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Wheat-Dependent Exercise-Induced Anaphylaxis

  • Anaphylaxis (M Sánchez-Borges, Section Editor)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Opinion statement

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is presently gaining attention. Patients with WDEIA experience allergic symptoms when they exercise following wheat consumption. Some patients may be advised to restrict wheat consumption or exercise because of repeated allergic symptoms without adequate diagnosis or examination. Japanese guidelines recommend that WDEIA should be diagnosed using provocation tests with wheat and exercise. After wheat consumption, patients exercise using a treadmill or an ergometer during provocation tests. Once WDEIA is diagnosed, patients should not consume wheat before physical activity. Exercise is allowed at least 4 h after wheat intake. They may consume wheat if they do not exercise after wheat consumption, and they may exercise without consuming wheat before exercising. All WDEIA patients should be instructed regarding use of adrenaline auto-injector and should carry one with them. Some patients may respond to prophylactic treatment with anti-histamines. However, there is no established drug for preventing WDEIA; moreover, there is inadequate evidence for routine administration of these prophylactic drugs. Cofactors like nonsteroidal anti-inflammatory drugs (NSAIDs) may directly modulate immune reactions and could exacerbate the condition. Hence, patients should avoid these cofactors. The emergency treatment of WDEIA does not differ from that of immediate-type food allergy or anaphylaxis. Exercise should be stopped when patients show food allergy symptoms. When patients show anaphylactic reactions, adrenaline should be quickly administered. Indications for adrenaline auto-injector use are severe symptoms like persistent coughing, breathing with wheeze, persistent abdominal pain, and confusion. However, there is no evidence that anti-histamines and corticosteroids have lifesaving effects. Consequently, it is important that adrenaline auto-injector is used in an appropriate setting and that the patient is transferred to a hospital immediately. The mechanisms of WDEIA development are unknown. Further research is needed to clarify the mechanisms involved so that it can be treated.

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  1. Maulitz RM, Pratt DS, Schocket AL. Exercise-induced anaphylactic reaction to shellfish. J Allergy Clin Immunol. 1979;63:433–4.

    Article  CAS  PubMed  Google Scholar 

  2. Sheffer AL, Soter NA, McFadden ER Jr, Austen KF. Exercise-induced anaphylaxis: a distinct form of physical allergy. J Allergy Clin Immunol. 1983;71:311–6.

    Article  CAS  PubMed  Google Scholar 

  3. Urisu A, Ebisawa M, Ito K, Aihara Y, Ito S, Mayumi M, et al. Japanese guideline for food allergy 2014. Allergol Int. 2014;63:399–419.

    Article  CAS  PubMed  Google Scholar 

  4. Barg W, Medrala W, Wolanczyk-Medrala A. Exercise-induced anaphylaxis: an update on diagnosis and treatment. Curr Allergy Asthma Rep. 2011;11:45–51.

    Article  PubMed  Google Scholar 

  5. Chinuki Y, Morita E. Wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat protein in soap. Allergol Int. 2012;61:529–37.

    Article  CAS  PubMed  Google Scholar 

  6. De Silva NR, Dasanayake WM, Karunatilleke C, Malavige GN. Food dependant exercise induced anaphylaxis a retrospective study from 2 allergy clinics in Colombo, Sri Lanka. Allergy Asthma Clin Immunol. 2015;11:22.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Manabe T, Oku N, Aihara Y. Food-dependent exercise-induced anaphylaxis among junior high school students: a 14-year epidemiological comparison. Allergol Int. 2015;64:285–6.

    Article  PubMed  Google Scholar 

  8. Aihara Y, Takahashi Y, Kotoyori T, Mitsuda T, Ito R, Aihara M, et al. Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students. J Allergy Clin Immunol. 2001;108:1035–9.

    Article  CAS  PubMed  Google Scholar 

  9. Scherf KA, Brockow K, Biedermann T, Koehler P, Wieser H. Wheat-dependent exercise-induced anaphylaxis. Clin Exp Allergy. 2016;46:10–20.

