Hong Kong Institute of Allergy and Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases joint consensus statement 2018 on vaccination in egg-allergic patients

Abstract

Vaccination of egg-allergic individuals has been a historical concern, particularly for influenza and measles-mumps-rubella-varicella vaccines that are developed in chicken egg embryos or chicken cell fibroblasts. The egg proteins in these vaccines were believed to trigger an immediate allergic reaction in egg-allergic individuals. However, recently published international guidelines have updated their recommendations and now state that these vaccines can be safely administered to egg-allergic individuals. This joint consensus statement by the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases summarises the updates and provides recommendations for local general practitioners and paediatricians.

Background

Vaccination is an important and effective method to develop active immunity against certain pathogens. It helps to prevent or reduce the risks of developing certain infectious diseases as well as moderating disease severity. However, the administration of certain vaccines, including influenza, measles-mumps- rubella (MMR), measles-mumps-rubellavaricella (MMR-V) and yellow fever vaccines, has historically been relatively, if not absolutely, contra-indicated in egg-allergic individuals. This is because these vaccines are developed in chicken egg embryos or chicken cell fibroblasts, raising the concern that egg proteins (notably ovalbumin) in these vaccines may trigger an immediate allergic reaction in egg-allergic individuals. As a result, previous vaccination guidelines and vaccine product information have recommended avoidance of influenza and MMR or MMR-V vaccines in individuals with a history of anaphylactic reaction to egg exposure.

Local epidemiological studies have shown that 0.4%-0.7% of Hong Kong children were reported by their parents to have had an adverse reaction to intake of a hen's egg.^{1 2} No local data for the adult population are available. However, it is important to differentiate between adverse reactions and genuine egg allergy, especially when deciding the need for vaccine avoidance. A recent United Kingdom multi-centre study found that more than a third of patients with suspected egg allergy who were referred to a tertiary allergy centre for vaccination were not actually egg allergic, and all were vaccinated successfully.³

Despite the paucity of evidence, there remains some concern that administration of vaccines that could contain egg proteins, notably ovalbumin, might cause allergic reactions in egg-allergic subjects. The Centre for Health Protection recommends that mildly egg-allergic individuals can safely receive inactivated influenza vaccine in a primary care setting. However, those with confirmed or suspected egg allergy who have experienced severe reactions should be seen by an allergist/immunologist for evaluation of their egg allergy prior to administration of inactivated influenza vaccine.⁴

Recently published international guidelines have updated their recommendations regarding the administration of vaccines to egg-allergic individuals. This joint consensus statement by the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy [and] Infectious Diseases summarises recent updates and provides recommendations for local general practitioners and paediatricians. For practical reasons, this guideline will only cover influenza and MMR/MMR-V vaccines.

Yellow fever vaccine is less commonly administered and is commonly propagated in hens' eggs. Specialist evaluation is recommended prior to vaccination for evaluation of suspected egg allergies with vaccine skin testing or consideration for desensitisation.³ An egg-free yellow fever formulation is available as an alternative.

The Q fever vaccine is not available in Hong Kong and therefore is not covered in this guideline.

Influenza vaccine

Influenza vaccination is well known to be effective in preventing infections caused by influenza viruses and in reducing the risk of developing complications. We reviewed the product information recommendations of Vaxigrip (Sanofi Pasteur SA, Lyon, France), Fluarix Tetra (GlaxoSmithKline Biologicals, Dresden, Germany), and FluQuadri (Sanofi Pasteur SA, Lyon, France). All recommended that patients with egg or chicken protein hypersensitivity are contra-indicated to receive their vaccines. However, upon direct communication with the respective pharmaceutical companies, all of them were reported to contain [lesser than]0.1 ug/mL of ovalbumin in their vaccines. Therefore, we disagree with their recommendations.

Moneret-Vautrin et al⁵ reported that only 1% of egg-allergic patients would develop allergic reactions at a threshold as low as 1 mg. As the quantity of ovalbumin in influenza vaccines is ≤1 μg/dose, such a level of egg protein in influenza vaccines is very unlikely to trigger an allergic response in this group of patients. Thus, despite the product information recommendations and the trace amounts of ovalbumin present in these influenza vaccines, they should be safe for egg-allergic individuals, including those with a history of anaphylaxis to egg proteins.

Our view is supported by numerous international guidelines on administration of influenza vaccines to egg-allergic individuals, summarised in the Table.^{6 7 8 9 10 11 12}

Table. Summary of international recommendations onadministrating vaccines to egg-allergic individuals

Measles-mumps-rubella and measles-mumps-rubella-varicella vaccines

The MMR and MMR-V vaccines are safe and effective in preventing mumps, measles, rubella, and varicella. The vaccination schedule in Hong Kong recommends that the first dose be administered at age 1 year and the second dose at Primary 1 (age 5-6 years).¹³ We reviewed the product information recommendations of two MMR-V vaccines available in Hong Kong: Priorix-Tetra (GlaxoSmithKline plc [GSK], Brentford, UK) and ProQuad (Merck [and] Co, Inc, Kenilworth [NJ], US). The manufacturers of both of these products recommend that patients with severe allergic reactions after egg ingestion should take extra precaution when receiving the vaccines. However, in direct communication with the manufacturers, GSK replied that Priorix-Tetra may contain traces of egg protein but the amount is not measured in the final product. In contrast, Merck replied that internal analysis was done for ProQuad for its egg protein content; however, they refused to disclose the information as they consider it proprietary. We disagree with their recommendations. The Table summarises international recommendations for administration of MMR/MMR-V vaccines to egg-allergic individuals.^{6 11 14 15 16} It is recommended that all patients, including those with suspected or confirmed egg allergy, should receive the MMR/MMR-V vaccination as a matter of routine in primary care, as the vaccine does not contain egg allergen.

