Multiple Drug Allergy

Opinion statement

The tendency to develop multiple drug hypersensitivity (MDH), defined as a hypersensitivity to two or more structurally unrelated drugs, occurs in up to 10% of people who have a severe and proven immune-mediated drug hypersensitivity reaction (DHR). There are two subtypes of MDH: in the first type, MDH develops if different drugs are administered simultaneously; in the second, MDH develops if different drugs are administered sequentially, sometimes years apart. MDH presents clinically as immediate and/or non-immediate reactions. The main drugs responsible for MDH are antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), antiepileptics, hypnotics, antidepressants, corticosteroids, and local anesthetics. There are two pathogenic mechanisms of developing MDH: the first is T cell mediated and the second is IgE mediated. Activated T cells are directed against the culprit drug or its metabolites. MDH can be proven by positive responses to patch tests and/or delayed-reading intradermal tests as well as a positive lymphocyte transformation test. During the first DHR, the immune stimulation may lower the threshold of T cell reactivity to that drug and facilitate the immune response to the second drug, similar to viral infections. The drug-reactive T cells in patients with MDH display an enhanced state of activation. Less frequently, the pathogenic mechanism is IgE mediated. This can be proven by positive responses to an immediate-reading intradermal test and provocation test, as well as with positive specific IgE to culprit drug and a basophil activation test (BAT). A T cell-mediated reaction might be built on the IgE-mediated reaction. It is well-known that the tolerance mechanism to small molecular compounds fails in MDH patients, although the pathogenic mechanisms of this syndrome are still unknown.

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