My youngest son has been allergic to peanuts and sesame since he was a toddler. Though he has never had a life-threatening reaction, the risk of one hangs over him constantly. He can’t eat out in most restaurants or travel to many parts of the world. Grocery shopping is an ordeal. He has his own place now, and I live in constant anxiety. We always hoped he would grow out of his allergies. At 21, he almost certainly won’t.
He is in an increasingly crowded boat. For reasons that aren’t well understood, food allergies have grown explosively in the 21st century. Peanuts are a common trigger, as are wheat, cow’s milk, egg, soya, other nuts, fish and shellfish. Beyond the “big eight” lies a long tail of allergies to other foods, including many fruits, vegetables and seeds. Some people are allergic to beer, others to cannabis. If humans consume it, chances are somebody, somewhere, is allergic to it.
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This rise has translated into an increased burden on healthcare and a reduced quality of life for many, as they strive to avoid a potentially fatal reaction. Until recently, there was only one way to avert this outcome: don’t eat the trigger food. That is easier said than done, however, with unexpected ingredients incorporated into processed foods and labelling often ambiguous or inaccurate.
But now, finally, there is hope on the horizon, with the arrival of several new therapies that can help people avoid an allergic reaction, not just to food, but other kinds of triggers too. “An exciting era is near,” says at Emory University in Atlanta, Georgia.
How common are food allergies?
Getting a firm handle on the prevalence of food allergies is quite difficult, as there are various ways of measuring it. But most studies have found a recent increase, at least in adults. carried out by the US Food and Drug Administration (FDA) found that the number of adults self-reporting a food allergy increased from 9.1 per cent in 2001 to 13 per cent in 2010. In 2019, a different research group found that . The prevalence in children has remained at about 8 per cent for the past decade or so.
At the same time, hospital admissions for severe allergic reactions have risen dramatically. In the US, the number per 100,000 people . The equivalent figure in the UK from 1998 until 2018.
The rise in adult cases has belatedly captured the attention of epidemiologists who were previously focused on childhood allergies, says . It is in part due to children with allergies growing up, but as frequently as expected – . But it is also due to adult-onset allergies, which “seem increasingly common”, according to Warren.
First and foremost among these is pollen food syndrome. In this case, the primary allergy is to some variety of airborne pollen, which triggers hay fever as a result of the immune system mistakenly recognising proteins (or “allergens”) within the pollen as dangerous. People with this allergy also tend to have a reaction to foods containing closely related allergens. The main one in birch pollen, for example, is almost identical to those found in apples and hazelnuts. An allergy to mugwort pollen can also make people sensitive to wheat, peach, walnuts, soy and latex.
Seafood is also a common trigger in adults: in the US, about and 40 per cent of finfish allergies arise in adulthood, according to at the University of Tennessee Health Science Center in Memphis. We don’t know why these foods are tolerated for years then suddenly trigger allergies, he says.
What causes allergies?
Childhood food allergies are also a bit of a head-scratcher. There is clearly a genetic component that can put people at higher risk of developing one, but what makes some people’s bodies react to an otherwise innocuous environmental trigger is still unknown (see “How to prevent your child from developing food allergies”, below). The hygiene hypothesis, which posits that living in an excessively sterile environment in early childhood leads to poor immune tolerance later in life, lacks convincing evidence, according to at King’s College London.
The most promising explanation for child-onset allergies is cutaneous exposure, where food allergens penetrate broken skin and trigger an immune response, which is then encoded into an immune memory, says Ezhuthachan. This fits with what is known as the “allergic march”, where children who initially develop eczema are much more likely to subsequently develop food allergies, asthma and hay fever. The broken skin that characterises eczema may be the route by which food allergens first encounter the immune system. However, “the processes governing this loss of tolerance are incompletely understood”, says at Stanford University in California.
On the other hand, the mechanics of allergic reactions are now well-known, which is partly the reason for the recent surge of new treatments. A reaction starts when the immune system misidentifies something innocuous as a threat and goes into blitz-defence mode. In a classic reaction, a type of white blood cell called a helper T-cell recognises an allergen and sounds the alarm, stimulating B-cells to release an antibody called immunoglobulin E (IgE). This binds to target cells, triggering a flood of inflammatory molecules, including histamines. Cue the classic allergic reaction: swelling, itching, streaming eyes and nose, hives and, in the case of food, vomiting and diarrhoea.
Histamines also cause blood vessels to dilate, leading to a rapid drop in blood pressure. In severe cases, these immune responses can be fatal. Swelling of the airways and tongue make it difficult to breathe, while catastrophically low blood pressure can progress to a state called anaphylactic shock, where not enough blood reaches tissues. This can lead to unconsciousness and cardiac arrest.
