DOI QR코드

DOI QR Code

Genetic markers of severe cutaneous adverse reactions

  • Jung, Jae-Woo (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Kim, Jae-Yeol (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Park, In-Won (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Choi, Byoung-Whui (Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Kang, Hye-Ryun (Department of Internal Medicine, Seoul National University College of Medicine)
  • 투고 : 2018.04.06
  • 심사 : 2018.04.12
  • 발행 : 2018.09.01

초록

Adverse drug reactions can cause considerable discomfort. They can be life-threatening in severe cases, requiring or prolonging hospitalization, impeding proper treatment, and increasing treatment costs considerably. Although the incidence of severe cutaneous adverse reactions (SCARs) is low, they can be serious, have permanent sequelae, or lead to death. A recent pharmacogenomic study confirmed that genetic factors can predispose an individual to SCARs. Genetic markers enable not only elucidation of the pathogenesis of SCARs, but also screening of susceptible subjects. The human leukocyte antigen (HLA) genotypes associated with SCARs include HLA-B*57:01 for abacavir (Caucasians), HLA-B*58:01 for allopurinol (Asians), HLA-B*15:02 (Han Chinese) and HLA-A*31:01 (Europeans and Koreans) for carbamazepine, HLA-B*59:01 for methazolamide (Koreans and Japanese), and HLA-B*13:01 for dapsone (Asians). Therefore, prescreening genetic testing could prevent severe drug hypersensitivity reactions. Large-scale epidemiologic studies are required to demonstrate the usefulness and cost-effectiveness of screening tests because their efficacy is affected by the genetic differences among ethnicities.

