National Center for Immunization & Respiratory Diseases

Influenza Vaccination of Persons with Egg Allergy:

Evidence to Recommendations Discussion and Work Group Considerations

Lenee H. Blanton

Lisa A. Grohskopf

Influenza Division, CDC/NCIRD

Advisory Committee on Immunization Practices

June 21, 2023
• Donna Hummell • Karen Broder • Pedro Moro • Geta Aynalem • Shashi Sharma • Elaine Miller • Andrew Leidner • Rebecca Morgan • Doug Campos-Outcalt

Acknowledgements

2
Background
• Affects approximately 1-3% of children by age 3 years.1,2

• Resolves for many during later childhood and adolescence.

– In one study,3

› 4% developed tolerance by age 4 years, 

› 12% by age 6 years, 

› 37% by age 10 years, 

› 68% by age 16 years.

• Reactions range from mild to life-threatening.

• Diagnosis:

– Clear history of immediate allergic reaction to egg or egg-containing foods.2

– Skin prick testing (SPT) or estimation of egg-specific IgE levels. 2

Egg Allergy

1. Eggesbo M et al. Allergy 2001;56(5):403-411

2. Erlewyn-Lajeunesse M et al. BMJ 2009;339:b3680.

3. Savage JH et al. J Allergy Clin Immunol 2007;120(6):1413-7.

4
Ovalbumin Content of U.S. Influenza Vaccines, 2022-23 

Vaccine (manufacturer) Approved age 

indication

Ovalbumin, mcg/dose* 

(per package insert)

Egg-based

Afluria Quadrivalent (Seqirus) ≥6 mos <1

Fluarix Quadrivalent (GSK) ≥6 mos ≤0.05

FluLaval Quadrivalent (GSK) ≥6 mos ≤0.3

Fluzone Quadrivalent (Sanofi Pasteur) ≥6 mos Not stated

FluMist Quadrivalent (AstraZeneca) 2 through 49 yrs <0.024

Fluad Quadrivalent (Seqirus) ≥65 yrs ≤1

Fluzone High-Dose Quadrivalent (Sanofi Pasteur) ≥65 yrs Not stated

Egg-free

Flucelvax Quadrivalent (Seqirus) ≥6 mos Egg-free

Flublok Quadrivalent (Sanofi Pasteur) ≥18 yrs Egg-free

* 0.5 mL for injectable vaccines and 0.2 mL for LAIV 5
• Persons with a history of egg allergy of any severity should receive influenza vaccine.

• Any licensed, recommended influenza vaccine (i.e., any IIV4, RIV4, or LAIV4) that is 

otherwise appropriate can be used.

• For persons with previous reactions to egg involving symptoms other than urticaria:

– “If a vaccine other than ccIIV4 or RIV4 is used, the selected vaccine should be 

administered in an inpatient or outpatient medical setting, including but not 

necessarily limited to hospitals, clinics, health departments, and physician 

offices. Vaccine administration should be supervised by a health care provider 

who is able to recognize and manage severe allergic reactions.”

• No specific observation period recommended.

Current ACIP Recommendations1

1. CDC/ACIP. MMWR Recomm Rep 2022;71(No. RR-1):1–28. IIV4= quadrivalent inactivated influenza vaccine

LAIV4=quadrivalent live attenuated influenza vaccine

ccIIV4=quadrivalent cell culture based inactivated influenza vaccine

RIV4=quadrivalent recombinant influenza vaccine 6
• American Academy of Pediatrics

– Since 2016-17, no additional measures recommended for persons with egg allergy.1

– “Children with egg allergy can receive any influenza vaccine without any additional precautions

beyond those recommended for all vaccines.”2

– Measures related to use of specific vaccines, observation periods, or restricting vaccination to 

specific medical settings not warranted and constitute a barrier to vaccination.3

– Not necessary to inquire about or screen for egg allergy prior to influenza vaccination. 3

• Joint Task Force, AAAAI/ACAAI

– “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.” 4

Influenza Vaccines and Egg Allergy: Other Guidance

1. Recommendations for Prevention and Control of Influenza in Children, 2016–2017 | Pediatrics | American Academy of Pediatrics (aap.org)

2. Recommendations for Prevention and Control of Influenza in Children, 2022–2023 | Pediatrics | American Academy of Pediatrics (aap.org).

3. AAP. Technical Report for the 2022-23 Recommendations for the Prevention and Control of Influenza in Children, 2022-23

4. Greenhawt M et al. Ann Allergy Asthma Immunol 2018;120:49-52. 7
• From chapter titled “Preventing and Managing Adverse Reactions”:

– “Although allergic reactions are a common concern for vaccine providers, these 

reactions are uncommon and anaphylaxis following vaccines is rare, occurring at 

a rate of approximately one per million doses for many vaccines. Epinephrine 

and equipment for managing an airway should be available for immediate use.”

General Best Practices Guidelines for Immunization1

1. Kroger AT et al. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html

8
• Vaccine skin testing prior to vaccination.1,2

– Skin prick and/or intradermal testing with dilution of vaccine

– If positive, vaccination deferred or administered via alternative dosing protocol

• Graded administration of vaccine.3

– Incrementally increasing volumes, often in 5 to 6 steps; sometimes with dilutions in early steps

– E.g., 0.05 mL of 1:100 dilution→0.05 mL of 1:10 dilution→0.05 mL→0.1 mL→ 0.15 mL→0.2 mL, 

with observation periods after each dose (e.g., 15 minutes).

• Split dosing of vaccine.4

– Most commonly 10% of dose volume→observation period→remaining 90% of dose volume, 

often with additional observation after final dose.

Past Approaches to Influenza Vaccination of Persons with 

Egg Allergy (Not Currently Recommended)

1. Bierman CW et al. J Infect Dis 1977;136:S652-S655.

2. Miller JR et al. J Allergy Clin Immunol 1983;71:568-173.

3. Murphy KR et al. J Pediatr 1985;106(6):931-933.

4. James JM et al. J Pediatr 1998;133:624-628.

9
• Whether to no longer recommend additional safety measures for 

persons with egg allergy of any severity, beyond what is recommended 

for any other persons presenting for influenza vaccination.

– In the discussion that follows, the proposed intervention is to no longer make 

the recommendation regarding vaccination setting for those with a history of 

severe allergic reaction to egg.

Policy Question

1

0
EtR Domain 1: Public Health Importance
• Egg allergy more common in younger children, and often co-exists with asthma:

– In a cross-sectional survey of 38,408 children,1

› Egg allergy prevalence was 0.9% overall; 1.3% for those <5 yrs.

› Asthma prevalence higher with egg allergy (46.5%) with other 8 most common food allergies (33.2%).

• Younger children and people with asthma are at increased risk of severe influenza 

illness.

Is Vaccination of Egg-Allergic Persons an Issue of Public 

Health Importance?

1. Samady W, Warren C, Wang J, et al. Egg allergy in US children. J Allergy Clin Immunol Pract. 2020;8(9):3066-73. 12
Public Health Importance: WG Considerations

• Current recommendations might be 

a real or perceived barrier to 

vaccination (e.g., by promoting 

hesitancy based on safety concerns, 

or providing a reason to decline 

vaccination).

