Pharmacogenomics and Cutaneous Adverse Drug Reactions

  • Ren-You Pan
  • Chun-Bing Chen
  • Wen-Hung ChungEmail author


Cutaneous adverse drug reactions (cADRs) are unpredictable and may range from mild maculopapular exanthema (MPE) to life-threatening severe cutaneous adverse drug reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing pharmacogenomic studies showed specific HLA alleles are strongly associated with cADRs. The pathogenic checkpoints of cADRs include genetic polymorphisms affecting the immune synapse of HLA/drugs/T cell receptor interactions, specific HLA loci, T cell-mediated responses, and drug metabolism. Recently, pharmacogenomic screening for specific HLA alleles or high-risk genes prior to drug prescriptions to prevent cADRs has been widely implemented in clinical practice.


Cutaneous adverse drug reactions (cADRs) Drug reaction with eosinophilia and systemic symptoms (DRESS) Human leukocyte antigen (HLA) Stevens-Johnson syndrome (SJS) T cell receptors (TCR) Toxic epidermal necrolysis (TEN) 



Cutaneous adverse drug reactions




Cytochrome P450 family 2 subfamily C member 9*3


Drug reaction with eosinophilia and systemic symptoms


Human leukocyte antigens


Hypersensitivity syndrome




Maculopapular exanthema






Severe cutaneous adverse reactions


Stevens–Johnson syndrome


T cell receptors


Toxic epidermal necrolysis



Source of Funding: This work was supported in part by grants from the Ministry of Science and Technology, Taiwan (MOST 104-2314-B-182A-148-MY3, MOST 104-2325-B-182A-006, MOST 106-2314-B-182A-037-MY3), and Chang Gung Memorial Hospital (CLRPG2E0051~3, CORPG3F0041~2).

Conflict of Interest: The authors report no disclosures relevant to the manuscript.


