Food Allergy

Question 1

What is allergy

Answer 1

Allergy is not a disease itself, but a mechanism leading to a disease. The term was first coined in 1906 when it was referred to a specifically altered reactivity of the organism.
A more current definition could be ‘an immunological hypersensitivity that can lea to a variety of different diseases via different patho-mechanisms with different approaches in diagnosis, therapy and prevention.
Allergy therefore presents as a number of diseases.

Question 2

Describe the epidemiology of allergy

Answer 2

1. Allergy is common. For example, in the UK allergic rhinitis affects up to 30% of adults, asthma is diagnosed in more than 1 in 10 children and food allergies are present in about 6% of children and 1-2% of adults. Nearly half of British adults will suffer from at least one allergic condition.

Question 3

Describe the morbidity and mortality of allergy

Answer 3

F 2. Allergy is associated with significant morbidity. The persistent symptoms of allergic rhinitis impair sleep and affect daytime function with reduced productivity in adults and poorer school performances in children. Asthma is a common cause of hospital admissions with one child being admitted to hospital every 20 minutes in the UK. Food allergies, although not symptomatic with effective dietary avoidance, also significantly impair quality of life not only of the affected individual but the family as well. Careful dietary exclusions for example require longer times for shopping to read ingredient labels and impact of social activities limiting eating out, going to parties and so on.
3. Allergy can be fatal. Every year about 1200 people die from asthma in the UK. Admissions to anaphylaxis have increased more than 600% in the 20 years to 2012, although thankfully there has not been a rise in mortality.

Question 4

What is an allergen

Answer 4

Allergen: any substance stimulating the production of IgE or a cellular immune
response. Allergens are usually proteins, but not always. They can for example be
carbohydrates.

Question 5

Define sensitivity, hypersensitivity

Answer 5

carbohydrates.

2. Sensitivity: Normal response to a stimulus.
3. Hypersensitivity: Abnormal strong response to a stimulus.

Question 6

Define sensitisation

Answer 6

Sensitisation: Production of IgE antibodies (detected by serum IgE assay or skin
prick test) after repeated exposure to an allergen.

Question 7

Define story

Answer 7

Atopy: A personal or familial tendency to produce IgE in response to exposure to
potential allergens. Atopy is strongly associated with asthma, allergic rhinitis,
eczema and food allergy.

Question 8

Define anaphylaxis

Answer 8

Anaphylaxis: A serious allergic reaction with bronchial, laryngeal and
cardiovascular involvement that is rapid in onset and can cause death.

Question 9

What is a food allergy

Answer 9

Food allergy: A immunologically mediated adverse reaction to foods.

Question 10

What is allergic rhinitis

Answer 10

Allergic rhinitis or hay fever, which presents with the classical symptoms of
persistent or recurrent blocked or runny nose, itch and sneezing. Common
symptom triggers are grass and tree pollens and house dust mites.

Question 11

What is allergic conjunctivitis

Answer 11

Allergic conjunctivitis where the symptoms are red, swollen, watery and itchy eyes. Itch is a key symptom to distinguish this form of conjunctivitis from others.
It occasionally occurs with hay fever and thus has similar allergy triggers.

Question 12

What is allergic asthma

Answer 12

Allergic asthma presents with the classical asthma symptoms of wheeze, cough, shortness of breath and tight chest. Allergens are not common triggers for asthma
attacks.

Question 13

What is atopic dermatitis or eczema

Answer 13

Atopic dermatitis or eczema is the commonest chronic inflammatory skin disease.
The presentation of an itchy skin causes scratching which leads to chronic skin changes. Whilst eczema is recognised as an allergic condition, triggers are rarely recognised and allergen avoidance, particularly dietary exclusions, rarely provide symptomatic improvement.

Question 14

What is urticaria

Answer 14

. Urticaria or hives can occur in isolation as a maculopapular pruritic or itchy rash. It is classified as acute or chronic based on symptom duration. If it lasts less than 6 weeks it is termed acute and where more than 6 weeks it is regarded as chronic. The full term for chronic urticaria is chronic spontaneous urticaria; spontaneous as it occurs without identifiable trigger.
When patients present with urticaria they almost always expect to identify and thus eliminate the cause. The association with allergy is because it is a common symptom of the symptom complex of acute allergic reactions.

Question 15

What is insect allergy

Answer 15

Insect allergy in the UK is caused by stings from wasps or bees. The presentation can be mild with a large localised sting reaction characterised by redness, swelling and itch around the sting site to severe with life-threatening anaphylaxis.

Question 16

What is drug allergy

Answer 16

Drug allergy is much less common than reported by patients. Allergies can however occur to all drugs as well as to excipients.

