Dr Isabel Skypala

Consultant Allergy Dietitian

Royal Brompton & Harefield NHS Foundation Trust

Honorary Senior Clinical Lecturer

Imperial College

Food allergy versus intolerance –

understanding free-from dietary needs

Adverse Food Reactions

Immune-mediated

(Food Allergy and Coeliac

Disease)

Non Immune-mediated

(primarily food Intolerance)

IgE-mediated

Metabolic

Pharmacological Non IgE-

mediated

Toxic

Other

Idiopathic

Mixed

IgE and

Non IgE-

mediated

Cell-mediated

Adapted from:

Guidelines for the Diagnosis and Management of Food

Allergy in the United States (Boyce et al 2010)

Food-induced Allergic Disorders

IgE-mediated

Pollen

Food

Allergy

Syndrome

Urticaria

Angioedema

Mixed IgE and Non

IgE-mediated

Cell-mediated

Adapted from:

EAACI Food Allergy and Anaphylaxis

Guidelines: diagnosis and

management of food allergy (Muraro et

al 2014)

Rhinoconjunctivitis

Asthma

Gastrointestinal

Anaphylaxis

Food-dependent

Anaphylaxis

Atopic eczema

Dermatitis

Eosinophilic

Gastrointestinal

Disorders

Dietary protein

-induced

Proctitis &

Proctocolitis

Food

Protein-

Induced

Enterocolitis

Syndrome

(FPIES)

Perception of Food Allergy 20% of the population alters their diet because they

believe they have an adverse reaction to a food or food

component (Sicherer and Sampson 2006)

Children 12 months – reported rate 7.2%, actual rate 4%

3 years – reported rate 37%, actual rate 6%

Teenage – reported rate 18.7%, actual rate 1%

(Venter, Pierera and colleagues)

Adults Study authors Date Country Reported

rate

Actual or

estimated rate

Young et al 1994 UK 19.9% 1.4%

Jansen et al 1994 Netherlands 12.4% 2.4%

Zuberbier et al 2004 Germany 34% 3.6%

Vierk et al 2007 USA 9.1% 5.3%

Osterballe et al 2009 Denmark 19.6% 1.7%

Skypala et al 2013 UK 15.5% 5.3%

Burney et al 2014 Europe 21% 4.4%

Lifetime prevalence of self-reported food

allergy was 17.3% (95%CI: 17.0-17.6)

Point prevalence for challenged verified FA

was 0.9%

Incidence stable but prevalence increasing

Who is at risk? Children

• Parental atopy

• Eczema -33% of children with moderate/severe eczema may present

with a food allergy (NICE 2007)

• Relationship between asthma, allergic rhinitis and food allergy in

school age children (Penard-Morand et al 2005)

• Food allergy associated with severe asthma in children (Roberts et al

2003)

Adults

• Associated with urticaria, eczema, asthma and hayfever (Schafer

2001, Skypala 2013)

• Asthma - 90% of people who suffered fatal food anaphylaxis had

daily asthma treatment (Pumphrey and Gowland 2007)

• Female sex, rhinitis, eczema and sensitisation to aeroallergens

independently associated with new-onset food allergy (Patelis 2014)

IgE v Non IgE FA v Food Intolerance IgE Non-IgE Intolerance

Onset Rapid Delayed Rapid/delayed

Symptoms Itch, rash, flushing,

swelling, hives,

angiooedema, wheeze,

sneeze, anaphylaxis

Eczema, vomiting,

diarrhoea,

constipation, food

impaction

Rash, flushing,

nausea and

vomiting, rapid

heart beat,

diarrhoea,

constipation,

wheeze, sneeze

Typical

Foods

Milk, egg, wheat,

seafood, nuts, seeds,

legumes, fruits

Not clear but often

wheat, milk, soy

?? seafood

Composite foods,

unrelated foods

Diagnosis History, validated tests,

oral food challenge

History, exclusion

diet, oral food

challenge

History, few

validated tests,

exclusion diet, oral

food challenge

• Bioresonance, kinesiology, irridology, hair analysis,

cytotoxic test, IgG and IgG4, are not currently validated

and cannot be recommended for the diagnosis of food

allergy

• Food-specific IgG4 levels indicate repeated exposure to

high doses of a particular food

Which foods in kids? • Milk, egg, wheat and soy

• IgE and non IgE-mediated

• Usually resolve by teenage years

• Peanut and tree nuts

• Usually start in childhood

• 80% continue into adulthood

• Fish – usually lifelong

IgE-mediated food allergy in adults

• Seafood – especially shellfish (Kamdar et al 2014)