- No data specifically examining or 

confirming that current 

recommendations are a barrier found, 

but existence of real or perceived 

barriers is plausible.

13

• Current recommendations might be 

less of a barrier now, since cellbased (egg-free) inactivated vaccine 

is approved for ages ≥6 mos. 

- However, there is only one such vaccine 

licensed for children <18 years, compared 

with four egg-based vaccines available for 

this age group. 
Is Vaccination of Egg-Allergic Persons an Issue of Public 

Health Importance?

14

0

6

33

61

0

0

No

Probably no

Probably yes

Yes

Varies

Don't know

% of respondents (N=18)
EtR Domain 2: Benefits and Harms
• Does the available evidence concerning the safety of influenza vaccines 

in persons with a history of egg allergy favor routine vaccination without 

additional safety measures, regardless of severity of previous allergic 

reaction to egg?

– Review focused on Harms (safety)—did not include review of 

effectiveness/efficacy data.

Review Question

16
Population, Intervention, and Comparators

▪ Population: Persons of any age with a history of allergy to eggs, or who 

have had an allergic reaction to influenza vaccine believed to be 

secondary to egg allergy.

▪ Intervention: Any influenza vaccine.

▪ Comparators: Placebo, non egg-based influenza vaccine, non-influenza 

control vaccine, no vaccine, no comparator

17
Outcomes

Important

• Allergic reaction symptoms 

requiring outpatient or emergency 

department medical attention†

• Allergic reaction including 

cardiovascular symptoms, 

respiratory symptoms, angioedema, 

or generalized urticaria

Critical

• Death

• Anaphylaxis meeting Brighton 

criteria Levels 1-3*

• Anaphylaxis otherwise 

classified*

• Allergic symptoms requiring 

hospitalization

* These two outcomes are combined in the tables that follow.

† Includes instances treated with medications, without explicit mention of outpatient or emergency department care.

18

Within 4 hours of vaccination:
Study Designs, Vaccines, and Comparison Groups

▪ 47 reports describing 52 studies.

• 1 randomized study (compared full-dose with 10%/90% split dose).

• 1 VAERS report summary.

• Remainder retrospective/prospective cohort studies and case series.

• 2 involved only recombinant vaccine (egg-free).

▪ No studies include a relevant comparison group (e.g., an alternative or no vaccine).

▪ 14 abstracts only (no related paper found).

▪ All studies were reviewed descriptively.

▪ 28 reports (31 studies) included in GRADE:

• Egg-based vaccines only (seasonal and monovalent).

• Full-dose or split-dose administration.

• For the randomized study, full- and split-dose groups combined; treated as a cohort study.

• Data with unknown/unclear vaccine type, unspecified administration protocol, graded (≥3 steps) 

dosing, and/or unknown denominator excluded.

• Since there are no comparators, data are summarized as frequencies. 19
Summary of Events by Vaccine Type: Egg Allergy of All severities

Outcome Seasonal IIVs* Monovalent IIVs* LAIV Importance Certainty

Death 0/1591 (0%) 0/5235 (0%) 0/1129 (0%) Critical Very low

Anaphylaxis 0/1591 (0%) 0/5235 (0%) 0/1129 (0%) Critical Very low

Reaction requiring hospitalization 0/1591 (0%) 0/5235 (0%) 0/1129 (0%) Critical Very low

Reaction requiring outpatient/ED 

attention (includes those given 

symptomatic medications)

3/1591 (0.2%) 77/5235 (1.5%) 0/1129 (0%) Important Very low

Allergic reaction including 

cardiovascular symptoms, respiratory 

symptoms, angioedema, or 

generalized urticaria

5/1591 (0.3%)† 33/5235 (0.6%) 10/1129 (0.8%) Important Very low

20

*Includes several papers for which vaccine type not explicitly stated, but presumed based upon season, study 

location, and/or use of graded/split dosing. Seasonal IIV data include one paper describing a virosomal vaccine.

†One study reported 6 instances of reactions including “wheezing, eczema exacerbation, or hives on chest”, but 

not specifying number with each symptom. If assumed that all six included wheezing, frequency would be 

11/1591=0.7% 
Summary of Events by Vaccine Type: Persons with Anaphylaxis to Egg

Outcome Seasonal IIVs* Monovalent IIVs* LAIV Importance Certainty

Death 0/322 (0%) 0/68 (0%) 0/412 (0%) Critical Very low

Anaphylaxis 0/322 (0%) 0/68 (0%) 0/412 (0%) Critical Very low

Reaction requiring hospitalization 0/322 (0%) 0/68 (0%) 0/412 (0%) Critical Very low

Reaction requiring outpatient/ED attention 0/295 (0%) 0/68 (0%) 0/412 (0%) Important Very low

Allergic reaction including cardiovascular 

symptoms, respiratory symptoms, 

angioedema, or generalized urticaria

0/291 (0%) 0/68 (0%) 0/27 (0%) Important Very low

21

*Includes several papers for which vaccine type not explicitly stated, but presumed to be IIV based upon season, 

study location, and/or use of graded/split dosing.
Summary of Evidence for Outcomes of Interest

Outcome Importance Included in 

profile

Certainty

Death Critical Yes Very low

Anaphylaxis Critical Yes Very low

Allergic reaction symptoms requiring hospitalization Critical Yes Very low

Allergic reaction symptoms requiring outpatient or 

emergency department medical attention

Important Yes Very low

Allergic reaction including cardiovascular symptoms, 

respiratory symptoms, angioedema, or generalized urticaria

Important Yes Very low

22
Report of Brighton Level 1 Anaphylaxis

▪ One report of Brighton Level 1 anaphylaxis in person with “possible” egg allergy 

within 30 minutes of receiving monovalent vaccine.

• In paper summarizing VAERS reports following monovalent pandemic influenza vaccine during 

2009-10 season.1

• Unclear from paper whether documented to be egg-allergic.

▪ Doses administered that season unknown

• Reaction not included in counts in GRADE evidence profiles (as denominator undefined).

▪ Paper states approximately 127 million doses distributed that season.

▪ Other reactions: 

• 2 of respiratory hypersensitivity

• 1 sensation of throat closure

1. Halsey NA, et al. Vaccine. 2013 Dec 9;31(51):6107-12. doi: 10.1016/j.vaccine.2013.09.066. Epub 2013 Oct 8. PMID: 24120547.
Descriptions Of Reactions Following Egg-free Vaccines

24

• Woo et al 2015, 2017: summaries of VAERS reports following 

recombinant influenza vaccine (RIV):

• Reports of serious allergic reactions following RIV, some of which occurred 

among persons with egg allergy.

• RIV is egg, gelatin, antibiotic, and preservative-free.

• Authors note that the occurrence of such reactions might reflect an 

underlying predisposition to atopy.

• Reports also highlight unpredictability of severe allergic reactions, and 

importance of being prepared in all vaccination settings, for all 

recipients, and with all vaccines. 
Limitations and WG Considerations

▪ Observational data with no comparator groups meeting criteria.

▪ Some data only available from abstracts.

▪ Many (particularly older) studies employed skin testing with egg proteins and/or 

vaccine prior to decision to vaccinate.

▪ Considerable variability in level of detail in which outcomes are described.

▪ Observation time post-vaccination varied; time elapsed post-vaccination not often 

reported for delayed reactions.

