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Wheat Allergy
Lalita Tearprasert; M.D.
• Prevalence
• Wheat proteins and allergens
• Cross-reactivity
• Clinical manifestations
• Wheat allergy and others allerg...
Food Allergy : Top 8
90% of food allergy
Reactions to foods. Middleton's 8th Edition. 1310-39.
Prevalence of wheat
allergy
• Varies depending on age and region : 0...
• In Asia
- Marked differences in prevalence
- Prominent in Japanese school children (unknown reason)
0.21% in Japanese ad...
Urisu A et al. Japanese Guideline for Food Allergy 2014.
Japan
Urisu A et al. Japanese Guideline for Food Allergy 2014.
Lee AJ, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2013.
0.08-0.37%
0.22-0.5%
Korea
UK
USA...
Thailand
• The prevalence of wheat allergy was 4.85% (unpublished data).
• During 1998-2005
• 103 patients who had a histo...
Wheat proteins
& Allergens
Taxonomy of Wheat
D.-A. Moneret-V autrin. Et al. Eur Ann Allergy Clin Immunol. Vol 40, N 3, 67-76, 2008.
Durum wheat is ve...
Wheat grain Wheat proteins
Water/ Salt-soluble
1.) Albumins : Water - soluble
2.) Globulins : Salt - soluble
3.) Gliadins (Prolamins) : Ethanol - sol...
M. J. Makela et al. Clinical & Experimental Allergy, 2014 (44) 1420–1430.
D.-A. Moneret-V autrin. Et al. Eur Ann Allergy C...
Nonspecific lipid transfer proteins
(LTP)
• Wheat LTP (Tri a 14)
• 24/40 patients (60%) of baker's asthma sensitized to wh...
Gluten
• Form a continuous network when wheat flour is mixed with water
to form dough and processed into bread, noodles an...
A.S. Tatham & P. R. Shewry. Clinical and Experimental Allergy, 38, 1712–1726.
Palosuo et al. J Allergy Clin Immunol 2001;1...
Omega-5-gliadin (Tri a19)
• Related to the immediate symptoms after ingestion of wheat
in wheat-sensitized children
• Asso...
• Associated with
>> WDEIA symptoms in patients that do not have IgE
antibodies to omega-5-gliadin
>> Marker of severity o...
Wheat allergens
2015 : 27 allergens
2015 : 27 allergens
(15 Food allergens)
Alpha-Purothionin (Tri a 37),
a new wheat allergen associated
with severe allergy
• Novel water- and salt-soluble wheat fo...
IgE reactivity to Tri a 37 was highly specific for wheat food allergy because patients
with grass pollen allergy and nonal...
• The sequence identity of Tri a 37 from wheat, rye, and barley
was high (ie, >80%), whereas from oat, rice, and other pla...
Baker's asthma WIA, WDEIA
- 1.) Alpha - amylase inhibitor
- (water/salt soluble)
- 1.) Omega-5-gliadin (Tri a 19)
- (water...
Cross-reactivity
Sampson et al. Food allergy. Practice parameter 2014.
Cross-reactivity among
grains
- Rye : γ-70 and γ-35 secalins
- Barley : γ-3 hordein
wheat : ω-5 gliadin
K. Palosuo et al. Clinical and Experimental Alle...
Cross-reactivity
between grains & grass
Family Poaceae
Jones et al. J Allergy Clin Immunol 1995;96:341-51.
Jones et al. J Allergy Clin Immunol 1995;96:341-51.
• Patients with IgE-mediated wheat allergy alone show extensive
in vitro cross-reactivity to other cereal grains and grass...
Clinical
manifestations
Clinical manifestations
• Clinical types of wheat allergies depend on
1.) Age
- Children : Atopic dermatitis (common)
- Ad...
• IgE-mediated immediate symptoms
(within minute - 2 hr. after ingestion)
- Skin : Urticaria, Angioedema
- Respiratory : W...
Keet et al. RA. Ann Allergy Asthma Immunol. 2009;102:410–415.
• Johns Hopkins Pediatric Allergy Clinic from 1993 to 2007
•...
• One of the most common forms of occupational asthma
• 4-10% of bakery workers in European countries
• Mostly sensitized ...
• 7 children (5 boys, 2 girls)
• Aged from 6 months to 13 years
• Department of Pediatrics, Siriraj Hospital in Bangkok
Da...