• Tree nuts and peanuts – mainly as cross-reactive

allergies

• Seeds and legumes - sesame, mustard, sunflower

seed, soy, lupin, chick pea

• Fruit and vegetables – usually cause problems due to

cross-reactions between plant foods and pollen (Patelis

2014)

• Cross-reactive food allergy due to pollen common

• Cross-reactions between house dust mite/shellfish,

latex/fruit, cat/pork/beef, meat/tick bites can also occur

Wheat, rye, barley - Coeliac disease

Milk and milk products - Lactose intolerance

Milk, wheat, fruits and vegetables - Fermentable carbohydrates

Additives – preservatives and flavour enhancers

Sulphites - May affect up to 5% of asthmatics

Benzoates – may affect up to 2% of people with urticaria

Naturally occurring ‘food chemicals’

Biogenic Amines

- Headache, hay fever symptoms, flushing, itching, rashes, asthma,

arrhythmia, low blood pressure, abdominal cramping, brochospasm

- Scombroid poisoning

Non-IgE or non-immune mediated food allergy

Co-factors • Cause food allergy only when the food and the co-

factor are co-located

• Exercise most common co-factor –FDEIA – usually

involving wheat but also seafood and tomatoes

- Blood flow redistribution (Morita et al. 2007)

- Uptake of incompletely digested food proteins (Cheng

et al 2007)

- Suppression of gastric acid (Chen et al 2013 )

• Aspirin, NSAID, alcohol and food additives can

also act as co-factors (Cardona et al 2012)

Dietary Management Current Diet

• Food preferences

• Other dietary restrictions

(e.g. for cultural or ethical

reasons)

• Social factors (e.g.

cooking facilities, time)

• Changing nutritional

requirements e.g. growth

in children/pregnancy in

adults

• Nutritional adequacy

Proposed Diet

• What foods/nutrients are

being removed from the

diet?

• Will food substitutes be

required?

• How many foods are being

removed?

• How long will foods be

eliminated – weeks/months?

• Level of avoidance and

other routes of exposure

Other routes of exposure

• Inhalation of aerosolized allergens

• Transfer of allergens during cooking

• Touch and absorption through the skin

• 5-12% of accidental exposures causing

reaction are due to kissing

Level of avoidance IgE mediated food allergy

• Most often need to completely avoid the food and even trace amounts of the food

• Some people can tolerate baked milk or egg

Non-IgE mediated food allergy

• May tolerate small amounts of the trigger food

• Severe cases of non-IgE mediated allergy requires complete avoidance

Food Intolerance

• Reactions are often dose dependent

Nutritional Deficiency in Children • Infants presenting with food allergy have low weight for age

and low height for age Z scores (Viera et al 2010, Flammarion et al 2012)

• The avoidance of 3 or more food groups significantly impacts on weight for age scores (Flammarion et al 2012, Meyer R et al. 2014)

• Red flags are:

Growth faltering or static weight

Poor motor skills and other developmental milestones

Choice and tolerance of formula

Feed volume

Avoidance of multiple foods

Dietary restrictions not associated with food allergy

Presence of another chronic condition

Nutritional deficiency- adults • Diets of adults on milk and wheat free diets low in iron, B

vitamins, Vitamin D, calcium and energy

• Deficiencies in zinc, iron and vitamin D may contribute to

the development of allergies in the elderly (Diesner et al.

2011)

• Vitamin C - could be sub optimal if multiple fruits and

vegetables being avoided (des Roches et al 2006)

• A greater number of food allergies linked to increasing

number of nutritional deficiencies (Kim et al 2013)

• Full nutritional dietary and serum screen essential where

multiple foods have been avoided for some time

• Bone densitometry in those with asthma avoiding milk

Milk

Milk - Heat treatment

reduces allergenicity of β-

lactoglobulin but not α-

casein

Milk –90% cross-reactivity

to goat’s milk

mare and camel milk 4%

cross-reactivity

75% of milk allergic children tolerated baked milk – (Nowak et al JACI 2008)