• Observation for immediate reactions under 4 hours for most studies; generally 30 min to 2 hours.

▪ Ovalbumin content was not reported/unknown in most instances. 

• In most instances where noted, was <1μg/dose; in some cases substantially less. 

• Difficult to know how this compares with current vaccines, since expressed as an upper limit.

▪ Data specifically for persons with anaphylaxis to egg were limited.

• Not all studies specified that persons with severe egg allergy were included.

• Where included, not all studies reported reactions specifically for this subgroup. 25
Egg Allergy and Anaphylaxis Reports after IIVs in 

VAERS, 2017-2022

• 178 anaphylaxis reports after any IIV

• 18 had an egg allergy (based on VAERS report)

• Clinical review revealed 7 reports of anaphylaxis and egg allergy (all in 2017-18):

• 4 in children (ages 2, 4, 9, 11 yrs); 3 in adults (ages 21, 52, 61 yrs)

• 4 Brighton level 1; 1 Brighton level 3; 2 did not meet Brighton

• Influenza vaccines:

› Fluarix quadrivalent: 2

› Fluzone quadrivalent: 2

› Fluvirin trivalent: 1

› Flucelvax quadrivalent: 1

› Flublok quadrivalent: 1

• Difficult to assess if reaction was due to egg protein due to limited laboratory data.

Vaccine Adverse Event Reporting System (VAERS) (hhs.gov) 26
How Substantial are the Undesirable Anticipated Effects? 

27

39

44

6

0

11

0

Minimal

Small

Moderate

Large

Varies

Don't Know

% of respondents (N=18)
EtR Domain 3: Values
• No direct evidence found.

• Change in recommendations might be reassuring to some who have 

wanted to be vaccinated but were hesitant/perceived it is unsafe;

• Or might be source of concern.

– WG member expressed that change might be viewed unfavorably if it is 

perceived as trade-off between safety vs. increasing coverage/reducing missed 

opportunities for vaccination.

Does the Target Population Feel that the Desirable Effects 

are Large Relative To Undesirable Effects?

29
Does the Target Population Feel that the Desirable Effects 

are Large Relative To Undesirable Effects?

30

0

6

22

17

6

50

No

Probably no

Probably yes

Yes

Varies

Don't Know

% of respondents (N=18)
• No direct evidence found.

– Presumably, greater value attached to the more serious outcomes (death, 

anaphylaxis, hospitalization).

Is There Important Uncertainty About, or Variability In, How 

Much People Value the Main Outcomes?

31
Is there important uncertainty about, or variability in, how 

much people value the main outcomes?

32

0

28

67

6

0

Important uncertainty or variability

Probably important uncertainty or 

variability

Probably not important uncertainty or 

variability

No important uncertainty or variability

No known undesirable outcomes

% of respondents (N=18)
EtR Domain 4: Acceptability
• No direct evidence found.

• Several US professional societies (AAP, AAAAI, ACAAI) already recommend no special 

measures (screening, observation periods, selection of specific vaccines, specific 

vaccination settings) for those with egg allergy.

• As of 2022-23, package inserts for egg-based vaccines continue to carry a 

contraindication of severe hypersensitivity reaction to any vaccine components.

– However, ACIP has previously recommended influenza vaccination with any appropriate vaccine 

(egg-based or not), regardless of severity of reaction to egg.

Is the Intervention Acceptable to Key Stakeholders?

34
Acceptability: WG Considerations

• Alignment of recommendations 

among public health organizations 

and professional societies facilitates 

consistent messaging to providers 

and patients.

35

• Concern that some settings might 

not be prepared to manage severe 

reactions (e.g., retail).

• Acceptability will be severely 

impacted if anaphylaxis occurs in a 

setting unprepared to manage it. 

- Importance of stressing that every

setting must be able to manage 

anaphylaxis, or should not administer 

any vaccines to any recipient. 

• Concern for potential liability issues.
Is the Intervention Acceptable to Key Stakeholders?

36

0

0

56

44

0

0

No

Probably no

Probably yes

Yes

Varies

Don't know

% of respondents (N=18)
EtR Domain 5: Resource Use
• No economic analysis was conducted.

– The target population is small.

– Lack of data for some factors.

› No reliable estimate of the proportion of those with egg allergy who have had 

severe reaction to egg.

› Proportions of individuals with egg allergy by age uncertain.

› Proportions of persons receiving egg-based vs. egg-free vaccines uncertain.

• Primary emphasis of assessment was safety rather than cost.

Is the Intervention a Reasonable and Efficient Allocation of 

Resources?

38
• CMS payment allowances and VFC costs higher for egg-free vaccines that are approved for children 

(rounded to nearest dollar):

Relative Costs of Egg-Based vs. Egg-Free Influenza Vaccines

39

Vaccine (based on 0.5mL dose) CMS Rate 2022-231 VFC List 2023-242

Egg-based

Average for egg-based vaccines for ≥6 mos: Multidose $20.00 $20.00

Average for egg-based vaccines for ≥6 mos: Preservative-free $22.00 (IIV4s)

$27.00 (LAIV4)

$21.00 (IIV4s)

$24.00 (LAIV4)

Fluzone High-Dose Quadrivalent: Preservative-free (≥65 yrs only) $70.00 -

Fluad Quadrivalent: Preservative-free (≥65 yrs only) $72.00 -

Egg-free

Flucelvax Quadrivalent: Multidose (≥6 mos) $31.00 $29.00

Preservative-free (≥6 mos) $32.00 $30.00

Flublok Quadrivalent Preservative-free (≥18 yrs only) $70.00 -

1. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Part-B-Drugs/McrPartBDrugAvgSalesPrice/VaccinesPricing

2. CDC Vaccine Price List (Private sector cost per dose)
Resource Use: WG Considerations

• Removing existing restrictions 

could result more efficient 

allocation of resources, if data 

suggest no or minimal increase in 

adverse events.

40

• Change in recommendations and 

lower cost of egg-based vaccines 

might lead to their increased use, 

which might be associated with 

increased costs if these is an 

increase in reactions requiring 

medical attention.
Is the Intervention a Reasonable and Efficient Allocation of 

Resources?

41

0

0

24

76

0

0

No

Probably no

Probably yes

Yes

Varies

Don't know

% of respondents (N=17)*

* Answer from one respondent who selected “Probably yes” and “Yes” excluded
EtR Domain 6: Equity
• No direct evidence found.

• Some racial/ethnic groups at increased risk for severe influenza illness, highlighting 

importance of vaccination:

– Influenza associated hospitalization and ICU admission rates higher among Black, Hispanic, and 

American Indian/Alaska Native children <4 yrs of age compared with White children.1

– Black children were disproportionately represented among children with egg allergy in one 

series (23.4%, relative to comprising 13.2% of the U.S. pediatric population).2

– If current recommendations are a barrier to vaccination, the intervention could improve equity 

with regard to risk of severe influenza illness.

What Would Be the Impact on Health Equity?

43

1. O’Halloran et al JAMA Netw Open. 2021 Aug 2;4(8):e2121880

2. Samady W et al. J Allergy Clin Immunol Pract. 2020 Oct;8(9):3066-3073.e6. doi: 10.1016/j.jaip.2020.04.058. 
• Issues related to trust in the healthcare system, from the patient’s 

perspective:

– A change in recommendations might mean vaccination occurs more widely in 

more settings than previously, and perhaps increased use of egg-based vaccines 

rather than egg-free vaccines in some settings. 

