Drug Allergy

Clinical Findings

A. Symptoms and Signs
The development of symptoms and the nature of the reaction can suggest whether an immunologic process is responsible for symptoms. In previously sensitized individuals, immediate hypersensitivity is manifested by rapid development of urticaria, angioedema, or anaphylaxis. Delayed onset of urticaria accompanied by fever, arthralgias, and nephritis may indicate the development of an immune complex-mediated disorder. Drug fever and Stevens-Johnson syndrome probably act by immune hypersensitivity mechanisms. Some drugs are clearly more immunogenic than others, and this can be reflected in the incidence of drug hypersensitivity. A partial list of drugs frequently implicated in drug reactions includes ß-lactam antibiotics, sulfonamides, phenytoin, carbamazepine, allopurinol, muscle relaxants used for general anesthesia, nonsteroidal anti-inflammatory drugs, antisera, and antiarrhythmic agents.

Many drugs can be associated with recognizable known toxicities, drug interactions, or idiosyncratic reactions that are not immune-mediated. These must be distinguished from true hypersensitivity reactions because the prognosis and management differ. Some estimate that only 10% or less of adverse reactions to drugs are true hypersensitivity reactions. Patients with multidrug hypersensitivity are quite rare, and those reporting "allergies" to more than three distinct classes of drugs should be carefully evaluated since intolerance to many of these drug classes may not be immunologic.

B. Laboratory Findings

1. Allergy testing
Allergy skin testing is available for a limited number of drugs, since patients may react to the native drug as well as any metabolite that covalently binds to native protein and becomes immunoreactive. Skin testing is available for patients with suspected immediate hypersensitivity to penicillin or ß-lactam antibiotics. The degree of cross-reactivity between the cephalosporin antibiotics and penicillins is uncertain. The incidence of IgE-mediated hypersensitivity appears to be less than 5%. There appears to be no allergic cross-reactivity between the monobactam antibiotics (aztreonam) and penicillin or other ß-lactam antibiotics. A high degree of cross-reactivity exists between penicillin and the carbapenem, imipenem, so this drug should be given to the penicillin-allergic patient with the same degree of caution as if the patient were to receive penicillin.

If the likelihood of immunologic reaction is low - based on the history and the assessment of likely offending agents - and if no allergy testing is available, judicious test dose challenges may be considered in a monitored setting. If the likelihood of IgE-mediated reaction is significant, these challenges are risky and rapid drug desensitization is indicated.

Occasionally, direct allergen challenge of the target organ or tissue under controlled conditions is required for definitive diagnosis. Such challenges may be bronchial, nasal, conjunctival, oral, or cutaneous. A positive test confirms that the test substance can cause the reaction, but it does not prove that an immunologic mechanism is responsible.