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Infusion and Injection Site Reactions
Clinical Presentation
Infusion reactions, both acute and delayed types, are defined as any adverse event
related to the drug administration [ 1 ]. Acute infusion reactions occur within the first
hours after drug administration and can be categorized as mild or severe. Mild acute
infusion reactions can be seen in 10–40% of patients receiving infliximab [ 2 , 3 ].
Symptoms include fever, nausea, vomiting, formation of a wheal, and/or pruritic
erythema [ 1 , 2 ]. Severe acute infusion reactions are less common, occurring in
about 8% of patients receiving infliximab [ 2 ]. Patients with severe acute infusion
reactions can present with fever, hypotension, bronchospasm, dyspnea, generalized
urticaria, angioedema, and in some cases anaphylaxis [ 1 , 2 ].
Delayed infusion reactions have been reported in up to 7% of patients receiving inf-
liximab [ 3 ]. Patients with delayed infusion reactions often present with serum sickness-
like symptoms including fever, malaise, arthralgia, myalgia, and urticaria 3–14 days
after the infusion [ 1 , 2 ]. Because the symptoms are nonspecific, delayed infusion reac-
tions must be differentiated from other conditions including viral syndromes, drug-
induced lupus, and extraintestinal manifestations of IBD [ 4 ]. Serum sickness syndrome
is typically self-limiting, with symptoms subsiding within days or weeks [ 1 , 2 ].
Another hypersensitivity reaction patient can experience is injection site reaction
localized to the area where the biologic agent is administered. Injection site reac-
tions occur in 8–20% of patients receiving adalimumab [ 5 , 6 ]. The skin lesions
appear within 24–48 h after the injection and are characterized by cutaneous erup-
tions, erythema, pruritus, tenderness, swelling, and irritation [ 1 , 5 ]. Injection site
reactions are typically self-limiting and resolve after 3–5 days [ 2 ].
Risk Factors
Risk factors for developing hypersensitivity reactions to biologics are related to
both the patient and the drug [ 1 ]. Predisposing factors related to the patient include
genetic predisposition (human leukocyte antigen class and presence of genetic
defects), age, immune competency, and the presence of other diseases [ 7 ]. Risk fac-
tors associated with the drug include dose, frequency of dosing, and route of admin-
istration [ 7 ]. Theoretically, intravenous dosing is less immunogenic than
subcutaneous or intradermal dosing; however, this has not been the experience of
most providers clinically, and there is no available data to support this theory [ 7 ].
Acute infusion reactions are more likely to occur in those receiving episodic or
reinitiation of therapy after a drug-free interval due to immunogenicity [ 3 ]. Baert
and colleagues reported that among 128 patients who were reinitiated on infliximab,
15 patients developed acute infusion reactions, and 10 had delayed infusion
reactions, after a median drug-free interval of 15 months [ 8 ]. In another study
U. Wong and R.K. Cross