WP 2.3 - Risk of Anaphylaxis in patients with IgE-mediated allergy to penicillin

Background:

Hypersensitivity reactions to beta-lactams are the most frequent cause of drug reactions mediated by specific immunological mechanisms. Currently the diagnosis is based on positive specific IgE or skin tests and if negative a drug provocation. Specific IgE response to beta-lactams is not a long-lasting phenomenon and it is known that the level of IgE decreases over time at a variable rate. In a preliminary study we have challenged a total of 12 patients with previous IgE sensitization and negative skin tests with beta-lactams and the results suggest that a positive specific IgE alone is insufficient for the diagnosis of penicillin allergy. The same pattern is seen in a population-based study  from our group where a fraction of the 1501 unselected young adults have a positive IgE to penicillin but no history of hypersensitivity reactions towards beta-lactams (unpublished). To date only one paper has studied the positive predictive value of specific IgE determination and concluded it reasonable to question the value of specific IgE in the diagnosis of penicillin allergy.

 

Hypothesis:

Are all patients with positive specific IgE and negative skin tests truly allergic to penicillin without performing a drug challenge test? A drug challenge test is still necessary in order to determine if a positive IgE in patients with a history of penicillin hypersensitivity is of importance in order to avoid unnecessary use of less efficient or more expensive alternatives.

 

Methods:

A selected group of patients with IgE sensitization and negative skin tests will be challenged with penicillin under anaphylaxis surveillance in consecutive steps at the Allergy Centre. Today we perform penicillin challenge to patients with negative specific IgE and negative skin tests in the four consecutive steps:

1. titrated I.v challenge with benzylpencillin,

2. Single dose oral challenge with phenoxymethylpenicillin,

3. One week prolonged oral treatment (p.o.7)

4. If negative, addition of challenge with culprit beta-lactam. 

An identical protocol with more dosing steps added for safety reasons will be applied in patients with positive specific IgE, with addition of serial measurement of specific IgE during the challenges (see figure).

 

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