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Food Allergy Testing and Diagnosis – WSJ article

Grayson Grebe started getting eczema on his cheeks when he was just 4-weeks-old. At 6 months, he was diagnosed with allergies to wheat, dairy, eggs, nuts, oats, rice, barley, chicken, pork, corn and beans; his mother, who was breast-feeding him, had to stop eating them all. At 10 months, doctors cut out 20 more foods, including all fruits and vegetables, and put Grayson on a hypoallergenic formula. Even so, his eczema was so bad that his parents put him in mittens, long-sleeved shirts and long pants so no skin was exposed. “Otherwise, he’d scratch himself until he would bleed,” says his mother, Amy Grebe of Albuquerque, N.M.

Is It Really a Food Allergy?

Amy Grebe Photography

The first step in diagnosing two-year-old Grayson Grebe’s allergies was to treat his severe eczema.

At wit’s end, the Grebes took Grayson to National Jewish Health, a hospital in Denver that specializes in allergies and respiratory diseases. Doctors there suspected that his food allergies might not be causing the eczema—and that some might not be food allergies at all. After carefully supervised “food challenges”—giving him tiny amounts and monitoring him closely for signs of a reaction—a number of foods went back in his diet. “We came home with 12 foods he could eat,” says Amy Grebe. “It’s made so much difference in our lives.”

For parents of children with food allergies, this may be both welcome and unsettling news: Many kids whose allergies were diagnosed on the basis of blood or skin tests alone may not be truly allergic to those foods, experts say.

Blood tests measure the level of antibodies, called immunogloblin E (IgE), a body makes to a particular food. But having IgE antibodies doesn’t mean that a person will actually have an allergic symptom when they encounter it.

Skin-prick tests are slightly more predictive, but there, too, a red wheal in response to a skin prick doesn’t necessarily mean that a child will have an actual allergic reaction to that food.

The only way to know for sure—short of encountering the food in real life—is with a food challenge test in a doctor’s office or hospital. But those can be time consuming, expensive and nerve wracking, especially for parents who have seen a child encounter an anaphylactic shock, a life-threatening reaction in which multiple organs quickly shut down.

With use of allergy tests booming, more parents are coming away not fully understanding what they mean. That sometimes frustrates allergy experts. “When I first started doing this, my biggest job was convincing families to avoid a food. Now, the biggest job is to get families back on a food,” says Hugh Sampson, a professor of pediatrics in the division of allergy and immunology at Mount Sinai School of Medicine in New York.

Several recent studies have underscored the gap between IgE antibodies and actual allergies. In this month’s Journal of Allergy and Clinical Immunology, researchers in Manchester, England, reported that when 79 children who tested positive for peanut IgE antibodies were given food challenges, 66 of them could eat peanuts safely. At the American Association of Allergy, Asthma and Immunology (AAAI) conference last year, doctors from National Jewish reported that of 125 young patients given food challenges, more than half could tolerate foods they’d been told to avoid.


Confusion over test results has also made it harder to track the true prevalence and growth of the allergies. It’s widely estimated that some 12 million Americans, including four million children, have food or digestive allergies, up 18% from 1997. But that includes food intolerances, which don’t involve the immune system.

A national sampling from 2005-2006, which also included blood tests, found that 9% of U.S. children had a sensitivity to peanuts, 7% to egg; 12% to milk and 5% to shrimp. But experts believe that only about one-tenth of those children will actually have allergic reactions to those foods. Even the true rate of fatal reactions to food allergies is hard to gauge: Estimates range from as low as five to as high as 200 per year.

Experts agree that the most important part of a food-allergy diagnosis is a history: What did the child eat and what kind of reaction did he have? Even if it seems clear-cut, most doctors will also do a blood test or skin-prick test to confirm that the child has antibodies to the suspect food.

“If you come to me and say, ‘My child ate a peanut butter sandwich and within 15 minutes, his lips turned blue, he got hives and threw up,’ that’s enough to tell me the child has a peanut allergy,” says Dr. Sampson. “The more typical history is that they were eating a meal and he had this horrible reaction and they think it’s peanuts. It’s important to do a skin or blood test to make sure.”

Some experts believe it’s not helpful to test for food allergies when there’s no history of problems with those foods. But what often happens is that a child has a bad reaction to one food and the family is anxious to know if they should avoid others, too. Or a parent or a sibling has a food allergy, and a family wants to know if others are at risk. Some doctors will then screen the child with extensive panels of allergy blood tests that may come back showing the child has IgE antibodies to a wide range of foods.

