Allergen Data Collection: Almond (Prunus dulcis)
Internet Symposium on Food Allergens 3(2):71-85  (2001) [http://www.food-allergens.de]
1 Prevalence of Almond Allergy

Prevalence data are based on different diagnostic procedures. While the prevalence of sensitization (sensitivity) can be estimated by SPT, RAST, and immunoblot, a clinical relevant sensitization (allergy) is evaluated by convincing history (anamnesis) or food challenge tests (ideally by DBPCFC).

1.1 General Population

Prevalence estimates within the author's selected populations are listed. Those that are assigned randomly selected ("unselected") with numbers more than 500 may be regarded as representative of the "general populations". Inclusion criteria may involve circumstances not related to atopic predisposition according to current knowledge.
 
Country / Subjects Allergy / Sensitivity References
Australia, Victoria
a) 332 unselected new-born infants
b) 4078 children with suspected peanut or tree nut allergy (age < 14 years) (study 1990-96)
c) 620 children at risk of atopy (followed from birth for 2 years)
almond 0.02% (calculated)
(frequency of almond allergy in b), corrected for prevalence ratio to peanut allergy in b) and c), extrapolated by risk of atopy in a)
Hill et al. 1997

1.2 Subjects with Atopic or Other Diseases
 
Country / Subjects Allergy / Sensitivity References
Australia, Victoria
4078 children with suspected peanut or tree nut allergy (age < 14 years) (study 1990-96)
almond 4.2% (SPT >3+, n=336) Sporik & Hill 1996
Canada, Toronto, Ontario
45 patients with classic food allergic symptoms and/or subjective food related complaints
almond, walnut 2.2% (SPT) Parker et al. 1990
Costa Rica
171 children (68 asthmatics, 103 non-asthmatics) 
almond 50% (specific IgE in MAST) Soto-Quiros et al. 1998
Croatia
71 confectionary workers with occupational respiratory allergies (bronchitis, dyspnea, asthma)
almond 4.2% (SPT) Zuskin et al. 1994
Finland
80 food handlers with hand dermatitis
almond 5% (n=60, scratch chamber test) Niinimaki 1987
France, Nancy
196 cases of involving plant food allergens (from 509 cases of food allergy)
Rosaceae fruits including almonds 17%  (clinical evaluation) Moneret-Vautrin et al. 1997
France, Nancy
142 patients with peanut allergy
almond 50% (clinical evaluation) Moneret-Vautrin et al. 1998
France, Nancy and Toulouse
544 food allergic children
almond 0.6% (food challenge) Rance et al. 1999
France, Pierre Benite
60 cases of anaphylaxis (study period 1984-92)
almond 1.7% Andre et al. 1994
Germany, Ulm
80 patients with pollen associated food allergy
almond 65% (clinical history, SPT) Boehncke et al. 1998
Italy, Ferrara
169 grass pollen allergic patients (age of 9-54 years, mean 27.9)
almond 4% (clinical history) Boccafogli et al. 1994
Italy, Genoa
132 pollen and food sensitive patients
almond 6.6%
(incidents of hypersensitivity)
Troise et al. 1992
Italy, Milan
262 fruit and/or vegetable allergic patients
almond 22% (clinical history) Ortolani et al. 1988
Italy, Milan
100 fruit and/or vegetable allergic patients
almond 6% (clinical history) Ortolani et al. 1989
Italy, Milan
30 apricot allergic patients
almond 13% (clinical history) Pastorello et al. 2000
Israel, Tel-Aviv
112 patients with food allergy (onset after 10 years of age)
a) almond 55% (SPT, n=108)
b) almond 39% (food challenge, n=71)
Kivity et al. 1994
Spain, Barcelona
102 patients allergic to dried fruits
almond 89%, 81%, and 60%
(SPT, HR, and RAST)
Amat Par et al. 1990
Spain, Gran Canaria
