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• W2033482867 abstract "To the Editor: In areas where birch trees are endemic, hazelnut allergy is often the result of primary sensitization to cross-reactive birch pollen allergen Bet v 1, usually resulting in mild oral allergy syndrome (OAS) in both adults and children.1Hirschwehr R. Valenta R. Ebner C. Ferreira F. Sperr W.R. Valent P. et al.Identification of common allergenic structures in hazel pollen and hazelnuts: a possible explanation for sensitivity to hazelnuts in patients allergic to tree pollen.J Allergy Clin Immunol. 1992; 90: 927-936Abstract Full Text PDF PubMed Scopus (262) Google Scholar, 2Cudowska B. Kaczmarski M. Diagnostic value of birch recombinant allergens (rBet v 1, profilin rBet v 2) in children with pollen-related food allergy.Rocz Akad Med Bialymst. 2004; 49: 111-115PubMed Google Scholar On the other hand, sensitization to hazelnut in early childhood has been related to sensitization to other tree nuts and peanut,3Pumphrey R.S. Wilson P.B. Faragher E.B. Edwards S.R. Specific immunoglobulin E to peanut, hazelnut and Brazil nut in 731 patients: similar patterns found at all ages.Clin Exp Allergy. 1999; 29: 1256-1259Crossref PubMed Scopus (45) Google Scholar, 4Clark A.T. Ewan P.W. The development and progression of allergy to multiple nuts at different ages.Pediatr Allergy Immunol. 2005; 16: 507-511Crossref PubMed Scopus (93) Google Scholar which can all cause serious reactions.5Sicherer S.H. Furlong T.J. Munoz-Furlong A. Burks A.W. Sampson H.A. A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants.J Allergy Clin Immunol. 2001; 108: 128-132Abstract Full Text PDF PubMed Scopus (316) Google Scholar Children can be sensitized to hazelnut at an early age.3Pumphrey R.S. Wilson P.B. Faragher E.B. Edwards S.R. Specific immunoglobulin E to peanut, hazelnut and Brazil nut in 731 patients: similar patterns found at all ages.Clin Exp Allergy. 1999; 29: 1256-1259Crossref PubMed Scopus (45) Google Scholar Remarkably, a large proportion has never to their knowledge ingested hazelnut, and most allergic reactions to nuts in childhood occur after the first known exposure.6Sicherer S.H. Burks A.W. Sampson H.A. Clinical features of acute allergic reactions to peanut and tree nuts in children.Pediatrics. 1998; 102: e6Crossref PubMed Scopus (376) Google Scholar This is the first study to determine the clinical relevance of hazelnut sensitization and eliciting doses (EDs) in childhood by double-blind placebo-controlled food challenge (DBPCFC). Furthermore, we investigated the relation between hazelnut allergy and sensitization to birch pollen and other species of nut and peanut. Twenty-eight sensitized children (8 female, 20 male; age 4-16 years) with suspected allergy to hazelnut were recruited. All children were atopic, with atopic dermatitis the most frequently reported condition (86%). Sixteen children (57%) had seasonal rhinoconjunctivitis. Asthma-related symptoms were reported by 13 children (47%). Sensitization was re-evaluated before DBPCFC by a skin prick test (SPT) with commercial hazelnut extract (ALK-Abelló, Nieuwegein, The Netherlands) and specific IgE levels using the CAP system FEIA (Pharmacia Diagnostics, Uppsala, Sweden) to hazelnut, birch pollen, almond, pecan, walnut, Brazil nut, pistachio, cashew, and peanut. Double-blind placebo-controlled food challenges were performed as described previously,7Flinterman A.E. Pasmans S.G. Hoekstra M.O. Meijer Y. van Hoffen E. Knol E.F. et al.Determination of no-observed-adverse-effect levels and eliciting doses in a representative group of peanut-sensitized children.J Allergy Clin Immunol. 2006; 117: 448-454Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar but not in the tree pollen season between mid-February and mid-June. Briefly, the challenge was composed of 9 portions of defatted hazelnut flour in series: 10 μg, 100 μg, 500 μg, 1 mg, 10 mg, 100 mg, 300 mg, 1 g, and 3 g (protein content, 15.5%; kindly provided by the Food Allergy Research and Resource Program, University of Nebraska). Four placebos were randomly interspersed by the pharmacist to complete the procedure in 1 day. The last dose was unblind and consisted of 10 hazelnuts (5 g; approximately 635 mg protein), because this amount could not be masked in edible portions for children. The challenge was only discontinued after the occurrence of an objective reaction. Sixteen children (57%) did not show any reaction on hazelnut ingestion during the challenge procedure. In 12 children (43%), hazelnut allergy was confirmed by challenge. Doses