Version May 2024
INTRODUCTION — The majority of the intramuscular inactivated influenza vaccines (IIVs) and the intranasal live-attenuated influenza vaccine (LAIV) are cultured on fluid from chicken embryos. As a result, there is a small amount of egg protein in these vaccines. Thus, there is a theoretical risk of inducing an allergic reaction when administering the influenza vaccine to a person with hen's egg (HE) allergy. However, many of these same patients are also at higher risk of an adverse outcome due to influenza infection (eg, age less than two years, history of asthma) and would therefore benefit from vaccination.
This topic reviews the risks and benefits of administration of the influenza vaccine in patients with HE allergy. Other issues related to HE allergy (including prevalence) and allergic reactions to vaccines are discussed separately. (See "Egg allergy: Clinical features and diagnosis" and "Allergic reactions to vaccines".)
The measles, mumps, and rubella (MMR) vaccine is not contraindicated in patients with HE allergy. This is discussed in detail separately. (See "Allergic reactions to vaccines", section on 'Measles, mumps, and rubella' and "Egg allergy: Management", section on 'Avoidance'.)
RISKS ASSOCIATED WITH INFLUENZA INFECTION — Both seasonal and pandemic influenza infection can lead to severe infection and death, particularly in certain high-risk groups. Seasonal influenza results in higher mortality rates among patients with certain chronic medical conditions (eg, asthma), pregnant females, and those at the extremes of age. (See "Seasonal influenza in adults: Clinical manifestations and diagnosis", section on 'Complications' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Complications' and "Seasonal influenza and pregnancy", section on 'Effects on pregnancy'.)
Influenza vaccination is recommended for all individuals six months of age and older and is particularly important in those at increased risk of complications. (See "Seasonal influenza vaccination in adults" and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups'.)
RISK OF ANAPHYLAXIS TO VACCINES — Allergic reactions to a vaccine may be caused by the immunizing agent itself or to other proteins/haptens that are introduced into the vaccine during the production process. These may include residual animal proteins, antibiotics, preservatives, stabilizers, virus-inactivating compounds, and latex [1]. Thus, episodes of anaphylaxis caused by the influenza vaccine may be due to components other than egg.
As an example, there were 12 adverse events consistent with possible anaphylaxis after administration of an egg-free influenza vaccine (Flublok) that were reported between January 16, 2013 and July 31, 2014 through the Vaccine Adverse Event Reporting System (VAERS) in the United States [2]. These reactions occurred in adults with self-reported hen's egg (HE) allergy or a previous allergic reaction to inactivated influenza vaccine (IIV). Had these patients received an egg-containing vaccine, their reactions may have been erroneously attributed to egg.
In another example, a particular brand of influenza vaccine used in Japan during the 2011 to 2012 season was associated with a high rate of anaphylaxis. These patients had elevated levels of immunoglobulin E (IgE) against the immunizing agent (hemagglutinin) compared with controls with and without HE allergy [3]. (See "Allergic reactions to vaccines".)
Overall, anaphylaxis induced by influenza vaccine is a rare event [4-7]. As examples:
●A survey of children and adolescents enrolled at four health maintenance organizations from 1991 to 1997 revealed no episodes of anaphylaxis to influenza vaccine out of 197,964 doses administered during this time period [4].
●A survey of children and adults enrolled at nine health maintenance organizations from 2009 to 2011 revealed 10 episodes of anaphylaxis to influenza vaccine out of 7,434,628 doses given alone during this time period for a rate of 1.35 per million doses [7].
●The rate of confirmed anaphylaxis to two versions of H1N1 pandemic vaccines was approximately 2 per million doses administered (97 cases) [5]. Insufficient information was available to confirm anaphylaxis in an additional 117 cases. Anaphylaxis was excluded in 181 cases of reported anaphylaxis to the vaccines. The rate of anaphylaxis was within the range expected for vaccines in general (1 to 10 per million doses of vaccine).
●Several cases of anaphylaxis to the intranasal influenza vaccine have been reported, although these cases were not directly linked to HE allergy [6]. No studies have directly compared the rate of anaphylactic reactions between the intranasal live-attenuated vaccine and the injectable inactivated vaccine. It is not possible to compare the two forms of the influenza vaccine with regard to the risk of anaphylaxis, because it is such a rare event.
Fatal anaphylaxis — A review of reports to the VAERS over a 15-year period from 1990 to 2005, during which 747 million doses of influenza vaccine were administered in the United States, revealed four reports of death shortly after influenza vaccination that identified anaphylaxis as the cause [8]. No information on HE allergy was provided nor was any evaluation performed to determine whether these were allergic reactions.