– The fact that egg-based vaccines are less expensive might reinforce belief that 

providers/healthcare systems do not care to use the necessary resources to 

provide a potentially safer vaccine.

Equity: WG Considerations

44
What Would Be the Impact on Health Equity?

45

0

17

11

50

0

6

17

Reduced

Probably reduced

Probably no impact

Probably increased

Increased

Varies

Don't know

% of respondents (N=18)
EtR Domain 7: Feasibility
Is the Intervention Feasible to Implement?

• Considerations favoring feasibility:

- The proposed change is a simplification 

of the previous recommendation.

- It does not specify particular vaccines.

- It does not change recommendations 

for emergency equipment and 

resources.

› The General Best Practices indicate that 

epinephrine and equipment to manage 

an airway should be available in all 

vaccination settings.1

47

• Consideration against feasibility:

- Vaccination settings not already 

prepared to manage severe allergic 

reactions would need to address 

these needs. 

› However, all settings are already 

recommended to be prepared for 

severe allergic reactions when 

administering any vaccine to any 

recipient.1

1. Kroger AT et al. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html. 
Is the Intervention Feasible to Implement?

48

0

0

11

89

0

0

No

Probably no

Probably yes

Yes

Varies

Don't know

% of respondents (N=18)
Balance of Consequences and Sufficiency 

of Information
Balance of Consequences

50

0

0

0

39

61

0

Undesirable consequences clearly outweigh desirable consequences

in most settings

Undesirable consequences probably outweigh desirable consequences

in most settings

The balance between desirable and undesirable consequences is

closely balanced or uncertain

Desirable consequences probably outweigh undesirable consequences

in most settings

Desirable consequences clearly outweigh undesirable consequences

in most settings

There is insufficient evidence to determine the balance of consequences

0 10 20 30 40 50 60 70 80 90 100

% of respondents (N=18)
Is There Sufficient Information to Move Forward With a 

Recommendation?

51

• Of 18 respondents,

– 18 responded “Yes”

– 0 responded “No”
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.
Search

• First search 03-14-2019; updated search 10-26-2022.

• Medline, Embase, PsycInfo, CINAHL, NTIS, Scopus, Cochrane Library, 

ClinicalTrials.gov; no date or language restriction.

Included reports

• Randomized Controlled trials, Observational studies, Case reports, Case series, 

Safety surveillance system reports (including Vaccine Adverse Event Reporting 

System and other safety surveillance system reports).

• Abstracts for which no papers found were included.

Excluded reports

• Animal studies, duplicate reports, reviews*, clinical trial registry summaries.*

Literature Search, Inclusion/Exclusion Criteria

* Used to help identify other potentially relevant reports 53
PRISMA Diagram

381 reports excluded

• 255 review/other non-primary source

• 67 wrong study design

• 20 wrong patient population

• 16 abstract (paper found) or registry summary

• 6 wrong intervention

• 3 wrong outcomes

• 14 insufficient information

477 reports retrieved

47 reports abstracted

428 full-text reports assessed

454 reports screened

23 duplicates removed

26 studies irrelevant

19 reports excluded from GRADE

• 12 unclear dosing protocol

• 4 unclear vaccine

• 2 egg-free vaccine

• 1 graded dosing only 28 reports included in GRADE

54
1. Question and PICO

Policy 

question:

Whether available evidence concerning safety of influenza vaccines in persons with a history of 

egg allergy favors routine vaccination without additional safety measures, regardless of severity of 

previous allergic reaction to egg. 

Population Persons of any age with a history of allergy to eggs, or who have had an allergic reaction to 

influenza vaccine believed to be secondary to egg allergy.

Intervention Receipt of any influenza vaccine. 

Comparison Placebo, nonegg-based influenza vaccine, non-influenza control vaccine, no vaccine, no 

comparator.

Outcomes Critical:

• Death

• Anaphylaxis meeting Brighton criteria Levels 1-3*

• Anaphylaxis otherwise classified*

• Allergic reaction symptoms requiring hospitalization

Important:

• Allergic reaction symptoms requiring outpatient or emergency department medical attention†

• Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or 

generalized urticaria

*These outcomes are combined in the evidence profile tables. 

†Includes instances treated with medications, without explicit mention of outpatient or emergency department care. 55
2. Outcomes and Rankings

Outcome Importance Included in 

evidence profile

Death Critical Yes

Anaphylaxis meeting Brighton criteria Levels 1-3* Critical Yes

Anaphylaxis otherwise classified* Critical Yes

Allergic reaction symptoms requiring hospitalization Critical Yes

Allergic reaction symptoms requiring outpatient or 

emergency department medical attention†

Important Yes

Allergic reaction including cardiovascular symptoms, 

respiratory symptoms, angioedema, or generalized urticaria

Important Yes

56

*These outcomes are combined in the evidence profile tables. 

†Includes instances treated with medications, without explicit mention of outpatient or emergency department care.
3a. Summary of Studies and Outcomes—Seasonal IIV (1)

*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60-62. Domains assessed included Selection, Ascertainment, 

Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting

†Abstract only.

Author 

Publication year

Age/other 

characteristics

N Comparator Events by outcome Methodological 

quality concern*

Anvari 2011 Not specified 86 None None Unclear

Chung 2010 Skin test group: 

Average 6.2

(95%CI 5.1-7.2) yrs

Non-skin test 

group: Average 3.9 

(95%CI 3.3-4.5) yrs

171 None None Moderate

Comeau 2016† Not specified 88 None None Serious

Des Roches 2012-1 <2 yrs: 27

2-4 yrs: 83

5-11 yrs: 82

>12 yrs: 37

230 None None Low

DesRoches 2012-2 <2 yrs: 29

2-4 yrs: 53

5-11 yrs: 51

>12 yrs: 4

137 None None Low

Erlewyn-Lajeunesse 2010† Not specified 16 doses None Cardiovascular, respiratory, angioedema, 

or generalized urticaria: 1 

Moderate

57
3a. Summary of Studies and Outcomes—Seasonal IIV (2)

Author 

Publication year

Age/other 

characteristics

N Comparator Events by outcome Methodological 

quality concern

Esposito 2008 6.03 +/- 3.33 yrs 44 Non-allergic group Outpatient or emergency department 

medical attention: 1

Cardiovascular, respiratory, angioedema, 

or generalized urticaria: 1 

Low

Greenhawt 2012-1 Median 11-12 mos 31 Comparison of full- vs. 

split-dose (combined in 

this review)

None Low

Greenhawt 2012-2 Median 12 mos at 

diagnosis

112 None None Low

Hotte 2008† Not provided 115 None None Unclear

Howe 2011 Not specified 69 Non-allergic group None Unclear

James 1998 Median 3 (1-46) yrs 83 Non-allergic group Outpatient or emergency department 

medical attention: 2

Cardiovascular, respiratory, angioedema, 

or generalized urticaria: 3

Low

Leo 2010† Not provided 31 None None Unclear

Park 2008† Mean 36.1 +/- 19.1 

(11 to 105 mos)

