Allergy Testing and Diagnosis

In an ideal world, humanity would be able to collect all of the biological data for a patient and accurately simulate their reaction to different allergens. Currently, we don’t have the capability to do this, but we have tests that come pretty close.

Anecdotal evidence

Anecdotal evidence is the starting point for every allergy diagnosis. Since allergy testing is only performed on patients who are suspected of having allergies, you will most likely experience an allergic reaction before being diagnosed. Read up on the symptoms of allergies and see if your experience aligns, then contact your doctor to be assessed for allergies.

Keeping track of symptoms and the triggers of your reactions will help guide the next steps of testing. What allergens need to be tested? How severe was your reaction? This is useful information for your doctor.

It is important to understand that anecdotal evidence is not sufficient enough to confirm the presence of an allergy. Further metrics that identify the allergen trigger and severity of immune reaction are necessary.

Skin prick test

The skin prick test uses a lancet to introduce allergens into the upper layers of the skin, where most of the biological factors come into play to provide a snapshot that closely models the severity of a real-world immediate IgE-mediated response. The degree of allergic sensitivity is characterized by measurements of a wheal and surrounding erythema (flare) that may develop within 30 minutes of exposure.

Prick-Prick testing is a variation whereby a fresh food sample is pricked followed by immediate pricking of the skin and can provide greater sensitivity.

A skin prick test is useful because the results are indicative of the body's overall reactivity to a specific allergen. It provides a reliable confirmation of allergic sensitization, and it gives foresight into how a patient would react to real-world allergen exposure.

What are the risks of a skin prick test?

The typical result is minor discomfort from the wheal, which may be itchy or painful. Very rarely, an anaphylactic reaction could occur.

Skin patch test

A skin patch test is when a specific allergen is placed on the skin in a closed and air-tight environment, which is created using a patch. This patch is left on for 24-48 hours and then the resulting reaction is measured and recorded.

A skin patch test is useful because it measures the delayed immune reaction to specific allergens without triggering an immediate IgE-mediated response. This is useful for understanding non-IgE or mixed-IgE allergies such as contact dermatitis, non-IgE mediated food allergies, EoE, and atopic dermatitis. Additionally, immune cells in the skin can mimic those in the stomach, so the resulting reaction can also indicate the degree of gastrointestinal sensitivity.

What are the risks of a skin patch test?

The typical result is minor discomfort from the resulting wheal, which may be itchy.

Intradermal test

An intradermal test is performed by using a needle to inject allergens into the skin, which provides similar results to a skin prick test but with additional sensitivity that lowers false negatives. This type of test is commonly performed for suspected insect sting or penicillin allergies.

What are the risks of a skin prick test?

The typical result is minor discomfort from the wheal, which may be itchy or painful. Very rarely, an anaphylactic reaction could occur.

Blood testing

A person’s blood contains many different biomarkers such as IgE that indicate the potential presence and severity of an allergy. By collecting this blood through a blood draw or fingerstick, the biomarkers can be measured.

The most common biomarkers measured are total IgE and allergen-specific IgE, which indicate the presence of sensitization to allergens. Sometimes IgG or IgG4 are measured to better predict a real-world reaction since IgG4 is considered to compete with IgE for binding to an allergen, thereby inhibiting histamine release. In cases where celiac disease is suspected, specific IgA antibodies may be measured.

What do allergy blood test results mean?

Total IgE measures the amount of IgE antibodies in the blood and indicates the likelihood that you will experience allergic reactions.

Allergen-specific IgE measures the amount of IgE antibodies that target a specific allergen and indicates the likelihood that you will experience allergic reactions toward that allergen.

Real-world example

Here are the results from my own allergen-specific blood test:

As you can see, peanut and banana are my most sensitized food allergens. In practice, it just so happens that these are also my most symptomatic allergens as they both induce anaphylaxis. Wheat and corn are elevated for me as well, but mostly only produce delayed gastrointestinal symptoms. Pork and beef induce immediate mouth swelling and vomiting, textbook allergy symptoms, but IgE wasn’t detected. This probably means the allergen extracts used for testing did not contain the proteins that I am allergic to. It is important to understand that allergy testing is not perfect, so don’t let the results upstage real-world experiences.

What are the risks of a blood test?

Since a blood test doesn’t directly expose the patient to an allergen, it doesn’t carry any serious risks such as anaphylaxis, making it very safe.

Oral food challenge

An oral food challenge is the gold standard for diagnosing food allergy. It doesn’t just simulate a real-world reaction, it is a real-world reaction in a controlled environment.

A patient eats a calculated amount of sensitized food in a short period of time, likely given in ramping doses. The resulting reaction will confirm or deny the presence of a food allergy to the ingested food and determine the allergy's severity. An oral food challenge can catch all types of food allergies, both IgE and non-IgE mediated.

If the patient is asymptomatic after ingesting the food, they will perform rigorous exercise on something like a treadmill. This dilates the blood vessels and promotes an allergic reaction to occur. Exercise also enables the test to catch food-dependent exercise-induced anaphylaxis. If an allergic reaction doesn't occur after exercise, it is not going to occur, and the patient is safe to go home. It allows the supervision time post-challenge to be reduced and decreases the chance of a reaction occurring outside the clinic.

Are there different kinds of oral food challenges?

Yes, there are different measures that can be taken to increase the accuracy of the test.

In a Double-Blind, Placebo-Controlled Food Challenge the patient has two separate tests, one using the food allergen and the other using a placebo. The food allergen and placebo are made to look identical so that both the doctor and patient will not know which one is being given. This process helps to eliminate psychosomatic reactions in the patient and preconceived notions from the doctor.

A Single-Blind Food Challenge lets the doctor know which one is being given, but the patient is still in the dark. This process helps to eliminate psychosomatic reactions in the patient but introduces potential preconceived notions from the doctor.

An Open-Food Challenge doesn’t involve a placebo and everybody knows that the food allergen is being given. This kind of challenge is done when the patient’s nervousness is not suspected to affect test results.

What are the risks of an oral food challenge?

An oral food challenge brings on all the risks of a real-world reaction, so anaphylaxis or severe reactions are possible. However, since it is a controlled environment, measures are taken to decrease the chance of a severe reaction and emergency medical equipment is available if needed. Despite the risks, it is much safer to confirm food allergy during an oral food challenge than for the patient to accidentally experience an allergic reaction outside the clinic.

Basophil activation test⁷⁷

The basophil activation test uses a patient’s collected blood to measure the degree of degranulation following exposure to an allergen and correlates directly with histamine release. Basophils are more readily available in blood than tissue mast cells and are a more accessible relevant sample to study immediate allergic reactions and anaphylaxis.

This test can be used to diagnose allergies and provides a snapshot of a real-world allergic reaction without directly exposing the allergen to the patient.

What are the risks of a blood test?

Since a basophil activation test doesn’t directly expose the patient to an allergen, it doesn’t carry any serious risks such as anaphylaxis, making it very safe.