Food allergy in adults:
what’s new on the menu?
Penny Fitzharris
August 2010
Food allergy in adults
 What
is it?
 What foods are involved?
 Who is affected?
 How, when and why does it develop?
 How is it diagnosed and managed?
 What treatment is available?
 What problems are associated?
 How do we improve services?
Food allergy is an immune-mediated adverse
reaction to food – failure of immune tolerance

In developed countries food allergy present in
6 - 8 % of children, 2 - 3 % of adults

Immune mechanisms include:
- IgE mediated e.g. anaphylaxis
- non IgE mediated
e.g. coeliac disease
- reactions involving IgE and non-IgE
e.g. eosinophilic oesophagitis
IgE mediated mast cell mediator release
Symptoms of IgE-mediated Food
Allergy




rapid onset (minutes, up to 2 hours)
multiple organ systems often involved
result from chemical mediators released from mast cells and
basophils
manifestations include:
- acute urticaria (hives), angioedema
- throat tightness, stridor, chest tightness, wheezing, persistent
cough, voice change, rhinitis, conjunctivitis
- nausea, vomiting, abdominal pain, diarrhoea
- alteration of consciousness, hypotension
- anaphylaxis
Food allergy in adults
 What
is it?
 What foods are involved?
 Who is affected?
 How, when and why does it develop?
 How is it diagnosed and managed?
 What treatments are available?
 What problems are associated?
 How do we improve services?
Food allergens of plant origin


Legumes
- peanuts roasted > boiled or fried
- soya
- lentils, beans, peas, lupin
Cereal grains - wheat, barley, rye, oats, corn, rice
cross reactivity between cereal and grass
pollens
cereal allergens in bourbon, whisky


Umbelliferae - celery, carrot, parsley, fennel, dill
Solanaceae - tomato, potato, peppers, aubergine,
coffee


Tree nuts, seeds - hazel, almond, brazil, sesame
Fruits - increasingly common in Europe
Allergens of animal origin

cow’s milk

hen’s egg - egg white > egg yolk but chicken allergy may
- several allergens, heat labile and heat
stable
occur with yolk allergy (egg-bird syndrome)

fish

crustacea - cross reactions within crustacea family
- cooking vapours may be a problem, not cross
reactive with crustacea
frequent

molluscs - true allergy not frequent
- snails: cross reactivity with mite


goat and sheep milk
meat e.g. pork, beef, chicken
What makes a protein an allergen is still not known
but…

Allergens have been mapped to only 5% of
structural protein families:
e.g. profilins from plants
tropomyosins and caseins from animals
pathogenesis related proteins from both

Biochemical functions of allergens are also
limited
and include enzymes, binding and storage proteins,
Prolamin family
Suspected precipitant for community onset anaphylaxis
(Smith & Empson)
2000/2001 (129)
Medication
44 (34)
Antibiotic
18 (14)
Β-lactam
14 (11)
NSAID
11 (9)
ACEI
5 (4)
Food
40 (31)
Shellfish / fish
21 (16)
Peanut
7 (5)
Treenut
2 (2)
Other food
10 (8)
Hymenoptera sting 10 (8)
Honey bee
7/10 (5)
Other*
2
(2)
Unknown
32 (25)
2005/2006 (116)
27 (23)
9
(8)
7
(6)
11 (10)
5
(4)
32 (28)
15 (13)
4
(3)
3
(3)
10 (9)
7
(6)
4/7 (3)
2
(2)
48 (41)
*This includes multiple possible precipitants, exercise etc
Allergy to fish/shellfish?

May develop in adult life.

Allergy to seafood (scaly fish, crustaceans and
mollusks, including bivalves, cephalopods, gastropods)
is more common where fish is commonly eaten.

Individuals may react only to scaly fish or crustaceans
or mollusks, but some react to more than one group.
Within each group there is often cross reactive allergy.

Other causes include…
Histamine fish poisoning (scombroid poisoning)

Histamine fish poisoning (HFP) is a chemical
intoxication which occurs after eating fish of the dark
meat varieties including tuna, kahawai, mackerel,
bonito, butterfly kingfish, anchovies

Histamine is commonly the result of high temperature
spoilage (>21°C), and often occurs if dead fish remain
in set nets during warm sea temperatures, or improper
or delayed refrigeration.