Question 17

What is the allergic march

Answer 17

The predominant pre-school allergic conditions are eczema and food allergy, both of which decrease in incidence with increasing age as the diseases improve spontaneously. Asthma predominates in school-aged children and then improves in many and thus decreases in prevalence to adult levels. Rhinitis and conjunctivitis are rare in young children and evolve through childhood and continue to increase in prevalence into adulthood. We call this change with age the ‘Allergic march’.

The clinical presentations are mirrored by sensitivities as illustrated from the Danish cohort study. We note that food sensitivities occur early and peak in young children whilst pollen allergies are detected initially in young children and then increase with age.

Question 18

Define food allergy

Answer 18

Food allergy is defined as ‘an adverse health effect arising from a specific immune response that occurs on exposure to a food. The definition encompasses responses that are classified as IgE-mediated or non-IgE mediated.

Question 19

Define food intolerance

Answer 19

Food intolerance is by contrast the numerous and frequently reported adverse responses to foods that do not involve the immune response.

Question 20

Describe the prevalence of food allergy

Answer 20

Prevalence. IgE-mediated reactions have been reported to more than 170 foods, so one can be allergic to any food; but food allergies and hence the prevalence estimates are limited to few foods – the commonest being milk, egg and peanuts. The prevalence of self-reported allergy can be up to 6 times higher than challenge
proven allergy. The estimated prevalence is higher in children affecting about 6% compared 1-2% of adults.

Question 21

How can adverse reaction to food be classified

Answer 21

Non-immune mediated or primary food intolerances VS Immune mediated or food allergy and Coeliac disease.

Question 22

What are non-immune mediated/primary food intolerances

Answer 22

Non-immune mediated or primary food intolerances. These are either:
a. Food characteristics such as reactions to pharmacologically active food components (e.g. caffeine) or illness in response to toxins from microbial contamination or to scromboid fish toxin. This is a reaction that results from eating spoiled oily fish (mackerel, tuna) where excess histamine, produced from fish decay, producing symptoms similar to allergy.
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b. Host characteristics include metabolic disorders such as lactose intolerance and psychological or neurological responses such as food aversion or rhinorrhoea caused by spicy foods.

Question 23

What ae immune mediated food allergy

Answer 23

Immune mediated or food allergy and Coeliac disease. Food allergy is classified by immune mechanism into IgE and non-IgE mediated types. These have classical presentations but are further classified into a number of conditions depending on clinical picture and severity.

Question 24

What are e 2 main phenotypes o food allergy

Answer 24

Sn • Immediate-onset IgE mediated (40%)
• Typical allergy symptoms affecting skin, respiratory and GI tracts.
• Symptoms of urticaria, cough, wheeze, vomiting and diarrhoea.
• Can cause anaphylaxis and even be fatal.
• Delayed-onset non-IgE mediated (60%)
• Predominantly multiple GI symptoms.
• Difficult to diagnose: younger presentation similar to colic, reflux.

Question 25

Give an overview of the types of adverse reaction to foods

Answer 25

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Question 26

Compare ige vsnon-ige mediated food allergy

Answer 26

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Question 27

What a re the symptoms of ige mediated food allergy

Answer 27

IgE mediated food allergic symptoms:
a. Skin: pruritus, erythema, acute localised or generalised urticaria (hives) or angioedema (swelling)(mostly of lips, face and eyes).

b. Gastrointestinal symptoms: Angioedema of lips, tongue and palate and oral pruritus. Colicky abdominal pain. Nausea, vomiting and diarrhoea.
c. Respiratory system (usually with skin and/or gastrointestinal symptoms): upper respiratory symptoms of runny and/or blocked nose, sneezing and itchy nose, croupy cough, stridor; lower respiratory symptoms of breathlessness, cough and wheeze.

d. Cardiovascular symptoms (uncommon in food allergy and rarely alone): pallor, drowsy and hypotension
IgE-mediated food allergy can also manifest with behavioural changes manifest as mood changes (quiet, anxiety), agitation and a ‘sense of impending doom’ (described in older children and adults).

Question 28

What are the symptoms of non0ge mediated food allergy

Answer 28

2. Non-IgE mediated food allergy
   Symptoms of non-IgE mediated food allergy can often be ascribed to other
   conditions as they can be vague (e.g. abdominal pain), not clearly associated with the food contact (i.e. presentation delayed) and can mimic other common gastrointestinal conditions (e.g. colic, gastro-oesophageal reflux in infants).
   The symptoms predominantly affect the gastrointestinal tract, are often multiple and are resistant to medication e.g. reflux. Eczema is a rare presentation of food allergy.

