A. Case study
A 7-month-old boy with eczema was referred to a dietitian for a dietary intervention. The child had been exclusively breastfed for the first few months after birth. At 4 months of age he started to develop slight eczema. At 5 months, the mother started to include solid foods in his diet. The eczema got progressively worse until she decided to take him to a doctor (at age 7 months). She was still breastfeeding him at this point.

These are the results of the blood tests the doctor ordered (in KU/L):
Phadiatop: 0.46 (class 1)
[This is a screening test that measures the level of IgE to a combination of the common inhalant allergens. A positive result indicates that the subject is sensitized to 1 or more of these inhalants, but does not indicate which. From there one can test for specific allergens.]
FX5: 40.10 (class 4)
[This is a screening test that measures the level of IgE to a combination of the 6 most common food allergens. A positive result indicates that the subject is sensitized to 1 or more of these foods, but does not indicate which. From there one can test for specific allergens.]
Egg white: 10.2 (class 3)
Egg yolk: 1.25 (class 2)
Cow's milk: 26.50 (class 4)
Soya: 1.23 (class 2)
Wheat: 3.43 (class 2)
Maize: <0.35 (class 0)
Peanut: 9.47 (class 3)
Rice: 0.39 (class 1)

The reasons these specific tests were done are not entirely clear. It is, however, established that the mother was concerned about maize and rice causing the reaction. These are not common foods to be allergic to at this infant's age, and therefore it would not be routine to request the relevant blood tests (as it would be in the case of the other foods).

THOUGHT PROCESS
What can cause or exacerbate eczema?
a. Stress
b. Chemicals and environmental allergens
c. Foods

DISCUSSION
a. Stress was not a factor.
b. The mother was questioned about these, but no specific problems could be identified. The low IgE level shown by the Phadiatop CAP RAST blood test also suggested that the common inhalant allergens were probably not causing the reaction.
c. The FX5 test result showed relatively high IgE, but sensitization to individual allergens appeared to vary widely. At this stage the boy was eating sweet potato, butternut squash, paw paw, avocado, broccoli, apple, banana, and pear. The mother had stopped giving rice and maize a week before. As no correlation could be found between the adverse reaction and possibilities in a and b (above), the possibility of a food-related cause was investigated further.

THOUGHT PROCESS
What do the blood results mean?
Recent literature has shown that a low level of IgE to a specific allergen indicates that the individual is probably merely sensitized to the allergen and not yet symptomatic. The higher the IgE level to a specific allergen, the more likely that the person is reacting to it. Here, the blood results for egg yolk, soya, wheat, maize and rice indicated that the child was probably merely sensitised to these foods and that they were not necessarily eliciting a reaction. The milk result, belonging to class 4, and egg white and peanut results, belonging to class 3, probably indicated that the child was reacting to these as a result of being exposed to them in some form. But if the child had not been ingesting any cow's milk, egg or peanut, what could be the cause of these increased IgE levels?
a. The child had been exposed to these as hidden allergens in his diet.
b. The child had been exposed to these as hidden allergens in non-food products.
c. The mother ate milk, egg and peanut, and the child was reacting to the allergens transferred through breast milk.

DISCUSSION
a. The foods the child had eaten were all plain and unprocessed, so that they were very unlikely to contain hidden allergens.
b. After investigation, it was determined that one of the baby-care products used did contain peanut oil. Highly refined peanut oil is unlikely to contain peanut proteins and would therefore not elicit a reaction, but less refined oil may. Baby-care products therefore needed to be considered as a possible cause of the reaction.
c. This could be possible, as the mother, being a lacto-ovo-vegetarian, did eat dairy products and egg, and a very small amount of peanuts.

It was decided to ask the mother to replace the peanut oil-containing baby-care product with one that did not contain peanut oil. Also, the question arose whether the mother should exclude milk, egg and peanut from her diet in an effort to improve her son's symptoms. As she was a vegetarian, this would have restricted her diet immensely and possibly compromised her nutritional status and the quantity and quality of her breast milk.

As small amounts of peanut have been shown to elicit a reaction, it was decided to see whether there were an improvement in symptoms after the baby-care product was changed. The symptoms did not improve. But as the quality of the peanut oil present in the previously used product could not be guaranteed as consistent, the mother was advised to keep on using the peanut-free product: regular exposure to even a low level of peanut could sensitize the child to a greater extent, which could result in a reaction in the future.

