Bravin K, Luyt D. Home-based oral immunotherapy with a baked egg protocol. J Investig Allergol Clin Immunol. 2016;26(1):61-63.
To develop a home-based oral immunotherapy with baked egg and to find out if it is a safe, practical, and effective treatment for children with egg allergies
Case series design
Immunotherapy protocol was designed in 5 stages, starting with 125 µg of egg protein, increasing it daily over a period of 60 days to a target maximum dose of 6.25 g of egg protein. The first dose was administered in a hospital and the rest was continued at home.
Baked egg biscuit recipe consisted of 4 ingredients: flour (40 g at stages 1-4 and 80 g at stage 5); sugar (40 g); margarine (25 g at stages 1-3, 15 g at stage 4, and none at stage 5); and egg (0.1 mL at stage 1, 0.5 mL at stage 2, 1.0 mL at stage 3, 10 mL at stage 4, and 50 mL at stage 5). The amount of biscuit eaten was gradually increased on a daily basis.
Fifteen children with IgE-mediated egg allergy; 9 boys and 6 girls ranging from age 6 to 17, with median age of 11 years and 2 months. Inclusion criteria were age >5 years, persistent IgE-mediated egg allergy with a positive skin prick test (wheal> 3 mm) to egg white and egg yolk, and symptoms of allergic reaction to baked egg in the previous 6 months or a positive open food challenge result.
Primary Outcome Measures
Ability to tolerate whole boiled egg without adverse reactions
Eight children completed the whole program successfully, 4 children within the target of 60 days and 4 children between 80 and 270 days. Seven children did not complete the study; 2 could not tolerate the first dose without symptoms and 5 achieved partial tolerance at days 10 to 47, allowing them to include trace amounts of egg in their diet. Adverse reactions were minor and could be controlled by antihistamine medications.
Study design and small number of participants
Food allergies are very common, and the prevalence is growing globally. Up to 15 million Americans have food allergies, including 1 in every 13 children under age 18.1 According to a 2013 study by the Centers for Disease Control and Prevention, incidence of food allergies among American children has increased.2 Other countries also are experiencing more cases of food allergies.3
Kids at risk for food allergies are more likely to have parents with allergic disorders, and the children themselves are more likely to have related conditions, such as asthma and other allergic reactions. Food allergies can actually trigger many allergic disorders, such as food-induced anaphylaxis, gastrointestinal (GI) food allergies (eg, eosinophilic GI disorders), skin reactions (eg, urticaria, eczema), respiratory manifestations, and Heiner’s syndrome, a rare milk-induced pulmonary disease.4
Oral immunotherapy is a great way to introduce allergens in the form of food, as they are encountered in real life.
Each year, food allergies in children are responsible for over 300,000 doctor visits5 and 200,000 emergency department visits.6 They are the leading cause of anaphylaxis occurring outside of a hospital setting. Current treatment guidelines recommend identification and strict avoidance of allergenic foods.4 However, diet and unintentional exposures to allergens have significant impact on the quality of life.7 Better treatment options are needed, and the latest efforts have been concentrated on oral immunotherapy (or OIT, which was used in this study) and sublingual immunotherapy (or SLIT, which employs liquid sublingual preparations of allergenic extracts).
The most common culprits that account for 90% of immunoglobulin (Ig) E-related food allergies are known as the big 8: milk, eggs, peanuts, tree nuts, wheat, soy, fish, and shellfish. About 18% of children don’t outgrow egg allergies.4 Reaction to eggs is commonly triggered by the proteins in egg whites, although egg yolk proteins can cause allergies as well.
Oral immunotherapy is a great way to introduce allergens in the form of food, as they are encountered in real life. Cooking processes (heating, acid, mixing) can change allergenicity of the food proteins.8 Heating egg protein with wheat can form a matrix with the wheat protein, which changes digestibility of the egg protein,9 making egg biscuits a good choice for the study.
