food allergy and anaphylaxis guidelines allergy supplementary v1.pdf · food allergy and...
Post on 29-May-2020
14 Views
Preview:
TRANSCRIPT
-
European Academy of Allergy and Clinical Immunology
Supplementary materials
Food Allergy and Anaphylaxis Guidelines
European Academy of Allergy and Clinical Immunology
-
EAACI GUIDELINES Food Allergy and Anaphylaxis
Editors
Antonella Muraro
Graham Roberts
Editorial BoardIoana Agache
Carsten Bindslev-JensenAndy Clark
Anthony DuboisSusanne Halken
Karin Hoffmann-Sommergruber Aziz Sheikh
Thomas WerfelMargitta Worm
Supplementary materials
-
EAACI
Hagenholzsltrasse 111
3rd Floor
8050 Zurich
Switzerland
The European Academy of Allergy and Clinical Immunology, EAACI, is a non-profit organisation active in the field of allergic and immunologic diseases such as asthma, rhinitis, eczema, occupational allergy, food and drug allergy and anaphylaxis. EAACI was founded in 1956 in Florence and has become the largest medical association in Europe in the field of allergy and clinical immunology. It includes over 7800 members from 121 countries, as well as 47 National Allergy Societies.
© - European Academy of Allergy and Clinical Immunology (EAACI) 2014
All rights reserved.
-
To all the members of EAACIand to our patients
-
Contents
Food allergy: diagnosis and managementE-3 The epidemiology of food allergy in Europe: systematic review and meta-analysisE-35 Prevalence of common food allergies in Europe: systematic review and meta-
analysisE-65 The diagnosis of food allergy: systematic review and meta-analysisE-75 Acute and long-term management of food allergy: systematic review
1
2 Primary prevention of food allergyE-109 Primary prevention of food allergy in children and adults: systematic review3 Quality of life in food allergy E-139 Disease-specific health-related quality of life instruments for IgE-mediated food allergy: systematic review4 Anaphylaxis E-151 The epidemiology of anaphylaxis in Europe: systematic reviewE-185 Management of anaphylaxis: systematic review
-
FOOD ALLERGY DIAGNOSIS
AND MANAGEMENT
1SECTION
Supplementary materials
-
BI Nwaru1, L Hickstein2, SS Panesar3, A Muraro4, T Werfel5, V Cardona6, AEJ Dubois7, S Halken8, K Hoffmann-Sommergruber9, LK Poulsen10, G Roberts11-13, R Van Ree14, BJ Vlieg-Boerstra15, A Sheikh3, 16 on
behalf of The EAACI Food Allergy & Anaphylaxis Guidelines Group
EAACI Food Allergy & Anaphylaxis Guidelines Group: CA Akdis, R Alvarez, K Beyer, C Bindslev-Jensen, V Cardona, P Demoly, A Dubois, P Eigenmann, M Fernandez Rivas, A Host, E Knol, G Lack, MJ Marchisotto, B
Niggeman, N Papadopolous, I Skypala, M Worm
1.1THE EPIDEMIOLOGY
OF FOOD ALLERGY IN EUROPE
SYSTEMATIC REVIEW AND META-ANALYSIS
Supplementary materials
-
AFFILIATIONS1 School of Health Sciences, University of Tampere, Finland
2 Institute for Medical Informatics, Biometry and Epidemiology, University of Munich, Germany3 Allergy & Respiratory Research Group, Center for Population Health Sciences, The University of Edinburgh, UK
4 Department of Pediatrics, Center for Food Allergy Diagnosis and Treatment, Veneto Region, University of Padua, Italy5 Hannover Medical School, Hanover, Germany
6 Hospital Valld’Hebron, Barcelona, Spain7 Department of Paediatrics, Division of Paediatric Pulmonology and Paediatric Allergy, University Medical Centre Groningen,
University of Groningen, Groningen, The Netherlands8 Odense University Hospital, Odense C, Denmark
9 Department of Pathophysciology and Allergy Research Medical University of Vienna, Vienna, Austria10 Laboratory of Medical Allergology, Allergy Clinic, Copenhagen University Hospital, Hellerup, Denmark
11 David Hide Asthma and Allergy Research Centre, St Mary’s Hospital, Newport, Isle of Wight, UK12 NIHR Southampton Respiratory Biomedical Research Unit, University of Southampton and University Hospital Southampton
NHS Foundation Trust, UK13 Human Development and Health and Clinical and Experimental Sciences Academic Units, Faculty of Medicine, University of
Southampton, UK14 Departments of Experimental Immunology and of Otorhinolaryngology, Academic Medical Center, University of Amsterdam,
The Netherlands15 Department of Pediatric Respiratory Medicine and Allergy, Emma Children’s Hospital, Academic Medical Center, University of
Amsterdam, The Netherlands16 Division of General Internal Medicine and Primary Care Brigham and Women’s Hospital/Harvard Medical School, Boston, MA,
USA
-
E-5EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
METHODSSearch strategyArticles were retrieved using a highly sensitive search strategy implemented in four electronic databases (OVID MEDLINE, OVID EMBASE, CINAHL, and ISI Web of Science). The search strategy was devised on OVID MEDLINE and then adapted for the other databases (see Box E1). Systematic reviews were retrieved by using the systematic review filter developed at McMaster University Health Information Research Unit (HIRU) (http://hiru.mcmaster.ca/hiru/HIRU_Hedges_MEDLINE_Strategies.aspx#Reviews). We also adapted the search filter from York University Centre for Reviews and Dissemination (http://www.york.ac.uk/inst/crd/intertasc/epidemiological_studies.html) to retrieve the characteristics describing the epidemiology of FA. The McMaster filter (http://hiru.mcmaster.ca/hiru/HIRU_Hedges_EMBASE_Strategies.aspx#Prognosis) was applied for retrieving studies on prognostic factors. Additional references were located byhand search. Unpublished work and research in progress were searched through discussion with experts in the field. There were no language restrictions, and where possible the literature in languages other than English was translated. The literature we were unable to translate is shown in the PRISMA flow diagram (Figure 1).
Inclusion and exclusion criteriaAs per the study design, we included systematic reviews and meta-analyses, cohort studies, case-control studies, cross-sectional studies, and routine healthcare studies. We excluded review and discussion papers, non-research letters and editorials, case studies and case series, animal studies, and all randomized controlled trials. Our initial inclusion criteria were broad by including studies published worldwide between January 1990 and September 2012. However, after assessing the large amount of articles, we made further restrictions to include studies published only in Europe (based on the United Nations definition (http://unstats.un.org/unsd/methods/m49/m49regin.htm#europe accessed on December 28, 2012) between January 1, 2000 and September 30, 2012, with the exception of Greenland and Turkey, which were included in the review because we believe they are culturally and politically more European than North American and Asia, respectively.
Term Definition
1 exp Food Hypersensitivity/
2 food allerg*.mp.
3 food hypersensitivity.mp.
4 food hypersensitivities.mp.
5 allergy, food.mp.
6 (rat or rats or cow or cows or chicken? or horse or horses or mice or mouse or bovine or animal$).ti.
7 exp animals/ not humans.sh.
8 6 or 7
9 *Incidence/
10 *Prevalence/
11 (incidence or prevalence or epidemiol$).ti.
12 epidemiologic methods/
13 *cohort studies/
14 controlled clinical trial.pt.
15 *case-control studies/
16 exp Food Hypersensitivity/ep [Epidemiology]
17 exp Hospitalization/
18 exp Hospitalization/sn, td [Statistics & Numerical Data, Trends]
19 exp Mortality/sn, td [Statistics & Numerical Data, Trends]
20 exp Epinephrine/ad, tu, th [Administration & Dosage, Therapeutic Use, Therapy]
21 exp "Cause of Death"/
22 ((adrenaline or epinephrine) adj3 (dispens$ or prescrib$)).tw.
