Hypersensitivity Reaction

The Gell and Coombs scheme sorts drug hypersensitivity by mechanism. Type I is IgE-mediated and immediate, producing urticaria, angioedema, bronchospasm and at the extreme anaphylaxis. Type II is antibody-mediated destruction of cells carrying the drug or a drug-modified antigen, such as immune cytopenias. Type III involves immune complexes and appears as serum sickness, vasculitis or arthralgia days after exposure. Type IV is T-cell mediated and delayed, from contact dermatitis and rash through to severe cutaneous reactions.

Type I reactions to injected material occur within minutes and nearly always inside two hours. Type IV reactions typically appear at forty-eight to seventy-two hours, and severe cutaneous forms can take weeks. In peptide products the culprit is frequently not the peptide. Preservatives such as metacresol and benzyl alcohol, the polyethylene glycol chain in PEGylated products and residual trifluoroacetate from purification have all been implicated in reactions first attributed to the active ingredient. Species-foreign sequences carry their own risk, which is why salmon calcitonin, animal-source insulins and protamine feature so heavily in this literature.

Mechanism determines what can be done next. Some IgE-mediated reactions can be managed by supervised desensitisation; a severe delayed cutaneous reaction is an absolute bar to re-exposure. Identifying an excipient rather than the peptide as the antigen can preserve access to a whole class.

The habitual error is calling every unwanted local response an allergy. A weal at an injection site is usually irritant or a local delayed response, not systemic sensitisation, and treating it as proof of allergy closes off drugs that would have been fine in another vehicle. The reverse error carries the risk: attributing a genuine early systemic reaction to injection anxiety.