Influenza Vaccine Adverse Reactions

Other Vaccines Adverse Reactions

Key Parts of Medical History

  • Patient’s age
  • Specific symptoms that were noted - was the reaction consistent with an IgE-mediated reaction?
  • Timing of onset of the symptoms relative to the administration of the vaccine
  • Other exposures to possible allergens (e.g. NSAIDs)
  • Any information from office visits/emergency department visits
  • Treatment that was administered
  • Duration of symptoms, time course of resolution
  • Previous vaccine reaction history
  • History of other atopic disease, including food allergy, drug allergy, atopic dermatitis, asthma, and allergic rhinitis
  • Specific vaccine(s) that was administered, including the manufacturer and lot number
  • Will the patient need additional doses of this vaccine or other vaccines with common constituents?
  • Should be classified according to the extent (local, systemic) and the timing of the reaction (immediate, non-immediate). The frequency (common, rare) and severity (minor, moderate, major) of the reaction should also be noted.

Vaccine Reaction Types and Clinical Implications

Small local reactions
  • Tissue damage by the puncture itself and injection of foreign material into tissues is responsible for a non-specific inflammatory reaction of the skin
  • Longer needles being associated with a lower rate of local reactions, therefore proper needle length should be used
  • Self-resolving, not a contraindication to revaccination
Large local reactions
  • Less common overall than SLR; may be more likely with vaccines containing toxoids or adjuvants and with additional doses of the same vaccine
  • LLR types:
    • Typical LLR occurs 24-72 h after injection, possibly due to antigen/adjuvant TLR-induced inflammation and/or an antibody-mediated Arthus-type reaction
    • Another pattern of LLR is benign reactive edema (often WITHOUT pain, reduced limb movement, redness, fever) occurring <24 h, which can be extensive and extend to elbow or knee; can occur with first injection
  • Both types of LLRs are self-resolving, and are not a contraindication to revaccination
    • Lieberman: to help decrease risk of LLR recurrence, consider dividing vaccine dose over days, e.g. 0.5 mL vaccine given as 0.1 mL daily x 5 days
  • If an Arthrus reaction is suspected, consider checking IgG titers and delaying the next vaccination (vs. revaccination as usual)
Systemic reactions
  • Normal systemic symptoms occur in 5-13%, most often fever, irritability, drowsiness, and rash; result from non-specific mechanisms and do not recur with future boosters
    • Mild generalized urticarial reactions of delayed onset often result from a non-specific degranulation of mast cells and do not contraindicate (re)vaccination; though controversial, oral antihistamines can be given for 48 h to ensure patient comfort after administration of the vaccine
  • IgE-mediated reactions, anaphylaxis - very rare, 1-3 per million doses of vaccine, must be evaluated prior to revaccination
  • Other immunologic reactions (serum sickness-like, HSP, specific organ damage) are even rarer than IgE-mediated reactions

Potential Vaccine Allergens and Clinical Implications (Caubet)

  • Microbial components themselves (tetanus and diphtheria toxoids) have been reported as allergens
  • Gelatin (stabilizer)
  • Egg proteins (remnants from vaccine production)
  • Aluminum (adjuvant)
    • Persistent itching, subcutaneous nodules, or granulomas at the injection site after vaccination with Al-adsorbed vaccines have been described but is considered to be rare
    • In aluminum contact-sensitized (i.e. positive patch test) patients requiring a vaccine containing Al, it should be administered deep enough as IM injection may prevent the formation of granulomas; some patients may develop local or systemic contact dermatitis reactions
  • Thimerosal (preservative)
    • Found in fewer vaccines due to mercury content
    • Vast majority of patients with positive patch test to thimerosal tolerate thimerosal-containing vaccines uneventfully, but it should still be avoided if possible to decrease risk of local reactions
  • Phenoxyethanol, and formaldehyde (preservatives)
    • Potential contact allergens
  • Latex - see below
  • Antibiotics - theoretical risk of IgE-mediated reactions but never reported, more likely to cause contact dermatitis reactions (especially neomycin)
    • Vaccination is not contraindicated in patients with contact allergy to neomycin, as the risk of a mild local reaction is outweighed by the vaccine benefit
    • Committee on Infectious Diseases of the AAP no longer considers contact hypersensitivity to neomycin a contraindication to vaccination
  • Yeast - Hep B and HPV vaccines are manufactured using recombinant strains of Saccharomyces cerevisiae (common bakers’ yeast) and contain residual yeast proteins
    • In patients with clinical reactivity to Baker’s or Brewer’s yeast and sensitized to S. cerevisiae, skin tests with yeast-containing vaccines should be performed; In case of positive results, the vaccine can still be given in graded doses
  • Milk - see below
  • Dextran - implicated in severe immediate reactions to BCG (particularly during the neonatal period), and to some MMR vaccines (withdrawn from market)
    • Reactions associated with presence of IgG to dextran; hypothesized that complement activation and anaphylatoxin release were the main mechanisms
  • Note that NSAIDs are often given concomitantly with vaccines

