This document summarizes information about wheat allergy, including its prevalence, wheat proteins and allergens, clinical manifestations, diagnosis, and management. Some key points: - Wheat allergy prevalence varies by age and region, ranging from <1% to over 3% in Europe and the US. It is less common in Asia-Pacific regions. - Major wheat allergens include alpha-amylase inhibitors, lipid transfer proteins, gliadins like omega-5-gliadin, and glutenins. These can cause reactions from baker's asthma to food allergy. - Clinical manifestations depend on exposure route and age. Symptoms include immediate reactions like anaphylaxis as well as

1. Wheat allergy
Tharida Khongcharoensombat, MD
1st year fellow, Division of Pediatric Allergy and Immunology
Department of Pediatrics, Faculty of Medicine
Chulalongkorn University, King Chulalongkorn Memorial Hospital
20 Aug 2021

2. Scope
• Prevalence
• Wheat proteins and allergens
• Cross-reactivity
• Clinical manifestation
• Wheat allergy in Adult Vs children
• Diagnosis
• Management
• Wheat OIT
• Natural history

3. Prevalence : Europe
• The prevalence of WA varies according to the age and region.
• In Europe, a WA prevalence <1% has been reported in different studies.
• In a systematic review¹ (Europe, Allergy2014)
• Prevalence of positive wheat challenges was 0.1%
• A lifetime and point self-reported prevalence of 3.6% and1.5%, respectively
• The difference between self-reported and challenge-verified prevalence of WA can be
due to parents mistaking other adverse reactions to food (i.e., gluten sensitivity) for
food allergy
• UK, a prevalence of 0.48%has been reported in children, according to positive OFC
• US, data from skin prick test (SPT) suggest a WA prevalence higher than 3%, even if it is
more likely estimated to be 0.2% to 1%
1 Nwaru, B.I.; et al. Allergy2014,69, 992–1007
Ricci, G., et al, 2019. Wheat Allergy in Children: A Comprehensive Update. Medicina 55, 400.

4. Lee AJ, et al Asthma and clinical immunology 2013
Taiwan, Hong Kong, China : Wheat allergic children was uncommon
Prevalence : Asia - Pacific

5. • Healthy population
: 0.16 to 0.37%
• Subjects with
allergy symptoms :
10.4% to 26.1%
J Gastrointestin Liver Dis, March 2019 Vol. 28 No 1: 95-105

6. Increase in numbers of children with wheat allergy in Thailand
Witchaya Srisuwatchari and Pakit Vichyanond, Asia Pac Allergy. 2018 Apr;8(2):e21
Prevalence : Thailand

7. Gluten-related disorders
J Gastrointestin Liver Dis, March 2019 Vol. 28 No 1: 95-105

8. Triticeae
Triticum : Wheat
Secale : Rye
Hordeum : Barley
Kirsi M Jarvinen-Seppo. Grain allergy: Allergens and grain classification, Uptodate, Last updated: Aug 26, 2019.

9. Durum wheat (Triticum durum) : rich in gluten
Pasta produce
Bread wheat
bread and bakery products
Major cultivated species of wheat
Mastrangelo, A.M., 2021. Trends in Plant Science 26, 677–684.

10. Wheat protein and allergens
F. Battais. Et al, Eur Ann Allergy Clin Immunol, VOL 40, N 3, 67-76, 2008

11. 30-40% 35-40%
Prolamin or Gluten : major storage protein
>> for baking product
Share a great degree of sequence and
structural homology with the corresponding
proteins in rye and barley
baker’s asthma
AD with or without asthma
WDEIA
F. Battais. Et al, Eur Ann Allergy Clin Immunol, VOL 40, N 3, 67-76, 2008
10-15%
(Triticum aestivum, Tri a)

14. Alpha amylase inhibitor
• Route of exposure : Inhale, ingest
• Associated with
• Baker’s asthma
• Food allergy with AD in children and adult
• Anaphylaxis
• WDEIA
• Heat resistant, present in cooked wheat (5 min at100°C) can
still cause an allergic reaction
• Lacks significant cross-reactivity to grass pollen
Mäkelä, M.J., et al. Clinical & Experimental Allergy 44, 1420–1430.

