Introduction
Review
Clinical approach
Potential allergens
Vaccine component
|
Studies
|
Partecipants, N
|
Allergic reactions N (%)
|
---|---|---|---|
Egg | Measles-mumps-rubella | ||
Goodyear-Smith et al. 2005 [9] | 73 | 0 (0%) | |
Erlewyn-LajeunesseM et al. 2008 [10] | 100.000 | 42 (0.04%) | |
Govindaraj P et al. 2009 [11] | 45 | 0 (0%) | |
Cronin J et al. 2012 [12] | 310 | 6 (1.9%) | |
Andersen DV et al. 2013 [13] | 32 | 0 (0%) | |
Total | 100.460 | 48 (0.04%) | |
Influenza | |||
Cerecedo C et al. 2007 [27] | 26 | 0 (0%) | |
Esposito S et al. 2008 [28] | 44 | 3 (6.8%) | |
Chung E et al. 2010 [29] | 171 | 29 (16.9%) | |
Gagnon R et al. 2010 [24] | 830 | 9 (1.08%) | |
Greenhawt MJ et al. 2010 [30] | 105 | 0 (0%) | |
Pien GC et al. 2010 [31] | 62 | 0 (0%) | |
Webb et al. 2011 [32] | 152 | 2 (1.3%) | |
Erlewyn-Lajeunesse M et al. 2011 [21] | 3640 | 88(2.41%) | |
Howe et al. 2011 [25] | 135 | 0 (0%) | |
Owens et al. 2011 [33] | 64 | 4 (6.25%) | |
Shuler JE et al. 2011 [34] | 62 | 4 (6.4%) | |
Fung et al. 2012 [35] | 56 | 2 (3.5%) | |
Greenhawt MJ et al. 2012 [26] | 105 | 0 (0%) | |
Wainwaring Upton JE et al. 2012 [36] | 77 | 0 (0%) | |
Des Roches et al. 2012 [23] | 367 | 13 (3.54%) | |
Forsdhal BA et al. 2012 [37] | 80 | 3 (3.75%) | |
Total | 5982 | 157 (2.62%) | |
Yeasts | DiMiceli L et al. 2006 [45] | 107 | 15 (14%) |
Dextran | Zanoni G et al. 2008 [62] | 100.000 | 19 (0.01%) |
Thimerosal | Wattanakrai P et al. 2007 [72] | 46 | 0 (0%) |
Egg
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MMR vaccine - Measles-Mumps-Rosolia (MMR) vaccine is grown on cell cultures employing chicken embryo-fibroblasts. This vaccine contains minimal amounts of egg proteins, from nanograms to picograms, often not precisely reported. Therefore, this vaccine shows a very low risk of allergic reactions, even in egg’s anaphylaxis [9-13] (Table 1). In Europe, prevalence of anaphylaxis due to MMR vaccine is estimated at 1.2 cases per million doses [14]. In the US, an incidence of 3.5 cases per 1,000,000 doses has been reported [15]. Interestingly, the vast majority of allergic reactions to MMR is observed in patients without egg allergy [16]; hence, it is probable that the real triggers are other vaccine’s components, such as gelatin [17]. Available data show no additional risk for immediate reactions in egg-allergic children, compared to non allergic, with commercial MMR or measles vaccines. In the Italian National Health Instiute website it is clearly reported that all children with egg-allergy must be vaccinated and no specific precautions are needed, not even in previous egg anaphylaxis [18]. However, a review [16] that analyzed all severe allergic reactions to MMR referred from 1966 to 1999, reported 14 local reactions and 16 systemic reactions in 1803 egg-allergic children undergone to MMR vaccine. None of these reactions was fatal. In 3 out of 16 systemic reactions a proper anamnesis was collected and it was positive for a previous severe allergic reaction after egg ingestion and/or a chronic asthma. Therefore, it has been suggested, in case of severe previous egg anaphylaxis or moderate reactions in chronic active asthma, to administer the vaccine under hospital supervision. Sensitivity and specificity of skin prick test with MMR vaccine are low and not predictive of serious reactions, thus are not recommended [19,20].
