Wheat Allergy
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  • Although allergy to wheat is not an uncommon condition, anaphylaxis from wheat consumption is rarely observed. Wheat is not a common food consumed in Thailand. Nonetheless, wheat anaphylaxis has been increasing observed at our institution over the past ten years. We, herein, report 8 cases of wheat-inducedanaphylaxis from Thailand. Seven children (3 girls and 4 boys, age range 2-14 years, mean 9 years) presented with wheatinduced anaphylaxis. Their symptoms occurred at various ages, ranging from 7 months to 14 years old. Type of wheat containing foods causing anaphylaxis were cakes, bread, Kentucky fried chicken, pizza, crisp, Doughnut. noodle. Amount of wheat inducing symptoms ranged from a bite of cake to two roles of noodle. Symptoms were combination of angioedema ofmouth and eyelids, urticaria and with or without hypotension in six patients. Gastrointestinal symptoms together with skin manifestration (angioedema of mouth and eyelids) were presented in one case. Most symptoms occurred within 30 minutes after the ingestion. Our last patient was a 40 year-old male who presented with wheat-dependent exerciseinduced anaphylaxis (after ingestion of bread). Wheat was the only allergen sensitized in 4 patients whereas the other four patients were sensitized to other allergen as well. Treatment included avoidance and prescription of injectable adrenaline for emergency situation. No fatality was observed during the follow-up period. Anaphylaxis from ingestion of wheat has become one of the most common causes of anaphylaxis in Thailand. Systematic study of anaphylaxis including epidemiology and basic research will need to be elucidated in Thailand.
  • From Johns Hopkins pediatric allergy clinic 1999-2006 total 5000 children 103 patient had symptomatic reaction to wheat and positive wheat IgE test result
  • wheat-dependent exercise induced anaphylaxis (WDEIA) Tri aA_TI (alpha-amylase/tyrpsin inhibitor) - wheat allergen in raw and cooked food - play role in wheat-depedent exercise induce anaphylaxis High molecular weigh glutenin - associated with wheat-dependent exercise induce anaphylaxis Tri a gliadin - primary wheat sensitization (low-risk of pollen cross-reactivity)
  • Positive result to wheat flour extract อาจไม่ correlate กับ clinical symptom ซึ่งพบว่า Wheat commonly cross reacts with grass pollen ทำให้มีการ over Dx of wheat allergy เช่น บางกรณีที่แพทย์ตรวจ SPT to wheat or sIgE to wheat แล้ว +ve ในคนไข้ grass allergy เกิด cross reactive แพทย์อาจแปลผลว่าเป็น Wheat allergy and avoid wheat in diet การพัฒนา in vitro Dx ที่เป็น species specific for wheat น่จะช่วย improve การวินิจฉัย wheat allergy
  • Positive result to wheat flour extract อาจไม่ correlate กับ clinical symptom ซึ่งพบว่า Wheat commonly cross reacts with grass pollen ทำให้มีการ over Dx of wheat allergy เช่น บางกรณีที่แพทย์ตรวจ SPT to wheat or sIgE to wheat แล้ว +ve ในคนไข้ grass allergy เกิด cross reactive แพทย์อาจแปลผลว่าเป็น Wheat allergy and avoid wheat in diet การพัฒนา in vitro Dx ที่เป็น species specific for wheat น่จะช่วย improve การวินิจฉัย wheat allergy
  • Wheat IgE level correlated with resolution of allergy and peak wheat IgE level predict rate of resolution

Transcript

  • 1. A rising problem in the Asia - Pacific Wheat allergy Jaichat Mekaroonkamol, MD.
  • 2. Outline • Epidemiology of wheat allergy – Age – Varying manifestations • Diagnosis of wheat allergy • Difficulty in management • Tolerance to wheat • Specific oral tolerance induction (SOTI)
  • 3. Food allergy • Food allergies affect 6% of young children • Eight major causative food: – Milk – Eggs – Soy – Peanuts – Seafood – Wheat Sampson HA. Food allergy. J Allergy Clin Immunol 2003
  • 4. 1.4-1.8% 2.5-5.5%
  • 5. Causative food of immediate type food allergy USUS •Milk •Egg •Peanut JapanJapan •Egg •Diary product •Wheat
  • 6. Immediate-type food allergy in Japan Urisu et al. Allergology Iternational 2011
  • 7. Wheat Allergy-epidemiology
  • 8. 0.08-0.37% Asia Pac Allergy 2013;3:3-14
  • 9. In Thailand • During 1998-2005 • Data from 103 patients • Allergy Clinic, Department of Pediatrics, Siriraj Hospital, Mahidol University • The prevalence of wheat allergy was 4.85%
  • 10. Wheat Allergy-epidemiology • 0.4% in American adult JACI 2007;119:1504-1510 • 0.21% in Japanese adult Allergology International 2012
  • 11. Manifestations Anaphylaxis 54.1%
  • 12. Food Anaphylaxis
  • 13. Diagnosis of wheat allergyDiagnosis of wheat allergy
  • 14. Diagnosis • Relation between food intake and symptoms • Allergic testing • Diagnosis elimination of diet • Oral food challenge
  • 15. Classification of gluten related disorder
  • 16. • From Johns Hopkins pediatric allergy clinic 1999-2006 total 5000 children • 103 patient had symptomatic reaction to wheat and positive wheat IgE test result
  • 17. Keet et al .The natural history of wheat allergy :Ann Allergy Asthma immunol.2009;102:410-15
  • 18. Diagnosis • Relation between food intake and symptoms • Allergic testing • Elimination diet • Food challenge
  • 19. Allergens involved in wheat allergy Int Arch Allergy Immunol 2007; 144:10 – 22.