    Article  CAS  PubMed  Google Scholar 

  10. Roberts H, Ben-Shoshan M. Food-dependent exercise-induced anaphylaxis to chickpea in a 17-year-old female: a case report. J Med Case Rep. 2015;9:186.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ono R, Motomura C, Takamatsu N, Kondo Y, Akamine Y, Matsuzaki H, et al. A case of food-dependent exercise-induced anaphylaxis caused by ingestion of orange. Arerugi. 2015;64:149–55. [Article in Japanese]

  12. Miceli Sopo S, Monaco S, Giorgio V, Calvani M, Mistrello G, Onesimo R, et al. Food-dependent exercise-induced anaphylaxis (FDEIA) by nectarine in a paediatric patient with weakly positive nectarine prick-by-prick and negative specific IgE to Pru p 3. Allergol Immunopathol (Madr). 2013;41:201–3.

    Article  CAS  Google Scholar 

  13. Baek CH, Bae YJ, Cho YS, Moon HB, Kim TB. Food-dependent exercise-induced anaphylaxis in the celery-mugwort-birch-spice syndrome. Allergy. 2010;65:792–3.

    Article  PubMed  Google Scholar 

  14. Sato S, Nagao R, Hujioka T, Suzuki K, Tsuyuki K, Hoshika A. A case of food-dependent exercise-induced anaphylaxis due to ingestion of peach. J Investig Allergol Clin Immunol. 2009;19:337.

    CAS  PubMed  Google Scholar 

  15. Matsumoto R, Ogawa T, Makino T, Okano M. A clinical study of admitted the review of cases of food-dependent exercise-induced anaphylaxis. Arerugi. 2009;58:548–53. [Article in Japanese]

    PubMed  Google Scholar 

  16. Lee SE, Lee SY, Jo EJ, Kim MY, Kim SH, Chang YS. Wheat-induced anaphylaxis in Korean adults: a report of 6 cases. Clin Nutr Res. 2013;2:76–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. • Asaumi T, Yanagida N, Sato S, Shukuya A, Nishino M, Ebisawa M. Provocation tests for the diagnosis of food-dependent exercise-induced anaphylaxis. Pediatr Allergy Immunol. 2016;27:44–9. Many provocation tests with FDEIA were performed

  18. Aihara Y, Kotoyori T, Takahashi Y, Osuna H, Ohnuma S, Ikezawa Z. The necessity for dual food intake to provoke food-dependent exercise-induced anaphylaxis (FEIAn): a case report of FEIAn with simultaneous intake of wheat and umeboshi. J Allergy Clin Immunol. 2001;107:1100–5.

    Article  CAS  PubMed  Google Scholar 

  19. Yokooji T, Kurihara S, Murakami T, Chinuki Y, Takahashi H, Morita E, et al. Characterization of causative allergens for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap. Allergol Int. 2013;62:435–45.

    Article  CAS  PubMed  Google Scholar 

  20. Hiragun M, Ishii K, Yanase Y, Hiragun T, Hide M. Remission rate of patients with wheat allergy sensitized to hydrolyzed wheat protein in facial soap. Allergol Int. 2016;65:109–11.

    Article  CAS  PubMed  Google Scholar 

  21. Sugiyama A, Kishikawa R, Honjo S, Shimoda T, Nishie H, Motomura C, et al. Angiotensin-converting enzyme genotype is a risk factor for wheat-dependent exercise-induced anaphylaxis sensitized with hydrolyzed wheat protein. Allergol Int. 2016;65:115–6.

    Article  CAS  PubMed  Google Scholar 

  22. Morita E, Matsuo H, Chinuki Y, Takahashi H, Dahlström J, Tanaka A. Food-dependent exercise-induced anaphylaxis—importance of omega-5 gliadin and HMW-glutenin as causative antigens for wheat-dependent exercise-induced anaphylaxis. Allergol Int. 2009;58:493–8.

    Article  CAS  PubMed  Google Scholar 

  23. Chinuki Y, Kaneko S, Dekio I, Takahashi H, Tokuda R, Nagao M, et al. CD203c expression-based basophil activation test for diagnosis of wheat-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol. 2012;129:1404–6.