Are we ready to apply oral immunotherapy to our clinical practice? While it is a very promising approach to treat egg allergies,10 as well as other food reactions,11,12 there are a number of issues that make it difficult. Safety is a big factor since the severity of a reaction cannot be predicted by past responses, IgE level, or the size of the prick test wheal. The most common known factor associated with severe reaction is a concurrent diagnosis of asthma.4 Additionally, the search for optimal doses and duration of treatment is ongoing, and the ease of use outside of the research environment is questionable. Nevertheless, it is very encouraging to see the desensitization of allergic reactions in subjects participating in studies. Oral immunotherapy seems to work faster but has higher rates of systemic reactions. Sublingual immunotherapy reactions are more frequent but are typically milder and confined to the oropharynx, therefore showing a better safety profile at this time.13
Meanwhile, as providers we need to counsel our patients regarding hidden sources of food allergens to prevent unintended exposures and remind them to check expiration dates on their EpiPen prescriptions. We also want to consider additional factors related to the development of allergies. Interestingly, introduction of cooked egg earlier on, at 4 to 6 months of age, might protect against egg allergy.14 Vitamin D deficiency is associated with increased risk of sensitization to food allergens.15,16 Encouraging our patients to eat unprocessed foods can help decrease inflammation, because there is some association between food allergies and increased intestinal permeability.17 Glutamine and curcumin,17 as well as flavonoids,18 are helpful in maintenance of good GI function. The gut microbiome, which plays an important role in the development of allergies,19 is another potential area of research.
- Food Allergy Research and Education. Food Allergy Facts and Statistics for the U.S. http://www.foodallergy.org/file/facts-stats.pdf. Accessed August 15, 2016.
- Jackson KD, Howie LD, Akinbami LJ. Trends in Allergic Conditions among Children: United States, 1997-2011. Hyattsville, MD: National Center for Health Statistics; 2013.
- Prescott SL, Pawankar R, Allen KJ, et al. A global survey of changing patterns of food allergy burden in children. World Allergy Organ J. 2013;6(1):21.
- Boyce, JA, Assa’ad A, Burks AW, et al. Guidelines for the diagnosis and management of food allergy in the United States. Report of the NIAID-Sponsored Expert Panel. J Allergy Clin Immunol. 2010;126(6 Suppl):S1-58.
- Branum AM, Lukacs SL. Food allergy among U.S. children: Trends in prevalence and hospitalizations. Hyattsville, MD: National Center for Health Statistics; 2008.
- Clark S, Espinola J, Rudders SA, Banerji A, Camargo CA. Frequency of US emergency department visits for food-related acute allergic reactions. J Allergy Clin Immunol. 2011;127(3):682-683.
- Sicherer SH, Noone SA, Munoz-Furlong A. The impact of childhood food allergy on quality of life. Ann Allergy Asthma Immunol. 2001;87(6):461-464.
- Verhoeckx KCM, Vissers YM, Baumert JL, et al. Food processing and allergenicity. Food and Chemical Toxicol. 2015;80:223-240.
- Netting M, Makrides M, Gold, M, Quinn P, Irmeli P. Heated allergens and induction of tolerance in food allergic children. Nutrients. 2013;5(6):2028-2046.
- Burks AW, Jones SM, Wood RA, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367(3):233-243.
- Sheikh A, Nurmatov U, Venderbosch I, Bischoff E. Oral immunotherapy for the treatment of peanut allergy: systematic review of six case series studies. Prim Care Respir J. 2012;21(1):41-49.
- Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol. 2012;129(2):448-455.
- Narisety SD, Keet CA. Sublingual vs oral immunotherapy for food allergy: identifying the right approach. Drugs. 2012;72(15):1977-1989.
- Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol. 2010;126(4):807-813.
- Beek JH, Shin YH, Chung IH, et al. The link between serum vitamin D level, sensitization to food allergens, and the severity of atopic dermatitis in infancy. J Pediatr. 2014;165(4):849-854.e1.
- Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML. Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2011;127(5):1195-1202.
- Rapin JR, Wiernsperger N. Possible links between intestinal permeability and food processing: a potential therapeutic niche for glutamine. Clinics (Sao Paulo). 2010;65(6):635-643.
- Suzuki T, Hara H. Role of flavonoids in intestinal tight junction regulation. J Nutr Biochem. 2011;22:401-408.
- Riiser A. The human microbiome, asthma, and allergy. Allergy Asthma Clin Immunol. 2015;11:35.