S1 L1 Food allergy- assessment and diagnosis

Question 1

What is allergy?

Answer 1

• Not a disease but a mechanism leading to disease
• A variety of different disease via different patho-mechanisms with different approaches in diagnosis, therapy and prevention
• Seen in almost every organ, especially the skin and mucous membranes

Question 2

Why is allergy important?

Answer 2

• Allergy is common
  → Allergic rhinitis affects up o 30% of adults
  → Asthma is a diagnosis in >1 in 10 UK schoolchildren
  → Food allergy is confirmed in about 6% of children
  → Nearly half of UK adults suffer from at least one allergy
• Associated with significant morbidity
  → Persistent symptoms of allergic rhinitis can impair sleep and reduce productivity
  → Recurrent hospital admission for asthma causes high absenteeism
  → Restrictive diets → social exclusion and malnutrition
• Can be fatal
  → Around 1200 people die from asthma in the UK each year
  → Admissions for anaphylaxis increased >600% in the 20 years to 2012

Question 3

Define allergen?

Answer 3

Any substance stimulating the production of IgE or a cellular immune response
Usually a protein but can be carbohydrates (much less common)

Question 4

Define sensitivity?

Answer 4

Normal response to a stimulus

Question 5

Define hypersensitivity?

Answer 5

Abnormally strong response to a stimulus

Question 6

Define sensitisation?

Answer 6

Production of IgE antibodies (detectedby serum IgE assay or SPT) after repeated exposure to an allergen

Question 7

Define allergy?

Answer 7

A hypersensitivity reaction initiated by specific immunological mechanisms
This can be IgE mediated (e.g. peanut allergy) or non-IgE mediated (e.g. milk allergy)

Question 8

Define atopy?

Answer 8

Tendency to produce IgE antibodies in response to ordinary exposure to potential allergens
Strongly associated with asthma, rhinitis, eczema and food allergy

Question 9

Define anaphylaxis?

Answer 9

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

Question 10

Define food?

Answer 10

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

Question 11

Define food allergy?

Answer 11

Immunologically mediated adverse reaction to food

Question 12

How does allergy present?

Answer 12

1. Allergic rhinitis → blocked/runny nose, itchy nose, sneezing, triggered by pollen, pet or HDM
2. Allergic conjunctivitis → red, swollen, itchy, watery eyes, can occur with allergic rhinitis
3. Asthma → chest symptoms of wheeze, cough, SoB and chest tightness, not always allergic
4. Atopic dermatitis eczema → commonest chronic inflammatory skin disease with itch and excoriation
5. Urticaria (hives) → acute/chronic (+/-6wks), maculo-papular pruritic rash without or with angioedema
6. Insect allergy → mainly to bee or wasp sting, mild (local), moderate (urticaria) or severe (anaphylaxis)
7. Drug allergy → Especially to antibiotics, but only a minority who are allergic and truly allergic
8. Food allergy → clinically broad symptoms spectrum varying in timing of presentation and in severity

Question 13

How does allergen presentation change with age?

Answer 13

• Predominant preschool age is eczema and food allergy → ↓incidence as we age
• Predominant school age is asthma → improves in many ↓incidence in older population
• Older age group predominant is rhinitis and conjunctivitis

Question 14

What is the change in allergen predominance with age called?

Answer 14

The allergic march

Question 15

What is food allergy?

Answer 15

Adverse health effects arising from a specific immune response that occurs reproducibly on exposure to a food
IgE mediated or non-IgE mediated

Question 16

What are food intolerances?

Answer 16

Numerous (frequently reported) adverse responses to food that do not involved an immune respones

Question 17

What is the prevalence of food allergies?

Answer 17

Althoug more than 170 foods have been reported to cause IgE-mediated reactions
Studies focus on most common foods - milk, eggs and peanuts
Prevalence of self-reported food allergy can be 6x higher then proven allergy - more prevalent in children 6% vs 1-2% in adults

Question 18

What are the different classifications of adverse food reactions?

Answer 18

Non immune mediated (primary food intolerances)
Or 
Immune mediated (food allergy and coeliac disease)

Question 19

What is the non immune mediated response to adverse food reactions?