  1. Carr DF, Chaponda M, Jorgensen AL, Castro EC, Van Oosterhout JJ, Khoo SH, Lalloo DG, Heyderman RS, Alfirevic A, Pirmohamed M (2013) Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population. Clin Infect Dis 56:1330–1339CrossRefGoogle Scholar
  2. Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, Hussein SH, Lim KS, Murad S (2017) Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population. Pharmacogenomics J 17(2):170–173CrossRefGoogle Scholar
  3. Chang CC, Too CL, Murad S, Hussein SH (2011) Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population. Int J Dermatol 50:221–224CrossRefGoogle Scholar
  4. Chantarangsu S, Mushiroda T, Mahasirimongkol S, Kiertiburanakul S, Sungkanuparph S, Manosuthi W, Tantisiriwat W, Charoenyingwattana A, Sura T, Chantratita W, Nakamura Y (2009) HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients. Pharmacogenet Genomics 19:139–146CrossRefGoogle Scholar
  5. Chen CB, Hsiao YH, Wu T, Hsih MS, Tassaneeyakul W, Jorns TP, Sukasem C, Hsu CN, Su SC, Chang WC, Hui RC, Chu CY, Chen YJ, Wu CY, Hsu CK, Chiu TM, Sun PL, Lee HE, Yang CY, Kao PH, Yang CH, Ho HC, Lin JY, Chang YC, Chen MJ, Lu CW, Ng CY, Kuo KL, Lin CY, Yang CS, Chen DP, Chang PY, Wu TL, Lin YJ, Weng YC, Kuo TT, Hung SI, Chung WH, Taiwan Severe Cutaneous Adverse Reaction Consortium (2017) Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians. Neurology 88(1):78–86CrossRefGoogle Scholar
  6. Chong KW, Chan DW, Cheung YB, Ching LK, Hie SL, Thomas T, Ling S, Tan EC (2014) Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore. Arch Dis Child 99:581–584CrossRefGoogle Scholar
  7. Choon SE, Lai NM (2012) An epidemiological and clinical analysis of cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia. Indian J Dermatol Venereol Leprol 78:734–739CrossRefGoogle Scholar
  8. 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 (2014) Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA 312:525–534CrossRefGoogle Scholar
  9. Chung WH, Chang WC, Stocker SL, Juo CG, Graham GG, Lee MH, Williams KM, Tian YC, Juan KC, Jan Wu YJ, Yang CH, Chang CJ, Lin YJ, Day RO, Hung SI (2015a) Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Ann Rheum Dis 74:2157–2164CrossRefGoogle Scholar
  10. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428:486CrossRefGoogle Scholar
  11. Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, Chin SW, Chiou CC, Chu SC, Ho HC, Yang CH, Lu CF, Wu JY, Liao YD, Chen YT (2008) Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med 14:1343–1350CrossRefGoogle Scholar
  12. Chung WH, Pan RY, Chu MT, Chin SW, Huang YL, Wang WC, Chang JY, Hung SI (2015b) Oxypurinol-specific T cells possess preferential TCR clonotypes and express granulysin in allopurinol-induced severe cutaneous adverse reactions. J Invest Dermatol 135:2237–2248CrossRefGoogle Scholar
  13. Gatanaga H, Yazaki H, Tanuma J, Honda M, Genka I, Teruya K, Tachikawa N, Kikuchi Y, Oka S (2007) HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS 21:264–265CrossRefGoogle Scholar
  14. Genin E, Chen DP, Hung SI, Sekula P, Schumacher M, Chang PY, Tsai SH, Wu TL, Bellon T, Tamouza R, Fortier C, Toubert A, Charron D, Hovnanian A, Wolkenstein P, Chung WH, Mockenhaupt M, Roujeau JC (2014) HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis. Pharmacogenomics J 14:281–288CrossRefGoogle Scholar
  15. Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses AD (2002) Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 359:1121–1122CrossRefGoogle Scholar
  16. Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, Hu SL, Wu MT, Chen GS, Wong TW, Hsiao PF, Chen WH, Shih HY, Fang WH, Wei CY, Lou YH, Huang YL, Lin JJ, Chen YT (2006) Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics 16:297–306CrossRefGoogle Scholar
  17. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CS, Wu JY, Chen YT (2005) HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 102:4134–4139CrossRefGoogle Scholar
  18. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC, Chu CY, Chen YT (2010) Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics 11:349–356CrossRefGoogle Scholar
  19. Ikeda H, Takahashi Y, Yamazaki E, Fujiwara T, Kaniwa N, Saito Y, Aihara M, Kashiwagi M, Muramatsu M (2010) HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia 51:297–300CrossRefGoogle Scholar
