Food allergy

Brayden is a 3-year-old boy who has been referred to your clinic due to concerns about food allergies. He has been having a lot of flare-ups of his eczema.

On only one occasion, he developed facial swelling and wheezing after ingesting peanuts.

The GP was wondering if it could be related to specific foods.

Is food allergy becoming more common?

There has been an increasing number of allergies in recent years, especially in young children.

10% of infants one year and below, 4-8% of children under five years old, and up to 2% of the adult population in Australia have a food allergy.

There is no clear explanation for the increase, but proposed ones include:

• Hygiene hypothesis
• Delayed introduction of allergenic foods
• Methods of food processing
• Development of allergy to food by skin exposure
• Vitamin D deficiency in the first year of life
• Medication to suppress gastric acid production

What exactly is a food allergy?

an abnormal immune-mediated reaction to ingested food, resulting in clinical symptoms

Food allergies can be classified by their immune mechanism:

• IgE-mediated (acute urticaria, oral allergy syndrome)
• Non-IgE-mediated (food protein-induced enteropathy syndrome)
• Mixed IgE and non-IgE-mediated (eosinophilic oesophagitis)
• Cell-mediated (allergic contact dermatitis)

What’s the difference between food allergy and food intolerance?

Food intolerance does not involve the immune system and does not result from IgE-mediated reactions nor does it cause anaphylaxis.

The exact mechanism by which some food intolerance occurs is not always clear.

There is no reliable skin or blood test to diagnose food intolerances, despite claims of an ability to do so using unproven/unorthodox testing methods (e.g. kinesiology, iridology, IgG food testing).

Non-immune mediated food reactions include:

• Metabolic (lactose intolerance)
• Pharmacologic (caffeine)
• Toxic (scombroid fish toxin)
• Other (sulphites)

How do mild-moderate reactions present?

These usually appear within 1-2 hours of ingesting the food and include:

• Swelling of lips, face, eyes
• Hives or welts
• Tingling mouth
• Abdominal pain, vomiting
• Eczema or rashes

How do severe reactions present?

• Difficult/noisy breathing
• Swelling of tongue
• Swelling/tightness in the throat
• Difficulty talking and/or hoarse voice
• Wheeze or persistent cough
• Persistent dizziness or collapse
• Pale and floppy (young children)

Note: previous mild or moderate reactions do not rule out a risk of subsequent anaphylaxis!

What are the most common food allergies?

90% of food allergies in children involve peanuts, tree nuts, sesame, cow’s milk, soy, egg, shellfish, fish, or wheat.

However, ANY food, including fruits and vegetables, can cause anaphylaxis.

Allergic reactions can occur on first known exposure to food. True initial exposure and sensitisation to allergens may be unintentional and unknown.

The most common cause of fatal food anaphylaxis is peanut allergy.

Is there a cross-reactivity to other foods?

Cow’s milk protein – 10% are also allergic to soy. This is particularly relevant when choosing an alternative infant formula or cow’s milk substitute.

Egg – 30% also have peanut or tree nut allergy.

In certain patients, allergy testing for co-reactive foods may provide useful information on co-existing allergies.

These are examples where the patient is clinically allergic to proteins in unrelated foods. However, more common is where there is a clinical allergy to similar proteins present in related foods.

• Cow’s milk: ~90% will be allergic to goat’s milk
• Cashew: almost all will be allergic to pistachio
• Walnut: most will be allergic to pecan
• Fish: ~75% will be allergic to other fish
• Prawn: most will be allergic to other crustaceans (e.g. crab, lobster)
• Peanut: ~5% are allergic to another legume (e.g. soy)
• Oral allergy syndrome: allergic to similar proteins in pollen and some fruit/vegetables

Are food allergies for life?

Peanut, tree nuts, sesame, shellfish, and fish allergies usually persist into adulthood.

Extensively heated egg or cow’s milk products (e.g. baked goods) may be tolerated in children who have shown clinical allergy to raw products. If tolerated, they can be continued regularly.

Few studies suggest this, but there is inconclusive evidence as to whether regular ingestion of these extensively heated products assists in outgrowing egg or cow’s milk allergy.

What is oral allergy syndrome?

This is known as pollen food syndrome. It occurs predominantly in pollen-sensitised individuals, and severity may worsen during the pollen season.