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Influenza vaccine - Despite a theoretical risk of hypersensitivity reactions to minimal amount of egg-proteins [21,22] in influenza vaccine, studies, including papers and abstracts, from 1977 to 2012 showed that in 4172 egg-allergic patients (and 513 with severe allergic reaction), safety of influenza vaccine has been proven, with especial regard to both severe anaphylactic reactions (respiratory distress or hypotension) and mild reactions (urticaria or mild wheezing) [23]. These allergic reactions rates did not differ significantly from those in non-egg-allergic controls [24-26]. In investigations published in the last ten years [21,23-37] the frequency of allergic reactions to vaccine was 2.62% in 6532 subjects (Table 1). The American Academy of Paediatrics [19] has recently stated that the risks of missing influenza vaccination outweigh those from vaccination itself. Therefore, egg allergy of any severity (including anaphylaxis) is not a contraindication to the administration of influenza vaccine. However, influenza vaccine should be administrated when resuscitation facilities are available, and the patient should be observed in the office for 30 minutes after immunization [19]. In egg-allergic patients the injectable vaccine should be preferred rather than intranasal preparation because of an higher amounts of ovalbumin in the latter [5]. Influenza vaccine contains less than 1 μg/dose of ovalbumin. Those with an higher amount (more than 1.2 μg/mL) should be avoided in egg-allergic subjects [38]. Influenza vaccine cultured on human cells or insect culture are not approved for pediatric use.
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Administration of influenza and MMR vaccines - All egg-allergic children can receive influenza or MMR vaccine in primary care physician’s office. Or in vaccination centre provided with appropriate equipment and medications and with a 60 minutes post-vaccine observation (Table 2). It is recommended to investigate all suspected egg allergy before vaccination. Due to low sensitivity and specificity, skin prick test with influenza vaccine is not recommended. As well, divided doses of vaccine is not required because even in most severe egg-allergy vaccine can be tolerated in full dose. Children with a previous history of severe reactions to egg (anaphylaxis) should instead receive their vaccine in a hospital supervision [16]. This recommendation, however, shows a low grade of strength and should be reviewed in the future guidelines [39].Table 2Vaccination protocols in allergic subjectsAllergenVaccineVaccination protocolSettingEggYellow fever* Rabies* ° Influenza MMR Tick-borne en- cephalitisMMR and Influenza:1) If egg-allergy normally administer with a 60 minutes observation1) Office2) If egg-anaphylaxis normally administer with a 60 minutes observation2) HospitalYellow fever:1) If skin tests are negative: normally administer with a 60 minutes observationHospital2) If skin tests are positive: desensitization/graded dosesCow’s milkOPV, DTP, DT, DTaP, PCV-13If previous anaphylaxis normally administer with a 60 minutes observationOfficeYeastsHepatitis B, Quadrivalent HPV, meningococcal , PCV-13, typhoid (oral)1) If skin tests with vaccine are negative: normally ad- minister with a 60 minutes observationHospital2) If skin tests with vaccine are positive: desensitiza- tion/graded dosesNeomycinMMR, IPV, rabies, influenza, varicella, Zoster HepA1) If local skin reaction: normally administerOffice/Hospital2) If anaphylactic reaction: no vaccineGelatinMMR*, Varicella*, Zooster*, Yellow fever* Rabies °, DTP Influenza1) If skin tests are negative: normally administered with a 60 minutes observationHospital2) If skin tests are positive: gelatin-free vaccine or de- sensitization/graded dosesLatexWhen vaccine has no removable contaminated part (prefilled syringe), vaccine should be normally administered with a 60 minutes observationHospital
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Yellow fever vaccine - Yellow fever is an acute viral disease caused by Flavivirus and transmitted by the bite of mosquito (Aedes Aegypti). It is endemic in South America and Africa and has an high mortality. Yellow fever vaccination is, therefore, required for traveling in endemic countries. Yellow fever vaccine is grown in chicken embryos and contains higher amounts of egg-proteins in comparison with MMR and influenza vaccines. Unlike influenza and MMR vaccines, all subjects with egg-allergy and previous systemic reactions should receive yellow fever vaccine under hospital supervision. Patients with egg allergy should be evaluated before vaccination, with skin prick test and serum specific IgE to eggs [39]. When there is an history of anaphylaxis to egg, it may be performed a skin prick test with a 1/10 dilution of vaccine, and, if negative, with undiluted vaccine. If skin prick tests are negative, an intradermal test should be performed with a 1/100 dilution (1/10 dilution has been demonstrated to be irritative) [39]. If all skin tests are nega-tive, vaccine could be normally administered, with a 60 minutes post-vaccine observation (Table 2). If skin tests are positive, vaccine should be injected in graded dose under hospital supervision. It has been demonstrated that an intradermal 1/5 dose of vaccine could be protective and safe in egg allergy subjects who have shown a severe local urticaria reactions [40].
