adverse reactions to vaccines for infectious diseases

Adverse Reactions to Vaccines for Infectious Diseases

Suda Sibunruang, M.D.

Picture from www.med.umich.edu

Contents• Overview of vaccine adverse events• Type of reactions• Potential allergens in vaccines • Diagnosis and management

The ideal vaccine should be…• Non- reactogenic • Easy to administer• Highly immunogenic• Long-lasting immunity

No currently available vaccine meets all of these criteria

Moylett E. and Hanson C. J Allergy Clin Immunol 2004;114:1010-20

Access from www.cdc.gov , 4 November 2014

Picture from http://sciencebasedpharmacy.filesAccess 4 November, 2014

Kelso J. and Greenhawt M. Middleton’s Allergy 8th edition, 2013, 1384-1403

Picture from www.vaclib.org

Evolution of an immunization program

Vaccine adverse events (AE)

• 20 vaccines are currently in use• Billions of doses are administered worldwide• Vaccine induced AE ranges between 3- 83 /100,000 doses according to post-marketing surveillance data

Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

Moylett E. and Hanson C. J Allergy Clin Immunol 2004;114:1010-20

Allergic reactions to vaccines

• Range from 1/50,000 doses for DTP vaccine to about 1 per 500,000 to 1,000,000 doses for most other vaccines

Wood RA, Setse R, Halsey N. J Allergy Clin Immunol 2007;120:478-81Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

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Access from http://thaihpvc.fda.moph.go.th 31 October 2014

Report of vaccine ADR in 2012 688/ 55,747 = 1.23%

Spontaneous reports of adverse drug reaction 2012 ศู�นย์�เฝ้�าระวั งควัามปลอดภั ย์ด�านผล�ตภั ณฑ์�สุ�ขภัาพ สุ าน กงานคณะกรรมการอาหารและย์า

Access from http://thaihpvc.fda.moph.go.th 31 October 2014

Example

Hypersensitivity reactions followingimmunization

• Extent: local - systemic• Timing: immediate - non-immediate• Frequency: common - rare• Severity: minor- moderate- major

Hypersensitivity reactions followingimmunization

• Extent: local - systemic• Timing: immediate - non-immediate• Frequency: common - rare• Severity: minor- moderate- major

Local reactions• Most frequent adverse event• Often falsely labeled as allergic

Caubet JC. and Ponvert C. Immunol Allergy Clin N Am 2014;34:597-613

Types of local reactions• Mild local reactions• Large local reactions/ Extensive limb swelling• Subcutaneous nodules• Local eczema• Nevi associated with hypertrichosis

Mild local reactions

• Most frequent• Non-specific inflammation - Tissue damage by the puncture - Injection of foreign material

Large local reactions

• Less common • Varied vaccines, particularly those

containing toxoids and/or adjuvants

Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403Caubet JC. and Ponvert C. Immunol Allergy Clin N Am 2014;34:597-613

Large local reactions

Two patterns1. Typical large local reactions2. Extensive limb swelling

Typical Large local reactions

• Occur typically within 24–72 h• Result of 2 mechanisms- Antigen/adjuvant Toll Like Receptor (TLR)-induced inflammation - Arthus reaction

Residual antibodies still present in the host due to previous sensitization

Picture from http://classconnection.s3.amazonaws.com

Rate of local reactions• Higher after receiving multiple

doses of certain vaccines• Shorter interval between the doses

was not associated with higher rates

Extensive limb swelling

• Less common but may be impressive• Extend at least to the elbow or knee• Arises within 24 h • Looks like a benign reactive edema • Probably results from extravasation

mechanisms• Usually painless

Subcutaneous nodules• Common in vaccines containing

aluminium salts (19% of patients)

Subcutaneous nodules

• Nonspecific inflammation • Correlation between concentration of

aluminium hydroxide and frequency and size of nodules

• Regress within a few weeks• Patch tests are often negative • Few cases of persistent nodules (most of

them had positive patch tests)

Local eczema

• Vaccines containing aluminium hydroxide, thimerosal and formaldehyde

• Reported mainly in adults• May extend beyond the injection area or

become generalized• A non-immediate hypersensitivity has

been suggested by positive patch testsCaubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