15. LTP
• Route of exposure : Inhale, ingest
• Tri a 14
• IgE-mediated food allergies (especially in Italian children)
• WDEIA
• Baker ’s asthma
Giampaolo Ricc et al. Medicina2019,55, 400

17. Gluten : Gliadin
Gamma-gliadin : An important marker for severity
Omega-5-gliadin ; Tri a 19
• More specific marker for wheat allergy diagnostics than whole wheat proteins
• Associated with
• WDEIA
• Anaphylaxis to wheat consumption
• AD exacerbate with wheat consumption
Jac-quenet and co-authors :
• 75 and 82% of patient with WDEIA had detectable specific IgE antibodies to omega-5 gliadin
Morita, Matsuo :
• 20% of WDEIA patients are not sensitive to omega-5 gliadin (specific IgE to other wheat protein : HMW
glutenin, AAI, LTP )
Carefully selected patients with symptoms suggestive of EIWA >> Useful of sIgE to omega-5 gliadin
Int Arch Allergy Immunol 2011;155:93–94

18. Gluten : Glutenin
• HMW-glutenin : important marker of severity of the oral wheat
challenge reaction
Mäkelä, M.J., et al. Clinical & Experimental Allergy 44, 1420–1430.

19. Alpha-Purothionin (Tri a 37)
• Wheat, rye, baley : Sequence identity > 80%
• Oat, rice, other plants : Sequence identity < 50%
• Stable and resistant to heat and digestion
• Wheat-induced anaphylaxis is more than 4-fold higher in the Tri
a 37–reactive patients (odds ratio, 4.6; 95% CI, 1.5-14.2).
Highly specific for wheat, not cross react with grass pollen
Marker for severe anaphylactic reactions
Pahr, S., et al. Journal of Allergy and Clinical Immunology 132, 1000–1003.e4.

20. • Baker’s asthma : AAI, LTP (Tri 14 )
• > 60% of patients with baker’s asthma recognized at
least one of these markers.
• Severe reaction (WIA, WDEIA)
• Omega-5-gliadin
• HMW glutenins
• Alpha-Purothionin
Gómez-Casado. et al. 2014 Journal of Allergy and Clinical Immunology 133, AB151

21. Cross reactivity
• Cereal grains share homologous proteins with grass pollen, which
may account for the high rate of sensitization to cereal grains but
lower rate of clinical reactivity
• True Clinical reactivity
• Wheat – Rye
• Wheat – Barley (less)
• Wheat – Other grains : oat, rice, corn (less so far)
• Prolamin like Rye (γ-70 andγ-35secalins ) and barley (γ-3 hordein ) :
cross-react with wheat ω-5 gliadin
• Wheat-Rye-Barley : Alpha prurothionin
Kirsi M Jarvinen-Seppo. Grain allergy: Allergens and grain classification, Uptodate, Last updated: Aug 26, 2019.

22. Practice parameter 2014
• IgE mediated wheat allergy alone show extensive in vitro cross
reactivity to other cereal grains and grass pollen
• Clinical cross react to multiple cereal grain occurs in a minority
of patient sensitized to multiple grains
• All grain eliminate (wheat, rye, barley, oat, rice, corn) : not
recommend

24. W.Srisuwatchari et al. Allergol Immunopathol (Madr). 2020; 48(6) : 589-596

25. • Wheat Vs Barley and Rye : clinical cross reactivity < 25%
• Exclusion of all cereals is not warranted in patients with a primary IgE
mediated wheat or other single grain allergy.
• Nevertheless, given frequent cereal grain cross-sensitization and poor
predictive values of SPT and sIgE levels, clinical tolerance will often need
to be assessed by food challenge
• Millet, corn, sorghum, teff, and pseudocereals such as amaranth and
quinoa are gluten-free and generally safe for those allergic to wheat and
gluten-containing grains
J Allergy Cli Immunol Pract, January 2021

26. Risk factor of wheat allergy
• In children with wheat allergy, atopic disorders often coexist
• Atopic dermatitis (78%– 87%).
• Asthma (48–67%)
• Allergic rhinitis (34–62%)
• About 90% of infants have been reported to be allergic to other foods.
• Cow’s milk and/or egg are more frequently associated with WA, less frequently
fish, soya, and nuts
• Sensitization to grasses is associated with an increased risk for
occurrence of sensitization to wheat over time.
• In children with positive IgE to Phl p12 (profilin) and to MUXF3 CCD (Cross-
reactive Carbohydrate Determinant),the grass–wheat cross-reactivity seems to
be more common.
Giampaolo Ricc et al. Medicina2019,55, 400
Czaja-Bulsa, G. Allergy Asthma Clin. Immunol. 2014; 10: 12.

