The Prevalence of Tree Nut Allergy: A Systematic Review

Abstract

Tree nuts are one of the most common foods causing acute allergic reactions and nearly all tree nuts have been associated with fatal allergic reactions. Despite their clinical importance, tree nut allergy epidemiology remains understudied and the prevalence of tree nut allergy in different regions of the world has not yet been well characterised. We aimed to systematically review the population prevalence of tree nut allergy in children and adults. We searched three electronic databases (OVID MEDLINE, EMBASE and PubMed) from January 1996 to December 2014. Eligible studies were categorised by age, region and method of assessment of tree nut allergy. Of the 36 studies identified most were in children (n = 24) and from Europe (n = 18), UK (n = 8) or USA (n = 5). Challenge-confirmed IgE-mediated tree nut allergy prevalence was less than 2 % (although only seven studies used this gold standard) while probable tree nut allergy prevalence ranged from 0.05 to 4.9 %. Prevalence estimates that included oral allergy syndrome (OAS) reactions to tree nut were significantly higher (8-11.4 %) and were predominantly from Europe. Prevalence of individual tree nut allergies varied significantly by region with hazelnut the most common tree nut allergy in Europe, walnut and cashew in the USA and Brazil nut, almond and walnut most commonly reported in the UK. Monitoring time trends of tree nut allergy prevalence (both overall and by individual nuts) as well as the prevalence of OAS should be considered given the context of the overall recent rise in IgE-mediated food allergy prevalence in the developed world.

Full text

FOOD ALLERGY (T GREEN, SECTION EDITOR)
The Prevalence of Tree Nut Allergy: A Systematic Review
Vicki McWilliam
1,2,4
&Jennifer Koplin
1,3
&Caroline Lodge
3
&Mimi Tang
1,2,4
&
Shyamali Dharmage
1,3
&Katrina Allen
1,2,4,5
Published online: 2 August 2015
#Springer Science+Business Media New York 2015
Abstract Tree nuts are one of the most common foods causing
acute allergic reactions and nearly all tree nuts have been asso-
ciated with fatal allergic reactions. Despite their clinical impor-
tance, tree nut allergy epidemiology remains understudied and
the prevalence of tree nut allergy in different regions of the
world has not yet been well characterised. We aimed to system-
atically review the population prevalence of tree nut allergy in
children and adults. We searched three electronic databases
(OVID MEDLINE, EMBASE and PubMed) from January
1996 to December 2014. Eligible studies were categorised by
age, region and method of assessment of tree nut allergy. Of the
36 studies identified most were in children (n=24) and from
Europe (n=18), UK (n=8)orUSA(n=5). Challenge-
confirmed IgE-mediated tree nut allergy prevalence was less
than 2 % (although only seven studies used this gold standard)
while probable tree nut allergy prevalence ranged from 0.05 to
4.9 %. Prevalence estimates that included oral allergy syn-
drome (OAS) reactions to tree nut were significantly higher
(8–11.4 %) and were predominantly from Europe. Prevalence
of individual tree nut allergies varied significantly by region
with hazelnut the most common tree nut allergy in Europe,
walnut and cashew in the USA and Brazil nut, almond and
walnut most commonly reported in the UK. Monitoring time
trends of tree nut allergy prevalence (both overall and by indi-
vidual nuts) as well as the prevalence of OAS should be con-
sidered given the context of the overall recent rise in IgE-
mediated food allergy prevalence in the developed world.
Keywords Tree nut allergy .Systematic review .Prevalence .
Epidemiology
Abbreviations
Primary tree
nut allergy
IgE-mediated allergic reaction upon exposure
to tree nuts that is due to a specific immune
response directed against tree nut allergens
Secondary
tree nut
allergy
IgE-mediated allergic reaction upon exposure
to tree nuts that is due to cross-reactivity of
specific IgE directed against non-tree nut
allergens
Tree nut
sensitisation
Presence of tree nut allergen-specific IgE
measured by skin prick test (SPT) or specific
IgE blood testing (sIgE)
Oral allergy
syndrome
(OAS)
A secondary tree nut allergy that occurs pre-
dominantly in pollen-sensitised individuals,
mediated by cross-reactive IgE responses to
allergens present in pollen and other plants.
Presents with oral pharyngeal symptoms
(itching mouth/tongue)
Pollen food
syndrome
(PFS)
Another term for oral allergy syndrome
This article is part of the Topical Collection on Food Allergy
*Katrina Allen
katie.allen@rch.org.au
1
Murdoch Childrens Research Institute, Royal Children’sHospital,
Flemington Rd, Parkville 3052, Victoria, Australia
2
Department of Paediatrics, University of Melbourne,
Parkville, Australia
3
Allergy and Lung Health Unit, Centre for Epidemiology and
Biostatistics, The University of Melbourne, Melbourne, Australia
4
Department of Allergy and Immunology, The Royal Children’s
Hospital, Flemington Road, Parkville, Australia
5
Institute of Inflammation and Repair, University of Manchester,
Manchester, UK
Curr Allergy Asthma Rep (2015) 15: 54
DOI 10.1007/s11882-015-0555-8