45 None None Unclear

Paschall 2011† Mean 3.8 yrs 65 doses None None Unclear

Shimizu 2016 Median 15

(IQR 13-20) mos

17 None None Low

Thanik 2010 Not specified 214 doses None None Unclear

58

*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60-62. Domains assessed included Selection, Ascertainment, 

Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting

†Abstract only.
3b. Summary of Studies and Outcomes—Monovalent IIV (1)

Author 

Publication year

Age/other 

characteristics

N Comparator Events by outcome Methodological 

quality concern*

Didenko 2010 median 4 (2-11) yrs 6 None None Moderate

Forsdahl 2012 Mean 6.25 yrs

(10 mos-16.5 yrs)

80 None Outpatient or emergency department 

medical attention: 1

Cardiovascular, respiratory, angioedema, 

or generalized urticaria: 1 

Moderate

Gagnon 2010-1 173 <2 yrs

280 2-4 yrs

277 5-11 yrs

100 ≥12 yrs

830 Non-allergic group Outpatient or emergency department 

medical attention: 4

Cardiovascular, respiratory, angioedema, 

or generalized urticaria: 6

Low

Gagnon 2010-2 Not specified 3460 None Outpatient or emergency department 

medical attention: 68

Cardiovascular, respiratory, angioedema, 

or generalized urticaria: 26

Unclear

Greenhawt 2010 Mean 5.5 (range 

0.4-20.4) yrs

105 Non-allergic group None Low

59

*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60-62. Domains assessed included Selection, Ascertainment, 

Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.
3b. Summary of Studies and Outcomes—Monovalent IIV (2)

Author 

Publication year

Age/other 

characteristics

N Comparator Events by outcome Methodological 

quality concern*

Leo 2010† Not specified 50 None None Unclear

Paschall 2011† Mean 3.8 yrs 66 None None Unclear

Pien 2010 Mean 3.7 +/- 3.0 yrs 59 None None Moderate

Pitt 2011 Mean 5.6 (1-27) yrs 59 None None Moderate

Schuler 2011 Mean 4.5 yrs 

(10 mos-16 yrs)

62 None Outpatient or emergency department 

medical attention: 4

Moderate

Siret-Alatrista 2010† Unclear 53 None None Unclear

Spiegel 2010† Range 1-56 yrs 150 None None Unclear

Upton 2012 3-5 yrs:12

6-9 yrs:24

10-13 yrs:28

14+ yrs:10

75 None None Moderate

60

*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60-62. Domains assessed included Selection, Ascertainment, 

Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting

†Abstract only.
3c. Summary of Studies and Outcomes—LAIV

Author 

Publication year

Age/other 

characteristics

N Comparator Events by outcome Methodological 

quality concern*

Des Roches 2015 2-16 yrs 68 Non-allergic group None Low

Turner 2015a Median 4.9 yrs

(2-17 yrs)

282 None Cardiovascular symptoms, respiratory 

symptoms, angioedema, or generalized 

urticaria: 6

Low

Turner 2015b Median 5.3 yrs

(2-18 yrs)

779 None Cardiovascular symptoms, respiratory 

symptoms, angioedema, or generalized 

urticaria: 4

Low

61

*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60-62. Domains assessed included Selection, Ascertainment, 

Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting

†Abstract only.
Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

17 Observational Seriousa Not serious Seriousb Seriousc None 0/1591 (0%) 

instances Very Low CRITICAL

1. Death

17 Observational Seriousa Not serious Seriousb Seriousc None 0/1591 (0%) 

instances Very Low CRITICAL

17 Observational Seriousa Not serious Seriousb Seriousc None 0/1591 (0%) 

instances Very Low CRITICAL

2. Anaphylaxis

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All are cohort studies without comparator interventions, with the exception of one randomized study which compared administration of full dose vs split dose. Full dose and split dose 

administration are treated as equivalent in this review, and so this study is treated as a cohort study. Six of 17 are of unclear methodological quality. Six of 17 are abstracts. 

b. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

3. Allergic reaction symptoms requiring hospitalization

4a: Seasonal IIV administered full- or split-dose, egg allergy of all severities (1)

62
Certainty Assessment

Impact Certaint

y

Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

17 Observational Seriousa Not serious Seriousb Seriousc None 3/1591 (0.2%) 

instances Very Low IMPORTANT

4. Allergic reaction symptoms requiring outpatient or emergency department medical attention

17 Observational Seriousa Not Serious Seriousb Seriousc None 5/1591 (0.3%)† 

instances Very Low IMPORTANT

5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed 

included Selection, Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

† One study reported 6 instances of reactions included “wheezing, eczema exacerbation, or hives on chest”, but not specifying number with each symptom. These are 

excluded here. If assumed that all six included wheezing, frequency would be 10/1591=0.6% 

a. All are cohort studies without comparator interventions, with the exception of one randomized study which compared administration of full dose vs split dose. Full 

dose and split dose administration are treated as equivalent in this review, and so this study is treated as a cohort study. Six of 17 are of unclear methodological 

quality. Six of 17 are abstracts. 

b. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

4a: Seasonal IIV administered full- or split-dose, egg allergy of all severities (2)

63
Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

10a Observational Seriousb Not serious Not serious Seriousc None 0/322 (0%) 

instances Very Low CRITICAL

1. Death

10a Observational Seriousb Not serious Not seriousb Seriousc None 0/322 (0%) 

instances Very Low CRITICAL

10a Observational Seriousb Not serious Not serious Seriousc None 0/322 (0%) 

instances Very Low CRITICAL

2. Anaphylaxis

3. Allergic reaction symptoms requiring hospitalization

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting

a. Includes only studies which explicitly mentioned inclusion of egg-anaphylactic patients for whom data are specifically reported.

b. All are cohort studies without comparator intervention groups, including administration via either full dose or split-dose (2-step) protocols. Two of 10 studies are abstracts, and 3 of 10 have 

uncertain methodological quality. 

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed. 

d. Studies removed from denominator which included persons with a history of anaphylaxis to egg and reported event(s), but which did not indicate whether these occurred in a person with a 

history of anaphylaxis to egg. 

4b: Seasonal IIV administered full- or split-dose, persons with anaphylaxis to egg (1)

64
Certainty Assessment

Impact Certaint

y

Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

9

a Observational Seriousb Not serious Not serious Seriousc None

0/295 (0%) 

instancesd

Very Low IMPORTANT

4. Allergic reaction symptoms requiring outpatient or emergency department medical attention

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting

a. Includes only studies which explicitly mentioned inclusion of egg-anaphylactic patients for whom data are specifically reported.

b. All are cohort studies without comparator intervention groups, including administration via either full dose or split-dose (2-step) protocols. Two of 10 studies are abstracts, and 3 of 10 have 

uncertain methodological quality. 

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed. 

d. Studies removed from denominator which included persons with a history of anaphylaxis to egg and reported event(s), but which did not indicate whether these occurred in a person with a 

history of anaphylaxis to egg. 