  20. Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z, Bharadwaj M, Miles JJ, Kjer-Nielsen L, Gras S, Williamson NA, Burrows SR, Purcell AW, Rossjohn J, McCluskey J (2012) Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486:554–558CrossRefGoogle Scholar
  21. Kang HR, Jee YK, Kim YS, Lee CH, Jung JW, Kim SH, Park HW, Chang YS, Jang IJ, Cho SH, Min KU, Kim SH, Lee KW, Adverse Drug Reaction Research Group in Korea (2011) Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics 21:303–307CrossRefGoogle Scholar
  22. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, Furuya H, Takahashi Y, Muramatsu M, Kinoshita S, Abe M, Ikeda H, Kashiwagi M, Song Y, Ueta M, Sotozono C, Ikezawa Z, Hasegawa R, JSAR Research Group (2010) HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Epilepsia 51:2461–2465CrossRefGoogle Scholar
  23. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, Sawada J, Furuya H, Takahashi Y, Muramatsu M, Kinoshita S, Abe M, Ikeda H, Kashiwagi M, Song Y, Ueta M, Sotozono C, Ikezawa Z, Hasegawa R, JSAR Research Group (2008) HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics 9:1617–1622CrossRefGoogle Scholar
  24. Kazeem GR, Cox C, Aponte J, Messenheimer J, Brazell C, Nelsen AC, Nelson MR, Foot E (2009) High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenet Genomics 19:661–665CrossRefGoogle Scholar
  25. Kim BK, Jung JW, Kim TB, Chang YS, Park HS, Moon J, Lee ST, Jung KH, Jung KY, Chu K, Lee SK, Kang HR, Park HW (2017) HLA-A*31:01 and lamotrigine-induced severe cutaneous adverse drug reactions in a Korean population. Ann Allergy Asthma Immunol 118(5):629–630CrossRefGoogle Scholar
  26. Kim SH, Kim M, Lee KW, Kim SH, Kang HR, Park HW, Jee YK (2010) HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics 11:879–884CrossRefGoogle Scholar
  27. Kim SH, Lee KW, Song WJ, Kim SH, Jee YK, Lee SM, Kang HR, Park HW, Cho SH, Park SH, Min KU, Chang YS, Adverse Drug Reaction Research Group in Korea (2011) Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res 97:190–197CrossRefGoogle Scholar
  28. Knowles SR, Dewhurst N, Shear NH (2012) Anticonvulsant hypersensitivity syndrome: an update. Expert Opin Drug Saf 11:767–778CrossRefGoogle Scholar
  29. Kongpan T, Mahasirimongkol S, Konyoung P, Kanjanawart S, Chumworathayi P, Wichukchinda N, Kidkeukarun R, Preechakul S, Khunarkornsiri U, Bamrungram W, Supharatwattanakun B, Mootsikapun P, Kwangsukstid S, Denjanta S, Vannaprasaht S, Rungapiromnan W, Suwankesawong W, Tassaneeyakul W, Tassaneeyakul W (2015) Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics 25:402–411CrossRefGoogle Scholar
  30. Kwan PK, Ng MH, Lo SV (2014) Association between HLA-B*15:02 allele and antiepileptic drug-induced severe cutaneous reactions in Hong Kong Chinese: a population-based study. Hong Kong Med J 20(Suppl 7):16–18PubMedGoogle Scholar
  31. Lin YF, Yang CH, Sindy H, Lin JY, Rosaline Hui CY, Tsai YC, Wu TS, Huang CT, Kao KC, Hu HC, Chiu CH, Hung SI, Chung WH (2014) Severe cutaneous adverse reactions related to systemic antibiotics. Clin Infect Dis 58:1377–1385CrossRefGoogle Scholar
  32. Littera R, Carcassi C, Masala A, Piano P, Serra P, Ortu F, Corso N, Casula B, La Nasa G, Contu L, Manconi PE (2006) HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients. AIDS 20:1621–1626CrossRefGoogle Scholar
  33. Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, Kangwanshiratada O, Hirankarn N, Suphapeetiporn K, Shotelersuk V (2008) Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia 49:2087–2091CrossRefGoogle Scholar
  34. Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, Naldi L, Bouwes-Bavinck JN, Sidoroff A, De Toma C, Schumacher M, Roujeau JC, Hovnanian A, Mockenhaupt M, Regi SSG (2008) A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18:99–107CrossRefGoogle Scholar
  35. Lowin B, Peitsch MC, Tschopp J (1995) Perforin and granzymes: crucial effector molecules in cytolytic T lymphocyte and natural killer cell-mediated cytotoxicity. Curr Top Microbiol Immunol 198:1–24PubMedGoogle Scholar
  36. Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, Day CP, Ruiz-Cabello F, Donaldson PT, Stephens C, Pirmohamed M, Romero-Gomez M, Navarro JM, Fontana RJ, Miller M, Groome M, Bondon-Guitton E, Conforti A, Stricker BH, Carvajal A, Ibanez L, Yue QY, Eichelbaum M, Floratos A, Pe’er I, Daly MJ, Goldstein DB, Dillon JF, Nelson MR, Watkins PB, Daly AK, Spanish DILI Registry, EUDRAGENE, DILIN, DILIGEN, International SAEC (2011) Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology 141:338–347CrossRefGoogle Scholar
