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Allergies—Misery for All Seasons

Slim and serious, he mounts his bike. His long fingers grasp the handlebars firmly, and he checks his balance. Today he has a cold, and the circles under his eyes are darker than usual. When he explains his situation, he speaks with deliberation. "I don't eat much, unless Mom can check the ingredients. Then I can eat. But not 'til then."

Photo: Spores of Aspergillus
Spores of Aspergillus are common contaminants of starchy foods.
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Why so cautious? Maybe it's the result of spending so much of his childhood trying to make himself understood to doctors while gasping for air. Knowing that the simplest things can kill you…well, it does make a guy careful.

Cameron Liflander has allergies. This makes him no different from more than 50 million other Americans today. But his problem is not merely the watery eyes or scratchy throat we associate with that word. Cameron's seven-year-old body is waging a fierce war with his environment. And his mother fears that one day the environment could win.

"A pediatrician told me I was being silly," says Pamela Liflander, who repeatedly asked about her infant's oozing, blistering rashes, his constant spitting up. "The doctor said no child under three has real allergies, and the rashes and vomiting would go away. But I'd had a child before Cameron. I knew what a healthy baby looked like. This was not a healthy baby."

Cameron continued to look sickly, but his growth rate was on the charts. He drank breast milk for almost a year, and Pamela introduced other foods gradually. One day she gave him a bite of tuna. Cameron turned red, swelled like a sea sponge, and choked. Benadryl took care if it, but with the next anaphylactic reaction they ended up in the emergency room near their Riverside, Connecticut, home. It would be the first of many visits.

Just how many things could one child be allergic to? Over the next few years, the Liflanders would find out.

Suppose that 54.3 percent of U.S. citizens had cancer. That figure might set off a nationwide panic—a search for something wrong with our diet, our environment, our activity levels…something. In fact, that's the number of Americans who show a positive skin response to one or more allergens (although not everyone who tests positive has an actual allergic disease such as rhinitis, asthma, or eczema).

The manifestations of allergy—sneezing, wheezing, itching, and rashes—are signs of an immune system running amok, attacking foreign invaders that normally mean no harm. Allergens include pollen, dust mites, mold, food, latex, drugs, stinging insects, or any of the other oddball substances to which the body can choose to react, or overreact.

Asthma is a big contributor to keeping allergists in business. This chronic inflammation that causes airways to constrict affects about 20 million Americans, twice as many as 20 years ago. About 4,000 die each year. But all told, allergies rarely kill. They just make the sufferer miserable—sometimes for brief periods, and sometimes for life.

The U.S. is not the only country with high allergy rates. In the U.K. more than 20 percent of the population has active allergies. New Zealand, Australia, Ireland, and the U.K. have the highest prevalence of asthma in the world. Allergies, like obesity, are essentially an epidemic of modernity. As countries become more industrialized, the percentage of population afflicted tends to grow higher. There are remote areas of South America or Africa, for example, where allergies are virtually nonexistent.

At first glance the problem of allergies seems simple, and for most of us the solution is simple too: a handy drug like Zyrtec or Atrovent to treat the symptoms.

But maybe it's not so simple. We live in a nation where states have enacted legislation permitting asthmatic children to carry their inhalers to school (one in 13 must do so). A federal labeling law mandates manufacturers clearly state in plain English whether major allergens—peanuts, soy, shellfish, eggs, wheat, milk, fish, and tree nuts—are ingredients in any product. And Americans spend billions of dollars annually on antihistamincs to treat the symptoms of allergies.

Those of us over 40 don't remember having so much as a conversation about food allergies in school. Today 6 percent of young children have food allergies—and the number of those with potentially fatal peanut allergy doubled between 1997 and 2002. Children like Cameron sit at special tables at lunchtime; there are websites and support groups for parents homeschooling their severely allergic children.

Still, most allergies seem relatively innocuous. And it's true that more people believe they have allergies than actually do. For example, the gas and stomach pain of lactose intolerance? Not an allergy. But the rise in allergies is real. On a global level we need to better understand what's happening.

Here's how an allergy unfolds: One day, a body is exposed to a protein in something that seems perfectly harmless—the wheat flour, say, in a home-baked muffin. But for some unclear reason, the body looks at the protein and sees Trouble. There will be no symptoms at first, but the body is remembering—and planning.