102 adults with symptoms after ingestion of specific foods
almond 7.5% (SPT, RAST) Castillo et al. 1996
Spain, Madrid???
40 patients with fruit or vegetable allergy
almond 43% (SPT, RAST, PK tests) Hernandez et al. 1985
Spain, Madrid
a) 48 children with pollinosis
b) 42 children with fruit or vegetable allergy
a) almond 0% (SPT), 2.1% (RAST)
b) almond 17% (SPT), 12% (RAST)
Caballero et al 1994
Spain, Madrid
355 food allergic children
almond 3.7% (clinical history,  open food challenge, SPT, RAST) Crespo et al. 1995a
Spain, Madrid
29 plant-derived food allergic patients
almond 6.9% (SPT)
almond 0% (RAST)
Diez-Gomez et al. 1999
Spain, Plasencia (Caceres)
262 patients with pollinosis
almond 2.2% (self-reported)
almond 1.5% (SPT)
Garcia-Ortiz et al. 1995
Spain, Salamanca
a) 84 mugwort sensitive patients without other pollen sensitizations
b) 57 fruit allergic patients (age of 6-56 years, mean 21.5)
a) almond 1.2% (RAST)
b) almond 14%(clinical history)
a) Garcia-Ortiz et al. 1996
b) Garcia Ortiz et al. 1998
Spain, Salamanca
95 pollen allergic patients (age 10-58 years, mean 27)
almond 16% (SPT)
almond 1% (food challenge)
Cuesta-Herranz et al. 2000
Sweden
60 severe allergic reactions caused by food
soybean, nuts, and almonds >70% Foucard et al. 1997
Sweden, Halmstad / Malmö
a) 380 birch pollen allergic patients
b) 103 patients without birch pollen allergy
a) almond 27%
b) almond 3%
(questionaire)
Eriksson et al. 1982
Switzerland, Zurich
a) 402 food allergic adults (study period 1978-87)
b) 383 food allergic patients (study period 1990-94)
a) almond 1.7%
b) almond 11%
(anamnesis, clinical relevance, diagnostic tests)
a) Wüthrich 1993
b) Etesamifar & Wüthrich 1998
United Kingdom, London
119 patients with possible food allergies
almond 3.4% (RAST, elimination-challenge test) Wraith et al. 1979
USA, Boston, MA
63 asthmatic adults with positive food-induced skin scratch tests
almond 3.2% (skin scratch test) Rackemann 1931
USA, Galveston, TX / Philadelphia, PA
26 patients with atopic dermatitis associated with ingestion of various foods
almond 3.8% (clinical history, elimination diet) Livingood & Pillsbury 1949
UK, Manchester
90 patients expierenced anaphylactic reactions to foods (from 1994-1996)
almond 3.3% (suspected cause of patients' worst reaction) Pumphrey & Stanworth 1996
USA, Little Rock, AR / New York City, NY
54 tree nut allergic patients
almond 24% (acute allergic reactions) Sicherer et al. 1998b
USA, Los Angelos, CA
127 pediatric patients who reported one or more food allergies
almond 3.9% (RAST) Hoffman & Haddad 1974
USA, Memphis, TN
89 patients with food- induced anaphylaxis (age of 12-75 years, study period 1978-92)
almond or peach 5.6% (clinical history) Kemp et al. 1995
USA, Mineola, NY
30 patients with gastrointestinal symptoms associated with food allergies
almond and Brazil nut 1 case
almond, walnut, and Brazil nut 1 case
(intracutaneous skin test, oral challenge with mixture of foods)
Fries & Zizmor 1940
USA, Rochester, MN
a) 18 patients with food- related anaphylaxis
b) 81 patients
a) almond 5.6% (history, SPT, and RAST)
b) almond 19% (SPT)
Yocum & Khan 1994
USA, Torrance, CA
8 patients with oral allergy syndrome to avocado and positive history
almond 12.5% (self-reportedly cause of OAS; no clinical confirmation) Telez-Diaz et al. 1995
USA, Torrance, CA
40 of 62 patients from an adult outpatient HIV clinic who reported symptoms compatible with food allergy
almonds and peanuts 1 case 
(self-reportedly cause of diarrhea and headache; no clinical confirmation)
Tubiolo et al. 1997