  37. Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte C, Maxwell D, James I, Christiansen FT (2002) Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359:727–732CrossRefGoogle Scholar
  38. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jagel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A, Team P-S (2008) HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358:568–579CrossRefGoogle Scholar
  39. Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, Ng MH (2007) Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 48:1015–1018CrossRefGoogle Scholar
  40. Martin AM, Nolan D, James I, Cameron P, Keller J, Moore C, Phillips E, Christiansen FT, Mallal S (2005) Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS 19:97–99CrossRefGoogle Scholar
  41. McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperaviciute D, Carrington M, Sills GJ, Marson T, Jia X, de Bakker PI, Chinthapalli K, Molokhia M, Johnson MR, O’Connor GD, Chaila E, Alhusaini S, Shianna KV, Radtke RA, Heinzen EL, Walley N, Pandolfo M, Pichler W, Park BK, Depondt C, Sisodiya SM, Goldstein DB, Deloukas P, Delanty N, Cavalleri GL, Pirmohamed M (2011) HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364:1134–1143CrossRefGoogle Scholar
  42. Mehta TY, Prajapati LM, Mittal B, Joshi CG, Sheth JJ, Patel DB, Dave DM, Goyal RK (2009) Association of HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians. Indian J Dermatol Venereol Leprol 75:579–582CrossRefGoogle Scholar
  43. Middleton D, Menchaca L, Rood H, Komerofsky R (2003) New allele frequency database: Tissue Antigens 61:403–407CrossRefGoogle Scholar
  44. Monshi MM, Faulkner L, Gibson A, Jenkins RE, Farrell J, Earnshaw CJ, Alfirevic A, Cederbrant K, Daly AK, French N, Pirmohamed M, Park BK, Naisbitt DJ (2013) Human leukocyte antigen (HLA)-B*57:01-restricted activation of drug-specific T cells provides the immunological basis for flucloxacillin-induced liver injury. Hepatology 57:727–739CrossRefGoogle Scholar
  45. Nassif A, Bensussan A, Dorothee G, Mani-Chouaib F, Bachot N, Bagot M, Boumsell L, Roujeau JC (2002) Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol 118:728–733CrossRefGoogle Scholar
  46. Ng CY, Yeh YT, Wang CW, Hung SI, Yang CH, Chang YC, Chang WC, Lin YJ, Chang CJ, Su SC, Fan WL, Chen DY, Wu YJ, Tian YC, Hui RC, Chung WH, Taiwan Severe Cutaneous Adverse Reaction Consortium (2016) Impact of the HLA-B(*)58:01 allele and renal impairment on allopurinol-induced cutaneous adverse reactions. J Invest Dermatol 136:1373–1381CrossRefGoogle Scholar
  47. Nguyen DV, Chu HC, Nguyen DV, Phan MH, Craig T, Baumgart K, Van Nunen S (2015) HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese. Asia Pac Allergy 5:68–77CrossRefGoogle Scholar
  48. Ostrov DA, Grant BJ, Pompeu YA, Sidney J, Harndahl M, Southwood S, Oseroff C, Lu S, Jakoncic J, De Oliveira CA, Yang L, Mei H, Shi L, Shabanowitz J, English AM, Wriston A, Lucas A, Phillips E, Mallal S, Grey HM, Sette A, Hunt DF, Buus S, Peters B (2012) Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proc Natl Acad Sci U S A 109:9959–9964CrossRefGoogle Scholar
  49. Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M, Shirakata Y, Ikezawa Z, Iijima M, Shiohara T, Hashimoto K, Kamatani N, Nakamura Y (2011) Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet 20:1034–1041CrossRefGoogle Scholar
  50. Padovan E, Bauer T, Tongio MM, Kalbacher H, Weltzien HU (1997) Penicilloyl peptides are recognized as T cell antigenic determinants in penicillin allergy. Eur J Immunol 27:1303–1307CrossRefGoogle Scholar
  51. Pan RY, Dao RL, Hung SI, Chung WH (2017) Pharmacogenomic advances in the prediction and prevention of cutaneous idiosyncratic drug reactions. Clin Pharmacol Ther. Scholar
  52. Ramirez E, Bellon T, Tong HY, Borobia AM, De Abajo FJ, Lerma V, Moreno Hidalgo MA, Castaner JL, Cabanas R, Fiandor A, Gonzalez-Ramos J, Herranz P, Cachafeiro L, Gonzalez-Herrada C, Gonzalez O, Aramburu JA, Laosa O, Hernandez R, Carcas AJ, Frias J (2017) Significant HLA class I type associations with aromatic antiepileptic drug (AED)-induced SJS/TEN are different from those found for the same AED-induced DRESS in the Spanish population. Pharmacol Res 115:168–178CrossRefGoogle Scholar
  53. Revuz J, Penso D, Roujeau JC, Guillaume JC, Payne CR, Wechsler J, Touraine R (1987) Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients. Arch Dermatol 123:1160–1165CrossRefGoogle Scholar