The mother decided to stop breastfeeding rather than change her diet. The question then became which formula should be given to the child. Here are the main possibilities:
a. Cow's milk-based formula
b. Soya formula
c. Partially hydrolysed formula
d. Extensively hydrolysed formula

DISCUSSION
a. This formula was not a good choice, as there was a high probability that the child would develop an allergy because of the high level of IgE to milk.
b. This formula was also ruled out, as there was a risk that the child would develop an allergy, though his level of IgE to soya was not high. About 25% of milk-allergic individuals could be expected to be allergic to soya as well.
c. Partially hydrolysed formulas have shown some benefits in preventing the development of allergy, but not in its treatment.
d. Extensively hydrolysed formulas are preferred in the case of milk allergy. But it must be kept in mind that about 20% of cow's milk-allergic individuals have been shown to react to extensively hydrolysed formula. If this occurs, an elemental feed may be required.

The child was put on an extensively hydrolysed formula and his symptoms improved dramatically. The mother was advised to exclude cow's milk, egg and peanut from his diet until the age of 2-3 years as part of normal measures to prevent the development or progression of allergy. Thereafter he could be re-examined to see whether he had outgrown the allergy.

TIP for Allergy Advisor users: When selecting a suitable alternative feed for a cow's milk-allergic infant, Allergy Advisor can assist by the allowing the user to read up about cross-reactions between cow's milk and other milks. This can be done by entering "milk - cow's" into the search function and selecting the "CrossReactions" tab. If a patient is planning a family, the patient information sheet, "Allergy prevention strategies for pregnancy and infancy", can be printed out. This can be found under "Management", "Patient information sheets" and will give the person some guidance on what strategies can be implemented to prevent their child of developing an allergy.

B. More information:
This newsletter will focus on the prevention and delay of the development of allergy. The following are definitions of important terms concerning this topic:

Sensitization vs. elicitization
When the body is first exposed to an allergen, it may see the allergen as foreign and respond by activating the immune system. Allergen-specific IgE antibodies are produced in an attempt to combat the allergen. The body is thus "sensitized" to the allergen, but for some time may not show any adverse reactions upon exposure to the allergen. But a sufficient dose of the allergen may "elicit" a reaction at some point. The phenomenon is called "elicitization".¹

Allergic march In many children, allergies follow a stereotyped course: children tend to "outgrow" certain allergies and then develop certain new ones. Before the age of 3 years, allergy usually expresses itself as eczema and food allergy. In middle childhood, eczema and food allergy generally resolve and give place to asthma. In the adolescent years, asthma begins to stabilize and allergic rhinitis becomes more prominent. A child with a food allergy is therefore more likely to develop asthma and allergic rhinitis later in life. This progression has been termed the "allergic march" (also known as the "atopic march"). (See the chart demonstrating the allergic march below.)2

High-risk infant
There are various indications that an infant is at high risk for developing allergic disease. Among these indications are 1) having at least 1 immediate family member (mother, father or biological sibling) with allergic disease, and 2) EITHER allergic disease in both parents OR in one parent or sibling, combined with elevated cord blood IgE. (There is an association between newborns having raised levels of cord blood IgE, and increased risk of the development of allergic disease.) It has been suggested that one should complement these criteria with tests to determine whether the parents' allergies are IgE-mediated or non-IgE-mediated.^3,4

3) Kjellma has suggested the following method of determining whether a child is a "high-risk infant":
Scoring is as follows:
2 points each for a mother, a father or a sibling with a medically confirmed allergic disease
1 point each for a mother, a father or a sibling with a medically unconfirmed but suspected allergic disease
0 points: mother, father and siblings with no allergic disease

⁵ Among high-risk infants, prevention strategies can result in a lower prevalence and severity of allergic disease.

PREVENTION IS BETTER THAN CURE
Genetic predisposition represents a major risk for developing allergies, including food allergies. The chance of developing an allergy is:
5-15% if neither parent is atopic
20-40% if one parent is atopic
25-35% if one sibling is atopic
40-60% if both parents are atopic
If both parents have the same allergy, the child has a 60-80% chance of developing that allergy.