27. Clinical Manifestation
• Route of exposure/ Age group
EAACI molecular Allergology User’s Guide 2016

28. IgE-mediated immediate symptoms
• Within minutes to 1-2 hr after ingestion of wheat
• Urticaria, angioedema, erythema, pruritus, vomiting, abdominal
pain, persistent cough, hoarse voice, wheeze, stridor,
respiratory distress, nasal congestion, anaphylaxis
• Delayed-type symptoms : worsening of atopic dermatitis, GI
symptoms such as stomach pain, diarrhea
• Wheat allergen involved : Omega-5-gliadin, HMW glutenins,
LMW glutenins, AAI’s EAACI molecular Allergology User’s Guide 2016

29. • A cross-sectional study among Thai children who presented with IgE-
mediated wheat allergy during 2001 to 2015
Srisuwatchari W, et al.. Asian Pac J Allergy Immunol. 2020 Mar 29
• WA presented very early in life at a median age of 7 months
• 90% developed their first reaction after their first ingestion of wheat
• Atopic dermatitis (AD) was found to be the only significant difference
between groups and found more commonly in SO than in WA
(59.2% vs. 35.3%, p = 0.02)
• Median mean wheal diameter (MWD) of skin prick test (SPT) and
median sIgE level to wheat were higher in WA than in SO (8 vs. 3
mm, p < 0.001; and, 33.3 vs. 3.6 kUA/l, p < 0.001).
Anaphylaxis risk increased
• MWD size of SPT was 7.5 mm or larger than the normal saline
control
• The level of sIgE to wheat was at least 30.9 kUA/l or greater
• The level of sIgE to ω5G was at least 3.1 kUA/l or greater
Which suggests that these cut-offs of could be useful predictors for
determining the severity of wheat allergy.

30. Baker’s asthma
• 4% to 25% of bakery workers worldwide
• Inhalation of wheat flour and dust during grain processing and subsequent
sensitization to water-soluble antigen
• More frequent in atopic subjects who are exposed to high levels of wheat
allergens for several hours per day
• Baker’s asthma is often preceded by rhinitis, and skin symptoms are often
concomitant
• Diagnosis : A clinical history with typical exposure-related symptoms and
confirmation of type I sensitization by skin prick tests, ImmunoCAP tests,
or both and specific inhalation challenge tests (SICTs) when indicated
• Wheat allergen involved : AAI’s (particularly Tri a 15, 30)
EAACI molecular Allergology User’s Guide 2016

31. A bakery is a complex environment
with a multitude of potential
sensitisers, and there are case reports
of baker’s asthma caused by moulds,
yeast, eggs, sesame seeds, nuts, and
insects
Occup Environ Med 2002;59:498–502

32. Nam YH, et al. J Korean Med Sci. 2013;28(11):1697-1699.

33. WDEIA
• Symptoms occurs only when the patient exercises within 2 to 4 hours of ingesting wheat,
but in the absence of exercise, the patient can ingest wheat without any apparent reaction
• Pruritus, cough, chest tightness, angioedema, urticaria, wheezing, and
gastrointestinal complaint
• Mechanism
• Increases the bioavailability and influences the distribution of certain allergens
• Decreases the threshold for activation of mast cells and basophils
• Trigger factor
• Common : Exercise, NSAIDS, Alcohol
• Less common : Increase body temperature, infection, Physical stress, sleep
deprivation, premenstrual or menstrual phase, narcotics/opioid
• Wheat allergen involved : Omega-5-Gliadin, LTP (Tri a 14) , alpha/beta-gliadin (Tri a 21),
HMW glutenin (Tri a 26), LMW glutenin (Tri a 36)
EAACI molecular Allergology User’s Guide 2016
J Allergy Clin Immunol Pract. Mar-Apr 2017;5 (2):283-288