as large as 1 mg (0.16 mg protein) were tolerated by all children (Table I). Four children (4/12; 33%) reported only OAS without developing objective symptoms at doses starting from 10 mg. One child (#17) refused further portions after aggravating symptoms of OAS at 3 subsequent doses. These children with only OAS were all sensitized to birch pollen. The interval between ingestion and OAS was always less than 10 minutes.Table ISensitization to hazelnut, pollen, and other species of nut, and the results of DBPCFC per individual (n = 28)HazelnutPollen∗Specific IgE in kUA/L; 0: <0.35; 100: >100.Other species of nut and peanut∗Specific IgE in kUA/L; 0: <0.35; 100: >100.DBPCFC HazelnutNo.Age (y)IgE∗Specific IgE in kUA/L; 0: <0.35; 100: >100.SPT†SPT diameter in millimeters.GrassBirchAlmondPecanWalnutBrazilPistachioCashewPeanutSymptoms‡Symptoms: ap, abdominal pain; bro, bronchoconstriction; dia, diarrhea; rc, rhinoconjunctivitis; urt, urticaria; vom, vomiting.ED OAS (mg)ED objective (mg)189410010011114210None——292649760000004None——31417100561000101None——48441001000—0—1015None——516141000010087None——6142621839191022020100None——77150270000339None——8408000—0——40None——9412215301106312None——10603000000441None——1174§Individual with allergic reaction to hazelnut by history.571001111638None——12511258100764810010048None——134126800001122None——147122420001333None——156451001000101101None——1640400.40000003None——17128§Individual with allergic reaction to hazelnut by history.8751136263654OAS100—1842626273332527OAS>3000—19101455800001412725OAS10—20517230000000OAS>3000—2141611329321710840OAS, ap, vom>3000>30002264§Individual with allergic reaction to hazelnut by history.7335122140212866OAS, urt100>300023845126010011322310565952OAS, rc, ap, vom3000>3000241320103462974—1815100OAS, urt, ap100>300025438§Individual with allergic reaction to hazelnut by history.1710222223663OAS, ap, vom100300268481771007131218272750OAS, ap, vom100300027627700.5017410162OAS, urt, rc, bro>3000>300028655100012313710010066OAS, ap, dia>3000>3000∗ Specific IgE in kUA/L; 0: <0.35; 100: >100.† SPT diameter in millimeters.‡ Symptoms: ap, abdominal pain; bro, bronchoconstriction; dia, diarrhea; rc, rhinoconjunctivitis; urt, urticaria; vom, vomiting.§ Individual with allergic reaction to hazelnut by history. Open table in a new tab Eight children (8/12; 67%) developed an objective reaction to hazelnut, such as systemic urticaria, rhinoconjunctivitis, vomiting, and dyspnea. ED for objective reactions ranged from 300 mg to 10 hazelnuts. In 5 children, the objective reactions were preceded by OAS on previous doses (100 mg to 3 g). In 3 children, OAS and objective symptoms developed on the same dose. Late reactions (as long as 24 hours after DBPCFC) were not reported. Three of the children with an objective reaction had low or undetectable birch pollen–specific IgE (<0.35-0.5 international kilounits allergen-specific IgE per liter [kUA/L]), as well as grass pollen-specific IgE (<0.35-1.0 kUA/L). Skin prick test reactivity was significantly different between children without hazelnut allergy, children with only OAS, and children with objective symptoms; the latter group had the highest SPT reactivity. Specific IgE to hazelnut, but also to other species of nut, was significantly higher in children with objective reactions compared with children without objective reaction (children with only OAS or children without any reaction; P < .05 for all nuts, except for peanut, P = .205). Children with objective reactions were sensitized to more species of nuts (median, 6; range, 5-6) than children with only OAS (median, 4.5; range, 0-6) or no reaction (median, 2.5; range, 0-6). IgE reactivity to cross-reactive carbohydrate determinants of glycoproteins was determined in all children using RAST.8Van de Veen M.J. van Ree R. Aalberse R.C. Akkerdaas J. Koppelman S.J. Jansen H.M. et al.Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins.J Allergy Clin Immunol. 1997; 100: 327-334Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar This was negative in all but 1 patient (#23; data not shown) and was not associated with the type of reaction. Challenges are an important tool in diagnosing food allergy.9Bindslev-Jensen C. Ballmer-Weber B.K. Bengtsson U. Blanco C. Ebner C. Hourihane J. et al.Standardization of food challenges in patients with immediate reactions to foods: position paper from the European Academy of Allergology and Clinical Immunology.Allergy. 