8

a Observational Seriousb Not serious Not serious Seriousc None

0/291 (0%)

instancesd

Very Low IMPORTANT

5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 

4b: Seasonal IIV administered full- or split-dose, persons with anaphylaxis to egg (2)

65
4c: Monovalent IIV administered full- or split-dose, egg allergy of all severities (1)

Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

13 Observational

Very 

seriousa Not serious Seriousb Seriousc None 0/5235 (0%) 

instances Very Low CRITICAL

1. Death

13 Observational

Very 

seriousa Not serious Seriousb Seriousc None 0/5235 (0%) 

instances d

Very Low CRITICAL

13 Observational

Very 

seriousa Not serious Seriousb Seriousc None

0/5235 (0%)

instances

Very Low CRITICAL

2. Anaphylaxis

3. Allergic reaction symptoms requiring hospitalization

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All were cohort studies without comparator intervention groups, including administration via either full dose or split-dose (2-step) protocols. Concerns regarding methodological quality were 

"Low" for only two studies, moderate for 6, and unclear for 4. History of egg allergy was by self report only for the largest study (n=3640).

b. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.

c. Cannot assess imprecision as these are proportions without confidence intervals; however some degree of imprecision must be assumed.

d. One instance of Brighton Level 1 anaphylaxis was reported in a VAERS surveillance data summary from the 2009-10 influenza season. This instance is not represented in the table as no 

denominator is available for this paper. However, it was reported that 127,075,320 doses of monovalent influenza vaccine were distributed in the United States for the season. 66
Certainty Assessment

Impact Certaint

y

Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

13 Observational

Very 

seriousa Not serious Seriousb Seriousc None 77/5235 (1.5%) 

instances Very Low IMPORTANT

4. Allergic reaction symptoms requiring outpatient or emergency department medical attention

13 Observational Seriousa Not serious Seriousb Seriousc None 33/5235 (0.6%) 

instances Very Low IMPORTANT

5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All were cohort studies without comparator intervention groups, including administration via either full dose or split-dose (2-step) protocols. Concerns regarding methodological quality were 

"Low" for only two studies, moderate for 6, and unclear for 4.

b. Only 143 of total participants reported to have a history of anaphylaxis to egg. 

c. Cannot assess imprecision as these are proportions without confidence intervals; however some degree of imprecision must be assumed.

d. One instance of Brighton Level 1 anaphylaxis was reported in a VAERS surveillance data summary from the 2009-10 influenza season. This instance is not represented in the table as no 

denominator is available for this paper. However, it was reported that 127,075,320 doses of monovalent influenza vaccine were distributed in the United States for the season. 

4c: Monovalent IIV administered full- or split-dose, egg allergy of all severities (2)

67
4d: Monovalent IIV administered full- or split- dose, persons with anaphylaxis to egg (1)

Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

3

ObservationalVery 

Seriousa Not Serious Not Serious Seriousb None

0/68 (0%)

Instances

Very Low CRITICAL

1. Death

3

ObservationalVery 

Seriousa Not Serious Not Serious Seriousb None 0/68 instances Very Low CRITICAL

3

ObservationalVery 

Seriousa Not Serious Not Serious Seriousb None 0/68 instances Very Low CRITICAL

2. Anaphylaxis

3. Allergic reaction symptoms requiring hospitalization

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. Cohort studies without comparator intervention groups, including administration via either full dose or split-dose (2-step) protocols.

b. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

68
Certainty Assessment

Impact Certaint

y

Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

3

ObservationalVery 

Seriousa Not Serious Not Serious Seriousb None 0/68 instances Very Low IMPORTANT

4. Allergic reaction symptoms requiring outpatient or emergency department medical attention

3

ObservationalVery 

Seriousa Not Serious Not Serious Seriousb None 0/68 instances Very Low IMPORTANT

5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. Cohort studies without comparator intervention groups, including administration via either full dose or split-dose (2-step) protocols.

b. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

4d: Monovalent IIV administered full- or split- dose, persons with anaphylaxis to egg (2)

69
4e. Seasonal LAIV, egg allergy of all severities (1)

Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

3

Observational Seriousa Not serious Seriousb Seriousc None 0/1129 instances Very Low CRITICAL

1. Death

3

Observational Seriousa Not serious Seriousb Seriousc None 0/1129 instances Very Low CRITICAL

3

Observational Seriousa Not serious Seriousb Seriousc None 0/1129 instances Very Low CRITICAL

2. Anaphylaxis

3. Allergic reaction symptoms requiring hospitalization

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All are cohort studies without a comparison intervention.

b. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

70
Certainty Assessment

Impact Certaint

y

Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

3

Observational Seriousa Not serious Seriousb Seriousc None 0/1129 instances Very Low IMPORTANT

4. Allergic reaction symptoms requiring outpatient or emergency department medical attention

3

Observational Seriousa Not serious Seriousb Seriousc None 10/1129 (0.8%) 

instances Very Low IMPORTANT

5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All are cohort studies without a comparison intervention.

b. Majority of persons in each study did not have history of anaphylaxis to egg. 

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

4e. Seasonal LAIV, egg allergy of all severities (2)

71
Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

3

Observational Seriousa Not serious Not serious Seriousb None 0/412 instances Very Low CRITICAL

1. Death

3

Observational Seriousa Not serious Not serious Seriousb None 0/412 instances Very Low CRITICAL

3

Observational Seriousa Not serious Not serious Seriousb None 0/412 instances Very Low CRITICAL

2. Anaphylaxis

3. Allergic reaction symptoms requiring hospitalization

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All are cohort studies with no comparison groups.

b. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed. Very low denominator count. 

4f. Seasonal LAIV, persons with anaphylaxis to egg (1)

72
Certainty Assessment

Impact Certainty Importance

No. of 

studies

Study 

Design

Methodological 

Quality*

Inconsistency Indirectness Imprecision Other 

considerations

3

Observational Seriousa Not serious Not serious Seriousb None 0/412 instances Very Low IMPORTANT

4. Allergic reaction symptoms requiring outpatient or emergency department medical attention

1

Observational Seriousa Not serious Not serious Very 

seriousc None 0/27 instances Very Low IMPORTANT

5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 

*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60-62 [51]. Domains assessed included Selection, 

Ascertainment, Causality (excluding items pertaining to alternative causes and dose-response effect), and Reporting.

a. All are cohort studies with no comparison groups.

b. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed.

c. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision should be assumed. Very low denominator count. 

d. Studies removed from denominator which included persons with a history of anaphylaxis to egg and reported event(s), but which did not indicate whether these occurred in a person with a 

history of anaphylaxis to egg. 

4f. Seasonal LAIV, persons with anaphylaxis to egg (2)

73
Appendix 1. Event Summary: Death

Author 

Publication year

Age N egg allergic N anaphylaxis to egg Events

No studies reported this outcome.

74
Appendix 2. Event Summary: Anaphylaxis

Author 

Publication year

Age N egg allergic N anaphylaxis to egg Events

No studies reported this outcome.

75
Appendix 3. Event Summary: Hospitalization

Author 

Publication year

Age N egg allergic N anaphylaxis to egg Events

No studies reported this outcome.

76
Appendix 4. Event Summary: Outpatient/Emergency Care (1)

Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis to 

egg

Events

Esposito 2008 Mean 6.03 +/-3.33 Seasonal 

virosomal

44 11 • 1 bronchospasm in mildly 

allergic child, treated with 

bronchodilator and 

steroid.