France
Moneret-Vautrin et al. Allergy 2005: 60: 443–451.
• Between 2002 and 2004
• Department of Internal Medicine, Clinic...
E. Morita et al. Journal of Dermatological Science (2007) 47, 109—117.
Food-dependent exercise-induced anaphylaxis
(FDEIA)
100% 80%
• January 2002 - December 2006
• 5 Childrens with a Hx of WDEIA
• The mean ± SD of the patients'
age at the onset...
Wheat-dependent exercise-induced anaphylaxis
(WDEIA)
• Diagnosis
1.) History of ingestion & Exercise
2.) An exercise chall...
Before tTG After tTG
Palosuo et al. J Allergy Clin Immunol 2003;111:1386-92.
Tissue transglutaminase (tTG)
• Enzyme in gut...
Digested gliadin forms peptide
Cross-linked to tTG
HMW complex
Strong binding serum IgE Ab
Palosuo et al. J Allergy Clin I...
Inomata N. Current Opinion in Allergy and Clinical Immunology 2009, 9:238–243.
• Management & Prevention
1.) Avoidance of ...
Wheat allergy &
Other allergy
CDC/NCHS, National Health Interview Survey. October 2008.
Keet et al. RA. Ann Allergy Asthma Immunol. 2009;102:410–415.
90% allergic to at least
1 other food allergen
(Most common ...
Most : Eczema
Most : Milk 80%
- In all the children other food
allergies had been diagnosed
before wheat
Czaja-Bulsa and B...
Kotaniemi-Syrjanen et al. Pediatr Allergy Immunol 2010: 21: e421–e428.
Diagnosis
of wheat allergy
• Relation between food intake and symptoms
• Diagnostic testing
• Elimination diet
• Oral food challenge
How to diagnosis...
Reactions to foods. Middleton's 8th Edition. 1310-39.
sIgE to wheat
• IgE levels have been regarded as a useful predictor ...
Reactions to foods. Middleton's 8th Edition. 1310-39.
Cross-reactivity of
wheat allergens with
grasses
IgE antibodies to omega-5 gliadin
• Challenge positive children showed that with severe reactions
had significantly higher...
Ito et al. Allergy 2008: 63: 1536–1542.
• Significantly higher concentrations of specific IgE antibodies to omega-5-gliadi...
Palosuo et al. J Allergy Clin Immunol 2001;108:634-8.
• 40 children (mean age, 2.5 years;
range, 0.7-8.2 years)
• Suspecte...
Hae-Sim Park. Et al. Int Arch Allergy Immunol 2012;157:147–150.
Hae-Sim Park. Et al. Int Arch Allergy Immunol 2012;157:147–150.
Serum IgE ratio of omega-5 gliadin to wheat may be a usefu...
Palosuo et al. J Allergy Clin Immunol 2001;108:634-8.
Explained by the use of antigen extracts containing wheat proteins m...
Wheat sIgE Omega-5 gliadin sIgE
Urisu A et al. Japanese Guideline for Food Allergy 2014.
Natural history
Rate of resolutions
Age
Rate of resolutions
Keel et al.
Ann Allergy Asthma Immunol, 2009
Czaja-Bulsa et al.
Ann Allergy As...
Predictors of
tolerance
1.) Peak wheat IgE
2.) Age of reaching peak wheat IgE
Keel et al. Ann Allergy Asthma Immunol, 2009...
Peak wheat IgE level &
Persistence of wheat allergy
Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415.
median age 3...
Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014,10:12.
Peak wheat IgE level &
Persistence of wheat allerg...
Relationship of Wheat IgE level & Age
Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415.
In general, the peak wheat...
Wheat IgE level & Resolution
• Higher wsIgE levels : a poorer prognosis
• Decreases in sIgE over time might signal resolut...
• Compared with other food allergies, wheat specific IgE level is
less helpful in predicting clinical reactivity and progn...
Management
• Wheat avoidance
• WDEIA
1.) Avoidance of exercise for approximately 4 hr. after
ingestion of wheat
2.) Wheat should not ...
Difficult to
Avoidance !!!
Foods containing/possibly
containing wheat
Urisu A et al. Japanese Guideline for Food Allergy 2014.
www.wholegrainscouncil.org.
