Allergen Data Collection - Update: Hazelnut (Corylus avellana)
Internet Symposium on Food Allergens 3(Suppl.1):1-22  (2001) [http://www.food-allergens.de]
1 Prevalence of Hazelnut 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

Prevalences 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 population". 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)
hazelnut 0.18%
(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
UK
16420 randomly selected adults (age of >15 years)
tree nuts 0.4% (interview survey, questionnaire) Emmett et al. 1999
UK, Isle of White
1218 children of general population
tree nuts 0.7%
hazelnut 0.1% (SPT, Clinical history)
Tariq et al. 1996
USA
a) adults and b) children of general population
peanut and/or tree nuts 
a) 1.6% b) 0.6%
(telephone survey, estimated corrected prevalence: 1.1% in general population)
Sicherer et al. 1999

1.2 Subjects with Atopic or Other Diseases
 
Country / Subjects Allergy / Sensitivity References
Croatia, Zagreb
71 confectionary workers
hazelnut 6% (SPT) Zuskin et al. 1994
Denmark, Copenhagen
101 birch pollen and/or hazelnut sensitive patients
hazelnut 72% (SPT) Andersen & Lowenstein 1978
France
20 latex allergic or at risk patients
hazelnut 15% (RAST) Leonard et al. 1996
France
80 cases of food- related anaphylaxis (study period 1993-97)
hazelnut, cashew nut, pistachio 7.5% (reported to CICBAA databank) European Commission 1998
France, Nancy and Toulouse
544 food allergic children
hazelnut 2.7% (food challenge) Rance et al. 1999
France, Paris
19 patients with exercise-induced anaphylaxis
tree nuts 32% (SPT, RAST) Guinnepain et al. 1996
France, Pierre Benite
580 patients with adverse reactions to food
hazelnut 22% (RAST) Andre et al. 1994
France, Toulouse
142 food allergic children
hazelnut 1.4 % (labial food challenge) Rance & Dutau 1997
Germany, Berlin
167 pollen and food sensitive patients
hazelnut 90% and 78%
(SPT and case history)
Jankiewicz et al. 1996
Germany, Cologne
225 hazel pollen allergic patients
hazelnut 92% (scratch test) Herkenrath et al. 1982
Germany, Ulm
80 patients with pollen associated food allergy
hazelnut 71% (clinical history, SPT) Boehncke et al. 1998
Italy, Florence
54 episodes of food-dependent anaphylaxis in 44 children (age of 1 month to 16 years) (from 1994-1996)
hazelnut 1.9% Novembre et al. 1998
Italy, Genoa
132 pollen and food sensitive patients
hazelnut 22%
(incidents of hypersensitivity)
Troise et al. 1992
Italy, Milan
262 fruit and/or vegetable allergic patients
hazelnut 37 % (clinical history) Ortolani et al. 1988
Italy, Milan
100 fruit and/or vegetable allergic patients
hazelnut 32 % (clinical history) Ortolani et al. 1989
Netherlands
131 cases of food- induced anaphylaxis
(from 1993-1997)
tree nuts 18% (survey, reported to the TNO Nutrition and Food Research Institute) European Commission 1998
Netherlands, Rotterdam
79 tree-pollen allergic patients
hazelnut 90%, 40%, and 44%
(SPT, RAST, and case history)
de Groot et al. 1996
Poland
163 food allergic infants
hazelnut 42% (RAST) Hofman 1994
Spain, Barcelona
102 patients allergic to dried fruits
hazelnut 76%, 58%, and 69%
(SPT, HR, and RAST)
Amat Par et al. 1990
Spain, Madrid
355 food allergic children
hazelnut 5.4% (SPT, RAST) Crespo et al. 1995
Spain, Madrid
29 plant-derived food allergic patients
hazelnut 10% (SPT) Diez-Gomez et al. 1999
Spain, Pamplona
74 patients with atopic dermatitis
nuts 6.8%(SPT, RAST, Histamine Release) Resano et al. 1998
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) hazelnut 2.4% (RAST)
b) hazelnut 8.8%(clinical history)
a) Garcia-Ortiz et al. 1996
b) Garcia Ortiz et al. 1998
Sweden
60 severe allergic reactions caused by food
soybean, nuts and almonds >70% Foucard et al. 1997
Sweden
a) 61 cases of food- induced anaphylaxis (from 1994-1996)
b) 55 cases of food- induced anaphylaxis (from 1994-1996)
a) tree nuts 18% (reported to the National Food Administration)
b) tree nuts 16%(Hospital Reports)
European Commission 1998
Sweden, Halmstad / Malmö
a) 380 birch pollen allergic patients
b) 103 patients without birch pollen allergy
a) hazelnut 53%
b) hazelnut 7%
(questionaire)
Eriksson et al. 1982
Sweden, Skövde
47 birch pollen allergic patients
nuts and apples 68% (Clinical history) Fogle-Hansson & Bende 1993
Switzerland, Bern
22 patients with severe food-induced anaphylaxis (study period 1994-96)
nuts 14% Rohrer et al. 1998
Switzerland, Zurich
a) 402 food allergic adults (study period 1978-87)
b) 383 food allergic patients (study period 1990-94)
a) hazelnut 2.5%
b) hazelnut 37%
(anamnesis, clinical relevance, diagnostic tests)
a) Wüthrich 1993
b) Etesamifar & Wüthrich 1998
UK, Cambridge
62 peanut and/or nut allergic patients
hazelnut 21% (SPT) Ewan 1996
UK, London
100 patients with food intolerance
nuts/peanuts 22% (repeated challenge) Lessof et al. 1980
UK, Manchester
90 patients expierenced anaphylactic reactions to foods (from 1994-1996)
hazelnut 4.4% (suspected cause of patients' worst reaction) Pumphrey & Stanworth 1996
USA, Denver, CO
a) 180 food allergic children
b) 32 peanut allergic children
a) nuts 10% (DBPCFC)
b) nuts 0% (DBPCFC)
Bock & Atkins 1990
USA, Little Rock, AR
54 tree nut allergic patients
hazelnut 13% (acute allergic reactions) Sicherer et al. 1998