Introduction
Tree nut is the collective term used to describe nuts that grow
on trees. Contrary to popular belief, peanuts are not tree nuts
and are in fact a groundnut and classified as a legume. Tree
nuts most likely to result in an IgE-mediated food allergy
reaction are almond, brazil nut, cashew nut, hazelnut,
macadamia, pecan, pistachio and walnut. Although botanical-
ly unrelated, tree nut and peanut allergies share many clinical
similarities. Peanut and tree nuts are two of the most common
foods reported to cause IgE-mediated food allergic reactions.
IgE-mediated food allergy reactions can occur after ingestion
of very small amounts of peanut and tree nut, typically within
minutes of ingestion with symptoms including hives, angio-
edema or vomiting. Reactions can also be life threatening,
with the most severe reactions termed anaphylaxis. Peanut
and tree nuts together account for 70–90 % of reported food-
induced anaphylaxis fatalities, with tree nuts alone accounting
for around 18–40 % [1–4]. Allergies to peanut and tree nuts
also commonly co-exist with around 20–30 % of people with
a peanut allergy also allergic to one or more tree nuts [5,6].
For individuals with one tree nut allergy, around 30 % will
have at least one additional tree nut allergy [6]. Tree nut and
peanut allergies are usually lifelong [7]. Peanut allergy has
been well described and widely reported with population
prevalence estimates between 1 and 6 % [8•,9]. Despite the
similarities to peanut allergy, the population prevalence of tree
nut allergy has been less well characterised.
Determining tree nut allergy prevalence at a population
level can be complex. Firstly, the definition of a ‘tree nut’
may vary. Some studies include peanut and tree nuts together
as ‘nuts’, while other studies only include one or two tree nuts.
Few studies investigate allergy to all eight common individual
tree nuts. Secondly, allergic reactions to tree nuts can result
from primary IgE-mediated mechanisms or, alternatively, via
secondary cross-reactivity mechanisms to birch pollen, in a
form of food allergy known as oral allergy syndrome (OAS)
or pollen food syndrome (PFS). In individuals with birch pol-
len sensitisation, birch pollen-specific IgE can cross-react with
similar proteins found in a range of fresh fruits, vegetables and
nuts (apple, apricot, carrot, celery, hazelnut, peach, peanut,
pear, potato and plum) resulting in oral pharyngeal symptoms
[10,11]. Finally, the method of tree nut allergy diagnosis may
vary from self-reported methods such as surveys and question-
naires (which have been found to overestimate the true prev-
alence of food allergy) [8•,9], IgE testing methods such as
skin prick testing (SPT) or specific IgE (which are limited to
IgE-mediated food allergy and are indicative of sensitisation
not clinical allergy), to the most objective but time-consuming
and cumbersome methods of oral food challenge (OFC) and
double-blind placebo-controlled food challenges (DBPCFC).
One previous systematic review by Zuidmeer et al., of
studies published between 1990 and 2006, reported the
prevalence of perceived reactions to tree nut as ranging be-
tween 0 and 7.3 %; however, most studies included in this
review (n=27 of 36) were based in Europe where the preva-
lence of oral allergy syndrome is high, and few studies used
objective definitions of tree nut allergy such as challenge con-
firmed outcomes [12•]. A more recent systematic review by
Nwaru et al. was confined to European studies only and did
not distinguish between individual tree nuts [13•]. A more up-
to-date global prevalence estimate of tree nut allergy is needed
since 20 new studies have been published since 2006, and
understanding the regional variation in tree nut allergy is im-
portant given the overall rising burden of food allergy [14,15]
in developed countries and the importance of tree nuts as a
cause of severe allergic reactions.
The aim of this paper is to provide a comprehensive, up to-
date systematic review of the population prevalence of tree nut
allergy in children and adults including details of all individual
tree nuts in various regions of the world.
Methods
Search Strategy
Following closely the methods and procedures of the Pre-
ferred Reporting Items for Systematic Reviews and Meta-
analyses (PRISMA) guidelines [16], we systematically
searched three electronic databases (OVID MEDLINE,
EMBASE and PubMed) based on a search strategy formulat-
ed with the assistance of a research librarian. The search strat-
egy was created in OVID MEDLINE and modified for
EMBASE and PubMed. Figure 1outlines the full OVID
MEDLINE search strategy.
Study Selection
Tree nuts were defined as walnut, almond, pistachio, cashew,
pecan, hazelnut, macadamia and Brazil nut. Studies reporting
on all forms of allergic reactions (primary and secondary IgE-
mediated and non-IgE-mediated reactions) were included and
there were no age restrictions applied. All tree nut allergy
outcomes were included for both individual and combined
tree nut allergies. We included eligible studies that reported
tree nut allergy based on self-report, sensitisation (sIgE or
SPT), OFC/DBPCFC or convincing clinical history. The
search was limited to English-language articles and, to capture
more recent publications, limited to the period January 1996
to December 2014. To ensure unbiased estimates of tree nut
allergy prevalence in the community, we excluded studies in
selected patient groups or those performed in hospital or aller-
gy clinic settings and included only population-based cross-
sectional and cohort studies. Reviews and case reports were
54 Page 2 of 13 Curr Allergy Asthma Rep (2015) 15: 54