34. Proposed pathomechanism
• Exercise and Aspirin increase gastrointestinal permeability and facilitate allergen
absorption into the circulating blood
• Activation of tissue transglutaminase
• Activated during exercise, which results in conjugates between wheat peptides and
TG2 followed by IgE binding
• Enhance degranulation on mast cell or basophil
• Exercise-induced release of endorphins may enhance MC or basophil activation.
• Exercise mobilizes and activates immune cells from gut-associated depots stimulating
pro-inflammatory responses that are normally countered by anti-inflammatory responses
• Blood flow redistribution during exercise may carry allergens to tissues containing mast
cells that are not tolerant to these allergens. This may result in an allergic reaction during
exercise and tolerance at rest
• Exercise induces locally increased osmolality in the intestine, enhances mast cell
degranulation, and thus, increases gut permeability K. A. Scherf et al. Clinical & Experimental Allergy, 46, 10–20

35. K. A. Scherf et al. Clinical & Experimental Allergy, 46, 10–20

36. Jan 2002-Dec2006
• 5 children with WDEIA
• Male
• Skin and respiratory
symptoms
ASIAN PACIFIC JOURNAL OF ALLERGY AND IMMUNOLOGY (2009) 27: 115-120

37. K. A. Scherf et al. Clinical & Experimental Allergy, 46, 10–20
IgE to crude Gliadin extract IgE to crude omega-5-gliadin

38. K. A. Scherf et al. Clinical & Experimental Allergy, 46, 10–20
Patient who do not have antibodies specific to omeaga-5-gliadin
(around 20%), have IgE antibodies specific to HMW-GS

39. Comparisons of in-house wheat skin prick test
extracts for the diagnosis of wheat dependent
exercise induced anaphylaxis (WDEIA)
• 9 WDEIA and 9 controls with history of wheat allergy and negative wheat
challenges
• Method :
• SPT using 4 in-house extracts (wheat Coca’s, wheat sodium base
(SB), gliadin and glutenin solutions), and commercial extract
• SIgE to wheat and omega-5-gliadin
• Result : WDEIA
• Significantly older (15.3 vs 5.3 years, p50.01)
• Had later onset of symptoms compared to controls (5.5 vs 0.6 years,
p=0.001).
• The mean wheal diameter of SPT of all, except commercial extract,
were significantly larger in WDEIA compared to controls (p=0.0001)
Siwaporn S. et al., J Allergy Clin Immunol, February 01, 2019

40. SPT Sensitivity Specifity
wheat-Coca’s 77.8% 66.7%
Wheat sodium base 66.7% 77.8%
gliadin 88.9% 88.9%
glutenin 77.8% 88.9%
commercial extracts 44.4% 88.9%
Sensitivity Specifity
sIgE for wheat 77.8% 66.7%
sIgE for omega-5-gliadin 88.9% 100%
SIgE to omega-5-gliadin and SPT with gliadin extract were useful tools in diagnosing WDEIA.
Siwaporn S. et al., J Allergy Clin Immunol, February 01, 2019

41. Contact urticaria
• Hydrolysed wheat gluten protein (HWP), which is the water-
soluble, emulsifying, and foaming product obtained after
different procedures of gluten hydrolysis with acid, alkaline, or
enzymes.
• HWP is used as additive for soaps, shampoos, creams
• Exposure to HWP can cause either contact urticaria or even
anaphylaxis when consuming deamidated gluten containing
food
EAACI molecular Allergology User’s Guide 2016

42. Predominant symptom
• Angioedema on eyelids
• Less frequently from hypotension than
patients with CO-WDEIA
Yuko Chinuki. Allergology International Vol 61, No4, 2012

43. Yuko Chinuki. Allergology International Vol 61, No4, 2012

44. Yuko Chinuki. Allergology International Vol 61, No4, 2012

45. HWP-WDEIA IgE antibodies bound to
alpha/beta-, gamma-, and omega1,2-gliadins and an epitope from gamma-gliadin (QPQQPFPQ) was identified
BAT, SPT using Glupearl 19S is recommend.
Yuko Chinuki. Allergology International Vol 61, No4, 2012

