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Upon completion of the chapter, the reader will be able to:

  1. Describe the potential incidence of immunoglobulin-E (IgE)- and non-IgE-mediated (immune and nonimmune) drug hypersensitivity reactions and why it is difficult to obtain accurate estimates.

  2. Understand the Gell and Coombs categories of immunologic reactions and more recently described immunologic mechanisms.

  3. Identify the classes of drugs most commonly associated with IgE- and non–IgE-mediated drug hypersensitivity reactions.

  4. Recommend specific treatment for anaphylaxis.

  5. Recommend an approach to drug selection in patients with multiple drug sensitivities.

  6. Understand the utility of drug challenge and desensitization procedures.


Drug hypersensitivity reactions collectively encompass immunoglobulin E (IgE)- and non–IgE-mediated (immune and nonimmune, previously “pseudoallergic”) drug hypersensitivity reactions. These reactions are rarely confirmed by testing and are subject to both overreporting and underreporting, making statistical analysis imprecise. image Approximately 5% to 10% of adverse drug reactions occur on an allergic or immunologic basis. However, these represent a disproportionate 24% of reported adverse drug reactions in hospitalized patients and are costly, with accompanying morbidity and mortality.1,2 Between 10% and 20% of hospital inpatients experience drug adverse events versus 7% in the general population, with about one-third possibly due to hypersensitivity; however, many such reactions may not be reported, especially in pediatrics.1,3,4 Costs of inpatient drug hypersensitivity reactions (in US dollars) are estimated at up to $600 million annually in 2002, which equates to at least $850 million in 2020.5 Financial burden calculations include indirect costs: time and lost labor, use of more expensive alternative medications, and treatment failures, in addition to direct reaction treatment costs. Accurate data regarding outpatient reaction rates are even more elusive. The term “drug allergy” in a patient record/electronic medical record (EMR) often conveys little medical meaning, as such information is self-reported, and may not delineate symptoms or incorporate provider assessment of probable causality (eg, adverse effect vs IgE-mediated). Potential clinical outcomes might therefore range from inappropriately excessive treatment to lack of recognition of anaphylaxis risk. Clearly, an understanding of mechanisms of drug hypersensitivity reactions and how these might be accurately identified, documented, managed, and ideally prevented is of vital importance.


Drug hypersensitivity reactions are a result of diverse mechanisms of immune recognition and activation, resulting in a broad array of clinical findings. The fundamental Gell and Coombs classification, used for decades, remains a framework for considering mechanisms of immunologic drug reactions (Table 54–1).6,7

Table 54–1Reaction Classification, Clinical Symptoms, and Potential Causative Drugs6,7

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