How do you treat allergies?
The only , also known as adrenaline, which rapidly dilates the airways, constricts blood vessels and speeds up the heart. That is why people with life-threatening allergies often carry injectable doses of epinephrine in an EpiPen or similar. Swift action can make the difference between life and death.
Still, around and roughly a third have been hospitalised. In the US, after ingesting peanuts every year.
Anaphylaxis can escalate, with subsequent attacks worse than the previous one. And about 20 per cent of people experience a , with a second wave of anaphylactic symptoms hours or even days after the first. “People with severe food allergy, especially those who are allergic to multiple foods, have a substantial need for effective and safe treatments,” says at the Chinese University of Hong Kong.
Such treatments finally appear to be on the horizon after years of promise. Back in the 1980s, scientists at biotech company Tanox in Houston, Texas, hit on a potentially life-saving concept. If severe allergies were triggered by IgE, why not target that? They developed a drug called TNX-901 that binds tightly to IgE and stops it from latching on to cells that would otherwise release inflammatory molecules like histamines. The idea was to give regular injections of TNX-901 to people with severe allergies to protect them from an IgE storm if they accidentally ate their trigger food.
In a subsequent published in 2003, involving 84 volunteers aged 12 to 60 who had a peanut allergy, Tanox showed that the concept worked: four injections of TNX-901 over 12 weeks “significantly and substantially” increased participants’ tolerance threshold from an average of about half a peanut to almost nine peanuts. That, according to the researchers, was sufficient headroom to protect against most unintended ingestions.
Unfortunately, this promising tool didn’t get off the ground. The trial was halted due to a legal dispute between Tanox and its industry partners, Novartis and Genentech, over who owned the right to develop the drug. TNX-901 never saw the light of day.
Oral immunotherapy
In the meantime, however, a different strategy called oral immunotherapy (OIT) was being tested. This involves feeding people with food allergies tiny but escalating doses of their trigger allergen. The idea is that doses initially too small to provoke a reaction will gradually retrain the immune system to tolerate the offending substance.
This technique isn’t actually new – the , concerning a 13-year-old boy with a severe egg allergy. His doctor, a practitioner at London’s Harley Street called Alfred Schofield, hypothesised that egg proteins were causing the boy’s blood vessels to become leaky, so he started feeding him tiny amounts of egg to make his system tolerate the foodstuff. He initially administered a ten-thousandth of an egg per day and built up gradually to a sixth of an egg. Within months, the boy was able to eat whole eggs without a reaction.
Despite the positive result, the approach was considered too risky and OIT fell by the wayside. It wasn’t until the 1990s that it was revisited, and have since successfully used it in people, mainly children, for peanuts, cow’s milk, eggs and fish. that OIT could induce “sustained unresponsiveness” to eggs, meaning that people could eat normal quantities of this food with no reaction. In 2017, the European Academy of Allergy and Clinical Immunology , eggs or peanuts. In 2020, the FDA and the European Medicines Agency approved an oral peanut formulation for 4 to 17-year-olds called , developed by Aimmune Therapeutics of Bridgewater, New Jersey.
But OIT is far from perfect. One problem, says at Stanford University, is that it is laborious. It can only desensitise people to one allergen at a time, but she says at least . It is also still risky, she says: allergic reactions, even anaphylaxis, during the process are common.
Fortunately, the IgE-blocking concept was also eventually revived. Before teaming up with Tanox, Genentech and Novartis had developed their own anti-IgE monoclonal antibody called omalizumab, trade name Xolair. They initially tested it against asthma triggered by airborne allergens and won regulatory approval for that use in 2003.
Latest results
Next in the crosshairs were peanuts. Things got off to a rocky start: the first clinical trial of omalizumab for peanut allergy had to stop recruiting when two of the volunteers had anaphylactic shocks during tests to measure their baseline tolerance to this food. But the nine volunteers who got the drug showed an 80-fold increase in their tolerance.
Since then, more trials of the drug have been carried out on peanut allergy with good results. Some doctors started giving omalizumab to people with food allergies even though it didn’t have regulatory clearance, says Wong.
The . A team led by Chinthrajah and at Johns Hopkins University in Maryland gave 177 children and adolescents who were highly allergic to peanuts a course of omalizumab injections or a placebo, then tested whether their sensitivity to peanuts decreased. About two-thirds of the volunteers who received the drug experienced at least a six-fold increase in their tolerance, from less than half a peanut to around 2.5 peanuts. That is enough to prevent anaphylaxis after most accidental ingestions, the researchers say.
