Vaccine Update
Influenza vaccine safety in patients with egg allergy 
J Am Pharm Assoc. 2013;53:214-216. doi:10.1331/JAPhA.2013.13511
Egg allergy is one of the most common food allergies in pediatric patients, with a parent-reported prevalence ranging from 1.6% to 2.6% of children in the general population. 1 An egg allergy early in life has been correlated with respiratory allergic symptoms (asthma and/or rhinitis). 2 In addition, adult patients with asthma are at a high risk for complications from influenza. 3 Until recently, all influenza vaccines had been prepared by inoculation of virus into chicken eggs. 4 In 2012, the Food and Drug Administration announced the approval of Flucelvax (Novartis), the first influenza vaccine produced using cultured animal cells instead of fertilized chicken eggs. 5 Therefore, understanding the current recommendations and concerns for influenza vaccination in patients with egg allergy is important.
Egg intolerance occurs when the body is not able to properly digest or reacts adversely to certain components of the egg. This happens if a person lacks specific enzymes or if he/she has a gastrointestinal reaction to a component of the egg product. People with egg intolerance usually can eat small amounts of egg without having a serious reaction. Individuals with food intolerance to egg typically can get the influenza vaccine without any risks or harm. 6
A true egg allergy is a systemic immune response and occurs when the body produces immunoglobulin E (IgE) antibodies to a protein in the egg. The individual must have been exposed to the substance causing the allergic reaction previously. The exposure could have been through diet or previous vaccination. IgE recognizes and binds an egg protein. With the allergen bound, the IgE crosslinks on the mast cell, releasing potent chemicals such as histamine and cytokines. 6 These chemicals mediate an allergic reaction in the body that can present as a variety of symptoms (e.g., urticaria, angioedema, pruritus, vomiting, diarrhea, dyspnea, wheezing, swelling of the mouth and throat). Although some symptoms of egg intolerance and allergy overlap, an egg allergy is much more serious. 6
The allergic response to exposure to the allergy-causing food usually occurs within minutes. Individuals react at varying levels of severity during a food allergy reaction. Classification of the allergic reaction is important when considering vaccination. Mild symptoms of egg allergy are defined as hives only. Severe symptoms (e.g., anaphylaxis) generally require epinephrine or emergency treatment and involve cardiovascular changes (e.g., hypotension), respiratory symptoms (e.g., wheezing, dyspnea), and gastrointestinal symptoms (e.g., nausea, vomiting). Individuals requiring epinephrine must be sent for further medical evaluation.
The Advisory Committee on Immunization Practices recommends administering the influenza vaccine with caution to patients with mild egg allergy; it is no longer contraindicated. Patients with a mild allergic reaction to egg can receive the injectable influenza vaccine with careful observation for 30 minutes after vaccination. Patients with a history of a severe allergic reaction to egg should be referred to a physician with expertise in managing allergic conditions. 4 The safety of live attenuated influenza vaccine (LAIV; FluMist—MedImmune) in patients with egg allergy has not been established; therefore, LAIV should not be used in this population at this time ( Figure 1). 7 In addition, procedures such as skin prick testing and dividing the injectable vaccine into a two-step dose have been found to be unnecessary. 4
Figure 1. Pharmacists' algorithm for patients with suspected egg allergy
aBased on state laws, employer policy, and/or protocol.
bPrecautions when administering influenza vaccine to a patient with presumed egg allergy include observation for 30 minutes and appropriate resuscitative equipment available.
Modified from: Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011.www.cdc.gov/mmwr/preview/mmwrhtml/mm6033a3.htm. Accessed January 24, 2013.
Ovalbumin is used as a marker for the egg protein content in influenza vaccines. A number of studies have reported the content of ovalbumin safely administered to egg-allergic patients to be as high as 1.4 µg/mL (0.7 µg/0.5 mL dose). Ovalbumin content in vaccines can vary among seasons, manufacturers, and lots. 4However, the maximum threshold of safe ovalbumin concentration is unknown. 8, 9
Unfortunately, a single source of information regarding ovalbumin content does not exist. Currently, three sources of information on ovalbumin content are available. The most readily available sources are the various package inserts. However, some manufacturers do not include ovalbumin content on the package insert. Second, pharmacists can contact the vaccine manufacturer and request ovalbumin content of the product. Third, the Centers for Disease Control and Prevention publishes vaccination recommendations each summer/fall with updated information for individuals with egg allergy. 4
Patients with mild egg allergy may be vaccinated by a pharmacist familiar with the potential manifestations of egg allergy and trained to manage an anaphylactic reaction. 4 Before administering the vaccine, a thorough medical history should be taken, with special attention focused on previous vaccines and the patient's response. Patients should be observed on site for at least 30 minutes following administration of the vaccine dose for signs and symptoms of allergic reaction. The pharmacist should be able to recognize a severe allergic reaction at its early stages and must have emergency resuscitative equipment available for immediate treatment in case of anaphylaxis. This should include injectable epinephrine and an oral antihistamine, such as diphenhydramine or hydroxyzine. 10 Because of the severe nature of the reaction, some community pharmacies may not be appropriate sites for this approach. Pharmacists should offer advice and refer patients with an egg allergy who may benefit from influenza immunization.
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Food and Drug Administration. FDA approves first seasonal influenza vaccine manufactured using cell culture technology.www.fda.gov/newsevents/newsroom/pressannouncements/ucm328982.htm. Accessed January 24, 2013.
NIAID-Sponsored Expert Panel. 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.
Vasu N, Ghaffari G, Craig ET, Craig TJ. Adverse events associated with intranasal influenza vaccine in the United States. Ther Adv Respir Dis. 2008; 2( 4): 193– 8. [CrossRef]
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Upton JE, Hummel DB, Kasprzak A, Atkinson AR. No systemic reactions to influenza vaccination in egg-sensitized tertiary-care pediatric patients. Allergy Asthma Clin Immunol. 2012; 8:2.
Greenhawt MJ, Li JT, Bernstein DI, et al. Administering influenza vaccine to egg allergic recipients: a focused practice parameter update. Ann Allergy Asthma Immunol. 2011; 106( 1): 11– 6.[CrossRef]
Send your immunization questions to the JAPhA Contributing Editors who coordinate the Vaccine Update column:
- Mary S. Hayney, PharmD, BCPS, Associate Professor of Pharmacy, School of Pharmacy, University of Wisconsin, Madison ( mshayney@pharmacy.wisc.edu)
- John D. Grabenstein, PhD, Director of Scientific Affairs, Merck Vaccine Division (john_grabenstein@merck.com)
This article is supported by a Cooperative Agreement provided by the Centers for Disease Control and Prevention (CDC) entitled “Pharmacists: Connecting, Communicating and Collaborating for Improved Community Health” (1U66 IP000114). The opinions expressed in this article do not represent the viewpoints of the CDC.
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