New hope for kids with serious food allergies

"Eating is terrifying when we are not the ones in control,” says Alexandria Durrell, a Brooklin, Ont., mom and allergy blogger whose five-year-old son, Mason, has multiple food allergies, including one to peanuts. Symptoms of a food-allergy reaction can range from a mild, itchy rash to a rapidly progressing, potentially deadly attack called anaphylaxis (which involves a dangerous drop in blood pressure and swelling inside the throat)—and there’s no way to predict the severity. Consequently, Durrell says, every meal that’s not prepared from scratch at home feels like a gamble.

This is the reality that families of kids with food allergies—five percent of Canadian kids or roughly one per classroom—live with every day. It also indirectly affects all of that family’s contacts, wherever the child could potentially be exposed, including preschool, daycare and school. “In effect, food allergy has a substantive impact on 50 percent of the Canadian population,” says Allan Becker, site leader of the Canadian Healthy Infant Longitudinal Development (CHILD) study, which is examining the root causes of allergy and asthma, including genetic and environmental triggers.

Food allergies in kids are a bigger problem today than ever before, having become more common, longer lasting and more severe. “The prevalence of peanut allergy has tripled over the past 20 years,” says Edmond Chan, author of allergy prevention guidelines for the Canadian Paediatric Society (CPS) and head of allergy and immunology at BC Children’s Hospital in Vancouver. Peanuts are one of the foods most commonly linked with severe reactions, while milk is the most widespread food allergy worldwide. “Fifteen or 20 years ago, 80 percent of kids would outgrow their milk allergy between the ages of three and five,” says Bruce Mazer, director of child health research at Montreal Children’s Hospital McGill University Health Centre. “Now, by the teen years, only 60 percent have outgrown it.”

It’s not clear what’s driving these concerning trends, though there are likely multiple causes. Possible culprits include fewer early-life exposures to parasites, viruses and bacteria that help teach the immune system to tell friend from foe. For instance, babies born by C-section tend to have less diverse gut bacteria because they bypass the beneficial bugs that live in the birth canal. However, one emerging suspect is the route by which kids are first exposed to potential allergens and how regularly they eat them afterward.

Allergy is a result of the immune system—after at least one previous encounter—mistaking an otherwise harmless substance for an invader, such as a virus. The first step in this allergic cascade is called sensitization. It’s believed that during infancy, when the immune system is still learning the ropes, children who are genetically susceptible to allergies are more likely to become sensitized to peanut protein, for example, simply by inhaling or absorbing it through the skin (say, as an ingredient in diaper cream). If we delay feeding babies peanuts, they’re more likely to encounter it this way. Indeed, in Israel, where Bamba, a peanut snack, is commonly fed to babies, the rate of peanut allergy is much lower than in North America.

Thankfully, researchers are aggressively searching for solutions. Here in Canada, Toronto’s Hospital for Sick Children has expanded its research into food allergies, recruiting several prominent scientists in the field. “I believe we [the] will probably find cures to some food allergies within the next decade,” says Eyal Grunebaum, head of immunology and allergy at Sick Kids. And in fact, a recent discovery suggests that a way to reverse the upward trend in peanut allergies is already within reach.

It’s a pretty major piece of information, and there’s more. Here’s some new hope for families struggling to keep their allergic children safe.

Preventing peanut allergy
Status: Coming soon

The conventional wisdom—to delay introducing problematic foods like peanuts, milk and eggs—might be completely wrong. As a recent UK study shows, it’s likely possible to sharply reduce the odds of peanut allergy in high-risk kids simply by giving them a taste of it much sooner.

The trial involved more than 600 children who had eczema (common in food-allergic kids) and/or an egg allergy. At the start of the study, infants aged four to 11 months were skin-tested for sensitivity to peanuts, which involves pricking the skin, applying a small amount of the allergen and waiting to see if the area develops a hive. This indicates the body has antibodies to the food. (Babies who developed welts larger than five millimetres weren’t included in the trial.) The rest were divided into two groups, based on positive and negative skin tests, and followed for five years: Within each group, half were given two grams of peanuts (either in Bamba or peanut butter) three times a week, while the other half avoided peanuts altogether. At the end of the study, all kids were given a heftier dose of peanut butter to test for a true allergy.

The results were “amazing,” says Adelle Atkinson, a clinical immunologist at Sick Kids. Among children who’d had a negative skin test, only 1.9 percent of peanut eaters developed a full-blown allergy, compared with 13.7 percent of peanut avoiders. The difference was just as striking in kids with positive skin tests: Peanut eaters had a 10.6 percent rate of allergy versus 35.3 percent in the avoiders. “This shows that not only do we not need to delay introduction of certain foods, but we should probably be intentionally giving the food to high-risk kids early on,” Atkinson says.