“Even in the most careful families, mistakes happen,” says Chinthrajah. “So to have a drug that offers another level of protection I think is really priceless.”
And it didn’t just desensitise the participants to peanuts. To qualify for the trial, the volunteers also had to be allergic to at least two other trigger foods, out of cashews, eggs, hazelnuts, milk, walnuts and wheat. Participants who got the drug experienced a similar increase in tolerance to those other foods. On the back of that data, on 16 February, the , ending a decades-long wait. “It’s really exciting to have something approved,” says Ezhuthachan, who wasn’t involved in the trial. “I think it’s going to have a really good role.”
But it isn’t the final answer, she says. The drug is expensive and its effects wear off, necessitating injections every two to four weeks.
The lack of success in a third of volunteers is also an issue, says Chinthrajah. “It is critical for us to understand the biology behind responders and non-responders, but that will enable us to fine-tune our therapeutics and push the needle beyond two-thirds. There’s a lot more to be done, but I do think we should take a moment and celebrate this great victory.”
These results are just the start. Two other trials of omalizumab are also ongoing, . The hope is that giving the drug during the OIT’s escalation phase will make the process safer, and that it can later be withdrawn, whereupon tolerance can be maintained by OIT alone.
There are also more potent IgE blockers in the pipeline. One, , is being tested against peanut allergy. A late-stage trial was recently Novartis for undisclosed reasons, but the company says it will start another trial later this year. Yet another IgE blocker, from Taiwanese company United BioPharma, is being tested against eczema and, according to Chinthrajah, has “great potential in food allergy”.
Stopping an allergic reaction
A slightly different approach is to disrupt IgE as well as block it. Once IgE has bound to its target cells, initiating the release of histamine, blockers are largely powerless to intervene. But a new class of drugs called not only stop IgE from binding, but also lever it off target cells once it has bound. They aren’t yet in clinical trials, but show promise as a rapid rescue remedy for anaphylaxis, according to Chinthrajah. People who start to have an allergic reaction could use them like an EpiPen to halt the potentially deadly cascade.
Multiple existing drugs are also being eyed with a view to repurposing them for food allergy, and there are several vaccines in development, though these are at a very early stage. As a result, after decades of having little to offer people with food allergies, there is suddenly a sense of a new dawn. “It’s a game changer,” says Chinthrajah.
Ultimately, the hope is to take the sting out of all severe allergies. Most anaphylactic shocks are caused by food, but they can also be triggered by latex, insect stings and animal venoms. There is also a condition called where the shock comes on with no apparent cause. IgE blockers could, in principle, deal with all of these.
Then there is allergic asthma, which is triggered by airborne allergens such as pollen and pet dander. It accounts for the majority of asthma attacks, which . Omalizumab is already approved for this condition, but better IgE blockers could transform that illness too.
My son also has asthma, which is well-controlled but occasionally flares up. I know that a new drug to eliminate this risk, and also remove the threat of food-related anaphylaxis, would improve his – and my – life immeasurably, and those of millions of people in a similar position. Is that in our future? Yes, says Ezhuthachan. “I think that’s eventually where we’re going to get to.”
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How to prevent your child from developing food allergies
Most people with severe food allergies have a genetic susceptibility, according to Idil Ezhuthachan at Emory University in Atlanta, Georgia. If allergies run in your family, then your children are at higher risk of developing one. But biology isn't destiny and there are things that parents can do to prevent an allergy arising.
Number one is early exposure. When my late wife was carrying and breastfeeding our peanut-allergic son (see main story), the advice in the UK was for her to avoid eating peanuts, which she did. We were also advised to delay introducing peanuts into his diet during weaning. But research subsequently showed that these strategies have no benefit and the advice was withdrawn in 2008.
Indeed, such measures may be counterproductive. have shown that early introduction of multiple typical allergens, such as peanut and egg, reduces the risk of any allergy, and infant weaning guidelines in the US now encourage the early addition of common allergy triggering foods. In early life, the gastrointestinal tract is primed to promote tolerance to allergens and will do so if exposed to them early.
Another is to keep an eye out for the skin condition eczema, which often precedes the development of food allergies. Eczema causes broken skin, allowing potential food allergens to access the immune system deep under the skin, which is less tolerant of them. Early introduction of common allergens can help prevent this, and so can treatments for eczema. "I get excited whenever I see a baby with eczema in my clinic because I feel like 'oh, now I can make a difference in your life, let's fix your eczema so that we prevent food allergy'," says Ezhuthachan.
Graham Lawton is a staff writer at 91av