That first exposure causes the immune system to produce an antibody called IgE (immunoglobulin E). Then IgE antibodies attach to certain cells, called mast cells, in tissue throughout the body. There they stay like wary sentinels waiting for war. With a second exposure, even months later, some of the allergen binds with the IgE on the mast cell. This time the mast cell releases a cascade of irritating chemicals: histamine, prostaglandins, and leukotrienes, which cause inflammation, work on nerve endings to make you itch, affect blood pressure and muscle contractions, and act on glands to cause mucus production and vasodilation, so you clog up.

A minor or isolated reaction can become chronic with repeated exposure to an allergen, or when other cells involved in the immune system, the T cells, come into play. Certain T cells remember the "insult" of the allergen and ensure that some part of the body keeps becoming inflamed. Often the allergen and the immune system become increasingly antagonistic, and the reaction worsens.

Sometimes, however (particularly with food allergies), the process is not gradual at all. This is what happened when Cameron Liflander ate tuna fish. He had to have been exposed to the allergen at least once before for IgE to be attached to mast cells and ready to react, but once the reaction was triggered by a subsequent exposure, an anaphylactic crisis occurred immediately. An allergist's tests showed that Cameron was severely allergic to fish, shellfish, mustard, sesame, peanuts, tree nuts, soy, dogs, cats, some antibiotics, mold, pollen, and dust mites. "The doctor said Cameron tested positive to more substances than almost any child he'd ever seen," Pamela Liflander says.

Fortunately not all Cameron's allergies are deadly. But some are. Parents whose children don't have allergies tend to think Pamela Liflander is overly protective. Those parents haven't had a child come close to suffocation.

National Jewish Medical and Research Center was opened in Denver in 1899 as a sanatorium for tuberculosis patients. The hospital still focuses on respiratory diseases, and is one of the premier research centers in the country for the treatment of allergies and asthma. There are air-locked rooms here for issuing "challenges" to people with every conceivable severe allergy. For some people even boiling shrimp or snapping a latex glove can release enough allergens into the atmosphere to cause anaphylaxis. One of the important issues at National Jewish: Why the epidemic of allergies now?

There is, unquestionably, a hereditary component to allergies. A child with one asthmatic parent has a good chance of developing the condition. If both parents have asthma, the chance of occurrence increases. Studies show that pairs of identical twins have asthma more frequently than pairs of fraternal twins.

Still, the rise in allergies is too rapid to be explained solely by genetics. "The genetic pool can't change that much in such a short time," says Donald Y. Leung, the director of the hospital's pediatric allergy-immunology program and editor in chief of the Journal of Allergy and Clinical Immunology. "There have to be environmental and behavioral factors as well."

Dozens of theories blame everyone from urban landscapers for favoring male plants, which are the ones that produce pollen, to women who don't breast-feed. Breast-feeding, the theory goes, confers greater protection against allergies. After all, it does seem to give babies greater immunity from colds and other infections.

Another probable factor: diet. "Reduced fresh fruit and vegetable intake, more processed food, fewer antioxidants, and low intake of some minerals—these are all shown to be a risk," says Harold Nelson, a professor of medicine at National Jewish who is considered one of the wise men of allergy and immunology.

The use of antibiotics may also be a cause of rising allergy rates. Certain bacteria in the intestine are associated with greater or lesser chances of having allergies. Researchers believe, as Donald Leung says, "Overuse of antibiotics may be disrupting certain gut flora that suppress allergy."

Stress and the hormone cortisol, which plays a role in the body's reaction to stress, also affect allergic illnesses. In times of stress the immune system pumps itself up, ready to fight infection or otherwise do battle. Then later the pituitary gland secretes cortisol, which acts as an anti-inflammatory, essentially turning down the immune system so it doesn't overreact. "But," says Kimberly Kelsay, National Jewish's resident psychiatrist, "some people don't produce enough cortisol in response to stress to turn down the immune system, so you're left with a greater risk for inflammation. In studies of adults and kids who receive a stressor in a lab, the ones with atopic dermatitis [ chronic and likely inherited inflammation of the skin] don't show as big an increase in cortisol levels." There are some studies suggesting the same pattern occurs with asthma and hay fever.

Another key culprit: environmental pollutants. Exactly what pollutants and in what quantities are a source of heated debate. One of dozens of examples: Epidemiological studies show that children who are raised near major highways and are exposed to diesel fumes from trucks have an increased sensitivity to allergens they already react to.

Ironically it's not just the pollutants that are doing us in. It may be too much cleanliness—or rather, cleanliness of a certain sort. A prevalent theory among allergists is known as the hygiene hypothesis. The theory has its complexities and contradictions, but the basic idea is this: If the Liflanders had wanted to prevent Cameron's allergies, they should have moved a cow into their living room. People who live with farm animals almost never have allergies.

