The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash
Current advances in the study of cutaneous adverse drug reactions can be attributed to the recent understanding that the skin is both a metabolically and immunologically competent organ. The ability of the skin to serve as a protective barrier with limited drug biotransformation ability, yet highly...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Immunotoxicology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/1547691X.2018.1514444 |
| _version_ | 1819238492149907456 |
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| author | Amy Sharma Yoshiro Saito Shuen-Iu Hung Dean Naisbitt Jack Uetrecht Jeanine Bussiere |
| author_facet | Amy Sharma Yoshiro Saito Shuen-Iu Hung Dean Naisbitt Jack Uetrecht Jeanine Bussiere |
| author_sort | Amy Sharma |
| collection | DOAJ |
| description | Current advances in the study of cutaneous adverse drug reactions can be attributed to the recent understanding that the skin is both a metabolically and immunologically competent organ. The ability of the skin to serve as a protective barrier with limited drug biotransformation ability, yet highly active immune function, has provided insights into its biological capability. While the immune response of the skin to drugs is vastly different from that of the liver due to evolutionary conditioning, it frequently occurs in response to various drug classes and manifests as a spectrum of hypersensitivity reactions. The skin is a common site of adverse and idiosyncratic drug reactions; drug-specific T-cells, as well as involvement of an innate immune response, appear to be key mechanistic drivers in such scenarios. Association of other factors such as human leukocyte antigen (HLA) polymorphisms may play a significant role for particular drugs. This review aims to integrate emerging findings into proposed mechanisms of drug metabolism and immunity in the skin that are likely responsible for rashes and other local allergic responses. These unique biological aspects of the skin, and their translation into implications for drug development and the use of animal models, will be discussed. |
| first_indexed | 2024-12-23T13:37:05Z |
| format | Article |
| id | doaj.art-50540a0dcbe54145b367ce2b61c7d736 |
| institution | Directory Open Access Journal |
| issn | 1547-691X 1547-6901 |
| language | English |
| last_indexed | 2024-12-23T13:37:05Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj.art-50540a0dcbe54145b367ce2b61c7d7362022-12-21T17:44:59ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012019-01-0116111210.1080/1547691X.2018.15144441514444The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rashAmy Sharma0Yoshiro Saito1Shuen-Iu Hung2Dean Naisbitt3Jack Uetrecht4Jeanine Bussiere5Amgen ResearchNational Institute of Health SciencesNational Yang-Ming UniversityUniversity of LiverpoolUniversity of TorontoAmgen ResearchCurrent advances in the study of cutaneous adverse drug reactions can be attributed to the recent understanding that the skin is both a metabolically and immunologically competent organ. The ability of the skin to serve as a protective barrier with limited drug biotransformation ability, yet highly active immune function, has provided insights into its biological capability. While the immune response of the skin to drugs is vastly different from that of the liver due to evolutionary conditioning, it frequently occurs in response to various drug classes and manifests as a spectrum of hypersensitivity reactions. The skin is a common site of adverse and idiosyncratic drug reactions; drug-specific T-cells, as well as involvement of an innate immune response, appear to be key mechanistic drivers in such scenarios. Association of other factors such as human leukocyte antigen (HLA) polymorphisms may play a significant role for particular drugs. This review aims to integrate emerging findings into proposed mechanisms of drug metabolism and immunity in the skin that are likely responsible for rashes and other local allergic responses. These unique biological aspects of the skin, and their translation into implications for drug development and the use of animal models, will be discussed.http://dx.doi.org/10.1080/1547691X.2018.1514444skin toxicologyidiosyncraticpharmacogenomicsmechanismsmetabolismskin rash bioactivationadverse drug reactionimmunology |
| spellingShingle | Amy Sharma Yoshiro Saito Shuen-Iu Hung Dean Naisbitt Jack Uetrecht Jeanine Bussiere The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash Journal of Immunotoxicology skin toxicology idiosyncratic pharmacogenomics mechanisms metabolism skin rash bioactivation adverse drug reaction immunology |
| title | The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash |
| title_full | The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash |
| title_fullStr | The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash |
| title_full_unstemmed | The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash |
| title_short | The skin as a metabolic and immune-competent organ: Implications for drug-induced skin rash |
| title_sort | skin as a metabolic and immune competent organ implications for drug induced skin rash |
| topic | skin toxicology idiosyncratic pharmacogenomics mechanisms metabolism skin rash bioactivation adverse drug reaction immunology |
| url | http://dx.doi.org/10.1080/1547691X.2018.1514444 |
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