Published in the Summer 2005 issue of Allergy Today. For more articles like this, subscribe to Allergy Today, click here.

A decade ago, few of us knew anyone with a food allergy. Now it is almost impossible to find a kindergarten or primary school that doesn’t have a child with an allergy. Is this a case of middle class neuroses, or is food allergy on the rise? Inga Stünzner reports.

The new epidemic

It says a lot when the world’s foremost expert in food allergy actually went into this area of research to prove that food allergy was a figment of neurotic mothers’ minds.

Hugh Sampson, Professor of Paediatrics and Immunobiology at the Mount Sinai School of Medicine, Director of the Jaffe Food Allergy Institute, Director of the General Clinical Research Centre at the Mount Sinai Medical Centre, New York and all-round food allergy guru, has humbly eaten his words.

He now dedicates his professional life to trying to understand why food allergies are on the rise, why they can be life threatening and how to develop a vaccine.

On a recent trip to New Zealand, Professor Sampson told health professionals that food allergy is on the increase: it has actually doubled from between 1.5 and 2 per cent of the population a decade ago to between 3.5 and 4 per cent today.

“This is a global problem and no Westernised country stands alone,” he says. “But despite our varied diets there are really a limited number of foods responsible for the majority of food-induced allergic reactions in children.”

In young children, it tends to be milk and egg, and while there are some differences the further down the list you go, peanut is one of the major ones for the US, Canada, Britain, Europe, Australia and New Zealand.

The highest prevalence of food allergy is found within the first three years of life, with between 6 and 8 per cent of children affected.

“For children under three, milk, egg and peanut predominate. Half a dozen studies around the world confirm that about 2.5 per cent of children under age of three experience milk allergic reactions, 1.5 per cent have egg and 0.8 per cent have peanut allergy,” Professor Sampson says.

About 80 per cent of children with milk allergy will outgrow their allergy by their third year; egg allergy is a little slower with about 50 per cent outgrowing it at this age. By five to six years, about 60 per cent have outgrown egg allergy and it is up to 80 per cent by the end of the first decade.

“Peanut allergy, however, is very different. Most children don’t outgrow their peanut allergy, and by five years of age only 20 per cent have.”

When you start looking at the older populations, the foods causing the allergic reactions tend to shift, moving to peanuts, tree nuts, fish and shellfish.

“In a recent study we did the US, we were a little bit surprised to find that shellfish allergy affected about 2 per cent of our population.”

How does an allergic reaction happen?

When we eat a food, this is largely broken down in the gastrointestinal tract, Professor Sampson explains. We have a sophisticated bowel wall that allows nutrients and substances our body needs to be absorbed and keeps out other substances, such as bacteria and other products. With each meal, however, we do have a small amount of food protein that enters our blood stream; if you were to drink a glass of milk or eat an egg and a blood sample was taken an hour later, circulating milk protein or egg protein would be found in your blood.

“But happily our immune system has learned to recognise that these foreign proteins are safe, whereas normally you would react against a foreign protein. So we have a certain kind of cell that says this is safe and ignores it.”

“However, there are the food allergic individuals whose immune systems don’t do this appropriately and we are still trying to understand why this happens. In these cases, the person’s body will make an allergic antibody, called an IgE antibody, which then will coat the surface of cells which release chemicals that bring about a severe allergic reaction.”
The symptoms of an allergic reaction can involve one of more of the following:

• Skin: flushing, itching, hives, eczema
• Gastrointestinal tract: abdominal pain, nausea, vomiting or diarrhoea.
• Respiratory system: upper tract, such as hay fever-like systems such as watery, itchy eyes, stuffy nose, sneezing; or lower respiratory, where you get difficulty breathing, wheezing.
• Very serious: cardiovascular system where have a loss of blood pressure and anaphylactic shock.

How is it diagnosed?

The gold standard for diagnosing a food allergy often comes down to an oral food challenge, where a person is given small amounts of food until a reaction occurs. The double blind placebo controlled food challenge excludes patient and observer bias, but there is risk of severe reaction.

Because of this, other methods of diagnosis are used: history, skin prick test and quantitative IgE level (Cap Rast), which all come with their drawbacks.

With history, the physician will take a history of what happened when the infant of child had the food, and they will try and correlate the symptoms with the different types of disorders.

“One place where this becomes difficult is where a child has atopic dermatitis because frequently, when the child ingests the food and they are ingesting it on a regular basis, the eczema will get worse and worse, but you don’t see any acute change,” Professor Sampson points out.

The second method, skin prick testing, is where a small amount of food protein is put on the skin, and a prick is made. Within 15 minutes, there will be a wheal if the test is positive. The problem with this is it isn’t a well-standardised test, and it only reveals that the patient has an allergic antibody and not whether they will react to the food. Generally, however, the larger the wheal, the greater the likelihood the person will react.