Specific oral
tolerance induction
(SOTI)
Indication
1. Severe reactions to food proven by challenge
2. History of accidental exposures recently
3. Unable to avoid ...
• 20 children with a history of wheat allergy
(allergic episodes were confirmed within a year prior to the study entry)
• ...
Taniuchi S. el al. The Journal of Applied Research. Vol.9 , No.4 , 2009.
S group
M group
C group
"Twice - weekly dose"
at ...
Results
• Group S
- 6/8 children (75%) : achieved a daily intake of 100g of wheat product
• Group M
- 5/7 (71.4%) : achiev...
• 2 children with high wheat sensitivity (4 and 14 years old boys)
• Oral challenges indicated eliciting doses of 300 mg, ...
Pacharn P, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2014.
Patients could tolerate 45 g, ...
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Wheat allergy

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Wheal Allergy

Presented by Lalita tearprasert, MD.

November17, 2015

Published in: Health & Medicine
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Wheat allergy

  1. 1. Wheat Allergy Lalita Tearprasert; M.D.
  2. 2. • Prevalence • Wheat proteins and allergens • Cross-reactivity • Clinical manifestations • Wheat allergy and others allergy • Diagnosis of wheat allergy • Natural history • Management • Specific oral tolerance induction (SOTI) Scope
  3. 3. Food Allergy : Top 8 90% of food allergy
  4. 4. Reactions to foods. Middleton's 8th Edition. 1310-39. Prevalence of wheat allergy • Varies depending on age and region : 0.4-1% M. J. Makela et al. Clinical & Experimental Allergy, 2014 (44) 1420–1430.
  5. 5. • In Asia - Marked differences in prevalence - Prominent in Japanese school children (unknown reason) 0.21% in Japanese adults - Increasingly reported in Thailand • Most common cause of food dependent exercise-anaphylaxis (FDEIA) in Japan and Korea Lee AJ, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2013. Prevalence of wheat allergy
  6. 6. Urisu A et al. Japanese Guideline for Food Allergy 2014. Japan
  7. 7. Urisu A et al. Japanese Guideline for Food Allergy 2014.
  8. 8. Lee AJ, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2013. 0.08-0.37% 0.22-0.5% Korea UK USA Japan
  9. 9. Thailand • The prevalence of wheat allergy was 4.85% (unpublished data). • During 1998-2005 • 103 patients who had a history of food allergy • At Allergy Clinic, Department of Pediatrics, Siriraj Hospital Pacharn, Et al. Asian Pacific Journal Of Allergy And Immunology (2009) 27: 115-120.
  10. 10. Wheat proteins & Allergens
  11. 11. Taxonomy of Wheat D.-A. Moneret-V autrin. Et al. Eur Ann Allergy Clin Immunol. Vol 40, N 3, 67-76, 2008. Durum wheat is very rich in gluten >> used to produce semolina flour and pasta products
  12. 12. Wheat grain Wheat proteins
  13. 13. Water/ Salt-soluble 1.) Albumins : Water - soluble 2.) Globulins : Salt - soluble 3.) Gliadins (Prolamins) : Ethanol - soluble 4.) Glutenins : Alkali/Acid - soluble Water/ Salt-insoluble Osborne T. The proteins of the wheat kernel. Washington DC: Carnegie Inst.1907,84. D.-A. Moneret-V autrin. Et al. Eur Ann Allergy Clin Immunol. Vol 40, N 3, 67-76, 2008. A.S. Tatham & P. R. Shewry. Clinical and Experimental Allergy, 38, 1712–1726. Gluten Wheat proteins • T.B. Osborne developed a classification (Osborne fractions) >> based on their solubility
  14. 14. M. J. Makela et al. Clinical & Experimental Allergy, 2014 (44) 1420–1430. D.-A. Moneret-V autrin. Et al. Eur Ann Allergy Clin Immunol. Vol 40, N 3, 67-76, 2008. Water/ Salt - soluble Albumins, Globulins • Most important allergen in this group • Associated with - Baker's asthma (adults) - Food allergy in atopic dermatitis (children) Alpha-amylase inhibitor (AAI)
  15. 15. Nonspecific lipid transfer proteins (LTP) • Wheat LTP (Tri a 14) • 24/40 patients (60%) of baker's asthma sensitized to wheat strongly recognized specific IgE to Tri a 14 • Major inhalant allergen associated with baker's asthma • Peach LTP, Pru p 3, showed a sequence identity of 45%, but the low cross-reactivity between both allergens Palacin et al. J Allergy Clin Immunol 2007;120:1132-8.