  • 20. In water/salt-soluble albumin/globulin • Most important allergen are amylase/trypsin inhibitor subunit • Responsible for classic food allergy in – children with atopic dermatitis – adult with Baker’s Asthma (Albumin) Int Arch Allergy Immunol 2007; 144:10 – 22.
  • 21. In water/ salt-insoluble gluten • gliadins are involved in WDEIA, some cases of atopic dermatitis and in anaphylaxis in adults and children. • Among the gliadins, ώ-5 gliadin (Tri a 19) was identified as a major allergen of WDEIA JACI 1999; 103 :912 -17 J Dermatol Sci 2003; 33: 99 – 104.
  • 22. Non specific lipid transfer protein (nsL TP) • Tri a 14 with a molecular weight of 9 kDa was recently identified as a new wheat allergen • nine out of 22 patients with wheat food allergy: positive SPT with purified wheat LTP • 28% of 60 patient with wheat food allergy shower IgE reaction with purified wheat LTP • Wheat nsLTP has also been reported as an inhalant allergen in baker asthma Int Arch Allergy Immunol 2007; 144:10 – 22. J Allergy Clin Immunol 2007; 120:1132-8.
  • 23. sensitivity specitivity PPV(%) NPV(%) Wheat CAP RAST (>0.35 KU/L) 95 67 72 93 Wheat CAP RAST (>26 KU/L) 61 92 74 87 Wheat CAP RAST (>100 KU/L) 13 100 100 76 Wheat SPT wheal diameter(3 mm) 89 71 74 88 Palosuo, et al. J Allergy Clin Immunol 2001 Sampson HA. J Allergy Clin Immunol 2005
  • 24. Middleton's Allergy: Principles and Practice. 7th edition • Mixtures of water/salt soluble wheat proteins • Lack allergens from the insoluble gliadin fraction
  • 25. Middleton's Allergy: Principles and Practice. 7th edition Cross-reactivity of wheat allergens with grasses
  • 26. • 70 subjects (41 females; mean age 32 years) – history of grass pollen allergy • 20 healthy controls (13 females; mean age 24 years) • SPT and sIgE • Tested by open food challenge (OFC) with cereals and peanut
  • 27. Diagnosis of wheat allergy • ώ-5 gliadin has been identified as the major antigen in children with wheat- dependent, exercised-induced anaphylaxis • IgE antibodies to ώ-5 gliadin have been found in children with immediate reactions to ingested wheat J Dermatol Sci 2003; 33: 99 – 104. J Allergy Clin Immunol 2001;108:634-8
  • 28. Predictive capacity sensitivity specitivity PPV(%) NPV(%) ώ-5 gliadin ELISA (>0.04 AU) 84 100 100 88 Wheat CAP RAST (>26 KU/L) 61 92 74 87 Palosuo, et al. J Allergy Clin Immunol 2001
  • 29. • 50 WDEIA • 25 atopic dermatitis • 25 healthy subjects Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA. Allergy 2008;63:233-36
  • 30. Sensitivity in 50 Japanese WDEIA: cutoff 0.35 kU/L Specific IgE to rώ5 gliadin 80% Specific igE to wheat 48% Specific IgE to gluten 56% B cell epitope peptide of ώ5 gliadin 76% B cell epitope of HMW glutenin 22% By immunoCAP system Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA. Allergy 2008;63:233-36
  • 31. • Maximum efficiency of ώ-5 gliadin for diagnosis WDEIA was 0.89kUa/l • Sensitivity 78% specificity 96% Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA. Allergy 2008;63:233-36
  • 32. • 311 children and young adults at three separate pediatric clinics • ages 6 months to 20.4 years (median: 2.3 years)
  • 33. Int Arch Allergy Immunol 2012;158:71–76 18.1 kUA/L 1.2 kUA/L5.2 kUA/L < 0.35 kUA/L
  • 34. Diagnostic ability sensitivity specitivity PPV(%) NPV(%) LR+ LR- ώ-5 gliadin CAP RAST (>0.41 KU/L) 72 79 81 69 3.4 0.5 Wheat CAP RAST (10.1KU/L) 61 74 75 60 2.4 0.5 Int Arch Allergy Immunol 2012;158:71–76
  • 35. Int Arch Allergy Immunol 2012;158:71–76 The risk of WA increased with increasing levels of IgE for children •</= 1 year: 5.4 fold •> 1 year: 2.5 fold