1.3 Prevalence of Associated Allergies
 
Country / Subjects Sensitization / Allergy References
France, Italy, Netherlands
37 patients with Rosaceae allergy and positive SPT to lipid-transfer protein enriched extracts (plum / peach peel)
peach 81%
apple 43%
apricot 30%
cherry 24%
plum 22%
almond 19%
pear 16%
(clinical history)
walnut 51%
hazelnut 41%
peanut 24%
(self reported)
Asero et al. 2000
Germany, Ulm
52 almond allergic patients selected out of 80 patients with pollen associated food allergy
birch pollen 98% (clinical history, SPT) Boehncke et al. 1998
Spain, Barcelona
78 almond allergic patients
tree pollen tree (elm, olive, birch, plane, ash) 59%
weed pollen (parietaria, mugwort) 38%
grass pollen 13%
(2 positive results from SPT, HR, and RAST)
Amat Par et al. 1990
Spain, Madrid
55 children sensitized to almonds
pollen 80% (SPT) Crespo et al. 1995b
Spain, Madrid and Toledo
Patients with allergy to Rosaceae fruits
a) 11 without pollinosis (mean age 26 years)
b) 22 with associated pollinosis (mean age 22 years)
Clinical history and 
SPT and/or RAST
a) b)
peach 91% 100%
apple 91% 68%
pear 27% 55%
cherry 36% 27%
apricot 18% 23%
plum 36% 23%
strawberry - 14%
almond 9% 14%
melon, watermelon, cucumber 0% 50%
nuts and seeds 50% 59%
various plant foods 18% 41%
Fernandez-Rivas et al. 1997
Spain, Madrid
28 patients with positive SPT and/or specific IgE to one or more fruits of the Rosaceae family
peach 79%
apple 21%
apricot 18%
plum 14%
almond 3.6%
pear 3.6%
strawberry 3.6%
(DBPCFC or convincing episode of anaphylaxis)
Rodríguez et al. 2000
Spain, Salamanca
8 almond allergic patients
latex 75% (SPT and/or RAST)
latex 25% (clinical history)
Garcia Ortiz et al. 1998
UK, Cambridge
62 patients with peanut and/or nut allergy (age of 11 months to 53 years)
peanut 65%
brazil nut 29%
almond 23%
hazelnut 21%
walnut 13%
cashew nut 4.8%
(clinical history, SPT)
Ewan 1996

2 Symptoms of Almond Allergy
 
Symptoms & Case Reports References
Systemic reactions
anaphylaxis (5), life-threatening reactions (7), loss of consciousness (4)

Symptoms of skin and mucous membranes
angioedema (3, 9), urticaria (1, 3, 8)

Gastrointestinal symptoms
oral angioedema (4, 7), laryngeal edema (2, 4, 9), oral hives (7), oral itching (7), oral allergy syndrome (2, 3, 6, 8, 9), vomiting (4)

Respiratory symptoms
asthma (4), dyspnea (9)

Other symptoms
general malaise (9)

(1) Schloss 1912
(2) Ortolani et al. 1988
(3) Boccafogli et al. 1994
(4) Ewan 1996
(5) De las Marinas et al. 1998
(6) Garcia Ortiz et al. 1998
(7) Roux et al. 1999
(8) Asero et al. 2000
(9) Pasini et al. 2000
Percentage of reactions
Oral allergy syndrome in 75% (plus systemic reactions in 16%) and extra-oral symptoms in 25% in 57 almond allergic patients (1)
(1) Ortolani et al. 1988