23 or/9-22
24 or/1-5
25 23 and 24
26 25 not 8
27 limit 26 to yr="1990 - 2012"
Box E1 Ovid Medline search strategy
-
Epidemiology of food allergy in Europe: a review
E-6 EAACI Supplementary materials
Analysis, synthesis and reportingWe recalculated all the frequency estimates of FA occurrence if adequate data were provided by authors. If any discrepancies were observed between our recalculated estimates and those of the authors, we reported our recalculated estimates. Our recalculated estimates were based on the minimal measured events rather than extrapolated estimates. In studies where inadequate data were given to enable recalculation, we reported the estimates provided by the authors. Where needed and possible, we contacted authors of primary studies for clarifications. The 95% confidence intervals (95% CI) of our recalculations were computed by using the Wilson score method without continuity correction (15). Different reports from the same primary study were reported as one study. Although several specific food allergies were reported across the studies, the focus of the current report is to present the estimates for ‘any FA’. The other specific foods will be presented in a future report. In studies reporting estimates of sensitization to food allergy alongside cross-reactivity to pollen (wheat and grass), we always used the true estimates without pollen cross-reactivity, where possible.
We performed a random-effects meta-analysis for clinically and methodologically comparable studies to estimate the frequency of FA. The following outcomes were considered: 1. point and life-time prevalence of self-reported FA; 2. point prevalence of specific IgE positivity; 3. point prevalence of SPT positivity; 4. point prevalence of symptoms plus IgE positivity; 5. point prevalence of symptoms plus SPT positivity; 6. point prevalence of clinical history or OFC/DBPCFC-positivity; 7. point prevalence of positive response to food challenge (open food challenge [OFC] or DBPCFC). For outcomes 6 and 7 above, where a study reported estimates for both OFC and DBPCFC, the DBPCFC estimates were always used; otherwise OFC estimates were used if DBPCFC was not done in the study. We did not present pooled estimates for cumulative incidence of FA due to inconsistencies and very few data across studies.
We aimed to present stratified pooled estimates by different age groups (1 year and under, 2-5 years, 6-10 years, 11-17 years, 18-60 years, and older than 60 years). However, due to several overlapping ages of participants across the studies, the age-stratified pooled estimates were more feasibly computed for the age groups 0-17 years (children) and 18 years
and over (adults). A study with overlap between these two age groups was included in either age group if the age distribution was skewed to that age group. For studies that gave frequency estimates at different ages for the same individuals, we used the estimates for the highest age in computing the pooled estimates. We also present the pooled estimates stratified by geographical region in Europe (i.e., East, West, South, North, and ‘Europe’; the last group being for studies that included several European countries and gave overall estimate for all the countries and in which it was not possible to calculate the frequency for each country studied) using the classification by the UN (http://unstats.un.org/unsd/methods/m49/m49regin.htm#europe accessed December, 2012). Due to methodological differences across the studies investigating the risk and prognostic factors for FA (varied risk and prognostic factors studied, differences in study design, differences in statistical methods employed across studies, differences in factors considered for adjustment, and others), we did not perform meta-analysis for these studies.
RESULTS
Study characteristicsThe characteristics, main results, and the overall risk of bias grading of the studies included for review are shown in Table E1. Of the 56 studies reviewed, 31 were cross-sectional, 19 cohort, three were systematic reviews, and three case-control studies. Over 50% of the studies were conducted in northern European countries. A majority of the studies (n=37) were undertaken only in children. Ten studies assessed FA only by self-report, 10 only by specific-IgE or SPT positivity, while the remainder was a combination of self-report, specific-IgE or SPT sensitization, and food challenge. Twenty-six of the studies undertook food challenges for verifying FA, and 22 of these employed DBPCFC. A majority of the studies (n=49) reported point prevalence as the occurrence measure for estimating the frequency of FA. The majority of studies had a moderate risk of bias (Table E2).
Frequency of FASelf-reported FA: details of studiesEighteen of the 27 studies on self-reported FA included children (i.e., < 18 years). Two studies
-
E-7EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
reported cumulative incidence in children: one study from Denmark reported the cumulative incidence of self-reported FA by the age of 6 years as 11.6% (27-29), whereas one study from the UK reported estimate of 25.8% by the age of 1 year and 28.1% by the age of 3 years (85-87). The lowest (1.6%) and highest (38.7%) point prevalence of FA were reported in Italy (20) and Norway (52), respectively (Figure E1). The lowest and highest life-time prevalence of FA was found in Turkey (5.7%) (59) and Poland (41.8%) (53), respectively (Table E3). The range of point prevalence of self-reported FAfor all age groups was 1.6% to 38.7% and the highest point prevalence was found in the age group 2-5 years (Table 1). The range of life-time prevalence of self-reported FA for all age groups was 5.7% to 41.8% and the highest life-time prevalence was found in the age group 6-10 years (Table E3).
FA by positive SPT or IgE to specific food allergens: details of studies
Of the 18 studies (17-19,27-29,35-42,47,50-52,61-64,67-70,76,77,81,82,85-88) that defined FA by means of specific sensitization (positive SPT or IgE) to food allergens, 12 were undertaken among children (Table E4). The frequency of FA as defined by positive specific-IgE was generally higher than corresponding positive SPT, and often the correlation between the two types of tests was low. The cumulative incidence of positive SPT or specific-IgE to at least one food by the age of 4 years was reported to be 5.5% in Finland (69). The cumulative incidence of positive specific-IgE by 6 years was 47.3% in Denmark (27-29), while that of positive SPT was 5.3% by the age of 3 years in the UK (Table E4) (85-87). The point prevalence of positive SPT to at least one food was lowest in France (1.8%) (67) and highest in the UK (7.7%) (88). In general, the point prevalence of SPT positivity was highest in Northern Europe than other regions (Figure E3), with only one study each being undertaken in Western and Southern Europe. No study was found from Eastern Europe on FA by SPT positivity to any specific food allergen. Studies on specific-IgE positivity to food allergens were from only Northern and Western Europe. The point prevalence of positive specific-IgE was lowest in Finland (2.0%) (41) and highest in Germany, Italy, Norway, and Denmark (each country having approximately 22%) (Table E4) (18). In general, the point prevalence was higher in Western than in Northern Europe (Figure E2), although only
one study was undertaken in Western Europe. The range of the prevalence of positive SPT positivity for all age groups was 1.8% to 6.1%, with the highest prevalence in the age group the 6-10 years; that of positive specific-IgE ranged from 2.0% to 52.0%, the age group 6-17 also having the highest prevalence (Table 1).
FA defined by symptoms plus allergic sensitization and by clinical history or food challenge
Nine studies (23,48,53,60,67,68,78-80,85-88) defined FA based on symptoms plus sensitization (SPT and IgE) to specific food allergens (n=5) or based on convincing clinical history or positivity to food challenge (OFC or DBPCFC) (n=4) (Table E5). All of these studies were among children and a majority from Northern Europe (n=6) (23,48,53,68,85-88). FA based on symptoms plus sensitization involved subjects who were symptomatic for FA (usually by self-report) and subsequently had positive results when they underwent SPT or IgE tests. On the other hand, FA based on clinical history or food challenge was defined as either having a convincing clinical history (without any food challenge) or being positive with food challenge.
The pooled point prevalence of symptoms plus positive IgE to at least one food was similar in Northern and Western Europe (Figure 3). The lowest (2.2%) and highest (4.6%) point prevalence of symptoms plus positive specific-IgE to at least one food were both found in Germany (78-80). The range of the point prevalence of symptoms plus positive specific-IgE by age group was 1.3% to 4.6%, those 1 year and less having the lowest frequency (Table 1).