VACCINE EGG PROTEIN CONTENT — In the past, influenza vaccine manufacturers did not state the egg protein content of the vaccines. Now, most manufacturers of these vaccines provide this information in the package inserts.
The vaccine ovalbumin content is typically expressed in micrograms per 0.5 mL dose. All of the vaccines are reported to contain ≤1 mcg per 0.5 mL dose.
Independent investigators assayed several brands and lots of the 2009 to 2010 seasonal and H1N1 influenza vaccines and found that the actual ovalbumin content of the vaccines was one or two orders of magnitude lower than the manufacturers' claimed maximum levels [9,10]. All lots tested of the seasonal influenza vaccines approved for use in the United States for 2010 to 2011 contained less than 0.17 mcg of ovalbumin per 0.5 mL dose [11], although it is possible that untested lots had higher levels.
SAFETY OF VACCINES IN PATIENTS WITH EGG ALLERGY — Safe administration of injectable influenza vaccine (containing up to 0.7 mcg ovalbumin per 0.5 mL dose) to over 4000 individuals with hen's egg (HE) allergy has been reported [12-21]. These studies included more than 500 patients with a history of anaphylaxis to egg ingestion who were vaccinated with trivalent inactivated influenza vaccine (IIV), all without serious reactions.
Safe administration of the intranasal live-attenuated influenza vaccine (LAIV) containing <0.24 mcg ovalbumin per 0.2 mL dose has been demonstrated in over 1000 patients with HE allergy [22-24]. Of these patients, 39 percent had a history of anaphylaxis to egg, and 63 percent had a diagnosis of asthma or recurrent wheezing. No acute systemic allergic reactions were reported.
ALTERNATIVE METHODS OF VACCINE PRODUCTION — Most influenza vaccines are produced in fluid from embryonated eggs. Alternative methods of influenza virus propagation have been developed, including a cell culture-based vaccine (Flucelvax) and a recombinant vaccine (Flublok), although there is no preference for the use of these vaccines in hen's egg (HE) allergic recipients, because egg-based vaccines are not associated with any increased risk, and allergic reactions to egg-free vaccines are still possible [25-32]. (See 'Risk of anaphylaxis to vaccines' above.)
APPROACH TO EVALUATION AND VACCINE ADMINISTRATION
Risk assessment — Skin testing (prick or intradermal) with influenza vaccine prior to administration is no longer recommended for patients with hen's egg (HE) allergy [1,33,34]. In studies of patients with HE allergy, the presence of a positive skin test to influenza vaccine was not predictive of a subsequent reaction. Skin testing with the vaccine is still appropriate when evaluating a patient with a history of a reaction to the influenza vaccine itself as opposed to a history of reaction to egg. (See "Allergic reactions to vaccines".)
Vaccine choice — The choice of vaccine depends upon the age of the patient, as well as comorbidities and risk factors for severe or complicated influenza or adverse reactions, but is unrelated to HE allergy status. (See 'Risks associated with influenza infection' above and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Seasonal influenza in children: Prevention with vaccines", section on 'Choice of vaccine'.)
Professional society recommendations — All US professional society and government guidelines specifically recommend that patients with HE allergy receive any age-appropriate influenza vaccine, including egg-based vaccines [33-35].
US allergy guidelines from the American Academy of Allergy, Asthma, and Immunology (AAAAI)/American College of Allergy, Asthma, and Immunology (ACAAI) Joint Task Force on Practice Parameters [35] state the following regarding influenza vaccines (both inactivated influenza vaccine [IIV] and LAIV):
●"Influenza vaccines should be administered to individuals with egg allergy of any severity, just as they would be to individuals without egg allergy."
●"No special precautions beyond those recommended for the administration of any vaccine to any patient are necessary for administration of influenza vaccine to egg-allergic individuals."
●"Vaccine providers and screening questionnaires do not need to ask about the egg allergy status of recipients of influenza vaccine."
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases, in its Recommendations for Prevention and Control of Influenza in Children, 2020 to 2021 [33], states the following regarding HE allergy and influenza vaccine:
●"There is strong evidence that egg-allergic individuals can safely receive influenza vaccine without any additional precautions beyond those recommended for any vaccine."
●"The presence of egg allergy in an individual is not a contraindication to receive an IIV or LAIV."
●"[Influenza] vaccine recipients with egg allergy are at no greater risk for a systemic allergic reaction than those without egg allergy."
●"Precautions, such as choice of a particular vaccine, special observation periods, or restriction of administration to particular medical settings, are not warranted and constitute an unnecessary barrier to immunization."
●"It is not necessary to inquire about egg allergy before the administration of any influenza vaccine, including on screening forms."
