Egg Allergy and the Influenza Vaccine -- A New Perspective

An expert interview with Matthew J. Greenhawt, MD, MBA

Laurie Scudder, DNP, NP


February 18, 2011

In This Article

Editor's Note

The American Academy of Asthma, Allergy, & Immunology (AAAAI) issued a paper titled Administering Influenza Vaccine to Egg Allergic Recipients in October 2010.[1] The report offered guidance in the administration of influenza vaccine to egg-allergic (EA) individuals, concluding that most of these patients can safely be vaccinated. A follow-up practice parameter published in January 2011 provided more information about the quality of the evidence underpinning recommendations for vaccine administration.[2] Matthew J. Greenhawt, MD, MBA, Assistant Professor, University of Michigan Medical School, Division of Allergy and Clinical Immunology, and co-author of both reports discussed issues around implementation of these recommendations for both the primary care and allergy/immunology settings with Medscape editor Laurie Scudder DNP, NP.

The Evidence for Administration of Vaccine

Medscape: The report describes 3 recent studies that have examined the use of trivalent inactivated influenza vaccine (TIV) in egg-allergic individuals. Can you describe these studies?

Matthew J. Greenhawt, MD, MBA: During the 2009-2010 influenza season and H1N1 pandemic, 3 studies emerged examining this issue. The first was a retrospective study conducted by researchers at Boston Children's Hospital that examined their institution's experience in vaccinating their population of children with non-anaphylactic egg allergy.[3]

A total of 171 patients met eligibility criteria and were vaccinated with trivalent influenza vaccine using a 2-step protocol without skin testing prior to vaccination. The 2-step protocol involved administering approximately 10% of the volume of the vaccine, then monitoring the child for 30 minutes to make sure that no symptoms developed, and then administering the residual 90% of the vaccine. This is a common dosing protocol many allergists use to safely provide the vaccine to egg-allergic children. In this study, there were 29 localized reactions, mostly redness or induration at the injection site. There were 7 reactions considered to be systemic, 6 of which occurred within the initial 30-minute observation period after the 10% dose and one that occurred outside of that 30-minute observation period for the 90% dose.

The researchers' overall conclusion was that for egg-allergic children without a history of anaphylaxis, use of a 2-step graded dose approach is a valid and safe method of providing vaccination, and this can be done without any pretesting to the influenza vaccine. This study did not report the ovalbumin content of the vaccines used. Ovalbumin is the egg protein that is a contaminant in influenza vaccine. Additionally, it was a retrospective study and had fairly restrictive selection criteria, both factors that introduce some bias. The design excluded kids who had a prior positive influenza vaccine skin test and/or a history of severe symptoms attributable to eggs. So, although the patient population in this study was not entirely representative of the general egg-allergic population, this study importantly introduced the concept that vaccination can be safely performed without skin testing using a 2-step protocol.

The second study was a prospective multicenter trial conducted in Canada during the 2009-2010 pandemic.[4] This study used H1N1 influenza A vaccine that had been specifically formulated to contain approximately 0.3 μg/mL ovalbumin. This was a special vaccine not available in the United States. Patients were not skin tested to the vaccine prior to administration. Two dosing strategies were used: 72 patients with a history of severe cardiovascular/respiratory symptoms attributable to egg or with uncontrolled asthma were vaccinated with a 2-step graded challenge; the remaining 758 egg-allergic individuals without such a history were vaccinated with a single dose. A very low rate of reactions was found, with approximately 3% experiencing mild symptoms within a 1-hour observation period. At 24 hours after vaccination, 13% had reported some mild symptoms, mainly gastrointestinal or runny nose. Thus, the vaccine was well tolerated in this egg-allergic population.

Based on those results, a separate group of 3640 patients with self-reported egg allergy were vaccinated according to the same protocol. Among this additional group, symptoms consistent with an allergic reaction developed in approximately 2% of patients, with 2 patients requiring epinephrine. This study offered proof that a single-dose approach is acceptable and prospectively demonstrated that vaccine skin testing was not necessary to safely administer the vaccine. Although this study was prospective and involved multiple centers, it did use a very specific vaccine type that was not available in the United States, which may hinder the ability to generalize these findings. However, and most importantly, this study showed that egg-allergic patients without a history of a severe reaction could receive a low-ovalbumin containing vaccine safely without vaccine skin testing, and as a single dose.

The third study was done by our group at Michigan using H1N1 vaccine.[5] We conducted a controlled prospective study of 105 egg-allergic children and 19 non-egg-allergic controls. All patients, including controls, received skin testing. All control patients received a single-dose injection. In the egg-allergic group, only those with negative vaccine skin testing received a single dose. If the skin testing was positive, these patients were given a 2-step graded challenge.

The specific questions we were interested in were as follows:

  • Is skin testing predictive of vaccine tolerance?

  • Is a 2-step graded challenge rather than a single dose necessary?

  • Does a patient's past egg allergy severity affect vaccine tolerance (given that influenza vaccine is technically contraindicated in children with anaphylaxis or with a severe reaction to egg)?

  • Is vaccine ovalbumin content a factor in vaccine tolerance?

We found that 44 of our total group of both egg-allergic and non-egg-allergic patients had positive vaccine skin tests, but all received the vaccine without an allergic reaction developing. Therefore, we concluded that the skin testing was not predictive of vaccine tolerance. Interestingly, we found that as the vaccine ovalbumin content increased, all patients were more likely to have a positive skin test to the vaccine, which suggested that the vaccine may act as a skin irritant during testing.

We enrolled 25 egg-allergic patients with a history of anaphylaxis attributable to egg. Thirteen had a positive skin test and were vaccinated using a 2-step graded challenge. The remaining 12 had a negative skin test and received a single dose. All 25 received the vaccine safely without any symptom development.

Additionally, past recommendations suggested that booster doses of vaccine should be given using the same manufacturer lot because of concerns that different lots may contain different levels of ovalbumin. In our study, 94 patients received a booster from a different lot, and none of the patients had any symptoms of allergic reaction, demonstrating that concerns about lot-to-lot variability may not be valid.

A limitation of our study was that the highest ovalbumin level in any of the vaccine lots used was 50 ng/mL. However, in a published study of vaccine ovalbumin levels, all 2009-2010 H1N1 ovalbumin levels analyzed were found to contain under 100 ng/mL, which was several-fold less than the trivalent influenza vaccine lots.[6]

The findings from these studies, each using a different approach and methodology, all point to the same conclusions: that the vaccine is well tolerated in most egg-allergic patients, that vaccine skin testing is not necessary, and that there is evidence to support the use of either a single dose or a 2-step approach to safely administer the vaccine.

Medscape: The report also notes that a larger multicenter trial examining administration strategies for EA patients is currently underway. Are you able to tell us any more about that trial and the questions you hope it will answer?

Dr. Greenhawt: There is a study currently underway exploring the safety of this season's combined trivalent influenza vaccine (which contains H1N1) among a population of patients with severe egg allergy and/or anaphylaxis to egg, to evaluate the safety of providing the vaccine to this population.


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