SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

11/25/03

Delayed drug hypersensitivity reactions

Summary
The best characterized allergic reactions to drugs are the immediate IgE-mediated reactions, responsible for the acute urticaria and/or anaphylaxis seen most commonly in allergic reactions to beta-lactam antibiotics. However, much less is known about delayed onset hypersensitivity (DH) reactions seen in adverse reactions to a variety of drugs. Pichler of the Univ. of Bern in Switzerland recently reviewed the subject of drug-induced DH reactions. He pointed out that in many drug DH reactions, T lymphocytes of both CD4+ and CD8+ types may express receptors to the suspect drug (either the drug alone or the drug acting as a haptene which binds to host tissue proteins). Based mainly on studies by his own group, Pichler concluded that distinct functional sub-types of such T cells appear to be responsible for particular types of clinical reactions. For example, in maculo-papular drug reaction, perforin-positive and granzyme B positive CD4+ T cells kill activated keratinocytes. In comparison, drug-induced vesiculo-bullous skin reactions are associated with large numbers of cytotoxic CD8+ T cells accumulating in the epidermis. Drug-specific T cells also may orchestrate inflammatory skin reactions through the release of one or more cytokines. Depending on the cytokines released. These may be secondary activation of neutrophils, eosinophils, or monocytes. The end result may be a pathogenically complex profile of delayed onset reactions to drugs.

Reference
Ann Intern Med 2003; 139:683-93

Editor's Comments
The findings described above are of considerable interest in unraveling the mechanisms involved in a common but poorly understood clinical problem. I think that one has to defer drawing definitive conclusions about the clinical relevance of these findings for several reasons: 1) although Dr. Pichler's group has a fairly extensive experience as a basis for his conclusions described above, I am not aware that most of their observations have been yet confirmed by other groups; 2) although it does seem reasonable to postulate a key role of T cell sub-populations in drug induced DH reactions in the skin, the mechanism by which involvement of other organ systems in drug DH reactions occurs is not known; 3) there is not yet a reliable diagnostic test for detecting current DH to a particular drug when a previous reaction occurred during therapy with multiple drugs (a common scenario in hospitalized patients).

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