3 Diagnostic Features of Almond Allergy
 
Parameters / Subjects Outcome References
Skin test
A boy with urticaria provoked by ingestion of almond, egg, and oatmeal
Skin testing with demonstration of urticarial lesion Schloss 1912
Skin test, Systemic Reaction
An almond sensitive individual
A case of systemic reaction following skin test Kahn 1942
IgE
tree nut allergic patients:
a) 11 reacting
b) 25 not reacting to almonds
Almond specific serum IgE (RAST):
mean median
a)  17.1 kU/L 3.8 kU/L
b)  14.5 kU/L 1.8 kU/L
(no significant differences, P value 0.81)
Sicherer et al. 1998b
IgE and Clinical Relevance
25 patients with atopic dermatitis
44% had positive RAST to almonds. However, none of the patients apparently mentioned almonds as a cause of allergic sensitivity Hoffman et al. 1975
IgE and Clinical Relevance
67 asthmatic children
Agreement of history of almond allergy and almond specific serum IgE (MAST):
positive history and positive MAST in 3 children, positive MAST and no positive history in 4 children and, positive history and a negative MAST in 3 children
Adler et al. 1991
IgE and Clinical Relevance
43 patients with clinical history and positive SPT to almond
Almond specific RAST:
positive 42%
negative 58%
Boehncke et al. 1998
IgE and Clinical Relevance
A 3 year old boy with peanut allergy
Strong positive RAST to almond, although no almond allergy was described in history; also high RAST to peanut, hazelnut, Brazil nut, pecan, pistachio, walnut, and pea. Sicherer et al. 1998a
SPT, IgE and Clinical Relevance
a) 24 and b) 43 patients with clinical history of almond allergy
a) RAST (specific IgE):
positive results in 25%
b) SPT with fresh food:
positive results in 30%
Ortolani et al. 1988
SPT, IgE and Clinical Relevance
6 patients with clinical history of almond allergy
RAST (specific IgE > 0.7 kU/L):
positive results in 17%
SPT with fresh food:
positive results in 17%
Ortolani et al. 1989
SPT, RAST, Histamine Release and Clinical Relevance
102 patients allergic to dried fruits
Correlation of tests to clinical history of almond allergy:
89% for SPT
87% for HR
68% for RAST
Amat Par et al. 1990
SPT, IgE, and DBPCFC
28 patients with suspected allergy to fruits of the Rosaceae family
Almond Positivity
SPT 54%
RAST 21%
DBPCFC* 3.6%
* or convincing episode of anaphylaxis
Rodríguez et al. 2000
Immunoblot and Clinical Relevance
a) 2 symptomatic patients with almond allergy (SPT positive, RAST negative)
b) 3 asymptomatic subjects with positive RAST
IgE binding almond proteins:
a) 37-kDa protein
b) 50-kDa and 62-kDa glycoproteins (Con A reactive bands)
(SDS-PAGE Immunoblot)
Pasini et al. 2000
Open Challenge
17 children with perceived peanut or tree nut allergy (almond suspected cause in 2 cases)
Open challenge procedure, where negative tests (SPT, RAST) indicate tolerance of nuts: 15 showed no reactions, all of them continued to ingest foods containing nuts without incidents. Baker et al. 1999

4 Therapy of Almond Allergy
 
Treatment* Outcome References
Tree Pollen Immunotherapy
72 children with birch pollinosis (age of 6-16 years), prevalence of adverse reactions to almond before immunotherapy 50%
I. subcutaneous immunotherapy for 3 years with a) birch pollen preparation or b) a mixture of birch, alder, and hazel pollen
II. oral immunotherapy for 10 months with c) birch pollen preparation or d) placebo capsules
Assessment of food allergy after treatment (self-reported):
  improved unchanged worse
a) (n=19) 37% 42% 21%
b) (n=20) 55% 30% 15%
c) (n=14) 21% 64% 14%
d) (n=14) 14% 86% 0%
no significant more decrease in birch pollen immunotherapies as compared to placebo oral immunotherapy
Möller 1989
* Studies may be experimental, unproved, or controversial. Please notice the disclaimer !
 

5 Composition of Almond
 

6 Allergens of Almond
 
 
Proteins / Glycoproteins Allergen Nomenclature References
37-kDa Allergen   Pasini et al. 2000
Almond Profilin   van Ree et al. 1992, 2000
Allergens: 45-50, and 70 kDa
Minor Allergens: 15 kDa
  Bargman et al. 1992
Allergens: 50 kDa and 66 kDa
Minor Allergens: 10, 28, 37, and 39-44 kDa
  Roux et al. 1999