Canadian allergy specialists are working behind the scenes with their US colleagues to put this new information into practice. “Hopefully, within the next half-year or so, there will be some concrete guidelines,” says Atkinson. Currently the CPS doesn’t recommend delaying the introduction of any food (other than honey, which poses a risk of infant botulism, before one year of age). However, in the past, notes Atkinson, many Canadian doctors followed outdated recommendations from the American Academy of Pediatrics, counselling parents of high-risk kids to avoid dairy, eggs and peanuts until one, two and three years of age, respectively.

Predicting food allergies
Status: Under investigation

With this new evidence that it’s possible to prevent food allergies—or at least peanut allergy—it’s even more important to find a better way of identifying exactly who is at risk. Currently, doctors rely largely on factors like the presence of eczema, an immediate family history of allergy or the severity of previous reactions, but these aren’t always reliable indicators. For instance, even if both parents have allergies, their baby’s chance of developing one is still only about 45 percent, says Grunebaum. And it may manifest as asthma or hay fever instead of, or in addition to, a food allergy.

However, two new studies give hope for more accurate identification via gut bacteria and genes. Using data on 166 infants enrolled in the huge, long-term CHILD study, funded by the Canadian Institutes of Health and the Allergy, Genes and Environment Network, researchers discovered that babies who had fewer varieties of bacteria in their stool and altered levels of two specific bacteria at three months of age were more likely to become sensitized (measured by skin test) to milk, eggs and peanuts by one year. Meanwhile, a US study of 3,000 children found changes in the DNA of kids with peanut allergies, which “theoretically, would allow for detecting them at birth,” says Grunebaum. Researchers there are also working on finding genetic markers that would identify kids as being susceptible to other allergies.

The CHILD study may also soon provide answers about how Mom’s diet during pregnancy and breastfeeding, the introduction of solid foods and genetic makeup affect the likelihood of developing food allergies in a much broader range of kids. “Allergies are the earliest chronic disease to show up and are by far the most common in childhood, so that’s our initial focus,” says Becker. One thing CHILD has discovered so far: Having a mother who eats peanuts and tree nuts during pregnancy doesn’t seem to raise a baby’s risk of developing allergies to these foods.

Preventing food allergies
Status: Under investigation

Early exposure may not be the only way to reduce the risk of food allergies. For instance, the CHILD study suggests that manipulating gut bacteria (possibly with diet, prebiotics or probiotics) might be another method. However, more research is needed to sort out whether the differences in bacteria are a cause of allergy or simply a marker, notes Meghan Azad, assistant professor of paediatrics and child health at the University of Manitoba, research scientist with the Children’s Hospital Research Institute of Manitoba, and one of the co-authors of the new research on gut microbia and food allergies.

Research at Sick Kids suggests medication may be another route. A few years ago, the transplant team noticed that about 20 percent of kids who had undergone liver and heart transplants developed various types of immune “dysregulation,” including severe food allergies. Doctors knew age was likely a factor, since these transplants are performed much earlier in life than those for kidneys and lungs. Was there something else that made these kids different?

Grunebaum and his colleagues discovered that not only did the food-allergic kids have far fewer specialized white blood cells called regulatory T cells (which are involved in regulating the immune system), but the ones they did have were much less active. Further investigation revealed that some of the anti-rejection medications the kids were given specifically targeted those regulatory T cells. So the doctors switched to meds that instead promote and nurture regulatory T cells—and the incidence of allergy dropped significantly. Because of this, Grunebaum says these medications are now being considered to promote regulatory T cells in kids at high risk of developing allergies.

Of course, anti-rejection drugs come with serious risks, such as vulnerability to infection, so researchers are also investigating other ways to apply their findings. “There are now techniques where we can make cells from bone marrow or umbilical cord blood into regulatory T cells,” Grunebaum says.

Predicting/preventing severe reactions
Status: Under investigation

A frustrating reality of food allergies is there is no reliable way to predict which kids are truly at risk of anaphylaxis, which affects roughly two percent of food-allergic kids, according to Grunebaum. Peanuts may be most commonly linked with severe reactions, but other foods, like milk, mangoes and sesame, can also trigger anaphylaxis. “At this point, neither skin tests nor conventional blood tests can predict severity—they can only predict possibility or likelihood of a reaction,” explains Mazer.

One promising lead: A small study found high blood levels of a substance called platelet-activating factor (PAF) in adults who had suffered anaphylactic reactions; further research in mice revealed that blocking PAF activity could prevent life-threatening anaphylactic reactions. (PAF, which acts on blood vessels, is behind the dramatic and potentially deadly drop in blood pressure during anaphylaxis.) Sick Kids recruited the lead author of that study, Peter Vadas, to learn more about how PAF works. If PAF levels could reliably pinpoint exactly which kids would go on to have a severe reaction, “it would be very helpful for families,” Atkinson says.