Nevi associated with hypertrichosis

• Reported after BCG, tetanus, and smallpox vaccination (rarely)• The causal components responsible

for the reaction, as well as the exact pathomechanisms remain unknown

Systemic reactions• 5–13% of the patients being vaccinated• Most frequent symptoms include fever,

rash, drowsiness and irritability• Most result from non-specific

mechanisms

Systemic reactions• Distinguish between immediate

reactions (IgE-mediated) and non-immediate reactions (non-IgE-mediated)• Vasovagal attacks associated with

injections are common

Vanlandera A. and Hoppenbrouwers K. Vaccine 2014;32:3147–54

Number of students suffering adverse events following MMR campaign in Australia, 1998 (n=651,615 students)

Adverse event Faint/syncopeSyncopal fitAnaphylaxisHyperventilationRashLocal allergic reactionSevere immediate local reactionArthropathyFeverAnxietyLymphadenopathy

Number 1713432211111

Source : Communicable Disease Intelligence (Australia), 29 October 1998

Bohlke K. et al. J Allergy Clin Immunol 2004;113:536–42

Method: identified anaphylaxis between 1991-1997 from automated databases and reviewed medical record Result: 5 cases of vaccine-associated anaphylaxis after 7,644,049 vaccine doses (0.65 cases/million doses)

Immediate reactions• 1–3 reactions per million vaccine doses • Amounts of patients reported reaction after

first vaccination suggests either a pre-sensitization to a vaccine component or

non-immunologically mediated reaction• Identification is important because risk of life

threatening anaphylaxis if re-exposure

Kelso J. et al. J Allergy Clin Immunol 2012;130:25–43Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

Fritsche P.,Helbling A.,Ballmer-Weber BK. Swiss Med Wkly 2010;140:238 – 46

Non-immediate reactions• Common symptoms include MP rash, delayed

onset urticaria, and erythema multiforme• Other immunologic reactions (i.e. serum sickness, Henoch Schonlein Purpura) are even rarer

Picture from www.biofarma.co. Access 31 October 2014

Components of vaccines

Kelso J. et al. J Allergy Clin Immunol 2012;130:25–43

Picture from www.vaccinesafety.edu

Vaccine components• Microbial components• Gelatin• Egg & chicken protein• Milk• Yeast• Latex

• Aluminium• Thimerosal• Antibiotics• Dextran• Rare allergic

components

Microbial components• Anaphylactic reactions have been reported• However, IgE-mediated reactions to vaccines

are more often caused by additive or residual vaccine components

Kelso J. et al. J Allergy Clin Immunol 2012;130:25–43Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

Gelatin• Produced by partial hydrolysis of

collagen extracted from connective tissues of animals, such as cows or pigs

• Contains potentially allergenic protein• Bovine and porcine gelatins are

extensively cross-reactive

Kelso J. J Allergy Clin Immunol 2014;133:1509–18

Gelatin• The incidence of gelatin allergy appears

to be higher in Japan, perhaps because of an HLA type (DR 9) common in Japanese

Kelso J. J Allergy Clin Immunol 2014;133:1509–18Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

• Influenza (Fluzone, FluMist)• Japanese

encephalitis• MMR• MMRV• Rabies (RabAvert)

• Tick-borne encephalitis

• Typhoid vaccine, live oral

• Varicella• Yellow fever• Zoster

Gelatin-containing vaccines

Kelso J. Ann Allergy Asthma Immunol 2013;110:397-401

Ranging from 250 to 15,580 µg per dose

Kelso J. et al. J Allergy Clin Immunol 1993;91:867-72

Sakaguchi M., et al. J Allergy Clin Immunol 1996;98:1058-61

Objective: relation between systemic allergic reactions to vaccines and the presence of anti-gelatin IgE Patients: 26 children who had systemic immediatereactions to vaccines-containing gelatinControl: 26 children without allergic reactions to vaccines

• Nine showed severe anaphylaxis (Skin + airways +/- shock)• Ten had mild anaphylaxis (skin +/- airways + others)• Seven had only urticaria

All the control children had no anti-gelatin IgE

7/26 had allergic reactions on ingestion of gelatin-containingfoods

Conclusion: 1. Strong relationship between the systemic reactions and anti-gelatin IgE in the sera2. Questioning of vaccine recipients about allergy associated with the ingestion of gelatin-containing foods may help to prevent anaphylaxis3. It appears that vaccination triggered the later onset of food allergic reactions to gelatin

