It's 1 p.m. at Mercer Elementary School in Shaker Heights, Ohio, and Lena Paskewitz's kindergarten class is filled with the happy hum of kids getting ready for their favorite part of the day: lunch. Caleigh Leiken, 6, is toting a pink Hello Kitty bag her mom has packed with goodies: strawberry yogurt, string cheese, some veggies and a cookie. But there's one childhood staple missing—a PB&J. Caleigh was diagnosed with a peanut and tree-nut allergy when she was just 7 months old. Nuts are a no-no at her table in the Mercer lunchroom. Her allergy-free friends can sit there, but only if their lunches have been stored in a special bin and carefully inspected by the teacher. Home, too, is a nut-free zone for Caleigh. When she goes trick-or-treating this week, her candy will be scarier than any costume; she won't be able to eat any of it for fear it's tainted with peanut residue. For Caleigh's mom, Erika Friedman—whose other two kids also have allergies—food can seem like an enemy. "We plan everything," says Friedman. "It's our job—actually, everyone's job—to keep them safe."
There was a time when food allergies were of little concern to the medical community. Today about 11 million Americans suffer from them, and many scientists agree the numbers are climbing. Most significantly, peanut allergies—among the most dire—doubled between 1997 and 2002 in children under 5. "Clearly, the number has increased in the younger population," says Dr. Hugh Sampson, a food-allergy pioneer at Mount Sinai School of Medicine in N.Y. "We suspect that [in the future], the numbers in general are going to increase." Allergists say they're now seeing more children with multiple allergies than ever before, not just to 1950s staples such as milk and wheat—but to global foods we have adopted since, like sesame and kiwi. And allergies many kids outgrow—like those to eggs—seem to be lingering longer than they did in the past.
Parents of very young children now worry over the introduction of each new food, on alert for the first signs of trouble, such as rashes, diarrhea and vomiting. Deaths are rare, but the most-sensitive kids' throats may swell and completely close up if they're exposed to the wrong foods. Even if your school-age child is allergy-free, you still have to be concerned about inadvertently triggering an allergic reaction in one of your kid's friends or classmates. Dairy-free birthday cakes are de rigueur these days, as are no-peanut Halloween parties.
But why do allergies appear to be on the rise? One of the most intriguing theories, dubbed the "hygiene hypothesis," is that we've all become too clean. The immune system is designed to battle dangerous foreign invaders like parasites and viruses and infections. But clean water, antibiotics and vaccines have eliminated some of our most toxic challenges. Intriguing research even posits that kids born by Caesarean section, which have risen 40 percent in the last decade, could be at higher risk for allergies, perhaps because they were never exposed to healthy bacteria in their mothers' birth canals. Without hard-core adversaries, the theory goes, the immune system starts battling the innocuous—egg or wheat—instead.
Almost everyone, it seems, has had to adapt to the rise in food allergies. Affected kids are carrying EpiPens, syringelike devices loaded with epinephrine, in case of severe reactions. Many schools, like Mercer Elementary, maintain "peanut-free zones," where allergic students can eat in safety. A growing number of states are establishing allergy guidelines. Manufacturers, thanks to a federal law implemented last year, now list the eight most common allergens (from milk to fish) on their food labels. And many airlines offer their passengers pretzels instead of peanuts.
While scientists have a basic understanding of how allergies work, they can still be stumped by the immune system, which is too complex to submit easily to their control. There are no cures for food allergies—only treatments for some of the symptoms—and the best parents and children can do now is avoid the culprits. Still, in recent years, researchers have begun to make exciting progress. They're studying a radical approach: introducing the offending ingredients early to see if they can treat, cure or even prevent food allergies from developing. In one study, children allergic to peanuts are being given tiny amounts of peanut flour to see if they can build up tolerance. In another, funded by the Consortium of Food Allergy Research (coFAR), a five-year $17 million initiative launched in 2005 by the National Institute of Allergy and Infectious Diseases, researchers will give peanut-allergic adults small doses of an engineered peanut protein to ward off reactions and possibly eliminate the problem. The idea is ultimately to have a peanut-allergy vaccine. For Sampson, who is working on it, the quest for a solution is more urgent than ever. "We're desperate," he says.