●"Standard vaccination practice for all vaccines in children should include the ability to respond to rare acute hypersensitivity reactions."
●"Children who have had a previous allergic reaction to the influenza vaccine should be evaluated by an allergist to determine whether future receipt of the vaccine is appropriate."
The Advisory Committee on Immunization Practices (ACIP) has revised its guidance for the 2023 to 2024 influenza season. The ACIP now also states that egg allergy does not necessitate additional safety measures for influenza vaccination, including with egg-based vaccines, beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg [34]. All vaccines should be administered in settings where personnel and equipment needed for prompt recognition and treatment of acute hypersensitivity reactions are available.
We recommend choosing any age-appropriate, approved injectable influenza vaccine (table 1 and table 2 and table 3) for patients with HE allergy, including those with a history of anaphylaxis to egg.
Our approach — Our approach to the administration of influenza vaccine to recipients with HE allergy is based upon observational studies and extensive clinical experience (see 'Safety of vaccines in patients with egg allergy' above). It is consistent with guidelines from the AAP [33], ACIP [34], and the AAAAI/ACAAI Joint Task Force on Practice Parameters [35].
We recommend that all patients ≥6 months of age with HE allergy, including those with a history of anaphylaxis to egg ingestion, receive annual immunization with an influenza vaccine according to the indications for all other patients without HE allergy. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Seasonal influenza vaccination in adults", section on 'Whom to vaccinate'.)
●We would administer any age-appropriate, approved influenza vaccine (table 1) in these patients in the usual manner according to the indications and contraindications outlined in the tables (table 2 and table 3).
●Any provider who administers any vaccine to any individual must have the personnel, medications, and resuscitative equipment available to treat potential anaphylaxis [36].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Seasonal influenza vaccination".)
SUMMARY AND RECOMMENDATIONS
●Egg protein in influenza vaccines – Most intramuscular inactivated influenza vaccines (IIVs) and live-attenuated influenza vaccines (LAIVs) contain a small amount of egg protein. The amount of egg protein in the vaccines has decreased significantly over the years, and all egg-based vaccines now have low ovalbumin levels. No serious reactions have been reported after administration of egg-based LAIV or IIV (containing <0.24 mcg per 0.2 mL dose for LAIV and up to 0.7 mcg ovalbumin per 0.5 mL dose for IIV) in recipients with hen's egg (HE) allergy, including in those with a history of anaphylaxis to egg ingestion. (See 'Vaccine egg protein content' above and 'Risk of anaphylaxis to vaccines' above and 'Safety of vaccines in patients with egg allergy' above.)
●Assessment prior to vaccination – Vaccine providers and screening questionnaires do not need to ask about the HE allergy status of recipients of influenza vaccine. Skin testing with influenza vaccine prior to administration in patients with HE allergy is no longer suggested. Skin testing with the vaccine is still appropriate when evaluating a patient with a history of a reaction to the influenza vaccine itself, as opposed to a history of reaction to egg. Patients with a history of an allergic reaction to the influenza vaccine should be referred to an allergy specialist for evaluation. (See 'Risk assessment' above and "Allergic reactions to vaccines".)
●Who to vaccinate – Many patients with HE allergy are at increased risk of influenza complications, including young children and those with a history of asthma or wheezing, and therefore would benefit from vaccination. We recommend that all patients ≥6 months of age with HE allergy, including those with a history of anaphylaxis to egg ingestion, receive annual immunization with an influenza vaccine according to the indications for all other patients without egg allergy (Grade 1A). (See 'Approach to evaluation and vaccine administration' above and "Seasonal influenza in children: Prevention with vaccines", section on 'Target groups' and "Seasonal influenza vaccination in adults", section on 'Whom to vaccinate'.)
●Which influenza vaccine – We would administer any age-appropriate, approved injectable influenza vaccine (table 1) in these patients according to the indications and contraindications outlined in the tables (table 2 and table 3). (See 'Our approach' above.)
●How to vaccinate – The vaccine is administered in the usual manner (ie, in a single dose rather than in two or more doses as a graded challenge and without a special observation period following the vaccine). (See 'Our approach' above.)
●Safety precautions – Any provider who administers any vaccine to any person should have the personnel, medications, and resuscitative equipment available to treat potential anaphylaxis.
●Allergic reactions to vaccines – Allergic reactions to the influenza vaccine, including anaphylaxis, may still occur, as with any vaccine. These reactions can be caused by the immunizing agent itself or to other proteins/haptens besides egg that are introduced into the vaccine during the production process. Patients with a history of an allergic reaction to the influenza vaccine should be referred to an allergy specialist for evaluation. (See 'Risk of anaphylaxis to vaccines' above and "Allergic reactions to vaccines".)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
