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Jyothi Gadde, MD; Michael Spence, MD, MPH; Barbara Wheeler, RN; N. Franklin Adkinson, Jr, MD

JAMA. 1993;270(20):2456-2463.

Abstract
Objective.
—To establish (1) the prevalence of positive penicillin skin tests among outpatients with well-defined but variable history of penicillin allergy and (2) the reproducibility, safety, and negative predictive value of skin testing with benzylpenicilloyl polylysine (PPL) and a minor-determinant mixture (MDM).

Design.
—Serial consenting outpatients with current indications for penicillin therapy were skin-tested in duplicate with PPL and MDM. Subjects with negative skin tests (93% of those positive by history and 95% of those negative by history) received therapeutic courses of benzylpenicillin (81%) or ampicillin (19%). Negative predictive value of skin testing was established by 72-hour follow-up for adverse reactions to drug.

Setting/Patients.
—A total of 5063 consecutive, qualifying outpatients in a Baltimore, Md, sexually transmitted disease (STD) clinic. The study group was young (73% between 20 and 40 years old), 66% male, and 90% black; 25% had history of atopy. Follow-up was 94% complete.

Results.
—Positive skin tests were observed in 7.1% of 776 individuals with previous history of penicillin allergy and in 1.7% of 4287 subjects negative by history (P<<.001). Previous history of anaphylaxis or urticaria was associated with significantly higher rates of positive skin tests of 17.3% and 12.4%, respectively (P<<.001). Only 4% with history of exanthem had positive skin tests (P=.03). The coefficient of variation for duplicate skin tests was 11%. Time intervals since last penicillin treatment did not influence the rate of positive skin tests. Adverse reactions to skin tests occurred in 13 (1.2% of patients positive by history; 9.4% of those with positive skin tests). A mild anaphylactic reaction occurred in one individual whose preliminary scratch testing was inadvertently omitted; systemic pruritus or urticaria occurred in 11 subjects; one had a large local reaction. After penicillin administration to individuals with negative skin tests, acute allergic reactions occurred in 0.5% of subjects negative by history compared with 2.9% of subjects positive by history (²=33.3;P=.0001). Reactions were generally mild and self-limited; only two cases of mild anaphylactic reaction occurred, both in patients with history of severe IgE-mediated reaction.

Conclusions.
—Skin testing with both major and minor penicillin determinants is safe using current recommendations, and both reagents are necessary for maximizing the identification of sensitized subjects. Routine penicillin skin testing can facilitate the safe use of penicillin in 90% of individuals with a previous history of penicillin allergy.

(JAMA. 1993;270:2456-2463)

Author Affiliations
From the Division of Allergy and Clinical Immunology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md. At the time of the study, Dr Spence was affiliated with the Baltimore City (Md) Eastern Health District Clinic for Sexually Transmitted Disease. He is now with the Department of Obstetrics and Gynecology, Hahnemann Hospital, Philadelphia, Pa.

Footnotes
Reprint requests to The Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Cir, Baltimore, MD 21224 (Dr Adkinson).

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