There are IgE-mediated cross-reactive responses to allergens present in pollen and other plants.

It presents with an itchy mouth/throat when eating uncooked fresh fruits, vegetables, spices, sometimes nuts, and latex. There is mouth/laryngeal swelling.

Oral allergy syndrome can result in anaphylaxis, but this is uncommon.

Management of oral allergy syndrome depends on the food type.

Nuts – avoid, even if cooked, as they usually still cause symptoms. Roasting peanuts/tree nuts can enhance symptoms.

Fruits/veg – cooking, baking (even briefly microwaving) raw fruits/veg helps.

If patients can tolerate the cooked form, then they can continue to take them regularly.

Dietician input is helpful if there are severe dietary restrictions, as patients may need nutritional supplements.

There is conflicting evidence for inhaled allergen immunotherapy, which is not currently recommended.

Is eczema implicated in food allergy?

Eczema itself is cell-mediated. The early onset of eczema (<3 months of age) and severe eczema make co-existent food allergy more likely.

Food allergy may aggravate pre-existent eczema in some individuals but is not the cause. Most cases are IgE-mediated.

There can be acute flares of eczema after ingestion of food – subtle symptoms if passive transfer through breastmilk. Patients have positive food allergy tests.

Less commonly, cases are non-IgE-mediated. Here, the onset of symptoms is delayed (6-48 hours). Patients have negative food allergy tests.

The most common non-IgE triggers are dairy, wheat and soy.

Treatment for both IgE and non-IgE mediated is an elimination trial and rechallenge in 1-2 weeks (via maternal diet if breastfed).

What are the gastrointestinal syndromes associated with food allergy?

Food protein-induced enteropathy (non-IgE)

• Occurs in early infancy (<3 years)
• Protracted diarrhoea, vomiting, abdominal distension, failure to thrive, oedema
• Usually to cow’s milk, soy, or wheat
• If breastfeeding, there should be a maternal dietary exclusion of the suspected food.
• If formula fed – extensively hydrolysed formula, or amino acid formula if eHF is not tolerated.

Food protein-induced proctocolitis (non-IgE)

• Occurs in the first weeks to months of life (<3 months)
• Isolated, bloody stools, otherwise well and thriving
• Usually to cow’s milk, soy and 50% are breastfed
• Management is as per food protein-induced enteropathy

Food protein-induced enterocolitis (FPIES) (non-IgE)

• Occurs in young infants (4-6 months) at the onset of introduction to new foods
• Protracted diarrhoea, projectile vomiting, hypovolaemic shock
• Usually to cow’s milk, soy, rice, beef, poultry, grains
• In breastfed babies, there should be a specialist review before any maternal dietary exclusion
• In bottle-fed babies, management is as per food protein-induced enteropathy

Eosinophilic oesophagitis (EoE) (mixed IgE/non-IgE)

• Can occur at any age
• GORD, post-prandial nausea, vomiting, food impaction, abdominal pain, and diarrhoea
• Usually to cow’s milk, soy, wheat, egg, and sometimes to meat and grains
• In breastfed babies, there should be a specialist review before any maternal dietary exclusion.
• In bottle-fed babies, they can go onto an amino acid formula

One other to be aware of is food-dependent exercise-induced anaphylaxis.

Symptoms develop if exercise occurs within a few hours after eating. Occasionally it can occur when food is eaten post-exercise. Patients develop extreme fatigue, warmth, flushing, pruritus, urticaria, and this progresses to anaphylaxis.

Patients should avoid food 4-6 hours before exercise.

Diagnosing food allergies

Brayden is a 3-year-old boy who has been referred to your clinic following one occasion where he developed some facial swelling and wheeze after ingesting peanuts. Brayden sounds like he may have a food allergy to peanuts. But how do we actually make the diagnosis?