1.3 Associated Allergies
 
Country / Subjects Allergy / Sensitivity References
Multicenter (Copenhagen, Milan, Zurich)
67 patients with positive DBPCFC to hazelnut
birch pollen 87% (SPT) Ortolani et al. 2000
Switzerland, Zurich
19 patients with positive DBPCFC to hazelnut
hazel pollen 100%
birch pollen 100%
alder pollen 100%
ash pollen 68%
grass pollen 53%
rye pollen 53%
mugwort pollen 16% (SPT)
Ballmer-Weber et al. 2000

2 Symptoms of Hazelnut Allergy
 
Symptoms & Case Reports References
systemic reactions
anaphylaxis (3, 5, 11, 13), exercise-induced anaphylaxis (8, 10)

cutaneous symptoms
angioedema (1, 7, 13), atopic dermatitis (7), eyelid angioedema (2, 7), eczema (9), seasonal rhinoconjunctivitis (13), urticaria (1, 3, 4, 7, 13)

gastrointestinal symptoms
angioedema of lips and tongue (7), diarrhea (7), glottis edema (7), laryngeal edema (3, 9), oral itching (2, 4, 5, 9), swelling of lips, tongue, and throat (4), vomiting (7, 9), oral allergy syndrome (2, 12, 13), perioral erythema and itching (4), in general (4)

respiratory symptoms
allergic rhinitis (9), asthma (3, 7, 9), bronchial obstruction (1), dyspnoea (9)

other symptoms
migraine (intolerance reaction) (6)

