EPITOMES-ALLERGY AND IMMUNOLOGY
456 45IPTMSALRYADIMNLG
Penicillin Allergy FOR MORE THAN 50 years, the penicillins have been among the most useful antibiotics available for the treatment of human infections. The use of the penicillins and other j-lactam antibiotics has been limited, however, by relatively high rates of allergic reactions among patients and the failure of physicians adequately to identify those patients who are at risk for such reactions. Treatment courses with penicillins are complicated by hypersensitivity reactions in as many as 10%, anaphylactic reactions in 0.01%, and fatal reactions in 0.0015%, or about 1 per 50,000 treatment courses. Identification of the immunologic metabolites of penicillin has enabled a prospective identification of many patients at risk for systemic or potentially fatal type 1 immediate (IgEmediated) hypersensitivity reactions to these antibiotics. In vivo, a small portion of administered penicillin is metabolized to biochemically active compounds that can covalently bind to plasma proteins and elicit immunologic responses. The penicilloyl product is the most abundant metabolite, accounting for 95% of protein-bound drug metabolites, and is thus termed the "major determinant." This determinant is commercially available for skin testing. Three other penicillin metabolites, termed the "minor determinants," consisting of penicillin, penicilloic acid, and penilloic acid may play an important role in penicillin allergy. Although not currently available commercially, they have been synthesized in several laboratories at academic centers. Skin testing is simple, sensitive, and specific for predicting immediate-type hypersensitivity reactions to the penicillins. When testing is done by trained personnel, patients with a history of an adverse reaction to penicillin and negative epicutaneous and intradermal skin tests with major and minor determinants (and appropriate positive and negative controls) have less than a 1% risk of a subsequent IgE-mediated systemic reaction. Skin test reactions to any of the penicillin determinants carries about a 70% chance of systemic reactions when the drug is subsequently administered. The sensitivity of testing with the penicilloyl (major) determinant alone is only 76%, whereas the sensitivity of testing with the penicilloyl and benzylpenicillin determinants is approximately 93%. In the absence of available minor determinants, physicians have relied on the clinical history alone and the availability of alternative antibiotics. In one report, only 10% of patients with a history of penicillin allergy were found to have positive skin tests with both the major and minor determinants. As many as 90% of patients are thus unnecessarily deprived of a highly effective, nontoxic, often less expensive class of antibiotics. Some practitioners have suggested using "old" aqueous penicillin for skin testing, erroneously thinking that the aging process will lead to the formation of hydrolysis products that will cross-react with minor determinants; this is an unacceptable practice. It is hoped that the penicillin minor determinants will be commercially available in the near future. Although cross-reactivity between cephalosporins and penicillin has been shown in many animal systems, the true in vivo incidence of such cross-reactivity is not known. Cephalosporin skin testing is limited to the native drug because the relevant degradation products are unknown, but the use of the native drug alone appears to have little predictive value. Ongoing prospective studies suggest that the incidence of cross-
reactivity is probably low, but more accurate determination is needed. In studies to determine the level of allergic crossreactivity between the monobactam antibiotics and the penicillins, there was no evidence of immunologic cross-reactivity. Moreover, to date, patients with a history of true IgE-mediated penicillin reactions have had no adverse reactions from monobactam antibiotics. Studies have also been conducted comparing skin test reactivity between the penicillin determinants and the major and minor determinants of the carbapenam antibiotic, imipenem. A high degree of cross-reactivity between the minor determinants of penicillin and the analogous determinants of imipenem was found, suggesting that this drug should be given to penicillin-allergic persons with the same degree of caution as if the patients were to receive penicillin. DANIEL ADELMAN, MD
San Francisco, California REFERENCES Adkinson NF, Saxon A, Spence MR, Swabb EA: Cross-allergenicity and immunogenicity of aztreonam. Rev Infect Dis 1985; 7(Suppl 4):S613-S621 Saxon A, Adelman DC, Patel A, Hajdu R, Calandra GB: Imipenem cross-reactivity with penicillin in humans. J Allergy Clin Immunol 1988; 82:213-217 Saxon A, Beall GN, Rohr AS, Adelman DC: Immediate hypersensitivity reactions to f3-lactam antibiotics. Ann Intern Med 1987; 107:204-215 Weiss ME, Adkinson NF: Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy 1988; 18:515-540
Points to Consider in the Care of Patients Infected With the Human Immunodeficiency Virus As HUMAN IMMUNODEFICIENCY VIRUS (HIV) disease is recognized more as a progressive chronic illness, primary care practitioners will be assuming more responsibility for the care of these patients. Practitioners need to be familiar with the initial staging of the disease, current health maintenance recommendations, and prophylaxis and treatment regimens. The initial staging of HIV infection relies on the patient's history, pertinent physical findings, the CD4:CD8 cell ratio, and the absolute CD4 and CD8 cell counts. A history of opportunistic infections, malignant neoplasms, or wasting symptoms is important, but a history of tuberculosis, syphilis, or herpes simplex or zoster infections should also be obtained. A thorough travel history is important because disseminated coccidioidomycosis or histoplasmosis can be the initial presentation of an HIV-infected patient from an endemic area.