Answer 19

Non immune mediated or primary food intolerances
→ Food characteristics - reactions to pharmacologically active food components or illness in response to toxin from microbial contamination or to scromboid fish toxin - eating spoiled oily fish (mackerel, tuna) where excess histamine, produced from fish decay, producing symptoms similar to allergy
→ Host characteristics - include metabolic disorders such as lactose intolerance and psychological or neurological response such as food aversion or rhinorrhoea caused by spicy foods

Question 20

What is the immune mediated response to adverse food reactions?

Answer 20

Immune mediated - food allergy and coeliac disease
→ IgE mediated -
- Immediate 5-30 mins
- Acute
- Variable age- depends on age of contact (milk allergy will be by 1 year, pollen food syndrome in adolescence)
- Common foods- milk and eggs, peanuts and tree nuts, fish and shellfish, fruit and vegetable
- Milk and egg allergy tend to resolve, others persist
→ Non-IgE mediated -
- Delayed hours to days
- Infancy and early childhood (milk allergy by 1 year)
- Common foods- milk and soya, wheat, rice, oats
- Favourable prognosis with resolution before IgE mediated

Question 21

What is the system presentation of IgE mediated or immediate onset food allergy response?

Answer 21

1. Skin
   → Pruritus, erythema, acute urticaria- localised or generalised, acute angioedema- most commonly of lips, face and around eyes
2. Gastrointestinal system
   → Angioedema of lips, tongue and palate, oral pruritus, nausea, vomiting, diarrhoea and colicky abdominal pain
3. Respiratory system (usually with above)
   → Upper resp - blocked/runny nose, sneeze, itch, lower resp- wheeze, cough, DIB
4. Cardiovascular system (rarely in food allergy)
   → Pallow, drowsy, hypotensive

Question 22

What is the system presentation of non-IgE mediated or delayed onset food allergy response?

Answer 22

1. Skin 
→ Pruritis, eczema, atopic eczema* 
2. Gastrointestinal system 
→ Food refusal or aversion, abdominal pain, infantile colic, GORD*, loose or frequent stools, blood and/or mucus in stools, constipation*, perianal redness, pallor and tiredness, faltering growth with at least one or more GI symptoms (+/- eczema) 
(do not respond adequately to treatment)

Question 23

What are the different presentation of immediate onset food allergy?

Answer 23

IgE mediated
→ Acute urtucaria/angioedema - acute hives with GI but not CVS or respiratory symptoms (any- reported in about 170 foods)
→ Anaphylaxis - rapidly progressive, potentially fatal, multiple organ system reaction with respiratory symptoms an can include cardiovascular (nuts, fish, shellfish, milk and eggs)
→ Pollen-food syndrome (PFS) - pruritus and mild oedema confined to the oral cavity (lips, tongue, mouth and throat) uncommonly progressing, associated with hayfever (raw fruits and veg and nuts)
→ Food associated exercise induced anaphylaxis - food triggers anaphylaxis only if ingestion is followed temporally (within 2 hours) by exercise (wheat, shellfish, celery)

Question 24

What are the different presentation of delayed onset food allergy?

Answer 24

Non IgE mediated
→ Proctocolitis - passage of bright red blood in mucousy stools in otherwise asymptomatic infants (milk, even through breast milk)
→ Enterocolitis - multiple and varying GI symptoms including feed refusal, persistent vomiting, abdominal cramps, loose and frequent stools and constipation (milk, eggs, wheat)
→ Eosinophillic oesophagitis - symptoms from oesophageal inflammation and scarring of feeding disorders, reflux symptoms, vomiting, dysphagia and food impaction (milk, eggs, wheat)
→ Food protein induced enterocolitis syndrome (FPIES) - primarily affects infants, profuse vomiting leading to pallor, lethargy and possibly shock, diarrhoea in 25% (milk, soya, rice, wheat and meat)

Question 25

What is the food allergy march?

Answer 25

Change in food allergies with increasing age
- Infancy → milk, egg, peanut
- Early childhood → soya, wheat, tree nuts, fish, shellfish, kiwi and sesame
- Adolescence → fresh fruit and vegetables - pollen food syndrome - due to cross reaction between pollens of fruits, vegetables and nuts and pollens causing hay fever
Natural history of foods is to improve, resolve or persist

Question 26

What is the food matrix?

Answer 26

Food in combination with other foods

Question 27

What is the effects of high temperatures and food matrix on common food allergens?

