Self & Other · Allergies: When the Guards Panic

The Treatments

There’s one more piece of recent allergy science worth telling carefully, because it changed how doctors talk to parents and because it is one of the cleanest cases in modern medicine where conventional wisdom turned out to be exactly backward.

In the late 1990s and early 2000s, peanut allergies in children were rising sharply in many wealthy countries. The standard advice from medical societies, given to parents of infants who might be at risk, was to delay introducing peanut into the child’s diet. Don’t give peanut butter to a baby. Wait until the child was at least three. The thinking was that delaying exposure would give the immune system time to develop without being primed against peanut.

In 2008, a British researcher named Gideon Lack noticed something strange. Israeli children, who routinely eat a peanut-based snack called Bamba from infancy, had peanut allergy rates ten times lower than genetically similar Jewish children growing up in the United Kingdom, where peanut was being delayed. The pattern was hard to explain if delayed exposure was protective. It was easy to explain if delayed exposure was the cause.

Lack ran a careful clinical trial — the LEAP study, published in 2015 — that randomly assigned high-risk infants either to avoid peanut or to consume peanut-containing foods regularly from a few months of age. The result was unambiguous. The infants who ate peanut early had peanut allergy rates roughly 80% lower than the infants who avoided it. The protective effect was strong, statistically rock-solid, and the opposite of what the field had been recommending for decades.

The advice, accordingly, reversed. As of the late 2010s, pediatric guidelines in most wealthy countries actively recommend introducing peanut early, often around four to six months, especially in infants at higher risk. Peanut allergy rates in the populations that have followed the new advice have begun to drop.

The mechanism is consistent with the broader picture of this chapter. The infant immune system seems to learn what to tolerate and what to attack partly through what it encounters, in food and on skin and in the surrounding environment. Encountering peanut early, in the gut, in normal eating, allows the system to register peanut as a normal food. Avoiding peanut while exposing the child to peanut traces in other ways — through skin, through household contact — may inadvertently teach the system to treat it as a foreign threat.

This is one of the more hopeful stories in this part of the book. A common, sometimes-fatal allergic disease turned out to be substantially preventable through a simple change in early feeding. The change came from careful science, applied honestly, even when the result contradicted decades of advice.

The Treatments

Mild allergies are usually managed with antihistamines — drugs that block the histamine receptors mast cells fire onto. This is why your loratadine, your cetirizine, your fexofenadine all work the same way: each blocks one or more types of histamine receptor, dampening the cascade.

Asthma, which is in many cases an allergic disease of the airways, is managed with a combination of drugs that open the airways (bronchodilators) and drugs that calm the underlying inflammation (inhaled steroids). Severe asthma, in the last decade, has begun to be treated with biologics — monoclonal antibodies that target specific cytokines or specific kinds of IgE. We’ll talk about biologics more in the next chapter, because they have transformed autoimmune disease as well, but the same approach works here. A drug called omalizumab, for instance, binds free IgE and prevents it from latching onto mast cells. For some people with severe allergic asthma, it is, more or less, life-changing.

Anaphylaxis is treated with epinephrine, given quickly, by injection. The autoinjectors most allergic people carry — the most familiar brand name is EpiPen — contain a single dose. The drug constricts blood vessels, opens airways, and counteracts most of the major effects of mass mast-cell discharge. It buys time. People in anaphylaxis still need to go to a hospital after epinephrine. The dose is a bridge, not a cure.

The most interesting recent development, and one that may transform parts of allergy treatment over the next decade, is the careful use of controlled re-exposure to teach the immune system to tolerate things it has already learned to react to. This is called allergen immunotherapy. It can take years. It works best for some allergies and not others. It is not without risk. But for severe peanut allergy, for some pollen allergies, for some venom allergies, immunotherapy can convert someone whose mast cells will explode at trace exposure into someone who can tolerate the substance with only mild discomfort.

The underlying logic is roughly the opposite of Richet’s original mistake. Richet thought small doses would teach the immune system to tolerate. Instead they sensitized it. Modern allergen immunotherapy starts even smaller, escalates more slowly, and uses our better understanding of regulatory T cells and tolerance to encourage the immune system, gently, into a state where it sees the allergen as ordinary background. When it works, it works because it pushes the system from Type 2 mode back toward regulation.

So this is allergy. A real disease, often a serious one, sometimes a fatal one, caused by an immune system doing exactly what it evolved to do, in a world that no longer needs it to do it.

The cells are not broken. The IgE is not defective. The mast cells are doing what mast cells were always supposed to do. They are simply doing it in response to pollen, or peanut, or cat dander, or shellfish — things that, in another world, would not have set them off, but in this one do.

The remarkable thing is that we are starting to understand why. The miscalibration of childhood immune development, the shift from a microbial-rich to a microbial-poor environment, the way early food exposures train tolerance, the way Tregs can be coaxed back into balance — these are not the kind of things scientists understood twenty years ago, and many of the recommendations doctors give now are different from what they gave then. The next decade will likely change them further. This is a field where the science is moving.

Allergy is the milder cousin of the next chapter’s subject, and the comparison is worth holding onto as we turn the page. In allergy, the immune system attacks something harmless from the outside — a peanut, a pollen grain, a cat. In autoimmune disease, the immune system attacks something not from the outside at all. It attacks part of the person it lives in. The mechanisms overlap. The ethics of how we talk about it do not.

That’s the next chapter. And it is the chapter this book has been building toward all along.

All 21 chapters of Self & Other · Library · All courses