| Country / Subjects | Sensitivity to | 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, 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 |
| Gran Canaria
142 food allergic adults |
nuts 20% | Castillo et al. 1996 |
| 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, 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, Salamanca
84 mugwort sensitive patients without other pollen sensitizations |
hazelnut 2.4% (RAST) | Garcia-Ortiz et al. 1996 |
| 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) 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, Zurich
402 food allergic adults |
hazelnut 2.5% | Wüthrich 1993 |
| UK, Cambridge
62 peanut and/or nut allergic patients |
hazelnut 21% (SPT) | Ewan 1996 |
| UK, Isle of White
1218 children of general population |
tree nuts 0.7%
hazelnut 0.1% (SPT, Clinical history) |
Tariq et al. 1996 |
| UK, London
100 patients with food intolerance |
nuts/peanuts 22% (repeated challenge) | Lessof et al. 1980 |
| UK, Manchester
172 patients expierenced anaphylactic reactions |
tree nuts 13% (suspected cause of patients' worst reaction) | Pumphrey & Stanworth 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 |
| 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 |
2 Symptoms of Hazelnut Allergy
| Symptoms & Case Reports | References |
| systemic reactions
anaphylaxis (3, 5, 11, 13), exercise-induced anaphylaxis (8, 10) cutaneous symptoms
gastrointestinal symptoms
respiratory symptoms
other symptoms
* symptoms, which could be involved in oral allergy syndrome: local symptoms as intra-oral and lip-irritation, angioedema and systemic symptoms as rhino- conjunctivitis, urticaria- angioedema, asthma, and anaphylaxis (2) |
(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 |
| 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) |
(1) Sicherer et al. 1998 |
3 Diagnostic Features and Therapy 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 |
| 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 |
| 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 |
| Birch Pollen Immunotherapy
67 children with birch pollinosis and reportedly food sensitivity (nuts, apples etc) |
Neither subcutaneous nor oral immunotherapy with birch pollen allergen preparations improved food sensitivity significantly | Moller 1989 |
5 Allergens of Hazelnut and Pollen
| Nut Proteins / Glycoproteins | Allergen Nomenclature | References |
| 18-kDa Allergen | Hirschwehr et al. 1992 | |
| 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 |
| Pollen Proteins / Glycoproteins | Allergen Nomenclature | References |
| Major Pollen Allergen | Cor a 1 | Rohac et al. 1991
Breiteneder et al. 1993 |
| Allergens: 14, 17, 37, 44, 60, and 69 kDa | Hirschwehr et al. 1992 |
5.1 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:
Hazelnut:
|
Hirschwehr et al. 1992 | |||||||||||||||||||||||||||||||||||||||||||||
| Germany, Munich
7 hazelnut allergic patients |
Hazelnut:
20 kDa allergen in 71% 14 - 67 kDa allergens (SDS-PAGE / immunoblot) |
Vocks et al. 1993 |
5.2 18-kDa Allergen
5.3 Major Pollen Allergen (Cor a 1)
| 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 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 |
| Cross-Reacting Allergens | Subjects / Methods | References |
| Hazelnut
birch pollen * |
Partial identity between birch pollen and hazelnut antigens (CLIE using rabbit anti- birch Ab) | Andersen & Lowenstein 1978 |
| Hazelnut
birch pollen * |
Correlation between birch pollen allergy and hazelnut hypersensitivity (1129 adults with bronchial asthma and/or allergic rhinitis, questionaire) | Eriksson 1978 |
| Hazelnut
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, Hazel 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 (Cor
a 1)
birch pollen |
Inhibition of IgE- binding to Cor a 1 by birch pollen extract | Rohac et al. 1991 |
| Hazel 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
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 (17-,
42-, <16-kDa)
mugwort pollen allergens (33-, 65-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
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
significant associations: peanut, walnut, almond * |
262 fruit and/or vegetable allergic patients
(clinical history, SPT, RAST) |
Ortolani et al. 1988 |
| Hazelnut
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 |
| Hazelnut
rye flour * |
Correlation between specific IgE to rye flour and nuts (peanut, almond, brasil nut, coconut, hazelnut) (3310 atopic patients, RAST, r = 0.5 to 0.8) | Seifert et al. 1988 |
| Hazelnut
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 |
| Hazelnut
kiwi fruit, poppy seeds, sesame seeds |
8 Patients with food / pollen allergy (immunoblot inhibition) | Vocks et al. 1993 |
| Hazelnut
kiwi fruit |
3 kiwi allergic patients: moderate inhibition of IgE- binding to kiwi extract by hazelnut extract (RAST inhibition) | Gall et al. 1994 |
| Hazelnut
walnut, brazil nut, almond, 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 |
8 Stability of Hazelnut Allergens
| Treatment | Effects | References |
| Hazelnuts
heat (30 min, 100°C) |
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 |
| 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 |
| 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 |
10 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 |