An update on food allergy Introduction Adverse reaction to food is a frequent clinical complaint, yet the subject of food allergy is one of the most misunderstood in clinical medicine. The wide array of symptoms ascribed to food ‘allergies’ often seem confusing to the clinician, and diagnostic tests are usually not easily available to non-specialists. This review will address the common clinical problems associated with food allergies, the approaches to establishing a diagnosis, and the available treatment strategies.
Adverse reactions to food can present in many different ways. In order to make a
correct diagnosis, some form of categorisation is necessary. The European Academy
of Allergy and Clinical Immunology proposed a classification of adverse food
reactions based on mechanism1. These reactions can be either toxic or non-toxic;
toxic food reactions can occur in anyone, whereas non-toxic reactions require
individual susceptibility and may or may not be immunologically-mediated. An
example of toxic reactions is scombroid fish poisoning where bacteria in poorly
preserved fish break down the amino acid histadine in muscles into histamine. The
symptoms of this reaction are very similar to an IgE-mediated allergic reaction, but
may occur in anyone provided a sufficient quantity of histamine is ingested. Food
intolerances are non-immunologically mediated food reactions that occur in
susceptible individuals. This may include flushing after alcohol, migraine headaches
after ingesting tyramine-rich foods, arrhythmias after ingesting caffeine, and the
Chinese restaurant syndrome after ingesting monosodium glutamate (MSG). The
term food allergy should be confined to those clinical syndromes caused by
immunological reactions to food proteins or chemicals. A substantial proportion of
food allergic reactions are caused by immunoglobulin E (IgE) directed against food
proteins. Such reactions are usually immediate, and may lead to GI symptoms,
urticaria, angioedema, hypotension and frank anaphylaxis. Other reactions caused by
IgA (coeliac disease) or cell-mediated immunity may also occur. The rest of this
article will focus on immunologically-mediated food reactions.
There is very little published data on food allergies in Southeast Asia. A prospective
study of American children followed for the first three years of life revealed that 28%
of parents reported food allergy in their children, but only 8% could be confirmed by
challenge tests2. 2.5% of infants experience cow’s milk allergy in the first year of
life3-5. 1.3% of young children are allergic to egg6, and 0.5% of them are allergic to
peanut7,8. Surveys from the UK indicated that 1.4% to 1.8% of adults experience
adverse food reactions9, and similar surveys from the Netherlands indicated a 2%
adult prevalence10. In general, people with a strong personal or family history of
atopic diseases such as asthma and atopic dermatitis have a significantly higher risk of
developing food allergies. Experience from our allergy clinic in Hong Kong suggests
that the pattern of food allergy may be different from the West. Whereas cow’s milk,
egg, wheat, peanut, tree nuts, soy and fish constitute the majority of allergenic foods
in the west, we see many more cases of shellfish allergies. Other more exotic foods
rarely seen in the west, such as Chinese medicinal herbs, royal jelly11, limpets and fish
sauce also cause a substantial number of allergies. Peanut allergy, though less
common, is also seen in Chinese patients in Hong Kong and can be equally lethal.
Gastrointestinal manifestations of food allergy
Since the GI tract is the first site to come into contact with food allergens, GI
symptoms are frequent in patients with food allergy. IgE-mediated reactions that
cause nausea, vomiting, abdominal pain and diarrhoea may occur sometimes within
minutes of ingestion. Repeated ingestion of allergenic foods may lead to poor
appetite, intermittent abdominal pain and malabsorption. Direct contact of allergenic
food with the oral mucosa causing itching and swelling of the lips, tongue, palate and
throat is called the oral allergy syndrome. This is usually caused by fresh fruits and
vegetables, and patients with pollen allergy are especially susceptible. This is because
there is substantial cross-reactivity in allergens found in ragweed pollen, melons and
bananas12,13. There is also cross-reactivity between allergens found in birch pollen
and apples, potatoes. hazelnut, celery, carrots and kiwi14,15. Since these allergens are
heat labile, patients can usually eat these foods without symptoms if they are cooked.
