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Pathogenesis of oral allergy syndrome (pollen-food allergy syndrome)

Anna Nowak-Węgrzyn, MD
Section Editor
Scott H Sicherer, MD, FAAAAI
Deputy Editor
Anna M Feldweg, MD


Pollen-food allergy syndrome (PFAS or PFS) describes allergic reactions, usually limited to the oropharynx, which occur upon ingestion of certain fresh fruits, nuts, or vegetables in individuals who are sensitized to plant pollens [1,2]. These reactions are a form of immunoglobulin E (IgE)-mediated hypersensitivity. The causative allergens in these plant foods are homologous to pollen allergens [3,4]. The disorder is also called "pollen-food syndrome" and "pollen-associated food allergy syndrome" [5].

Oral allergy syndrome (OAS) is a term used variably as a synonym of PFS or to describe just the isolated oropharyngeal symptoms caused by pollen-related foods. In this review, OAS is applied to isolated oropharyngeal symptoms.

The symptoms of OAS result from contact urticaria of the oropharynx. Symptoms are usually limited to the mouth and throat and only observed with raw forms of the food because the causative allergens are rapidly inactivated by digestion and cooking, although this is not uniformly true. Systemic reactions as well as reactions to cooked foods are observed in a small proportion of patients.

This topic review will present the pathogenesis of PFS. The clinical manifestations, risk factors, diagnosis, and management of PFS are presented elsewhere. (See "Clinical manifestations and diagnosis of oral allergy syndrome (pollen-food allergy syndrome)" and "Management and prognosis of oral allergy syndrome (pollen-food allergy syndrome)".)


Fruit and vegetable allergens are highly conserved and share varying degrees of homology with allergens from other fruits and vegetables as well as pollens. This structural and functional homology underlies the extensive cross-reactivity observed clinically [6-8].

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Literature review current through: Nov 2017. | This topic last updated: Oct 24, 2017.
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  1. Rodriguez J, Crespo JF, Burks W, et al. Randomized, double-blind, crossover challenge study in 53 subjects reporting adverse reactions to melon (Cucumis melo). J Allergy Clin Immunol 2000; 106:968.
  2. Rodriguez J, Crespo JF, Lopez-Rubio A, et al. Clinical cross-reactivity among foods of the Rosaceae family. J Allergy Clin Immunol 2000; 106:183.
  3. Ortolani C, Ispano M, Pastorello E, et al. The oral allergy syndrome. Ann Allergy 1988; 61:47.
  4. Vieths S, Hoffmann A, Holzhauser T, et al. Factors influencing the quality of food extracts for in vitro and in vivo diagnosis. Allergy 1998; 53:65.
  5. NIAID-Sponsored Expert Panel, Boyce JA, Assa'ad A, et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010; 126:S1.
  6. Valenta R, Kraft D. Type 1 allergic reactions to plant-derived food: a consequence of primary sensitization to pollen allergens. J Allergy Clin Immunol 1996; 97:893.
  7. Kazemi-Shirazi L, Pauli G, Purohit A, et al. Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy. J Allergy Clin Immunol 2000; 105:116.
  8. Werfel T, Asero R, Ballmer-Weber BK, et al. Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens. Allergy 2015; 70:1079.
  9. Fernández-Rivas M, Bolhaar S, González-Mancebo E, et al. Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin Immunol 2006; 118:481.
  10. Smole U, Wagner S, Balazs N, et al. Bet v 1 and its homologous food allergen Api g 1 stimulate dendritic cells from birch pollen-allergic individuals to induce different Th-cell polarization. Allergy 2010; 65:1388.
  11. Bégin P, Des Roches A, Nguyen M, et al. Freezing does not alter antigenic properties of fresh fruits for skin testing in patients with birch tree pollen-induced oral allergy syndrome. J Allergy Clin Immunol 2011; 127:1624.
  12. Enrique E, Cisteró-Bahíma A, Bartolomé B, et al. Platanus acerifolia pollinosis and food allergy. Allergy 2002; 57:351.
  13. Lauer I, Miguel-Moncin MS, Abel T, et al. Identification of a plane pollen lipid transfer protein (Pla a 3) and its immunological relation to the peach lipid-transfer protein, Pru p 3. Clin Exp Allergy 2007; 37:261.
  14. Ebner C, Birkner T, Valenta R, et al. Common epitopes of birch pollen and apples--studies by western and northern blot. J Allergy Clin Immunol 1991; 88:588.