키워드

과제정보

연구 과제 주관 기관 : Ministry of Food and Drug Safety

참고문헌

  1. Eichelbaum M, Ingelman-Sundberg M, Evans WE. Pharmacogenomics and individualized drug therapy. Annu Rev Med 2006;57:119-137. https://doi.org/10.1146/annurev.med.56.082103.104724
  2. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998;279:1200-1205. https://doi.org/10.1001/jama.279.15.1200
  3. Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology 2005;209:123-129. https://doi.org/10.1016/j.tox.2004.12.022
  4. Mockenhaupt M, Schopf E. Epidemiology of drug-induced severe skin reactions. Semin Cutan Med Surg 1996;15:236-243. https://doi.org/10.1016/S1085-5629(96)80036-8
  5. Strom BL, Carson JL, Halpern AC, et al. A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures. Arch Dermatol 1991;127:831-838. https://doi.org/10.1001/archderm.1991.01680050075007
  6. Mockenhaupt M. The current understanding of Stevens-Johnson syndrome and toxic epidermal necrolysis. Expert Rev Clin Immunol 2011;7:803-813. https://doi.org/10.1586/eci.11.66
  7. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis 2010;5:39. https://doi.org/10.1186/1750-1172-5-39
  8. Roujeau JC. Immune mechanisms in drug allergy. Allergol Int 2006;55:27-33. https://doi.org/10.2332/allergolint.55.27
  9. Roujeau JC, Huynh TN, Bracq C, Guillaume JC, Revuz J, Touraine R. Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol 1987;123:1171-1173. https://doi.org/10.1001/archderm.1987.01660330082014
  10. Chung WH, Hung SI, Chen YT. Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol 2007;7:317-323. https://doi.org/10.1097/ACI.0b013e3282370c5f
  11. Ko TM, Chung WH, Wei CY, et al. Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol 2011;128:1266-1276. https://doi.org/10.1016/j.jaci.2011.08.013
  12. Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358:568-579. https://doi.org/10.1056/NEJMoa0706135
  13. Hetherington S, Hughes AR, Mosteller M, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002;359:1121-1122. https://doi.org/10.1016/S0140-6736(02)08158-8
  14. Mallal S, Nolan D, Witt C, et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 2002;359:727-732. https://doi.org/10.1016/S0140-6736(02)07873-X
  15. Hughes AR, Mosteller M, Bansal AT, et al. Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations. Pharmacogenomics 2004;5:203-211. https://doi.org/10.1517/phgs.5.2.203.27481
  16. Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis 2008;46:1111-1118. https://doi.org/10.1086/529382
  17. Lee KW, Oh DH, Lee C, Yang SY. Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens 2005;65:437-447. https://doi.org/10.1111/j.1399-0039.2005.00386.x
  18. Park HJ, Park JW, Yang MS, et al. Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: a multicentre retrospective cohort study. Eur Radiol 2017;27:2886-2893. https://doi.org/10.1007/s00330-016-4682-y
  19. Park WB, Choe PG, Song KH, et al. Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir? Clin Infect Dis 2009;48:365-367. https://doi.org/10.1086/595890
  20. Gatanaga H, Honda H, Oka S. Pharmacogenetic information derived from analysis of HLA alleles. Pharmacogenomics 2008;9:207-214. https://doi.org/10.2217/14622416.9.2.207
  21. Phillips EJ, Chung WH, Mockenhaupt M, Roujeau JC, Mallal SA. Drug hypersensitivity: pharmacogenetics and clinical syndromes. J Allergy Clin Immunol 2011;127(3 Suppl):S60-S66. https://doi.org/10.1016/j.jaci.2010.11.046
  22. Chantarangsu S, Mushiroda T, Mahasirimongkol S, et al. HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients. Pharmacogenet Genomics 2009;19:139-146. https://doi.org/10.1097/FPC.0b013e32831d0faf
  23. Martin AM, Nolan D, James I, et al. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS 2005;19:97-99. https://doi.org/10.1097/00002030-200501030-00014
  24. Gatanaga H, Yazaki H, Tanuma J, et al. HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS 2007;21:264-265. https://doi.org/10.1097/QAD.0b013e32801199d9
  25. Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428:486. https://doi.org/10.1038/428486a
  26. Chen P, Lin JJ, Lu CS, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med 2011;364:1126-1133. https://doi.org/10.1056/NEJMoa1009717
  27. Dong D, Sung C, Finkelstein EA. Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology 2012;79:1259-1267. https://doi.org/10.1212/WNL.0b013e31826aac73
  28. Kuehn BM. FDA: epilepsy drugs may carry skin risks for Asians. JAMA 2008;300:2845. https://doi.org/10.1001/jama.2008.890
  29. Ferrell PB Jr, McLeod HL. Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 2008;9:1543-1546. https://doi.org/10.2217/14622416.9.10.1543
  30. Lonjou C, Thomas L, Borot N, et al. A marker for Stevens-Johnson syndrome ...: ethnicity matters. Pharmacogenomics J 2006;6:265-268. https://doi.org/10.1038/sj.tpj.6500356
  31. Kaniwa N, Saito Y, Aihara M, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics 2008;9:1617-1622. https://doi.org/10.2217/14622416.9.11.1617
  32. Devi K. The association of HLA B*15:02 allele and Stevens-Johnson syndrome/toxic epidermal necrolysis induced by aromatic anticonvulsant drugs in a South Indian population. Int J Dermatol 2018;57:70-73. https://doi.org/10.1111/ijd.13812
  33. Man CB, Kwan P, Baum L, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 2007;48:1015-1018. https://doi.org/10.1111/j.1528-1167.2007.01022.x
  34. Tassaneeyakul W, Tiamkao S, Jantararoungtong T, et al. Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia 2010;51:926-930. https://doi.org/10.1111/j.1528-1167.2010.02533.x