46. Diagnosis
• Wheat allergy diagnosis is difficult because not all of the major wheat
grain allergens are recognized.
• Characteristic extractability properties of wheat grain proteins have
significant implication for commercially available diagnostic products
• Wheat ImmunoCAP® contains a significantly higher amount of salt-soluble
fraction
• Glutenin and/or ω-5 gliadin ImmunoCAP contains the salt insoluble fraction.
• Diagnosis of an IgE mediated wheat allergy is based on an accurate
history and symptoms
• Diagnostic test (IgE mediated) : Skin prick test, sIgE
• Oral food challenge
• Elimination of diet (non-IgE mediated)
Journal of Asthma and Allergy 2016:9

47. Journal of Asthma and Allergy 2016:9
Lack of gliadin
fraction
Cross - reactivity

48. • Wheat-sIgE in serum cannot predict the severity of reaction
• Wheat-specific IgE is common among atopic children without
true food allergies
• OFCs remain mandatory where there is a no clear history of IgE
mediated reaction to wheat, even if IgE specific to wheat can be
demonstrated
• Most studies have found that wheat OFCs are generally safe,
with a rate of failure (30%–50%) and use of epinephrine (10%–
20%) similar to other foods (ie, milk, egg, and peanuts), but
near fatal reactions can occur.
Journal of Asthma and Allergy 2016:9

49. Oral food challenge test
Whole wheat starting from small doses of wheat-specific protein (1–50 mg) followed by
increasingly larger hourly doses ending with a cumulative dose of up to 0.5–1 g of wheat protein.
J Allergy Clini Immuol Pract 2019

50. Diagnosis of baker’s asthma
The diagnosis of baker’s asthma or allergic rhinitis is based on
1. Clinical history
• Any new onset of asthma or allergic rhinitis in a worker exposed to significant wheat
allergen
• Not only the current job but also past jobs and exposure
2. SPT, Specific IgE to wheat
3. In selected individuals, a positive nasal or bronchial response to provocation.
• Nebulization of commercial aqueous flour solutions in increasing concentrations
(0.01, 0.1, 1, 10, and 100 mg/mL by tidal volume breathing for 10 minutes) or by
inhaling wheat flour dust (commercially available or obtained from the workplace)
filled in capsules via spinhaler (King Pharmaceutical, Tennessee, TN, USA)
• Baker’s asthma is diagnosed if a bronchial provocation test induces at least a
20% decrease in forced expiratory volume in 1 second or a threefold increase in
nonspecific bronchial hyperreactivity accompanied by an increase in sputum
eosinophilia.
Journal of Asthma and Allergy 2016:9 13–25

51. • Signs and symptoms consistent with anaphylaxis that occurred
during (or within an hour of) exercise but only when exercise was
preceded by food ingestion.
• No symptoms on ingestion of that food in the absence of exertion
and no symptoms if exercise occurs without ingestion of that food.
• Food + exercise challenge confirms the diagnosis
• If a specific food is implicated, there should be evidence of specific
IgE to the implicated food, either by skin testing or by food-specific
IgE immunoassays
• No other diagnosis that explains the clinical presentation.
• A serum tryptase level should be measured in all patients and should
be normal in individuals with FDEIA when the patients are in their
usual state of health
Diagnosis of WDEIA
J Allergy Clin Immunol Pract. Mar-Apr 2017;5 (2):283-288

52. Diagnosis of WDEIA
• WDEIA : prolong time lag (32–62 months)
• Rarity of the disease and the lack of recognition from physicians
• WDEIA is often mistaken for other more common diseases such as urticaria, EIA, or
idiopathic anaphylaxis
• SPT, or specific IgE to wheat, gluten and ω-5 gliadin should be performed
• OFC followed by a maximal exercise on a treadmill may be necessary to confirm the
diagnosis
• A negative challenge does not rule out WDEIA because several cofactors may be
missed in a controlled challenge environment (ie, the intensity of exercise, pollen
exposure, concomitant ingestions of non-steroidal anti-inflammatory drugs or
alcohol, and the presence of menses in females)
• A recent study has indeed shown that alcohol and non-steroidal antiinflammatory
drugs are a significant risk factor for WDEIA, and can induce WDEIA even in the
absence of exercise in a small subgroup of patients
Journal of Asthma and Allergy 2016:9