Recommendation• Patients experienced anaphylaxis after

ingestion of gelatin should be evaluated prior to receiving a gelatin-containing vaccine

• Symptomless consumption of gelatin does not exclude an allergy to gelatin, as other routes of sensitization have been incriminated

Recommendation• Patients sensitized to pork or beef are at

higher risk of reaction to gelatins, and caution should be taken when administrating gelatin-containing vaccines

Nakayama T. and Onoda K. Vaccine 200;25:570–6

Prick test to gelatin• Dissolve 1 teaspoon (5 grams) of

sugared gelatin powder in 5 cc NSS

Ovalbumin-containing vaccines

• Influenza (IIV, LAIV)• MMR• Rabies (PCEC)• Yellow fever

Picture from www.medindia.net

Picture from http://online.wsj.com

Kelso J. J Allergy Clin Immunol 2014;133:1509–18Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

MMR & PCEC contain negligible of egg protein, thus can be administered to recipients with egg allergy

in the usual manner

Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403.

Raw egg allergy

Kelso J. J Allergy Clin Immunol 2000;106:990

Raw egg allergy• Vaccine is not heated at any time during

the manufacturing process• Perhaps some of reactions are due to

unrecognized raw egg allergy

Kelso J. J Allergy Clin Immunol 2000;106:990

Rutkowski K. et.al. Int Arch Allergy Immunol 2013;161:274–8

Chicken proteins• Can also be found in some vaccines (i.e.

yellow fever vaccine) • May be responsible for reactions in chicken-

allergic recipients

Milk• Casamino acids• Casein• Lactalbumin

Casamino acids/casein -containing vaccines

• Growth media for these vaccines contain casamino acids derived from casein

• Nanograms quantities of casein are present in the vaccines

Casamino acids-containing vaccines

• DTaP (Daptacel)• DTaP-IPV/Hib (Pentacel)• Td (Tenivac)• Tdap (Adacel)• Meningococcal (Menomune)• Pneumococcal (PCV13 – Prevnar 13)

Casein-containing vaccines

• DTaP (Infanrix)• DTaP + HepB + IPV (Pediarix)• DTaP + IPV (Kinrix)• Tdap (Boostrix)• Typhoid (Vivotif)

lactalbumin-containing vaccines

• OPV

Kattan JD, et al. J Allergy Clin Immunol 2011;128:215-8

Background:Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein or that the C. tetani is grown in modified Mueller-Miller casamino acid mediumMethod: 1. Reviewed 8 children with anaphylaxis to booster doses of DTaP, DTP, or Tdap2. Tested 8 lots of the vaccines for residual casein

Result:• 6/8 of the patients had prior acute allergic reactions to cow’s milk• All had an increased milk-specific IgE level documented within 2 years of the reaction to the vaccine

Conclusion:Continuing the standard practice for DPT vaccination in all children, but advise caution when administering booster doses in highly sensitive milk-allergic children

Yeast• Hepatitis B and human papillomavirus

(HPV) vaccines are manufactured using recombinant strains of Saccharomyces cerevisiae (common bakers’ yeast) and contain residual yeast proteins

Picture from www.ied.edu.hk

Yeast protein • Hepatitis B vaccines - up to 25 mg/dose• Quadrivalent HPV vaccine < 7 mg/dose

DiMiceli L. et al. Vaccine 2006;24:703–7

Period: 1990 – 2004Method: passive surveillanceResult: • 1991–2001,276 million doses of HBV were distributed• 180,895 (all vaccines) AE reports to VAERS• 107 patients had prior history of allergy to yeast• 82/107 received HBV• 15/107 had anaphylaxis (11 HBV+ 4 other vaccines)

DiMiceli L. et al. Vaccine 2006;24:703–7

Conclusion:Recombinant yeast derived HBV pose minimal riskof allergic reactions in yeast sensitive individuals

Yeast• Skin tests with yeast-containing vaccines

should be carried out prior to administration to patients with history of yeast allergy

• If positive, vaccine can still be administered, but in graded doses

Latex • Contains naturally occurring impurities (e.g., plant proteins and peptides)• Can be processed in 2 different ways1. Natural rubber latex (NRL) - Medical gloves, catheters2. Dry natural rubber (DNR) - Vial stoppers and tip of syringe plungers