Answer 27

• 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 3D structure of the protein, conformational epitopes, will be altered or destroyed by heat and loose their allergenic potential
• Protein interaction with other proteins, fats and sugars in processed foods are also important, in general resulting in decreased availability of protein for interaction with the immune system

Question 28

What are specific examples of the effects of high temperature and food matrix on foods?

Answer 28

1. Cow’s milk
   → Casein more heat resistant than whey (heating raw milk does not seem to reduce allergenicity sufficiently for clinical use),
   → Forms bonds in the food matrix to reduce availability and allergenicity, up to 70% of people allergic to milk can tolerate baked milk (baked in wheat e.g. in a biscuit)
2. Egg whites
   → 4 major proteins in egg whites, all except ovomucoid are heat labile (comprises 10% of egg),
   → Well cooked egg (whole egg) much less allergenic than a whole egg
   → Up to 70% of egg-allergenic can tolerate baked egg (in wheat) e.g. in a cake
3. Peanut
   → Allergenicity ↑ if dry roasted, ↓if boiled or fried
   → Perhaps explains why there is more allergy in the Western societies compared to Asian
4. Fish
   → Fish protein is very heat stable, but canned tuna and salmon are significantly less allergenic
5. Apple
   → Apple proteins are exquisitely heat sensitive
   → Patients with pollen food syndrome can eat processed apple e.g. apply juice

Question 29

What is the implication of cross-reactive food allergens?

Answer 29

• Food allergies can share protein that can have implications in individuals allergic manifestations
  e.g. Cow’s milk and goat’s milk contain similar proteins (92% cross reactivity),
  walnut and brazil nut contain similar proteins (37% cross reactivity)

Question 30

How is food allergy diagnosed?

Answer 30

1. Medical history
   → Context of reaction - age of symptom onset, route of exposure, any incurrent illness etc…
   → Presentation of symptoms - all observed, timing of symptoms, duration etc…
   → Food considerations - minimal quantity of food exposure, manner in which food was prepared
2. Physical examination
   → Identify manifestations of food allergy
   → Differential diagnosis
   → Other allergic conditions e.g. eczema
3. Screening tests
   → IgE mediated FA: Skin Prick test, blood specific IgE
   → IgE and non-IgE: elimination diet
4. Diagnosis verification
   → Controlled oral food challenges

Question 31

What is useful to think about when trying to get a history from patient?

Answer 31

EATERS

• Exposure → food allergies occur when a food is eaten, also handling raw food, kissed, aerosol (frying)
• Allergen → common food allergens (milk, eggs, nuts, shellfish)
• Timing → most IgE-mediated reaction are immediate, non-IgE mediated reactions are delayed
• Environment → weaning- most reactions with first exposure, eating away- daycare, nursery, parties and holidays
• Reproducibility → symptoms should abate with dietary elimination, re-exposure should produce same symptoms
• Symptoms → immediate: skin, gut, respiratory +/- neuro/CVS, delayed: gut predominantly also skin

Question 32

How do we test for allergies?

Answer 32

IgE mediated → skin prick test or blood specific IgE

Non-IgE mediated → elimination diet

Question 33

How do IgE mediated allergy tests work?

Answer 33

Detect IgE in the:
- Blood → circulating IgE levels
- Skin → response of skin mast cells to allergens
Determines the presence of sensitivity not of allergy
Level of serum IgE/ size of skin prick test correlates with likelihood of allergy
Does not correlate with or predict the severity of allergic reaction
Test selection determined by: clinical history, possible cross-reactivity, targeting likely antigens

Question 34

Why is the skin prick test good?

Answer 34

• Suspected allergen injected into the top layers of skin
• See if a reaction occurs → positive reaction - area becomes red and swollen
• Number of suspected allergens are tested on the skin at the same time
• Quick → results within 15 minutes
• Prick to prick test → prick food, prick skin - can test food for which no blood test are available

Question 35

Why is the clinical history important for food allergy diagnosis?

Answer 35

1. Multiple tests without allergy-focused clinical history
   - Likelihood of allergy not higher than background rate
   - True positive test less likely
   - False positive more likely
2. Allergy focused clinical history
   - Likelihood of allergy increased
   - Focused testing
   - True positive and true negative more likely
   - False positive and false negative less likely