  • 36. sensitivity specitivity PPV(%) NPV(%) Wheat CAP RAST (>0.35 KU/L) 95 67 72 93 Wheat CAP RAST (>26 KU/L) 61 92 74 87 Wheat CAP RAST (10.1KU/L) 61 74 75 60 ώ-5 gliadin CAP RAST (>0.41 KU/L) 72 79 81 69 Palosuo, et al. J Allergy Clin Immunol 2001 Sampson HA. J Allergy Clin Immunol 2005 Int Arch Allergy Immunol 2012
  • 37. Alpha-purothionin, a new wheat allergen associated with severe allergy Alpha-purothionin, a new wheat allergen associated with severe allergy J Allergy Clin Immunol 2013
  • 38. sensitivity specitivity PPV(%) NPV(%) LR+ LR- Alpha- purothionin (r Tri a 37) For anaphyla xis 31 90 56 77 1.28 0.29 ώ-5 gliadin CAP RAST (>0.41 KU/L) 72 79 81 69 3.4 0.5 • Tri a 37 is a novel water- and salt-soluble wheat food allergen that can be found in the albumin/globulin fraction • Frequently recognized by patients with severe anaphylactic reactions to wheat • represent a diagnostic marker for an increased risk of wheat-induced anaphylaxis
  • 39. Diagnosis • Relation between food intake and symptoms • Allergic testing • Elimination diet • Food challenge
  • 40. Ann Allergy Asthma Immunol. 2011
  • 41. Difficulty in managementDifficulty in management
  • 42. Wheat avoidance!!
  • 43. • Wheat is hidden in various kinds of food • Food labeling is neglected by sellers and customers • Sometimes need more than one factor to trigger symptoms
  • 44. Natural history
  • 45. Natural history
  • 46. Resolution of wheat allergy over time Keet et al .The natural history of wheat allergy :Ann Allergy Asthma immunol.2009;102:410-15
  • 47. Rate of resolution Keet et al .The natural history of wheat allergy :Ann Allergy Asthma immunol.2009;102:410-15
  • 48. Peak wheat IgE level vs Persistence of wheat allergy Keet et al .The natural history of wheat allergy :Ann Allergy Asthma immunol.2009;102:410-15
  • 49. Predictors of prognosis Keet et al .The natural history of wheat allergy :Ann Allergy Asthma immunol.2009;102:410-15
  • 50. Natural history
  • 51. Natural history
  • 52. Natural history
  • 53. Wheat challenge outcomeWheat challenge outcome
  • 54. Wheat challenge outcome JACI 2008 Ann Allergy Asthma Immunol. 2011 In germany ,US study Most patient have history of atopic dermatitis Rumiko Shibata et al, Japan No correlation with level of ώ5 gliadin specific IgE and outcome of oral wheat challenge High concentration of IgE specific to ώ5 gliadin had high risk of failing wheat challege
  • 55. 24 children (aged 1–15 years) with a wheat allergy diagnosis underwent an open wheat challenge.
  • 56. Int Arch Allergy Immunol 2013;162:50–57 • Combining – wheat CD-sens >150 – IgE-Ab to wheat >20 kU A /l or ω-5 gliadin >0.1 kU A /l • Predicted the challenge outcome in 83% of the patients
  • 57. Specific oral tolerance induction (SOTI) Specific oral tolerance induction (SOTI)
  • 58. Specific oral tolerance induction (SOTI)
  • 59. The Journal of Applied Research, 2009
  • 60. • 20 Children with a history of wheat allergy • Age 4.1 +/- 2.3 year (1-10 yr) • Three group – Severe wheat allergy:8 – Mild wheat allergy:7 – No desensitizing:5 = control group
  • 61. S group M group Twice weekly dose C group
  • 62. • Severe wheat allergy: S group – 6/8 (75%): achieved a daily intake of 100 gm of wheat product • Mild wheat allergy: M group – 5/7 (71.4%): achieved a daily intake of 100 gm of wheat product • No desensitizing: C group – 4/5 (80%): severe allergic reaction
  • 63. Specific oral tolerance induction (SOTI)
  • 64. Wheat anaphylaxis in a Thai boy
  • 65. Specific oral tolerance induction (SOTI)
  • 66. Cross-reactivity among cereals?? Cross-reactivity among cereals??
  • 67. Cereals • Wheat • Rye • Barley • Oat
  • 68. Scott H. Sicherer, M.D., is associate professor of pediatrics, Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York. He is also a member of FAAN’s Medical Advisory Board.
  • 69. Conclusion