The point prevalence of symptoms plus SPT positivity was just highest in Southern Europecompared toother regions (Figure 4). The lowest point prevalence was found in France (0.1%) (66) and the highest in Germany (13.1%) (77-79). The range of the point prevalence of symptoms plus positive SPT by age group was0.1% to 13.1%, the age groups 6-10 and 11-17 years having the lowest estimates.
The overall pooled point prevalence of clinical history or food challenge positivity was lowest in the UK (1.1%) (87) and highest in Norway (6.8%) (53) (Table E5). The range of the point prevalence of clinical history or food challenge by age group was 1.1% to 6.8%, the age group 2-5 years having the highest frequency (Table 1). Differences may be explained by the use of
-
Epidemiology of food allergy in Europe: a review
E-8 EAACI Supplementary materials
OFC versus DBPCFC.
There was significant heterogeneity between the studies (P < 0.05 for I2) despite stratification by age and region.
Challenge-verified FA: details of studies
Of the 12 primary studies (23,27-29,34,48,60,65,66,68-70,78-80,85-88) that assessed FA by performing food challenge (OFC or DBPCFC), eight only included children (23,27-29,48,60,68-70,85-88) and nine came from Northern Europe (23,27-29,48,65,66,68-70,85-88), two from Southern Europe (34,60), and one from Western Europe (78-80) (Table E6). Three of the studies reported cumulative incidence of challenge positive FA by 1 year (1.5% [95% CI 0.9-2.5]) (27-29), by 4 years (3.3% [95% CI 2.8-3.9]) (69,70), and by 6 years (3.6% [95% CI 2.3-5.4]) (85-87). The lowest point prevalence of challenge-verified FA was found in the UK (almost zero per cent) (85-87) while the highest was found in Germany (5.7%) (78-80) (Table E6). The range of the point prevalence of challenge-verified FA was from 0% to 5.7%, with the age group 11-17 having the highest frequency (Table 1). There was significant heterogeneity between the
studies (P < 0.05 for I2) even after stratification by age and region.
Cumulative incidence
Only one of the nine studies in these categories reported estimates for cumulative incidence (84-86), showing that the cumulative incidence of FA by the age of 3 years was 6.0% (95% CI 4.6-6.7) based on clinical history or OFC positivity and 5.0% (95% CI 3.8-6.5) based on clinical history or DBPCFC positivity.
Risk and prognostic factors for FAAlthough a number of the reviewed studies examined the risk and prognostic factors for self-reported FA and sensitization to specific food allergen, a priori, we were interested in studying the risk and prognostic factors for clinician-diagnosed or objectively-verified FA, which is expected to give stronger evidence for causality and would be more meaningful for clinical intervention. Thirteen studies (22,24-26,32,34,40,46,53,58,68-70,73,84-87) were found of which 11 were among children (Table 3). Due to several methodological differences between the studies, they were not combined in a meta-analysis.
-
E-9EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
Tabl
e E1
The
mai
n fe
atur
es, m
ain
resu
lts o
f fre
quen
cy o
f FA
, and
ove
rall
risk
of b
ias
asse
ssm
ent o
f the
stu
dies
incl
uded
in th
e sy
stem
atic
revi
ew
on th
e ep
idem
iolo
gy o
f FA
in E
urop
e: s
tudi
es p
ublis
hed
1 J
anua
ry 2
00
0 -
30
Sep
tem
ber
20
12
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Ban
t et a
l. 2
00
8,
Pola
nd
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
15
61
8-2
7
year
s ol
dA
ny fo
od a
llerg
enSP
T, s
IgE
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
ast
le
ast o
ne F
A: 1
1%
Mod
erat
e
Bur
ney
et a
l. 2
01
0; W
oods
et
al. 2
00
1, E
urop
e,
Uni
ted
Stat
es
of A
mer
ica,
A
ustr
alia
, New
Ze
alan
d
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
17
28
02
0-4
4
yrs
old
Any
FA
, fish
, egg
, cow
’s
milk
, mus
tard
, mel
on, p
op-
py s
eed,
soy
a, s
unflo
wer
, w
alnu
t, ba
nana
, pea
nut,
buck
whe
at, r
ice,
tom
ato,
co
rn, c
eler
y, k
iwifr
uit,
car-
rot,
sesa
me,
app
le, w
heat
, sh
rim
p, p
each
, haz
elnu
t
Self-
repo
rted
, sI
gE
Poin
t and
lif
e-tim
e pr
eval
ence
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
at
leas
t one
FA
for
all
coun
trie
s 1
2.3
%
Mod
erat
e
Caffa
relli
et a
l. 2
01
1, I
taly
Cros
s-se
ctio
nal
stud
y9
00
62
55
-14
ye
ars
old
Any
FA
, cow
’s m
ilk,
egg,
tom
ato,
pea
nut,
whe
at, c
hoco
late
, kiw
i, st
raw
berr
y, m
elon
, or
ange
, haz
elnu
t, se
sam
e
Self-
repo
rted
Poin
t and
lif
e-tim
e pr
eval
ence
Poin
t pre
vale
nce
of
self-
repo
rted
FA
:1
.6%
(0.9
-2.9
)M
oder
ate
Chaf
en e
t al.
20
10
, Wor
ld-
wid
e
Syst
emat
ic
revi
ew
12
37
8
stud
ies
iden
tified
72
stu
dies
in
clud
edA
ll ag
e gr
oups
Cow
’s m
ilk, e
gg, p
eanu
t, fis
h, s
hellfi
sh
Self-
repo
rted
, ph
ysic
ian-
diag
nosi
s, S
PT,
sIgE
, OFC
, D
BPC
FC
Poin
t, pe
riod
, lif
e-tim
e pr
eval
ence
; cu
mul
ativ
e in
cide
nce,
in
cide
nce
rate
The
sam
e fr
eque
ncy
estim
ates
as
give
n in
Ro
na e
t al.
20
07
Stro
ng
Colv
er e
t al.
20
05
, UK
and
Ir
elan
d
Cros
s-se
ctio
nal
stud
y 1
30
28
93
31
30
28
93
3Ch
ildre
n<
16
ye
ars
Any
food
alle
rgic
re
actio
nPh
ysic
ian
diag
nosi
sPo
int
prev
alen
ce
Freq
uenc
y es
timat
es
not o
btai
nabl
e fr
om
the
stud
yM
oder
ate
Du
Toit
et a
l. 2
00
8, U
K a
nd
Isra
el
Cros
s-se
ctio
nal
stud
y1
07
86
88
26
4-1
8
year
s ol
d
Pean
ut, s
esam
e, tr
ee
nuts
, egg
, milk
Self-
repo
rted
, cl
inic
al h
isto
ry,
OFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of D
B-
PCFC
-con
firm
ed p
eanu
t al
lerg
y: 0
.4%
(0.3
-0.6
) in
UK
and
Isra
el
Mod
erat
e
Dub
akie
ne e
t al.
20
12
, Lith
uani
aCo
hort
st
udy
15
58
15
58
6-1
2
mon
ths
old
Any
FA
, milk
, egg
, whe
at,
pean
ut, p
otat
o, a
nd fi
sh
Self-
repo
rted
, SP
T, s
IgE,
D
BPC
FC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
FA: 0
.3%
(0.1
-0.7
)M
oder
ate
-
Epidemiology of food allergy in Europe: a review
E-10 EAACI Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Egge
sbø
et a
l. 2
00
3, 2
00
1a
and
20
01
b,
Nor
way
Coho
rt
stud
y4
97
33
75
42
.5
year
s ol
d
Any
FA
, cow
’s m
ilk,
hen’
s eg
g, fi
sh, n
uts,
ce
real
s, c
hoco
late
, fru
its,
vege
tabl
es
Self-
repo
rted
, ph
ysic
ian
diag
nosi
s, S
PT,
sIgE
, OFC
, D
BPC
FC
Poin
t pr
eval
ence
, cu
mul
ativ
e in
cide
nce
Poin
t pre
vale
nce
of
OFC
/DBP
CFC-
confi
rmed
eg
g al
lerg
y 0
.3%
(0.2
-0
.6) a
nd m
ilk a
llerg
y 0
.4%
(0.2
-0.7
)
Mod
erat
e
Elle
r et
al.