Histamine is not destroyed by freezing, cooking,
smoking, curing or canning.
Should be considered in a patient who regularly eats
fish, without a previous reaction

Anisakis: a nematode which infects marine
animals
Food allergy in adults
 What
is it?
 What foods are involved?
 Who is affected?
 How, when and why does it develop?
 How is it diagnosed and managed?
 What treatments are available?
 What problems are associated?
 How do we improve services?
Community-onset anaphylaxis (Smith & Empson)
Number of patients (%)
Female
Age (avg, range)
European
NZ Maori
Pacifika
Asian
Other
Atopic disease
Asthma
Hx of allergic reaction
Prev seen at allergy clinic
Precipitant known
Prev Anaphylaxis
Had adrenaline autoinjector
2000/2001
77/129 (60)
40.7 (15-81)
81 (63)
8
(6)
13 (10)
14 (11)
13 (10)
60 (47)
44 (34)
68 (53)
8/68 (12)
47/68 (69)
55
(43)
6/55 (11)
2005/2006
73/116 (63)
43.8 (15-88)
71 (61)
5
(4)
16 (14)
17 (15)
7
(6)
34 (29)
29 (25)
59 (51)
15/59 (25)
43/59 (88)
40
(34)
10/40 (25)
Food allergy in adults
 What
is it?
 What foods are involved?
 Who is affected?
 How, when and why does it develop?
 How is it diagnosed and managed?
 Who should diagnose and manage?
 What problems are associated?
 How do we improve services?
Why has May become allergic to peanut?

Family history?
Neither parents has atopic disease

As a first child she is at higher risk of allergy
“Hygiene hypothesis” – microbial exposures

Infant diet? allergens and other nutrients

Weaning advice in the last decade?
What aspects of route, timing,
duration and extent of exposure
may be relevant?
June 1998
COT recommended that
“pregnant women who are atopic, or for whom the
father or any sibling of the unborn child has an
atopic disease, may wish to avoid eating
peanuts and peanut products during pregnancy
and lactation”.
It was also recommended that these infants
should avoid peanut and peanut products during
weaning and until at least 3 years of age.
In common with all children, exclusive breast
feeding for 4-6 months was recommended
Hourihane et al JACI 2007;119:1197202

1072 children born 1999 / 2000 (after COT
advice)

61% of mothers recalled hearing advice,
unaffected by atopic status

Many mothers (42%) reduced peanut
consumption

Few (3.8%) avoided peanut entirely

Diet change more likely with first child and when
child’s father was atopic
 65%
of the children had consumed peanut
by age 4-5y
 mean
introduction of peanut was at 36m
Isle of Wight cohort born 1989/90 - 12.6m
 1.8%
had peanut allergy (challenge)
2.8% were sensitised to peanut
 children
with peanut allergy had high
likelihood of eczema history
Avon Longitudinal Study of Parents and Children
(ALSPAC) Lack et al, NEJM 2003 348 977-85





Study children were history positive to age 38m,
studied at age 4-6y
23 of 29 with positive skin test had a positive
DBPCFC (50mg-8g) (No responses to placebo)
children with eczema were 4 times more likely to
have peanut allergy
if oozy, crusted eczema then 25 times more
likely to have peanut allergy
If had used creams containing peanut oil were 8
times more likely to have peanut allergy
Household consumption as a risk factor for the
development of peanut allergy - Fox AT JACI 2009;123:417-23

Study examined different routes of peanut
exposure in the development of allergy

Questionnaires at time of allergy clinic
attendance, usually with eczema. Known peanut
allergy excluded. Routine investigations in
clinic.

peanut allergy cases
(133)
high risk controls -egg allergy (160)
low risk controls
(150)
Fox AT JACI 2009;123:417-23

Eczema present in first year in 92% PA cases, 88% egg
allergy cases, 42% low-risk controls

90% breast fed (no group differences)

Median household peanut protein consumption:
Household peanut
protein
consumption
Low risk controls
6.9g/week
High risk controls
(egg allergic)
1.9g/week
Peanut allergic
cases
18.6g/week
Du Toit G et al, JACI 2008;122:984-91