  16. 16. Gluten • Form a continuous network when wheat flour is mixed with water to form dough and processed into bread, noodles and other foods. • Comprises approximately equal amounts of the gliadin and glutenin A.S. Tatham & P. R. Shewry. Clinical and Experimental Allergy, 38, 1712–1726. Water/ Salt - insoluble Gluten
  17. 17. A.S. Tatham & P. R. Shewry. Clinical and Experimental Allergy, 38, 1712–1726. Palosuo et al. J Allergy Clin Immunol 2001;108:634-8. Fast Intermediate Slow Severe allergic reactions (WDEIA or WIA) associated with 1.) Omega-5 gliadin (Tri a 19) 2.) High-molecular-weight glutenin subunits • Triggering Coeliac disease
  18. 18. Omega-5-gliadin (Tri a19) • Related to the immediate symptoms after ingestion of wheat in wheat-sensitized children • Associated with a strong convincing history of wheat anaphylaxis • Risk marker for clinical reactivity • Associated with severe allergic reactions - Wheat-induced anaphylaxis (WIA) - Wheat-dependent exercise-induced anaphylaxis (WDEIA) Ito et al. Allergy 2008: 63: 1536–1542. Palosuo et al. J Allergy Clin Immunol 2001;108:634-8.
  19. 19. • Associated with >> WDEIA symptoms in patients that do not have IgE antibodies to omega-5-gliadin >> Marker of severity of oral wheat challenge Ito et al. Allergy 2008: 63: 1536–1542. M. J. Makela et al. Clinical & Experimental Allergy, 2014 (44) 1420–1430. High molecular weight glutenin (HMW)
  20. 20. Wheat allergens 2015 : 27 allergens
  21. 21. 2015 : 27 allergens (15 Food allergens)
  22. 22. Alpha-Purothionin (Tri a 37), a new wheat allergen associated with severe allergy • Novel water- and salt-soluble wheat food allergen 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 J Allergy Clin Immunol. October 2013. Volume 132, Number 4.
  23. 23. IgE reactivity to Tri a 37 was highly specific for wheat food allergy because patients with grass pollen allergy and nonallergic subjects did not show IgE reactivity J Allergy Clin Immunol. October 2013. Volume 132, Number 4. Food allergy Grass pollen allergy Nonallergic
  24. 24. • The sequence identity of Tri a 37 from wheat, rye, and barley was high (ie, >80%), whereas from oat, rice, and other plants showed a much lower sequence identity of 50% or less J Allergy Clin Immunol. October 2013. Volume 132, Number 4.
  25. 25. Baker's asthma WIA, WDEIA - 1.) Alpha - amylase inhibitor - (water/salt soluble) - 1.) Omega-5-gliadin (Tri a 19) - (water/salt insoluble) - 2.) Nonspecific lipid transfer - proteins/ LTP (Tri a 14) - (water/salt soluble) - 2.) High molecular weight - glutenin/ HMW - (water/salt insoluble) - 3.) Alpha-Purothionin (Tri a 37) - (water/salt soluble)
  26. 26. Cross-reactivity
  27. 27. Sampson et al. Food allergy. Practice parameter 2014. Cross-reactivity among grains
  28. 28. - Rye : γ-70 and γ-35 secalins - Barley : γ-3 hordein wheat : ω-5 gliadin K. Palosuo et al. Clinical and Experimental Allergy, 2001, Volume 31, pages 466-473. Rye Barley WheatWheat Wheat & Rye, Barley 23 patients with WDEIA showed IgE binding - 21 (91%) to g-70 secalins - 19 (83%) to g-35 secalins - 21 (91%) to g-3 hordein Cross-reactivity WDEIA
  29. 29. Cross-reactivity between grains & grass Family Poaceae Jones et al. J Allergy Clin Immunol 1995;96:341-51.
  30. 30. Jones et al. J Allergy Clin Immunol 1995;96:341-51.
  31. 31. • Patients with IgE-mediated wheat allergy alone show extensive in vitro cross-reactivity to other cereal grains and grass pollens • However, clinical cross-reactivity to multiple cereal grains occurs in a minority of patients sensitized to multiple grains • Elimination of all grains (eg, wheat, rye, barley, oats, rice, and corn) from the diet of a patient with grain allergy is not recommended and might be nutritionally harmful. Sampson et al. Food allergy. Practice parameter 2014.