  15. Ebner C, Hirschwehr R, Bauer L, et al. Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin). J Allergy Clin Immunol 1995; 95:962.
  16. Breiteneder H, Radauer C. A classification of plant food allergens. J Allergy Clin Immunol 2004; 113:821.
  17. Schimek EM, Zwölfer B, Briza P, et al. Gastrointestinal digestion of Bet v 1-homologous food allergens destroys their mediator-releasing, but not T cell-activating, capacity. J Allergy Clin Immunol 2005; 116:1327.
  18. Bohle B, Zwölfer B, Heratizadeh A, et al. Cooking birch pollen-related food: divergent consequences for IgE- and T cell-mediated reactivity in vitro and in vivo. J Allergy Clin Immunol 2006; 118:242.
  19. Jahn-Schmid B, Radakovics A, Lüttkopf D, et al. Bet v 1142-156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1-related food allergens. J Allergy Clin Immunol 2005; 116:213.
  20. Bohle B. The impact of pollen-related food allergens on pollen allergy. Allergy 2007; 62:3.
  21. Santos A, Van Ree R. Profilins: mimickers of allergy or relevant allergens? Int Arch Allergy Immunol 2011; 155:191.
  22. Tordesillas L, Pacios LF, Palacín A, et al. Characterization of IgE epitopes of Cuc m 2, the major melon allergen, and their role in cross-reactivity with pollen profilins. Clin Exp Allergy 2010; 40:174.
  23. Pastorello EA, Farioli L, Pravettoni V, et al. The major allergen of peach (Prunus persica) is a lipid transfer protein. J Allergy Clin Immunol 1999; 103:520.
  24. Sánchez-Monge R, Lombardero M, García-Sellés FJ, et al. Lipid-transfer proteins are relevant allergens in fruit allergy. J Allergy Clin Immunol 1999; 103:514.
  25. Schocker F, Lüttkopf D, Scheurer S, et al. Recombinant lipid transfer protein Cor a 8 from hazelnut: a new tool for in vitro diagnosis of potentially severe hazelnut allergy. J Allergy Clin Immunol 2004; 113:141.
  26. Tejera ML, Villalba M, Batanero E, Rodríguez R. Identification, isolation, and characterization of Ole e 7, a new allergen of olive tree pollen. J Allergy Clin Immunol 1999; 104:797.
  27. Cuesta-Herranz J, Lázaro M, Martínez A, et al. Pollen allergy in peach-allergic patients: sensitization and cross-reactivity to taxonomically unrelated pollens. J Allergy Clin Immunol 1999; 104:688.
  28. Romano A, Scala E, Rumi G, et al. Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food-dependent exercise-induced anaphylaxis. Clin Exp Allergy 2012; 42:1643.
  29. Krause S, Reese G, Randow S, et al. Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population. J Allergy Clin Immunol 2009; 124:771.
  30. Scala E, Till SJ, Asero R, et al. Lipid transfer protein sensitization: reactivity profiles and clinical risk assessment in an Italian cohort. Allergy 2015; 70:933.
  31. Fernández-Rivas M, van Ree R, Cuevas M. Allergy to Rosaceae fruits without related pollinosis. J Allergy Clin Immunol 1997; 100:728.
  32. Blein JP, Coutos-Thévenot P, Marion D, Ponchet M. From elicitins to lipid-transfer proteins: a new insight in cell signalling involved in plant defence mechanisms. Trends Plant Sci 2002; 7:293.
  33. Díaz-Perales A, Lombardero M, Sánchez-Monge R, et al. Lipid-transfer proteins as potential plant panallergens: cross-reactivity among proteins of Artemisia pollen, Castanea nut and Rosaceae fruits, with different IgE-binding capacities. Clin Exp Allergy 2000; 30:1403.
  34. Asero R, Mistrello G, Roncarolo D, et al. Immunological cross-reactivity between lipid transfer proteins from botanically unrelated plant-derived foods: a clinical study. Allergy 2002; 57:900.
  35. Asero R, Mistrello G, Roncarolo D, et al. A case of allergy to beer showing cross-reactivity between lipid transfer proteins. Ann Allergy Asthma Immunol 2001; 87:65.
  36. Breiteneder H, Mills C. Nonspecific lipid-transfer proteins in plant foods and pollens: an important allergen class. Curr Opin Allergy Clin Immunol 2005; 5:275.
