The egg-allergic patient population we evaluated for vaccination was a tertiary pediatric practice with a high level of anaphylaxis, significant co-morbid conditions, and some with positive flu vaccine tests. Despite this we successfully vaccinated 77 of 79 patients and only skin tested 8/79 patients by using a risk-stratified approach. The only 2 we did not vaccinate were due to patient refusal. No patients had a systemic reaction to vaccination.Some patients received a different administration of vaccine than dictated by their egg allergy alone. There were 13 patients with "mild egg allergy" that were given the vaccine in two graded doses whereas the algorithm suggested a single dose by their egg history alone. Some of these patients had complex medical conditions. For example, one had sickle cell anemia, one had a liver transplant, and one had cerebral palsy and was in a wheelchair. While these conditions are not related to atopy, they may make the recognition and management of a serious allergic reaction more difficult or lessen the parents or physician's comfort level with risk. Administration of vaccine without prior testing was a change from previous years so the use of the perceived more cautious approach (split dosing rather than single dosing) was not surprising. Three patients that were not tested to the vaccine were given the vaccine in a single dose when two were suggested by our algorithm. Two of these patients had hives and angioedema to egg and one had a combined skin and gastrointestinal reaction. These reactions were determined by the treating physician to be mild and were thus triaged to a single dose. None of these patients had a systemic reaction to the vaccine. The algorithm was only a suggestion and the flexibility for the physician or family to choose a more cautious regimen likely helped compliance.
All of our vaccinated patients tolerated the vaccine so it is certainly possible that they would have all tolerated the vaccine in a one dose method, although our patient who received the vaccine in 5 steps had localized hives at the injection site to the first diluted dose; we do not know what the reaction would have been if this patient had received only split dosing or full dosing. Likely this was just a reflection of her cutaneous sensitivity to the vaccine as evidenced by her positive skin tests. A multi-center trial is ongoing to establish the safety of single dosing of influenza vaccine versus split dosing in patients with severe reactions [16
] so there may soon be more evidence that even patients with severe reactions can tolerate single dosing without prior vaccine testing.
In addition, there have been a number of papers published on different experiences with the 2009 vaccination campaign in egg-allergic individuals. The largest study to date of influenza vaccination in egg-allergic patients [17
] is a prospective study in which patients were risk-stratified by history to receive the vaccine without prior vaccine testing in one dose if low-risk or in a split-dose regimen if they were high-risk. In this study none of 830 vaccinations resulted in anaphylaxis, but one patient needed an antihistamine in the first hour, and one needed salbutamol. Further vaccination of more than 3600 patients resulted in 69 patients developing a possible allergic reaction and two uses of epinephrine. This study supports that egg-allergic patients can receive the egg containing vaccine without prior vaccine testing, but some caution is required.
As of October 2010, the American Academy of Allergy, Asthma and Immunology (AAAAI) no longer recommends routine influenza vaccine skin testing for egg-allergic individuals and has updated guidelines for November 2011 [18
] . This organization now recommends a single step vaccine strategy for most patients. A one step or two step approach with no routine skin testing of vaccine is recommended in a recent editorial [19
] and in a new focused practice parameter update for the Joint Task Force on Practice Parameters [20
]. However, for example, a Cincinnati group [21
] and the British Society of Allergy and Clinical Immunology endorse a skin testing based approach [22
]. The Red Book [1
] has issued an update to their guidelines that some egg-allergic individuals may be vaccinated without prior skin testing with a low albumin vaccine in one or two steps in an appropriate setting, but these recommendations are said to be not applicable to the egg-allergic person with a history of anaphylaxis or severe allergy. Recently, the Advisory Committee on Immunization Practices from the Centers for Disease Control and Prevention issued their recommendations [23
] that someone who experiences only hives to eating egg can receive the killed influenza vaccine in one dose with at least a 30 minute wait. Patients with more significant symptoms should be evaluated by an allergist. In October 2011 the Canadian Pediatric Society issued guidelines [24
] in which a risk stratification system is recommended to decide between one or two step vaccination with no prior influenza vaccine testing. In these guidelines, people who experienced generalized reactions, including generalized urticaria, to egg would be deemed "higher risk" and vaccinated with a two step regimen. The presence of multiple differing guidelines suggests that more information is still needed.
There are some limitations to our study. Egg allergy was not confirmed by oral challenge, therefore there were likely some skin test positive only children not actually allergic to eggs. However, these children only totaled 17 patients. Another limitation is that only 16 patients (20.3%) had a history of egg reaction within the past 2 years. Therefore, some patients, including some of these patients that we described as having a recent reaction, may have outgrown clinical egg allergy. Follow-up for delayed reactions was by voluntary reporting although our observation period was long enough to assess for most anaphylactic reactions. This vaccine had very low egg content and therefore these findings may not apply to higher egg content vaccines. Our overall patient numbers were small; however our number of patients with a history of anaphylaxis, 24, contributes to the literature because the largest number of patients with a severe reaction receiving an egg containing influenza vaccine reported in a study so far has been the 72/830 reported by Gagnon et al.
Risk stratifying patients by their prior reaction to eating egg suggests that the prior history is indicative of their risk of reaction. This presumption may not be true [25
]. As another level of caution, in our protocol we suggested that the follow up vaccine (if required) should be from the same lot. This may also be unnecessary [25
We had two patients referred with positive intradermal testing to the vaccine diluted to 1:100 of the final concentration who did not test positive when tested without adjuvant. Given this potentially irritant response, as well as issues regarding the potential immunological effects of intradermal squalene, we recommend that if squalene containing vaccines need to be intradermally tested they are tested without the adjuvant. Although our numbers are small, to our knowledge there is no other reported experience of intradermal testing of a vaccine with squalene.