Lecture 3- Food allergy

Question 1

What is allergy?

Answer 1

Allergy is not a disease itself, but a mechanism leading to a disease.

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

allergy is defined as a variety of different diseases

Answer 2

• Immunological-mediated and allergen-specific hypersensitivity
• Seen in almost every organ, especially skin and mucous membranes
• Have different path mechanisms and
• With different approaches in diagnosis, therapy and prevention

Question 3

allergy is associated with significant morbdiity

Answer 3

• Persistent symptoms of AR impair sleep and reduce productivity.
• Recurrent hospital admissions for asthma cause high absenteeism.
• Restrictive diets in food allergy cause social exclusion and malnutrition.

Question 4

Allergen:

Answer 4

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

Sensitivity:

Answer 5

Normal response to a stimulus.

Question 6

Hypersensitivity:

Answer 6

Abnormal strong response to a stimulus.

Question 7

Sensitisation:

Answer 7

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

Question 8

Allergy:

Answer 8

A hypersensitivity reaction initiated by a specific immunological mechanism, that is IgE-mediated (e.g. peanut allergy) or non-IgE-mediated (e.g. milk allergy).

Question 9

Atopy:

Answer 9

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 10

Anaphylaxis:

Answer 10

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

Question 11

Food:

Answer 11

A substance, whether processed, semi-processed or raw intended for human consumption (including liquids), and any substance used in the manufacture, preparation of treatment of food.

Question 12

Food allergy:

Answer 12

A immunologically mediated adverse reaction to foods

Question 13

Allergy presentation

Answer 13

• Allergic rhinitis
• Allergic conjunctivitis
• Asthma
• Atopic dermatitis / eczema
• Urticaria (HIVES)
• Insect allergy
• Drug allergy
• Food allergy

Question 14

allergic diseases evolve in a characteristic manner with age

Answer 14

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’.

Question 15

Why is allergy important?

Answer 15

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.

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 17

Food allergy is defined as

Answer 17

‘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 18

Food intolerance

Answer 18

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

Question 19

So we classify adverse reactions to food as follows:

Answer 19

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

Question 20

Non-immune mediated or primary food intolerances.

Answer 20

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.

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 21

2. Immune mediated or food allergy and Coeliac disease.

Answer 21

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 22

How does food allergy present?

Answer 22

The two main phenotypes of food allergy are

1. immediate-onset or IgE-mediated and
2. delayed-onset or non-IgE-mediated.

Question 23

IgE mediated

Answer 23

• immediate

Question 24

Non IgE mediated

Answer 24

delayed

Question 25

**Food allergy presentation: _Immediate onset_ of IgE-mediated food allergy phenotypes**

Answer 25

* **Urticaria/angioedema** * Acute (rarely chronic) **hives** and swelling with **gastro**- **intestinal** but not respiratory or CVS symptoms. (*any*) * **Anaphylaxis** * Rapidly progressive, potentially **fatal**, multiple organ system reaction **with respiratory symptoms** and can include cardiovascular. (*nuts, fish, shellfish, milk, eggs* * **Food- associated exercise induce anaphylaxis (FRIES)** * Food triggers anaphylaxis only if ingestion is **followed temporally** (within 2 hours) by **exercise**. (*wheat, shellfish, celery*) * **Pollen food syndrome** * Pruritus and mild oedema confined to the oral cavity (lips, tongue, mouth and throat) uncommonly progressing. Associated with hay fever (***raw*** *fruit and vegetables*)

Question 26

**Food allergy presentation: _Delayed onset_ of IgE-mediated food allergy phenotypes**

Answer 26

* **Proctocolitis** * Passage of **bright red** blood in mucousy stools in otherwise **asymptomatic** infants. (*milk, through breast feeding*) * **Enterocolitis** * **Multiple** and **varying** gastrointestinal symptoms including feed refusal, persistent vomiting, abdominal cramps, loose and frequent stools and constipation. (*milk, eggs, wheat*) * **Eosinophilic oesophagitis** * Symptoms from oesophageal inflammation and scarring of feeding disorders, reflux symptoms, vomiting, dysphagia and **food impaction**. (*milk, eggs, wheat*) * **Food protein-induced entero-colitis syndrome** * Primarily affects infants. Profuse vomiting leading to pallor, lethargy and possibly shock; diarrhoea in 25%. (*milk, soya, rice, wheat, meat*)

Question 27

food allergy march

Answer 27

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). 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 28

summary of IgE vs non-IgE mediated reaction

Answer 28

Question 29

Effects of high temperature and food matrix on food proteins.

Answer 29

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

Question 30

Examples of the heat and matrix effect are milk and egg.

Answer 30

**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 31

Implications of cross-reactive food allergens

Answer 31

* 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 32

**Summary of food allergy presentation**

Answer 32

* Not all reported food reactions are due to allergy. * True food allergy has two major phenotypes. * IgE mediated or immediate-onset * Non-IgE mediated or Delayed-onset * Different presentations in each phenotype. * ‘Food allergy march’ describes different food allergy timing. * Processing affects allergenicity by altering proteins. * Varying degrees of cross-reactivity amongst ‘related’ foods.

Question 33

**Food allergy diagnosis**

Answer 33

Question 34

Medical history : context of reaction

Answer 34

* 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 35

medical history: presenting symptoms

Answer 35

• 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. b. 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 36

medical history: Details about food ingested.

Answer 36

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

Question 37

the eaters history

Answer 37

Question 38

. Physical examination

Answer 38

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 39

Screening tests

Answer 39

A patient who presents with symptoms suggestive of IgE-mediated food allergy must have the presentation confirmed with the demonstration of IgE sensitisation e.g. skin prick test

Question 40

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.

Answer 40

Question 41

Tests for IgE antibodies alone determine

Answer 41

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 42

**Treatment options**

Answer 42

* **Appropriate assessment** * Allergy focused history and examination. * Appropriately selected allergy investigations. * Identify food causing symptoms. * **Dietary advice** * **Exclusions** – which food/food groups/food formats to avoid. * **Inclusion** – which food/groups/formats **not** to avoid. * **Label reading**: * Ingredient labelling. * Patient Advisory Labels. * Food **reintroductions**. * **Medical advice** * Emergency management of allergic/anaphylactic reaction.

Question 43

Early food introductions in infancy.

Answer 43

This is central to active management where lower allergenic forms of foods e.g. baked milk or baked egg are introduced early as exposure will enhance further tolerance. This is to accelerate tolerance in established allergy. There is evolving evidence that early weaning onto so-called allergenic foods will prevent the development of food allergy.

Question 44

Desensitisation to food allergens.

Answer 44

In children with milk and egg allergy that does not resolve as expected, treatment plans are available to attempt to induce tolerance or desensitise these patients and thereby ‘cure’ these allergies. This treatment is also be available for peanut allergy but as yet not widely available for clinical practice.

Question 45

Oral food challenges

Answer 45

for diagnostic verification.

Question 46

**What is lactose intolerance?**

Answer 46

**Lactase evolution and action** * Detection from 8 weeks gestation; rise from 32 weeks to peak at birth. * Activity decreases within months. * Present on **jejunal brush border apex**. * **Hydrolysis** of lactose into **mono- saccharides** galactose and glucose **Lactose intolerance (Lactase non-persistence)** * Occurs in most humans; variable. * Typical symptoms: **bloating**, **flatulence**, **explosive diarrhoea**. * Onset **subtle**; **progressive** over years. * Most diagnosed as **adolescent** or adult. * Not always symptomatic with milk

Question 47

**Milk reintroduction using the ‘Milk ladder’**

Answer 47