Vaccine Hypersensitivity

Vaccine hypersensitivity is an allergic or allergy like reaction to a vaccine or one of its components. Anaphylaxis is rare, and most reactions are not allergic, so a patient should rarely be denied vaccination.

Pathophysiology. Reactions may be IgE-mediated against the antigen or an excipient (gelatin, egg protein, yeast, latex, neomycin, polyethylene glycol, polysorbate 80, tromethamine), or non-IgE mast cell activation. Delayed reactions are T cell mediated and include injection site nodules and large local swelling.

Anaphylaxis occurs in about 1 in a million doses of traditional vaccines, and about 5 in a million doses of mRNA vaccines. Polyethylene glycol (in mRNA vaccines) and polysorbate 80 (in some adjuvanted and protein vaccines) are cross-reactive excipients.

Vasovagal syncope and anxiety related reactions are far more frequent than true allergy.

• Immediate (within 30 minutes to 4 hours): urticaria, angio oedema, wheeze, throat tightness, hypotension, anaphylaxis
• Vasovagal reaction: pallor, sweating, bradycardia and fainting within minutes, without hives or wheeze
• Large local reaction: extensive arm swelling and redness over 24 to 72 hours, usually non-allergic
• Delayed urticaria or rash, or injection site nodule (aluminium adjuvant)
• Arthus type reaction after repeated tetanus or diphtheria toxoid
• Rare delayed severe reactions

• History: vaccine, dose number, time to onset, features, treatment needed, and previous tolerance of other vaccines.
• Serum tryptase within 1 to 2 hours of an immediate reaction, with a baseline later.
• Skin prick test with the vaccine (undiluted) and intradermal test (diluted 1 in 10) and with excipients (polyethylene glycol, polysorbate 80): positive results support allergy, but some vaccines cause irritant false positives.
• Specific IgE to gelatin, egg, latex and alpha gal where relevant. Basophil activation test where available.
• Assessment for another trigger such as concurrent drugs, food or infection.

Differential diagnosis.

• Vasovagal syncope and anxiety related reaction
• Large local reaction (non-allergic)
• Coincident idiopathic anaphylaxis or food allergy
• Mast cell disorder
• Excipient allergy (polyethylene glycol, polysorbate, gelatin)
• Serum sickness like illness

• Before vaccination: check for a previous severe reaction to the vaccine or a component. Egg allergy, penicillin allergy and previous large local reactions are not contraindications.
• Observation: at least 15 minutes after vaccination, and 30 minutes for patients with a previous allergic reaction to a vaccine or with an anaphylaxis history, in a place with resuscitation equipment.
• Anaphylaxis: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh, repeated after 5 minutes if no improvement, plus oxygen and intravenous fluids, and observation for at least 6 hours.
• After an immediate allergic reaction: refer for testing. Do not give a further dose of the same vaccine until assessed. Options are a different vaccine without the culprit excipient, or the same vaccine given as a divided dose under observation after a negative skin test.
• Mild or non-allergic reactions: reassurance, and vaccination can continue. Large local reactions: cold compress and an oral antihistamine (cetirizine 10 mg once daily in adults; children 1 to 5 years 2.5 mg twice daily; 6 to 11 years 5 mg twice daily).
• Vasovagal reactions: lie flat with legs raised, and vaccinate seated or lying down in future.
• Gelatin- or egg containing vaccines: use gelatin free or low ovalbumin products where available. Yellow fever vaccine needs specialist assessment in egg allergy.
• Record the reaction in the immunisation record and the allergy record.

Special groups.

• People with polyethylene glycol allergy: avoid mRNA vaccines and consider a protein based vaccine without polyethylene glycol or polysorbate.
• Mast cell disorders: vaccinate with premedication (cetirizine 10 mg and a second antihistamine) and extended observation.

Monitoring. Observe for 15 to 30 minutes after vaccination. Review within 1 to 2 weeks after a reaction for delayed features.

Referral and escalation. Refer to allergy after any immediate generalised reaction. Emergency for anaphylaxis.