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Although sometimes straightforward, diagnosing and testing for food allergies is often more difficult than patients imagine. One of the main challenges is that the traditional skin prick testing (which is very good at picking up environmental allergies) is not very good for diagnosing food allergies. In fact, when they come up positive, these skin prick tests can be wrong 60 to almost 80% of the time! It sounds unbelievable but it is true. You can read all about it in a Scientific American article from November 2015. The article also points out that most family physicians and pediatricians are not aware of this, so they often tell patients who may have had an allergic reaction that all they need to do is get a panel of food allergy tests to find the cause of their reaction. But with the high rate of false positive tests, this can lead to the wrong conclusions, unnecessary dietary restriction, and in extreme cases, even malnutrition. Worse, there can be false negative tests. That means that even if the patient is allergic, it doesn’t always show on the skin prick tests, and if they eat the food again, they are at risk of having another allergic reaction. (Why there are false positive and false negative reactions is detailed below). It is important to understand that skin prick tests at most give us some probability about whether or not you are allergic to a particular food.

If the tests are so inaccurate, how are food allergies diagnosed? Well, the most important thing is the patient’s history, that is your observations about what exactly happens and when it happens in relation to eating a specific food. In practice guidelines for allergists, it is stated that diagnosing food allergies starts with a METICULOUS history. A series of tests, described below, may lead up to the final test: an oral challenge. This involves the patient eating the food in question under medical supervision, so that if allergic symptoms occur, they can be treated promptly. This is often done in a hospital setting, as sometimes the reactions can be severe.

Allergic reactions involve certain molecular and cellular processes that will predictably cause certain symptoms within a certain range of time after ingesting the offending food. That is where your observations are so important. If the nature of the symptoms are not those caused by allergic reactions, or occur well outside the time for allergic reactions, then testing for allergies may not be required at all. Essentially, if you are eating a particular food, and don’t have symptoms of allergy, you have done your own oral challenge, that is eating the food, and you do not have allergies.

Food allergy versus food intolerance: 2 common examples

Lactose Intolerance vs. Milk Allergy:

Many people have lactose intolerance, and confuse this with allergy. Allergy testing will not detect lactose intolerance. Lactose intolerance occurs when someone lacks the enzyme, called lactase, which breaks down lactose, a sugar naturally found in milk and certain other dairy products. When a person with lactose intolerance ingests milk or dairy products with lactose, the lactose is not broken down, and it gets into the intestine. There, the lactose is fermented by bacteria normally present in the intestine. This causes gas, bloating, cramping and can lead to diarrhea. Lactose intolerance can be diagnosed by special breath tests, but these are often unnecessary. The person can simply try eating lactose free products, or they can take a supplement that contains the lactase enzyme.

In contrast, milk allergy occurs when a person’s immune system makes particular antibodies, those of the class we call IgE, or allergic antibodies. These IgE antibodies recognize the molecular structure of the milk proteins. When the milk protein is consumed, the protein fits like a key into the “lock” of the allergic antibody. The “doors” open on the cells (called mast cells) where these allergic antibodies sit, and release specific compounds, like histamine. These compounds, made naturally in your body, cause blood vessels to dilate and get leaky (so one experiences redness and swelling, and if a lot of fluid leaves the blood vessels, blood pressure can drop dangerously low), they stimulate itch nerves, so you may want to scratch, they can cause smooth muscles, like those in your intestines, to contract, so you may feel stomach cramps and have diarrhea, or those in your lungs and breathing tubes, so you may have wheezing, and they can increased mucous production, so you may have runny nose or wheezing. These reactions usually occur within minutes to a few hours after ingestion of the offending food, are relatively short lived. They usually resolve in a few hours, though if severe swelling occurs, it may take a few days for the fluid to re-adsorb. Strict avoidance of milk and milk containing foods is important, as ingestion can result in anaphylaxis.

Celiac Disease (Gluten Intolerance) vs. Wheat Allergy:

Another example of food intolerance is that of gluten intolerance or celiac disease. This occurs when a person’s immune system mounts an inappropriate response to gluten in wheat and some other grains, and in doing so, causes damage to the lining of the intestine. This results in bloating, diarrhea, and the inability to absorb nutrients properly. Patients with celiac disease may therefore lose weight, become anemic, have low bone density, and develop problems with their nervous system. Screening for celiac disease usually begins with a blood test to look for the characteristic antibodies that are associated with celiac disease. These antibodies are not allergic IgE antibodies, and therefore they cannot be detected by allergy skin prick testing. In order for the blood test for celiac disease to be reliable, the person must have been consuming gluten containing foods in their diet. If they have avoided gluten for some time, the celiac antibodies may temporarily decrease, and the test will give a false negative result. Done properly, the celiac blood test is about 90-95% accurate. The final diagnosis of celiac disease is made on the basis of a small bowel biopsy, obtained by doing an upper endoscopy procedure. The patient is sedated, and a small tube is put down the throat, through the stomach and into the upper small bowel where a tiny sample of tissue is taken for examination. Again, the person must have gluten in their diet, or the characteristic damage caused by gluten ingestion may have already healed. If someone has celiac disease, strict avoidance of gluten is necessary to prevent further damage to the intestine. This can be very difficult and expensive; not something you want to do unless necessary.

