Classification and epidemiology of hypersensitivity drug reactions

Hypersensitivity drug reactions are adverse effects of drugs taken at a dose that is tolerated by normal subjects that clinically resemble allergy. Although they are a frequent and almost constant worry for prescribing physicians, extensive epidemiologic studies are lacking, because numerous reactions with symptoms suggestive of an allergy are often considered real drug allergies. Only when immunologic mechanisms are involved should these reactions be classified as drug allergy [1]. The vast majority of allergic drug reactions are found to be IgE-mediated or T-cell mediated. Unfortunately, allergic drug reactions may not be differentiated easily from nonimmunologic hypersensitivity drug reactions or from another diagnosis such as an infectious exanthema. Many persons who experience a hypersensitivity drug reaction are cataloged as being allergic to the drug without further investigation [2-5]. The diagnostic work-up of a hypersensitivity drug reaction is difficult [5]. Reasons for this include the following: (1) the reaction itself is rarely documented; (2) the clinical presentation is heterogeneous, mirroring many distinct pathophysiologic events; (3) several drugs are often taken simultaneously; (4) many factors besides the drug can be involved; and (5) when the reaction occurred a long time ago, sensitivity could be lost. Another problem is the lack of consensual diagnostic procedures for many drugs [6], although efforts are underway to overcome this deficiency [6-10]. Indeed, test reagents are not standardized for in vitro or in vivo (skin) tests, and provocation tests are cumbersome and possibly harmful for the patient. Many physicians (and epiderniologic references) rely on the clinical history without attempting to prove the relationship between drug intake and symptoms or clarifying the underlying pathophysiology of the reaction. Such an attitude leads to a misunderstanding of the epidemiology and pathophysiology of this highly relevant field. Additionally, the frequency of drug hypersensitivities may be affected by changes in the output of pharmaceutical industry and prescription patterns. Before considering the importance of hypersensitivity drug reactions as a public health problem, one must define as precisely as possible what is meant by drug hypersensitivity.