James 1998 Mean 6.25 

(10mos-16.5 years)

Seasonal IIV 83 27 • 1 delayed (>1 hour postvaccination) emesis, mild 

cough, wheeze treated 

with nebulizer.*

• 1 delayed (>1 hour postvaccination) erythema at 

injection site treated.*

*Uncertain whether occurred in individual with anaphylaxis to egg.

77
Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis to 

egg/severe allergy

Events

Forsdahl 2012 Mean 6.25 yrs

(10 mos-16.5 yrs)

Monovalent IIV 80 19 • 1 wheal on lip, diffuse 

rash, and loose stools a 

few minutes after 90% 

step; treated with 

antihistamine.

Gagnon 2010-1 173 <2 yrs

280 2-4 yrs

277 5-11 yrs

100 ≥12 yrs

Monovalent IIV 830 - • 1 wheeze treated with 

bronchodilator.

• 1 hives treated with 

antihistamines

• 1 ocular pruritis treated 

with antihistamines

• 1 angioedema treated 

with antihistamines.

Appendix 4. Event Summary: Outpatient/Emergency Care (2)

78
Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis to 

egg/severe allergy

Events

Gagnon 2010-2 Not provided Monovalent IIV 3460 - • 1 mouth/throat tingling 10-15 min 

post-vaccination; received two 

doses epinephrine and observed in 

emergency department; recovered.

• 1 continuous crying with wheezing 

30 min post-vaccination. Received 

epinephrine and bronchodilator (6 

treatments), observed 4 hours, 

recovered. 

• 66 skin and respiratory symptoms, 

treated with antihistamines

• 42 with skin involvement

• 17 with throat 

tingling/tightening

• 7 with cough (4 also treated 

with bronchodilator)

Appendix 4. Event Summary: Outpatient/Emergency Care (3)

79
Author 

Publication year

Age Vaccine N egg 

allergic

N anaphylaxis to 

egg/severe allergy

Events

Schuler 2011 Mean 4.5 yrs 

(10 mos-16 yrs)

Monovalent IIV 62 - • 1 vasovagal response requiring 

symptomatic management.

• 1 hyporesponsive episode; 

referred to emergency 

department.

• 2 hives treated with 

antihistamines.

Appendix 4. Event Summary: Outpatient/Emergency Care (4)

80
Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis 

to egg/severe 

allergy

Events

ErlewynLajeunesse 2010 Children Seasonal IIV 16 doses 4 • 1 instance subjective wheeze*

Esposito 2008 Mean 6.03 +/-3.33 Seasonal IIV 44 11 • 1 instance bronchospasm in mildly 

allergic child, treated with 

bronchodilator and steroid.

James 1998 Mean 6.25 

(10mos-16.5 years)

Seasonal IIV 83 27 • 1 with mild throat itching, cough, 

and wheeze.*

• 1 delayed (>1 hour post-vaccination) 

emesis, mild cough, wheeze treated 

with nebulizer.*

• 1 mild URI symptoms.*

*Uncertain whether occurred in individual with anaphylaxis to egg.

Appendix 5. Event Summary: Cardiovascular, Respiratory, Angioedema, or 

Generalized Urticaria (1)

81
Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis to 

egg/severe allergy

Events

Forsdahl 2012 Mean 6.25 yrs

(10 mos-16.5 yrs)

Monovalent IIV 80 19 • 1 sneezing without 

bronchospasm.

Gagnon 2010-1 173 <2 yrs

280 2-4 yrs

277 5-11 yrs

100 ≥12 yrs

Monovalent IIV 830 - • 1 sensation of throat 

closure

• 1 hoarse voice

• 1 angioedema

• 1 bilateral wheeze

• 2 generalized urticaria

Appendix 5. Event Summary: Cardiovascular, Respiratory, Angioedema, or 

Generalized Urticaria (2)

82
Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis to 

egg/severe allergy

Events

Gagnon 2010-2 Not provided Monovalent IIV 3460 - • 1 mouth/throat tingling 10-15 

min post-vaccination; 

received two doses 

epinephrine and observed in 

emergency department; 

recovered.

• 1 continuous crying with 

wheezing 30 min postvaccination. Received 

epinephrine and 

bronchodilator (6 treatments), 

observed 4 hours, recovered. 

• 17 with throat 

tingling/tightening

• 7 with cough (4 also treated 

with bronchodilator)

Appendix 5. Event Summary: Cardiovascular, Respiratory, Angioedema, or 

Generalized Urticaria (3)

83
Author 

Publication year

Age Vaccine N egg allergic N anaphylaxis to 

egg/severe allergy

Events

Turner 2015a Median 4.9 yrs

(2-17 yrs)

LAIV3 282 115 • 6 rhinitis within 30 min postvaccination.

Turner 2015b Median 5.3 yrs

(2-18 yrs)

LAIV4 779 157 • 4 rhinitis within 2 hours postvaccination.

Appendix 5. Event Summary: Cardiovascular, Respiratory, Angioedema, or 

Generalized Urticaria (4)

84
Summary of Evidence for Outcomes of Interest

Outcome Importance Included in profile Certainty

Death Critical Yes Very low

Anaphylaxis Critical Yes Very low

Allergic reaction symptoms requiring hospitalization Critical Yes Very low

Allergic reaction symptoms requiring outpatient or 

emergency department medical attention

Important Yes Very low

Allergic reaction including cardiovascular symptoms, 

respiratory symptoms, angioedema, or generalized 

urticaria

Important Yes Very low

85
1. Anvari, S., et al., Influenza vaccine testing and administration in Egg allergic children. Journal of Investigative Medicine, 2011. 59 (2): p. 477-478.

2. Chan D. The safety of influenza vaccination in children with anaphylactic egg allergy. Internal Medicine Journal 2009; 39 (Suppl. 5): A139.

3. Chung, E.Y., L. Huang, and L. Schneider, Safety of influenza vaccine administration in egg-allergic patients. Pediatrics, 2010. 125(5): p. e1024-30.

4. Comeau, J., et al., Why is Australian policy still cautious with influenza vaccination in severe egg allergic children? Internal Medicine Journal, 2016. 46 (Supplement 4): p. 6.

5. Des Roches, A., et al., Egg-allergic patients can be safely vaccinated against influenza. Journal of Allergy & Clinical Immunology, 2012. 130(5): p. 1213-1216.e1.

6. Des Roches, A., et al., Safe vaccination of patients with egg allergy by using live attenuated influenza vaccine. The Journal of Allergy & Clinical Immunology in Practice, 2015. 

3(1): p. 138-9.

7. Didenko, I., et al., Influenza A (H1N1) vaccination in individuals with egg allergy. Revista Portuguesa de Imunoalergologia, 2010. 18(3): p. 243-252.

8. Dona, D., et al., Special immunization service: A 14-year experience in Italy. PLoS ONE, 2018. 13 (4) (no pagination)(e0195881).

9. Dorsey MJ. Influenza vaccine in 55 patients with egg allergy. J Allg Clin Immunol 2005: S250.

10. Erlewyn-Lajeunesse, M., et al., Multicentre audit of influenza immunisation in children allergic to egg. Allergy: European Journal of Allergy and Clinical Immunology, 2010. 

92): p. 364-365.

11. Esposito, S., et al., Safe administration of an inactivated virosomal adjuvanted influenza vaccine in asthmatic children with egg allergy. Vaccine, 2008. 26(36): p. 4664-8.

