Egg-Allergic Children Shown to Safely Receive Flu Vaccine

Even children with severe egg allergies safely received a full dose of trivalent seasonal influenza vaccine, adding to evidence that egg allergy may not be a barrier to vaccination, according to a study published online October 24, 2012, and in the December issue of the Annals of Allergy, Asthma & Immunology.

Matthew J. Greenhawt, MD, MBA, assistant professor, Division of Allergy and Clinical Immunology, University of Michigan Medical School, Ann Arbor, and colleagues conducted a 2-part trial at 7 study sites on children with a history of severe allergic reaction to egg, including anaphylaxis, who also had a positive skin test or evidence of serum-specific immunoglobulin E antibody to egg.

In the randomized, double-blind, placebo-controlled part of the trial, 14 egg-allergic children (EAC) received an injection of 0.1 mL of influenza vaccine. If the test brought no adverse reaction, it was followed 30 minutes later with the full vaccine. A second group of 17 EAC received an injection of saline followed in 30 minutes by a full dose of age-appropriate vaccine if the initial injection brought no reaction.

In the second part of the trial, investigators performed a retrospective analysis of a single-dose vs a split-dose influenza vaccine in 112 eligible EAC study participants who declined participation in the randomized trial.

No participant in either part of the trial had a severe allergic reaction on receiving a full dose of the vaccine. In the randomized portion of the trial, 45.1% of children had a history of anaphylaxis after eating eggs. In the retrospective portion of the study, 77.6% of children had a history of anaphylaxis after egg ingestion.

"We demonstrate, through 2 distinct study methods, that [trivalent seasonal influenza vaccine] administration to EAC with severe allergy is safe and that graded dosing methods are not necessary," the study authors write. The authors say this research is the first to look at vaccine tolerance by comparing dosing methods.

Guidelines Need to Change

"These are very reassuring results," Robert A. Wood, MD, director, Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News. Dr. Wood has no connection with the study. "This study moves us one step forward."

Egg-allergic patients historically have been advised against receiving influenza vaccine, which is usually grown in embryonated chicken eggs and contains some amount of the egg allergen, ovalbumin. A study published in 1998 showed that egg-allergic patients could safely receive influenza vaccine without adverse effect but also demonstrated that the levels of ovalbumin in vaccine differed by as much as 100-fold, making a change in clinical practice unlikely, Dr. Wood said. The only safe way to administer an influenza vaccine to an allergic patient was by first conducting a skin test with the vaccine to determine patient sensitivity.

"What's really changed in this landscape has been much more consistency in the very, very low egg content in vaccines," Dr. Wood said. As egg content decreased across the board and manufacturers grew willing to divulge how much ovalbumin vaccines contain, the need to continue prevaccination skin testing has decreased, he said.

In 2011, the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention loosened guidelines for the administration of influenza vaccines to children with egg allergies, advising that children with mild allergic reactions to eggs, such as hives, could be inoculated by their primary care physician if they were observed for 30 minutes after for adverse events. However, children with more serious egg allergies, such as those in the current study, should go to an allergist for their influenza vaccine, the recommendations state.

"With this new data, and other studies that say the same thing, we might ultimately get to the point where anybody, no matter what the allergy severity, will not need an allergist," study coauthor John M. Kelso, MD, from the Division of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, California, told Medscape Medical News.

Until those guidelines change, however, "There is not a pediatrician in the world who will give a kid with a severe egg allergy a flu vaccination in their office," Dr. Wood said.

"This paper adds to what's really been a mountain of evidence on this subject," Dr. Kelso said. Between 1998 and 2012, 8 studies that included 241 children with severe egg allergy were vaccinated without adverse event. "There have been no reports of any serious reaction, no respiratory distress, no low blood pressure, no serious anaphylaxis," Dr. Kelso noted. Levels of mild allergic reaction, such as hives or wheezing, were the same in nonallergic children and EAC, he added.

"What's often overlooked in this evaluation is the risk of not getting the vaccine," Dr. Kelso said. Nearly 300,000 people are hospitalized each year with influenza A, including 21,000 children younger than 5 years. About 1.5% of children have egg allergy, and a third of them also have asthma.

He cautioned that new influenza vaccines that are not grown in eggs are not approved for anyone younger than 18 years. Such vaccines may not be as protective in children and could carry adverse effects if used off-label, he said. In addition, no published study has looked at intranasal influenza vaccines, which have very low amounts of ovalbumin.

Dr. Greenhawt received support from the American College of Allergy, Asthma, and Immunology 2010 Young Faculty Award and was supported in part by a grant from the National Center for Research Resources. The study authors and Dr. Wood have disclosed no other relevant financial relationships.

Ann Allergy Asthma Immunol. 2012;109:426-430. Abstract