Prevalence of peanut allergy:
Jewish children in UK (5171)
1.85%
Jewish children in Israel (5615) 0.17% (p<.001)

Introduction of peanut by 9 months of age:
69% of Israelis v 10% of UK infants

Median monthly consumption in first year:
7.1g in Israel, 0 in UK
Du Toit G et al, JACI 2008;122:984-91

Introduction of egg, soya, wheat, vegetables,
fruit and tree nuts was similar in both countries

Small differences in introduction of cow’s
milk/dairy, breast feeding and exclusive breast
feeding

Peanut protein and major peanut allergen
content similar in commonly used products
COT Dec 2008
 “There
is now limited human evidence,
consistent with a larger body of animal
data, suggesting that non-oral routes of
exposure to peanut, such as the skin, may
be relevant.”
COT statement Dec 2008
 “The
shift in the balance of evidence since
1998 is such that the Committee believes
that the previous precautionary advice to
avoid peanut consumption during
pregnancy, breast feeding and infancy,
where there is atopy or atopic disease in
family members, is no longer appropriate.”
 Expert
opinion in Europe, US and
Australasia is similar
May
 Is
it possible to predict
whether her allergy will persist?
whether she is at risk of a more severe
reaction?
can persisting allergy be treated?
Skin prick tests – detect sensitisation
(presence of IgE) not clinical allergy
Used for inhalants, foods, venoms and some drugs
Detect specific IgE bound to mast cells in the skin
Can skin tests predict clinical response?

100% of children with wheals over a certain size
reacted to food challenge (urticaria, severe eczema,
asthma, rhinitis, vomiting, other g-I, anaphylaxis)
Cow’s milk
Egg
Peanut
8mm
7mm
8mm

Specificity of 100%

May’s skin test:
Peanut
13mm
Sporik et al, Clin Exp Allergy, 1999
< 2years
<2 years
< 2 years
6mm
5mm
4mm
Measurement of specific IgE in the blood eg RAST
HA Sampson 2004
Does further investigation of purified allergen
component specificity help in prognosis?

Not yet- potential for the future.
Peeters et al, Clin Exp Allergy 2007;37:108-115
“Component resolved diagnosis”
allergen specific diagnosis
Gradual transition towards component
resolved diagnosis seems inevitable.
Many purified or recombinant allergens are now available
for use in the ImmunoCAP RAST method.
First available allergen at Lab+ is the wheat allergen
rTri a 19 (omega-5 gliadin).
Sensitisation to this allergen is associated with wheatdependent exercise induced anaphylaxis
Louise

4-6 episodes itching and urticaria in different
circumstances since December 2007

April 2008- shopping at K-Mart after BK chicken
fillet burger – collapse-adrenaline used at EM

September 2008 K-Mart, BK chicken fillet burger
again and Nurofen. Collapse, Epipen used

Eats wheat, bread, chicken, many foods without
problem
Louise (2)

Skin tests showed:
weak positive (3mm) wheat, RAST to wheat 2+, 3KU/L,
wide range of other foods negative, negative to chicken
 Clinical Impression:
probably food-dependent exercise induced anaphylaxis
advised to avoid wheat before exercise and NSAIDs before
exercise
Subsequently:
 skin tested “fresh” BK burger and fries – negative
 2 further episodes anaphylaxis after eating small very
amounts of wheat, followed by exercise (hospital treatment)
 RAST to omega-5 gliadin peptide 4+, 13KU/L
 Subsequent exercise challenge (avoiding wheat) negative
If allergy persists into older childhood?
 Desensitisation
(immunotherapy) is an
effective treatment in IgE mediated allergy
to insect venoms and inhalant allergens
 Can
it be used in IgE-mediated food
allergy?
Successful oral tolerance
induction in severe peanut
allergy
Clark AT et al, Allergy 2009
50mg approx ¼ - 1/5 of a
peanut
1 peanut approx 200-240mg
protein
800mg peanut protein=2.5mls
smooth peanut butter
JACI 2009
Hofmann, 2009, JACI
Safety aspects
Oral IT to foods
 Large
resource implications for paediatric
and adult allergy services!
 Not
just peanut but many other foods
 Safety
 Will
concerns remain an issue
effects persist if oral intake is
discontinued?
Food allergy in adults
 What
is it?
 What foods are involved?
 Who is affected?
 How and When does it develop?
 How is it diagnosed and managed?
 What treatments are available?
 What are the effects on quality of life?
 How do we improve services?
RB limitations due to behavioural problems
BP severity/frequency of pain/limitations assoc
GH perceptions of overall health
SF social functioning
VT vitality and liveliness
GH general health
SF social functioning
RP physical problems
BP pain
GH general health
Food allergy in adults
 What
is it?
 What foods are involved?
 Who is affected?
 How and When does it develop?
 How is it diagnosed and managed?
 What treatments are available?
 What problems are associated?
 How do we improve services?
PPV – proportion of those identified as positive by the (skin) test where this is correct
Specificity – proportion of those who don’t have the condition, correctly identified as
negative
In summary







