D3.373 - Non-immediate Hypersensitivity Reactions To Both Penicillin and Aminopenicillin and Diagnostic approach – A Real Life Retrospective Study

Suspicion of penicillin allergy is a common cause for referral to allergy clinics worldwide with a 10% self-reported population prevalence. Of those, only 1/10 are allergic, and the majority with a non-immediate (late-phase) hypersensitivity reaction. Compared to the well-defined diagnostic workup for immediate reactions, evaluation of late-phase reactions varies considerably between allergy centers. Most evaluations consist of a culprit drug provocation test with an oral course at home. If the culprit drug is unknown, amoxicillin is usually chosen, and if a reaction occurs, the diagnostic workup frequently ends with a general contraindication to all penicillins. However, amoxicillin is an aminopenicillin, consisting of a penicillin core with an attached amino sidechain opening the possibility for selective sensitivity towards the side chain only. This phenomenon is well described for immediate reactions, but has not been sufficiently investigated for delayed reactions.

We hypothesized that a substantial number of patients are unnecessarily labeled as allergic to the entire penicillin class due to delayed reactions to aminopenicillins, and we evaluated the safety of our recommended diagnostic algorithm.

Retrospective analysis of patients with confirmed delayed hypersensitivity reactions to aminopenicillins who subsequently underwent evaluation for delayed reactions to penicillin, either by intradermal testing with delayed reading (IDT) or by oral provocation test (OPT). The severity of delayed reactions was classified as mild, moderate, severe, or severe cutaneous adverse reactions (SCARs). Reactions were verified by photo documentation and patient self-reporting.

Reaction to aminopenicillin: 62 patients

Positive IDT: 9

Positive OPT: 53

- Reactions:    Mild to moderate, presenting as rash or mild urticaria/angioedema

Reaction also to penicillin: 11 patients

Positive IDT: 1

Positive OPT: 10, mainly milder or similar reactions

82% of patients with delayed hypersensitivity reactions to amoxicillin tolerate penicillin

All delayed reactions observed during penicillin home testing were mild to moderate, indicating that in-hospital provocation testing prior to home testing is not necessary

We therefore recommend that patients with delayed reactions to amoxicillin undergo subsequent home testing with penicillin