Clinical history is paramount. Symptoms suggestive of IgE-mediated reactions include:

• Acute urticaria, angioedema, persistent cough, severe vomiting soon after eating
• Contact urticaria to food

Symptoms suggestive of IgE-mediated or non-IgE-mediated reactions:

• Severe eczema unresponsive to standard therapies and treatment in children <2 years (co-existing food allergy rather than causal)
• Failure to thrive or poor nutrition not attributable to other causes in children <2 years
• Ongoing diarrhoea with or without blood loss in children <2 years
• Refractory vomiting in infancy

The tests to identify IgE sensitisation to an allergen include:

• Skin prick testing (SPT).
• Serum allergen-specific IgE (a blood test formerly known as RAST).
• Medically supervised food allergen challenge if equivocal tests or doesn’t correlate with history.
• Patch testing and intradermal testing are not useful to confirm IgE-mediated food allergy.

What are the types of skin prick testing?

There are three types of skin prick testing used in allergy diagnosis.

1. Skin prick testing: main mode of testing for immediate IgE-mediated allergy, low risks.
2. Intradermal testing: IgE (drug allergy, e.g. penicillins, venom, vaccines) and delayed-type hypersensitivity, not used for food allergy testing. Higher risks of adverse reactions need high levels of expertise.
3. Patch testing: contact hypersensitivity, delayed-type hypersensitivity, not immediate/IgE-mediated allergy. Conducted by dermatologists and immunologists

How does skin prick testing work?

Small amounts of allergens are introduced into the epidermis and non-vascular superficial dermis. This interacts with IgE bound to mast cells. Histamine and other mediators are released. There is a wheal and flare reaction, peaking at 15 minutes.

Indications:

• Food reactions
• Allergic rhinitis/conjunctivitis/sinusitis
• Eczema
• Asthma
• Latex allergy
• EoE, eosinophilic GE, allergic bronchopulmonary aspergillosis

Food allergen SPT uses positive and negative controls:

• The volar surface of the forearm or outer upper arm
• >5cm from the wrist and 3 cm from the antecubital fossa
• Drop then prick
• Read positive control at 10 minutes, and allergen results at 15-20 minutes
• Measure the mean diameter of the wheal
• Observe the patient for 20-40 minutes after the test

SPT increases the accuracy of diagnosis when added to the history and examination.

It differentiates allergic conditions and helps with allergen avoidance strategies, improved use of medications, and desensitisation treatment (allergen immunotherapy). It delivers safe, fast results within half an hour.

However, it needs expertise to conduct and interpret correctly, especially for under 2-year-olds. It can only be used on normal, healthy skin (e.g., it can’t be used in eczema flare – severe dermatographism can cause non-specific wheal and flare reactions to skin pricking alone). It also needs a cooperative subject.

Antihistamines and other interfering drugs (e.g. antidepressants and topical steroids reduce skin reactivity) should be stopped prior to SPT.

What are the indications for skin prick testing?

SPT is not routinely indicated for:

• Non-specific rash without allergic features
• Chronic urticaria without allergic features
• Food intolerance without allergic features
• Chronic fatigue without allergic features
• Migraines/behavioural disorders
• Reactions to inhaled/resp irritants, e.g. smoke/perfume
• Screening for allergy in the absence of symptoms e.g. family history
• LMW substances, e.g. food additives
• Most occupational allergens

Testing for food allergens is valid but complex, and needs specialised practice.

Positive tests occur without clinical allergy, and negative tests can occur in the presence of clinical reactivity. There is a greater risk of anaphylaxis compared with aeroallergens. Commercial allergen extracts are available but non-standardised – sometimes it is better to use freshly prepared food extracts or the food itself.

How can we interpret the results?

It’s important when delivering post-test counselling that we explain the significance of the results.

• Positive SPT, not clinically reactive = clinically silent sensitisation
• Size of reaction does not correlate with severity of allergic manifestations
• Positive SPT does not predict the nature of allergic symptoms
• Positive SPT, clinically reactive but irrelevant as patient is not exposed to allergen and thus not cause of symptoms
• Positive SPT remains even when allergy has remitted e.g. pollen
• Negative SPT does not mean child will not develop allergy in the future
• Negative SPT can be due to insufficient representation of allergen in extract
• There are also non-IgE mediated reactions
• Food challenge may be indicated if SPT is equivocal or doesn’t correlate with the history

How should a food challenge be managed?

Pre-challenge:

Elimination diet, avoid food being challenged for at least two weeks. Note that prolonged elimination can result in acute severe reactions when challenged.

Atopic and chronic diseases must be stable.

Avoid antihistamines or meds with anti-histamine properties. Avoid for five half-lives of the agent.

