is….

The Double Blind, Placebo Controlled Food Challenge

The double blind, placebo controlled food challenge is considered the gold standard for diagnosing food allergy.  In this test two foods are prepared, the test food and a placebo food made to look and taste like the test food.  Neither the patient nor those conducting the test  know which is the true food and which is the placebo until after the test is completed.  The use of the placebo removes the chance that symptoms may be related to the patient (or test giver) having symptoms caused by anxiety.

Because of difficulty associated with developing a suitable placebo for every test food, double blind, placebo controlled food challenges are infrequently done.   In stead, open, graduated challenges of the suspected food have become more popular.

Graduated Food Challenge

In this test, the patient is given a very tiny amount of the suspected food while being closely monitored for any signs of a reaction.  If there are no problems after 15-30 minutes, the dose of the food is increased.  This process is continued until a target dose is achieved or until any objective symptoms suggesting a reaction occur.

Allergy testing is always done prior to a food challenge.  If the allergy test is negative or if the patient has a clear history of having eaten the food without problems,  the chance of passing a food challenge is very high.   A food challenge is not recommended in someone who has a clear history of a severe allergic reaction to a food and has a positive allergy test.  Again, this patient is allergic by definition and a food challenge is not needed.

What about the macadamia nut?

More challenging is the question of conducting a food challenge in a patient who shows a strongly positive result on an allergy test and who has never eaten the food.  This is the case with Hanna and the macadamia nut.   Because she has never eaten macadamia nut, there is insufficient information to make a diagnosis of allergy.  On the other hand, the likelihood that she would fail a food challenge test is high because of the strongly positive skin test result.   In this case, the safest recommendation would be for her to avoid macadamia nut.   Although not perfect, cut off values for the size of skin test reaction likely to result in a failed food challenge have been published.

Delayed introduction of allergenic foods because of allergy testing may cause the problem that well-meaning parents are trying to prevent. 

There is increasing evidence that early introduction of allergenic foods to infants is associated with a decrease in food allergy.  For this reason, the unintended consequence of allergy testing of children to foods they have never eaten in hopes that it will be prevent them from having an allergic reaction, is that parents will be afraid to introduce foods that show positive on the test.  Delayed introduction of allergenic foods because of allergy testing may therefore cause the problem that well-meaning parents were trying to prevent.

I have been teaching medical students in my office for the past several weeks. These first year University of Arizona students have recently completed a block of studies on the immune system and are spending time in an allergy clinic to learn how memorizing a million obscure names and pathways  applies to the real world of clinical medicine.

Each student spends only half a day with us so there is not much time to impart wisdom. Since this may be their only exposure to the specialty, I have tried to come up with a few important “pearls” for them to take with them.

Here is one of those pearls: “There is no such thing as an allergy test.”

Since we spend a lot of time in our practice testing patients to find out what they are allergic to, this statement is usually greeted by the students with a polite stare as if waiting for the punch line.

First year medical students are understandably a bit nervous when introduced to the real world of doctoring for the first time. They are quite sure of one thing: They do not know very much now and that somehow, over the course of just four years, they will be expected to know practically everything. They are also quite sure that they have no idea how this miracle of knowledge transfer is supposed to happen.

So the students typically smile politely and try not to say anything that would make them look any stupider than they feel. I try to reassure them and suggest that if there ever was a time to ask stupid questions, your first few years of medical school would be it.

The assumption that somehow you should know and that surely everyone but you knows is pervasive but also foolish and can be a serious hindrance to learning. Wisdom begins when we are able to put our pride in our pocket,  acknowledge our ignorance, and ask the stupid question. The other students, contrary to your assumption,  are also quite clueless,  and certain to be relieved when you do.

Back to the point. Why is there no such thing as an allergy test and why is this so important for medical students to learn?

The answer is in the definition of allergy.

Allergy is an adverse condition and symptoms caused by immunologic sensitization and exposure to an allergen.  An allergen, almost always a protein, is the thing (food, animal, pollen, mold, etc) that your immune system decides – arguable by mistake – you need to be defended against.  The resulting production of specific antibodies that react with the allergen is called sensitization.   Without it, you are not allergic.

Sensitization is the part that we learn from an allergy test.

However, having symptoms when exposed to the allergen you are sensitive to is also part of the definition of allergy. Without symptoms, you are not allergic. No matter what the results of an allergy test say.

A diagnosis of allergy cannot be made without a careful  history. In fact, when allergy tests alone are used to make a diagnosis of allergy – which is often the case when patients ask their family doctor to order an allergy test to find out what they are allergic to – the results can be confusing and misleading and even dangerous. In my experience, this is often the case.

Inappropriate diagnosis made on the basis of allergy tests alone have led to unnecessary restriction of foods, elimination of loving pets from the home, disruptive changes at home and at school, and prescriptions for insanely expensive medications such as Epipens.

On their own, blood tests and skin tests for allergy can give falsely positive results as often as 50% of the time. That means that if an allergy test is positive for peanut, and no consideration if given to the patient’s history, there is a 50% chance that the patient is allergic to peanuts and a 50% chance that they are not.

If history is not taken into account to make the diagnosis, an allergy test is about as good as flipping a coin.

Coupled with a thorough and accurate history, however, an allergy test is an essential tool for a making a diagnosis of allergy.

The history – listening! – is the most important skill for a physician to learn. And this is why it is important for medical students to remember: “There is no such thing as an allergy test”.