(1) Aas 1978
(2) Ortolani et al. 1989
(3) Gluck 1990
(4) Hirschwehr et al. 1992
(5) Fogle-Hansson & Bende 1993
(6) Guariso et al. 1993
(7) Vocks et al. 1993
(8) Martin-Munoz et al. 1994
(9) Ewan 1996
(10) Guinnepain et al. 1996
(11) Pumphrey & Stanworth 1996
(12) Asero 1997
(13) Diez-Gomez et al. 1999
Onset of Symptoms
Symptoms occurred immediately or within a few minutes in all patients after ingestion of hazelnut, 1 patient had additional reactions of conjunctivitis and rhinitis after 4 hours (67 DBPCFC positive patients)
(1) Ortolani et al. 2000
Percentage of reactions
Asthma 65%, atopic dermatits 80%, allergic rhinitis 55%, and food hypersensitivity 90% in 20 tree nut allergic patients without peanut allergy (1)

Symptoms of first acute allergic reactions to tree nuts in 54 patients: skin only 28%, respiratory only 11%, gastrointestinal only 3%, skin and respiratory 31%, skin and gastrointestinal 5%, gastrointestinal and respiratory 1%, all 3 systems 21% (1)

Symptoms after DBPCFC with hazelnut in 67 patients: oral allergy syndrome in 88%, oral and gastrointestinal symptoms in 4.5%, and oral and systemic symptoms in 7.5% (2)

(1) Sicherer et al. 1998
(2) Ortolani et al. 2000
Threshold for Elicitation of Symptoms
A dose of 500 mg filbert (Corylus maxima) induced symptoms of asthma, conjunctivitis, and urticaria in a hazelnut allergic patient (DBPCFC) (1)
The mean provocative doses were 1.4 g, 2.7 g, and 15.3 g hazelnut in hazelnut allergic patients from Copenhagen, Zurich, and Milan, respectively (DBPCFC) (2)
(1) Bock 1978
(2) Ortolani et al. 2000