    Article  CAS  PubMed  Google Scholar 

  24. Povesi Dascola C, Caffarelli C. Exercise-induced anaphylaxis: a clinical view. Ital J Pediatr. 2012;38:43.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Nakagawa T, Sakai K, Hayashi N, Sato A, Sasaki K, Matsui T, et al. Six cases of wheat-dependent exercise-induced anaphylaxis in children. Arerugi. 2015;64:1169–73. [Article in Japanese]

    PubMed  Google Scholar 

  26. Ogura K, Iikura K, Yanagida N, Sato S, Ebisawa M. Two patients with acute pancreatitis after undergoing oral food challenges. J Allergy Clin Immunol Pract. 2016;4:984–6.

    Article  PubMed  Google Scholar 

  27. •• Brockow K, Kneissl D, Valentini L, Zelger O, Grosber M, Kugler C, et al. Using a gluten oral food challenge protocol to improve diagnosis of wheat-dependent exercise-induced anaphylaxis. J Allergy Clin Immunol. 2015;135:977–84 e974. This is an important new vision that exercise may be a just augmenting factor of food allergy

    Article  CAS  PubMed  Google Scholar 

  28. Matsukura S, Aihara M, Sugawara M, Kunimi Y, Matsuki M, Inoue Y, et al. Two cases of wheat-dependent anaphylaxis induced by aspirin administration but not by exercise. Clin Exp Dermatol. 2010;35:233–7.

    Article  CAS  PubMed  Google Scholar 

  29. Juji F, Suko M. Effectiveness of disodium cromoglycate in food-dependent, exercise-induced anaphylaxis: a case report. Ann Allergy. 1994;72:452–4.

    CAS  PubMed  Google Scholar 

  30. Adachi YS, Itazawa T, Okabe Y, Higuchi O, Ito Y, Adachi Y. A case of mite-ingestion-associated exercise- induced anaphylaxis mimicking wheat-dependent exercise-induced anaphylaxis. Int Arch Allergy Immunol. 2013;162:181–3.

    Article  PubMed  Google Scholar 

  31. Sanchez-Borges M, Iraola V, Fernández-Caldas E, Capriles-Hulett A, Caballero-Fonseca F. Dust mite ingestion-associated, exercise-induced anaphylaxis. J Allergy Clin Immunol. 2007;120:714–6.

    Article  PubMed  Google Scholar 

  32. Cardona V, Luengo O, Garriga T, Labrador-Horrillo M, Sala-Cunill A, Izquierdo A, et al. Co-factor-enhanced food allergy. Allergy. 2012;67:1316–8.

    Article  CAS  PubMed  Google Scholar 

  33. Matsuo H, Morimoto K, Akaki T, Kaneko S, Kusatake K, Kuroda T, et al. Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis. Clin Exp Allergy. 2005;35:461–6.

    Article  CAS  PubMed  Google Scholar 

  34. Aihara M, Miyazawa M, Osuna H, Tsubaki K, Ikebe T, Aihara Y, et al. Food-dependent exercise-induced anaphylaxis: influence of concurrent aspirin administration on skin testing and provocation. Br J Dermatol. 2002;146:466–72.

    Article  CAS  PubMed  Google Scholar 

  35. •• Niggemann B, Beyer K. Factors augmenting allergic reactions. Allergy. 2014;69:1582–7. Figure is clear to understand the role of exercise or augmenting factors for WDEIA

    Article  CAS  PubMed  Google Scholar 

  36. Zogaj D, Ibranji A, Hoxha M. Exercise-induced anaphylaxis: the role of cofactors. Mater Sociomed. 2014;26:401–4.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shadick NA, Liang MH, Partridge AJ, Bingham CO III, Wright E, Fossel AH, et al. The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study. J Allergy Clin Immunol. 1999;104:123–7.

    Article  CAS  PubMed  Google Scholar 

  38. Ii M, Sayama K, Tohyama M, Hashimoto K. A case of cold-dependent exercise-induced anaphylaxis. Br J Dermatol. 2002;147:368–70.

    Article  CAS  PubMed  Google Scholar 

  39. Shimizu T, Furumoto H, Kinoshita E, Ogasawara Y, Nakamura C, Hashimoto Y, et al. Food-dependent exercise-induced anaphylaxis occurring only in winter. Dermatology. 2000;200:279.