20
09
, K
jaer
et a
l. 2
00
8,
John
ke e
t al.
20
06
, Den
mar
k
Coho
rt
stud
y1
09
55
62
6 y
ears
ol
d
Any
FA
, cow
’s m
ilk, h
en’s
eg
g, p
eanu
t, w
heat
, co
dfish
, so
y, s
hrim
p, h
a-ze
lnut
, Bra
zil n
ut, c
eler
y
Self-
repo
rted
, SP
T, s
IgE,
OFC
, D
BPC
FC
Poin
t pr
eval
ence
, cu
mul
ativ
e in
cide
nce
Poin
t pre
vale
nce
of O
FC/
DB
PCFC
-co
nfirm
ed F
A a
t 6
year
s: 1
.2%
(0.5
-2.9
)
Mod
erat
e
Falc
aõ e
t al.
20
04
,Po
rtug
al
Cros
s-se
ctio
nal
stud
y1
56
56
59
>3
9
year
s ol
d
Any
FA
, fre
sh fr
uits
, m
eat,
fish,
egg
s, o
ctop
us
and
squi
d, c
hoco
late
, m
ilk, s
pice
s, le
gum
es
Self-
repo
rted
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
self-
repo
rted
FA
: 5
.2%
(3.7
-7.1
)M
oder
ate
Flok
stra
-de
Blo
k et
al.
20
11
, The
N
ethe
rland
s
Cros
s-se
ctio
nal
stud
y
No
info
rmat
ion
22
84
11
-20
ye
ars
old
Any
FA
Self-
repo
rted
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
self-
repo
rted
FA
: 2
.1%
(1.6
-2.8
)W
eak
Fox
et a
l. 2
00
9,
UK
Case
-co
ntro
l st
udy
13
3 c
ases
, 3
10
co
ntro
ls
13
3 c
ases
, 3
10
con
trol
s<
4
year
sPe
anut
alle
rgy
SPT,
sIg
E,
DB
PCFC
Poin
t pr
eval
ence
Case
-con
trol
stu
dy:
freq
uenc
y es
timat
es
not g
iven
Mod
erat
e
Fron
gia
et a
l 2
00
5, I
taly
Cros
s-se
ctio
nal
stud
y5
04
04
60
21
-2
year
s ol
d
Any
FA
, pea
nut,
egg,
m
ilk, t
omat
oSe
lf-re
port
edLi
fetim
e pr
eval
ence
Life
time
prev
alen
ce
of F
A: 7
.8%
(7.0
-8
.6)
Mod
erat
e
Gel
inci
k et
al.
20
08
, Tur
key
Cros
s-se
ctio
nal
stud
y1
70
64
11
81
6≥
18
ye
ars
old
Any
FA
, any
non
-alle
rgic
fo
od h
yper
sens
itivi
ty, t
o-m
atoe
s, h
en’s
egg
, cac
ao,
oran
ge, e
ggpl
ant,
pean
ut,
stra
wbe
rry,
car
rot,
bana
na,
haze
lnut
, pea
r, s
pina
ch,
red
chili
, bla
ck p
eppe
r,
food
add
itive
s, c
hoco
late
, w
alnu
t, po
tato
, fish
Self-
repo
rted
, SP
T, s
IgE,
D
BPC
FC
Poin
t and
lif
e-tim
e pr
eval
ence
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
FA: 0
.1%
(0.1
-0.2
)M
oder
ate
Gru
ndy
et a
l. 2
00
2, U
KCo
hort
st
udy
28
58
12
73
3-4
ye
ars
old
Pean
ut a
llerg
ySe
lf-re
port
, SPT
, O
FCPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
OFC
-con
firm
ed p
eanu
t al
lerg
y: 0
.6%
(0.3
-1.2
)M
oder
ate
Tabl
e E1
(co
ntin
ued)
-
E-11EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Gup
ta e
t al.
20
07
, 20
04
, 2
00
3, U
K
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
Not
indi
cate
dA
ll ag
e gr
oups
Any
FA
Phys
icia
n di
agno
sis
Cum
ulat
ive
inci
denc
ePl
ease
see
resu
lts in
Ta
ble
7 (t
ime
tren
ds)
Mod
erat
e
Høs
t et a
l. 2
00
2,
Den
mar
kCo
hort
st
udy
17
58
17
49
15
ye
ars
old
Any
FA
, cow
’s m
ilk
alle
rgy
SPT,
sIg
E, O
FC,
DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
hist
ory
or O
FC/D
BP-
CFC-
confi
rmed
milk
al
lerg
y 2
.2%
(1.6
-3.0
)
Mod
erat
e
Hou
riha
ne e
t al.
20
07
, UK
Cros
s-se
ctio
nal
stud
y5
07
21
12
54
-5
year
s ol
dPe
anut
alle
rgy
SPT,
sIg
E,
DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
pean
ut a
llerg
y: 1
.4%
(0
.8-2
.3)
Mod
erat
e
Isol
auri
et a
l. 2
00
4, F
inla
nd
Cros
s-se
ctio
nal
stud
y4
00
4
00
7, 2
7,
47
, 67
ye
ars
Any
FA
, milk
Self-
repo
rted
, sI
gE
Life
time
prev
alen
ce
and
poin
t pr
eval
ence
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
at
leas
t one
FA
at 6
7
year
s: 9
% (5
-18
)
Mod
erat
e
Joha
nsso
n et
al.
20
05
, Sw
eden
an
d N
orw
ay
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
Swed
en 1
00
2;
Nor
way
50
0A
dults
Any
FA
, pea
nut,
soya
be
an, e
gg w
hite
, cow
’s
milk
, cod
fish
, whe
at fl
our,
pe
nici
lloyl
G, s
uxam
etho
ni-
um, l
atex
, haz
el n
ut
sIgE
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
at
leas
t one
FA
for
both
N
orw
ay a
nd S
wed
en
3.6
% (2
.8-4
.7)
Mod
erat
e
Julg
e et
al.
20
01
, Vas
ar e
t al
. 20
00
, Est
onia
Coho
rt
stud
y4
55
29
85
yea
rsEg
g w
hite
, cow
’s m
ilkSP
T, s
IgE
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
SPT
posi
tivity
to e
gg
at 5
yea
rs 0
% a
nd
sIgE
pos
itivi
ty to
egg
at
5 y
ears
2.4
%
Mod
erat
e
Kan
ny e
t al.
20
01
, Fra
nce
Cros
s-se
ctio
nal
stud
y4
40
00
31
11
0≤
60
ye
ars
Any
FA
Self-
repo
rted
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of s
elf-
repo
rted
FA
3
.5%
(3.3
-3.7
)M
oder
ate
Kot
z et
al.