Practice Parameter Algorithm


Note 1. Are nature and timing of reaction consistent with anaphylaxis?
  • Probable Anaphylactic Reaction: reaction occurring within 4 hours of vaccine administration to include signs and/or symptoms from more than 1 of the following systems:
    • Dermatologic: urticaria, flushing, angioedema, pruritus
    • Respiratory: rhinoconjunctivitis (red, watery, itchy eyes, stuffy, runny, itchy nose, sneezing), upper airway edema (change in voice, difficulty swallowing, difficulty breathing), bronchospasm/asthma (cough, wheeze, shortness of breath, chest tightness)
    • Cardiovascular: hypotension, tachycardia, palpitations, light-headedness, loss of consciousness (Note: hypotension or loss of consciousness with pallor and bradycardia is much more likely a vasovagal reaction.)
    • GI: cramping, nausea, vomiting, diarrhea
    • Possible Anaphylactic Reaction: Signs and/or symptoms from only 1 system (as above) or signs and/or symptoms from more than 1 system (as above) but occurring more than 4 hours after vaccination

Note 2. Skin tests with vaccine and components including gelatin, egg, chicken and/or yeast vaccine skin tests:
  • Prick test with full strength vaccine (consider 1:10 or 1:100 dilution if history of life-threatening reaction)
    • If SPT with full strength vaccine negative, intradermal test with 0.02 mL vaccine 1:100 (which is thought to be non-irritating for vaccines; at 1:100 irritant reactions seen in 5% for DT and DTaP and 15% for influenza)
    • Note:
      • Vaccine skin tests are unstandardized and may cause false positive or negative reactions
      • Delayed responses to vaccine skin tests are common, most likely representing prior immunity, and should not raise concern in the evaluation of IgE-mediated vaccine allergy
      • If ID is negative, an IgE-mediated allergy to any vaccine constituent is very unlikely and the vaccine can be administered in the usual manner, but the patient should be observed for at least 30 min afterward

  • Vaccine component/food skin tests:Vaccine skin testing allergens.png
    • Egg - SPT with commercial extracts of whole egg or egg white (influenza and yellow fever), chicken (yellow fever )
    • Yeast - SPT with Saccharomyces cerevisiae yeast (Hep B and HPV4)
    • Gelatin - SPT with sugared gelatin (e.g. Jell-O®: dissolve 1 teaspoon (5 grams) of gelatin powder in 5 mL normal saline)
      • Vaccines that contain gelatin: DTaP (some brands), influenza (some brands), Japanese encephalitis, MMR/ MMRV (given together or in their individual components), rabies (some brands), typhoid (oral), yellow fever, zoster
      • Reported cases of gelatin tolerated orally but not when injected
      • Strong association between gelatin allergy and HLA-DR9, which is particularly prevalent in Japan
      • Association between gelatin and alpha-gal allergy has also been established
    • Milk - case report of milk proteins in DTP vaccines (DTaP, Tdap) causing anaphylaxis in children with severe cow's milk allergy
    • Latex - There is a theoretical risk of reaction in latex allergic individuals due to natural rubber latex stoppers/plungers
    • Thimerosal, neomycin - IgE-mediated reactions to these substances is very rare/unlikely; no commercially available skin test reagents or sIgE tests are available for these

Note 3. If fewer than the recommended number of doses received, consider measuring level of IgG antibodies to immunizing agent. If at a level associated with protection from disease, consider withholding additional doses although magnitude and duration of immunity may be less than if all doses received.

Note 4. Vaccine administration in graded doses
  • If vaccine or vaccine component skin tests are positive, and an alternative is not available, the vaccine should still be administered in graded doses
    • For a vaccine where usual dose is 0.5 mL, administer graded doses of vaccine at 15 minute intervals: 0.05 mL of 1:10 dilution, 0.05 mL of full strength, 0.10 mL of full strength, 0.15 mL of full strength, 0.20 mL of full strength
    • Wood: considered on a case by case basis, recognizing that a graded dose protocol still carries the risk of anaphylaxis. This should be conducted with informed consent and only in a setting prepared to treat severe allergic reactions should one occur.
  • If vaccine or vaccine component skin test is negative, give in usual manner and observe for 30 minutes
  • Exception: for influenza vaccine in egg-allergic patients, refer to vaccination in egg-allergy page

Wood Algorithm


Vaccine Allergens and Excipients