3 Diagnostic Features of Hazelnut Allergy
 
Parameters / Subjects Outcome References
Age and Onset of Symptoms
54 tree nut allergic patients
Age of patients at first reactions:
62 months (10 to 264 months)
Time of onset after ingestion: 2 min (0.3 to 30 min)
(median / range)
Sicherer et al. 1998
Age and Gender
731 tree nut allergic patients
(age 7 months to 65 years, median 6.6 years)
Similar sensitization pattern to peanut, hazelnut, and brazil nut at all ages and gender (RAST) Pumphrey et al. 1999
IgE
patients who believed they never ingested tree nuts
Hazelnut specific serum IgE (RAST):
2.7 kIU/L (median)
Sicherer et al. 1998
IgE
birch pollen allergic patients:
a) responding and b) non-responding to DBPCFC with birch pollen related foods
Hazelnut specific serum IgE (RAST):
a) 17.4 kU/L
b) 8.6 kU/L
(mean values, no significant difference)
Reekers et al. 1999
SPT, IgE and Clinical Relevance
nut allergic patients
SPT and RAST were found to be reliable for the diagnosis of allergy to nuts Aas 1978
SPT, IgE and Clinical Relevance
43 to 67 hazelnut allergic patients
positive reactions in 51% and 12% of patients with clinical hazelnut allergy tested with fresh hazelnuts and commercial extracts, respectively (SPT)
hazelnut specific IgE in 55% of patients with clinical hazelnut allergy (RAST)
Ortolani et al. 1988
a) RAST and Clinical Relevance
b) SPT and Clinical Relevance
27 patients with clinical history of hazelnut allergy
a)  RAST (specific IgE > 0.7 kU/L):
positive results in 48%
positive preditive value 72% 
negative preditive value 52%
b) SPT with commercial extracts and fresh food:
positive results in 22% and 41%
positive preditive value 66% and 73%
negative preditive value 45% and 51%
Ortolani et al. 1989
RAST and Clinical Relevance
46 patients with clinical history and positive SPT to hazelnut
Hazelnut specific RAST:
positive 87%
negative 13%
Boehncke et al. 1998
SPT, RAST, Histamine Release and Clinical Relevance
102 patients allergic to dried fruits
Correlation of tests to clinical history of hazelnut allergy:
87% for SPT
80% for HR
89% for RAST
Amat Par et al. 1990
SPT, RAST and Histamine Release
30 birch pollen allergic patients with clinical symptoms of hazelnut allergy
Positive results to hazelnut in:
50% by SPT
43% by RAST
80% by Histamine Release
Bindslev-Jensen et al. 1991
RAST and Open Challenge
children considered on history to be allergic to tree nuts
Children with positive IgE tree nut titres:
>50% negative challenge test
Armstrong & Rylance 1999
SPT, RAST, and DBPCFC
86 patients with history of hazelnut allergy (from Copenhagen, Milan, Zurich) 
Positivity in DBPCFC: 78% (8 placebo responders; 11 non-responders of which 4 had positive open- challenge)