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Rabies vaccine - A rabies vaccine without egg and gelatin is available. Therefore such vaccine should be administered to subjects with severe allergy to egg protein or gelatin (Table 2).
Milk
Yeasts
Additives
Stabilizers
Gelatin
Dextran
Preservatives
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Thimerosal - Thimerosal is an organic mercurial (46% mercury) compound, metabolized to ethyl-mercury and thiosalicilate. This preservative has been used by pharmaceutical corporations since 1930 for ophthalmological, dermatological, otolaryngological purposes, for endovenous immunoglobulin, and vaccine preparation. Previously available vaccines containing thimerosal were DTP, Haemophilus Influentiae, DT, hepatitis B, Influenza, Neisseria Meningitis, Steptococcus Pneumoniae and Rabies vaccines. In 1998 the “Centers of Disease Control and Prevention” has recommended the complete removal of thimerosal from vaccine, because of a possible cerebral toxicity induced by this preservative. Indeed, the cumulative amount of methyl-mercury to which children were exposed in the first 6 months of life exceeded the recommended dose of 187,5 mcg, that has been assessed as inoffensive [64]. From 2001, in developed countries, thimerosal has been removed from pediatric vaccines. Nevertheless, some preparations of Td, DT, influenza (mainly in multi dose vials), meningococcal (multidose vials) vaccines could contains minimal, not significant, trace amounts (<1 mcg/0,5 ml). However mercury’s toxicity has never been fully demonstrated by scientific studies, and toxic levels were extrapolated from studies conducted on methyl-mercury’s toxicity, which is way more toxic and has a half-life 7 times less than mercury [65]. Current evidence sustains the safety of the use of thimerosal as a preservative for inactivated vaccines [66] . This supports the administration of multidose vials of thimerosal-preserved vaccines, especially in low- and middle-income countries, where they are a critical part of immunization programs [67]. Thimerosal’s sensitization could be investigated by patch tests and it is detectable in 10% of the general population. It is more frequent in those countries that are more exposed to thimerosal containing preparations, in patients affected by atopic dermatitis or conjunctivitis and in subjects treated with desensitization thimerosal-containing therapies [68]. Thimerosal is responsible for delayed hypersensitivity reactions, among which atopic dermatitis and local skin injection reactions [69]. Only one generalized cellular-mediated reaction has been reported after influenza vaccination [70]. Even in patch positive subjects, exposure to thimerosal is considered safe [68,71] and no contraindications are reported [72].
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Phenoxyethanol – 2-phenoxyethanol (2-PE) is an antibacterial additive associated with delayed hypersensitivity reactions. Sensitization’s rate to 2-PE is pretty low, local allergic reactions are rare and no systemic reaction has been reported [73].
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Antibiotics - Many vaccines contain little amounts of antibiotics such as neomycin, aminoglycosides, streptomycin, polymixin, tetracycline, and the fungicide amphothericin B, to prevent bacterial and fungal contamination. No vaccine contains beta-lactams or sulfonamides. Until now, only a few case-reports of vaccine adverse reactions due to antibiotics has been reported [5]. Although, a proven anaphylaxis or allergy to one or more antibiotics contained in vaccines is considered an absolute contraindication to those vaccines.