Tree Nut Allergies May Be Massively Overdiagnosed

Millions of Americans live in fear of the peanut. And for good reason: These humble legumes are associated with some of the most severe of all food-related allergic reactions, including life-threatening anaphylaxis. Moreover, studies show that peanut allergies in children have more than tripled from 1997 to 2008, leading to what the National Institutes of Health have deemed a “growing public health problem.” 

It’s no wonder that the once-ubiquitous peanut butter and jelly sandwich has been quietly disappearing from school menus around the nation. But sadly for the peanut-allergic, the trouble often doesn’t end with PB&J. Many also know the frustration of having to studiously avoid chocolate chip cookies with walnuts, candy bars with almonds, ice cream with pistachios, or any other delicious treat made with tree nuts.

After all, as they’ve been warned by their doctors, skin and blood test results reveal that those with peanut allergies are also often allergic to tree nuts. Better safe than sorry, right?

A new study by a team of allergists suggests that those tests aren’t as accurate as we think—meaning tree nut allergies may be massively overdiagnosed. In many cases, peanut-allergic individuals who studiously avoid other nuts could be doing so without cause, the authors conclude. Not only that, but people who've had an allergic reaction to one type of tree nut may actually be able to eat all the ones they've never tried—even though blood or skin tests suggest otherwise.

Prior to their study, published March 27 in the journal Annals of Allergy, Asthma and Immunology, the authors noted that there was little research on nut allergies beyond peanuts—which are actually legumes—though they weren't sure exactly why. “[Allergy] research has focused primarily on peanut, egg, and milk allergies,” says Chris Couch, a Phoenix-based allergist and co-author of the study.

To fill that knowledge gap, Couch and his co-authors decided to (very, very carefully) feed tree nuts to a group of people with known peanut or other nut allergies.

The results were eye-opening. The peanut-allergic participants, they found, were able to eat other nuts without incident at a stunning rate of 96 percent. Moreover, more than 50 percent of participants with a known allergy to one tree nut tested negative to the others—meaning that many of those who had gone their whole life thinking they were allergic to all tree nuts could actually be enjoying other types of nuts.

“We want to liberate people's diet as much as we can,” says Couch. Unlike a peanut allergy, which renders many types of cuisines off-limits, "it's possible to just avoid one type [of tree nut] if that's all you're allergic to—that cashew or pistachio—while still eating others.” Based on the results, the researchers suggest that more people who have tested positive for tree nut allergies should consider trying small doses of nuts they haven't tried, under the supervision of a licensed allergist. 

Couch adds that the uncertainty and fear his patients often experience can be magnified when they believe they or their children are allergic to foods but don't know for sure, because they've never actually tried them. The new findings, he hopes, will “relieve a lot of anxiety.”

An allergy occurs when your body reacts inappropriately to food or another substance, thinking it’s an invader. When this happens, your immune system produces antibodies known as immunoglobulin E (IgE) to “fight off” the allergen. Reactions can vary, but allergic responses to both peanuts and tree nuts are more likely to induce severe reactions including anaphylaxis, a sometimes life-threatening condition in which blood pressure plunges, and breathing can be difficult.

While death by any food allergy is rare—food-related deaths likely total fewer than 50 cases per year according to a study of U.S. healthcare databases—these allergies are responsible for about 200,000 emergency room visits annually. Besides the obvious psychological cost to the individual, systematically over-diagnosing allergies has a larger economic cost as well. In a study last year, Couch and co-authors calculated that delaying food challenges for a patient who turns out not to be allergic costs the health care system more than $4,000 per year for extraneous services.

An estimated .6 to 1.3 percent of the U.S. population has a peanut allergy, according to a 2014 report by the National Institute of Allergy and Infectious Diseases. About half that number have a tree nut allergy. Given those numbers—coupled with the difficulty of determining exactly which kinds of nuts were in different foods—allergists have historically taken a conservative approach to nut allergies. If you've had a reaction showing you're allergic to peanuts or one kind of tree nut, many advised simply avoiding all other tree nuts.

According to the new study, though, the assumption that one nut allergy is usually linked to other nut allergies may not always be true. The allergists studied 109 people with known allergies to one type of tree nut, because they'd had a physically adverse reaction in the past. Such patients are considered more likely to have other nut allergies, and indeed, study participants did often test positive for allergies to nuts other than the type that had caused their reaction.