  54. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, Touraine R (1987) Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 123:1171–1173CrossRefGoogle Scholar
  55. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T, Auquier A, Bastuji-Garin S, Correia O, Locati F et al (1995) Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 333:1600–1607CrossRefGoogle Scholar
  56. Roujeau JC, Stern RS (1994) Severe adverse cutaneous reactions to drugs. N Engl J Med 331:1272–1285CrossRefGoogle Scholar
  57. Rzany B, Mockenhaupt M, Baur S, Schroder W, Stocker U, Mueller J, Hollander N, Bruppacher R, Schopf E (1996) Epidemiology of erythema exsudativum multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis in Germany (1990–1992): structure and results of a population-based registry. J Clin Epidemiol 49:769–773CrossRefGoogle Scholar
  58. Schnyder B, Pichler WJ (2013) Allergy to sulfonamides. J Allergy Clin Immunol 131(256-7):E1–E5Google Scholar
  59. Shi YW, Min FL, Liu XR, Zan LX, Gao MM, Yu MJ, Liao WP (2011) Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population. Basic Clin Pharmacol Toxicol 109:42–46CrossRefGoogle Scholar
  60. Sun D, Yu CH, Liu ZS, He XL, Hu JS, Wu GF, Mao B, Wu SH, Xiang HH (2014) Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China. J Huazhong Univ Sci Technol Med Sci 34:146–150CrossRefGoogle Scholar
  61. Tassaneeyakul W, Jantararoungtong T, Chen P, Lin PY, Tiamkao S, Khunarkornsiri U, Chucherd P, Konyoung P, Vannaprasaht S, Choonhakarn C, Pisuttimarn P, Sangviroon A, Tassaneeyakul W (2009) Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics 19:704–709CrossRefGoogle Scholar
  62. Tassaneeyakul W, Prabmeechai N, Sukasem C, Kongpan T, Konyoung P, Chumworathayi P, Tiamkao S, Khunarkornsiri U, Kulkantrakorn K, Saksit N, Nakkam N, Satapornpong P, Vannaprasaht S, Sangviroon A, Mahasirimongkol S, Wichukchinda N, Rerkpattanapipat T, Tassaneeyakul W (2016) Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genomics 26:225–234CrossRefGoogle Scholar
  63. Wei CY, Chung WH, Huang HW, Chen YT, Hung SI (2012) Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome. J Allergy Clin Immunol 129:1562–1569.e5CrossRefGoogle Scholar
  64. White KD, Chung WH, Hung SI, Mallal S, Phillips EJ (2015) Evolving models of the immunopathogenesis of T cell-mediated drug allergy: the role of host, pathogens, and drug response. J Allergy Clin Immunol 136:219–234; quiz 235CrossRefGoogle Scholar
  65. Yang CY, Chen CH, Deng ST, Huang CS, Lin YJ, Chen YJ, Wu CY, Hung SI, Chung WH (2015) Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med 175:1550–1557CrossRefGoogle Scholar
  66. Yun J, Marcaida MJ, Eriksson KK, Jamin H, Fontana S, Pichler WJ, Yerly D (2014) Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01. J Immunol 192:2984–2993CrossRefGoogle Scholar
  67. Zeng T, Long YS, Min FL, Liao WP, Shi YW (2015) Association of HLA-B*1502 allele with lamotrigine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese subjects: a meta-analysis. Int J Dermatol 54:488–493CrossRefGoogle Scholar
  68. Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ, Yu YX, Chen MF, Low HQ, Li JH, Bao FF, Foo JN, Bei JX, Jia XM, Liu J, Liany H, Wang N, Niu GY, Wang ZZ, Shi BQ, Tian HQ, Liu HX, Ma SS, Zhou Y, You JB, Yang Q, Wang C, Chu TS, Liu DC, Yu XL, Sun YH, Ning Y, Wei ZH, Chen SL, Chen XC, Zhang ZX, Liu YX, Pulit SL, Wu WB, Zheng ZY, Yang RD, Long H, Liu ZS, Wang JQ, Li M, Zhang LH, Wang H, Wang LM, Xiao P, Li JL, Huang ZM, Huang JX, Li Z, Liu J, Xiong L, Yang J, Wang XD, Yu DB, Lu XM, Zhou GZ, Yan LB, Shen JP, Zhang GC, Zeng YX, de Bakker PI, Chen SM, Liu JJ (2013) HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med 369:1620–1628CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Ren-You Pan
    • 1
    • 2
  • Chun-Bing Chen
    • 1
    • 2
    • 3
    • 4
    • 5
  • Wen-Hung Chung
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of Dermatology, Drug Hypersensitivity Clinical and Research CenterChang Gung Memorial Hospital, LinkouTaipeiTaiwan
  2. 2.Chang Gung Immunology ConsortiumChang Gung Memorial Hospital and Chang Gung UniversityTaoyuanTaiwan
  3. 3.Whole-Genome Research Core Laboratory of Human DiseasesChang Gung Memorial HospitalKeelungTaiwan
  4. 4.Graduate Institute of Clinical Medical Sciences, College of MedicineChang Gung UniversityTaoyuanTaiwan
  5. 5.Department of DermatologyXiamen Chang Gung HospitalXiamenChina

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