excluded along with studies of which full-text articles were
not available.
Identified articles were screened via title and abstract by
two independent reviewers. Any discrepancies were resolved
by consensus and if necessary a third reviewer consulted. Ref-
erence lists of identified studies were reviewed for additional
articles. A full-text review was then undertaken for all articles
identified.
Quality assessment of the studies was performed by two
reviewers based on participation rate, ability of the study de-
sign to address tree nut allergy outcomes objectively and in-
clusion of individual tree nut information.
Analysis
Using a standardised method, relevant study details were
summarised including reference details, age, sample size
and response rate, prevalence estimates and 95 % confi-
dence intervals (CI) for all reported food allergy out-
comes (self-/parent report, specific IgE testing, skin prick
testing, symptoms and food challenges) for overall food
allergy and tree nut allergy. If not reported, prevalence
estimates were calculated as the observed proportion
with 95 % CI calculated on the assumption of a binomial
sampling distribution.
* The primary search was conducted in OVID MEDLINE and modified for EMBASE and PubMed. The
search involved a combinaon of three search groups as either MeSH terms or keywords, each of
which had to be present in order for an arcle to be included: 1) “nut s”, “tree nuts” or an individual
tree nut term; 2) “hypersensivity” or “allergy”; and 3) “prevalence” or “epidemiology”. The search
was limited to English language arcles. The exact search conducted in OVID MEDLINE is shown in the
box below.
1. (hazelnut* or hazel nut* or cashew*or pistachio* or almond* or treenut* or tree nut* or pecan* or brazilnut* or brazil nut*
or walnut*).af. 2. Nuts/ae, im, po, to 3. prevalence 4. Epidemiology 5. food hypersensitivity/ or nut hypersensitivity 6.
allerg*.af. 7. (1 or 2) and (3 or 4) and (5 or 6) 8. nut hypersensitivity/ep 9. food hypersensitivity/ep and (1 or 2) 10. 7 or 8 or
9 11. limit 10 to english language
Addional records idenfied
n= 10
Records aer duplicates removed
n= 333
Records screened (tle/ abstract)
n=333
Full text arcles excluded n= 46
Selected populaon = 26, Treenut allergy prevalence not
reported =7, Review arcle = 6,No Prevalence data = 7
Full text-arcles assessed for
eligibility
n=82
Records Excluded
n=261
Total
n=36
PubMed (Jan 2013-Dec 2014)
n=11
Embase(Jan 1996-Dec 2014)
n=230
Medline (Jan 1996-Dec 2014)*
n=130
Fig. 1 Summary of the search method
Curr Allergy Asthma Rep (2015) 15: 54 Page 3 of 13 54

We subclassified the prevalence estimates and 95 % CI for
age, region and method of tree nut allergy diagnosis.
For this review, the approaches used to determine tree nut
allergy have been grouped as follows:
1. Confirmed tree nut allergy—defined as food challenge
confirmed tree nut allergy (OFC or DBPCFC) or recent
history (<2 years) of IgE-mediated reaction with positive
allergy testing (SPT or sIgE) undertaken as part of the
study in the absence of a formal food challenge.
2. Probable tree nut allergy—defined as reported history
(>2 years) of IgE-mediated reaction with allergy or self-
report of doctor diagnosis (presumed to include allergy-
specific history and testing).
3. Self-reported tree nut allergy—defined as parent or self-
reported tree nut allergy in the absence of data on allergy
testing.
4. Sensitisation only (allergy testing via SPT or sIgE, with-
out confirmation of clinical allergy).
We performed a random effects meta-analysis and in an
attempt to address the significant heterogeneity observed
across the studies stratified by age, region and method of tree
nut allergy diagnosis. Statistical analyses were undertaken
using STATA 13 (Stata Corp, College Station, TX, USA).
Results
Study Selection and Characteristics
Figure 1summarises the search methodology. The systematic
search of the literature resulted in 333 articles after duplicates
were removed. Title and abstract review identified 261 that
did not meet the inclusion criteria. The remaining 72 articles
and an additional ten records identified through manually
searching reference lists underwent full-text review. Forty
six full-text articles were excluded (26 were in selected popu-
lations, seven did not report tree nut allergy prevalence, seven
did not include prevalence data and six were review articles).
Included studies are described in Table 1(n=36).Twenty
six studies were designed to measure overall food allergy
prevalence and reported tree nut allergy as a study outcome,
seven were studies specifically aimed at investigating tree nut
allergy prevalence and three studies included tree nut allergy
prevalence data as part of an investigation of peanut allergy
prevalence or associated factors.
Quality assessment of the studies based on participation rate,
ability of the study design to address tree nut allergy outcomes
objectively and inclusion of individual tree nut information re-
sulted in 28 studies graded as moderate and eight poor. Three of
the studies were assessed as poor because they were not de-
signed to measure tree nut allergy prevalence but reported some
tree nut prevalence data, which we have included in this review.
The majority (n=28) of the studies were population-based cross-
sectional studies and the remaining eight were cohort studies.
Six studies did not provide participation rate details, ten studies
hadaparticipationrateabove80%,13between50and80%
and seven less than 50 %. One study by Greenhawt et al. in
American college students had a participation rate of only 3 %
and reported a very high overall self-reported food allergy prev-
alence of 54 % and a self-reported tree nut allergy prevalence of
9.16 % (95% CI 6.8–11.9) [24]. This study has been included in
the summary table, but the prevalence estimates not discussed as
part of the review since the participation rate was extremely low
and the study therefore not necessarily representative of the
population from which it was sampled.
The random effects meta-analysis showed heterogeneity to
be too great to report pooled results (I
2
>98 %, p=0.000 for all
analyses).
Tree Nut Allergy Prevalence by Age and Allergy Diagnosis
Method
The majority (n=24) of studies in this review were in children
and adolescents, four studies included both adults and chil-
dren, six studies adults only and two studies reported an over-
all tree nut allergy prevalence without age breakdown; in one
of these studies, participants were >15 years [23] and the
second <61 years of age [25].
Prevalence estimate ranges for all allergy definitions,
categorised by age, are outlined in Table 2. Seven studies used
the most objective assessment of oral food challenge (or convinc-
ing recent history of allergic reaction together with positive
allergen-specific IgE) with an overall prevalence range of 0–
1.6 %. Nine studies combined self-reported food allergy with
additional objective assessment such as specific details regarding
doctor diagnosis or sensitisation details (sIgE/SPT) and were
classified as probable food allergy for this review. The overall
probable tree nut allergy prevalence range was 0.05–4.9 %, with
only one study reporting adult data. However, the majority of
prevalence estimates for tree nut allergy were based on self-
reported reactions (n=20 studies). The self-reported tree nut al-
lergy prevalence range was wider for adults (0.18–8.9 %) and
those studies including both adults and children (0.4–11.4 %)
than those studies including only children (0–3.8 %). Overall
self-reported tree nut allergy prevalence ranged from 0 to 11.4 %.
Three studies based tree nut allergy prevalence on sensiti-
sation alone (sIgE or SPT) without any clarification of pres-
ence of clinical allergy. One reported hazelnut sensitisation by
SPT in Russian children of 0.8 % (95 % CI 0.4–1.1) and
Finnish children of 6.3 % (95% CI 3.6–9.8) [52]. The second
study reported sensitisation based on SPT of 1.0 % in 7-year-
old children in the UK [40]. The third study in adults reported
sensitisation prevalence to hazelnut of 9.26 % and walnut
2.98 % (overall 12.2 % (95% CI 11.7–12.7)) [20]. This was
54 Page 4 of 13 Curr Allergy Asthma Rep (2015) 15: 54