Fraction Protein Allergen

Casein

80%

αs1-casein

Bos d 8

αs2-casein

ϐ-casein

ϒ1-casein

ϒ2-casein

ϒ3-casein

κ-casein

Whey or

serum

proteins

20%

α-lactalbumin Bos d 4

ϐ-lactoglobulin Bos d 5

Immunoglobulin Bos d 7

BSA Bos d 6

Lactoferrin

Cow’s milk substitutes

• Hydrolysed and elemental formula milks for infants

Partially hydrolysed formula

Extensively hydrolysed

Amino acid

• Soya milk – affects 7-14% of infants with IgE –mediated milk allergy

but up to 50% of non-IgE-mediated milk allergy

• Rice milk – not for children aged between 1 and 4.5 years

• Adults and older children

• Pea milk, almond milk, Oat milk, Coconut milk, Hemp milk

• Other milk substitutes – lacto-free milk

Eggs Allergen Common

name

Heat -

treated

Digestive

enzyme-

treated

Allergenic

activity

Gal d 1 Ovomucoid Stable Stable +++

Gal d 2 Ovalbumin Unstable Unstable ++

Gal d 3 Ovotransferrin

Conalbumin

Unstable

Unstable

+

Gal d 4 Lysozyme Unstable Unstable ++

Cross-reactivity with other birds eggs, birds

feathers and chicken

Egg Ladder

Well cooked egg Lightly cooked egg Raw egg

Cakes and biscuits

Egg pasta

Pancakes

Well-done Yorkshire

pudding

Sausages

Burgers

Quorn

Sponge cake

Milky Way or Mars bar

or Crème egg

Some soft-centred

chocolates

Waffles

Commercial marzipan

Scrambled, boiled, fried,

poached egg

Omelette

Egg fried rice

Meringues

Some marshmallows

Lemon curd

Quiche

Egg in batter or breadcrumbs

Hollandaise sauce

Quiche and flans (fruity and

savoury)

Egg custard, Crème caramel

Crème Brulée and ‘real’ custard

Runny Yorkshire pudding

Tempura batter

Mayonnaise or salad

cream

Mousse

Ice cream

Sorbet

Royal icing

Home-made marzipan

Cake mix

Egg glaze on pastry

Horseradish sauce

Tartar sauce

Cheese containing egg

white in the form of

lysozyme

Seafood Pan allergens –βParvalbumin in vertebrate fish and

invertebrate tropomyosin in crustaceans and molluscs

Allergens are heat-stable, water-soluble

Shrimp allergens detected in oil used to cook shrimp

and reported to cause problems in cooking vapours (Lehrer et al 2007, Carrillo et al 1992)

Species-specific reactions

Contamination

Differential diagnosis

Peanuts and Tree nuts

• Peanut

• Ground nuts

• Monkey nuts

• Earth nuts

• Goober peas

• Brazil

• Walnut

• Hazelnut

• Almond

• Cashew

• Pistachio

• Pecans

• Macadamia

Nutmeg, Coconut, pine nut

and palm nut are not

classified as nuts

• Cold-pressed ‘gourmet’

oils

• Marzipan

• Frangipan

• Amaretto products

• Macaroons

• Bakewell tarts

• Praline

• Noisette

• Marron e.g. marron glace

• Satay sauce

• Korma sauce

• Pesto sauce

• Cakes, biscuits and

pastries

• Ice cream, desserts

and dessert toppings

• Chocolate bars

• Cereal bars and

confectionery

• Savoury snack foods

• Breakfast cereals,

especially muesli or

nut mixtures

Peanuts and Tree nuts

• Cross-reactivity and cross-contamination

• Avoidance of all nuts or just specific nuts?

• May contain traces nut warnings

• Lifelong abstinence – is resolution

important to challenge for?

• Non-food sources of nuts and seeds

Soy Whole bean

products

Soy sprouts, Edamame, soy milk, tofu, Miso, Natto, Yuba, Tempeh,

Soy sauce, soy nuts, soynut butter, soy cereals, soy cheese, soy milk,

soy ice cream/yoghurt/desserts

Hull Products Bread, bakery products , snack bars

Protein

products

Soy flour, protein concentrate, protein isolate, textured soy

Baby foods, infant formulae, bread, biscuits, pancakes, pastry,

crackers, snack foods, noodles, pizza, breakfast cereals, soy milk, ice

cream, soy yoghurt and cheese, sausages, tinned meat and fish, soups

and gravy, beef burgers, salad dressing, stock cubes, sauces

Oil Products Refined oil, lecith in

Cooking oil, salad oil, margarine, salad dressing, mayonnaise, coffee

whiteners, chocolate, sweets, pastry filling, cheese dips, emulsifying

agents, dietary supplements and body building agents

Fruits & Vegetables • Pollen-food syndrome (PFS) or Oral Allergy Syndrome occurs in