Tests in DBPCFC-positive subjects:
a)  RAST (specific IgE > 0.7 kU/L):
positive preditive value 92% 
negative preditive value 5%
b) SPT with commercial extracts and fresh food:
positive preditive value 92% and 94%
negative preditive value 5% and 15%
Ortolani et al. 2000
Open Challenge
17 children with perceived peanut or tree nut allergy
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
HLA Genotypes
Birch pollen and hazelnut allergic patients
HLA-alleles DRB1*01, DQA1*0101, and DQB1*0501 were significantly decreased as compared to pollen allergic patients in general; insignificant differences as compared to birch pollen allergic individuals without hazelnut allergy Boehncke et al. 1998
Birch Pollen spec. IgE
103 birch pollen- hypersensitive patients free of oral allergy syndrome (at begin of the followed-up study)
Birch pollen specific serum IgE- levels in patients:
a) who developed Apiaceae (carrot, celery, fennel) sensitivity 15.5 AU/mL
b) who developed apple/hazelnut allergy only  8.5 AU/mL
c) who remained free of oral allergy syndrome 5 AU/mL
(median values, P < 0.05)
Asero 1997
Birch Pollen spec. IgE
19 patients with positive DBPCFC to hazelnut
All patients had Bet v 1-specific IgE and 5 patients had Bet v 2-specific IgE (RAST) Ballmer-Weber et al. 2000

4 Therapy of Hazelnut Allergy
 
Treatment* Outcome References
Treatment with Astemizole
30 birch pollen allergic patients with clinical symptoms of hazelnut allergy
Treatment with astemizole significantly reduced the symptoms after oral provocation with hazelnuts compared with placebo (P = 0.004) without completely abolishing symptoms Bindslev-Jensen et al. 1991
Tree Pollen Immunotherapy
72 children with birch pollinosis (age of 6-16 years), prevalence of adverse reactions to nuts before immunotherapy 79%
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 Hazelnut
 

6 Allergens of Hazelnut and Pollen
 
 
Nut Proteins / Glycoproteins Allergen Nomenclature References
Major Hazelnut Allergen [18 kDa] Cor a 1.0401 Hirschwehr et al. 1992, Lüttkopf et al. 1999 [GenBank]
Hazelnut Profilin   van Ree et al. 1992, 1995
Lipid-transfer protein [9 kDa]   Akkerdaas et al. 2000
Allergens: 14, 18, 37, 40, 46, and 69 kDa   Hirschwehr et al. 1992
Allergens:  2 allergens <16 kD, 17 kDa, and 42 kDa   Caballero et al. 1997
Allergens: 7, 9, 38, 42, and 50 kDa   Schocker et al. 1999
Allergens: 25, 37, and 55 kDa, and 14, 18, 22, and 69 kDa   Koppelman et al. 1999
4.8 kDa Allergen   Hird et al. 2000

 
Pollen Proteins / Glycoproteins Allergen Nomenclature References
Major Pollen Allergen [17 kDa] Cor a 1 Rohac et al. 1991, Breiteneder et al. 1993, Hoffmann-Sommergruber et al. 1997
Allergens: 14, 17, 37, 44, 60, and 69 kDa   Hirschwehr et al. 1992