20
11
, U
KCo
hort
st
udy
29
58
36
62
95
83
66
All
age
grou
psPe
anut
alle
rgy
Ph
ysic
ian
diag
nosi
s
Life
-tim
e pr
eval
ence
, in
cide
nce
rate
Plea
se s
ee re
sults
in
Tabl
e 7
(tim
e tr
ends
)M
oder
ate
Kra
use
et a
l. 2
00
2, G
reen
land
Cros
s-se
ctio
nal
stud
y1
21
31
06
85
-18
ye
ars
old
Any
FA
, egg
, milk
, fish
, pe
anut
, whe
at, s
oysI
gEPo
int
prev
alen
ce
Poin
t pre
vale
nce
of s
IgE
posi
tivity
to a
t lea
st o
ne
FA: 4
.1%
(3.0
-5.5
)M
oder
ate
Tabl
e E1
(co
ntin
ued)
-
Epidemiology of food allergy in Europe: a review
E-12 EAACI Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Kri
stin
sdot
tir e
t al
. 20
11
, Ice
land
Coho
rt
stud
yN
o in
form
atio
n1
34
11
yea
r ol
d
Any
FA
, hen
’s e
gg, c
ow’s
m
ilk, p
eanu
t, fis
h, w
heat
, so
y, s
hrim
p, c
ranb
erry
, po
tato
, pin
eapp
le, a
lmon
d,
nutr
amig
en, g
reen
pea
s
Self-
repo
rted
, SP
T, s
peci
fic
sIgE
, DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
FA: 1
.9%
(1.3
-2.7
)M
oder
ate
Kuc
ukos
man
oglu
et
al.
20
08
, Tu
rkey
Cros
s-se
ctio
nal
stud
y1
41
51
01
58
-18
m
onth
sEg
g al
lerg
ySP
TPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
SPT
posi
tivity
to e
gg
1.9
% (1
.2-2
.9)
Mod
erat
e
Kur
ulaa
ratc
hy e
t al
. 20
05
, Ars
had
et a
l. 2
00
1, T
ariq
et
al.
20
00
, UK
Coho
rt
stud
y1
53
61
45
64
yea
rs
old
Any
FA
, milk
, egg
, pe
anut
, cod
, whe
at, s
oya
SPT
Poin
t pr
eval
ence
, cu
mul
ativ
e in
cide
nce
Poin
t pre
vale
nce
of
SPT
posi
tivity
to a
t le
ast o
ne F
A: 3
.5%
Mod
erat
e
Kven
shag
en e
t al.
20
09
, Nor
way
Coho
rt
stud
yN
ot
indi
cate
d6
09
2 y
ears
ol
dA
ny F
A, e
gg, m
ilk,
pean
ut, h
azel
nut
Self-
repo
rted
, SP
T, s
IgE,
OFC
, D
BPC
FC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
Clin
ical
his
tory
or
OFC
/DB
PCFC
FA
6
.8%
(5.0
-9.4
)
Mod
erat
e
Maj
kow
ska-
Woj
ciec
how
ska
et
al. 2
00
9, P
olan
d
Cros
s-se
ctio
nal
stud
y 3
26
02
14
87
-10
ye
ars
old
Any
FA
, milk
, cho
cola
te,
dair
y, s
traw
berr
ies,
egg
s,
tom
atoe
s, c
ocoa
, nut
s,
frui
ts, o
rang
es
Self-
repo
rted
Life
-tim
e pr
eval
ence
Life
-tim
e pr
eval
ence
of
FA
41
.6%
(39
.5-
43
.7)
Mod
erat
e
Mar
klun
d et
al.
20
04
, Sw
eden
Cros
s-se
ctio
nal
stud
y2
06
41
48
81
3-2
1
year
s ol
d
Any
food
hy
pers
ensi
tivity
Se
lf-re
port
edPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
self-
repo
rted
FA
: 1
8.7
% (1
6.8
-20
.8)
Mod
erat
e
Mat
rica
rdi e
t al.
20
07
, Ger
man
yCo
hort
st
udy
76
09
13
14
2-1
0
year
s ol
d
Cow
’s m
ilk, h
en’s
egg
, so
y, a
nd w
heat
sIgE
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
at
leas
t one
FA
at 1
0
year
s: m
ilk 1
.0%
(0
.5-2
.3),
egg
0.9
%
(0.4
-2.0
), so
y 6
.1%
(4
.4-8
.3),
whe
at
8.8
% (6
.8-1
1.4
)
Mod
erat
e
Mos
sako
wsk
a et
al
. 20
08
, Pol
and
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
30
1>
10
0
year
s ol
d
Stra
wbe
rrie
s, b
anan
as, o
r-an
ges,
egg
s, p
eppe
r, ga
rlic,
ch
amom
ile, i
ce c
ream
Self-
repo
rted
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
FA: 3
.3%
(1.8
-6.0
)M
oder
ate
Tabl
e E1
(co
ntin
ued)
-
E-13EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Nic
olao
u et
al.
20
10
, UK
Coho
rt
stud
y1
49
91
08
58
yea
rs
old
Pean
ut, m
ilk, e
gg, fi
sh,
tree
nut
Self-
repo
rted
, SP
T, s
IgE,
OFC
, D
BPC
FC
Poin
t and
lif
etim
e pr
eval
ence
Poin
t pre
vale
nce
of O
FC-c
onfir
med
pe
anut
alle
rgy:
0.7
%
(0.3
-1.4
)
Mod
erat
e
Nig
gem
ann
et a
l. 2
01
1, G
erm
any
Cros
s-se
ctio
nal
stud
y2
67
87
17
64
10
-17
ye
ars
old
Pean
ut a
llerg
ysI
gEPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
pea
-nu
t alle
rgen
10
.9%
Mod
erat
e
Orh
an e
t al.
20
09
, Tur
key
Cros
s-se
ctio
nal
stud
y3
50
02
73
96
-9
year
s ol
d
Any
FA
, coc
oa, h
en’s
egg
, be
ef, c
ow’s
milk
, fish
, to-
mat
o, h
azel
nut,
kiw
i, bl
ack
pepp
er, c
hick
pea,
pea
nut,
wal
nut,
corn
, ban
ana,
st
raw
berr
y, p
otat
o
Self-
repo
rted
, SP
T, O
FC,
DB
PCFC
Life
-tim
e an
d po
int
prev
alen
ce
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
FA 0
.7%
(0.5
-1.1
)M
oder
ate
Öst
blom
et a
l. 2
00
8a,
20
08
b,
20
08
c an
d A
lmqv
ist e
t al.
20
05
, Sw
eden
Coho
rt
stud
y7
22
14
08
94
-8
year
s ol
d
Any
FA
, cow
’s m
ilk, c
itrus
, pe
anut
, tre
e nu
ts/a
lmon
d,
hen’
s eg
g, s
tone
frui
t, ch
oc-
olat
e, fi
sh, p
ea, s
oy b
ean,
w
heat
, ban
ana,
cod
fish
Self-
repo
rted
, sI
gE
Poin
t and
pe
riod
pr
eval
ence
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
at
leas
t one
FA
at 8
ye
ars:
13
.8%
(12
.5-
15
.4)
Mod
erat
e
Ost
erba
lle e
t al.
20
09
, Den
mar
k
Cros
s-se
ctio
nal
stud
y1
09
48
43
Mea
n ag
e 2
2
year
s
Any
FA
, ad
ditiv
es, c
odfis
h,
cow
’s m
ilk, h
en’s
egg
, oc
topu
s, p
eanu
t, sh
rim
p,
soy,
whe
at,
beer
, che
ese,
re
d w
ine
(oth
er s
econ
dary
fo
od a
llerg
ies
also
repo
rt-
ed in
the
pape
r
Self-
repo
rted
, SP
T, O
FC,
DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of O
FC/D
BPC
FC-
confi
rmed
FH
S: 1
.8%
(1
.1-2
.9)
Mod
erat
e
Ost
erba
lle e
t al.
