Abstract & Commentary
Synopsis: It may be worth doing skin tests for penicillin allergy in patients with a history of allergic reactions to penicillin. In the 80% or more who will be negative, penicillin can be given without risk of anaphylaxis but serious dermatologic reactions must still be considered.
Source: Solensky R, et al. Lack of penicillin resensitization in patients with a history of penicillin allergy after receiving repeated penicillin courses. Arch Intern Med. 2002;162: 822-826.
Members of the Allergy and Immunology Division at the University of Texas Southwestern set out to test the hypothesis that challenges that oral penicillin would be more likely to sensitize patients who had a history of an allergic reaction than those who did not. They found 58 volunteers who recalled a prior reaction to penicillin. Skin testing using major and minor determinants was positive in 5 people (9%), who were eliminated from evaluation.
The remaining 53 had a history of allergic reactions that consisted of urticaria (47%) anaphylaxis (17%), or a pruritic rash (36%). They were all given a course of oral Pen V (250 mg TID for 10 days). Two had a possible reaction (itching only in one, unobserved hives in another) and did not complete even the first course. None of the others had a reaction. They were again skin tested at least 4 weeks after therapy then given penicillin again. The cycle was repeated a third time if there was no reaction.
Remarkably, none of the people developed a positive skin test or any other type of adverse effect—even after 3 courses of penicillin. An analysis of the numbers with no apparent reactions suggests the chance of resensitization with a 95% confidence level would be less than 2%.
Comment by Alan D. Tice, MD, FACP
Approximately 10% of the American population reports an "allergy" to penicillin. This clearly discourages its use despite its value, which is unfortunate in the face of increasing antimicrobial resistance. Instead of risking penicillin therapy, many doctors rely on new, expensive, and broad-spectrum antibacterials with presumably fewer side effects. Anaphylaxis does appear to be more frequent with penicillin than other antibiotics. According to registries in Europe, it occurs with an incidence of about 1 in 10,000. The possibility of a life-threatening anaphylactic reaction to penicillin can be easily eliminated with skin testing using major and minor determinants.1 Other types of reactions include a rash, hemolytic anemia, renal failure, and urticaria although seizures and leukopenia may occur with intravenous dosages.
Why there was no reaction in the people studied is unclear. A rash is usually reported in about 2-5% of people without a history of penicillin allergy. It may well be that the historical "reaction" that was reported was actually from the infection or other medications received at the time—or some combination thereof. It may also be that the old preparations of penicillin were different and more likely to produce reactions than the Pen V used in this study. Another possibility is that the reaction mechanism and immune memory died off with no anamnestic response.
For many infections, penicillin is an ideal antimicrobial in terms of activity, cost, and narrow spectrum—a "silver bullet" if you will. However, one of the major reasons penicillin is not prescribed more often is because of the concern about allergic reactions. Recent studies have suggested a history of an allergic reaction confers only a slightly greater chance of a reaction with a new course but it is still a risk. The chances of a rash with penicillin is 2-3% in the naive population and even higher with amoxicillin but usually benign. If there is a history of a reaction such as Stevens-Johnson syndrome, a patient should not be rechallenged. Part of the problem with penicillin is also legal—there is good case law for major claims if a person with any history of allergic reaction to penicillin is given it again and has a severe reaction. There is no reward for those who try it anyway and there is no reaction. There is also no penalty or risk in prescribing a more expensive alternative.
This paper suggests that even for patients with a history of an allergic reaction to penicillin, the risk of a reaction is small if skin tests are negative—and that repeated courses of penicillin do not resensitize the person. Solensky and associates suggest skin tests be done on all people with a history of a reaction to penicillin and that a negative response would indicate it is safe to use one of the best antibiotics we have. Testing could be done while a person is well so that knowledgeable decisions about antibiotic use could be made the next time a bacterial infection occurs.
Whatever the reason for the unexpected lack of response, the message is to skin test patients, limit the legal perspectives, and try penicillin again if the skin tests are negative and there is no history of a severe rash.
Dr. Tice, Infections Limited, PS, Tacoma, WA; Infectious Disease Consultant, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, is Associate Editor of Infectious Disease Alert.
Reference
1. Sogn DD, et al. Results of the national institute of allergy and infectious diseases collaborative clinical trial to test the predictive value of skin testing with major and minor penicillin derivatives in hospitalized adults. Arch Intern Med. 1992;152:1025-1032.
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