6.1 Sensitization to Hazelnut Allergens
 
Country / Subjects Sensitivity to References
Austria, Vienna
a) 25 hazel pollen and hazelnut allergic patients
b) 18 hazel pollen  allergic patients without sensitivity to hazelnuts
Hazel pollen:
Allergen in a) in b)
14 kDa profilin
8%
17 kDa  (Cor a 1) 
100%
100%
30 kDa allergen
6%
37 kDa allergen
4%
6%
44 kDa allergen
12%
60 kDa allergen
24%
69 kDa allergen
12%
17%

Hazelnut:
Allergen in a) in b)
14 kDa allergen
8%
18 kDa allergen
100%
22%
37 kDa allergen
20%
40 kDa allergen
8%
46 kDa allergen
4%
69 kDa allergen
16%
(SDS-PAGE immunoblot)

Hirschwehr et al. 1992
Germany,  Berlin / Borstel / Langen
a) 27 hazelnut allergic patients
b) 28 hazelnut and birch pollen sensitive children
Hazelnut:
Allergen in a) in b)
17-18 kDa allergen 93% 79%
48 kDa glycoprotein 41% 61%
(SDS-PAGE / immunoblot)
Müller et al. 2000
Germany, Munich
7 hazelnut allergic patients
Hazelnut:
20 kDa allergen in 71%
14 - 67 kDa allergens
(SDS-PAGE / immunoblot)
Vocks et al. 1993
UK, Manchester / York
4 hazelnut-peanut sensitized patients
Hazelnut:
4.8 kDa allergen
(2D-PAGE / immunoblot, MALDI-TOF)
Hird et al. 2000

6.2 Major Hazelnut Allergen (Cor a 1.0401)
6.3 Major Pollen Allergen (Cor a 1)
 

7 Isolation & Preparation
 
Extract / Purified Allergens Methods References
Protein extract from nuts Nuts grounded under liquid nitrogen, extraction overnight at 4°C with potassium phosphate buffer (pH 7.0) containing PVPP, EDTA, sodium diethyldithiocarbamate and sodium azide, centrifugation, filtration, dialysis, and lyophylization, storage -20°C Hirschwehr et al. 1992
Protein extract from nuts Comparison of different extraction conditions (3 buffer systems, 3 temperatures for 4h): no differences in IgE- binding, maximum yield of soluble proteins with tris/tricine buffer at 45°C Vieths et al. 1998
Protein extract from nuts Nuts were peeled, chopped, and ground; extraction with ammonium carbonate buffer (pH 8.0) at 4°C for 4h; filtration, defatted extract centrifued, supernatant dialyzed and lyophylized, storage -20°C Caballero et al. 1997
Protein extract from nuts Nuts blended and added to ammonium bicarbonate buffer (pH 7.8), placed on ice, blended and rocked for 48 h at 4°C, centrifugation, storage at -70°C Teuber et al. 1997
Protein extract from nuts Hazelnuts were shelled, skinned, and ground; extraction with bicarbonate buffer (pH 9.2) containing tetramethylen sulphone; homogenization and stirring for 1 h at RT; centrifugation and protein precipitation with acetone at -20°C for 30 min; after centrifugation protein solids washed with butanol and dried Hird et al. 2000
Protein extract from oil Oil added to ammonium bicarbonate buffer (pH 7.8), rocked for 48 h at 4°C, centrifugation, and aqueous layer ultracentrifuged, storage at -70°C Teuber et al. 1997
18-kDa allergen from hazelnut Hazelnut protein extract treated 3 times with Bioacryl BPA-1000 (precipitation of nucleic acid and major proteins other than 18-kDa allergen), centrifugation, dialysis of supernatant, further purification with IEC and RP-HPLC Hirschwehr et al. 1992
Schenk et al. 1994
Hazelpollen allergen Cor a 1 Aqueous extract of hazelpollen followed by preparative RP-HPLC Ebner et al. 1993


