Determination of the incidence of sensitization after penicillin skin testing Jeffrey S. Nugent, MD; James M. Quinn, MD; Christianne M. McGrath, MD; David E. Hrncir, MD; William T. Boleman, MD; and Theodore M. Freeman, MD Background: Concerns for sensitization after penicillin skin testing are a factor in limiting the timing and population for whom this testing is offered. The sensitizing potential of the penicillin skin test has never been studied directly. Methods: A total of 329 volunteers underwent prick and intradermal skin testing with penicillin G, benzylpenicilloyl- polylysine, and a minor determinant mixture. Those with negative skin testing had repeat testing 4 weeks later. Medical history and antibiotic use were determined by interview, questionnaire, and electronic pharmacy records. Results: Seventy-two of the 329 subjects (22%) reported a history of previous -lactam reaction, of which 10 (14%) had a positive initial skin test. Overall, the initial skin test was positive in 23 of 329 (7%). Of the subjects with a negative initial skin test, 239 completed the second test 4 weeks later. Of these, 6 subjects (2.5%, 95% confidence interval 0.5% to 4.5%) converted to a positive skin test. None had taken a -lactam antibiotic between the two tests, and none had any previous history of -lactam reaction. One subject reported having never taken a -lactam antibiotic before. In comparison to the 233 subjects who did not convert their skin test, the statistically significant factors favoring sensitization were: female sex (odds ratio [OR] 6.53, P = 0.05), atopy (OR 5.31, P = 0.04), and history of food allergy (OR 6.35, P = 0.02). There was a trend toward more recent penicillin use in the newly sensitized subjects, but this was not statistically significant. Conclusion: Penicillin skin testing may sensitize a small number of individuals to penicillin. Ann Allergy Asthma Immunol 2003;90:398– 403. INTRODUCTION Despite advances in antimicrobial therapy, -lactam antibi- otics remain an important element in the treatment of infec- tious diseases. The prevalence of self-reported penicillin al- lergy ranges from 1 to 10% in the general population, although only 10 to 30% of these patients demonstrate serum- specific immunoglobulin E with skin testing. 1 Penicillin skin testing has been found to have an excellent negative predic- tive value, and 98% of patients with positive histories of penicillin allergy and negative skin test results can tolerate penicillin without difficulty. 2 There is controversy, however, regarding the length of time that a penicillin skin test remains valid, with recommendations ranging from 72 hours to no time limit. 3–5 Survey data of practicing allergists and allergy program directors have similarly revealed a wide range of opinion, as reported by Wickern et al 6 ; approximately 1 in 3 responders felt that skin test results were only valid if peni- cillin was immediately administered, 1 in 3 believed the results were good indefinitely, and the remaining one-third gave answers ranging from 24 hours to 1 year. 6 Concern that penicillin skin testing is valid for only a brief period stems from rare anecdotal cases and theoretical con- cerns. In one study 4 of penicillin skin testing in 740 patients, a patient with a positive history and negative skin tests subsequently had an acute urticarial reaction to penicillin 6 months after the skin testing without intervening antibiotic. Speculation as to the mechanism of penicillin immunoglob- ulin E sensitization in this patient included ingestion of an unknown dose of penicillin, sensitization from the skin test itself, or sensitization from environmental exposures. Studies have shown the presence of small amounts of penicillin in milk, 7,8 meat, 9 and possibly even soft drinks, 10 although many authors question the significance of these environmental ex- posures. 11 Therapeutic courses of penicillin given after neg- ative skin testing have been reported to induce resensitization at a rate between 0 and 16%. 5,11–14 The potential contribution of sensitization by the skin testing procedure itself has not been investigated, although some authors cite this potential in recommendations limiting the duration of time for which a negative result is valid. 3 The purpose of the present study was to evaluate the incidence of sensitization after penicillin skin testing alone and to identify any predisposing factors predic- tive of skin test conversion. METHODS Three hundred twenty-nine volunteer subjects over 18 years of age who were not pregnant or taking systemic steroids, antihistamines, or -blockers were enrolled in the study, Wilford Hall Medical Center, San Antonio, Texas. No grant support was obtained for this manuscript and the authors have no pharmaceutical industry affiliations. The opinions and assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Air Force, the Department of Defense, or the United States Govern- ment. Data from this study were accepted for oral presentation as a 10-minute slide show at the 2002 National ACAAI meeting in San Antonio, Texas (Novem- ber 18, 2002), and also selected for the 2002 Clemens von Pirquet Auxiliary Memorial Award. Received for publication October 12, 2002. Accepted for publication in revised form November 20, 2002. 398 ANNALS OF ALLERGY, ASTHMA, & IMMUNOLOGY