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Allied Health: Articles of Interest Penicillin hypersensitivity Approximately 10% of the general population claims to be penicillin allergic, and tertiary hospital reviews have found the rate of reported penicillin allergy in hospitalized adults to be as high as 16%. This forms a large group of individuals who are routinely excluded from the use of penicillin and cephalosporin. The high rate of reported allergy results in an increased use of the more expensive flouroquinolones and macrolides for outpatient populations, and unnecessary use of vancomycin in hospitalized patients. A study from Northwestern University, Chicago, IL, showed that 40% of hospitalized patients who report a history of penicillin allergy receive vancomycin instead of a beta-lactam. Li, et al, Mayo Clinic, Rochester, MN, showed that a pre-operative testing program allowed 56 of 60 patients who claimed penicillin allergy to be given a beta-lactam perioperatively, rather than vancomycin. Penicillin reactions can present in a number of different forms. Taking a detailed history is the first step to determining the individual’s reaction. Intolerance reactions, medication side effects, and C. Dificile complications are not true allergy reactions, and serum sickness, Stevens-Johnson and Toxic Epidermal Necrolysis (TEN) can be life threatening, but are unpredictable. If a patient has a history of these reactions, they should avoid penicillin antibiotics. Delayed hypersensitivity reactions are t-cell-mediated responses, usually presenting with a morbilliform pruritic rash several days into therapy. These are usually not life threatening, but often necessitate the discontinuation of the medication. Usually, patients remember very little about the events leading up the original reaction. However, certain historical elements can provide valuable clues including when the allergic event took place, the setting, and the reason the antibiotic was being given. If the patient was given an antibiotic during a viral illness resulting in a maculopapular eruption, this might suggest a viral associated rash, rather than an IgE-mediated drug reaction. If the patient required admission to an intensive care unit, this suggests either a severe IgE mediated reaction or an idiosyncratic reaction such as TEN. If the patient has a history of a blistering, exfoliative rash with oral involvement that required hospitalization, this is also suggestive of TEN and those patients should not have penicillin. True penicillin hypersensitivity can be a severe, acute, life-threatening reaction presenting within two hours of medication ingestion with symptoms ranging from urticaria, angioedema, pruritus and wheezing, to nausea, diarrhea and hypotension. Thus, a detailed history of the reaction can provide some very useful information. History can also be unreliable. In a study of an ICU population, Arroliga et al found that the rate of patients who were positive by history but negative to skin testing was 95%. Studies of other groups, including outpatient clinics, inpatient general medical wards, and pediatric departments, have shown that approximately 70-90% of patients who are history positive have negative skin tests. Conversely, a study of 1,037 patients who were reportedly penicillin allergic revealed that 323 had benign-sounding histories. It is well established that after an allergic reaction to penicillin, provided there is no additional exposure, patients lose detectable levels of IgE to penicillin as early as 55 days after the initial event. Ten years after a reaction, only 20% of individuals are still skin-test positive. This is illustrated by a study done at The Cleveland Clinic, Cleveland, OH, where only 5% of patients admitted to the hospital tested positive for penicillin hypersensitivity. Other studies have shown even fewer numbers. However, since some patients maintain penicillin specific IgE for 30 to 40 years, differentiation of patients who are still allergic and who are no longer allergic is paramount. Considering the potential to “lose” the allergy, patient histories that are not always helpful, and the possibility of a severe life-threatening anaphylactic episode, a more objective measure of sensitivity is required. The traditional and most established method for evaluating penicillin allergy is skin testing. Skin testing for penicillin allergy can only be carried out for The Gell and Coombs Type I reaction, mediated by IgE. Antibodies to the penicillin molecule are usually specific to the beta-lactam ring. When this molecule enters the serum, it spontaneously shifts into other forms, including the penicilloate and penilloate forms. These different metabolic forms of the beta-lactam ring need to be part of the skin-testing regimen. Although there are several different protocols in the literature, the preferred method of testing is to use three reagents: penicillin G, a derivative of penicillin call “pre-pen,” and the minor determinant mixture (MDM). Since MDMs are not commercially available, many allergist/immunologists test with the other two components. Without MDMs in the skin-testing regimen, 3-20 % of potential antigens may not be tested for. For that reason, a supervised medication challenge is often done if the initial prick test and subsequent intradermal tests are negative. An oral penicillin challenge can be conducted with 250mg of Pen V K. When skin testing with MDMs included, it is presumed that all potential antigens associated with beta-lactam allergies were evaluated. This does not include rare reactions to the molecular side chains of certain medications. If skin testing is unavailable, or if a patient cannot undergo skin testing, then penicillin RAST testing can be obtained. Determining the blood level of IgE for penicillin is only about 70-80% specific as it tests only for a few possible antigens. If patients are negative on skin testing and have no reaction to the medication challenge, then they should be able to tolerate penicillin. If a patient tests positive, then penicillin should be avoided as there is a two-thirds chance that the patient would have an adverse reaction if given penicillin. |
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