8 Cross-Reactivities
 
Cross-Reacting Allergens Subjects / Methods References
Hazelnut (Pollen)
birch pollen *
Partial identity between birch pollen and hazelnut antigens (CLIE using rabbit anti- birch Ab) Andersen & Lowenstein 1978
Hazelnut  (Pollen)
birch pollen *
Correlation between birch pollen allergy and hazelnut hypersensitivity  (1129 adults with bronchial asthma and/or allergic rhinitis, questionaire) Eriksson 1978
Hazelnut  (Pollen)
alder, hazel, aspen, and bog-myrde pollen *
Correlation between sensitization to hazelnut and pollen in birch pollen allergic patients (SPT) Eriksson et al. 1982
Hazelnut (Pollen)
tree (elm, olive, birch, plane, ash), weed (parietaria, mugwort), and grass pollen *
Sensitization to pollens in 63 hazelnut allergic patients: tree pollen 67%, weeds 40%, grasses 11%  (2 positive results from SPT, HR, and RAST) Amat Par et al. 1990
Hazel pollen (Pollen)
birch pollen, Cor a 1
Inhibition of IgE- binding to Cor a 1 by birch pollen extract Rohac et al. 1991
Hazelnut, Hazel pollen (Pollen)
birch pollen allergens: 
a) rBet v 1
b) rBet v 2 (profilin)
3 patients with hazel pollen and hazelnut allergy (pooled serum):
a) IgE- binding to 18 kDa hazelnut allergen and Cor a 1 was abolished by rBet v 1
b) IgE- binding to 14 kDa hazelnut and hazel pollen allergens was abolished by rBet v 2
(immunoblot inhibition)
Hirschwehr et al. 1992
Hazel pollen (Pollen)
birch pollen allergens: 
rBet v 1 and rBet v 2 (profilin)
102 patients from Austria, France, Sweden, and Switzerland: 75 to 84% inhibition of IgE- binding to hazel pollen extract by a combination of recombinant Bet v 1 and Bet v 2 (mean percentages, RAST inhibition)
11 tree pollen allergic patients:
inhibition of IgE- binding to 2 hazel pollen allergens of 12 to 17 kDa by Bet v 1 and Bet v 2 (immunoblot inhibition)
Niederberger et al. 1998
Hazelnut  (Pollen)
mugwort pollen
Serum pool from 28 patients with specific IgE to mugwort pollen and hazelnut:
63% inhibition of IgE- binding to hazelnut by mugwort; 36% inhibition of IgE- binding to mugwort by hazelnut (RAST inhibition)
Caballero et al. 1997
Hazelnut  (Pollen)
mugwort pollen allergens (33-, 65-kDa), hazelnut allergens (17-, 42-, <16-kDa)
Hazelnut extract inhibits IgE- binding to 33- and 65-kDa mugwort allergens; mugwort extract inhibits IgE- binding to all hazelnut allergens (SDS-PAGE and IEF-PAGE immunoblot inhibition) Caballero et al. 1997
Hazelnut  (Pollen)
hazel pollen
5 patients with hazel pollen and hazelnut allergy (pooled serum):
IgE- binding to hazelnut allergens was reduced by hazel pollen extract;
IgE- binding to hazel pollen allergens was not reduced by hazelnut extract
(immunoblot inhibition)
Hirschwehr et al. 1992
Hazelnut: (Pollen)
birch pollen, rBet v 1, rBet v 2 profilin, timothy grass pollen extract;
21 patients with clinical relevant allergy to pollen and plant-derived food
Mixture of rBet v 1 and rBet v 2 inhibited IgE-binding to 10-14 kDa (profilin related) and 17-21 kDa (Bet v 1 related) hazelnut allergens, timothy grass pollen inhibited IgE-binding to 30-100 kDa allergens from hazelnut (immunoblot inhibition);
83% (4-100%) inhibition of IgE-binding to hazelnut extract by mixture of rBet v 1 and rBet v 2 and 94% (17-100%) by mixture of rBet v1, rBet v 2, and timothy pollen extract  (26 sera)  (RAST inhibition)
Kazemi-Shirazi et al. 2000
Hazelnut  (Nuts)
walnut, cashewnut, pecannut, almond
6 hazelnut allergic adults: Inhibition of IgE binding to hazelnut proteins by walnut (30-35%), cashewnut and pecannut (appr. 15%), and almond (appr. 8%) (RAST inhibition) Koppelman et al. 1999
Hazelnut (Nuts, Peanuts)
significant associations: peanut, walnut, almond *
262 fruit and/or vegetable allergic patients
(clinical history, SPT, RAST)
Ortolani et al. 1988
Hazelnut  (Nuts, Peanuts, Seeds)
walnut, brazil nut, almond, pecan, pistatio, pine nut, peanut, sesame seeds *
111 peanut and/or tree nut allergic patients: strong correlation (r >0.7) between hazelnut and walnut, brazil nut, almond, and sesame; moderate correlation (r >0.6) between hazelnut and peanut, pecan, pistachio, and pine nut (RAST) Sicherer et al. 1998
Hazelnut (Fruits, Seeds)
kiwi fruit, poppy seeds, sesame seeds
8 Patients with food / pollen allergy (immunoblot inhibition) Vocks et al. 1993
Hazelnut  (Fruits)
kiwi fruit
3 kiwi allergic patients: moderate inhibition of IgE- binding to kiwi extract by hazelnut extract (RAST inhibition) Gall et al. 1994
Hazelnut (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
Hazelnut  (Various Foods)
kiwi fruit, poppy seeds, sesame seeds, rye flour
5 patients: 50 to 100% inhibition of IgE- binding to poppy seed by hazelnut;
2 patients each: 56 and 84% inhibiton to kiwi by hazelnut, 78 and 91% inhibition to sesame seed by hazelnut;
1 patient: 77 and 84% inhibition to rye flour by hazelnut and vice versa
(RAST inhibition)
Seifert et al. 1988
*  multiple sensitization (not proved by inhibition-tests)
 