  37. Sancho AI, Rigby NM, Zuidmeer L, et al. The effect of thermal processing on the IgE reactivity of the non-specific lipid transfer protein from apple, Mal d 3. Allergy 2005; 60:1262.
  38. Asero R, Mistrello G, Roncarolo D, et al. Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion. Int Arch Allergy Immunol 2001; 124:67.
  39. Fernández-Rivas M, González-Mancebo E, Rodríguez-Pérez R, et al. Clinically relevant peach allergy is related to peach lipid transfer protein, Pru p 3, in the Spanish population. J Allergy Clin Immunol 2003; 112:789.
  40. Ballmer-Weber BK. Lipid transfer protein as a potential panallergen? Allergy 2002; 57:873.
  41. Scheurer S, Pastorello EA, Wangorsch A, et al. Recombinant allergens Pru av 1 and Pru av 4 and a newly identified lipid transfer protein in the in vitro diagnosis of cherry allergy. J Allergy Clin Immunol 2001; 107:724.
  42. Gao ZS, Yang ZW, Wu SD, et al. Peach allergy in China: a dominant role for mugwort pollen lipid transfer protein as a primary sensitizer. J Allergy Clin Immunol 2013; 131:224.
  43. Schulten V, Radakovics A, Hartz C, et al. Characterization of the allergic T-cell response to Pru p 3, the nonspecific lipid transfer protein in peach. J Allergy Clin Immunol 2009; 124:100.
  44. Tolkki L, Alanko K, Petman L, et al. Clinical characterization and IgE profiling of birch (Betula verrucosa)--allergic individuals suffering from allergic reactions to raw fruits and vegetables. J Allergy Clin Immunol Pract 2013; 1:623.
  45. Klinglmayr E, Hauser M, Zimmermann F, et al. Identification of B-cell epitopes of Bet v 1 involved in cross-reactivity with food allergens. Allergy 2009; 64:647.
  46. Hoffmann-Sommergruber K, Vanek-Krebitz M, Ferris R, et al. Isolation and cloning of Bet v 1-homologous food allergens from celeriac (Api g1) and apple (Mal d1). Adv Exp Med Biol 1996; 409:219.
  47. Bolhaar ST, van de Weg WE, van Ree R, et al. In vivo assessment with prick-to-prick testing and double-blind, placebo-controlled food challenge of allergenicity of apple cultivars. J Allergy Clin Immunol 2005; 116:1080.
  48. Le TM, van Hoffen E, Lebens AF, et al. Anaphylactic versus mild reactions to hazelnut and apple in a birch-endemic area: different sensitization profiles?. Int Arch Allergy Immunol 2013; 160:56.
  49. Gomez F, Aranda A, Campo P, et al. High prevalence of lipid transfer protein sensitization in apple allergic patients with systemic symptoms. PLoS One 2014; 9:e107304.
  50. Kiewning D, Schmitz-Eiberger M. Effects of long-term storage on Mal d 1 content of four apple cultivars with initial low Mal d 1 content. J Sci Food Agric 2014; 94:798.
  51. Hsieh LS, Moos M Jr, Lin Y. Characterization of apple 18 and 31 kd allergens by microsequencing and evaluation of their content during storage and ripening. J Allergy Clin Immunol 1995; 96:960.
  52. Sancho AI, Foxall R, Browne T, et al. Effect of postharvest storage on the expression of the apple allergen Mal d 1. J Agric Food Chem 2006; 54:5917.
  53. Hirschwehr R, Valenta R, Ebner C, 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.
  54. Schocker F, Lüttkopf D, Müller U, et al. IgE binding to unique hazelnut allergens: identification of non pollen-related and heat-stable hazelnut allergens eliciting severe allergic reactions. Eur J Nutr 2000; 39:172.
  55. Flinterman AE, Akkerdaas JH, den Hartog Jager CF, et al. Lipid transfer protein-linked hazelnut allergy in children from a non-Mediterranean birch-endemic area. J Allergy Clin Immunol 2008; 121:423.
  56. Masthoff LJ, Mattsson L, Zuidmeer-Jongejan L, et al. Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults. J Allergy Clin Immunol 2013; 132:393.
  57. Faber MA, De Graag M, Van Der Heijden C, et al. Cor a 14: missing link in the molecular diagnosis of hazelnut allergy? Int Arch Allergy Immunol 2014; 164:200.