Maternal allergy appears to be a greater risk factor than paternal allergy. Boys tend to have an earlier onset of allergic disease than girls.⁶

A child is more likely to develop an allergy to 1 or more of the 6 major allergens (cow's milk, egg, soya, fish, peanut and wheat).⁷ There are, however, great differences in what are regarded as major allergens in different countries and cultures. (See table of common allergies in various countries below.)⁸

There are 3 types of allergy prevention:
Primary prevention: prevention of sensitisation
Secondary prevention: prevention of the manifestation of disease in an already sensitised individual
Tertiary prevention: attempting to reduce symptoms after allergic disease expression^7,9,10

The following are proposed to prevent allergy or slow the allergic march:

1. Maternal restriction during pregnancy Some studies suggest that in utero sensitisation, especially during the 2nd and 3rd trimesters, is the first step in the allergic march. This, however, has not been conclusively proven. Sensitisation during this period might occur either from exposure to allergens that cross the placenta, or from the fetus swallowing IgE from the amniotic fluid.11

The different points of view on what intervention should be recommended are:

The evidence is clearly not conclusive. Most authorities advise that foods not be excluded from the mother's diet, but the American Academy of Pediatrics suggests that peanut be avoided during pregnancy. The reason for this is that peanut avoidance will not lead to nutritional deficits and that its restriction during pregnancy can help prepare the mother for its avoidance postpartum.¹⁰ Overall, the approach should be individualized according to the child's family history. If a pregnant woman decides to exclude foods from her diet, a dietitian should assist in compiling a nutritionally adequate diet.⁷

2. Maternal restriction during lactation It has been proven that allergens can be transferred to an infant through breast milk and thereby sensitize the infant.10 Although the benefits of excluding allergens from the mother's diet to prevent sensitization have been proven, specific guidelines for intervention vary from country to country.4 If a child is shown to be allergic to a specific food and is still being breastfed, it is routinely recommended that the mother exclude the food from her diet. Aside from this, however, there are different points of view in the literature:

Again, the approach should be individualised. If there is a strong family history of allergies, addressing which by dietary exclusion would not result in a nutritionally inadequate diet, such exclusion may be worthwhile.⁷ If 1 or more allergens are excluded from the mother's diet, a dietitian should assist in compiling a nutritionally adequate diet.

3. Exclusive breastfeeding for at least 6 months Exclusive breastfeeding for at least 4 to 6 months to prevent or delay the onset of allergic disease has been recommended in many studies. This is very important, as even a single alternative feed could result in sensitisation. This breastfeeding period allows the gastrointestinal tract to mature sufficiently to be able to withstand exposure to allergens.4,13,14,15,16

The American Academy of Pediatric suggests exclusive breastfeeding until 6 months of age and then nonexclusive breastfeeding until at least 12 months of age. These breastfeeding recommendations are the same for all newborns, whether at risk for atopy or not.⁷

Benefits (both proven and proposed) of breastfeeding:

It should be noted that a large study on the relationship between breastfeeding and allergies, particularly asthma, suggested that breastfeeding in the early months of life can prevent allergies until the age of 2 years; but that breastfeeding may lead to an increased risk of allergies once the child is older than 2 years.¹⁶

If breastfeeding is impossible for the high-risk infant:
Cow's milk-based infant formulas should not be given as an alternative because of the risk of developing cow's milk allergy. Many clinicians suggest that soy formula should not be given, as it has been found to elicit a reaction in more than 25% of cow's milk-allergic individuals. But it should be kept in mind that 70-75% will not react, and soy could be used if proven to be safe in a particular infant.^6,10 The same would be the case with other milks such as goat's and sheep's milk. (It should be noted that 70-90% of cow's milk allergic patients will be intolerant to goat and sheep's milk.)^10,17

Extensively hydrolysed formula (eHF) is the formula of choice in the case of high-risk infants who cannot have breastmilk.^3,14,16 A concern is that even these feeds have been shown to elicit a reaction in about 20% of cow's milk-allergic infants.¹⁸ The formulas are often also not affordable in lower socio-economical groups.

What about partially hydrolysed formulas (pHF)? It has been claimed that pHF might induce tolerance because of the presence of some allergenic activity, but recent data indicate a greater benefit with eHF than with pHF.^3,4 PHF is not used if a child has already been diagnosed with cow's milk allergy. If a child reacts to eHF, an elemental formula should be given.¹⁰

4. Avoidance of the highly allergic foods for a certain period There is conclusive evidence that a high-risk infant should not be exposed to the major allergens early in life. But the exact period has not been determined. All 6 major allergens should definitely be avoided for at least the first 6 months, preferably 1 year.