9 Allergenicity of Different Hazelnut Varieties
 
Varieties / Subjects Differences References
6 Hazelnut Varieties
hazelnut allergic patients
No significant differences in relative amounts of allergens (SDS-PAGE / immunoblot) Vieths et al. 1998
5 Hazelnut Varieties
8 hazelnut allergic patients
Similar IgE binding patterns to all varieties, slight differences as regards intensity of detection (SDS-PAGE / immunoblot)
Minor differences in IgE-binding potencies of varieties: Contorta (Germany) > Barcelona (USA) > Levantiner (Turkey) and Neapler (Sicily) > Römer (Italy) (EAST inhibition)
Wigotzki et al. 2000b

 

10 Stability of Hazelnut Allergens
 
Treatment Effects References
Hazelnuts (Storage)
storage (1 to 19 weeks at room temperature)
No significant differences as compared to native hazelnuts (SDS-PAGE immunoblot, EAST inhibition) Wigotzki et al. 2000b
Hazelnuts (Heat)
heating to 100°C for 30 min
Heating of the food reduced allergenic activity in anti-birch pollen IgE system, while considerable activity was retained in anti- hazelnut IgE system (RBL cell mediator release assay) Vieths et al. 1998
Hazelnuts (Heat)
roasting to 140°C for a) 20 min and b) 40 min
Positivity in SPT with:
raw hazelnuts 95%
roasted hazelnuts a) 47%
roasted hazelnuts b) 11%
(19 patients with positive DBPCFC to hazelnut)
Ballmer-Weber et al. 2000
Hazelnuts (Heat)
heating of ground hazelnuts at 100-185°C for 15-90 min (dry heating oven) or microwave heating (630 W, 10 min)
No reduction of IgE binding after heating 100°C for 90 min or after microwave treatment; decrease of IgE binding after heating to >100°C for 15 min; after heating to >170°C the major allergens abolished in immunoblotting; a minor allergen with <14 kDa detectable after heating up to 185°C for 15 min  (19 hazelnut allergic patients, SDS-PAGE immunoblot, EAST inhibition) Wigotzki et al. 2000b
Hazelnuts (Hydrolysis)
2 step digestion with a) pepsin (2 h) and b) pancreatic enzymes (45 min) (extract from hazelnuts)
IgE-binding after combined hydrolysis (a + b)  of hazelnut proteins reduced to <10% as compared to native protein extract (EAST, hazelnut allergic patients) Vieths et al. 1999
Hazelnuts (Enzymic Hydrolysis)
hydrolysis of hazelnut proteins up to 240 min with 
a) pepsin
b) trypsin, elastase, and protease (from Tritirachium album)
c) pancreatin
a) only slightly decrease in IgE-binding after peptic hydrolysis for 60 min (maximum EAST inhibition appr. 65%); after 240 min maximum EAST inhibition was about 40% as compared to native hazelnut extract and 2/7 sera still showed IgE-binding in SDS-PAGE immunoblot
b) hydrolysis with trypsin, elastase, and protease (from Tritirachium album) significantly decreased IgE-binding after 30 min of treatment to a maximum EAST inhibition <30%
c). Hydrolysis with pancreatin for 60 min reduced IgE-binding to < 30% maximum inhibition
(15 hazelnut allergic patients)
Wigotzki et al. 2000a

11 Allergen Sources
 
Reported Adverse Reactions References
Food / Food additives
After ingestion of hazelnuts (1)
Ingestion of hazelnut fragment in muesli (2)
Accidental ingestion of tree nuts by 30% of tree nut allergic patients over a period of 5.5 years (3)
(1) see 2 Symptoms of Hazelnut Allergy
(2) Ewan 1996
(3) Sicherer et al. 1998
Chocolate
Asthma after ingestion of 3-6 g of chocolate containing 0.2% of hazelnut proteins (1)
(1) Malmheden Yman et al. 1994

 
Potential Adverse Reactions References
Food compounds
Nickel allergy: Consumption of hazelnuts in larger amounts may increase the nickel intake, which potentially could elicit nickel allergic reactions (2)
Salicylic acid intolerance: Correlation between acetylsalicylic acid intolerance and hazelnut hypersensitivity maybe due to natural content of salicylic acid  (1129 adults with bronchial asthma and/or allergic rhinitis, questionaire) (1)
(1) Eriksson 1978
(2) Flyvholm et al. 1984

 
Allergens in Hazelnut Products Content / Products References
Hazelnut Allergens
hazelnut oil (blend of refined and unrefined oils) and pool serum from 17 nut or peanut allergic patients 
Protein content in hazelnut oil: 62 µg/ml; IgE- binding to protein extract in dot immunoblot Teuber et al. 1997
Hazelnut Proteins
commercial food products without labeling of hazelnut
a) Amounts of hazelnut between 1.8 and 421 mg/kg  in 14 of 27 samples (ELISA, polyclonal antibodies, limit of detection 0.002%)
b) Qualitative detection of hazelnut in the same samples as a), no false positive results (hazelnut specific PCR detection of 182bp product from cDNA of Cor a 1.0401, limit of detection 0.001%)
a) Holzhauser & Vieths 1999
b) Holzhauser et al. 2000
Hazelnut Proteins
samples assumed to be free of hazelnuts: chocolate spread, chocolate bar, chocolate cookie, muesli cookie, and cake
Amounts of hazelnut between 3.4 and 752 mg/kg  in 15 of 26 samples; a complaint sample of chocolate spread contained 4 g/kg of undecleared hazelnut (ELISA, rabbit-antibodies) Koppelman et al. 1999

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

13 References


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