  32. 32. Clinical manifestations
  33. 33. Clinical manifestations • Clinical types of wheat allergies depend on 1.) Age - Children : Atopic dermatitis (common) - Adult : Anaphylaxis, WDEIA, Baker's asthma (common) 2.) Sensitization route - Ingestion, Contact : AD, Anaphylaxis, WDEIA - Inhalation : Baker's asthma, Rhinitis Inomata N. Current Opinion in Allergy and Clinical Immunology 2009, 9:238–243. D.-A. Moneret-Vautrin. Et al. Eur Ann Allergy Clin Immunol. VOL 40, N 3, 67-76, 2008.
  34. 34. • IgE-mediated immediate symptoms (within minute - 2 hr. after ingestion) - Skin : Urticaria, Angioedema - Respiratory : Wheezing - GI : Vomiting, Abdominal pain - Atopic dermatitis - Anaphylaxis • Delayed reaction - Worsening of atopic dermatitis - GI symptoms Palosuo K. Update on wheat hypersensitivity. Curr Opin Allergy Clin Immunol 2003: 3: 205–9.
  35. 35. Keet et al. RA. Ann Allergy Asthma Immunol. 2009;102:410–415. • Johns Hopkins Pediatric Allergy Clinic from 1993 to 2007 • 103 patients with IgE-mediated wheat allergy 76/103 (86%) : ingestion 12/103 (14%) : contact, inhalation
  36. 36. • One of the most common forms of occupational asthma • 4-10% of bakery workers in European countries • Mostly sensitized to raw flour particles inhaled via the respiratory mucosa • Never have problems with ingestion of cooked wheat • IgE-mediated • Diagnosis : SPT, sIgE to wheat • Allergen : alpha-amylase inhibitors D.-A. Moneret-Vautrin. Et al. Eur Ann Allergy Clin Immunol. VOL 40, N 3, 67-76, 2008. A.S. Tatham & P. R. Shewry. Clinical and Experimental Allergy, 38, 1712–1726. Baker's Asthma
  37. 37. • 7 children (5 boys, 2 girls) • Aged from 6 months to 13 years • Department of Pediatrics, Siriraj Hospital in Bangkok Daengsuwan et al. Allergy 2005: 60: 506–509. Wheat-induced Anaphylaxis Thailand
  38. 38. France Moneret-Vautrin et al. Allergy 2005: 60: 443–451. • Between 2002 and 2004 • Department of Internal Medicine, Clinical Immunology and Allergology, University Hospital, Nancy Cedex, France
  39. 39. E. Morita et al. Journal of Dermatological Science (2007) 47, 109—117. Food-dependent exercise-induced anaphylaxis (FDEIA)
  40. 40. 100% 80% • January 2002 - December 2006 • 5 Childrens with a Hx of WDEIA • The mean ± SD of the patients' age at the onset of the symptoms was 11 ± 2.23 years (8-14 years) Pacharn, et al. Asian Pacific Journal Of Allergy and Immunology (2009) 27: 115-120.
  41. 41. Wheat-dependent exercise-induced anaphylaxis (WDEIA) • Diagnosis 1.) History of ingestion & Exercise 2.) An exercise challenge test following wheat ingestion (which is time-consuming and unsafe) • Mechanism 1.) Activated tissue transglutaminase 2.) Increased absorption of allergens through GI tract • Factor triggers - Among of wheat ingested - Degree of exercise - Others : Aspirin, NSAIDs (COX-1 inhibitors) Hae-Sim Park. Et al. Int Arch Allergy Immunol 2012;157:147–150. Inomata N. Current Opinion in Allergy and Clinical Immunology 2009, 9:238–243.
  42. 42. Before tTG After tTG Palosuo et al. J Allergy Clin Immunol 2003;111:1386-92. Tissue transglutaminase (tTG) • Enzyme in gut epithelium • Released and activated after stress-liked condition • Forming complex with digested gliadin
  43. 43. Digested gliadin forms peptide Cross-linked to tTG HMW complex Strong binding serum IgE Ab Palosuo et al. J Allergy Clin Immunol 2003;111:1386-92.