Various studies have indicated that high-risk infants should not be given dairy until they are 1 year of age; eggs until age 2 years; and peanuts, nuts, and fish until 3 years.¹⁰ (Incidentally, it is also said that children under the age of 5 should not be given whole peanuts because of the risk of choking.¹¹) But these are only general guidelines. On the other hand, some have suggested that a nutritious diet (a diet which is less easily attainable if many foods are excluded) is more important during the first few years of life than strict allergen avoidance. Again, a regimen should be individualized according to the family history, and a dietitian should be consulted to ensure nutritional adequacy of the diet.

Attention should be given to avoiding exposure to hidden allergens as well. Many baby-care products contain allergens such as nut oils, cow's milk, egg, wheat and sesame proteins. Also avoid highly perfumed products, as they may contain substances that could sensitize the child. It is important to read product labels carefully.

5. Avoidance of environmental allergens Exposure to environmental allergens such as house dust mite, pets (cats, dogs, birds), molds and cockroaches could sensitize the infant. In the case of a high-risk infant, measures to reduce the allergen load (such as anti-house dust mite measures) should be implemented in the house and especially in the baby's room.6,10,19,20 Literature has reported that infants born in the spring months (when the pollen count is high) have a high risk of developing pollen-related allergies. It is recommended that, if possible, the birth of a high-risk infant be planned so that it does not coincide with these months.6 Smoking should also be avoided during pregnancy and lactation. Children should not be exposed to passive smoking.6,10,21

There has been conflicting evidence about the avoidance of contact with other infants or adults with viral infection within the first 6 months of a high-risk infant's life. The theory is that viruses could exacerbate the development of allergies. But it has also been said that children who are exposed to peers and to infections early in life have a lower risk of developing atopy. The evidence is not conclusive as yet.²²

6. Probiotics Several studies have shown promise for probiotics creating the correct balance of microbial flora in the gut and thereby slowing down the development of allergy. The immune system may develop protective responses, and gut defense barrier mechanisms may be strengthened. But the exact mechanism is not clear yet, and at this stage there is insufficient evidence to validate this intervention as a standard clinical practice.23,24,25,26

7. Medication Recent studies have shown that a specific long-acting antihistamine in high-risk infants markedly reduced or prevented the progression from atopic dermatitis to asthma, if the drug was used at the earliest appropriate moment.It seems, therefore, that in high-risk infants and children who are already showing symptoms of allergic disease, the use of this drug may significantly delay the progression of the allergic process and prevent more serious allergic conditions such as asthma. It has also been shown that, if administered daily for a prolonged period (i.e., 3 years), the drug may hamper the development of new sensitisations in monosensitised children: this makes it a potential means of tertiary prevention of allergy.6,27,28

2. True or false: Where the unborn child has a strong family history of allergy, 1 or more of the 6 major allergens should always be avoided in the pregnant woman's diet.
(a.) True
(b.) False

3. True or false: It has been proven that allergens can be transferred to the infant through breast milk and sensitize the infant to a specific allergen.
(a.) True
(b.) False

4. Which of the following is not a possible benefit of breastfeeding:
(a.) It provides the infant with nutrients for growth and development.
(b.) It provides immunological protection during the critical period when the infant's own defense mechanisms are immature.
(c.) It actively stimulates the development of the infant's own immune system.
(d.) The child is exposed, through its mother's milk, to a high enough dose of cow's milk proteins to guarantee tolerance rather than allergic disease.

5. Which is the formula of choice in high-risk infants who cannot have breast milk?
(a.) Cow's milk-based formula
(b.) Soya formula
(c.) Partially hydrolysed formula
(d.) Extensively hydrolysed formula

6. True or false: In the high-risk infant, the 6 major allergens should be avoided for at least the first 6 months, preferably for 1 year.
(a.) True
(b.) False

7. What are the suggested mechanisms by which probiotics may influence the development of allergy?
(a.) Creating the correct balance of microbial flora in the gut
(b.) Allowing the immune system to develop protective responses
(c.) Strengthening gut defense barrier mechanisms
(d.) All of the above.

8. True or false: Early use of a specific long-acting antihistamine in high-risk infants has been shown to markedly reduce or prevent the progression from atopic dermatitis to asthma.
(a.) True
(b.) False