Drug Skin Metabolites and Allergic Drug Reactions
Purpose of review: Presentation of recent studies about xenobiotica metabolism of the skin and its impact on drug-allergic reactions.
Recent findings: The skin possesses not only multiple cytochrome P450 isoenzymes but also influx and efflux transporter proteins. The pattern of cytochrome P450 isoenzymes in the skin differs from the pattern in the liver. Studies on the role of this metabolism in drug-induced hypersensitivity have mainly focused on sulphonamides, anticonvulsants, diclofenac and nevirapine. Studies with the contact sensitizer carvoxime provided evidence for the decisive role of xenobiotica metabolism in antigen-presenting cells.
Summary: The skin is a major target organ for allergic drug reactions that may be explained by its different barrier functions including immune system and the armamentarium of xenobiotica-metabolizing enzymes.
The skin is a major target organ for allergic reactions to small molecular weight compounds. Examples include drug-allergic reactions that can present with many different clinical manifestations including bullous drug reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, although morbilliform drug rashes are the most common. Another example is allergic contact dermatitis that can be induced by topically applied drugs. However, a multitude of other chemical compounds can also elicit similar reactions. The sensitization process that finally leads to allergic contact dermatitis has the following features that are in common with allergic drug reactions: they are induced in more than 90% by small molecular weight compounds, and allergic contact dermatitis as well as drug-induced exanthemas, which are, by far the most common type of allergic drug hypersensitivity reactions, delayed-type allergic reactions. Thus, lessons on the pathophysiology of these adverse drug reactions can be learnt from studies with contact sensitizers.
There are two main reasons for the observation that the skin is a major target organ for these allergic reactions. Firstly, the skin possesses antigen-presenting dendritic cells that are able in particular to elicit hypersensitivity reactions (in contrast to those in the gastrointestinal tract). Secondly, the skin possesses the armamentarium to metabolize xenobiotica to highly reactive species that are able to bind to high molecular weight compounds, which may lead to sensitization via the formation of haptens. In this review, we will summarize the recent evidence with regard to skin as a xenobiotica-metabolizing organ, studies on the role of metabolism in allergic reactions to sulphonamides, diclofenac, anticonvulsants and nevirapine, and finally some conclusions from studies with contact sensitizers that might be relevant to the pathogenesis of drug hypersensitivity reactions.
Abstract and Introduction
Abstract
Purpose of review: Presentation of recent studies about xenobiotica metabolism of the skin and its impact on drug-allergic reactions.
Recent findings: The skin possesses not only multiple cytochrome P450 isoenzymes but also influx and efflux transporter proteins. The pattern of cytochrome P450 isoenzymes in the skin differs from the pattern in the liver. Studies on the role of this metabolism in drug-induced hypersensitivity have mainly focused on sulphonamides, anticonvulsants, diclofenac and nevirapine. Studies with the contact sensitizer carvoxime provided evidence for the decisive role of xenobiotica metabolism in antigen-presenting cells.
Summary: The skin is a major target organ for allergic drug reactions that may be explained by its different barrier functions including immune system and the armamentarium of xenobiotica-metabolizing enzymes.
Introduction
The skin is a major target organ for allergic reactions to small molecular weight compounds. Examples include drug-allergic reactions that can present with many different clinical manifestations including bullous drug reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, although morbilliform drug rashes are the most common. Another example is allergic contact dermatitis that can be induced by topically applied drugs. However, a multitude of other chemical compounds can also elicit similar reactions. The sensitization process that finally leads to allergic contact dermatitis has the following features that are in common with allergic drug reactions: they are induced in more than 90% by small molecular weight compounds, and allergic contact dermatitis as well as drug-induced exanthemas, which are, by far the most common type of allergic drug hypersensitivity reactions, delayed-type allergic reactions. Thus, lessons on the pathophysiology of these adverse drug reactions can be learnt from studies with contact sensitizers.
There are two main reasons for the observation that the skin is a major target organ for these allergic reactions. Firstly, the skin possesses antigen-presenting dendritic cells that are able in particular to elicit hypersensitivity reactions (in contrast to those in the gastrointestinal tract). Secondly, the skin possesses the armamentarium to metabolize xenobiotica to highly reactive species that are able to bind to high molecular weight compounds, which may lead to sensitization via the formation of haptens. In this review, we will summarize the recent evidence with regard to skin as a xenobiotica-metabolizing organ, studies on the role of metabolism in allergic reactions to sulphonamides, diclofenac, anticonvulsants and nevirapine, and finally some conclusions from studies with contact sensitizers that might be relevant to the pathogenesis of drug hypersensitivity reactions.
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