53. Knut Brockow et al. J Allergy Clin Immunol, April 2015

54. • The threshold dose of gluten required to elicit a reaction ranged
from 10 to 80 g of gluten with or without cofactors
• Gluten alone was able to elicit reactions in 4 (25%) of 16 of the
patients.
• Cofactors were required in 12 of 16 of the patients:
• (1) submaximal exercise in 2 (33%) of 6 patients
• (2) 500 to 1000 mg of ASA and 10 to 30 mL of alcohol elicited reactions
in 10 (100%) of 10 patients, including 3 patients in whom submaximal
exercise as a cofactor had previously not induced symptoms
Knut Brockow et al. J Allergy Clin Immunol, April 2015

55. Knut Brockow et al. J Allergy Clin Immunol, April 2015

56. • WDEIA can be elicited with high allergen doses, even in the absence of exercise and other
cofactors.
• Thus the amount of allergen ingested appears to be important
• Augmentation factors might be necessary to achieve a reaction threshold, which would not
otherwise be reached with a normal diet
• “Augmentation factor– triggered food allergy’’ might be a more appropriate term for this
disease entity
• In challenge patient : SPT positive to
• Commercial wheat extract : 8 (50%)
• Native wheat 15 (94%)
• Gluten 16 (100%)
• Significantly larger wheal diameters for gluten (8.1 +- 3.5 mm; range, 4-15 mm)
compared with commercial wheat extract (2.5 +- 1.6 mm; range,0-6mm, P<0.01)
• Specific IgE to wheat, gluten, and omega-5-gliadin was present in 13 (81%), 16 (100%),
and 16 (100%) of tested patients, with a mean of 2.2, 7.7, and 12.8 kUA/L, respectively
Knut Brockow et al. J Allergy Clin Immunol, April 2015
Good screening test : SPT to gluten
Good confirmation test : Oral challenge with gluten

57. Wheat allergy in children Vs adult
• Data from the European Anaphylaxis Registry (12 European countries)
• Cases reported between 2007 and March 2019
• 250 patients (213 adults and 37 children) with a history of anaphylaxis
caused by wheat were analyzed (regardless of whether it was exercise
induced or not)
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

58. WDEIA is the most common form of wheat
anaphylaxis in adults in Europe
• 250 anaphylactic reactions
caused by wheat were reported,
which comprised 2.4% (2.1%-
2.7%) of all 10,636 reactions in
the database and 6.9% (6.1%-
7.7%) of the 3646 reactions to
food.
• Male = female
• Wheat anaphylaxis primary occur
in adulthood (n = 213), followed
by early childhood (n = 25)
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

59. 82.8%
23.5%
Associated with exercise
Delay
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

60. Adults with wheat anaphylaxis suffer less frequently from
atopic comorbidities than adult patients with other food
allergies
36.3%
63.2%
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

61. Wheat anaphylaxis in adults presents
with a distinct symptom profile
Skin/mucosal : similar in all group Respiratory symptoms : Less often
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

62. Wheat anaphylaxis in adults presents
with a distinct symptom profile
More cardiovascular symptoms and loss of consciousness
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

63. Wheat as an elicitor is an independent
indicator for reaction severity among adults
Wheat : more severe
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

64. Most wheat anaphylaxis cases among adults in
northeastern Germany were associated with
omega-5-gliadin sensitization
• In 36 of 39 cases, exercise was a cofactor of the reaction,
whereas it was not in 3 of 39 cases.
• Most patients were sensitized to Tri a 19 (31 of 39, 79.4%)
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

65. Wheat anaphylaxis in children differs
from reactions to wheat in adults
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

66. Wheat allergy in children Vs adult
• Adult
• WDEIA
• Less Atopic cormorbidity
• Less respiratory symptoms
• More Cardiovascular and loss of
concious
• Wheat allergy : predict severity
• Patients presenting with recurrent
urticaria or idiopathic anaphylaxis
should be evaluated to exclude
wheat allergy
• Children
• Male
• More atopic cormorbidity
• More skin and respiratory
symptoms
• More Cardiovascular and loss of
conscious
• Wheat allergy : predict severity
Kraft M, et al. J Allergy Clin Immunol Pract. 2021 Jul;9(7):2844-2852.e5.