12. Forsdahl, B.A., Reactions of Norwegian children with severe egg allergy to an egg-containing influenza A (H1N1) vaccine: a retrospective audit. BMJ Open, 2012. 2: p. 

e000186.

13. Fung, I. and J.M. Spergel, Administration of influenza vaccine to pediatric patients with egg-induced anaphylaxis. Journal of Allergy & Clinical Immunology, 2012. 129(4): p. 

1157-9.

14. Gagnon, R., et al., Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine. Journal of Allergy & Clinical Immunology, 2010. 126(2): p. 317-

23.

15. Grainger-Allen, E., et al., Safety of influenza immunisation in high risk egg allergy. Clinical and Experimental Allergy, 2013. 43 (12): p. 1433.

16. Greenhawt, M.J., et al., Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy. Annals of Allergy, Asthma, & Immunology, 2012. 

109(6): p. 426-30.

References
17. Greenhawt, M.J., et al., The safety of the H1N1 influenza A vaccine in egg allergic individuals. Annals of Allergy, Asthma, & Immunology, 2010. 105(5): p. 387-93.

18. Halsey, N.A., et al., Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: Reports to VAERS. Vaccine, 2013. 31(51): p. 

6107-6112.

19. Hotte SL. A 6-year Experience with Influenza Vaccination in Egg Allergic Patients. J Allerg Clin Immunol 2008;121:s239.

20. Howe, L.E., et al., Safe administration of seasonal influenza vaccine to children with egg allergy of all severities. Annals of Allergy, Asthma, & Immunology, 2011. 106(5): p. 

446-7.

21. James, J.M., et al., Safe administration of influenza vaccine to patients with egg allergy. Journal of Pediatrics, 1998. 133(5): p. 624-8.

22. Kawahara, H., et al., [Immediate adverse reactions after administration of the influenza vaccine to patients with positive CAP-RAST to egg white]. Arerugi - Japanese 

Journal of Allergology, 2002. 51(7): p. 559-64.

23. Kawahara, H., et al., [Safe administration of influenza vaccine in asthmatic children]. Arerugi - Japanese Journal of Allergology, 1998. 47(7): p. 679-86.

24. Khan, F.S., et al., Influenza vaccine administration in egg allergic children. Journal of Allergy and Clinical Immunology, 2012. 1): p. AB70.

25. Kletz, M.R., et al., Administration of egg-derived vaccines in patients with history of egg sensitivity. Annals of Allergy, 1990. 64(6): p. 527-9.

26. Leo, S.H., J. Dean, and E.S. Chan, Safety of H1N1 and seasonal influenza vaccines in egg allergic patients in British Columbia. Allergy, Asthma and Clinical Immunology. 

Conference: Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting, 2010. 6(SUPPL. 2).

27. Murad, M.H., et al., Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med, 2018. 23(2): p. 60-63.

28. Murphy, K.R. and R.C. Strunk, Safe administration of influenza vaccine in asthmatic children hypersensitive to egg proteins. Journal of Pediatrics, 1985. 106(6): p. 931-3.

29. Nickolls, C., et al., The safety of H1N1/seasonal influenza vaccination in egg allergic children - A prospective study. Internal Medicine Journal, 2010. 4): p. 16.

30. Owens, G. and A. MacGinnitie, Higher-ovalbumin-content influenza vaccines are well tolerated in children with egg allergy. Journal of Allergy & Clinical Immunology, 2011. 

127(1): p. 264-5.

31. Park, A., et al. Administration of influenza vaccine to patients with egg allergy. J Allergy Clin Immunol , 2008 (February). p. S240.

32. Paschall, V.L., et al., Do egg-specific IgE levels predict reactions to seasonal influenza or H1N1 vaccination? Journal of Allergy and Clinical Immunology, 2011. 1): p. AB182.

33. Pien, G.C., et al., Coordination of multidisciplinary resources for vaccination of egg-allergic individuals during an H1N1 (novel) influenza pandemic. Allergy & Asthma 

Proceedings, 2010. 31(6): p. 507-10.
34. Pitt, T., et al., Assessment of epicutaneous testing of a monovalent Influenza A (H1N1) 2009 vaccine in egg allergic patients. Allergy, Asthma, & Clinical Immunology : 

Official Journal of the Canadian Society of Allergy & Clinical Immunology, 2011. 7(1): p. 3.

35. Schuler, J.E., et al., Administration of the adjuvanted pH1N1 vaccine in egg-allergic children at high risk for influenza A/H1N1 disease. Can J Public Health, 2011. 102(3): p. 

196-9.

36. Seyerle, J., R. Scherzer, and E.A. Erwin, Testing and administration of seasonal and pandemic influenza vaccines in egg allergic patients. Annals of Allergy, Asthma and 

Immunology, 2010. 105 (5): p. A109.

37. Shimizu, M., et al., [Safety of Influenza Vaccination in Children with Severe Allergy to Hen's Eggs: A Prospective Case Series Study]. Arerugi - Japanese Journal of 

Allergology, 2016. 65(2): p. 128-33.

38. Siret-Alatrista, A., et al., The 2009-2010 H1N1 vaccination campaign for patients with egg allergy in a region of France. Allergy, 2011. 66(2): p. 298-9.

39. Spiegel, W. and R. Anolik, Administration of H1N1 vaccine in an eggallergic population. Annals of Allergy, Asthma and Immunology, 2010. 105 (5): p. A4.

40. Thanik, E.S., A.L. Cox, and H.A. Sampson, Administration of a low egg-containing influenza vaccine [fluarix] in an egg-alphallergic pediatric population. Journal of Allergy 

and Clinical Immunology, 2010. 1): p. AB25.

41. Tounian, P., et al., [Vaccinations of children allergic to eggs with vaccine prepared with egg]. Archives Francaises de Pediatrie, 1993. 50(3): p. 191-5.

42. Tozandehjani, S., et al., Safety of Inactivated Influenza Vaccine in Patients with Egg Allergy in Kurdistan Province, Iran. Iranian Journal of Public Health, 2019. 48(4): p. 758-

763.

43. Turner, P.J., et al., Safety of live attenuated influenza vaccine in atopic children with egg allergy. Journal of Allergy & Clinical Immunology, 2015. 136(2): p. 376-81.

44. Turner, P.J., et al., Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study. BMJ, 2015. 351: p. h6291.

45. Upton, J.E., et al., No systemic reactions to influenza vaccination in egg-sensitized tertiary-care pediatric patients. Allergy, Asthma, & Clinical Immunology : Official Journal 

of the Canadian Society of Allergy & Clinical Immunology, 2012. 8: p. 2.

46. Webb, L., et al., Single-dose influenza vaccination of patients with egg allergy in a multicenter study. Journal of Allergy & Clinical Immunology, 2011. 128(1): p. 218-9.

47. Woo, E.J., Allergic reactions after egg-free recombinant influenza vaccine: reports to the US Vaccine Adverse Event Reporting System. Clinical Infectious Diseases, 2015. 

60(5): p. 777-80.

48. Woo, E.J., et al., Postmarketing safety surveillance of trivalent recombinant influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Vaccine, 2017. 

35(42): p. 5618-5621.
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.