Russell M., et al. Vaccine 2004;23:664–7

Latex • Physical contact of the liquid vaccine

with the stopper can cause the release of latex allergens into the solution

• Passing the needle throughout the stopper and by retaining latex allergens in or on the needle

Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403Kelso J. and Greenhawt M. Middleton’s Allergy 8th edition, 2013, 1384-1403

Latex Theoretical risk • Administration of vaccines that have

been in contact with such packaging could induce immediate-type allergic reactions in latex allergic recipients

Russell M. et al. Vaccine 2004;23:664–7

Period: 1991 – 2003Method: Reviewed cases with prior allergy to latex and developed immediate reactionsResult: • 167,233 (all vaccines) AE reports to VAERS• 147(0.1%) patients had prior history of allergy to latex• 28/147 (19%) developed a possible allergic AE• 14 cases reported a history of allergy to various drugs, foods or aeroallergens

Result (continue):• 11 (39%) received influenza vaccines• 4 (21%) received hepatitis B vaccines• The remaining reported hepatitis A vaccine,MMR tetanus and diphtheria toxoids, IPV, varicella vaccine, anthrax vaccine adsorbed, and yellow fever vaccine

Conclusion:• Minimal risk of immediate allergic reactions to immunized latex-sensitive individuals using vaccines that contain DNR in the packaging

“ If a person reports severe allergy to latex, vaccines supplied in vials or syringes that contain natural rubber latex should not be administered

unless the benefit of vaccination clearly outweighs the risk for a potential allergic reaction.

In these cases, providers should be prepared to treat patients who are having an allergic reaction.

For latex allergies other than anaphylaxis, vaccines supplied in vials or syringes that contain

dry, natural rubber or natural rubber latex may be administered ”

General recommendations on immunization: recommendations of ACIP. MMWR 2011;60:RR1-64

Latex• Avoid passing the needle through the

stopper• Stopper should be removed and the

vaccine drawn up directly from the vial

Kelso J. Ann Allergy Asthma Immunol 2013;110:397-401Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

Latex • Vaccine vial stoppers and syringe

plungers are made of synthetic rubber and pose no risk to latex-allergic persons

www.cdc.gov/vaccines/pubs/pinkbook/pink-appendx.htm

Aluminium• Persistent itching, subcutaneous nodules, or

granulomas at the injection site• Hyper- and hypopigmentation, hypertrichosis,

and lichenification have been associated with such nodules

• In rare cases, nodules become inflammatory and turn into an aseptic abscess

• Transient but can sometimes persist for a few weeks or even years

Aluminium• In aluminium-sensitized patients requiring a

vaccine containing aluminium, the injection should be administered deep enough as intramuscular administration may prevent the formation of granulomas

Thimerosal• One of the most effective preservative,

improving vaccine stability, potency, and safety

• However, it has been less used over the last decades in childhood vaccines, as a precautionary measure due to its mercury content

Thimerosal• Not definitely caused immediate reactions• Non-immediate reactions (contact dermatitis and generalized MP rash)

Thimerosal• If possible, alternative vaccines not

containing this preservative should be chosen• The vast majority of patients with proven

sensitization to thimerosal as demonstrated by positive patch tests tolerate thimerosal-containing vaccines

Antibiotic containing vaccines

Antibiotics• Some vaccines (i.e. polio, MMR, and

influenza vaccines) may contain traces of antibiotics used for viral culture to avoid bacterial and fungal contamination during the manufacturing process

Antibiotics• Although antibiotics in vaccines theoretically

could cause anaphylactic reactions, there is no report of confirmed immediate reactions

• Nevertheless, the few patients who have a confirmed immediate allergy to one of these antibiotics should not receive vaccines containing them

Neomycin containing vaccines in Switzerland

Neomycin• Only single report of anaphylaxis• Topical neomycin is known to elicit contact

dermatitis (delay-type reactions: DTR)• However, amount of neomycin found in

vaccines is not believed to trigger DTR• Thus, these vaccines may be given to patients with DTR to neomycin

Kelso J. et al. J Allergy Clin Immunol 2012;130:25–43Fritsche P.,Helbling A.,Ballmer-Weber BK. Swiss Med Wkly 2010;140:238 – 46

Other antibiotics• Streptomycin, gentamycin, polymyxin B

sulphate and chlortetracycline have been reported to trigger allergic reactions in clinical use

• But… in term of vaccination they have not yet been identified as a causative agent of severe allergic reactions