Recommendations of the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy [and] Infectious Diseases

1. All patients with suspected or confirmed egg allergy should receive the MMR/MMR-V vaccination as a matter of routine in primary care.

2. Influenza vaccines can be safely administered, and are recommended, for disease prevention in egg-allergic individuals. They are recommended to be administered in an out-patient or ambulatory setting.

3. Only those patients who have previously required admission to an intensive care unit for severe anaphylaxis to egg should be referred to an allergist for further evaluation prior to influenza vaccination.

4. Should there be any significant concerns from patients, parents or health care professionals, health care professionals who are capable of recognising signs and symptoms of an allergic reaction can provide 15 to 30 minutes of monitoring following vaccination.

5. Specialist evaluation is recommended prior to yellow fever vaccination in egg-allergic individuals (Fig).

6. Individuals who have developed or are suspected to have developed an allergic reaction to the vaccine or other vaccine components (such as gelatine or neomycin) should not undergo further vaccination with these products. Referral to an allergy specialist for further evaluation can be considered (Fig).

7. A significant number of suspected egg-allergic patients may be misdiagnosed, so referral to an allergist for evaluation may be considered.

Figure. Proposed workflow for vaccinating patients withsuspected egg allergy

Author contributions

GT Chua and PH Li drafted the main text of the article, including the tables and figures. E Lai and V Ngai offered their expert opinion as clinical pharmacists and contacted pharmaceutical companies regarding the contents of the vaccines. MHK Ho, MYW Kwan, FYS Yau, TF Leung, and TH Lee contributed to the concept, analysis, and critical revision of the article.

Funding/support

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Declaration

All authors have disclosed no conflicts of interest. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.

References

1. Leung TF, Yung E, Wong YS, Lam CW, Wong GW. Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: epidemiology, clinical spectrum and risk factors. Pediatr Allergy Immunol 2009;20:339-46.

2. Ho MH, Lee SL, Wong WH, Ip P, Lau YL. Prevalence of self-reported food allergy in Hong Kong children and teens—a population survey. Asian Pac J Allergy Immunol 2012;30:275-84.

3. Li PH, Wagner A, Rutkowski R, Rutkowski K. Vaccine allergy: a decade of experience from 2 large UK allergy centers. Ann Allergy Asthma Immunol 2017;118:729-31.

4. Centre for Health Protection, Department of Health, Hong Kong SAR Government. Frequently asked question on seasonal influenza vaccine 2015/16. Q14. Who should not receive inactivated seasonal influenza vaccination? Available from: http://www.chp.gov.hk/en/view_content/26837.html. Accessed 20 Nov 2017.

5. Moneret-Vautrin DA, Kanny G. Update on threshold doses of food allergens: implications for patients and the food industry. Curr Opin Allergy Clin Immunol 2004;4:215-9.

6. ASCIA Guidelines—Vaccination of the Egg-allergic Individual. Australian Society of Clinical Immunology and Allergy; 2017.

7. Centers for Disease Control and Prevention, Department of Health & Human Service, USA Government. Flu vaccine and people with egg allergies. Available from: https://www.cdc.gov/flu/protect/vaccine/egg-allergies.htm. Accessed 20 Nov 2017.

8. Greenhawt M, Turner PJ, Kelso JM. Administration of influenza vaccines to egg-allergic recipients: a practice parameter update 2017. Ann Allergy Asthma Immunol 2018;120:49-52.

9. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2017-2018. Pediatrics 2017;140:e20172550.

10. British Society for Allergy & Clinical Immunology Paediatric Committee. 2015/16 Influenza vaccine recommendations for children with egg allergy. Available from: http://www.bsaci.org/Guidelines/Flu%20jab%20egg%20allergic%20kids.pdf. Accessed 20 Nov 2017.

11. Dreskin SC, Halsey NA, Kelso JM, et al. International Consensus (ICON): allergic reactions to vaccines. World Allergy Organ J 2016;9:32.

12. United Kingdom government. The Green Book. 2014. Available from: https://www.gov.uk/government/collections/immunisation-against-infectious-disease-thegreen-book. Accessed 20 Nov 2017.

13. Family Health Service. Department of Health. Hong Kong SAR Government. Hong Kong childhood immunization programme. Available from: http://www.fhs.gov.hk/english/main_ser/child_health/child_health_recommend.html. Accessed 20 Nov 2017.

14. Centers for Disease Control and Prevention. Vaccine safety—measles, mumps, rubella, and varicella vaccine. Available from: https://www.cdc.gov/vaccinesafety/vaccines/mmrv-vaccine.html. Accessed 20 Nov 2017.

15. American Academy of Pediatrics. Measles. In: Kimberlin DW, Brady MY, Hackson MA, editors. Red Books: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.

16. British Society for Allergy & Clinical Immunology. BSACI recommendations for combined measles, mumps and rubella (MMR) vaccination in egg-allergic children. 2007. Available from: http://www.bsaci.org/guidelines/mmreggrecommendations.pdf. Accessed 20 Nov 2017.