  35. Then SM, Rani ZZ, Raymond AA, Ratnaningrum S, Jamal R. Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients. Asian Pac J Allergy Immunol 2011;29:290-293.
  36. Yip VL, Marson AG, Jorgensen AL, Pirmohamed M, Alfirevic A. HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review. Clin Pharmacol Ther 2012;92:757-765. https://doi.org/10.1038/clpt.2012.189
  37. Ozeki T, Mushiroda T, Yowang A, et al. 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 2011;20:1034-1041. https://doi.org/10.1093/hmg/ddq537
  38. McCormack M, Alfirevic A, Bourgeois S, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 2011;364:1134-1143. https://doi.org/10.1056/NEJMoa1013297
  39. Khor AH, Lim KS, Tan CT, et al. HLA-A*31: 01 and HLA-B*15:02 association with Stevens-Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population. Pharmacogenet Genomics 2017;27:275-278. https://doi.org/10.1097/FPC.0000000000000287
  40. Kim SH, Lee KW, Song WJ, et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res 2011;97:190-197. https://doi.org/10.1016/j.eplepsyres.2011.08.010
  41. Hung SI, Chung WH, Liu ZS, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics 2010;11:349-356. https://doi.org/10.2217/pgs.09.162
  42. Ramirez E, Bellon T, Tong HY, et al. 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 2017;115:168-178. https://doi.org/10.1016/j.phrs.2016.11.027
  43. Kazeem GR, Cox C, Aponte J, et al. High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenet Genomics 2009;19:661-665. https://doi.org/10.1097/FPC.0b013e32832c347d
  44. Kim BK, Jung JW, Kim TB, et al. HLA-A*31:01 and lamotrigine-induced severe cutaneous adverse drug reactions in a Korean population. Ann Allergy Asthma Immunol 2017;118:629-630. https://doi.org/10.1016/j.anai.2017.02.011
  45. Koomdee N, Pratoomwun J, Jantararoungtong T, et al. Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol 2017;8:879. https://doi.org/10.3389/fphar.2017.00879
  46. Moon J, Park HK, Chu K, et al. The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population. Epilepsia 2015;56:e161-e167. https://doi.org/10.1111/epi.13087
  47. Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 2005;102:4134-4139. https://doi.org/10.1073/pnas.0409500102
  48. Tassaneeyakul W, Jantararoungtong T, Chen P, et al. Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics 2009;19:704-709. https://doi.org/10.1097/FPC.0b013e328330a3b8
  49. Kang HR, Jee YK, Kim YS, et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics 2011;21:303-307. https://doi.org/10.1097/FPC.0b013e32834282b8
  50. Lonjou C, Borot N, Sekula P, et al. A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 2008;18:99-107. https://doi.org/10.1097/FPC.0b013e3282f3ef9c
  51. Goncalo M, Coutinho I, Teixeira V, et al. HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population. Br J Dermatol 2013;169:660-665. https://doi.org/10.1111/bjd.12389
  52. Jung JW, Song WJ, Kim YS, et al. HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency. Nephrol Dial Transplant 2011;26:3567-3572. https://doi.org/10.1093/ndt/gfr060
  53. Jung JW, Kim DK, Park HW, et al. An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing. Genet Med 2015;17:807-814. https://doi.org/10.1038/gim.2014.195
  54. Ko TM, Tsai CY, Chen SY, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ 2015;351:h4848.
  55. Shirato S, Kagaya F, Suzuki Y, Joukou S. Stevens-Johnson syndrome induced by methazolamide treatment. Arch Ophthalmol 1997;115:550-553. https://doi.org/10.1001/archopht.1997.01100150552021
  56. Kim SH, Kim M, Lee KW, et al. HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics 2010;11:879-884. https://doi.org/10.2217/pgs.10.54
  57. Jee YK, Kim S, Lee JM, Park HS, Kim SH. CD8(+) T-cell activation by methazolamide causes methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Clin Exp Allergy 2017;47:972-974. https://doi.org/10.1111/cea.12919
  58. Yang F, Xuan J, Chen J, et al. HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese. Pharmacogenomics J 2016;16:83-87. https://doi.org/10.1038/tpj.2015.25
  59. Jiang YY, Nguyen GH, Jin HZ, Zeng YP. Methazolamide-induced toxic epidermal necrolysis in a man carrying HLA-B*59:01: successful treatment with infliximab and glucocorticoid. Int J Dermatol 2018;57:494-496. https://doi.org/10.1111/ijd.13924
  60. Shu C, Shu D, Tie D, et al. Toxic epidermal necrolysis induced by methazolamide in a Chinese-Korean man carrying HLA-B*59:01. Int J Dermatol 2015;54:1242-1245. https://doi.org/10.1111/ijd.12651
  61. Her Y, Kil MS, Park JH, Kim CW, Kim SS. Stevens-Johnson syndrome induced by acetazolamide. J Dermatol 2011;38:272-275. https://doi.org/10.1111/j.1346-8138.2010.00921.x
  62. Lorenz M, Wozel G, Schmitt J. Hypersensitivity reactions to dapsone: a systematic review. Acta Derm Venereol 2012;92:194-199. https://doi.org/10.2340/00015555-1268
  63. Zhang FR, Liu H, Irwanto A, et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med 2013;369:1620-1628. https://doi.org/10.1056/NEJMoa1213096
  64. Caudle KE, Rettie AE, Whirl-Carrillo M, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther 2014;96:542-548. https://doi.org/10.1038/clpt.2014.159
  65. Ciccacci C, Di Fusco D, Marazzi MC, et al. Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: a pharmacogenetics study. Eur J Clin Pharmacol 2013;69:1909-1916. https://doi.org/10.1007/s00228-013-1549-x

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