Building on the PAF research, scientists are hoping to go one step further and actually prevent anaphylactic reactions, thanks to a recently identified PAF-blocking compound. “We’re probably a year or two from implementing an anti-PAF pill,” says Grunebaum. The hope is that one day anaphylactic kids could take the anti-PAF pill before going to, say, a birthday party where they might be exposed to dangerous allergens.

Desensitizing to peanuts
Status: Under investigation

Researchers have also been studying various ways of desensitizing peanut-allergic kids so they can tolerate peanuts safely if they’re accidentally exposed. Eating tiny, gradually increasing portions of peanut with medically supervised increases is one method (though some kids are too reactive to undertake this treatment).

In a study underway in Hamilton, Ont., kids aged five to 10 years slowly work their way up to a maintenance dose of 500 milligrams (roughly two peanuts) a day. “When they’re stable after one year, we challenge them with a bigger dose to see how much more they can tolerate,” explains Susan Waserman, a professor of medicine, and an allergist and clinical immunologist at McMaster University. “Many of these kids can go on to tolerate accidental exposures that are far larger,” she says. However, this type of desensitization isn’t a cure. If kids stop eating peanuts regularly, it’s possible to become re-sensitized—in fact, most do.

It’s worth noting that oral desensitization “is still largely experimental,” says Chan, because not enough research has been done to determine things like how long the tolerance to peanut lasts or the possible risks.

A patch that constantly delivers a tiny dose of peanut protein through the skin is another treatment that’s being explored: In a recent US-led study of more than 200 people (including 113 kids under 12), half of those who wore a 250-microgram patch daily for a year were able to tolerate at least one gram of peanut—10 times the amount they could handle before treatment. Sick Kids’ researchers are planning a desensitization study to begin later this year and are currently debating the merits of the patch versus the food itself. “The patch may be more appealing to parents, but we’re finding it may not be as effective as giving peanut orally,” says Atkinson.

Desensitizing to milk & egg
Status: Under investigation

Rather than simply increasing the amount of food kids can tolerate during an accidental exposure, another study that’s underway at several Canadian centres is aimed at allowing milk-allergic children to have regular-size servings of dairy. This research is also funded by the Canadian Institutes of Health Research and AllerGEN NCE. “We’re working very hard to normalize kids,” with milk allergy, explains Mazer, the study’s lead investigator. “We take them from zero to 200 millilitres of milk, then we give them a challenge of 300 millilitres, and then we put them on as much dairy as they like, but a minimum of 200 millilitres of milk at least twice a week.”

The approach is not for the faint of heart—all kids in the study needed to show they had an allergy with an initial oral challenge (which can result in a severe reaction), and families have to visit the hospital weekly during desensitization. But “the responses have been phenomenal,” Mazer says. “The kids are happy, the families are happy. They’re less stressed. They can eat in restaurants. I have a gallery of pictures of their first pizza, their first ice cream cake—it’s really cool.”

Building tolerance with baked milk & egg
Status: In practice

Baking changes the proteins in milk and eggs in such a way that they provoke a milder reaction than an equal amount of the raw food—or no reaction at all. Today, allergy specialists commonly challenge allergic kids to eat gradually increasing amounts of baked goods containing milk and egg, a treatment pattern similar to that of conventional allergy shots. After first eating the food under medical supervision, kids regularly consume measured amounts at home. This opens up the possibility of children enjoying a piece of birthday cake at a party or buying a muffin at the mall—but that isn’t the only benefit, notes Atkinson. “If kids can tolerate milk and egg in baked foods, they’re more likely to outgrow the allergy and outgrow it faster.”

Unlabelling
Status: In practice

Because avoiding a particular food and having to carry an EpiPen everywhere is a big burden on kids and their families, allergy specialists want to ensure all of that effort is actually necessary. “There are a lot of kids who, for a variety of reasons, are labelled as having a food allergy who may not have one,” Atkinson explains. For instance, a baby may have coincidentally broken out in a rash caused by an undiagnosed virus right after eating a new food. And even positive skin tests are only reliable about half the time for the most common allergenic foods.

“We feel strongly that if there is any doubt, it is our responsibility to unlabel these kids,” Atkinson says, adding that the same goes for those who may have outgrown their allergies. This means carefully reviewing a child’s history and, if warranted, doing additional testing as well as an oral food challenge. For instance, if you were told to avoid giving your baby peanuts because she developed a rash a few days after her first taste of peanut butter, it’s actually quite unlikely an allergy was the real culprit, since reactions typically occur within minutes or hours of eating the offending food.

A version of this article appeared in the May 2015 issue with the headline "The good news on food allergies," pp. 31-34. 

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Looking for some fun foods to cook with your kids? Check out this Cooking with Kids video on making dressed-up kale chips!