  44. 44. Inomata N. Current Opinion in Allergy and Clinical Immunology 2009, 9:238–243. • Management & Prevention 1.) Avoidance of exercise for approximately 4 hr. after ingestion of wheat 2.) Wheat should not be consumed for several hours after intake of aspirin and other preferential COX-1 inhibitors 3.) Education : Reading food labels, Adrenaline autoinjection
  45. 45. Wheat allergy & Other allergy
  46. 46. CDC/NCHS, National Health Interview Survey. October 2008.
  47. 47. Keet et al. RA. Ann Allergy Asthma Immunol. 2009;102:410–415. 90% allergic to at least 1 other food allergen (Most common : Milk) Most : Eczema
  48. 48. Most : Eczema Most : Milk 80% - In all the children other food allergies had been diagnosed before wheat Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014,10:12.
  49. 49. Kotaniemi-Syrjanen et al. Pediatr Allergy Immunol 2010: 21: e421–e428.
  50. 50. Diagnosis of wheat allergy
  51. 51. • Relation between food intake and symptoms • Diagnostic testing • Elimination diet • Oral food challenge How to diagnosis ?
  52. 52. Reactions to foods. Middleton's 8th Edition. 1310-39. sIgE to wheat • IgE levels have been regarded as a useful predictor of food challenge outcom Ito et al. Allergy 2008: 63: 1536–1542. Mixture of water/ salt soluble wheat protein Lack of gliadin fraction
  53. 53. Reactions to foods. Middleton's 8th Edition. 1310-39. Cross-reactivity of wheat allergens with grasses
  54. 54. IgE antibodies to omega-5 gliadin • Challenge positive children showed that with severe reactions had significantly higher concentrations of specific IgE antibodies to omega-5-gliadin compared with mild or moderate symptoms (P < 0.001) Ito et al. Allergy 2008: 63: 1536–1542.
  55. 55. Ito et al. Allergy 2008: 63: 1536–1542. • Significantly higher concentrations of specific IgE antibodies to omega-5-gliadin - Children with a positive challenge (P < 0.01) - Children with a positive convincing history (P < 0.001)
  56. 56. Palosuo et al. J Allergy Clin Immunol 2001;108:634-8. • 40 children (mean age, 2.5 years; range, 0.7-8.2 years) • Suspected wheat allergy (AD and/or GI and/or respiratory symptoms) • oral wheat challenge, - 19 children (48%) : immediate - 8 children (20%) : delayed hypersensitivity • 16/19 (84%) of the children with immediate symptoms had IgE antibodies to purified ω-5 gliadin in ELISA
  57. 57. Hae-Sim Park. Et al. Int Arch Allergy Immunol 2012;157:147–150.
  58. 58. Hae-Sim Park. Et al. Int Arch Allergy Immunol 2012;157:147–150. Serum IgE ratio of omega-5 gliadin to wheat may be a useful marker for the diagnosis of WDEIA and WIA. (Cutoff value = 0.3, Sensitivity & Specificity 100%) Ratio of omega-5 gliadin to wheat
  59. 59. Palosuo et al. J Allergy Clin Immunol 2001;108:634-8. Explained by the use of antigen extracts containing wheat proteins mainly from the water/salt-soluble albumin and globulin fractions rather than from the ethanol-soluble gliadin fraction Predictive capability
  60. 60. Wheat sIgE Omega-5 gliadin sIgE Urisu A et al. Japanese Guideline for Food Allergy 2014.
  61. 61. Natural history
  62. 62. Rate of resolutions Age Rate of resolutions Keel et al. Ann Allergy Asthma Immunol, 2009 Czaja-Bulsa et al. Ann Allergy Asthma Immunol, 2014 4 yrs. 29% 20% 8 yrs. 56% 52% 12 yrs. 65% 66% 18 yrs. - 76% Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415. Czaja-Bulsa et al. Ann Allergy Asthma Immunol, 2014.10:12. Median age 6.5 yrs.
  63. 63. Predictors of tolerance 1.) Peak wheat IgE 2.) Age of reaching peak wheat IgE Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415. Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014, 10:12.
  64. 64. Peak wheat IgE level & Persistence of wheat allergy Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415. median age 31 mo. median age 54 mo. median age 145 mo. P < 0.001
  65. 65. Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014,10:12. Peak wheat IgE level & Persistence of wheat allergy Peak wheat IgE (kU/L) Median age of tolerance (mo.) < 10 41.4 10-19.9 44.5 20-49.9 84.9 50 up 190.5 80% of WT : peak wsIgE < 50 kU/L 40% of WT : peak wsIgE 50 kU/L up
  66. 66. Relationship of Wheat IgE level & Age Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415. In general, the peak wheat IgE level occurred before 4 years of age Reaching peak wheat IgE in older age is an important factor increasing the risk that the allergy will continue into adulthood Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014,10:12.