6.1 Sensitization to Almond Allergens
 
Country / Subjects Sensitivity to References
Italy, Padova
2 almond allergic patients
37 kDa allergen
(SDS-PAGE immunoblot)
Pasini et al. 2000
Netherlands, Amsterdam
2 patients with pollen profilin specific serum IgE
Specific IgE against
almond profilin 6.9 and 3.0 IU/ml
(RAST, L-proline Sepharose bound profilin)
van Ree et al. 2000
USA, Davis, CA
a) 14 patients with history of life-threatening reaction to almonds
b) 11 patients with history of non-life- threatening reactions to almonds
  a) b)
albumin/globulin fraction 86%
almond major protein 79%
66 kDa allergen 64% 55%
55 kDa allergen 18%
50 kDa allergen 64% 55%
39-44 kDa allergen 29%
37 kDa allergen 7%
28 kDa allergen 7% 27%
17 kDa allergen 9%
10 kDa allergen 21% 18%
(SDS-PAGE immunoblot)
Roux et al. 1999
USA, Lincoln, NE
8 almond sensitive patients
70 kDa allergen in 50%
45-50 kDa allergen in 50%
15 kDa allergen in 25%
(SDS-PAGE / immunoblot)
Bargman et al. 1992

7 Isolation & Preparation
 
Extract / Purified Allergens Methods References
Protein extract Ground whole almonds defatted with acetone and ethyl ether; dried almond powder extracted with NaCl pH 7.0, centrifuged, dialyzed, centrifuged again, and membrane filtered Bargman et al. 1992
Protein extract Almonds finely chopped, extracted with Tris-HCl-buffer pH 8.0 (containing glycerol, polyethylene glycol 8000, citric acid, L-cysteine, L-ascorbic acid, EDTA, and polyvinylpyrrolidone); followed by homogenization on ice, centrifugation, membrane filtration and membrane concentration Teuber & Peterson 1999
Salt-soluble proteins Raw whole almonds grounded, defatted with petroleum ether, extracted with 0.5-M NaCl for 2h; after centrifugation protein was precipitated with acetone at 4°C for 30 min; after centrifugation protein extract was resolubilized in SDS-PAGE sample buffer Pasini et al. 2000
Almond major protein [460 kDa] Defatted almond flour extracted with Tris-HCl buffer (pH 8.1), centrifuged and isolation of the almond major protein from supernatant by anion exchange (DEAE column) and gel filtration (Sephacryl column) chromatography, collected fractions pooled and concentrated by membrane filtration, further purification by gel filtration Acosta et al. 1999
Food extracts Food samples ground and extracted with PBS-buffer at 60°C for 2h, centrifuged and supernatant stored at -20°C Hlywka et al. 2000


8 Cross-Reactivities
 
Cross-Reacting Allergens Subjects / Methods References
Almond (Peanut)
peanut
Inhibition of IgE-binding:
by peanut to almond proteins (1 patient, RAST inhibition)
Gillespie et al. 1976
Almond (Peanut, Nuts)
significant associations: peanut, hazelnut, walnut*
262 fruit and/or vegetable allergic patients
(clinical history, SPT, RAST)
Ortolani et al. 1988
Almond (Nuts, Seeds)
hazelnut, brazil nut, sesame seeds *
111 peanut and/or tree nut allergic patients: strong correlation (r >0.7) between almond and hazelnut, brazil nut, and sesame (RAST) Sicherer et al. 1998b
Almond (Nuts)
hazelnut
6 hazelnut allergic adults: Inhibition of IgE binding to hazelnut proteins by almond proteins (appr. 8%) (RAST inhibition) Koppelman et al. 1999
Almond (Nuts)
coconut, walnut 
Strong inhibition of IgE binding to coconut allergens (35, 36.5 and 55 kDa) and to walnut allergen (36 kDa) by almond extract (SDS-PAGE immunoblot, 2 tree nut allergic patients) Teuber & Peterson 1999
Almond (Apple)
apple (indicating allergenic lipid-transfer proteins)
Approximately 98% inhibition of IgE binding to almond proteins by apple peel extract in 1 patient serum specific for lipid-transfer proteins without reactivity to Bet v 1, profilin, and carbohydrate epitopes (RAST inhibition) Asero et al. 2000
Almond (Rye)
rye flour *
Correlation between specific IgE to rye flour and nuts (peanut, almond, brazil nut, coconut, hazelnut)  (3310 atopic patients, RAST, r = 0.5 to 0.8) Seifert et al. 1988
*  multiple sensitization (not proved by inhibition-tests)
 