The initial physical examination should emphasize those findings that define the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex. The early signs of HIV dementia in particular can be subtle. Once a person tests positive for HIV antibodies, laboratory studies should include a complete blood count, a chemistry panel, and T-cell subsets. Serologic tests should include a hepatitis panel, rapid plasma reagin (RPR) or VDRL, and a Toxoplasma titer. A standard purified protein derivative (PPD) and a control skin test should be administered. In asymptomatic patients, the T-cell subsets and complete blood count should be repeated every three to six months. The chemistry panel should be repeated every six months or more frequently if symptoms develop or if the patient is taking a hepatotoxic medication. The RPR and PPD tests should be repeated annually. Vaccinations have been found to be variably effective in HIV-infected persons: the pneumococcal vaccine should be given once, a conjugate influenza
456 45IPTMSALRYADIMNLG
Penicillin Allergy FOR MORE THAN 50 years, the penicillins have been among the most useful antibiotics available for the treatment of human infections. The use of the penicillins and other j-lactam antibiotics has been limited, however, by relatively high rates of allergic reactions among patients and the failure of physicians adequately to identify those patients who are at risk for such reactions. Treatment courses with penicillins are complicated by hypersensitivity reactions in as many as 10%, anaphylactic reactions in 0.01%, and fatal reactions in 0.0015%, or about 1 per 50,000 treatment courses. Identification of the immunologic metabolites of penicillin has enabled a prospective identification of many patients at risk for systemic or potentially fatal type 1 immediate (IgEmediated) hypersensitivity reactions to these antibiotics. In vivo, a small portion of administered penicillin is metabolized to biochemically active compounds that can covalently bind to plasma proteins and elicit immunologic responses. The penicilloyl product is the most abundant metabolite, accounting for 95% of protein-bound drug metabolites, and is thus termed the "major determinant." This determinant is commercially available for skin testing. Three other penicillin metabolites, termed the "minor determinants," consisting of penicillin, penicilloic acid, and penilloic acid may play an important role in penicillin allergy. Although not currently available commercially, they have been synthesized in several laboratories at academic centers. Skin testing is simple, sensitive, and specific for predicting immediate-type hypersensitivity reactions to the penicillins. When testing is done by trained personnel, patients with a history of an adverse reaction to penicillin and negative epicutaneous and intradermal skin tests with major and minor determinants (and appropriate positive and negative controls) have less than a 1% risk of a subsequent IgE-mediated systemic reaction. Skin test reactions to any of the penicillin determinants carries about a 70% chance of systemic reactions when the drug is subsequently administered. The sensitivity of testing with the penicilloyl (major) determinant alone is only 76%, whereas the sensitivity of testing with the penicilloyl and benzylpenicillin determinants is approximately 93%. In the absence of available minor determinants, physicians have relied on the clinical history alone and the availability of alternative antibiotics. In one report, only 10% of patients with a history of penicillin allergy were found to have positive skin tests with both the major and minor determinants. As many as 90% of patients are thus unnecessarily deprived of a highly effective, nontoxic, often less expensive class of antibiotics. Some practitioners have suggested using "old" aqueous penicillin for skin testing, erroneously thinking that the aging process will lead to the formation of hydrolysis products that will cross-react with minor determinants; this is an unacceptable practice. It is hoped that the penicillin minor determinants will be commercially available in the near future. Although cross-reactivity between cephalosporins and penicillin has been shown in many animal systems, the true in vivo incidence of such cross-reactivity is not known. Cephalosporin skin testing is limited to the native drug because the relevant degradation products are unknown, but the use of the native drug alone appears to have little predictive value. Ongoing prospective studies suggest that the incidence of cross-