67. Management
• Avoiding both food and inhaled wheat allergens
• Patients with WA must be trained to identify relevant food
allergens in the labels, and written instruction should be given to
effectively eliminate wheat from their diet
• Adrenaline autoinjection
• WDEIA
1) avoidance of exercise within 4–6 hours following wheat
ingest
2) always carrying emergency medication
3) Avoid possible augmenting factor
Journal of Asthma and Allergy 2016:9

69. Wheat OIT
• Protect against cross contamination
• Protect from larger accidental exposure
• Regular ingestion of the food
Pepper et al jaci 2020; 146:2449

70. Starts at a subthreshold dose >>
rapidly increased every 30 minutes
over the course of several hours to
identify the highest tolerated dose.
Increase dose q 2 wk until
the target or highest
tolerate dose is reached
(Usually 6-12 mo)
Gernez, Y., Nowak-Węgrzyn, A., The Journal of Allergy and Clinical Immunology: In Practice 5, 250–272

71. Mechanism of oral
tolerance
• On passage through the epithelial
barrier, food protein allergen is
captured by the dendritic cell (DC).
• The DC migrates to the near by
mesenteric lymph nodes and
produces TGF-b, IL-10, and IL-
27,which induce secretion of
IgGA/IgG4 by B cells and
generation of Tregs.
• Tregs express CCR9 and a4b7,
the homing molecules that direct
them to migrate to the gut.
• Tregs secrete IL-10 and TGF-bthat
further induce and reinforce
tolerance
Gernez, Y., Nowak-Węgrzyn, A., The Journal of Allergy and Clinical Immunology: In Practice 5, 250–272

72. • 18 patients with wheat anaphylaxis underwent
wheat OIT for 2 years.
• OFC after OIT cessation at 2 weeks
• Sustain unresponsiveness :11 patients
(61.1%) passed a final oral food challenge
(OFC, 5200 mg of wheat protein ; 200 g of
boiled udon (Japanese wheat noodles)
Sato et. J Allery Clin Immunol 2015

73. 63 patient 44 patient 19 patient 11 patient
Sustain
unresponsiveness
= 58%
Makita et al. J Allergy Clin Immunol Pract 2019

74. It is difficult to estimate the risk of symptoms after OIT;
therefore, long-term follow-up after wheat OIT is necessary
No difference
Makita et al. J Allergy Clin Immunol Pract 2019

75. Natural history
• Wheat allergy and concomitant atopic dermatitis suggest that 25-33% of patients become tolerant
by follow-up 1 to 2 years later
• In a prospective study of 50 Polish children with positive wheat specific IgE and food challenge
results along with predominant gastrointestinal symptoms
• 20% by age 4
• 52% by age 8
• 66% by age 12
• 76% by age 18
• A larger retrospective study (Keet C. et al 2009))
• Median age at resolution of wheat allergy of 6.5 years
• 35% of patients remained allergic into their teens
• Peak wheat specific IgE : useful in determining the age at which tolerance develops, and higher
levels may be related to allergy persistence.
• However, high levels of wheat IgE do not preclude resolution of the allergy
Savage, J., Johns, C.B., 2015. Food Allergy. Immunology and Allergy Clinics of North America 35, 45–59.

76. • 83 children (born in 2005–2006) who had a history of immediate-type
allergic reaction to wheat and were followed until 6 years of age
• “Tolerant” (n = 55; tolerance acquired by 6 years of age) and “Allergic” (n =
28; tolerance not acquired by 6 years of age)
• OFC
• 1 year after the last immediate allergic response
• Decrease in wheat-specific IgE levels
• 15 or 40 g of udon noodles (equivalent to 0.4 or 1.3 g of wheat protein, respectively).
• Tolerant if they were able to eat 200 g of udon noodles or 1 piece of bread
(containing 5.2 g of wheat protein) Int Arch Allergy Immunol 2018;176:1–6

77. The rate of acquired tolerance was observed
to gradually increase with patient age.
Int Arch Allergy Immunol 2018;176:1–6

78. Predictor of
persistent disease
• History of anaphylaxis
all foods
• History of anaphylaxis to
wheat
• Prolonged high wheat-
related specific IgE levels
• >= approximately 13
UA/mL at 12 months
of age
Int Arch Allergy Immunol 2018;176:1–6

79. Thank you !!