PMID- 30318948
OWN - NLM
STAT- MEDLINE
DCOM- 20200528
LR  - 20210109
IS  - 1547-6901 (Electronic)
IS  - 1547-691X (Linking)
VI  - 16
IP  - 1
DP  - 2019 Dec
TI  - The skin as a metabolic and immune-competent organ: Implications for drug-induced 
      skin rash.
PG  - 1-12
LID - 10.1080/1547691X.2018.1514444 [doi]
AB  - 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.
FAU - Sharma, Amy
AU  - Sharma A
AD  - Amgen Research, Thousand Oaks, CA, USA.
AD  - Genentech Inc., South San Francisco, CA, USA.
FAU - Saito, Yoshiro
AU  - Saito Y
AD  - Division of Medicinal Safety Science, National Institute of Health Sciences, 
      Tokyo, Japan.
FAU - Hung, Shuen-Iu
AU  - Hung SI
AD  - Department and Institute of Pharmacology, School of Medicine, National Yang-Ming 
      University, Taipei, Taiwan.
FAU - Naisbitt, Dean
AU  - Naisbitt D
AD  - University of Liverpool, Liverpool, UK.
FAU - Uetrecht, Jack
AU  - Uetrecht J
AD  - Faculty of Pharmacy and Medicine, University of Toronto, Toronto, Canada.
FAU - Bussiere, Jeanine
AU  - Bussiere J
AUID- ORCID: 0000-0001-6439-4051
AD  - Amgen Research, Thousand Oaks, CA, USA.
LA  - eng
GR  - MR/L006758/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Review
DEP - 20181014
PL  - England
TA  - J Immunotoxicol
JT  - Journal of immunotoxicology
JID - 101201960
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Animals
MH  - Drug Hypersensitivity/*immunology/pathology
MH  - Exanthema/*immunology/pathology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - *Immunity, Innate
MH  - Skin/*immunology/pathology
MH  - T-Lymphocytes/*immunology/pathology
OTO - NOTNLM
OT  - Skin toxicology
OT  - adverse drug reaction
OT  - idiosyncratic
OT  - immunology
OT  - mechanisms
OT  - metabolism
OT  - pharmacogenomics
OT  - skin rash bioactivation
EDAT- 2018/10/16 06:00
MHDA- 2020/05/29 06:00
CRDT- 2018/10/16 06:00
PHST- 2018/10/16 06:00 [pubmed]
PHST- 2020/05/29 06:00 [medline]
PHST- 2018/10/16 06:00 [entrez]
AID - 10.1080/1547691X.2018.1514444 [doi]
PST - ppublish
SO  - J Immunotoxicol. 2019 Dec;16(1):1-12. doi: 10.1080/1547691X.2018.1514444. Epub 
      2018 Oct 14.