The final method, quantitative IgE level (or Cap Rast), measures IgE antibody to a particular food in a blood sample, and Professor Sampson says there is some evidence now that these numbers can be used to make a better diagnosis.

“The other thing we are looking at is the use of this quantitative IgE – or the amount of antibody that would correlate with the likelihood of someone having an allergic reaction.”
This is called the 95 per cent Predicative Decision Levels, a standard Professor Sampson and his team developed after studying 300 serum samples from children who had been challenged to different foods. Through this, they generated a probability curve, which takes away the need to undergo a food challenge.

“What we found with egg is if you have 7 kilounits per litre or greater of this IgE antibody to egg, it’s greater than 95 per cent likely that you are going to have a reaction. So this is essentially a medical positive. However, if the level gets lower, it doesn’t mean you’re not going to react, it just means that the probability goes down. So at 3.5 kU/L you have an 80 per cent chance of reacting, at 1.2 about a 50 per cent chance.”

Using this method, Professor Sampson’s team came up with 95 per cent Predictive Decision Levels for egg, milk and peanut.

“We never got these for wheat and soy because these allergens don’t appear to be adequate,” he says.

Age differences are also taken into account, so a younger child with a lower IgE level would still be 95 per cent predicative, meaning there is no need to conduct a food challenge.

Epitopes and peptides

Another exciting development is how the IgE antibody binds with the protein, and this could indicate how severe a person’s reaction may be and the likelihood of them outgrowing their allergy.

It has to do with sequential epitopes and conformational epitopes.

Professor Sampson explains: “When you look at a protein it is basically like a chain, with each link of the chain being an amino acid, and it’s all sort of wound around itself. And you have areas where the allergic antibody can attach and they are all in sequence along the chain. This is called the sequential epitope.

“You also have locations where two links of the chain may come in close proximity, and the antibody may bind to each of those portions of those loops in the chain. This is a conformational epitope.”

This helps explain a phenomenon where many children who are allergic to milk or eggs are able to tolerate them in baked products.

“The reason for this is that baking changes the shape of this protein. So in an individual who makes an antibody to the sequential epitope – if you cook that egg or milk, that epitope is still there because it’s along the sequence of that chain.”

This is only representative of 20 to 25 per cent of children with egg allergy, and it is these children who do not tend to grow out of their allergy. Most children with egg or milk allergy, no matter how high their IgE levels, recognise the conformational epitope.
A similar epitope structure has been seen in peanut allergy.

Using a method called Peptide Microarray Technology, researchers have studied IgE binding sites in individuals and then compared this with their histories. They discovered that someone with few or no epitope sites experienced only mild symptoms when they ingested peanut while those with many epitope sites had severe reactions.

“What this means is that we may have a test that gives us some kind of idea as to how severe a reaction someone may experience. If we can further develop this technology, then we have a way to show this correlation between the binding to specific epitopes and the likelihood that someone is going to have reactivity to this particular food,” says Professor Sampson.

“It is more specific than just measuring quantity of IgE. It also gives us an idea of whether this is a life-long problem or whether they will outgrow it and it will also give us some kind of idea of the potential of severity of reaction.”

Although there is no cure yet for food allergy, the amount of research in the last decade has increased exponentially and researchers are getting much closer to developing a vaccine.

But until this comes into fruition, we need to teach parents and patients how to read food labels to appropriately avoid the food they are allergic to, Professor Sampson says.

“Avoidance is key: learn obvious and ‘hidden’ sources of food allergen; learn the likely candidates for cross-contamination; learn to avoid ‘high-risk’ situations, such as buffets, ice cream parlours where spoons may be changed around; be aware of non-ingestion contact, for example airborne contact eg for a fish allergic person who goes into a restaurant where they cook a lot of fish because during the cooking process the protein is actually aerosolised and they can actually experience a reaction.”

In addition to this, it is important to learn to recognise early symptoms of a reaction and how to treat it, to have a written management plan, to have access to self-injectable adrenaline and to get support from organisations like Allergy New Zealand.

“Despite this, there are still some who go on to have reactions, which is why there is research into a peanut vaccine.”

Professor Sampson gave a series of seminars to health professionals in Christchurch, Wellington and Auckland in September. His tour was a join venture between Allergy New Zealand and the Australasian Society of Clinical Immunology and Allergy. It was made possible with an unrestricted educational grant from Nutricia, the project’s principal sponsor.

The atopic march

Many children with allergies follow what is called the atopic march. They start off with atopic dermatitis and often a food allergy, with egg allergy being the most common.
These disorders often go together and occur in the first few years of life. But they then progress on. If you have a child with atopic dermatitis and egg allergy, about 80 per cent of them will go on and develop asthma and the allergic rhinitis.