  58. Hansen KS, Ballmer-Weber BK, Sastre J, et al. Component-resolved in vitro diagnosis of hazelnut allergy in Europe. J Allergy Clin Immunol 2009; 123:1134.
  59. Mittag D, Akkerdaas J, Ballmer-Weber BK, et al. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol 2004; 114:1410.
  60. Hurlburt BK, Offermann LR, McBride JK, et al. Structure and function of the peanut panallergen Ara h 8. J Biol Chem 2013; 288:36890.
  61. van Ree R, Fernández-Rivas M, Cuevas M, et al. Pollen-related allergy to peach and apple: an important role for profilin. J Allergy Clin Immunol 1995; 95:726.
  62. Cuesta-Herranz J, Lázaro M, de las Heras M, et al. Peach allergy pattern: experience in 70 patients. Allergy 1998; 53:78.
  63. Cuesta-Herranz J, Lázaro M, Figueredo E, et al. Allergy to plant-derived fresh foods in a birch- and ragweed-free area. Clin Exp Allergy 2000; 30:1411.
  64. Pascal M, Muñoz-Cano R, Reina Z, et al. Lipid transfer protein syndrome: clinical pattern, cofactor effect and profile of molecular sensitization to plant-foods and pollens. Clin Exp Allergy 2012; 42:1529.
  65. Asero R, Mistrello G, Amato S, et al. Peach fuzz contains large amounts of lipid transfer protein: is this the cause of the high prevalence of sensitization to LTP in Mediterranean countries? Eur Ann Allergy Clin Immunol 2006; 38:118.
  66. Boyano-Martínez T, Pedrosa M, Belver T, et al. Peach allergy in Spanish children: tolerance to the pulp and molecular sensitization profile. Pediatr Allergy Immunol 2013; 24:168.
  67. Pastorello EA, Ortolani C, Farioli L, et al. Allergenic cross-reactivity among peach, apricot, plum, and cherry in patients with oral allergy syndrome: an in vivo and in vitro study. J Allergy Clin Immunol 1994; 94:699.
  68. Asero R. In patients with LTP syndrome food-specific IgE show a predictable hierarchical order. Eur Ann Allergy Clin Immunol 2014; 46:142.
  69. Hoffmann-Sommergruber K, O'Riordain G, Ahorn H, et al. Molecular characterization of Dau c 1, the Bet v 1 homologous protein from carrot and its cross-reactivity with Bet v 1 and Api g 1. Clin Exp Allergy 1999; 29:840.
  70. Ballmer-Weber BK, Wüthrich B, Wangorsch A, et al. Carrot allergy: double-blinded, placebo-controlled food challenge and identification of allergens. J Allergy Clin Immunol 2001; 108:301.
  71. Gómez M, Curiel G, Mendez J, et al. Hypersensitivity to carrot associated with specific IgE to grass and tree pollens. Allergy 1996; 51:425.
  72. Ballmer-Weber BK, Skamstrup Hansen K, Sastre J, et al. Component-resolved in vitro diagnosis of carrot allergy in three different regions of Europe. Allergy 2012; 67:758.
  73. Foetisch K, Scheurer S, Vieths S, et al. Identification of allergen-resolved threshold doses of carrot (Daucus carota) by means of oral challenge and ELISA. J Allergy Clin Immunol 2013; 131:1711.
  74. Ito K, Sjölander S, Sato S, et al. IgE to Gly m 5 and Gly m 6 is associated with severe allergic reactions to soybean in Japanese children. J Allergy Clin Immunol 2011; 128:673.
  75. Klemans RJ, Knol EF, Michelsen-Huisman A, et al. Components in soy allergy diagnostics: Gly m 2S albumin has the best diagnostic value in adults. Allergy 2013; 68:1396.
  76. Kleine-Tebbe J, Vogel L, Crowell DN, et al. Severe oral allergy syndrome and anaphylactic reactions caused by a Bet v 1- related PR-10 protein in soybean, SAM22. J Allergy Clin Immunol 2002; 110:797.
  77. Berneder M, Bublin M, Hoffmann-Sommergruber K, et al. Allergen chip diagnosis for soy-allergic patients: Gly m 4 as a marker for severe food-allergic reactions to soy. Int Arch Allergy Immunol 2013; 161:229.
  78. De Swert LF, Gadisseur R, Sjölander S, et al. Secondary soy allergy in children with birch pollen allergy may cause both chronic and acute symptoms. Pediatr Allergy Immunol 2012; 23:117.
