Overview

Drug hypersensitivity results from interactions between a pharmacologic agent and the immune system

Allergic reactions to medications represent a specific class of drug-hypersensitivity reactions mediated by the immunoglobulin IgE

However, some reactions involve additional, poorly understood mechanisms that are not easily classified

Drug-induced reactions are likely the most common iatrogenic illness

• – Complicating 5%–15% of therapeutic drug trials

• – Causing more than 100,000 deaths due to serious adverse drug-allergic reactions

Epidemiologic data support the existence of specific factors that increase the risk of general adverse drug reactions, such as female gender, history of asthma, systemic lupus erythematosus, or use of beta-blockers. Although atopic patients do not have a higher rate of sensitization to drugs, they are at increased risk for serious allergic reactions

Identifiable risk factors for drug-hypersensitivity reactions include age, female gender, concurrent illnesses, and previous hypersensitivity to related drugs

Larger molecular drugs with greater structural complexity are more likely to be immunogenic, although some drugs may have a smaller molecular weight but may become immunogenic by being coupled with carrier proteins

Another factor increasing the frequency of hypersensitivity drug reactions is the route of drug administration

• – Topical, intramuscular, and intravenous administrations are more likely to cause hypersensitivity reactions

• – These effects are caused by the efficiency and higher amount of allergic antigen being presented to the skin

• – Oral medications are less likely to result in drug hypersensitivity

Classification

Drug hypersensitivity is a clinical diagnosis based on available data at hand

Drug reactions can be classified into immunologic and nonimmunologic

The majority of adverse drug reactions are caused by predictable, nonimmunologic effects

The remaining minority of adverse drug events are caused by unpredictable effects that may or may not be immune mediated

Immune-mediated reactions account for 5%–10% of all drug reactions and constitute true drug-allergic hypersensitivity, with IgE-mediated drug allergies falling into this category

The more common, yet unpredictable, nonimmune drug reactions seen often in practice can be classified in three ways

• – Pseudoallergic reactions are the result of direct mast cell activating, histamine releasing by exposure to drugs such as opiates, vancomycin (Vancocin), and radiocontrast media

• – These reactions may be clinically indistinguishable from true immune-related drug reactions, but do not involve drug-specific IgE

Idiosyncratic reactions are qualitatively aberrant reactions that cannot be explained by the known pharmacologic action of the drug and occur only in a small percent of the population

• – A classic example of an idiosyncratic reaction is drug-induced hemolysis in persons with glucose-6-phosphate dehydrogenase (G6PD) deficiency

Drug intolerance occurs when a patient has a lower threshold toward experiencing the normal pharmacologic action of a drug

• – An example might include developing tinnitus after a single average dose of aspirin instead of the usual experience after chronic high-dose utilization

• – These are likely not true allergies and are often erroneously reported on hospital charts and electronic medical records (EMRs) as true allergies instead of side effect intolerances