By the same token, it is best to use fresh food extracts for skin testing in this
Aside from IgE-mediated reactions, food allergies may cause other forms of GI
pathologies. Eosinophilic oesophagitis or gastroenteritis is sometimes seen in infants
with cow’s milk allergy. Symptoms include gastroesophageal reflux16, vomiting,
abdominal pain, failure to thrive, hypoalbuminaemia, haematamesis and intestinal
obstruction17. Other food proteins may cause similar symptoms in older children.
Elimination of the offending foods will lead to resolution of symptoms in 3 to 8
Food proteins can also induce enteropathy in children; while cow’s milk is most
frequently implicated, soy, egg, chicken, rice and fish have also been reported. There
is overlap between food protein enteropathy and celiac disease, with small bowel
injury being a prominent feature19. Affected infants usually present gradually with
malabsorption, and cow’s milk intolerance also predisposes to soy protein enteropathy.
As soy protein is equally allergenic, hydrolysed formula should be used in cow’s milk
allergic infants. After the age of 1 year, cow’s milk can be re-introduced gradually.
Gluten-sensitive enteropathy or celiac disease appears to be rare in Chinese.
Food-induced enterocolitis has a more acute and severe presentation, and can start
within the first few days of life. Affected infants develop protracted bloody diarrhoea,
vomiting and dehydration. Small bowel injury leads to anaemia, hypoproteinaemia,
malabsorption and failure to thrive. An extensively hydrolysed formula should be
Cutaneous manifestations of food allergy
IgE-mediated reactions to food often present as urticaria and angioedema. Onset of
symptoms is rapid, sometimes within minutes of ingestion, and usually last for less
than 24 hours. Patients are usually able to identify and avoid the offending foods.
Food allergy is rarely a cause of chronic urticaria,20 although salicylates and food
additives have been implicated. Food allergy as a factor in the development of atopic
dermatitis (AD) is still a matter of debate especially amongst dermatologists. In a
recent study, 37% of children with moderate to severe AD were found to be allergic to
food by serum IgE tests and food challenge21. In a study of 55 children with severe
AD and egg allergy, those children randomised to an egg elimination diet improved
significantly compared to those children undergoing conventional treatment alone22.
The good news is, one-third of children with AD and food allergies “outgrow” their
allergies over 1 to 3 years23, with the exception of peanut, nuts, fish and shellfish
allergies. It is therefore pertinent that all children with moderate to severe AD should
be tested for food allergies, and if present, dietary advice should be given. A two to
three week elimination diet followed by gradual reintroduction of suspected foods one
by one while keeping a symptom diary is often sufficient for diagnosis. In some
severe cases, a trial of an elemental (antigen-free) diet may be warranted. Elemental
formulas from Alpha Nutrition, Vivonex or Neocate would be appropriate for this
Respiratory tract manifestations of food allergy
Respiratory symptoms are common in patients who develop food-induced
anaphylaxis, and are invariably present in fatal or near-fatal cases. Patients with a
history of asthma or a history of previous severe reactions are especially susceptible
to severe anaphylaxis. Food allergy is a rarely a factor in allergic rhinitis; a survey of
323 patients with chronic rhinitis revealed that only 2 patients had nasal symptoms
during blinded food challenges24. Most cases of food-induced asthma occur in early
infancy in relation to cow’s milk allergy. Estimates of asthma prevalence in milk-
allergic infants vary from 7% to 29% depending on the definition of milk allergy. A
study of 88 children with AD and asthma revealed that 15% wheezed during food
challenge, and 8% demonstrated a greater than 20% drop in FEV 25
induced respiratory symptoms appear to be rare in patients without AD.