Tab l e 1 Summary of the characteristics of studies in review: studies published January 1, 1996–Dec 31, 2014 (alphabetical by author)
Reference Country Study design Allergy outcome Type of allergy NParticipation
rate (%)
Age Individual
tree nuts
described
Prevalence
measure
Overall prevalence
%(95 %CI)(N)
Study
grading
Ahn et al. 2012 [17] Korea Cross-
sectional
2. Probable (self-
report of Dr
diagnosis and sIgE)
Primary and
secondary
7882 97 6–13 years NA Point and
lifetime
0.05 % (0.01–0.13)
(4/7882)
Moderate
Bedolla-Barajas
et al. 2014 [18]
Mexico Cross-
sectional
1. Self-report Primary and
secondary
1126 NA 18–50 years Yes Point 0.18 % (0.02–0.64)
(2/1126)
Poor
Ben-Shoshan et
al. 2010 [19]
Canada Cross-
sectional
1. Self-report
2. Probable (self-
report of Dr
diagnosis and sIgE)
Primary and
secondary
9667 34.6 All ages with
breakdown
NA Point Children 1.1.73
(1.16–2.3)
2.0.69 (0.4–0.97)
Adults: 1. 1.07
(0.84–1.30)
2. 0.35 (0.27–0.44)
Overall: 1. 1.22 %
(1.00–1.44)
(118/9667)
2. 0.68 %
(0.54–0.83)
Moderate
Burney et al.
2014 [20]
Multi
(Europe)
Cross-
sectional
4. Sensitisation
(sIgE)
Primary and
secondary
17,366 54.9 20–54 years Yes Point 12.2 % (11.7–12.7)
(2121/17326)
Moderate
Caffarelli et al.
2011 [21]
Italy Cross-
sectional
1. Self-report Primary and
secondary
625 69 5–14 years Yes 0.32 % (0.04–1.2)
(2/625)
Moderate
DuToit et al.
2008 [22]
UK
Israel
Cross-
sectional
1. Self-report Primary 4148 (UK)
4672 (Israel)
80.2 (UK)
83.2 (Israel)
4–18 years NA Point UK 1.85 % (1.5–2.3)
(77/4148)
Israel 0.13 %
(0.05–0.3)
(6/4672)
Moderate
Emmett et al.
1999 [23]
UK Cross-
sectional
1. Self-report NA 16,434 NA All ages NA Point 0.40 % (0.30–0.51)
(63/16,434)
Moderate
Greenhawt et. al.
2009 [24]
USA Cross-
sectional
1. Self-report NA 571 3.5 >18 years NA Point 9.16 % (6.8–11.9)
(47/571)
Poor
Kanny et al.
2002 [25]
France Cross-
sectional
1. Self-report Primary and
secondary
16,174 52 All ages
<60
NA Point 3 % (2.7–3.20) Moderate
Kaya et al.
2013 [26]
Turkey Cross-
sectional
1. Self-report
3. Confirmed
(DBPCFC)
Primary 10,096 89.9 11–15 years Yes Lifetime 1.1.2 % (0.1–1.4)
(121/10,096)
3.0.05 % (0.02–0.1)
(6/100,096)
Moderate
Kljakovic et al.
2009 [27]
Australia Cross-
sectional
1. Self-report NA 3851 85 4–5years No Lifetime 1.79%(1.4–2.3)
(69/3851)
Poor
Kristjansson
et al. 1999 [28]
Sweden
Iceland
Cross-
sectional
1. Self-report
3. Confirmed
(OFC)
NA 324
(Iceland)
328
(Sweden)
79 (Iceland)
90 (Sweden)
18 months No Point 1. Sweden 0.3 %
(0.0–1.6) (1/328)
Iceland 0 %
3.0 % for Iceland
and Sweden
Moderate
Curr Allergy Asthma Rep (2015) 15: 54 Page 5 of 13 54

