Background: Skin testing for immediate hypersensitivity to penicillins is usually carried out with reagents prepared from benzylpenicillin, and it is believed that side-chain-specific reactions to semisynthetic derivatives are rare. Because some experimental and clinical data suggest that antibodies can be induced to immunogenic epitopes on the side chains of penicillins, we looked for side-chain-specific reactions to skin testing in patients with a history of allergy to penicillins or semisynthetic penicillins.
Methods: One hundred twelve patients with a clinical history of allergic reactions to penicillins and other semisynthetic penicillins were skin tested an average of 4.9 +/- 0.7 years after their reactions with the major and minor determinants of benzylpenicillin and minor determinant mixtures of ampicillin, amoxicillin, or cloxacillin.
Results: In these patients the most common clinical reactions were urticaria and angioedema (36.6%) and exanthema (48.8%). It was found that 21 cases (18.8%) still exhibited immediate hypersensitivity reactions on skin testing. But of these 21 patients, skin test reactivity was limited in 47.6% to the semisynthetic penicillin reagents derived from ampicillin, amoxicillin, or cloxacillin; that is, skin tests were negative with the benzylpenicillin derivatives. Ampicillin and amoxicillin were the semisynthetic beta-lactams causing most clinical reactions (24.1% and 33.9%, respectively), and ampicillin was the most common penicillin derivative to which skin test reactivity occurred (38.1%), other than the benzylpenicillin derivatives (52.3%).
Conclusions: IgE antibodies appear therefore to discriminate between benzylpenicillin and ampicillin or other semisynthetic penicillins in a significant proportion of patients allergic to penicillin. Although it has not been proved that side-chain-specific skin reactivity implies the presence of clinically significant immediate hypersensitivity to semisynthetic penicillins, it is possible that side-chain-specific reagents may be required to exclude possible immediate hypersensitivity to the penicillins in patients who reacted to these antibiotics clinically.