    Article  CAS  PubMed  Google Scholar 

  40. Jo EJ, Yang MS, Kim YJ, Kim HS, Kim MY, Kim SH, et al. Food-dependent exercise-induced anaphylaxis occurred only in a warm but not in a cold environment. Asia Pac Allergy. 2012;2:161–4.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Alcoceba Borras E, Botey Faraudo E, Gaig Jané P, Bartolomé Zavala B. Alcohol-induced anaphylaxis to grapes. Allergol Immunopathol (Madr). 2007;35:159–61.

    Article  CAS  Google Scholar 

  42. Garcia-Robaina JC, de la Torre-Morín F, Sánchez-Machín I, Sánchez-Monge R, Barber D, Lombardero M. Anaphylaxis induced by exercise and wine. Allergy. 2001;56:357–8.

    Article  CAS  PubMed  Google Scholar 

  43. Pali-Scholl I, Jensen-Jarolim E. Anti-acid medication as a risk factor for food allergy. Allergy. 2011;66:469–77.

    Article  CAS  PubMed  Google Scholar 

  44. Bito T, Kanda E, Tanaka M, Fukunaga A, Horikawa T, Nishigori C. Cows milk-dependent exercise-induced anaphylaxis under the condition of a premenstrual or ovulatory phase following skin sensitization. Allergol Int. 2008;57:437–9.

    Article  PubMed  Google Scholar 

  45. Fischer J, Schuck E, Biedermann T. Wheat-dependent exercise-induced anaphylaxis exclusively during menstruation. Allergy. 2010;65:1347–8.

    Article  CAS  PubMed  Google Scholar 

  46. Kusunoki T, Mukaida K, Hayashi A, Nozaki F, Hiejima I, Kumada T, et al. A case of wheat-dependent exercise-induced anaphylaxis after specific oral immunotherapy. J Investig Allergol Clin Immunol. 2014;24:358–9.

    CAS  PubMed  Google Scholar 

  47. Calvani M, Sopo SM. Exercise-induced anaphylaxis caused by wheat during specific oral tolerance induction. Ann Allergy Asthma Immunol. 2007;98:98–9.

    Article  PubMed  Google Scholar 

  48. Sugimura T, Tananari Y, Ozaki Y, Maeno Y, Ito S, Yoshimoto Y, et al. Effect of oral sodium cromoglycate in 2 children with food-dependent exercise-induced anaphylaxis (FDEIA). Clin Pediatr (Phila). 2009;48:945–50.

    Article  Google Scholar 

  49. Katsunuma T, Iikura Y, Akasawa A, Iwasaki A, Hashimoto K, Akimoto K. Wheat-dependent exercise-induced anaphylaxis: inhibition by sodium bicarbonate. Ann Allergy. 1992;68:184–8.

    CAS  PubMed  Google Scholar 

  50. Choi JH, Lee HB, Ahn IS, Park CW, Lee CH. Wheat-dependent, exercise-induced anaphylaxis: a successful case of prevention with ketotifen. Ann Dermatol. 2009;21:203–5.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Ono E, Taniguchi M, Mita H, Fukutomi Y, Higashi N, Miyazaki E, et al. Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis. Clin Exp Allergy. 2009;39:72–80.

    Article  CAS  PubMed  Google Scholar 

  52. Denzlinger C, Haberl C, Wilmanns W. Cysteinyl leukotriene production in anaphylactic reactions. Int Arch Allergy Immunol. 1995;108:158–64.

    Article  CAS  PubMed  Google Scholar 

  53. Peroni DG, Piacentini GL, Piazza M, Cametti E, Boner AL. Combined cetirizine-montelukast preventive treatment for food-dependent exercise-induced anaphylaxis. Ann Allergy Asthma Immunol. 2010;104:272–3.

    Article  PubMed  Google Scholar 

  54. Inoue Y, Adachi A, Ueno M, Fukumoto T, Nishitani N, Fujiwara N, et al. The inhibition effect of a synthetic analogue of prostaglandin E1 to the provocation by aspirin in the patients of WDEIA. Arerugi. 2009;58:1418–25. [Article in Japanese]

  55. Dahl R, Zetterström O. The effect of orally administered sodium cromoglycate on allergic reactions caused by food allergens. Clin Allergy. 1978;8:419–22.

