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Am Fam Physician. 2019;99(3):156

Author disclosure: No relevant financial affiliations.

Clinical Question

Is oral immunotherapy an effective method for desensitizing children with egg allergy?

Evidence-Based Answer

Providing daily, steadily increasing doses of egg protein over an extended period of time effectively diminishes the immunoglobulin E (IgE)-mediated allergic response among children with egg allergy. Continued egg consumption maintains this desensitizing effect, with a return of the allergic response in the case of egg avoidance. However, this benefit is not achieved without risk; 75% of children in intervention groups experienced at least one adverse effect, with 8.4% of children experiencing a serious adverse effect requiring medication.1 (Strength of Recommendation: B, based on small, low-quality randomized controlled trials.)

Practice Pointers

After cow's milk, eggs are the second most common food allergy among infants and small children, with an estimated prevalence of 0.5% to 2.5%.2 Although some children will remain allergic throughout adulthood, approximately 70% of young children with egg allergy are able to tolerate baked egg with minimal to no symptoms, and most will outgrow the allergy entirely by adulthood.1 The diagnosis of egg allergy is supported by any combination of allergic reactions occurring within minutes to hours of ingesting eggs, especially if occurring on more than one occasion. Such reactions may include urticaria, periorbital edema, nasal congestion, dyspnea, wheezing, bronchospasm, nausea, emesis, diarrhea, and angioedema of the perioral region.3 The Expert Panel of the National Institute of Allergy and Infectious Diseases has concluded that insufficient evidence exists to recommend routine food allergy testing before the introduction of highly allergenic foods.3 Although skin prick and serum IgE tests have relatively low positive predictive value, they are adequate in the setting of symptoms representative of an allergic reaction. Still, oral food challenge remains the preferred method of diagnosing an egg allergy.

This Cochrane review is a meta-analysis of 10 randomized controlled trials with 439 participants one to 18 years of age.1 Immunotherapy protocols varied in each study, but none used sublingual immunotherapy. Seven studies used egg avoidance diets as the control intervention and three used placebo. Outcomes included tolerance to an increased amount of ingested egg while receiving allergen-specific oral immunotherapy and a complete recovery from egg allergy after completion of an immunotherapy regimen. In addition, quality of life and cost-effectiveness were considered. Generally, the protocols aimed to induce a state of tolerance to the allergen through regular administration of small amounts of egg protein over time. Doses began between 1 mg and 75 mg of egg white powder and were slowly increased to 10 g of egg white powder, the equivalent of one whole egg.1

Within the immunotherapy group, 82% of children receiving oral immunotherapy increased the amount of egg they could tolerate vs. 10% of the control group (relative risk [RR] = 7.48; 95% confidence interval [CI], 4.91 to 11.38). Although higher amounts of egg allergen were tolerated across the immunotherapy participants, the studies were small and the quality of evidence was low. In longer-term follow-up, 50% of children in the immunotherapy group achieved sustained unresponsiveness by the fourth year.4 Importantly, 75% of children receiving immunotherapy experienced mild-to-severe adverse effects (including 21 children who required treatment for serious reactions) compared with 6.8% of those in the control group (RR = 8.35; 95% CI, 5.31 to 13.12). Overall, there was inconsistent rigor among the methodologies, and the number of enrolled children was low. Additionally, a high risk of bias was identified in eight of the 10 trials.

Immunotherapy with egg proteins effectively builds tolerance over time and in at least one-half of those who participate, it may lead to complete resolution of egg allergy. However, most patients will also experience allergy-related adverse effects, with a small percentage of those reactions becoming life-threatening. Importantly, guidelines from the National Institute of Allergy and Infectious Diseases do not recommend specific immunotherapy to treat IgE-mediated food allergy, maintaining that allergen avoidance is currently the safest strategy for managing egg allergy.

The practice recommendations in this activity are available at

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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