"The hygiene hypothesis has been on the scene since people first started looking at allergies," says Andrew Liu, associate professor of pediatric allergy and clinical immunology at National Jewish. "John Bostock, the guy who first identified hay fever, noted that it was a condition of the educated. He couldn't report any cases among poor people."

Hygiene theorists say that while it's true that industrialization brings with it better health care and fewer serious childhood infections, it also brings an obsession with cleanliness. We are not exposed to dirt at a young enough age to give our immune systems a good workout. Also, because of the high cost of energy, more homes are built with an eye toward energy conservation, with better insulation—insulation that seals in mold and dust, enemies of allergy sufferers.

But if dirt is a good thing, why are allergies and asthma so prevalent in poor, inner-city neighborhoods? "It's not just a question of exposure to dirt that reduces allergies—it has to be the right kind of dirt," says Liu. "We're talking about exposure to endotoxin and good microbes in soil and animal waste."

Reams of research bear out the hygiene hypothesis. "There was a famous study," says National Jewish's Nelson, "where one of the protective factors for asthma was having a pig in the house."

It would be helpful it immunologists and epidemiologists were able to tease out each factor contributing to the escalation of allergies and say, J'accuse! That's probably not going to happen. Instead, researchers are attacking the problem on all fronts. Their unspoken attitude? We've made a mess of this planet, and we may not be able to fix it. The best science can do is help us fix ourselves.

Since most of us are unable to room with a pig, we have to come up with a plan. Can we avoid allergies altogether? Can we get rid of allergies we already have? Can we desensitize our immune systems?

"We still don't know exactly how to prevent allergies," says Andrew Liu. "We know the immune response is supposed to be a helpful one, that it's not supposed to be the cause of disease. We know that the immune system of someone with allergies needs to be reeducated. But how? It's not always clear."

Leung agrees, adding, "If you are exposed to endotoxin or other microbial products early in life, it may prevent allergies. But later in life the early exposure may actually make things worse." There are those who argue that to prevent allergies, we should reduce or eliminate exposure to harmful allergens at an early age. Others believe allergens should be administered in large quantities at an early age. Many believe it depends on the specific allergen. And food allergies may work on an altogether different principle. Confused? So are the allergists.

Improvements in immunotherapy have been hard to come by. The overall idea behind immunotherapy is to find something that alters the T-cell reaction to the allergen to one not associated with allergic symptoms when the allergen is reintroduced. Currently, the best method is to have injections containing increasingly larger quantities of the offending substance every week lor three to five years. "It requires time, investment, and money," says Harold Nelson.

At Johns Hopkins School of Medicine's Asthma and Allergy Center, clinical director Peter Socrates Creticos is studying what is essentially a ragweed vaccine. The vaccine contains the principal offending allergen from ragweed along with bits of DNA. The DNA acts as an adjuvant that allows the body to recognize the allergen more efficiently and begin a string of cellular events in the immune system that shuts down chronic inflammation.

Best of all, Creticos notes, "Just six weeks of injections before ragweed season caused people to experience 70 percent fewer symptoms. That's about the same degree of improvement we normally see with the earlier therapy after three years," he says. Better yet, the effects of the vaccine carried over to the next ragweed season. "We didn't just reduce symptoms," Creticos says, "we turned off the disease."

Some drugs are also being tested for treatment that works on a different principle. For example, Xolair, injected monthly, soaks up IgE like a sponge, ensuring that it cannot dock on mast-cell receptors and trigger an allergic reaction. It's no cure for the severely allergic, and a single injection costs $500.

Greg Rogers, a retired contractor, participated in the trial of a similar drug at National Jewish. "Before my treatment," Rogers says, "I would have to be rushed to the emergency room if I ate half a peanut. Now I can eat nine or ten of them and survive."

Not that Rogers would care to eat nine peanuts, or even one, but by raising his threshold of sensitivity, Rogers won't die by accidental ingestion.

What about preventing allergies in the first place? The greatest hope in this area may come from the studies of what immunologists call the atopic inarch. Two-thirds of kids with atopic dermatitis, or eczema, will develop hay fever, and 50 percent will develop asthma. For highly allergic kids such as Cameron Liflander, atopic dermatitis is often the first stop in the long march of allergies to come.

Most people have antimicrobial protectors in their skin that act as a first defense against microbial invaders. People who suffer from atopic dermatitis have low or nonexistent levels of these protectors, and as a result about 90 percent have Staphylococcus aureus on their skin. Some experts believe staph sets up the immune system for a life of allergies, beginning with rashes and working up to constriction of the airways.