Skin
Pruritis, eczema, atopic eczema*
Gastrointestinal system
Food refusal or aversion
Abdominal pain; infantile colic Gastro-oesophageal reflux disease*
Loose or frequent stools
Blood and/or mucus in stools
Constipation*
Perianal redness
Pallor and tiredness
Faltering growth with at least one or more of GI symptoms (± eczema)

Question 29

Describe urticaria/angioeema

Answer 29

Urticaria/angioedema: Acute hives with swelling and gastrointestinal symptoms of nausea and repeated vomiting. No respiratory or cardiovascular symptoms (any – reported in about 170 foods).

Question 30

Wha is anaphylaxis

Answer 30

Anaphylaxis: Rapidly progressive potentially fatal multiple organ system reaction with respiratory and possibly cardiovascular symptoms (nuts, fish, shellfish, milk, egg).

Question 31

Whar us food associated execrcise induced anaphylaxis

Answer 31

Food-associated exercise induced anaphylaxis: Food triggers anaphylaxis only if ingestion is followed temporally (within 2 hours) by exercise (wheat, shellfish, celery).

Question 32

What is pollen food. Syndrome

Answer 32

Pollen food syndrome: Pruritus and mild oedema of the oral cavity (lips, tongue, mouth and throat) uncommonly progressing. Usually associated with hay fever (uncooked fruit, vegetables and nuts). Most common manifestation of adult food allergy

Question 33

What is proctocolitic

Answer 33

Proctocolitis: Passage of bright red blood in mucousy stool in an otherwise
asymptomatic infant (milk, even through breast milk).

Question 34

Wha is enterocolitis

Answer 34

Enterocolitis: Multiple and varying gastrointestinal symptoms including feed
refusal, persistent vomiting, abdominal cramps, loose and frequent stools and
constipation (milk, eggs, wheat).

Question 35

What eosinophilia esophagitiss

Answer 35

. Eosinophilic oesophagitis: Symptoms from oesophageal inflammation and
scarring of feeding disorders, reflux symptoms, dysphagia and food impaction
(milk, egg, wheat).

Question 36

What is fpies

Answer 36

Food protein induced enterocolitis syndrome (FPIES): Primarily in infants with
symptoms of profuse vomiting leading to pallor, lethargy and possibly shock; diarrhoea occurs in about 25% (milk, soya, rice, wheat, meat).

Question 37

How is old allergy presentation influenced by age

Answer 37

Age: the so-called ‘Food allergic march’.
The age at which food allergies present are influenced mainly by individuals diet. The natural history of food allergies varies as, as already mentioned, food allergy resolves with increasing age.
Presentation might be divided into those presenting in infancy (milk, egg and peanut) or in early childhood as the child’s diet becomes and more diverse (soya, wheat, tree nuts, fish, shellfish, sesame, kiwi fruit).
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Pollen food syndrome is the commonest food allergy in adults. It usually manifests in adolescence and is as a result of cross-reactivity between the pollens of fruit, vegetables and nuts and pollens causing hay fever e.g. birch. Heat or stomach acids easily denature these allergens, so symptoms occur only in unprocessed food where that food has had mucosal contact. On entering the stomach the allergen is denatured preventing absorption and systemic symptoms.
The natural history of foods is either to improve or resolve or to persist. Examples of allergies that improve are milk, egg, wheat and fruit, and of those that persist are peanut, tree nut, seed, fish and shellfish allergies.

Question 38

What is the heat and Mari affect

Answer 38

Effects of high temperature and food matrix on food proteins.
The ability of food allergens to induce symptoms is influenced by their epitope structure and consequent heat stability. Allergens comprising sequential epitopes that are not damaged by heat tend to be heat stable, whilst those dependent on the three-dimensional structure of the protein, conformational epitopes, will be altered
or destroyed by heat and lose their allergenic potential.
Protein interactions with other ingredients such as proteins, fats and sugars in
processed foods are also important, in general resulting in decreased availability of protein for interactions with the immune system.
Examples of the heat and matrix effect are milk and egg. Baked milk (i.e. milk in processed biscuits) has lower allergenicity and availability to the immune system so can be used to reintroduce milk back in to the diet of children with milk allergy expected to be resolving. Heating raw milk does not seem to reduce allergenicity sufficiently for clinical use. Another possibly better example is hen’s egg. There are 5 main proteins in eggs, 4 of which are heat labile – the heat stable and thus immuno- dominant protein ovomucoid comprises about 10% of egg proteins. A chard boiled egg or well-cooked scrambled egg will therefore have about 80-90% less allergenicity than raw egg (used in mayonnaise). The allergenicity is further reduced by decreased availability to the immune system in baked egg (e.g. in wheat). Baked egg is thus used as the initial food in assessing and treating resolving egg allergy.