20
05
, Den
mar
kCo
hort
st
udy
Not
in
dica
ted
18
34
Child
ren
and
adul
ts
Any
FA
, add
itive
s,
codfi
sh, c
ow’s
milk
, hen
’s
egg,
pea
nut,
shri
mp,
soy
, w
heat
, fru
it/ve
geta
bles
Self-
repo
rted
, ph
ysic
ian
diag
nosi
s, S
PT,
sIgE
, OFC
, D
BPC
FC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
OFC
/DB
PCFC
-con
-fir
med
FH
S: a
t 3 y
ears
2
.3%
(1.3
-4.0
); ad
ults
3
.2%
(2.3
-4.5
)
Mod
erat
e
Pena
rd-M
oran
d et
al.
20
05
, Fr
ance
Cros
s-se
ctio
nal
stud
y9
61
57
78
19
-11
ye
ars
old
Any
FA
, nut
s, fr
uits
or
vege
tabl
es, e
gg, m
ilk,
pean
ut, fi
sh, s
eafo
od
Self-
repo
rted
, SP
TPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
sym
ptom
s pl
us S
PT
posi
tivity
to a
t lea
st o
ne
FA: 0
.1%
(0.1
-0.3
)
Mod
erat
e
Tabl
e E1
(co
ntin
ued)
-
Epidemiology of food allergy in Europe: a review
E-14 EAACI Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Pere
ira e
t al.
20
05
, UK
Cros
s-se
ctio
nal
stud
y3
14
41
53
21
1 a
nd
15
yea
r ol
d
Any
FA
, milk
, egg
, whe
at,
fish,
pea
nut,
sesa
me,
tr
ee n
uts,
add
itive
s,
shel
lfish
Self-
repo
rted
, ph
ysic
ian
diag
nosi
s, S
PT,
OFC
, DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
for
all c
hild
ren:
OFC
-con
-fir
med
FA
2.3
% (1
.6-
3.2
) DB
PCFC
-con
-fir
med
1.8
% (1
.2-2
.6
Mod
erat
e
Pyrh
önen
et a
l. 2
01
1 a
nd 2
00
9,
Finl
and
Coho
rt
stud
y 5
97
33
89
90
-4
year
s ol
d
Any
FA
, milk
, egg
, whe
at,
barle
y or
rye
, nu
t, fis
h,
citr
us fr
uit
Self-
repo
rted
, ph
ysic
ian-
diag
nosi
s, S
PT,
sIgE
, OFC
Life
-tim
e pr
eval
ence
, cu
mul
ativ
e in
cide
nce
Life
time
prev
alen
ce o
f se
lf-re
port
ed p
hysi
-ci
an-d
iagn
osed
FA
3
0.3
% (2
8.7
-31
.9)
Cum
ulat
ive
inci
denc
e of
O
FC-c
onfir
med
FA
by
4
year
s: 3
.3%
(2.8
-3.9
)
Mod
erat
e
Pyzi
ak a
nd
Kam
er 2
01
1,
Pola
nd
Cros
s-se
ctio
nal
stud
y1
15
83
6-1
7
year
s ol
d
Any
FA
, cow
’s m
ilk, h
en’s
eg
g, s
oy, p
ork,
bee
fSe
lf-re
port
ed,
sIgE
, SPT
, OFC
Poin
t pr
eval
ence
Freq
uenc
y es
timat
es
not g
iven
in th
e st
udy
Mod
erat
e
Ran
ce e
t al.
20
05
, Fra
nce
Cros
s-se
ctio
nal
stud
y3
50
02
71
6M
ean
age
8.9
ye
ars
Any
FA
, cow
’s m
ilk, e
gg,
kiw
i, pe
anut
, fish
, tre
e nu
t, sh
rim
pSe
lf-re
port
edPo
int a
nd
life-
time
prev
alen
ce
Poin
t pre
vale
nce
of
self-
repo
rted
FA
: 4.7
(3
.9-5
.5)
Mod
erat
e
Robe
rts
et a
l. 2
00
5 a
nd L
ack
et a
l. 2
00
3, U
K
Coho
rt
stud
y1
39
71
12
09
0
0-7
ye
ars
Egg,
milk
, cod
fish
, soy
a,
sesa
me,
pea
nut,
tree
nut
, ca
shew
, alm
ond,
wal
nut,
haze
lnut
, bra
zil n
ut, p
ecan
nu
t
Self-
repo
rted
, SP
T, D
BPC
FCPo
int
Prev
alen
ce
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
pean
ut a
llerg
y: 0
.2%
(0
.1-0
.3)
Mod
erat
e
Rona
et a
l. 2
00
7,
Wor
ld-w
ide
Syst
emat
ic
revi
ew9
34
stu
dies
id
entifi
ed
Num
ber
of s
tudi
es
incl
uded
in
revi
ew n
ot
indi
cate
d
All
age
grou
ps
Any
FA
, cow
’s m
ilk,
hen’
s eg
g, p
eanu
t, fis
h,
shel
lfish
Self-
repo
rted
, ph
ysic
ian-
diag
nosi
s, S
PT,
sIgE
, OFC
, D
BPC
FC
Poin
t, pe
riod
, lif
e-tim
e pr
eval
ence
, cu
mul
ativ
e in
cide
nce
and
inci
denc
e ra
te
Ran
ge o
f pre
vale
nce
of S
PT o
r sI
gE to
at
leas
t one
FA
: 2%
-5%
SPT
only
: 7%
-17
%
IgE
only
: 4%
-6%
Mod
erat
e
Ronc
hett
i et a
l. 2
00
8, I
taly
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
38
0
9 a
nd
13
ye
ars
old
Any
FA
, cow
’s m
ilk, h
en’s
eg
g, to
mat
o, w
heat
flou
rSP
TPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
SPT
posi
tivity
to a
t le
ast o
ne F
A fo
r all
chil-
dren
4.2
% (2
.6-6
.7)
Mod
erat
e
Tabl
e E1
(co
ntin
ued)
-
E-15EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Sand
in e
t al.
20
05
, Sw
eden
an
d Es
toni
a
Case
-co
ntro
l st
udy
All
98
5Sw
eden
6
45
Esto
nia
34
0
All
77
0Sw
eden
48
3Es
toni
a 2
87
10
-11
ye
ars
old
Any
FA
; app
le, p
each
, ki
wi,
or c
arro
t; nu
t or
pea
nut;
oran
ge,
man
dari
n or
tom
ato;
m
ilk, e
gg, fi
sh o
r w
heat
Self-
repo
rt, s
IgE
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of s
IgE
posi
tivity
to
at le
ast o
ne F
A fo
r Es
toni
a an
d Sw
eden
1
3.9
% (1
1.3
-16
.9)
Mod
erat
e
Schä
fer
et a
l. 2
00
1, G
erm
any
Nes
ted
case
-co
ntro
l st
udy
25
39
15
37
25
-74
Any
FA
Self-
repo
rted
, SP
T
Poin
t pr
eval
ence
, lif
etim
e pr
eval
ence
Poin
t pre
vale
nce
of S
PT
posi
tivity
to a
t lea
st o
ne
FA in
the
popu
latio
n of
the
alle
rgy
MO
NIC
A
stud
y: 1
6.8
%
Mod
erat
e
Schn
abel
et a
l. 2
01
0, G
erm
any
Coho
rt
stud
y3
09
71
08
26
yea
rs
old
Any
FA
Self-
repo
rted
, sI
gEPo
int
prev
alen
ce
Poin
t pre
vale
nce
of
sIgE
pos
itivi
ty to
at
leas
t one
FA
at 6
ye
ars:
11
.7%
(10
.0-
13
.8)
Mod
erat
e
Soos
t et a
l. 2
00
9
and
Zube
rbie
r et
al
. 20
04
, Roe
hr
et a
l. 2
00
4,
Ger
man
y
Cros
s-se
ctio
nal
stud
y1
33
00
All:
40
93
Age
0-1
7
year
s: 7
39
Age
18
-79
ye
ars:
32
27
0-7
9
year
s ol
d
Any
FA
, veg
etab
les,
leg-
umes
, soy
, spi
ces,
fish
, ce
real
s, m
eat a
nd fa
t, st
onef
ruit,
cho
cola
te/
swee
ts, c
ow’s
milk
, hen
’s
egg,
pip
frui
t, nu
ts, v
eg-
etab
le o
il, c
arro
t, ce
lery
, se
sam
e, a
pple
, app
le,
haze
lnut
, pot
ato,
whe
at,
pean
ut, w
alnu
t, sh
rim
p
Self-
repo
rted
, ph
ysic
ian
diag
nosi
s, S
PT,
sIgE
, OFC
, SB
PCFC
, DB
PCFC
Poin
t and
lif
e-tim
e pr
eval
ence
Poin
t pre
vale
nce
of O
FC/D
BPC
FC-
confi
rmed
FA
:A
ll: 2
.8%
(2.4
-3.4
)Ch
ildre
n: 4
.2%
(3.0
-5
.9)
Adu
lts: 2
.9%
(2.3
-3
.5)
Mod
erat
e
Stei
nke
et a
l. 2
00
7, E
urop
e
Cros
s-se
ctio
nal
stud
y
Not
in
dica
ted
40
42
6<
18
ye
ars
Any
FA
, fish
, sea
food
, w
heat
, mea
t, eg
gs,
milk
, fru
its, l
egum
es,
vege
tabl
es, n
uts
Self-
repo
rted
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
self-
repo
rted
FA
: A
ll co
untr
ies:
5.0
%
(4.5
-5.4
)
Mod
erat
e
Vent
er e
t al.