reactivity is probably low, but more accurate determination is needed. In studies to determine the level of allergic crossreactivity between the monobactam antibiotics and the penicillins, there was no evidence of immunologic cross-reactivity. Moreover, to date, patients with a history of true IgE-mediated penicillin reactions have had no adverse reactions from monobactam antibiotics. Studies have also been conducted comparing skin test reactivity between the penicillin determinants and the major and minor determinants of the carbapenam antibiotic, imipenem. A high degree of cross-reactivity between the minor determinants of penicillin and the analogous determinants of imipenem was found, suggesting that this drug should be given to penicillin-allergic persons with the same degree of caution as if the patients were to receive penicillin. DANIEL ADELMAN, MD
San Francisco, California REFERENCES Adkinson NF, Saxon A, Spence MR, Swabb EA: Cross-allergenicity and immunogenicity of aztreonam. Rev Infect Dis 1985; 7(Suppl 4):S613-S621 Saxon A, Adelman DC, Patel A, Hajdu R, Calandra GB: Imipenem cross-reactivity with penicillin in humans. J Allergy Clin Immunol 1988; 82:213-217 Saxon A, Beall GN, Rohr AS, Adelman DC: Immediate hypersensitivity reactions to f3-lactam antibiotics. Ann Intern Med 1987; 107:204-215 Weiss ME, Adkinson NF: Immediate hypersensitivity reactions to penicillin and related antibiotics. Clin Allergy 1988; 18:515-540
Points to Consider in the Care of Patients Infected With the Human Immunodeficiency Virus As HUMAN IMMUNODEFICIENCY VIRUS (HIV) disease is recognized more as a progressive chronic illness, primary care practitioners will be assuming more responsibility for the care of these patients. Practitioners need to be familiar with the initial staging of the disease, current health maintenance recommendations, and prophylaxis and treatment regimens. The initial staging of HIV infection relies on the patient's history, pertinent physical findings, the CD4:CD8 cell ratio, and the absolute CD4 and CD8 cell counts. A history of opportunistic infections, malignant neoplasms, or wasting symptoms is important, but a history of tuberculosis, syphilis, or herpes simplex or zoster infections should also be obtained. A thorough travel history is important because disseminated coccidioidomycosis or histoplasmosis can be the initial presentation of an HIV-infected patient from an endemic area.
The initial physical examination should emphasize those findings that define the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex. The early signs of HIV dementia in particular can be subtle. Once a person tests positive for HIV antibodies, laboratory studies should include a complete blood count, a chemistry panel, and T-cell subsets. Serologic tests should include a hepatitis panel, rapid plasma reagin (RPR) or VDRL, and a Toxoplasma titer. A standard purified protein derivative (PPD) and a control skin test should be administered. In asymptomatic patients, the T-cell subsets and complete blood count should be repeated every three to six months. The chemistry panel should be repeated every six months or more frequently if symptoms develop or if the patient is taking a hepatotoxic medication. The RPR and PPD tests should be repeated annually. Vaccinations have been found to be variably effective in HIV-infected persons: the pneumococcal vaccine should be given once, a conjugate influenza