Question 39

What are the implications of cross-reactive food allergens

Answer 39

Implications of cross-reactive food allergens
Food families share proteins that can implications in individual’s allergic
manifestations. It is important therefore to be aware of which foods are related and enquire whether these have previously been ingested when assessing an individual food allergy. Investigations should also target these potentially cross-reactive foods. An example is to test food all nuts in an individual presenting with a single nut allergy as the cross-reactivity rate approaches 40%.

Question 40

Give a summaryy f old allergy presentation

Answer 40

Summary of food allergy presentation:
1. Food allergy is confirmed by clinical assessment in about 6% of children and 1-2%
of adults. Self-reported adverse reactions to food are reported in about 30% of
the population, so only 1 in 5 adverse reactions if allergy.
2. Food allergy is classified by immune mechanism and presentation into IgE-
mediated or immediate onset and non-IgE mediated or delayed onset. There are at least 4 different phenotypes in each phenotype.
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3. Age, natural history of the allergy, effects of processing and cross-reactivity amongst related foods influence the presentation of food allergy.

Question 41

In terms of history, what information needs to be obtained in terms of contett of the reaction

Answer 41

Context of the reaction. Information here includes:
• Age of symptom onset. As mentioned in the ‘Food allergic march’ the age
at which one would expect foods to trigger symptoms differ with age and
therefore contact with the foods.
• Complete list of all foods suspected in causing the symptoms.
• Route of exposure (i.e. ingestion. Skin contact, inhalation).
• Activity at the time of exposure. Exercise or alcohol can potentiate
reactions; some foods cause reactions only when in the presence of
exercise.
• Any intercurrent illness at he time of the reaction because illness can
potentiate a reaction or might mimic a reaction.
• List of foods eaten previously without symptoms. It is unlikely that a child
can eat a food without symptoms and then develop allergy -with the
exception of Pollen Food Syndrome.

Question 42

What needs to asked about presenting symptoms

Answer 42

Presenting symptoms.
• All observed symptoms and their potential severity. Ask all symptoms from each system i.e. skin, gastrointestinal tract, upper and lower respiratory tract, cardiovascular system and central nervous system.
• Timing of symptoms in relation to food ingestion i.e. immediate or delayed.
• Duration of symptoms, treatment provided and the response to treatment.

Question 43

What eds to be asked about details about foods infected

Answer 43

Details about food ingested.
• Minimal quantity of food exposure required to cause symptoms.
• Manner in which food was prepared (cooked, raw, added ingredients).

Question 44

Describe teh physical examination

Answer 44

Physical examination
Patients presenting as an emergency following an acute reaction to foods may have
clinical manifestations of IgE-mediated food allergy. However most patients present for assessment to an outpatient clinic when these signs have long resolved.
Examination must include height and weight in children (and charting on growth chart. Comparison with previous weights to observe trends can also be helpful, particularly to determine whether there are trends of poor weight gain.
Examine for concomitant allergic conditions i.e. eczema, allergic rhinitis and asthma.

Question 45

What is a skin prick test

Answer 45

-

Question 46

Describe immunoassay to detect allergen-specific ige

Answer 46

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Question 47

What are screening tests

Answer 47

A patient who presents with symptoms suggestive of IgE-mediated food allergy
must have the presentation confirmed with the demonstration of IgE sensitisation. This is achieved by skin prick tests (SPTs) of assay of serum specific IgE. SPTs are widely used in allergy clinic because they provide information within 15 minutes. They are further useful as they can be used to test foods for which there are no blood tests available by pricking the food and then the skin (so-called prick-prick tests). Results between the two are equivalent.
Tests for IgE antibodies alone determine the presence of sensitivity and not allergy although the level of antibodies (measured in mm of the SPT wheal or specific units in blood tests) does correlate with the increased likelihood of allergy. Positive predictive thresholds have been established for commoner allergens. The level does not predict the severity of the allergic reaction.
Careful test selection based on clinical history and possible cross-reactivity increases the likelihood of true positive tests.

Question 48

Whaat is the purpose of screening tests

Answer 48

Using sIgE screening tests in immediate onset symptoms
• Detect IgE:
• Serum specific IgE – IgE circulating in blood
• Skin prick tests – Response of skin mast cells to allergens
• Determine presence of sensitivity not allergy
• Level of sIgE / size of SPT correlates with likelihood of allergy
• Positive predictive thresholds developed for common allergens
• Do not correlate with or predict severity of allergic reaction
• Test selection determined by: Clinical history
Possible cross-reactivity
Targeting likely allergens