Wheat Allergy

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

Wheat is one of the major crops grown and consumed by humankind and is associated with both intolerances (notably coeliac disease) and allergies.

Three types of allergy are particularly well characterized

- Food allergy to wheat. Some new allergens, including nonspecific lipid transfer protein (Tri a 14), have been identified.

- Wheat-dependent exercise-induced anaphylaxis (WDEIA), with the omega(5)-gliadins (part of the gluten protein fraction) being the major group of proteins which are responsible. Wheat is the most common food associated with food-dependent exercise-induced anaphylaxis.

- Bakers' asthma - results from the inhalation of flour and dust during grain processing.

Celiac disease is different from wheat allergy

Celiac disease is not a wheat allergy or gluten allergy. Celiac disease is an autoimmune disease triggered by eating gluten. Patients with celiac disease will not lose their sensitivity to gluten. Celiac disease requires a lifelong restriction of gluten.

The major grains that contain gluten are wheat, rye, and barley. These grains must be strictly avoided by patients with celiac disease.

Recent studies support the existence of the new condition nonceliac gluten sensitivity which is defined as symptoms with negative celiac antibodies and biopsy (http://goo.gl/57IlB).

Wheat-allergic people have an IgE-mediated response to wheat protein. These individuals must only avoid wheat. Most wheat-allergic children will outgrow the allergy.

Key figures: New nomenclature and classification of gluten-related disorders and Algorithm for the differential diagnosis of gluten-related disorders, including celiac disease, gluten sensitivity and wheat allergy. BMC Medicine 2012.

What is the cross-reactivity risk between wheat and other grains?

Twenty percent (20%).

Diagnosis of wheat allergy

Wheat allergy is rare in adults bit it can occur. In adults, specific IgE was more sensitive than skin test for wheat; however, specificity and predictive values were low for both tests. Thus, these tests should not be used to validate diagnosis of wheat allergy. An oral challenge should be performed to confirm or exclude the diagnosis of wheat allergy.

As with skin prick testing for inhalant allergens, wheal size has diagnostic value for many food allergens. In a study that evaluated subjects with a history of peanut allergy by skin-prick tests, antigen-specific IgE assays, and challenges, the positive predictive value for a clinical allergy was 94.4% for a wheal diameter of at least 8 mm, with a specificity of 98.5%.

Prevalence of wheat allergy in Japan is 0.2% - the assessment was based on questionnaire-based exam, skin prick test, and omega-5 gliadin sIgE (http://goo.gl/Mp4nW).

However, this does not apply to all allergens. For example, skin test results as well as antigen-specific IgE values should not be used to validate a diagnosis of wheat allergy because their specificity and predictive values are much lower.

Skin tests with commercial food allergen extracts are much less reliable than skin tests with inhalant allergens, and only a fraction of patients with positive food skin tests will react during a food challenge. Many patients having IgE antibodies to foods either do not react or have lost their clinical sensitivities.

With food extracts, prick-puncture tests ("prick-prick") seem to be more reliable. "Prick-to-prick" skin test testing with the fresh food in question can enhance the sensitivity of the skin test (AAAAI Ask the Expert, 2012).

Prognosis

In children, 85% of cow’s milk, egg, wheat, and soy allergy resolves by five years. In contrast, only 20% of children “outgrow” their peanut allergy, and only 9% of tree nut-allergic patients do so.

Food challenge

There is a strong correlation between the level of specific IgE and the need for medical intervention - the high-risk cut-offs are 17.5 kU/L for milk, wheat, and soy, and 3.5 kU/L for egg. Researchers recommended establishing intravenous access in children with specific IgE levels of 17.5 kU/L to milk or wheat or 3.5 kU/L to egg.

There are predetermined levels of specific IgE on ImmunoCAP below which a food challenge can be attempted. Those levels are shown in the grid below:


Levels of specific IgE below which a food challenge can be attempted. Image source: Dr. Hopp, Creighton University Division of Allergy & Immunology, used with permission.

These are proposed starting doses for oral challenges: peanut 0.1 mg, milk 0.1 mL, egg 1 mg, wheat 100 mg, soy 1 mg, cod 5 mg, shrimp 5 mg, and hazelnut 0.1 mg


8 top allergens account for 90 percent of food allergies. Specific IgE levels (sIgE) that predict the likelihood of passing an oral food challenge are shown in the figure. (click to enlarge the image).

References

Adkinson: Middleton's Allergy: Principles and Practice, 7th ed.
Allergens to wheat and related cereals. Tatham AS, Shewry PR. Clin Exp Allergy. 2008 Nov;38(11):1712-26. Epub 2008 Sep 24.
New classification proposed for gluten-related disorders: celiac disease; dermatitis herpetiformis; gluten ataxia; wheat allergy; gluten sensitivity. WSJ, 2012.
Food Allergies: Detection and Management. Am Fam Physician. 2008 Jun 15;77(12):1678-1686.
Wheat allergy. Inomata N. Curr Opin Allergy Clin Immunol. 2009 Jun;9(3):238-43.
Wheat allergy: a double-blind, placebo-controlled study in adults. Scibilia J, Pastorello EA, Zisa G, Ottolenghi A, Bindslev-Jensen C, Pravettoni V, Scovena E, Robino A, Ortolani C. J Allergy Clin Immunol. 2006 Feb;117(2):433-9.
Wheat Allergy. FoodAllergy.org.
Nonceliac gluten-sensitive enteropathy (NCGSE) common in allergic patients - biopsy part of the routine investigation? http://goo.gl/gwdT3
Cross Reactions Among Foods (PDF).
Celiac Disease - JAMA Patient Page (PDF)

Wheat allergy can manifest in different disease entities, rendering a detailed case history and challenge mandatory http://buff.ly/1Ji470Z

ClevelandClinic, October 11, 2010: Celiac disease is when the body doesn't tolerate gluten very well - the protein found in wheat, barley and rye. When people with celiac disease eat gluten it damages the small instestines. Symptoms are gas, bloating, indigestion, fatigue, and headaches. This disease is diagnosed by a blood test. Published: 07/28/2010 Updated: 03/16/2012

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