"So essentially, skin is the portal—allergens get absorbed quickly through the skin," says Donald Leung. "Our idea is that if we can quickly reestablish the integrity of cracked, inflamed skin, we may be able to stop the predictable progression of allergies."

National Jewish has spearheaded a five-year study on more than a thousand kids with atopic dermatitis to see if rapid treatment halts the onslaught of allergies. The hospital is comparing traditional steroidal creams, which have some unpleasant side effects with long-term use, with a nonsteroidal cream called Elidel. The cream blocks a molecule called calcineurin, which is a key early activator of the T cells that orchestrate allergic response.

For a child such as Tyler Mason, the outcome of this study is anything but academic. As with all the kids who end up at National Jewish, Tyler's eczema involved more than a lew patches of red, scaly, itchy skin. Tyler's skin was ripped up. He got a staph infection that brought him to the hospital, and anyone visiting his room had to scrub first with disinfectant. Tyler was repeatedly bathed, slathered from head to toe with a moisturizer and then a steroidal cream to reverse the skin inflammation, and finally wrapped like a mummy, with only his eyes uncovered.

Tyler's mother, Vickie, has a picture of what he looked like when he arrived at National Jewish: less a child than a piece of raw meat on legs. After 48 hours of treatment, Tyler was closer to a red-faced kid with a bad rash.

Another possible way to stop the atopic march: Get infants to chow down on probiotics, or friendly bacteria, such as Lactobacillus found in certain yogurts. Some studies have shown that these beneficial bacteria are reduced in the guts of the allergy-prone. At a trial in Perth, Australia, infants treated with probiotics showed significant improvement in their chronic eczema two months after finishing an eight-week course of treatment.

These days, Cameron Liflander says he feels fine most of the time. It takes a lot to make him feel fine. For his asthma he needs a daily cocktail of steroidal and nonsteroidal drugs: P'roventil and Flovent in his inhaler, and Nasonex nasal spray. For his eczema he uses an antihistamine called Zyrtec and a topical steroidal cream. The steroids do not seem to have stunted his growth—one of the worrisome side effects of long-term steroid use in children—and he has adjusted to the antihistamine so that he does not usually feel drowsy.

Life is looking up for Cameron. He has had some of his allergic responses retested. The reaction to certain substances is modulating with age: He now tolerates soy (a huge relief because it's contained in a vast array of products). He has also started shots for his environmental allergies, and Pamela hopes that soon he'll be able to live without the daily doses of steroids.

Still, the Liflanders' '60s-style ranch house has hardwood floors and tile instead of carpets to prevent accumulation of mold, and no window treatments that might collect dust. Teachers, friends, and the health staff at school help keep Cameron and peanuts apart. Pamela is careful about playdates. "It has to be where someone could deal with an allergic reaction. But we want to try to avoid keeping him in a plastic bubble."

The rise in the number of people with allergies is changing the way we live and what we buy. Suddenly there's a booming market for products and services that were unimaginable 30 years ago. Hotels offer allergy sufferers rooms with special ventilation systems and linens washed with nontoxic products. Architects such as Roy Prince of Santa Barbara, California, specialize in "healthy houses." "Here in Santa Barbara, I'd say the number of people interested in buying environmentally friendly, nontoxic, 'green' houses has doubled in the past couple of years," says Prince.

Pollen-free sunflowers, first developed for floral arrangements that wouldn't soil tablecloths or clothes with yellow dust, are now marketed to allergy sufferers. So, too, are certain breeds of dogs: Havanese and coton de tulears—fluff balls about the size of a shih tzu. More familiar "hypoallergenic" breeds include Wheaten terriers, poodles, and Portuguese water dogs. (Incidentally, no dog or cat is truly hypoallergenic. Allergens come from dander, saliva, and urine, not from hair.)

More important, scientists are finding ways to get rid of the allergenic proteins in common offenders. Researchers at the University of Melbourne in Australia claim to have developed, with gene silencing, the first hypoallergenic rye grass. (It doesn't cause hay fever.) The U.S. Department of Agriculture has developed a strain of soybean that lacks the major allergy triggering protein that once caused such misery for Cameron. Scientists are crossbreeding existing peanut types that have lower levels of the proteins that cause anaphylaxis.

So Cameron Liflander and others like him may one day live in a world that's far more comfortable. But the question remains: How much genetic engineering is feasible? And even if we can eliminate the allergens we fight today, what will our immune systems decide are the enemies tomorrow?

Extras: See photos, field notes, and more from this National Geographic article.

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