Avoid steroid treatment for 7-14 days to prevent confounding results.

Avoid beta 2-agonist use as it may affect treatment if anaphylaxis occurs.

Perform challenges on an empty stomach.

Challenge:

The preferred method for active and placebo challenges is on different days, but if on the same day, they need to be separated by at least three hours.

Start low and can increase the dose 2-10 times each time, with at least 15-20 minutes between doses.

Administer increasing (fixed) doses.

The challenge is discontinued when the participant exhibits objective symptoms (e.g. vomiting, diarrhoea, and urticaria) at a specific dose or when the top dose is consumed without evidence of reactivity.

Results:

The clinical judgment of an experienced investigator is the most important factor in calling results positive or negative.

Objective measures previously proposed:

• Exhaled nitric oxide (NO) measurement
• Facial thermography
• Serum histamine and tryptase level (concluded to be unhelpful in determining the positivity of results)

Exhaled NO and facial thermography will be helpful as an immediate, decisive tool to help standardisation, but there are practical issues, e.g. NO peaks 90 mins after the challenge.

Brayden is a 3-year-old boy who has been referred to your clinic following one occasion where he developed some facial swelling and wheeze after ingesting peanuts. 

Brayden’s allergy has been confirmed on skin prick testing. 

Brayden’s mum is pregnant and wonders how to prevent her second child from having a food allergy.

Can we prevent allergies?

Allergy prevention (with a strong family history of allergies) can be with breastfeeding or the use of a partially hydrolysed formula.

• Mothers should breastfeed for at least six months and not exclude potentially allergenic foods from the maternal diet. They should continue to breastfeed while introducing new foods.
• Introduce solids at 4-6 months of age when developmentally ready.
• Add a new food every 2-3 days to allow for observation of adverse food reactions.
• Do not delay the introduction of potentially allergenic foods.
• If there is an adverse food reaction – avoid the food and seek medical advice. Continue introducing other new foods.
• Educate families about cross contamination, food education, e.g. ingredients, always read food labels, travel action plan, eating out/alcohol/parties higher risk.

How are food allergies managed in infants?

In infants with IgE-mediated food allergy:

Breastfeeding is preferred over formula feeding. Anaphylaxis from maternal allergen ingestion is rare. Usually, it is not required to have maternal exclusion of food allergens, although patients can have a trial of maternal dietary exclusion. If symptoms improve with a trial, consider food challenges through maternal diet.

When breastfeeding is not possible or when supplementary feeding is needed, formula feeding can be commenced. Or when symptoms persist in an infant despite maternal dietary exclusion of cow’s milk protein and soy protein, then formula can be commenced.

In infants with cow’s milk allergy:

If there is cow’s milk anaphylaxis – can breastfeed, with no need for routine maternal dietary exclusion

If formula is indicated, use AAF – there should be immunologist review and soy challenge. Patients can then use soy if tolerated, or AAF if soy is not tolerated.

In cow’s milk allergy (not anaphylaxis) – eHF if <6 months, or soy if >6 months and tolerated.

Preparations we do not recommend:

• Cow’s milk based including anti-reflux and lactose free cow’s milk based formula
• Other mammalian milks e.g. goats milk
• A2 cow’s milk
• Rice drink
• Oat drink
• Soy drink
• Almond or other nut drinks
• Home-made cereal/soy/nut drinks

After infancy, there should be dietician review to determine the most appropriate option for dietary needs and calcium supplementation if required.

And finally, what does the future hold regarding immunotherapy for food allergies?

This has a research basis only – oral immunotherapy and sublingual immunotherapy are the most often studied. Subcutaneous (highest risk of anaphylaxis, affects safety profile), epicutaneous (preliminary reports promising).

Oral: highly effective, but results for clinical tolerance after ceasing therapy are disappointing. This requires ongoing therapy to maintain tolerance. Nevertheless, the rate of acquisition of tolerance is higher than that seen in those patients who avoid the allergen. Allergens studied include cow’s milk, egg white, fish, apple, orange, celery and peanut.

Sublingual: efficacy lower than oral but better safety profile.

There is no role for immunotherapy in food intolerance or adverse reactions to food chemicals, additives, preservatives, or artificial colours.