Injection site reaction refers to localized adverse reaction to a medication or vaccination at the site of subcutaneous or intramuscular administration. It is commonly characterized by erythema with pain and/or pruritus at the injection site.

Both immediate and delayed injection site reactions are possible. Immediate reactions may represent immune systemic activation due to aluminum salts or microbial components, or immune complex-mediated reaction. These reactions appear 1-8 hours after injection and rarely may become generalized.

Delayed injection site reactions occur days to weeks after initial injection and are thought to occur as a result of a delayed hypersensitivity reaction due to medication or vaccine components such as aluminum adjuvants, thimerosal, neomycin, or formaldehyde. Delayed injection site reactions have been reported following both intramuscular vaccines and subcutaneous medications; therefore, this reaction pattern is not limited to a single route of administration. Biologic therapies are common culprits, with rates between 0.08%-45%, depending on the agent and the study. The highest rates of injection site reactions occur with canakinumab, dupilumab, omalizumab, etanercept, and ixekizumab, whereas risankizumab, brodalumab, guselkumab, and secukinumab have the lowest risk. Other common culprits include vaccinations, such as COVID-19 (in up to 93% of cases), influenza and recombinant zoster vaccines, and glucagon-like peptide-1 (GLP-1) receptor agonists (in up to 3.5% of cases). 

Injection site reactions usually self-resolve within 1-4 days and in general are not considered a contraindication to future administration.

Related topics: cutaneous reactions after COVID-19 vaccination, vitamin K injection site reaction