Skin test evaluation in nonimmediate allergic reactions to penicillins

Background: Nonimmediate reactions (NIR) to aminopenicillins (AP) are frequent. Although patch testing (PT) and intradermal testing (IT) are used for diagnosis, comparative results have never been adequately performed. We compared PT and IT in subjects with NIR to AP. Methods: Twenty-one subjects with NIR to AP and positive IT were re-evaluated. Skin tests were performed with amoxicillin (AX) and ampicillin (AM) at different concentrations in petrolatum, 50, 25, and 5% w/w, for PT and in saline, 20, 2, and 0.2 mg/ml for both PT and IT. Skin biopsies from the site of the positive response were studied with haematoxylin-eosin and immunohistochemistry. Results: In the re-evaluation, one case was IT and PT negative and was excluded; 20 were IT positive and 18 PT positive for both AX and AM. Decreasing concentrations of AP induced a reduction in positivity in both methods when diluted in saline, but not when mixed in petrolatum (PT only). With both PT and IT, immunohistochemical studies showed a perivascular mononuclear infiltrate with CD4 and CD8 memory cells expressing perforin and granzyme B. Conclusions: Both tests appear valuable for the diagnosis of NIR to AP. However, IT diagnosed more patients than PT. The vehicle (saline or petrolatum) had no influence on the response, although in the former the concentration was critical. The immunohistochemical analysis showed skin infiltrates compatible with a T-cell drug reaction.