“I see it all the time. A family goes in for one thing and comes back with a laundry list of foods they are supposedly allergic to,” says Jodi Stokes, whose son Kevin has food allergies, and runs a support group for allergic families in Charlotte, N.C. “I tell them to go to a board-certified allergist who knows how to interpret these tests.”

Eat and Be Wary

  • An estimated 12 million Americans—including four million children—have food allergies.
  • From 1997 to 2007, the percentage of U.S. children with a reported food or digestive allergy increased from 3.3% to 3.9%.

“Are these blood tests being overused? Possibly. Misinterpreted? Absolutely,” says Robert Wood, director of Pediatric Allergy and Immunology at Johns Hopkins Hospital, who is part of a task force writing guidelines for diagnosing and managing food allergies. “A lot of these kids truly have food allergies, just not to all the foods that they are being told they have allergies to.”

In some cases, the blood or skin tests reveal antibodies to a food that the child has already been eating without problems. It’s easy to dismiss those results. It’s harder to know what to make of IgE antibodies to foods a child hasn’t yet tried. Children with eczema, like Grayson Grebe, tend to have IgE antibodies to a large number of foods, and it can be difficult to sort out which really do pose problems.

Allergy experts can make some guesses about the likelihood of a reaction based on test results, and they are starting to establish cutoff thresholds. In a skin-prick test, for example, a wheal smaller than 5 millimeters in diameter indicates a slim chance of a real allergy, says Dr. Sampson; a wheal greater than 10 millimeters is generally a good chance.

In blood tests, some research suggests that IgE antibody levels higher than 7 KUa/L to egg, 15 to milk and 14 to peanut are highly predictive of an allergic reaction. But some people have allergic reactions at lower levels, too.

And none of those tests can predict how severe an allergic reaction might be. A person with a peanut allergy might react with a tingle in the mouth, a case of hives or a full-blown anaphylaxis, depending on many variables, including how much peanut they ingested and in what form.

Complicating diagnoses further is the fact that food allergies are a moving target as children get older. It’s estimated that 80% of children with allergies to milk, eggs, wheat, diary and soy outgrow them, usually by about age 5. But only about 20% of those with allergies to peanuts, tree nuts and shellfish do. And for reasons not fully understood, some people can develop allergies later in life to foods they’ve previously tolerated, particularly shellfish.

Doctors can get some clues to an allergy’s progression by monitoring skin and/or blood tests regularly. And when IgE levels have been dropping consistently, or were never high to begin with, some may suggest trying a food challenge, usually done in a hospital or specially equipped doctor’s office, where help is immediately available in case of a bad reaction.

The Food Challenge

For some families, deliberately exposing a child to food they have scrupulously avoided for years is simply not worth the risk. But for those who have had to severely restrict a child’s diet, restoring some food groups can be life-changing.

“There is a kind of post-traumatic stress syndrome that happens after a bad allergic reaction,” says Dan Atkins, head of outpatient pediatrics at National Jewish Health. “But the payoff in successful food challenge is huge.”

“I thought it was pretty entertaining,” says 15-year-old Alex Simko of Geneva, Ill., who did a four-hour food challenge with hard-boiled eggs last year after avoiding them for 12 years. She made faces throughout because she hated the taste of eggs. But she didn’t have an allergic reaction—and allowing eggs into her diet has opened up a world of baked goods (“doughnuts!”) she previously had to avoid.

Some other kids aren’t as sanguine. Having been told all his life to avoid eggs all his life, 4-year old Kevin Stokes refused to try them during a food challenge at Duke University Medical Center last year. “He freaked out,” says Jodi Stokes, who holds out hope that he will try again. In the meantime, he is still allergic to peanuts, tree nuts and milk, so they have the same rule that many allergy families have about scrutinizing food labels: “If you can’t read it, you can’t eat it.”

A new kind of blood test could someday help doctors zero in more definitively on who is most likely to have allergic reaction to foods. Phadia AB, a maker of allergy tests, has developed a test, called Component-Resolved Diagnostis (CRD) that can determine which molecule within a food is sparking the antibody reaction. In the peanut, for example, only three of 14 different molecules are associated with anaphylaxis-causing reaction, according to the company. CRD has not yet been submitted for approval by the Food and Drug Administration, but it is in use in Europe.

In the Manchester study, for example, the researchers found that almost all of the children who were highly allergic to peanuts reacted to a specific protein call Ara h 2.

Knowing more about what specific molecules cause allergic reactions could help scientists understand more about the severity of allergic reactions, and someday help efforts to develop treatments to trick the immune system into behaving differently. In the meantime, parents with allergic children are often left walking a fine line, between taking potential life-threatening risks seriously, and not overreacting to tests that may not reflect a child’s actual risk.