It is hard to fathom how the joys of childhood—a peanut-butter sandwich, a warm chocolate-chip cookie, a cold glass of milk—can send a tiny body into battle mode. How just one bite can make the throat itch, the lips swell, the stomach clench in agony. How an immune system, exquisitely designed to protect us against bacteria and viruses, can perceive healthful nutrients as enemies of state. Bryan Bunning, 13, and his brother, Daniel, 11, of Lake Forest, Ill., know what it's like. Bryan was 6 months old when his body revolted against a sip of milk-based formula. "His lips blew up and his eyes went back in his head," says his mother, Denise. The boys share a list of verboten foods between them: eggs, tree nuts (including cashews, walnuts, almonds, hazelnuts), milk and shellfish. In March, Daniel was diagnosed with an allergy-related disorder of the esophagus that left him able to eat only apples and bacon. Now he gets most of his nutrients through a feeding tube. "It's really hard going to parties. You watch all your friends eat what they say are amazing foods, like ice- cream cake," says Daniel. "They're, like, 'Daniel, it's really good.' I say, 'I can't, I have food allergies'."
Nobody knows precisely what causes food allergies. A combination of genes—allergies run in families—and environment clearly play a role. The cascade of events begins when an allergy-prone person encounters a substance like pollen or peanut. The body sees it as trouble and launches phase one of its offensive: the production of antibodies called IgE (immunoglobulin E). These molecules attach themselves to "mast" cells, which line the lungs, intestines, skin, mouth, nose and sinuses. The next time the person encounters the pollen or peanut, the mast cells are primed for warfare, sending out powerful chemicals, like histamine, which lead to those nasty allergic symptoms—wheezing, stomach cramps, itching, stuffiness, swelling and hives. In rare instances, when the response to an allergen is sudden and severe, the airways can shut down completely and blood pressure can plummet, leading to anaphylaxis. Without immediate treatment with epinephrine, a hormone that opens the breathing passages and increases heart function, anaphylactic shock can kill.
Intriguing new research into the cause of allergies lends credence to the hygiene hypothesis. Studies have shown that children who grow up on farms, where they are in constant contact with dirt and animals, are less likely to develop allergies. Canadian research published earlier this month also suggests they're at less risk of asthma. At Duke, scientists have examined the phenomenon at the molecular level by comparing the immune systems of wild, parasite- and infection-ridden rodents with their cleaner, lab-raised cousins. In a setup intended to simulate an allergic response, researchers put the animals' immune cells in a petri dish, then challenged them with a plant protein—a known immune-system stimulus—to see how the cells reacted. Last year they published their findings: the lab rodents had a much higher immune response than their wild relatives did. Their immune systems were working overtime. And the wild animals, who were unfazed by the stimulus, showed higher levels of antibodies in their blood, suggesting that they'd already battled far greater enemies and couldn't be bothered by the small stuff. "We think the wild ones probably wouldn't get an allergy," says lead investigator William Parker. "They just don't have time to mess with a pollen grain when they're fighting off some horrible parasitic liver worm." Parasites, Parker says, might ultimately help scientists find a cure. Studies have shown that patients with irritable bowel syndrome, a digestive and immune disorder, may improve if they're exposed to a pig parasite, the porcine whipworm. Parker is eager to see if similar, controlled exposure can "stimulate the immune system in a good way" in allergic kids. No one's done the research—yet—but in theory, he says, it's "highly promising."
Fixing the immune system, so that it learns to distinguish good from bad without error 100 percent of the time, is every immunologist's dream. Unfortunately, researchers still don't know enough to make that dream a reality. But what if the system could be desensitized, so kids became more tolerant of the very foods they are allergic to? The approach, called immunotherapy, is already standard practice for seasonal allergies like hay fever. Patients receive allergy shots containing small but increasing amounts of the problematic substances—weeds or tree pollen—so the immune system gradually becomes used to the allergens. Researchers have tried immunotherapy by injection for food allergies, but it's unsafe; patients may develop hives or other troubling reactions. Now scientists led by Dr. Wesley Burks at Duke are carefully testing the immunotherapeutic approach by mouth rather than needle, and they're beginning to see promising results. In a small study published in The Journal of Allergy and Clinical Immunology in January, Burks and Dr. Stacie Jones at Arkansas Children's Hospital reported that immunotherapy helped children with egg allergies tame their allergic reactions. After two years of ingesting small but increasing amounts of egg powder, most of the children could eat the equivalent of two eggs without any adverse reaction. Kids in a similar study, published this month in the journal Allergy, also developed a tolerance to eggs—although that effect disappeared after they stopped eating the powder.
