Short communication Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins Skin tests are the most readily available diagnostic tools and continue to be essential for evaluating the subjects with hypersensitivity reactions to penicillins. Indeed, in such patients, the clinical history is not reliable (1, 2). In both the American practice parameters (3) and the European Network for Drug Allergy (ENDA) position paper (4), skin testing with penicilloyl-polylysine (PPL) and minor determinant mixture (MDM) represents the first-line method for evaluating immediate (i.e. occurring within 1 h after the last drug administration) reactions to b-lactams. Recent studies have emphasized the impor- tance of skin testing with PPL and MDM in diagnosing b-lactam hypersensitivity (5–7). However, the fact that both Hollister-Stier and Allergopharma ceased the pro- duction of penicillin reagents in 2004 is severely hamper- ing the diagnosis of b-lactam hypersensitivity and may produce negative consequences. In effect, a diagnostic approach based only on the clinical history might erroneously classify many patients suspected of being sensitive to b-lactams, but who could have a good tolerance after an appropriate allergologic workup. On the other hand, a protocol, which does not include skin tests with PPL and MDM, might not diagnose many cases of b-lactam hypersensitivity. In two recent series of subjects with hypersensitivity reactions to b-lactams (5, 6), 14.7% and 47.0% of positive cases would have been missed, respectively, if PPL and MDM had not been used in evaluating them. In this cohort study, using information from our database, we assessed the contribution of skin testing with benzylpenicillin to the diagnosis of immunoglobulin E Background: The fact that both Hollister-Stier and Allergopharma ceased the production of penicilloyl-polylysine (PPL) and minor determinant mixture (MDM) in 2004 is severely hampering the diagnosis of b-lactam hypersensitivity and may produce negative consequences. Objective: To assess the contribution of skin testing with benzylpenicillin to the diagnosis of immunoglobulin E-mediated hypersensitivity to penicillins, in order to determine how much such testing could compensate for PPL and MDM unavailability. Methods: We selected patients with histories of immediate reactions to penicil- lins and positive results to skin tests for one or more penicillin reagents (PPL, MDM, or benzylpenicillin), one or more semi-synthetic penicillins (ampicillin, amoxicillin, or piperacillin), or both. Results: A total of 300 patients were selected, 105 in the French center and 195 in the Italian centers. Amoxicillin and ampicillin were the main responsible drugs. The most common clinical manifestation was anaphylaxis. The reagents most frequently positive to skin tests were amoxicillin (188, 62.7%), ampicillin (151, 50.3%), and benzylpenicillin (111, 37.0%). Among the 300 subjects, 113 (37.7%) were positive only to semi-synthetic penicillins, 109 (36.3%) to both semi- synthetic penicillins and the classic penicillin reagents, and 78 (26.0%) only to the latter. In the last group, 64 (21.3% of the 300 subjects) were positive only to PPL and/or MDM and 14 (4.7%) to benzylpenicillin, of whom 8 (2.7%) were positive only to the latter. Conclusions: Skin testing with benzylpenicillin can partially compensate for PPL and MDM unavailability. Moreover, it can slightly increase the allergologic workupÕs sensitivity and therefore reduce the number of potentially dangerous challenges. A. Romano 1,2 , L. Bousquet-Rouanet 3 , M. Viola 1 , F. Gaeta 1 , P. Demoly 3,4 , P.-J. Bousquet 3,5 1 Department of Internal Medicine and Geriatrics, UCSC-Allergy Unit, Complesso Integrato Columbus, Rome, Italy; 2 IRCCS Oasi Maria S.S., Troina, Italy; 3 Exploration des Allergies, Hôpital Arnaud de Villeneuve, Montpellier Cedex 5, France; 4 INSERM, U657, Montpellier, France; 5 DØpartement Biostatistique, Epidemiologie Clinique, SantØ Publique et Information MØdicale, Hôpital CarØmeau, Nîmes Cedex 9, France Key words: benzylpenicillin; Drug Allergy and Hypersensitivity Database; hypersensitivity; penicillins; skin tests. Prof. Antonino Romano Unità di Allergologia Complesso Integrato Columbus Via G. Moscati, 31 00168 Rome Italy Accepted for publication 18 July 2008 Abbreviations: DAHD, Drug Allergy and Hypersensitivity Database; ENDA, European Network for Drug Allergy; IgE, immunoglobulin E; MDM, minor determinant mixture; PPL, penicilloyl-polylysine. Allergy 2009: 64: 249–253 Ó 2009 The Authors Journal compilation Ó 2009 Blackwell Munksgaard DOI: 10.1111/j.1398-9995.2008.01874.x 249