Dextran• Immediate reactions to BCG, and to some

MMR vaccines• MMR containing dextran have now been

withdrawn from the market• Now, may present in some rotavirus vaccines• Non-immediate reactions to dextran are rare

Rare allergenic components• Polysorbate (Tween), polygelines,

amphotericin B, protamine sulphate and phenol red

• No evidence for hypersensitivity reactions of these substances linked to vaccination

Diagnosis & Management

“ Accurate diagnosis of vaccine allergy is important not only to prevent serious or even life-threatening reactions, but also

to avoid unnecessary vaccine restriction ”

Two circumstances bring patients to allergists

1. Experienced adverse events following immunization

2. Possible allergy to some vaccine component, but have never received the vaccine

1. Experienced adverse events following immunization

Patient received an immunization experienced an adverse event

• Immunization may or may not have caused AE• If causal, the mechanism may or may not have been immunologic• If immunologic,the mechanism may or may not have been IgE mediated

Whether such patients can receive additional doses of the suspect vaccine ?

Determine nature of AE - IgE mediated ?

Testing for IgE to the vaccine andvaccine components

Determination of culprit allergen is important because the same ingredient may be

found in other vaccines

2. Possible allergy to some vaccine components, but have never received the vaccine

Whether such patients can receive vaccines that contain these components ?

Determine nature of reaction - IgE mediated ?

Testing for IgE to suspect allergen

Even patients have specific IgE to a vaccine and/or vaccine component,

it is still likely that they can be immunized with appropriate precautions

Caubet JC. and Ponvert C. Immunol Allergy Clin N Am 2014;34:597–613

+/- IgE

Start with a detailed history

Wood R., et al. Pediatrics 2008;122:e771–7

+/- IgE

Management of local reactions (1)

• Mostly, local reactions subside spontaneously without sequelae

• No association with a higher rate of systemic reactions on re-exposure

Management of local reactions (2)

• Usually, no allergy test is required• Serum vaccine-specific antibodies (IgM

or IgG) are indicated in patients with suspicion of Arthus reaction

Patch test• Demonstrate a delayed hypersensitivity to

preservatives or adjuvants• They are not accurate for the purpose of

assessing a patient’s ability to tolerate a vaccine

• Positive patch test may guide clinicians to administer a vaccine free of these components, if available

Prevention of local reactions (1)

• Correct needle length Longer needle - -> lower rate of local reactions• Site of injection Injection in the thigh in children < 3 years• Receive a vaccine free of the sensitized

component, if available

Prevention of local reactions (2)

• In patients reporting important local inflammatory reactions after injection of combined vaccines, sequential injections of single or limited numbers of vaccinating agents, every few days, preferably intramuscularly, are usually well tolerated

+/- IgE

Immediate reaction• Allergologic work-up should be carried out

even if no further doses of the suspected vaccine are required

• Potential for cross-reaction with common components in other vaccines and foods

Seitz C. et al. Vaccine 2009;27:3885–9

Method: patients diagnosed of vaccine-induced anaphylaxis were subjected to standardized allergy testingObjective: 1. identify vaccination-associated IgE-mediated anaphylaxis 2. proofed reliability of reporting vaccine-induced allergic anaphylaxis by HCW

Skin & SC Respiratory or CVS or GIHypoxia, hypotension, neuro

undiluted vaccine for prick testwith positive-negative control

10%;30%;60%1 hr interval

tetanus-/diphtheria-toxoid (17×), hepatitis A/B (8×),TBE (7×), influenza (6×)

without history ofallergy to egg, yeast, ATB

Conclusion:• History of anaphylaxis after vaccination may not be absolute contraindication for re-vaccination• All anaphylaxis in fact not induced by an IgE-mediated vaccine allergy

+/- IgE

Skin test• Should be performed with the same brand

Prick method with undiluted vaccine

Intradermal skin test with 0.02 cc of vaccine diluted 1:100

If negative

Skin test• If the initial vaccine reaction was life

threatening, it is appropriate to use diluted vaccine for the skin prick test

Diagnostic course of SPT with vaccines

Skin test• If positive skin test result, the same vaccine

skin test should be conducted in several control subjects who have received vaccine without adverse reaction

Skin test• Sensitivity and specificity are not optimal, but the main purpose of these tests is to identify patients who are at real risk of developing a severe anaphylactic reaction in case of re-exposure