people whose pollen antibodies recognise and cross-link with

homologous plant food proteins

• Main Birch pollen allergen Bet v 1 has 35-60% sequence identity

with many PR10 proteins in plant foods

• Immediate oral symptoms on contact with plant food

• 66% (50 to 93%) birch pollen allergic patients may have PFS

• Other pollens which can cross-react include grass, ragweed and

mugwort

• Only raw foods cause symptoms

• Typical foods include apples, peaches, cherries, kiwi fruit, tree nuts,

but can also involve tomatoes, carrots, celery, peeling potatoes,

melon, oranges and peanuts

FOODS TO AVOID FOODS WHICH CAN BE

CONSUMED

All bread,rolls, malt bread, chapatti,

pitta, nan, paratha, croissants, soda

bread, fancy breads, pizza,

breadcrumbs

Gluten-free, wheat–free foods –

breads, biscuits, cakes, pizza bases

Flour: cakes, biscuits, crackers, pastry,

pies, batters, pancakes, sauces

Gluten-free wheat flour, cornflour, rice

flour

Pasta, semolina and couscous Gluten-free pasta, rice, polenta

Breakfast cereals unless derived

solely from oat, rice and/or corn

Rice, oat and corn breakfast cereals

Other cereals – spelt, rye, barley,

triticale

Other cereals – sago, tapioca,

buckwheat, millet, arrowroot, quinoa

Wheat derived products – wheat

protein isolates, wheat starch, wheat

bran, wheat germ, wheat binder

Gluten-free baking powder

Other – cereal filler, rusk, modified

starch

Wheat

Semolina

Couscous Pearl barley

Spelt

Quinoa Potato flour Buckwheat

Tapioca Cornflour Polenta

Pizza – soy, celery,

mustard, wheat

protein isolate

Asian food – prawns,

sesame, peanuts,

buckwheat noodles,

Indian food – almonds,

pistachio, cashew,

peanuts, celery, mustard,

seafood

Bakery products – lupin, soy, other legumes,

buckwheat, barley, cochineal

Hidden allergens

Lactose Intolerance • Congenital -rare -poor growth + diarrhoea from first

exposure to breast milk

• Primary - 70% of humans from early childhood onwards

– can often tolerate foods that have lower lactose

content

• Secondary/transient - reversible loss of lactase activity

due to damage to brush border of small intestine e.g.

due to gastroenteritis or giardia

• Main foods - milk, soft cheese, ice cream, butter

30

Wheat, milk and IBS

Fermentable Oligo-Di-Monosaccharides and Polyols (FODMAP™)

• Fructo-oligosaccharides - wheat, rye, onions, garlic and artichokes

• Galacto-oligosaccharides – legumes

• Fructose - honey, apples, pears, watermelon and mango - affects

45%

• Lactose - affects 25%

• Sorbitol - peaches, plums, cherries, nectarines, sugar free mints and

gum

• Mannitol - mushrooms, cauliflower

Barrett et al. Aliment Pharmacol Ther. 2009;30:165-74

Benzoates Sulphites Amines

Meat, poultry,

seafood, milk

Yoghurt Meat burger,

sausages, prawns All cured meat, fresh

pork, oily fish, smoked

or processed fish,

mature and blue

cheese

Fruits Berries, nectarines,

peaches, papaya, dried

fruit,

Dried apricots,

sultanas, figs,

prunes, dates,

preserved lime and

lemon juice

Oranges, ripe

bananas, pumpkin,

tomatoes, pickled

cabbage

Vegetables Avocado, pumpkin, kidney

beans, soy beans, broccoli

and spinach, baked beans

in tomato/spicy sauce

Dried onions, pickled

onions, frozen chips

and roast potatoes

Broad beans, peanuts

Condiments &

miscellaneous

Curry powder, all spice,

mixed spice, nutmeg,

clove, cinnamon, jam,

pickled foods, salad cream

White vinegars

Drinks Tea, beer, chocolate,

cocoa

Cider, white wine Green tea,

champagne

Summary

• Many different presentations of food allergy and

intolerance

• Diagnosis not straightforward

• Food avoidance can depend on the type of food

allergy or intolerance experienced

• Dietary exclusion can be difficult and nutritional

problems are common, especially in children

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