Tab l e 1 (continued)
Reference Country Study design Allergy outcome Type of allergy NParticipation
rate (%)
Age Individual
tree nuts
described
Prevalence
measure
Overall prevalence
%(95 %CI)(N)
Study
grading
Leung et al. 2009
[29]
Hong Kong Cross-
sectional
1. Self-report
2. Probable (self-
report of Dr
diagnosis)
Primary and
secondary
3677 83.6 % 2–7 years NA NA 1. 0.41 (0.2–0.7)
(15/3677)
2. 0.3 % (0.2–0.5)
(11/3677)
Moderate
Marklund et al.
2004 [30]
Sweden Cross-
sectional
1. Self-report Primary and
secondary
1451 97 13–21 years NA Point 11.37 % (9.5–12.8)
(165/1451)
Moderate
Mustafayev et al.
2012 [31]
Turkey Cross-
sectional
1. Self-report
2. Probable (detailed
history and SPT)
3. Confirmed (OFC)
Primary 6963 NA 10–11 years Yes Point 1.3.5 % (3.1,3.9)
(223/6963)
2.4.9 % (4.4,5.4)
(341/6963)
3.0.05 % (0.03,0.15)
(4/6963)
Moderate
Nicolaou et al.
2010 [32]
UK Cohort 1. Self-report Primary 1029 94.9 8 years NA Lifetime 1.0 % (0.4,1.8)
(10/1029)
Poor
Orhan et al.
2009 [33]
Turkey Cross-
sectional
1. Self-report
2. Probable (SPT)
3. Confirmed (OFC)
Primary 2739 78.2 6–9 years Almond
and
walnut
Point 1.0.4 % (0.2,0.7)
(11/2739)
2.0.14 % (0.03,0.4)
(4/2739)
3.0 % (0,0.1) (0/2739)
Moderate
Ostblom et al.
2008 [34]
Sweden Cohort 1. Self-report Primary 2563 69 4 years NA Point 3.8 % (3.1,4.6)
(98/2563)
Moderate
Osterballe et al.
2009 [35]
Denmark Cohort 1. Self-report Specified primary
and secondary
843 77 22 years Yes Point 1. Primary 0 %
Secondary 8.9 %
(7.0,11.02)
(85/843)
Moderate
Penard-Morand
et al. 2005 [36]
France Cross-
sectional
1. Self-report Primary and
secondary
7781 81 9–11 years NA Lifetime 0.2 % (0.1,0.3)
(10/6672)
Moderate
Pereira et al.
2005 [37]
UK Cohort 1. Self-report Primary and
secondary
1532 48.7 11 and
15 years
NA Point 1.6 % (1.1,2.4)
(26/1532)
Poor
Pyrhonen et al.
2005 [38]
Finland Cross-
sectional
1. Self-report
2. Probable (self-
report of Dr
diagnosis)
Primary and
secondary
3308 69 1–4 years NA Lifetime 1.1.5 % (1.1,1.9)
(49/3308)
2.0.2 % (0.08,0.4)
(7/3308)
Moderate
Rance et al.
2005 [39]
France Cross-
sectional
1. Self-report Primary and
secondary
2716 77.6 2–14 years Yes Point 0.7 % (0.4,1.1)
(19/2716)
Moderate
Roberts et al.
2005 [40]
UK Cohort 4. Sensitisation
(SPT)
Sensitisation
only
5848 42 7 years Yes Point 1.04 % (0.8,1.3)
(61/5848)
Poor
Roehr et al.
2004 [41]
Germany Cross-
sectional
1. Self-report
2. Probable (SPT)
3. Confirmed (OFC)
Primary and
secondary
739 31.5 0–17 years Yes Point 1. NA
2. 2.7 % (1.6,4.1)
(20/739)
3. 1.4 % (0.7,2.5)
(10/739)
Moderate
54 Page 6 of 13 Curr Allergy Asthma Rep (2015) 15: 54

Tab l e 1 (continued)
Reference Country Study design Allergy outcome Type of allergy NParticipation
rate (%)
Age Individual
tree nuts
described
Prevalence
measure
Overall prevalence
%(95 %CI)(N)
Study
grading
Schafer et al.
2001 [42]
Germany Cross-
sectional
1. Self-report
SPT for hazelnut
only
Primary and
secondary
1537 60.7 25–74 years NA Point 1.8.5 % (7.1,9.9)
(130/1537)
Moderate
Shek et al.
2010 [43]
Singapore
Philippines
Cross-
sectional
1. Self-report
2. Probable (self-
report of Dr
diagnosis)
Primary 25,692 74.2 4–6 years and
14–16 years
NA Point 1.1.85 % (1.6,2.1)
(200/10775)
2.0.28 % (0.2,0.4)
(31/10,775)
Moderate
Sicherer et al.
1999 [44•]
USA Cross-
sectional
1. Self-report Primary and
secondary
4374 62 All ages with
breakdown
Yes Point Children (<18 years)
0.2 % (0.05,0.4)
(5/2998)
Adults (>18 yrs)
0.7 % (0.5,0.9)
(59/8049)
Overall 0.5 %
(0.0,0.6)
(64/12032)
Moderate
Sicherer et al.
2003 [45•]
USA Cross-
sectional
1. Self-report Primary and
secondary
13,493 52 All ages with
breakdown
Yes Point Children (<18 years)
0.2 % (0.1,0.4)
(7/3127)
Adults (>18 years)
0.1 % (0.4,0.6)
(50/9881)
Overall 0.4 %
(0.3,0.5)
(57/13,493)
Moderate
Sicherer et al.
2010 [46•]
USA Cross-
sectional
1. Self-report Primary and
secondary
5300 42 All ages with
breakdown
Yes Point Children (<18 years)
1.1 % (0.05,0.4)
(31/2902)
Adults (>18 years)
0.5 % (0.4,0.6)
(53/9845)
Overall 0.6 %
(0.5,0.8)
(84/12,658)
Moderate
Tar iq et a l.
1996 [47]
UK Cohort 1. Self-report Some
participants had
SPT
Primary 1218 NA 4 years NA Point 0.1 % (0.02,0.6)
(2/1218)
Poor
Taylor-Black
et al. 2014 [48]
USA Cross-
sectional
1. Self-report Primary 368 43 4–12 years NA Point 1.82 % (1.06,2.9)
(17/932)
Poor
Venter et al.
2006 [49]
UK Cohort 1. Self-report
3. Confirmed (OFC)
Primary 798 55.4 6 years Yes Point 1. 1.37 % (0.8,2.5)
(11/798)
3. 0.25 % (0.03,0.9)
(2/798)
Moderate
Curr Allergy Asthma Rep (2015) 15: 54 Page 7 of 13 54