2004; 59: 690-697Crossref PubMed Scopus (576) Google Scholar In this study, fewer than half of the children with sensitization to hazelnut appeared to be allergic to hazelnut. Moreover, challenges with increasing doses of hazelnut are the only way to determine ED. Doses as large as 1 mg hazelnut flour were tolerated by all children. The ED for OAS (≥10 mg; 1.6 mg protein) and for objective symptoms (≥300 mg; 46.5 mg protein) were in line with previous studies on hazelnut allergy in adults.10Wensing M. Penninks A.H. Hefle S.L. Akkerdaas J.H. van Ree R. Koppelman S.J. et al.The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges.Clin Exp Allergy. 2002; 32: 1757-1762Crossref PubMed Scopus (93) Google Scholar, 11Ortolani C. Ballmer-Weber B.K. Hansen K.S. Ispano M. Wuthrich B. Bindslev-Jensen C. et al.Hazelnut allergy: a double-blind, placebo-controlled food challenge multicenter study.J Allergy Clin Immunol. 2000; 105: 577-581Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar, 12Enrique E. Pineda F. Malek T. Bartra J. Basagana M. Tella R. et al.Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract.J Allergy Clin Immunol. 2005; 116: 1073-1079Abstract Full Text Full Text PDF PubMed Scopus (368) Google Scholar Similar EDs for objective symptoms to peanut were described in a comparable study in peanut-sensitized children: 100 mg peanut flour (50 mg protein).7Flinterman A.E. Pasmans S.G. Hoekstra M.O. Meijer Y. van Hoffen E. Knol E.F. et al.Determination of no-observed-adverse-effect levels and eliciting doses in a representative group of peanut-sensitized children.J Allergy Clin Immunol. 2006; 117: 448-454Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar Although ED for hazelnut appeared to be the same in children and adults, children experienced more objective reactions than adults from our hospital (8/12, 67%, vs 2/29, 6.9%).10Wensing M. Penninks A.H. Hefle S.L. Akkerdaas J.H. van Ree R. Koppelman S.J. et al.The range of minimum provoking doses in hazelnut-allergic patients as determined by double-blind, placebo-controlled food challenges.Clin Exp Allergy. 2002; 32: 1757-1762Crossref PubMed Scopus (93) Google Scholar It is unlikely that this is the result of a selection bias because the referral area is similar. In our study, children with only OAS were all sensitized to birch pollen. In contrast, 3 of the children with additional objective symptoms to hazelnut had low or even undetectable birch pollen–specific IgE. This suggests a nonpollen-related route of sensitization to hazelnut in at least some of the children from areas where birch trees are endemic. In particular, children with objective reactions to hazelnut had high levels of specific IgE to other nuts. The differences in sensitization to nuts between children with and without objective reactions to hazelnut did not appear to be explained by cross-reactive carbohydrate determinant reactivity. Atopic parameters such as total IgE levels and the scoring of atopic dermatitis were similar (data not shown); hence, this does not explain the differences in sensitization either. Although we did not investigate the clinical relevance of all nuts and the history did not provide information on previous exposure to most nuts, avoidance of all nuts may still be advisable in children with objective reactions to hazelnut. For future preventive and therapeutic strategies, it would be interesting to investigate which major allergens are responsible for the primary sensitization in children with objective reactions to hazelnut.13Pastorello E.A. Vieths S. Pravettoni V. Farioli L. Trambaioli C. Fortunato D. et al.Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results.J Allergy Clin Immunol. 2002; 109: 563-570Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar Our data indicate that sensitization to hazelnut is not clinically relevant in about half of the children. OAS was reported by all children with a reaction to hazelnut, at doses starting from 10 mg. Additional objective symptoms were observed in at least 67% of the reactions. These objective reactions to hazelnut were not always accompanied by sensitization to birch pollen, but always by sensitization to other nuts and peanut. This suggests that the route of clinically relevant sensitization to hazelnut in children, in an area where birch trees are endemic, can be nonpollen-related." @default.
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• W2033482867 date "2006-11-01" @default.
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• W2033482867 title "Clinical reactivity to hazelnut in children: Association with sensitization to birch pollen or nuts?" @default.
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