Drug Sensitivity (1998)

The most common medications that induce allergic drug reactions are penicillin antibiotics, with an incidence of allergic reaction that ranges from 1% to 10%. Although the most common allergic manifestations are cutaneous, the spectrum of immunologically mediated adverse reactions to penicillin is broad, including immunoglobulin E (IgE)-mediated anaphylaxis, T cell-mediated contact dermatitis, Ig-mediated hemolytic anemia, and immune complex-mediated serum sickness. Despite the availability of alternative antibiotics for treatment of patients who exhibit allergic reactions to penicillin, their future clinical management is greatly facilitated by proper evaluation of their penicillin allergy.Weiss described a classification of allergic reactions based on the time of onset of symptoms relative to the administration of the penicillin. Reactions are characterized as immediate if they occur within 1 hour of penicillin administration and can include anaphylaxis, hypo-tension, laryngeal edema,urticaria/ angioedema, and wheezing. Accelerated reactions occur from 1 to 72 hours after exposure to penicillin and are characterized by the development of urticaria/angioedema, laryngeal edema, and/or wheezing. Reactions occurring more than 72 hours after the initiation of penicillin therapy are classified as late and can include macular/ papular rashes,hemolytic anemia, and serum sickness.IgE-mediated reactions are the most important clinically because of their association with potentially fatal anaphylaxis; they can be evaluated best by skin testing. Because penicillin is a low molecular weight compound, it must bind to proteins, forming a hapten-protein complex, to become antigenic and thereby elicit an allergic reaction. More than 95% of penicillin is metabolized into a penicilloyl moiety referred to as the “major determinant”; the rest is metabolized into products called the “minor determinants.”Reagents for skin testing for reactivity to major determinants are available commercially, but the poor stability of minor determinants has prevented the development of commercial skin testing reagents. Therefore, to test for reactivity to the minor determinants, allergists combine various penicillin metabolites (such as benzylpenicillin and benzylpenilloate) into what is known as “the minor determinant mixture.” Accelerated and late urticarial reactions usually are mediated by IgE directed to the penicilloyl determinant; IgE antibodies to minor determinants mediate anaphylactic reactions to penicillin. Thus, skin testing with the minor determinant mixture is particularly important for screening patients who have a history of anaphylaxis.Lin correlated the clinical presentation of individuals who have penicillin allergies with their skin test reactivity. Although penicillin-associated fatalities usually occur within 1 hour of drug administration, symptoms in about 10% of fatal reactions begin more than 1 hour after treatment with penicillin. Immediate and accelerated reactions to penicillin each have been estimated to occur at a rate of 3 per 1,000;anaphylaxis occurs in about 1 to 5 per 10,000 treated individuals, and 1 to 2 per 100,000 individuals die from their reaction to penicillin. There appears to be no difference in the incidence of reaction between people taking penicillin for the first time and those who previously tolerated treatment without developing allergy. However, people who have reacted previously have a much greater rate of subsequent allergic reaction than those who never have exhibited allergy to penicillin.Several studies have established the safety of appropriately administered skin testing, and Weiss described the correlation among the history of penicillin allergy,reactivity to skin tests using the major and minor determinants, and development of allergic reactions after future treatment. About 2% of people who have no history of penicillin allergy are positive to skin testing compared with 7% to 35% of individuals who have a history of penicillin allergy. Patients who have both a history of reaction to penicillin and a response to skin testing have a 50% to 70% likelihood of an anaphylactic or accelerated urticarial response with future re-exposure to penicillin. In contrast, negative skin testing and a history of previous allergy suggests only a 1% to 3% risk of cutaneous reaction to a future dose. Skin testing,therefore, is extremely useful in determining whether patients who have a history of allergy to penicillin are at high or low risk for developing allergic reactions if subsequently treated with penicillin.Usually I try not to make my comments personal, but as someone who has had a serious allergic reaction, I can’t resist this opportunity to speak up for skin testing. My dilemma was that I had my reaction shortly after taking both a dose of penicillin and a healthy serving of shrimp. Should I admit that as I waited for the test response, I prayed it was the penicillin?