  79. Mittag D, Vieths S, Vogel L, et al. Soybean allergy in patients allergic to birch pollen: clinical investigation and molecular characterization of allergens. J Allergy Clin Immunol 2004; 113:148.
  80. Gall H, Kalveram KJ, Forck G, Sterry W. Kiwi fruit allergy: a new birch pollen-associated food allergy. J Allergy Clin Immunol 1994; 94:70.
  81. Alemán A, Sastre J, Quirce S, et al. Allergy to kiwi: a double-blind, placebo-controlled food challenge study in patients from a birch-free area. J Allergy Clin Immunol 2004; 113:543.
  82. Pastorello EA, Pravettoni V, Ispano M, et al. Identification of the allergenic components of kiwi fruit and evaluation of their cross-reactivity with timothy and birch pollens. J Allergy Clin Immunol 1996; 98:601.
  83. Bublin M, Pfister M, Radauer C, et al. Component-resolved diagnosis of kiwifruit allergy with purified natural and recombinant kiwifruit allergens. J Allergy Clin Immunol 2010; 125:687.
  84. D'Avino R, Bernardi ML, Wallner M, et al. Kiwifruit Act d 11 is the first member of the ripening-related protein family identified as an allergen. Allergy 2011; 66:870.
  85. Sirvent S, Cantó B, Gómez F, et al. Detailed characterization of Act d 12 and Act d 13 from kiwi seeds: implication in IgE cross-reactivity with peanut and tree nuts. Allergy 2014; 69:1481.
  86. Anderson LB Jr, Dreyfuss EM, Logan J, et al. Melon and banana sensitivity coincident with ragweed pollinosis. J Allergy 1970; 45:310.
  87. Liccardi G, Mistrello G, Noschese P, et al. Oral allergy syndrome (OAS) in pollinosis patients after eating pistachio nuts: two cases with two different patterns of onset. Allergy 1996; 51:919.
  88. Reindl J, Anliker MD, Karamloo F, et al. Allergy caused by ingestion of zucchini (Cucurbita pepo): characterization of allergens and cross-reactivity to pollen and other foods. J Allergy Clin Immunol 2000; 106:379.
  89. Wüthrich B, Stäger J, Johansson SG. Celery allergy associated with birch and mugwort pollinosis. Allergy 1990; 45:566.
  90. Egger M, Mutschlechner S, Wopfner N, et al. Pollen-food syndromes associated with weed pollinosis: an update from the molecular point of view. Allergy 2006; 61:461.
  91. Yagami A, Nakazawa Y, Suzuki K, Matsunaga K. Curry spice allergy associated with pollen-food allergy syndrome and latex fruit-syndrome. J Dermatol 2009; 36:45.
  92. Borghesan F, Mistrello G, Amato S, et al. Mugwort-fennel-allergy-syndrome associated with sensitization to an allergen homologous to Api g 5. Eur Ann Allergy Clin Immunol 2013; 45:130.
  93. Bublin M, Radauer C, Wilson IB, et al. Cross-reactive N-glycans of Api g 5, a high molecular weight glycoprotein allergen from celery, are required for immunoglobulin E binding and activation of effector cells from allergic patients. FASEB J 2003; 17:1697.
  94. Ballmer-Weber BK, Hoffmann A, Wüthrich B, et al. Influence of food processing on the allergenicity of celery: DBPCFC with celery spice and cooked celery in patients with celery allergy. Allergy 2002; 57:228.
  95. Sicherer SH. Clinical implications of cross-reactive food allergens. J Allergy Clin Immunol 2001; 108:881.
  96. Blanco C, Carrillo T, Castillo R, et al. Latex allergy: clinical features and cross-reactivity with fruits. Ann Allergy 1994; 73:309.
  97. García Ortiz JC, Moyano JC, Alvarez M, Bellido J. Latex allergy in fruit-allergic patients. Allergy 1998; 53:532.
  98. Blanco C, Carrillo T, Castillo R, et al. Avocado hypersensitivity. Allergy 1994; 49:454.
  99. Brehler R, Theissen U, Mohr C, Luger T. "Latex-fruit syndrome": frequency of cross-reacting IgE antibodies. Allergy 1997; 52:404.
  100. Nel A, Gujuluva C. Latex antigens: identification and use in clinical and experimental studies, including crossreactivity with food and pollen allergens. Ann Allergy Asthma Immunol 1998; 81:388.