Burks is using the same approach with peanuts, giving peanut-allergic children increasing amounts of a special flour with small amounts of peanut proteins. The first dose is the equivalent of about 1/1000th of a peanut; slowly, the kids have been working up to a peanut a day. Early in the trial, participant Noah Schaffer, 7, threw up after eating just 25 milligrams of peanut protein—equal to about 1/12 of a peanut. But at a food challenge last May, he ate the equivalent of 13 peanuts without any bad reaction. Burks says the results don't mean that Noah can now knowingly indulge in a Snickers bar—far from it. But his new tolerance could protect him if he accidentally had a bite of one. His mom, Robyn Smith, says she no longer worries that something terrible will happen. "That fear has been totally removed," she says.
Burks's peanut flour is a precursor to what researchers hope might one day be a peanut vaccine. Together, Burks and Sampson have developed a substance that looks like a peanut but contains proteins engineered to be less potent—and thus less likely to trigger an allergic response in patients. So far, the compound has been tested successfully in mice. "If it works in people," says Sampson, "we hope to shut off the allergic response."
There are still many mysteries about how allergies start and why they sometimes stop. Researchers know that babies with egg or milk allergies and the persistent rash known as eczema are more prone to some other allergic disorders later on. Take Emily Godwin. Neither of her parents has food allergies, but at 3 months, Emily developed eczema. Five months later, doctors diagnosed food allergies. Today, at 6, she can't eat eggs, wheat, tree nuts and grapes. But little Emily has had one victory: she recently outgrew a milk allergy. In fact, many kids get over milk and egg allergies naturally—another mystery that docs don't understand. Researchers at Mount Sinai and four other sites funded by CoFAR are now recruiting 400 infants who have milk or egg allergies. The infants will be monitored over five years to see how many develop peanut allergies and how many outgrow their milk or egg allergies. The goal: to better understand at the molecular level what triggers allergies and what makes them go away. Ultimately, that knowledge could lead to treatments.
The holy grail would be to stop allergies from developing in the first place. Prof. Gideon Lack, of King's College London, has studied allergy incidence worldwide and has discovered an intriguing paradox: countries that have advised avoidance of peanuts in early childhood, like the United States, have seen the greatest rise in peanut allergies. In some Asian and African countries, on the other hand, where children eat a variety of peanut products starting at a very young age, peanut allergies are far less common.
Now Lack has enrolled more than 200 babies with eczema or egg allergies—but no known peanut allergy—in a groundbreaking trial. He'll give half the babies a peanut-containing snack; the other half will avoid peanuts. He'll then follow them all until age 5 to see if he has stopped a peanut allergy before it takes hold. "We're going to try to intervene during a narrow window of immunological opportunity in the first year of life," says Lack. If it works with peanuts, it could apply to other foods as well. Lack is hesitant, however, to make predictions and warns that nobody yet knows which method—avoidance or exposure—will turn out to be the best way to go. "I don't want to give the impression that feeding peanuts is a safe way to prevent peanut allergy, because we really don't know," he says. If parents try to introduce peanuts early at home, "it could be dangerous." If the study is successful, however, it could lead to a turnaround in medical advice.
For now, parents must be hypervigilant. "They are always walking on eggshells," says Rep. Nita Lowey, who authored the federal labeling law. The labels—which require that ingredients be clearly described for consumers rather than scientists ("milk," not "casein")—are helping, and groups like the Food Allergy & Anaphylaxis Network (FAAN) applaud them. But FAAN, a nonprofit advocacy group, still worries about hidden threats. Schools sometimes use old peanut-butter jars to store crayons. Certain kinds of paint contain egg. And while the label on microwave popcorn may state that it contains milk, egg and fish, an allergic kid who isn't carefully checking the list might be at risk.
At home, Mom and Dad can control what their kids eat. The challenge is keeping them safe outside. Anne Bullard, director of Gwynn Valley Camp in Brevard, N.C., remembers the worry-free days of the past. "Twenty years ago, peanut butter was put out in the dining room for everyone," she says. "Not anymore." Today, even though just 1 percent of the 1,050 kids attending the camp have food allergies, the camp uses no nut products in its dining room. On mac-and-cheese nights, dairy-free options are on hand for campers who can't eat milk products.