the highest reported prevalence estimate of all four methods of
tree nut allergy definition.
Tree Nut Allergy Prevalence by Region
Prevalence estimate ranges for each method of allergy defini-
tion are summarised by region in Table 3. Regional variation
in self-reported tree nut allergy prevalence is illustrated in
Fig. 2. Most studies were from Europe (n=18), the UK (n=
8), or the USA (n=5). There were three studies from Asia and
one each from Canada, Central America and Australia. Strat-
ifying by region highlighted a markedly higher prevalence of
tree nut allergy in some European countries with a range of
0.04–11.4 %. OAS appeared to contribute to higher tree nut
allergy prevalence in some European countries since all three
of the studies reporting tree nut allergy prevalence over 8 %
were self-reported, all in adolescents and adults, and all from
Europe. Two of these studies directly reported that all tree nut
allergy found in their study was due to OAS [35,42] and the
third study did not specify the type of allergic reaction to tree
nuts, but overall 33 % of all allergy, to any food, was report-
edly due to OAS [30]. All other regions, regardless of allergy
definition, reported tree nut allergy prevalence less than 2 %.
Individual Tree Nut Allergy Prevalence
Tab le 4summarises the percentage of tree nut allergic partic-
ipants allergic to each individual tree nut by region. Fourteen
studies provided details of individual tree nut prevalence. The
prevalence of individual tree nut allergies varied by region.
Hazelnut was the most common tree nut allergy reported in six
of the seven studies from Europe accounting for 17–100 % of
all tree nut allergies. The two studies from the USA reported
walnut and cashew as the most common tree nut allergies
ranging from 20 to 30 % and 15–30 %, respectively. Brazil
nut allergy was reported commonly in the UK ranging from
24 to 33 %. The one study from Mexico reported low overall
tree nut allergy of 0.18 % (2/1126) with both participants
allergic to walnut. None of the studies reported on the preva-
lence of multiple tree nut allergies.
Tree Nut Allergy Prevalence Over Time
There is limited evidence to determine if the population
prevalence of tree nut allergy is increasing. Three studies
in the USA utilised random-digit telephone surveys in
1997, 2002 and 2008 [44•,45•,46•]. Study design was
consistent across each sampling period and included a
large number of participants (n=4374; 13,493 and 5300,
respectively). No significant increase in adult self-reported
tree nut allergy prevalence was found over the three time
points. However, the prevalence of self-reported tree nut
allergy in children younger than 18 years had increased
Tab l e 1 (continued)
Reference Country Study design Allergy outcome Type of allergy NParticipation
rate (%)
Age Individual
tree nuts
described
Prevalence
measure
Overall prevalence
%(95 %CI)(N)
Study
grading
Venter et al
2008 [50]
UK Cohort 1. Self-report
3. Confirmed (OFC)
Primary 891 91.9 3 years Yes Point 3.0.93 % (0.34,2.0)
(6/642)
Moderate
Vierk et al .
2007 [51]
USA Cross-
sectional
1. Self-report
2. Probable (self-
report of Dr
diagnosis)
Primary 4482 NA >18 years NA Point 1.0.65 % (0.43,0.9)
(29/4477)
2.0.5 % (0.06,0.32)
(7/4477)
Moderate
Von Hertzen
et al. 2006
[52]
Finland
Russia
Cross-
sectional
4. Sensitisation
(SPT)
Primary and
secondary
Finland 367
Russia 446
NA 7–16 years Hazelnut
only
Point Finland 6.3 %
(3.6,9.8)
(17/271)
Russia 0.8 %
(0.2,2.4)
(3/356)
Moderate
54 Page 8 of 13 Curr Allergy Asthma Rep (2015) 15: 54