Food allergy affects 1-2% of the population
Fish, shellfish, peanuts and nuts are the main
offenders
Food allergy is responsible for about 1/3 of
anaphylaxis in Auckland
Most (but not all) food allergy develops in
childhood
Food allergy strongly linked with early eczema
Allergen entry through the skin may be important
There is no evidence to advise maternal
avoidance






There is no evidence to recommend maternal
avoidance of allergens in pregnancy or breast
feeding (unless allergy in mother or child)
Early introduction of foods (not before 4 months)
may help induce oral tolerance
Oral desensitisation may become a useful
treatment. More research needed.
Quality of life affected in food allergy
Several bodies are developing diagnosis and
management guidelines which will be helpful.
Still a complex area!
Lack et al, NEJM 2003 348 977-85
Lack et al, NEJM 2003 348 977-85
Component-resolved diagnosis from latex allergy by microarray
Authors: Ebo, D. G.1; Hagendorens, M. M.2; De Knop, K. J.1; Verweij,
M. M.1; Bridts, C. H.1; De Clerck, L. S.1; Stevens, W. J.1
Source: Clinical & Experimental Allergy, Volume 40, Number 2,
February 2010 , pp. 348-358(11)

26 healthy controls

22 latex allergic patients
All showed specific IgE to Hev b 1, Hev b 3, Hev b 5 or Hev
b 6.02

20 latex sensitised but clinically non reactive
None were sensitised to above allergens. >75% sensitised
to Hev b 8
Tropomyosin family
Other candidates in the diet and geneenvironmental interactions?







Folic acid – potential epigenetic regulation
effects e.g. methylation influences IFNγ gene
promoter, affecting TH1 and Treg expression
n-3 polyunsaturated fatty acids (fish oil)
Prebiotics – oligosaccharides
Probiotics – effects appear strain specific
Vitamin D
Antioxidants
Role of breast milk TGFβ in inducing tolerance
Effects of oral IT with peanut
 Reduced basophil activation
 Initial
rise then fall in specific IgE
 Increase
in specific IgG and IgG4
 Changes
in FoxP3+ T regulatory cells
 Down-regulation
pathways
of genes in apoptotic
Prevalence of peanut allergy in three UK studies 1996-2006
No of children
Year of birth
Age (y) when
studied
Prevalence of
sensitisation
(95% CI)
Prevalence of
peanut allergy
(95% CI)
Tariq et al
1996
981
1989-90
4-5
SPT
1.1%
(0.5-1.6)
0.5%
(0.1-0.8)
Grundy et al
2002
1246
1994-1995
3-4
SPT, OFC
3.3%
(2.3-4.3)
1%
(0.8-2.1)
Hourihane et
al 2007
1072
1999-2000
4-5
SPT, sIgE,
DBPCFC
2.8%
(1.8-3.8)
1.8%
(1.1-2.7)
Hourihane et al JACI 2007;119:1197-202
Increasing prevalence of allergy
Hospital admissions data from 1990/91 to 2000/01 in England.
Over 11 years total
admissions for these
disorders increased from
0.02% - 0.06%.
(1960 to 6752 out of
49,300 admissions in
total).
Gupta et al, BMJ 2003