There have been anecdotal reports of asthma caused by food additives such as the
yellow dye tartrazine, monosodium glutamate (MSG) and sulphites. Sulphite-induced
asthma is well recognised, and can cause severe or even fatal reactions. Sulphites are
found in dried fruit and wine, and are sometimes used as antioxidants in salads and
potato fries. Intense bronchospasm may occur within minutes of ingestion in
susceptible individuals. It has been estimated that 5% of asthmatics are sensitive to
sulphites26. Data on other additives are less clear-cut. In one study, 11 out of 277
(4%) asthmatics challenged with tartrazine experienced a significant response27. In
another study, only one out of 28 patients with possible food-additive asthma reacted
to tartrazine28. In another recent study, 100 asthmatics including 30 with a history
suggestive of MSG sensitivity were challenged with MSG and no significant response
was seen29. MSG is widely used in restaurants in Hong Kong, and we rarely
encounter patients with a history of MSG-induced asthma. Such complaints seem to
be more prevalent in western countries, where MSG use is not as widespread.
Systemic manifestations to food allergies
Systemic anaphylaxis is the most dangerous of all allergic reactions, and food allergy
is the most common cause of anaphylaxis30. Any food protein can theoretically cause
anaphylaxis but certain foods are more likely. These include peanut, tree nuts, fish,
shellfish, cow’s milk, egg, seeds, beans, fruits and cereals. Reactions invariably occur
within 60 minutes and may include urticaria, angioedema, bronchospasm,
hypotension, laryngeal oedema, abdominal pain, emesis and diarrhoea. Severe
reactions will lead to asphyxia, vascular collapse, cardiac arrhythmia or myocardial
infarction. The quantity of food required to induce a reaction is dependent on patient
sensitivity, potency of the food allergen and other unknown factors. Some food such
as peanut and fish may invoke a fatal reaction in microgram amounts. It is well
known that some patients react to plain M&Ms because these were produced in vats
that previously contained peanut M&Ms. Peanuts are now banned on domestic flights
in the US because some patients developed reactions when neighbouring passengers
opened their packets of peanuts. One of my paediatric patients develops
bronchospasm whenever his neighbour fries fish next door. The sensitivity of
individual patients may change with time. Some patients might have tolerated a
certain amount of a particular food without significant ill effects in the past, but
nevertheless developed a severe reaction when they tried to ingest a similar amount
One interesting form of anaphylaxis is the food-associated exercise-induced
anaphylaxis. These patients develop anaphylaxis if they exercise within 2 to 4 hours
of ingesting a food that they are allergic to. However, ingesting the same food
without exercise will not elicit a reaction. Most of these patients will have a positive
skin test reaction to that particular food. There are also some patients who would
develop anaphylaxis if they exercise after eating; this may be a form of exerice-
induced anaphylaxis, and not a food allergy. I have also seen a patient who develops
anaphylaxis if she eats a certain food after exercising.
Diagnosis and management of food allergies
The history is the most important tool in the diagnosis of food allergy, yet it is
frequently inaccurate and only about 40% of such histories can be verified by food
challenges31. Important points to note in the history include the nature of the reaction,
the foods ingested at the time, the timing of the reaction relative to food ingestion,
repeatability and frequency of the reaction, and other exacerbating factors such as
exercise. Knowledge of the pattern of food allergy in the community is also helpful in
discerning the likely culprit. One must also bear in mind the “hidden allergens”,
especially in processed food. The Chinese diet is incredibly varied, and it is often
extremely difficult, if not impossible, to uncover all the food allergens present during
a restaurant meal. Persistent food-allergic symptoms without a clear pattern suggest
reactions to additives or spices. A food diary is often a helpful tool in revealing these
hidden allergens. If an IgE-mediated food allergy is suspected, skin prick tests (SPT)
are useful in screening for likely culprits. One must bear in mind that SPT have a low
positive predictive value (hence high false-positive rate) but a high negative
predictive value. Treatment based solely on positive SPT results would subject
patients to unnecessary food avoidance, but negative SPT will almost completely
exclude food allergies. Sources of false negative reactions include the intake of anti-
histamines prior to testing, and the use of commercial extracts for labile allergens
such as some fruits and vegetables32; under these circumstances, fresh food extracts
should be used. Children under the age of two may also lack skin reactivity33. For
patients who are on anti-histamines, have significant skin pathologies that preclude
the use of skin tests, or if there are a limited number of suspicious culprits,
measurement of serum food-specific IgE by the radioallergosorbent test (RAST) or
the Pharmacia CAP test is warranted. A recent study of children with AD showed
that quantitation of food-specific IgE improved the positive predictive value of SPT34.