  67. 67. Wheat IgE level & Resolution • Higher wsIgE levels : a poorer prognosis • Decreases in sIgE over time might signal resolution Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014,10:12. Sampson HA. et al. J Allergy Clin Immunol. Volume 133. Number 2. Febuary 2014.
  68. 68. • Compared with other food allergies, wheat specific IgE level is less helpful in predicting clinical reactivity and prognosis 1.) No clear cutoffs for wheat IgE levels that predict clinical reactivity 2.) Grass pollens and wheat can be cross-reactive in vitro, creating false-positive wheat IgE test results 3.) sIgE for wheat do not contain all the wheat grain allergens • Children passed wheat challenges with even the highest levels of wheat IgE - 25% of children with a peak wheat IgE level more than 50 kU/L outgrew their allergy - 20% of children with a peak wheat IgE level more than 100 kU/L outgrew their allergy Keel et al. Ann Allergy Asthma Immunol, 2009.102:410–415. Czaja-Bulsa and Bulsa Allergy, Asthma & Clinical Immunology 2014,10:12.
  69. 69. Management
  70. 70. • Wheat avoidance • WDEIA 1.) Avoidance of exercise for approximately 4 hr. after ingestion of wheat 2.) Wheat should not be consumed for several hours after intake of aspirin and other preferential COX-1 inhibitors • Education : Reading food labels, Adrenaline autoinjection Management Inomata N. Current Opinion in Allergy and Clinical Immunology 2009, 9:238–243.
  71. 71. Difficult to Avoidance !!! Foods containing/possibly containing wheat
  72. 72. Urisu A et al. Japanese Guideline for Food Allergy 2014.
  73. 73. www.wholegrainscouncil.org.
  74. 74. Specific oral tolerance induction (SOTI)
  75. 75. Indication 1. Severe reactions to food proven by challenge 2. History of accidental exposures recently 3. Unable to avoid food on daily life 4. Age limit beyond natural acquisition of tolerance to particular food SOTI Wheat Accidental exposure frequently occurs since wheat is commonly used in widely available processed foods Age of natural tolerance to wheat is poorly defined Pacharn P, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2014.
  76. 76. • 20 children with a history of wheat allergy (allergic episodes were confirmed within a year prior to the study entry) • 13 male, 7 female, Age 4.1±2.3 years • Divided into 3 group based on the value of ELISA of the hypoallergenic wheat at the time of study entry - Severe wheat allergy (group S) : IgE < 0.05 (8 children) - Mild wheat allergy (group M) : IgE > 0.05 (7 children) - No desensitization (group C) : 5 children Taniuchi S. el al. The Journal of Applied Research. Vol.9 , No.4 , 2009.
  77. 77. Taniuchi S. el al. The Journal of Applied Research. Vol.9 , No.4 , 2009. S group M group C group "Twice - weekly dose" at home
  78. 78. Results • Group S - 6/8 children (75%) : achieved a daily intake of 100g of wheat product • Group M - 5/7 (71.4%) : achieved the daily intake of 100g of wheat product • Group C - 4/5 (80%) : severe allergic reactions Conclusions • Hypoallergenic wheat is a useful food for inducing food tolerance of wheat by oral desensitization for children with wheat allergy. • Further study will be needed to evaluate the starting dose and the frequency of ingestion of hypoallergenic wheat Taniuchi S. el al. The Journal of Applied Research. Vol.9 , No.4 , 2009.
  79. 79. • 2 children with high wheat sensitivity (4 and 14 years old boys) • Oral challenges indicated eliciting doses of 300 mg, and wheat flour of 30 mg • Multirush/ maintenance regimen • OIT protocol - 5 days of build-up phase in the hospital intervening - 2 to 5 months of home maintenance phase Pacharn P, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2014.
  80. 80. Pacharn P, et al. Asia Pacific Association of Allergy, Asthma and Clinical Immunology 2014. Patients could tolerate 45 g, and 60 g of wheat flour per day 40 g./ pack15 g./ piece
  81. 81. Thank you

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