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.

BACKGROUND: A history (or lack thereof) of penicillin allergy is known to be unreliable in predicting reactions on subsequent administration of the drug. This study tests the usefulness of four penicillin allergen skin tests in the prediction of IgE-mediated reactions subsequent to administration of penicillin. METHODS: Eight centers cooperated in the National Institute of Allergy and Infectious Diseases trial of the predictive value of skin testing with major and minor penicillin derivatives. Hospitalized adults were tested with a major determinant (octa-benzylpenicilloyl-ocytalysine) and a minor determinant mixture and its components (potassium benzylpenicillin, benzylpenicilloate, and benzylpenicilloyl-N-propylamine). Patients then received a therapeutic course of penicillin and were observed, for 48 hours, for adverse reactions compatible with an IgE-mediated immediate or accelerated allergy. RESULTS: Among 726 history-positive patients, 566 with negative skin tests received penicillin and only seven (1.2%) had possibly IgE-mediated reactions. Among 600 history-negative patients, 568 with negative skin tests received penicillin and none had a reaction. Only nine of the 167 positive skin test reactors received a penicillin agent and then usually by cautious incremental dosing. Two (22%) of these nine patients had reactions compatible with IgE-mediated immediate or accelerated penicillin allergy; both were positive to the two determinants. CONCLUSIONS: These data corroborate previous data about the negative predictive value of negative skin tests to these materials. The reaction rate in skin test-positive patients was significantly higher than in those with negative skin tests, demonstrating the positive predictive value of positive tests to both major and minor determinants. The number of patients positive only to the major determinant or only to the minor determinant mix was too small to draw conclusions about the positive predictive value of either reagent alone.

Diagnostic tests for patients with suspected allergic disease. Utility and limitations.

STUDY OBJECTIVE: To evaluate the clinical efficacy of diagnostic tests used for persons with suspected allergic disease. DESIGN: Information synthesis based on historical review of developments in the understanding of the pathophysiology of allergic diseases and on selected recent literature on efficacy of specific diagnostic tests. MAIN RESULTS: Skin testing is most effective when based on clues from the patient's history. The sensitivity and specificity of skin testing methods are compared: skin prick testing alone is often sufficient to identify or exclude immunoglobulin E (IgE)-mediated hypersensitivity, including food allergy. Except for penicillin and certain macromolecules, skin testing is not useful for evaluating drug allergy. Skin test titration may be useful for determining the starting dose for immunotherapy; otherwise it is rarely necessary. The patch skin test helps identify the cause of allergic contact dermatitis. Bronchial provocation testing is useful in special cases. Oral provocation testing may be used to identify allergy or other intolerance to suspected foods, food additives, and certain drugs. Provocation testing is time-consuming and requires special precautions. In-vitro methods for identifying allergen-specific IgE are especially useful when skin testing is unreliable, equivocal, or cannot be done. In-vitro tests should be used as adjuncts to the clinical interview and examination. CONCLUSIONS: Tests that are effective for identifying allergenic substances usually can be determined from a careful patient interview. Clinicians should be aware of nonspecific test results and allergy tests of unproven effectiveness.

Drug reactions: allergy and near-allergy.

In this review, allergic drug reactions are discussed in terms of their immunologic mechanisms, with an emphasis given to new information that has appeared recently in the medical literature. Because of their recent emergence as important categories to recognize and manage appropriately, the pseudoallergic reactions next receive special attention. The last section on management covers diagnostic and preventive strategies, and concludes with a discussion of desensitization.

The value of skin testing for penicillin allergy diagnosis.

Skin testing is reliable and useful to rule out penicillin allergy in most patients who have a history of previous reactions. When we tested 291 inpatients in the University of Washington hospitals for the presence or absence of penicillin allergy, of 97 with a history of penicillin allergy, 12 (12.4%) had positive skin tests. Of 194 patients with no or an unknown history, only 4 (2%) had positive skin tests. Two of the 16 who had positive skin tests (12.5%) reacted only to minor determinant mixtures. Of the skin test-negative patients, 261 were treated with one of the penicillins and only two had any reactions.

Allergy and adverse drug reactions.

This review begins with a classification of adverse drug reactions and a summary of those features that distinguish allergic from toxic and idiosyncratic reactions. Factors that influence the risk of developing drug allergy are then reviewed, followed by a discussion of the known and suspected immunologic mechanisms responsible for the development of drug allergy. The next section-on the types of clinical reactions-begins with the reactions that are mediated, or suspected of being mediated, by antibodies of the immunoglobulin E class. These are followed by a description of reactions involving single organ systems and those involving several systems. The next section reviews the cutaneous reactions that are sometimes due to drug allergy, and those that may be mistakenly blamed on drug allergy. This is followed by a discussion of pseudoallergic drug reactions-caused by toxicity or side effects of some drugs. The review concludes with a discussion of the prevention and treatment of reactions that are allergic or commonly suspected of being allergic.

Role of cell-mediated immunity in Hymenoptera allergy.

Currently there is little information regarding the immunologic mechanisms responsible for large local reaction (LLR) after Hymenoptera stings. To investigate this question, we measured in vitro lymphocyte proliferation and delayed skin reactivity to venom antigens in 10 subjects with LLR (six with LLR only and four with LLR and systemic reactions), seven subjects with systemic reactions, and eight nonallergic controls. The lymphocyte response to venoms in the LLR group was greater than that in either the systemic reactor group (p less than 0.05) or the control group (p less than 0.001). In contrast, lymphoproliferative responses to Candida albicans, streptokinase-streptodornase, and phytohemagglutinin were comparable in the three groups. Forty percent of the LLR group had positive delayed skin tests to venom antigens, and none of the patients in the systemic reactor group had such responses. These findings suggest that cellular immune mechanisms play a role in the pathogenesis of LLR after Hymenoptera stings.

Drug therapy in the management of asthma.

In the past decade there has been substantial improvement in the quality of drug therapy for asthma. In part, this reflects the greater sophistication and confidence in the use of bronchodilator drugs, after their role in modifying the intracellular concentration of cyclic nucleotides was discovered. Another advance has come from the appearance of adequate information on theophylline blood levels and half-lives and their variability in man. The increasing availability of theophylline blood levels has aided not only in the selection of therapeutic doses but also in determining the effectiveness of newer products that, for example, promise to have a more sustained effect when given by mouth. The plight of asthmatic patients dependent on oral glucosteroid therapy has been substantially eased with the development of new steroid-sparing drugs that are effective by inhalation.

New drug evaluation using exercise-induced bronchospasm.

Exercise-induced asthma was used to demonstrate that a xanthone, a new orally active cromolyn-like drug, has significant activity in man. The effect of a single oral dose of 8 mg/kg was studied in a double-blind corss-over fashion at two and five hours after administration, with significant inhibition of post-exercise bronchospasm being seen at five hours. Further study seems indicated to determine optimal dosage and clinical effectiveness.