Skin test• Intradermal skin tests with some

vaccines, such as tetanus toxoid, can also induce delayed-type hypersensitivity responses

+/- IgE

Observe 30 min afterward

Negative skin test• If the patient has a history strongly

suggestive of a severe anaphylactic reaction• Some authors still recommend to administer

the vaccine in 2 doses (10% followed 30 min later by the remaining 90%)

Vaccine administration• Administration of a vaccine should be

performed in a secure environment (trained personnel onsite and emergency drugs available)

+/- IgE

Risk Benefit

Patient’s immune status to the vaccine

Immune status to the vaccine

• Measurement of antibodies to the immunizing agent in a vaccine

• If a patient has already maintains protective levels of antibody, withholding or delaying subsequent doses may be appropriate

Kelso J. Ann Allergy Asthma Immunol 2013;110:397-401Caubet JC., et al. Pediatr Allergy Immunol 2014: 25: 394–403

+/- IgE

Rutkowski K. et.al. Int Arch Allergy Immunol 2013;161:274–8

Micheletti F. et al. Clinical & Experimental Allergy 2012;42:1088-96

“ Egg allergy of any severity (including anaphylaxis) is not a contraindication to the administration of influenza vaccine but rather a precaution ”

• Skin testing before administration is not recommended because of its low sensitivity and specificity in predicting serious reactions

• Dividing the dose of vaccine is also not required because most even severely egg allergic patients can tolerate the full vaccine dose without reaction

• 27 published studies• 4172 patients with egg allergy received 4729 doses of inactivated influenza vaccine• Including 513 with severe allergy who

uneventfully received 597 doses

Egg-allergic patients and Influenza vaccinations

No cases of anaphylaxis

Very low amount of egg protein present in vaccine

McKinney K. et.al. J Allergy Clin Immunol 2011;127:1629–32

Background:1. Skin test might not be necessary if IIV contains low amount of ovalbumin2. Individual manufacturers produce 18-145 lots of IIV/season

Objective3. Determine ovalbumin content in influenza vaccines 4. Determine the lot-to-lot variability within a manufacturer

Method: Ovalbumin ELISA kit

McKinney K. et.al. J Allergy Clin Immunol 2011;127:1629–32

There is still uncertainty with lot-to-lot variability and variability from year to year and

manufacturer to manufacturer

Prevention and control of seasonal influenza with vaccines. Recommendations of ACIP. MMWR Morb Mortal Wkly Rep 2013;62:1-43

Two new IIVs not grown in eggs have beenapproved for patients ≥18 years

Flucelvax: virus propagated in cell culture

FluBlok: recombinant hemagglutinin proteins produced in an insect cell line

Picture from www.flublok.com

No published studies on the safety of LAIV in recipients with egg allergy, guidelines recommend

the use of IIV in these patients

Recommendations regarding influenza vaccination of persons who report allergy to eggs- US-ACIP,2014–15 influenza season

“ The only precaution is administration ina setting where anaphylaxis can be recognized and treated and patients should remain under observation for at least 30 minutes after vaccination ”

Egg-allergic patients and vaccinations

• Other vaccines containing egg protein, particularly yellow fever, it is still recommended to test the vaccine before administration. In case of positive testing, the vaccine can be administered in graded doses

Allergy to influenza vaccine• Additional evaluation is appropriate,

including skin testing with the vaccine and vaccine ingredients.

• If positive skin test, vaccine can be administered in multiple divided doses or can be withheld

In summary• Overview of vaccine adverse events• Type of reactions• Potential allergens in vaccines • Diagnosis and management

Take home messages (1)• Mild local reactions and fever after

vaccinations are common and do not contraindicate future doses

• Anaphylaxis to vaccines are rare and should be further evaluated

• If the test are negative, subsequent doses can be administered in the usual manner but under observation

Take home messages (2)• If the test are positive and the patient

requires subsequent doses, the vaccine can be administered in graded doses under observation

• Some non-anaphylactic reactions to vaccines might also require evaluation, but only a few are contraindications to future doses

Thank you for your attention

adverse reactions to vaccines for infectious diseases

pediatr allergy immunol

immunol allergy clin

j allergy clin immunol

middletons allergy

majorcaubet jc

patientscaubet jc

hypertrichosiscaubet

painlesscaubet jc

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