20
10
, UK
Coho
rt
stud
y5
28
33
38
23
-4
year
s ol
dPe
anut
alle
rgy
Phys
icia
n di
agno
sis,
SPT
, sI
gE, O
FC,
DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of O
FC-c
onfir
med
pe
anut
alle
rgy:
0.3
%
(0.1
-1.0
)
Mod
erat
e
Tabl
e E1
(co
ntin
ued)
-
Epidemiology of food allergy in Europe: a review
E-16 EAACI Supplementary materials
Refe
renc
e,
coun
try
Stud
y de
sign
Stud
y po
pula
tion
N (c
hild
ren/
adul
ts; s
ourc
e of
st
udy
popu
latio
n)A
ge o
f su
bjec
tsO
utco
me
stud
ied
and
asse
ssm
ent m
etho
dO
ccur
renc
e m
easu
re(s
)
Mai
n re
sults
of t
he
freq
uenc
y of
FA
(FA
)Pe
rcen
tage
(95
% C
I)
Ove
rall
risk
of b
ias
asse
ssm
ent
Num
ber
appr
oach
edN
umbe
r pa
rtic
ipat
edO
utco
me(
s) s
tudi
edM
etho
d of
out
-co
me
asse
ssm
ent1
Vent
er a
l 20
08
; D
ean
et a
l. 2
00
7;
Vent
er e
t al.
20
06
, UK
Coho
rt
stud
y1
06
39
69
3 y
ears
ol
dA
ny F
A, m
ilk, e
gg, fi
sh,
pean
ut, s
esam
e, w
heat
Self-
repo
rt, S
PT,
OFC
, DB
PCFC
Poin
t and
pe
riod
pr
eval
ence
, cu
mul
ativ
e in
cide
nce
Poin
t pre
vale
nce
of
OFC
-con
firm
ed F
A
at 3
yea
rs: 0
.8%
(0
.4-1
.6)
Mod
erat
e
Vent
er e
t al.
20
06
, UK
Cros
s-se
ctio
nal
stud
y1
44
07
98
6 y
ears
ol
d
Any
FA
, milk
, pea
nut,
egg,
add
itive
s &
col
our-
ings
, tre
e nu
ts, w
heat
, st
raw
berr
y, s
esam
e, fi
sh,
choc
olat
e, b
anan
a
Self-
repo
rt, S
PT,
OFC
, DB
PCFC
Poin
t pr
eval
ence
Poin
t pre
vale
nce
of
OFC
-con
firm
ed F
A
1.3
% (0
.7-2
.3) a
nd
DB
PCFC
-con
firm
ed
FA 0
.4%
(0.1
-1.1
)
Mod
erat
e
von
Her
tzen
et
al. 2
00
6, F
inla
nd
and
Rus
sia
Cros
s-se
ctio
nal
stud
y
Finl
and:
5
46
chi
ld-
mot
her
pair
s
Finl
and:
41
3
child
ren,
40
9
mot
hers
7-1
6
year
s ch
ildre
n
Fish
, egg
, whe
at, c
ow’s
m
ilk, p
eanu
t, ha
zeln
utSP
TPo
int
prev
alen
ce
Poin
t pre
vale
nce
of S
PT p
ositi
vely
to
pea
nut a
llerg
en:
child
ren:
8.2
%
(5.8
-11
.5),
mot
hers
: 1
0.1
% (7
.4-1
3.6
)
Mod
erat
e
Zuid
mee
r et
al.
20
08
, Wor
ld-
wid
e
Syst
emat
ic
revi
ew3
96
stu
dies
id
entifi
ed3
3 s
tudi
es
incl
uded
All
age
grou
psFr
uits
, veg
etab
les,
tree
nu
ts, s
oy, w
heat
Self-
repo
rted
, ph
ysic
ian-
diag
-no
sis,
SPT
, sIg
E,
OFC
, DB
PCFC
Poin
t, pe
riod
, and
lif
e-tim
e pr
eval
ence
Poin
t pre
vale
nce
of
DB
PCFC
-con
firm
ed
alle
rgy
to v
eget
able
s:
1.4
%
Mod
erat
e
DB
PCFC
: dou
ble-
blin
d, p
lace
bo-c
ontr
olle
d fo
od c
halle
nge;
OFC
: ora
l foo
d ch
alle
nge;
sIg
E: s
peci
fic im
mun
oglo
bulin
E te
st; S
PT: s
kin
pric
k te
st fo
r se
nsiti
zatio
n to
spe
cific
fo
od a
llerg
ens
Tabl
e E1
(co
ntin
ued)
-
E-17EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
Tabl
e E2
Qua
lity
asse
ssm
ent o
f stu
dies
incl
uded
in th
e sy
stem
atic
revi
ew: i
nclu
ded
stud
ies
1 J
anua
ry 2
00
0 -
30
Sep
tem
ber
20
12
Refe
renc
e, c
ount
ryO
vera
ll ri
sk o
f bia
s as
sess
men
t
Com
pone
nts
of r
isk
of b
ias
asse
ssm
ent
Stud
y de
sign
Sele
ctio
n bi
asEx
posu
re a
sses
smen
tO
utco
me
asse
ssm
ent
Ban
t et a
l. 2
00
8, P
olan
dM
oder
ate
Stro
ngW
eak
Not
app
licab
leM
oder
ate
Bur
ney
et a
l. 2
01
0; W
oods
et a
l. 2
00
1,
Euro
pe, U
SA, A
ustr
alia
, New
Zea
land
Mod
erat
eM
oder
ate
Mod
erat
eM
oder
ate
Mod
erat
e
Caffa
relli
et a
l. 2
01
1, I
taly
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Wea
k
Chaf
en e
t al.
20
10
, Wor
ld-w
ide
Stro
ngSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
Colv
er e
t al.