    Article  CAS  PubMed  Google Scholar 

  56. Kano H, Juji F, Shibuya N, Narita M, Naritaka S, Suko M, et al. Clinical courses of 18 cases with food-dependent exercise-induced anaphylaxis. Arerugi. 2000;49:472–8. [Article in Japanese]

    CAS  PubMed  Google Scholar 

  57. Benhamou AH, Vanini G, Lantin JP, Eigenmann PA. Antihistamine and sodium cromoglycate medication for food cold water exercise-induced anaphylaxis. Allergy. 2007;62:1471–2.

    Article  CAS  PubMed  Google Scholar 

  58. Maurer M, Rosén K, Hsieh HJ, Saini S, Grattan C, Gimenéz-Arnau A, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med. 2013;368:924–35.

    Article  CAS  PubMed  Google Scholar 

  59. Ledford D, Busse W, Trzaskoma B, Omachi TA, Rosén K, Chipps BE, et al. A randomized, multicenter study evaluating Xolair® Persistency Of Response After Long-Term Therapy (XPORT). J Allergy Clin Immunol. 2017, in press.

  60. Takahashi M, Taniuchi S, Soejima K, Hatano Y, Yamanouchi S, Kaneko K. Successful desensitization in a boy with severe cow’s milk allergy by a combination therapy using omalizumab and rush oral immunotherapy. Allergy Asthma Clin Immunol. 2015;11:18.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Bray SM, Fajt ML, Petrov AA. Successful treatment of exercise-induced anaphylaxis with omalizumab. Ann Allergy Asthma Immunol. 2012;109:281–2.

    Article  CAS  PubMed  Google Scholar 

  62. Yanagida N, Sato S, Asaumi T, Ebisawa M. Comparisons of outcomes with food immunotherapy strategies: efficacy, dosing, adverse effects, and tolerance. Curr Opin Allergy Clin Immunol. 2016;16:396–403.

    Article  PubMed  Google Scholar 

  63. Sato S, Utsunomiya T, Imai T, Yanagida N, Asaumi T, Ogura K, et al. Wheat oral immunotherapy for wheat-induced anaphylaxis. J Allergy Clin Immunol. 2015;136:1131–3 e1137.

    Article  PubMed  Google Scholar 

  64. Noh G, Lee GH. Specific oral tolerance induction using IFN-gamma in 2 cases of food-dependent exercise-induced anaphylaxis. Case Rep Med. 2013;2013:259692.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Muraro A, Roberts G, Worm M, Bilò MB, Brockow K, Fernández Rivas M, et al., EAACI Food Allergy and Anaphylaxis Guidelines Group. Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy. 2014;69:1026–45.

    Article  CAS  PubMed  Google Scholar 

  66. Pumphrey RS. Fatal posture in anaphylactic shock. J Allergy Clin Immunol. 2003;112:451–2.

    Article  PubMed  Google Scholar 

  67. Terao H, Kishikawa R, Kato M, Noda K, Iwanaga T, Shouji S, et al. A case of food-dependent exercise-induced anaphylaxis caused by various foods which contained flour for thirty years. Arerugi. 2004;53:1119–22. [Article in Japanese]

    PubMed  Google Scholar 

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Acknowledgements

We appreciate the aid of our colleagues at Sagamihara National Hospital. We also would like to thank Editage (www.editage.jp) for English language editing.

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Correspondence to Motohiro Ebisawa MD, PhD.

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Tomoyuki Asaumi declares that he has no conflict of interest. Tetsuharu Manabe declares that he has no conflict of interest. Noriyuki Yanagida declares that he has no conflict of interest. Sakura Sato declares that she has no conflict of interest. Motohiro Ebisawa declares that he has no conflict of interest.

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Asaumi, T., Manabe, T., Yanagida, N. et al. Wheat-Dependent Exercise-Induced Anaphylaxis. Curr Treat Options Allergy 4, 291–302 (2017). https://doi.org/10.1007/s40521-017-0135-3

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