significantly (0.2 % in 1997, 0.5 % in 2002 and 1.1 % in
2008). Proportionally, the increase was greater than that
observed for peanut over the same time periods (0.4 % in
1997, 0.8 % in 2002 and 1.4 % in 2008).
Tabl e 2 Summary of the range of
prevalence estimates of tree nut
allergy in the reviewed studies
according to allergy assessment
method and age
Allergy definition and age Number
of studies
Range of prevalence
estimates (%)
References
Self-reported
Children 0–18 years
Adult
All ages
Overall
22
8
3
0–3.8
0.18–8.9
0.4–11.4
0–11.4
[21,22,26–29,31–34,36–39,43,
44•,45•,46•,47–49,53]
[18,35,42,44•,45•,46•,51,53]
[23,25,30]
Probable
Children 0–18 years
Adult
All ages
Overall
9
2
0
0.05–4.9
0.35–0.5
NA
0.05–4.9
[17,19,29,31,33,38,41,43,51]
[19,51]
Confirmed
Children 0–18 years
Adult
All ages
Overall
7
0
0
0–1.4
NA
NA
0–1.4
[26,28,31,33,41,49,50]
Sensitisation
Children 0–18 years
Adult
All ages
Overall
2
1
0
0.8–6.3
12.2
NA
0.8–12.2
[40,52]
[20]
Some studies are included in more than one category as they reported prevalence estimates obtained using more
than one allergy assessment method.
Tabl e 3 Summary of the range of reported prevalence estimates for tree nut allergy according to allergy assessment method and region
Region Self-report
Range %
(number of studies)
Probable
Range %
(number of studies)
Confirmed
Range %
(number of studies)
Sensitisation
Range %
(number of studies)
Asia Children
Adults
Overall
0.3–1.85 (3)
NA
0.3–1.85
0.05–0.3 (3)
NA
0.05–0.3
NA
NA
NA
NA
NA
NA
Europe Children
Adults
All ages
Overall
0.04–3.1 (10)
8.5–8.9 (2)
3.0–11.7
0.04–11.7
0.2–4.9 (4)
1.6 (1)
NA
0.2–4.9
0–1.4 (6)
NA
NA
0–1.4
0.8 (1)
12.2 (1)
NA
0.8–12.2
UK Children
Adults
Overall
0.1–1.85 (5)
NA
0.1–1.85
NA
NA
0.25–0.93 (2)
NA
0.25–0.93
NA
NA
USA Children
Adults
Overall
0.2–1.82 (4)
0.5–0.7 (2)
0.2–1.82
NA
NA
NA
NA
NA
NA
Australia Children
Adults
Overall
1.79 (1)
NA
NA
NA
NA
NA
NA
NA
Canada Children
Adults
Overall
1.73 (1)
1.07 (1)
1.07–1.73
1.59 (1)
1.0 (1)
1.0–1.59
0.69 (1)
0.35 (1)
0.35–0.69
NA
NA
Central America Children
Adults
Overall
NA
0.02 (1)
NA
NA
NA
NA
NA
NA
Curr Allergy Asthma Rep (2015) 15: 54 Page 9 of 13 54

Fig. 2 Overall tree nut allergy
prevalence by region (%)
Tabl e 4 Percentage of tree nut allergics reporting reactions to the individual tree nuts by region
Region, study details (country) % of tree nut allergics reporting reactions to the individual tree nuts (number with specific tree nut
allergy/total number with any tree nut allergy)
Europe
Burney et al. 2014 [20] (multi-country)
Caffarelli et al. 2011 [21](Italy)
Mustafayev et al. 2012 [31](Turkey)
Kaya et al. 2013 [26](Turkey)
Osterballe et al. 2009 [35] (Denmark)
Rance et al. 2005 [39] (France)
Roehr et al. 2004 [41] (Germany)
Hazelnut 76 % (1605/2121), walnut 24 % (517/2121)
Hazelnut 100 % (2/2)
Hazelnut 42 % (104/243), walnut 34 % (83/243), pistachio 22 % (55/243)
Walnut 66 % (4/6), hazelnut 17 % (1/6), pistachio 17 % (1/6)
Hazelnut 75 % (56/75), Brazil nut 31 % (23/75), walnut 5 % (4/75), almond 3 % 2/75)
Hazelnut 53 % (10/19), walnut 32 % (6/19), almond 10 % (2/19), cashew 5 % (1/19)
Hazelnut 100 % (10/10)
USA
Sicherer et al. 1999 [44•]
Sicherer et al. 2010 [46•]
Walnut 37 % (24/65), cashew 12 % (5/65), Brazil nut 12 % (8/65), almond 11 % (7/65),
pecan 11 % (7/65), hazelnut 4.6 % (3/65), macadamia 3 % (2/65), unspecified 9 % (6/65)
Walnut 48 % (41/84), cashew 34 % (29/84), pecan 30 % (26/84), almond 29 % (25/84),
pistachio 22 % (19/84), Brazil nut 22 % (19/84), hazelnut 20 % (17/84),
macadamia 20 % (17/84), pine nut 13 % (11/84)
UK
Ve n t er et al . 2 0 0 8 [ 50]
Ve n t er et al . 2 0 0 6 [ 49]
Roberts et al. 2005 [40]
Tariq et al. 1996 [47]
Brazil nut 33 % (2/6), almond 33 % (2/6), hazelnut 17 % (1/6), cashew 17 % (1/6)
Almond 33 % (1/3), Brazil nut 33 % (1/3), hazelnut 33 % (1/3)
Walnut 24 % (10/41), Brazil nut 24 % (10/41), almond 22 % (9/41), cashew 15 % (10/41),
hazelnut 7 % (3/41), pecan 7 % (3/41)
Hazelnut 50 % (1/2), cashew 50 % (1/2)
Mexico
Bedolla-Barajas et al. 2014 [18]Walnut100%(2/2)
54 Page 10 of 13 Curr Allergy Asthma Rep (2015) 15: 54