But upon trying some of those other nuts for the first time, more than half of them found that they had no ill effects—meaning that despite blood and skin test results, they weren't allergic after all. Almonds were a special case: 100 percent of participants passed the almond challenge, with cashews being the most likely tree nut to cause a reaction.

(It should be noted that oral food challenges can be dangerous and should never be attempted at home, the researchers caution. These tests took place in a controlled environment, with researchers feeding participants carefully measured doses of food and closely monitoring them for any reaction. At the first sign of allergy, like flushing skin or hives, the test was stopped and the patient can be given any needed medical treatment.)

Andrew MacGinnitie, clinical director of immunology at Boston Children's Hospital, says the research supports an emerging consensus among many allergists that they aren't challenging enough kids. “We know from this work and other work, that the testing we have now isn't very good for predicting who's going to have a reaction and who isn't,” says MacGinnitie, who wasn't involved with the new study. “There can be two people with identical testing and one will react during a food challenge, and one won't.”

The study also paid close attention to participants who reported known peanut allergies. Researchers had those 46 peanut allergic patients take 68 different food challenge tests with various tree nuts. Surprisingly, the peanut-allergic participants passed allergy tests for other nuts at the high rate of 96 percent. “We found that the pass rate for tree nut challenges was pretty high for people with peanut allergies—and that's a little different from previous studies,” Couch says.

“It's a common clinical situation that we test someone who has reacted to peanut, and is clearly allergic to peanut, and their tests also show much lower values to tree nuts,” MacGinnitie adds. “Our practice has been to tell those people to avoid tree nuts. But I think that this study sort of shows that we are wrong about that and a lot more of those patients could tolerate tree nuts.” 

Food allergy tests, whether blood tests or skin prick tests, work by detecting the levels of IgE (the antibodies your body produces) that are associated with the food you've consumed. But that association isn't ironclad, notes Matthew Greenhawt, an allergist at the Children's Hospital of Colorado and a co-author on the study. Greenhawt is also a panel member on the National Institute of Allergy and Infectious Diseases’s Guidelines for Peanut Allergy Prevention and a member of physician and medical advisory boards for Aimmune, Nutricia, Kaleo Pharmaceutical, Nestle and Monsanto. 

In cases where no antibodies are detected the test results are pretty easy to interpret, says Greenhawt. “It's very hard to be allergic without any antibody detection,” he says. “But the presence of antibodies, we have a much harder time interpreting that, ... For example, you might test positive to a tree nut because you're allergic to birch pollen, which is in the air in your region. The test is detecting an antibody that's there, but it doesn't have the context that you need—and these things look alike.”

By giving food challenges to people whose test results show nut allergy at varying levels of IgE antibodies, Couch and Greenhawt hope to help identify new thresholds at which people would benefit from taking a food test. They suggest that in many cases, because of the inaccuracies in skin and blood tests they describe, those who tested positive actually had a 50/50 chance of passing a food test. “Hopefully, this is a reasonable ratio that could encourage providers to offer more testing,” Greenhawt says.

Currently the ratio used for recommending a food challenge is often much higher than that, MacGinnitie adds. “There's no exact ratio that's correct but I think it should be a lot closer to 50/50 than to 90/10.”

Testing decisions should also be individualized and factor in patient choices, MacGinnitie adds. He describes a situation that was recently documented by Robert Wood at Johns Hopkins:

“If you have a kid you know is allergic to five tree nuts, and has reacted to those, clearing her for Brazil nut probably isn't very important to her,” he says. “On the other hand, what if you have some kid whose only thought to be allergic to almonds and he is about to go off to college? Even if it's only 20 or 30 percent likely that he's not allergic, because of the chance that he can eat safely at the dining hall and not carry an EpiPen, taking a food challenge might be worth it.”

So yes, just because you’re allergic to peanuts or one type of tree nut doesn’t necessarily mean you can’t eat all the others. But until you've spoken with your licensed allergist and undergone the appropriate food challenges, you'd still be nuts to try eating them on your own.

Brian Handwerk | READ MORE

Brian Handwerk is a science correspondent based in Amherst, New Hampshire.