When a list of possible candidate food allergens can be established, a diagnostic
elimination diet is helpful in supporting the diagnosis. There should be significant
improvement in symptoms if the offending allergens are eliminated. After two weeks
of allergen elimination, food challenge should be carried out. In cases where there is
a risk of severe anaphylaxis, or if the history is strongly supported by SPT results,
food challenge can be omitted. Food challenges can be done open, single-blind or
double-blind. Double-blind, placebo-controlled food challenge (DBPCFC) is the gold
standard for the diagnosis of food allergies and should be used if several foods are
suspected, or when patient perception may significantly influence symptom
assessment. The time to reaction depends on the type of reaction expected; it may
take several minutes for an IgE-mediated reaction to occur, but up to 3 days for some
Elimination of allergenic foods is the only effective treatment for food allergies.
Patient education is extremely important, especially in identifying hidden allergens.
All patients at risk of anaphylaxis must carry injectible epinephrine. The dose of
epinephrine is 0.3mg for adults, and 0.15mg for children to be given intramuscularly.
If several foods are involved, the help of a dietician is invaluable in designing a diet
that will prevent malnutrition. In general, most children grow out of their food
allergies after several years, with the exception of peanut, nuts and shellfish allergies.
A prospective study of milk allergy in infants showed that 85% of the children lost
their milk allergy by three years of age35. In older children and adults, a substantial
proportion will lose their clinical sensitivity to a food after one to two years of
complete allergen elimination, again with the exception of peanut, nuts and shellfish
allergies. Skin test sensitivity tends to remain, however.
Allergies can be prevented or delayed by dietary control during the first few years of
life, and is a worthwhile endeavour in patients with a strong family history of atopy.
The use of whey-hydrolysate for infant feeding is associated with a reduction in the
risk of asthma and AD during the first five years of life36. A 17-year prospective
study on breastfeeding concluded that prolonged breastfeeding (>6 months) is
associated with a significant and long-lasting reduction in the risk and severity of
atopic diseases including AD, food allergies and respiratory allergies37. Infants with
cow’s milk allergy have an increased risk of developing allergies to other foods.
They are also at risk of developing other allergies and asthma later on in life. Highly
allergenic foods such as peanut, nuts, fish and shellfish should therefore be avoided in
such patients until at least their third birthday.
In this review, we have summarised briefly the major clinical syndromes associated
with food allergies, including the various enteropathies, atopic dermatitis, asthma and
anaphylaxis. A rational approach to the diagnosis of food allergy is outlined, in order
to avoid unnecessary food avoidances, psychological trauma, and disruption in the
patient’s lifestyle. The treatment of food allergy is avoidance, but this can be difficult
especially in teenagers where peer pressure and the urge to conform is strong. Work
on immunotherapy with mutated allergens and peptide epitope vaccines is underway
and may become a viable treatment alternative in the future. Proper dietary
management during the early years of life is effective in reducing the risk of allergic
diseases in high-risk individuals, and should be practised whenever possible.
Table 1. Possible symptoms of cow’s milk allergy in infants Table 2. Common allergenic foods Cow’s milk Fig. 1 Diagnosis of food allergies in children with atopic dermatitis.
Skin prick tests +/- patch skin tests with food extracts.
suspected, keep food diary and re-evaluate.
Symptoms recur. Diagnosis confirmed. Eliminate allergenic foods for 1 – 2 years.
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