Delayed Drug Hypersensitivity

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The summary below is from the full report titled "Delayed Drug Hypersensitivity Reactions." It is in the 21 October 2003 issue of Annals of Internal Medicine (volume 139, pages 683-693). The author is W.J. Pichler.

What is the problem and what is known about it so far?

Allergic drug reactions (hypersensitivity) are unpredictable. Many drug hypersensitivity reactions produce severe skin rashes. Drug-induced skin hypersensitivity reactions can occur rapidly after exposure (immediate-type hypersensitivity) or after a delay of a few days (delayed hypersensitivity). Delayed hypersensitivity is due to interactions between the drug and a particular type of white blood cell known as a T cell. Although T cells help the body develop immunity against infection, they can also cause adverse effects in certain circumstances. T cells produce harmful effects in allergic drug reactions through a series of complex biological reactions. Recent discoveries have broadened our understanding of how T cells produce drug hypersensitivity in the skin.

Why did the author do this review?

To educate physicians about newer theories on how allergic drug reactions are produced.

How did the author do this review?

The author reviewed recent publications that investigated the biological interactions that occur between drugs and T cells.

What did the author find?

T cells possess specialized chemical "receptors" on their outer surfaces, giving them the ability to recognize foreign substances. For a drug to react with a receptor, it must first be presented to the surface of the T cell by another cell in a way that holds the reactive portion of its structure in the correct position for interaction to take place. This often requires that the drug "hook a ride" on a larger chemical that clamps it into the correct position by forming a chemical bond with the drug. If the drug is not chemically reactive enough to produce a chemical bond, it can sometimes be modified by the body's metabolism into a form that can then effectively bond with the larger chemical. Recently, researchers have recognized a third way that a drug can react with T cells, even if it cannot form a chemical bond with the "carrier" chemical. This involves a much looser connection (known as a labile connection) with the T cell or the carrier. A labile connection is based on the structure of the drug rather than its chemical reactivity. In this method of reaction, the drug tucks into the receptor structure without forming a chemical bond but is still able to stimulate the immune receptor. The manner of drug presentation (chemical bond vs. labile connection) may determine what kinds of hypersensitivity reaction can occur in the skin. Drug hypersensitivity reactions may kill cells in various layers of the skin, forming blisters or severe destruction; alternatively, they may be characterized by inflammation. The actual form of the skin reaction depends on the specific chemicals released by the T cell in response to the offending drug.

What are the implications of this review?

Drug allergies are complicated reactions that involve many different chemical and biological interactions. Recognition of novel mechanisms may provide better methods of preventing and treating these diseases.