Schools vary in the accommodations they make. Julie Forrest, of Waldwick, N.J., transferred her 7-year-old son, who has peanut and tree-nut allergies, out of a school where she says she was told by the principal that his safety could not be guaranteed. A study published this month found that while two thirds of surveyed schools had allergy-emergency plans, most of the policies were "missing essential components"—things as basic as having emergency contacts and student- health histories on file. And schools aren't the only ones who are lax. Some restaurant chains try to avoid nut products—Burger King carries only the occasional pie with nuts, which arrives in a sealed box—but others take fewer precautions. Another study, published in July, found that even parents of kids with allergies were increasingly ignoring "may contain" labels; 75 percent of parents said they paid attention to them in supermarkets, compared with 85 percent in 2003. The fact that the warnings are now so common may have created a new problem—with so many foods labeled, it's hard to know which really might be dangerous. "All of a sudden, it says, 'Manufactured on equipment that's used for peanuts' … Who knows what that means?" says Mike Lade of Houston, whose son Andrew, 7, can't eat peanuts. "We need a uniform standard for all of these wishy-washy 40 variations of 'maybe it does, maybe it doesn't'."
Nonetheless, others are making major efforts to guard against allergic reactions. Eighteen percent of schools now ban peanuts entirely, up from 13 percent in 2005. At Mercer Elementary, where Caleigh Leiken and 11 other students have severe food allergies, teachers and bus drivers have been trained to use an EpiPen, and teachers explain allergies to all their students, not just the ones who suffer from them. In Connecticut, that's the law—the state's guidelines for schools require teachers to educate kids about allergies, so they won't harass classmates who can't indulge in, say, grilled cheese sandwiches. Massachusetts, Vermont and Tennessee also have statewide allergy guidelines for schools, and this year New York and New Jersey began to formulate their own. Proposed federal legislation would take things even further, giving schools up to $50,000 each to voluntarily implement uniform guidelines so that when children graduate from a school or cross state lines, parents won't have to start the education process all over again.
As awareness grows, some people wonder: are food allergies exaggerated? The numbers of children with allergies are substantial, but fewer than 1 percent of kids under 5 suffer from peanut allergies and severe reactions kill between 100 and 200 people a year. Parents—conditioned by overcautious pediatricians who've told them to keep their young kids away from nuts and eggs—may panic unnecessarily. Not every rash or stomachache after lunch is an allergy. If you are lactose intolerant, for example, your body is unable to digest lactose, the major sugar found in milk, and you may feel crampy or gassy. If you're allergic to milk, on the other hand, your immune system sees milk proteins as dangerous and revolts against them. Allergists say a fair number of kids are being told to avoid foods they aren't allergic to. "Studies have shown that up to 25 percent of parents think their children may have a food allergy," says Dr. David Fleischer, of National Jewish Medical and Research Center in Denver, "but they've only been confirmed in about 8 percent."
An accurate diagnosis takes time, skill and patience. Skin tests for allergies are exceedingly sensitive, which means they overpredict the number of people who would have a reaction about 60 percent of the time. Blood tests, combined with a carefully documented history of symptoms, are more helpful, allowing doctors to make predictions about a child's risk for allergies based on how many antibodies to a specific food allergen show up in their blood. The only way to diagnose an allergy for sure, however, is to do a food challenge: give a patient small and increasing amounts of the suspect egg or wheat or seafood under a doctor's watchful eye, then monitor reactions. Knowing one way or the other can lift the burden for parents and children alike. "If you don't need to avoid a food," says Fleischer, "it's such a relief to the family that their lives can go back to normal."
Normal could one day be a reality for allergic kids if the science pans out. Last year researchers at National Jewish announced they'd identified a gene that protects mice against developing severe allergic skin reactions. At Mount Sinai, researchers have blocked the allergic response in mice for six months—a quarter of their life span—with an herbal preparation; now they want to test it in humans. One day, Sampson predicts, it might be possible to screen a child's genes, determine if he's at risk, then intervene before the itching and wheezing begins.
But that's pie in the sky for now. Bryan Bunning's hopes are far less grand. He just wants to outgrow his egg allergy so he can finally indulge in "any sweet thing" he can find. High on his list: birthday cake. Having his cake and eating it too—a well deserved reward.