9 Allergenicity of Different Almond Varieties
 
Varieties / Subjects Differences References
3 Almond Varieties
8 almond sensitive patients
No significant differences in relative amounts and binding patterns of allergens (SDS-PAGE / immunoblot) Bargman et al. 1992

10 Stability of Almond Allergens
 
Treatment Effects References
Almond extract (Storage)
storage of water extract of almond meal
Incubation of a water extract in the presence of azide for about 12 days revealed degradation of the acidic polypeptides of amandin probably by endogenous proteinase(s) Wolf & Sathe 1998
Almonds (Heat, Processing)
commercial samples of almond butter, blanched, and roasted almonds
IgE-binding of protein extract from almond butter similar to that of raw almonds;
blanching and roasting did not affect IgE binding of 45-50 kDa almond allergen, essentially reduced IgE binding of 70 kDa allergen, and eliminated IgE binding of 15 kDa allergen (SDS-PAGE immunoblot, 8 almond sensitive individuals)
Bargman et al. 1992
Almonds (Heat, pH)
a) commercial samples of blanched almonds, roasted almonds, and almond paste
b) moist heating of purified almond major protein at 121°C for 15 min
c) incubation of almond major protein at pH 12.5 and 1.5-2.5
Immunoreactivity of protein extracts in comparison to purified almond major protein (polyclonal rabbit antibodies, noncompetitive ELISA):
a) reactivity of blanched almonds, roasted almonds, and almond paste was respectively  reduced by 50.0%, 56.6%, and 68.4%
b) moist heat pretreatment reduced reactivity by 87%
c) pH extremes (12.5 and 1.5-2.5) caused a 53% and 57% reduction in reactivity, respectively
Acosta et al. 1999
Almond protein isolate (Hydrolysis)
Pepsin digestion of almond protein isolate in 0.1-M HCl at 37°C for 0-60 min (protein enzyme ratios from 50:1 to 1000:1)
Major polypeptides with 38-42 kDa completely hydrolyzed within 2 min, with 20-22 kDa within 5 min; digestion products in the range of 15-36 kDa and 15-20 kDa are hydrolyzed after 45-60 min (SDS-PAGE)  Sze-Tao & Sathe 2000

11 Allergen Sources
 
Reported Adverse Reactions References
Essence in Curry
Severe allergic reactions in a 30 year old woman after ingestion of almond traces from an essence in curry (1)
(1) Ewan 1996
Various Foods
Registration of adverse reactions to foods in Sweden show that 51 out of 77 cases were the result of inadequate labelling; 3 of these cases were due to almond (1)
(1) Kjelkevik et al. 1997

 
Allergens in Food Products Content / Products References
Almonds in Cereals
commercial breakfast cereals
Detection of almond major protein by competitive ELISA inhibition (rabbit polyclonal antibody) Acosta et al. 1999
Chocolate-coated Peanuts
retail samples with undeclared almond content
2 of 4 samples contained 4 and 57 mg/kg almond in whole samples of chocolate-coated peanuts (ELISA, polyclonal antibodies specific for whole almond protein extract) Hlywka et al. 2000
Almond Oils
4 Commercially available almond oils (serum pool from 17 peanut and/or nut allergic patients)
IgE-binding potencies:
blend of unrefined and refined oil (90 / 190°C max. processing temperature) > unrefined oil (57°C)  > 2 refined, bleached, and deodorized oils (230-260°C) (dot immunoblot)
Protein contents of unrefined oils 62 µg/mL, 2 refined oils: 2.2 and 17 µg/mL, and blended oil 13 µg/mL
Teuber et al. 1997

12 Food Allergen Labelling
 
Food Allergen  Labelling / Regulation Status References
International Regulations
Tree nuts* and products of these
mandatory labelling of prepackaged food / advisary status (1) (1) Codex Alimentarius Commission 1999
European Regulations
Tree nuts* and products of these
labelling appropriate / recommendation (1) (1) Bousquet et al. 1998
* Including almond, brazil nut, cashew nut, hazelnut, pistachio, and walnut
 

13 References


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