Editing Stevens–Johnson syndrome (section)

=== ADME === 
Variations in [[ADME]], i.e. an individual's efficiency in absorbing, tissue-distributing, metabolizing, or excreting a drug, have been found to occur in various [[severe cutaneous adverse reactions]] (SCARS) as well as other types of adverse drug reactions.<ref name="pmid27955861">{{cite journal | vauthors = Alfirevic A, Pirmohamed M | title = Genomics of Adverse Drug Reactions | journal = Trends in Pharmacological Sciences | volume = 38 | issue = 1 | pages = 100–109 | date = January 2017 | pmid = 27955861 | doi = 10.1016/j.tips.2016.11.003 }}</ref> These variations influence the levels and duration of a drug or its metabolite in tissues and thereby impact the drug's or metabolite's ability to evoke these reactions.<ref name="Adler2017"/> For example, [[CYP2C9]] is an important drug-metabolizing [[cytochrome P450]]; it metabolizes and thereby inactivates [[phenytoin]]. Taiwanese, Japanese, and Malaysian individuals expressing the [[CYP2C9*3]]<ref>{{cite web|url=https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1057910|title=Reference SNP (refSNP) Cluster Report: rs1057910 ** With drug-response allele **|last=snpdev|website=www.ncbi.nlm.nih.gov}}</ref> variant of CYP2C9, which has reduced metabolic activity compared to the [[wild type]] (i.e. CYP2c9*1) cytochrome, have increased blood levels of phenytoin and a high incidence of SJS (as well as SJS/TEN and TEN) when taking the drug.<ref name=Adler2017/><ref name="pmid25096692">{{cite journal | vauthors = Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, Chen MJ, Lin JY, Hui RC, Ho JC, Wu WM, Chen TJ, Wu T, Wu YR, Hsih MS, Tu PH, Chang CN, Hsu CN, Wu TL, Choon SE, Hsu CK, Chen DY, Liu CS, Lin CY, Kaniwa N, Saito Y, Takahashi Y, Nakamura R, Azukizawa H, Shi Y, Wang TH, Chuang SS, Tsai SF, Chang CJ, Chang YS, Hung SI | title = Genetic variants associated with phenytoin-related severe cutaneous adverse reactions | journal = JAMA | volume = 312 | issue = 5 | pages = 525–34 | date = August 2014 | pmid = 25096692 | doi = 10.1001/jama.2014.7859 | doi-access = free }}</ref> In addition to abnormalities in drug-metabolizing enzymes, dysfunctions of the kidney, liver, or GI tract which increase a SCARs-inducing drug or metabolite levels are suggested to promote SCARs responses.<ref name="Adler2017" /><ref name=Ler2017/> These ADME abnormalities, it is also suggested, may interact with particular HLA proteins and T cell receptors to promote a SCARs disorder.<ref name=Adler2017/><ref name="pmid27154258">{{cite journal | vauthors = Chung WH, Wang CW, Dao RL | title = Severe cutaneous adverse drug reactions | journal = The Journal of Dermatology | volume = 43 | issue = 7 | pages = 758–66 | year = 2016 | pmid = 27154258 | doi = 10.1111/1346-8138.13430 | s2cid = 45524211 }}</ref>