Discussion
This review has confirmed that the majority of tree nut allergy
prevalence studies continue to be undertaken in Europe, where
there is a high prevalence of OAS, with most studies relying
on self-reported prevalence, limited to children and adoles-
cents. Using the most robust measure of tree nut prevalence
(challenge confirmed or history of reaction with IgE antibod-
ies), we estimate the overall prevalence to be <2 % in coun-
tries where OAS is not reported. Secondary tree nut allergy
(OAS) estimates for older age groups including adolescents
and adults is as high as 10 %, particularly in Europe. Few
studies reported the population prevalence of individual tree
nut allergies. However, how prevalent a particular tree nut
allergy is differs significantly by region with hazelnut the most
common tree nut allergy in Europe, walnut and cashew in the
USA and Brazil nut, almond and walnut most commonly re-
ported in the UK. There is limited evidence to determine if the
population prevalence of tree nut allergy is increasing.
This is the first systematicreview of the literature exploring
tree nut allergy prevalence exclusively across the age groups
and different regions of the world, utilising robust systematic
review methodology, closely following PRISMA guidelines.
A further strength of this review is we categorised prevalence
by robustness of the study methodology employed to define
tree nut allergy. We identified three studies with self-reported
tree nut allergy greater than 8 %, all from Europe demonstrat-
ing that studies which do not differentiate primary and sec-
ondary tree nut allergy prevalence rates are likely to inflate
prevalence estimates.
Precise estimates of true tree nut allergy were limited by the
small number of studies reporting challenge confirmed tree
nut allergy prevalence—the gold standard for diagnosis. As
for other epidemiological studies of food allergy prevalence
[8•,9], we also found higher prevalence estimates for self-
report and sensitisation. Self-report is known to overestimate
the true prevalence of food allergy [54] and asymptomatic
sensitisation to foods is relatively common [9]; therefore, ob-
jective measures are critical. We were also unable to accurate-
ly determine whether tree nut allergy is on the rise as only one
series of estimates was available. Finally, estimates of the
prevalence of individual tree nut allergies could not be reliably
estimated due to the paucity of data reported for individual
nuts, although it is clear that there is significant regional var-
iation in prevalence estimates [55].
We found overall tree nut allergy prevalence mirrors the
global pattern of overall food allergy with countries with
low prevalence of food allergy also reporting low levels of
tree nut allergy. Large population-based epidemiological stud-
ies such as the ISAAC and EuroPrevall studies have demon-
strated considerable regional variability of common food al-
lergens and sensitisation patterns, but the reasons for this re-
main largely unexplored. It has been hypothesised that
variation in dietary patterns at the population level might lead
to variations in sensitisation status and hence risk of subse-
quent food allergy. Du Toit et al. hypothesised that variations
in peanut allergy prevalence between genetically similar pop-
ulations in the UK and Israel might be due to differences in
infantile peanut consumption patterns [22], whilst others have
argued thatboiled versus roasted peanut dietary intakes may at
least partly explain the difference in allergy patterns across
different regions [56,57].
Our review found a higher self-reported tree nut allergy
range (0–11.4 %) than both previous published systematic
reviews. Nwaru et al. performed a meta-analysis of seven
studies and reported a pooled self-reported point prevalence
of 1.8 % (95% CI 1.63–1.99), although there was signifi-
cant heterogeneity across the studies (I
2
=99.4 %, p=0.00).
Zuidmeer et al. included studies from a wider range of
countries from 1990 to 2006 and reported a self-reported
tree nut allergy prevalence range of 0–7.3 % based on
seven studies [12•]. Prevalence varied based on type of tree
nut allergy, method of tree nut allergy diagnosis, age and
region. Similarly to Zudimeer et al., considering the large
heterogeneity between the studies, we have not presented a
pooled prevalence estimate since this would mask the dif-
ferences between populations.
Nwaru et al. reported confirmed tree nut allergy pooled
point prevalence of 0.45 % (I
2
=0.00 %, p=0.88) while
Zuidmeer et al. reported a range of 0.1–4.3, based on only
three studies. We found the prevalence of tree nut sensitisation
to be the highest of the four methods of allergy definition used
(1.0–12.2 %). Comparison to sensitisation prevalence esti-
mates in previous reviews is difficult as we reported sensitisa-
tion prevalence estimates based on population sensitisation.
Previous reviews both reported studies where SPT or sIgE
was performed only on participants that had previously self-
reported tree nut allergy. Neither of these reviews differentiat-
ed between primary and secondary tree nut allergy prevalence,
or reported on individual tree nut allergy prevalence nor the
nature or prevalence of multiple tree nut allergies.
In conclusion, this systematic review has highlighted
that there is considerable heterogeneity in tree nut allergy
prevalence from studies to date and pooling individual
study estimates risks masking the real differences between
populations. Data is limited to largely European, US and
UK studies using self-reported prevalence in children and
adolescents. There is a need for further studies to deter-
mine tree nut allergy by gold standard methodologies
such as food challenge, and differentiate between primary
and secondary tree nut allergy. Further detailed informa-
tion on individual tree nut prevalences will help inform
our understanding of regional variation and repeated esti-
mates over time will enable us to understand whether time
trends in tree nut allergy mirror the general rise in IgE-
mediated food allergy reported in developed countries.
Curr Allergy Asthma Rep (2015) 15: 54 Page 11 of 13 54

Acknowledgement This review forms work as part of VMc PhD,
funded by the Centre for Food and Allergy Research (CFAR).
Compliance with Ethics Guidelines
Conflict of Interest Drs McWilliam, Koplin, Lodge, Tang, Dharmage
and Allen declare no conflicts of interest.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
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