Some people have bloating and abdominal discomfort when eating gluten, but do not show evidence of celiac disease. Gluten is hard to digest for some people, and they are thought to have non-celiac gluten intolerance. There is no specific test for this condition. It is not thought to be dangerous, though it is unpleasant. Patients can avoid gluten, but small amounts are not particularly harmful.

In contrast, wheat allergy is caused by allergic IgE antibodies that recognize the molecular structure of the wheat proteins. When wheat is consumed, the wheat fits into the “lock” of the wheat allergic antibodies, causing the release of the compounds from mast cells, like histamine, that cause redness, swelling, contraction of smooth muscle in the intestine, and itching, just like milk allergy. This type of reaction can be detected by skin prick testing (although there can always be false positive and false negative results). Strict avoidance of wheat is necessary. as ingestion of wheat can lead to anaphylaxis.

Diagnosing Food Allergies

Sometimes this can be straightforward. For example, say a person has had 3 or 4 episodes of itchy welts, shortness of breath, wheezing, nausea and lightheadedness. All the episodes occurred within15 to 45 minutes of eating. The only food the person had eaten on those same 3 occasions, that he can recall was shrimp. The person has subsequently eaten the other ingredients he had eaten on the days of his reaction,with any symptoms, but had not had shrimp or other crustaceans (lobster or crab) since. On each occasion the patient was taken to the Emergency Department, and was given epinephrine, antihistamine, and corticosteroid, and was better in a few hours. The allergist may start with a skin prick test to detect IgE antibodies to shrimp, and say it is strongly positive. In this case, it is likely that the patient is allergic to shrimp, and further testing may not be required.

But what if the allergy test to the shrimp is negative? The history in this case is strongly suggestive of shrimp allergy, and we know that false negative results can occur, so the next step may be a blood test for IgE antibodies for shrimp. It is sometimes possible that the allergic antibodies can be detected in the blood, but not on the skin. If the blood test is strongly positive, then further testing is not usually required.

But what if the blood test is negative too? We know that there can be false negative results with the blood tests too. So the next step is sometimes done with an actual sample of the food in question. The patient is asked to bring in a sample of shrimp. The shrimp is scratched with a small lancet, and then the patient’s skin is scratched with that lancet, just enough to transfer a tiny bit of shrimp under the skin surface. If it is positive, then further testing may not be required.

But there can be false negative results with this test as well. So if this test is negative, but allergy is strongly suspected, the next step is a graded oral challenge. Under careful medical supervison, the patient is asked to ingest initially very small, but then increasing amounts of shrimp. Only if the patient tolerates this step is allergy ruled out. But it is important to know that even if the first 3 tests are negative, allergic reactions can occur during the oral challenge, which is why it is done under medical supervision.

Why not go directly to the oral challenge if allergy is suspected? Reactions to the oral challenge can be severe, and are best avoided if possible. If allergy can be convincingly designated with the other tests mentioned above, which are less likely to cause severe reactions, the oral challenge can sometimes be avoided.

Sometimes the allergy skin and blood tests are weakly positive, or there may be other reasons to suspect that that they represent false positive results. In those cases, an oral challenge may be suggested to confirm or exclude the possibility of allergy.

Why are there false positive results with food allergy skin prick testing or blood testing?

Most people will make low levels of allergic antibodies to one or more foods. These may be enough to give a positive skin or blood test, but other factors, which are not fully understood, are necessary for an allergic reaction to occur. For example, one study showed that if 100 people are selected at random (and no questions are asked about their symptoms when they eat peanuts) and undergo skin prick testing for peanut, 9 out of 100 people will have a positive skin prick test to peanut.

But if those 9 people with a positive skin test undergo an oral challenge (that is they are fed peanut under medical supervision), ONLY 2 OUT OF THE 9 will experience any allergic symptoms. So the test to see if the patients are allergic is wrong 7 out of 9 times, or over 70% !!!

That is one reason why history is so important. If you can eat peanuts, and you know you do not have any allergic symptoms, then you have done the most important test of all; you have done your own oral challenge, and skin or blood testing is not needed.

If I am really allergic to a food, why do the skin prick and blood tests not always show it?

There may be several reasons why allergy tests are negative when a person is actually allergic. This is why a series of tests leading up to an oral challenge is sometimes necessary.

First, if testing is done soon after an allergic reaction, it is possible that the food-specific antibodies have been “used up” and more have not had time to be replaced. Your allergist may wish to repeat the tests at a later date to see if this has happened.

The testing extracts used for skin prick testing have been processed from the original foods, but sometimes this results in changes in the shape of the food molecules so they no longer fit into the “lock” of the allergic antibodies, and the test can be falsely negative.

The blood tests use a different method to bind the allergens of the food in questions to a matrix that wily negative allow the detection of allergic antibodies in a sample of the patient’s blood, and sometimes the allergic antibodies can still recognize the allergens in this condition, but not always, so this test can be falsely negative too.

And sometimes a patient will make allergic antibodies “locally”, only in the gastrointestinal tract, but not in sufficient quantities to “spill over” into the bloodstream or skin, so skin prick test, and blood tests are negative, but the patient does react with an oral challenge.

Why are there no more accurate tests?

Better tests would be very helpful for patients and allergists alike. One test, called the basophil activation test has shown some promising early results. Further studies are required before it is put into practice. It is not available currently.

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