20
05
, UK
and
Irel
and
Mod
erat
eM
oder
ate
Wea
kM
oder
ate
Mod
erat
e
Du
Toit
et a
l. 2
00
8, U
K a
nd Is
rael
Mod
erat
eM
oder
ate
Mod
erat
eM
oder
ate
Stro
ng
Dub
akie
ne e
t al.
20
12
, Lith
uani
aM
oder
ate
Stro
ngM
oder
ate
Mod
erat
eSt
rong
Egge
sbø
et a
l. 2
00
3, 2
00
1a,
20
01
b, N
orw
ayM
oder
ate
Stro
ngM
oder
ate
Mod
erat
eSt
rong
Elle
r et
al.
20
09
, Kja
er e
t al.
20
08
, Joh
nke
et
al. 2
00
6, D
enm
ark
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
Falc
aõ e
t al.
20
04
, Por
tuga
lM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leW
eak
Flok
stra
-de
Blo
k et
al.
20
11
, The
Net
herla
nds
Wea
kSt
rong
Wea
kN
ot a
pplic
able
Wea
k
Fox
et a
l. 2
00
9, U
KM
oder
ate
Stro
ngM
oder
ate
Mod
erat
eSt
rong
Fron
gia
et a
l 20
05
, Ita
lyM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leW
eak
Gel
inci
k et
al.
20
08
, Tur
key
Mod
erat
eM
oder
ate
Wea
kM
oder
ate
Stro
ng
Gru
ndy
et a
l. 2
00
2, U
KM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leSt
rong
Gup
ta e
t al.
20
07
, 20
04
, 20
03
, UK
Mod
erat
eSt
rong
Wea
kN
ot a
pplic
able
Mod
erat
e
Høs
t et a
l. 2
00
2, D
enm
ark
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
Hou
riha
ne e
t al.
20
07
, UK
Mod
erat
eM
oder
ate
Wea
kM
oder
ate
Stro
ng
Isol
auri
et a
l. 2
00
4, F
inla
ndM
oder
ate
Stro
ngM
oder
ate
Mod
erat
e M
oder
ate
Joha
nsso
n et
al.
20
05
, Sw
eden
and
Nor
way
Mod
erat
eM
oder
ate
Wea
kN
ot a
pplic
able
Mod
erat
e
Julg
e et
al.
20
01
, Vas
ar e
t al.
20
00
, Est
onia
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Mod
erat
e
Kan
ny e
t al.
20
01
, Fra
nce
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Wea
k
-
Epidemiology of food allergy in Europe: a review
E-18 EAACI Supplementary materials
Refe
renc
e, c
ount
ryO
vera
ll ri
sk o
f bia
s as
sess
men
t
Com
pone
nts
of r
isk
of b
ias
asse
ssm
ent
Stud
y de
sign
Sele
ctio
n bi
asEx
posu
re a
sses
smen
tO
utco
me
asse
ssm
ent
Kot
z et
al.
20
11
, UK
Mod
erat
eM
oder
ate
Mod
erat
eM
oder
ate
Mod
erat
e
Kra
use
et a
l. 2
00
2, G
reen
land
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Mod
erat
e
Kri
stin
sdot
tir e
t al.
20
11
, Ice
land
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
Kuc
ukos
man
oglu
et a
l. 2
00
8, T
urke
yM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leM
oder
ate
Kur
ulaa
ratc
hy e
t al.
20
05
, Ars
had
et a
l. 2
00
1, T
ariq
et a
l. 2
00
0, U
KM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leM
oder
ate
Kven
shag
en e
t al.
20
09
, Nor
way
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Stro
ng
Maj
kow
ska-
Woj
ciec
how
ska
et a
l. 2
00
9,
Pola
ndM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leW
eak
Mar
klun
d et
al.
20
04
, Sw
eden
Mod
erat
e St
rong
M
oder
ate
Not
app
licab
leW
eak
Mat
rica
rdi e
t al.
20
07
, Ger
man
yM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leM
oder
ate
Mos
sako
wsk
a et
al.
20
08
, Pol
and
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Wea
k
Nic
olao
u et
al.
20
10
, UK
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Stro
ng
Nig
gem
ann
et a
l. 2
01
1, G
erm
any
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Mod
erat
e
Orh
an e
t al.
20
09
, Tur
key
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
Öst
blom
et a
l. 2
00
8a,
20
08
b, 2
00
8c;
A
lmqv
ist e
t al.
20
05
, Sw
eden
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Mod
erat
e
Ost
erba
lle e
t al.
20
09
, Den
mar
kM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leSt
rong
Ost
erba
lle e
t al.
20
05
, Den
mar
kM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leSt
rong
Pena
rd-M
oran
d et
al.
20
05
, Fra
nce
Mod
erat
eM
oder
ate
Mod
erat
eM
oder
ate
Mod
erat
e
Pere
ira e
t al.
20
05
, UK
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
Pyrh
önen
et a
l. 2
01
1 a
nd 2
00
9, F
inla
ndM
oder
ate
Mod
erat
eM
oder
ate
Mod
erat
eSt
rong
Pyzi
ak a
nd K
amer
20
11
, Pol
and
Mod
erat
e M
oder
ate
Wea
k M
oder
ate
Stro
ng
Ran
ce e
t al.
20
05
, Fra
nce
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Wea
k
Tabl
e E2
(co
ntin
ued)
-
E-19EAACI
Epidemiology of food allergy in Europe: a review
Supplementary materials
Refe
renc
e, c
ount
ryO
vera
ll ri
sk o
f bia
s as
sess
men
t
Com
pone
nts
of r
isk
of b
ias
asse
ssm
ent
Stud
y de
sign
Sele
ctio
n bi
asEx
posu
re a
sses
smen
tO
utco
me
asse
ssm
ent
Robe
rts
et a
l. 2
00
5 a
nd L
ack
et a
l. 2
00
3, U
KM
oder
ate
Stro
ngM
oder
ate
Mod
erat
eSt
rong
Rona
et a
l. 2
00
7, W
orld
-wid
eM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leSt
rong
Ronc
hett
i et a
l. 2
00
8, I
taly
Mod
erat
eM
oder
ate
Mod
erat
eN
ot a
pplic
able
Mod
erat
e
Sand
in e
t al.
20
05
, Sw
eden
and
Est
onia
Mod
erat
eM
oder
ate
Mod
erat
eN
ot a
pplic
able
Mod
erat
e
Soos
t et a
l. 2
00
9 a
nd Z
uber
bier
et a
l. 2
00
4,
Roeh
r et
al.
20
04
, Ger
man
yM
oder
ate
Mod
erat
eM
oder
ate
Mod
erat
eSt
rong
Schn
abel
et a
l. 2
01
0, G
erm
any
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Mod
erat
e
Schä
fer
et a
l. 2
00
1, G
erm
any
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Mod
erat
e
Stei
nke
et a
l. 2
00
7, E
urop
eM
oder
ate
Stro
ngM
oder
ate
Not
app
licab
leW
eak
Vent
er e
t al.
20
10
, UK
Mod
erat
eSt
rong
Mod
erat
eM
oder
ate
Stro
ng
Vent
er e
t al.
20
08
; Dea
n et
al.
20
07
; Ven
ter
et a
l. 2
00
6, U
KM
oder
ate
Stro
ngM
oder
ate
Mod
erat
eSt
rong
Vent
er e
t al.
20
06
, UK
Mod
erat
eSt
rong
Mod
erat
eN
ot a
pplic
able
Stro
ng
von
Her
tzen
et a
l. 2
00
6, F
inla
nd a
nd R
ussi
aM
oder
ate
Mod
erat
eM
oder
ate
Mod
erat
eM
oder
ate
Zuid
mee
r et
al.
20
08
, Wor
ld-w
ide
Mod
erat
eSt
rong
Wea
kN
ot a
pplic
able
Stro
ng
The
over
all r
top related