Date Published: November 10, 2011
Publisher: BioMed Central
Author(s): Richard Warrington, Fanny Silviu-Dan.
Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR) not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required.
Adverse drug reactions (ADRs) are defined as any harmful or unintended reaction to a drug that occurs at doses used for prevention, diagnosis, or treatment . ADRs are common in everyday clinical practice, affecting between 15-25% of patients; serious reactions occur in 7-13% of patients [2,3].
Immune-mediated allergic reactions to drugs are classified according to Gell and Coombs’ classification system, which describes the predominant immune mechanisms involved in these reactions. This classification system includes: immediate-type reactions mediated by immunoglobulin E (IgE) antibodies (type I), cytotoxic reactions mediated by immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies (type II), immune-complex reactions (type III), and delayed-type hypersensitivity reactions mediated by cellular immune mechanisms, such as the recruitment and activation of T cells (type IV) [7-9]. The mechanisms, clinical manifestations, and timing of these immune reactions are summarized in Table 2.
Factors associated with an increased risk of developing a drug allergy include age, gender, genetic polymorphisms, certain viral infections and drug-related factors (e.g., frequency of exposure, route of administration, molecular weight) (see Table 3). Drug allergy typically occurs in young and middle-aged adults, and is more common in women than men. Genetic polymorphisms in the human leukocyte antigen (HLA; a gene product of the major histocompatibility complex) as well as viral infections such as human immunodeficiency virus (HIV) and the Epstein-Barr virus (EBV), have also been linked to an increased risk of developing immunologic reactions to drugs. Susceptibility to drug allergy is influenced by genetic polymorphisms in drug metabolism. In addition, topical, intramuscular, and intravenous routes of administration are more likely to cause allergic drug reactions than oral administration; while intravenous administration is associated with more severe reactions. Prolonged high doses or frequent doses are more likely to lead to hypersensitivity reactions than a large single dose. Furthermore, large macromolecular drugs (e.g., insulin or horse antisera) or drugs that haptenate (bind to tissue or blood proteins and elicit an immune response), such as penicillin, are also associated with a greater likelihood of causing hypersensitivity reactions. Although atopic patients do not have an increased risk for drug allergy, they are at increased risk for serious allergic reactions [4,6,12-15].
The diagnosis of drug allergy requires a thorough history and the identification of physical findings and symptoms that are compatible with drug-induced allergic reactions. Depending on the history and physical examination results, diagnostic tests such as skin testing, graded challenges and induction of drug tolerance procedures may also be required. [1,4,6,15] Therefore, if drug allergy is suspected, evaluation by an allergist experienced in these diagnostic procedures is recommended.
The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents [1,11].
Prevention of future reactions is an essential part of patient management. The patient should be provided with written information about which drugs to avoid (including over-the-counter medications). The drugs should be highlighted in the hospital notes and within electronic records (where available), and the patient’s family physician should be informed of the drug allergy. Engraved allergy bracelets/necklaces, such as those provided by Medic Alert, should also be considered, particularly if the patient has a history of severe drug-induced allergic reactions .
Drug allergy is a common clinical problem; assessment by an allergist is important for appropriate diagnosis and management of the condition. Diagnosis relies on a careful history and physical examination and, in some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The mainstay of treatment for drug allergy is avoidance of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative medications. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug.
• Drug allergy encompasses a spectrum of immunologically mediated hypersensitivity reactions with varying mechanisms and clinical presentations.
Dr. Richard Warrington is the past president of the Canadian Society of Allergy & Clinical Immunology and Editor-in-Chief of Allergy, Asthma & Clinical Immunology. He has received consulting fees and honoraria from Nycomed, CSL Behring and Talecris.