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Pharmacogenomics: A New Approach for Preventing Severe Cutaneous Adverse Drug Reactions

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Genomics-Driven Healthcare

Abstract

Pharmacogenomics can be used to identify genetic predisposing factors for serious cutaneous adverse reactions and personalize drug therapy accordingly. Pharmacogenetic screening for severe cutaneous adverse reactions (SCARs) is a key opportunity and potential paradigm for reducing morbidity and mortality and finally eliminating some of the most devastating of adverse drug reactions. This chapter focuses on the current state of surveillance know-how, pathogenesis, and treatment of SCARs. The role of genomics and pharmacogenomics in the etiology, treatment, and eradication of preventable causes of drug-induced SCARs is discussed. Drugs associated with hypersensitivity reactions with strong genetic predisposing factors include abacavir, nevirapine, carbamazepine, allopurinol, etc. The gaps, unmet needs, and priorities for future research are identified in order to eliminate genetically mediated SCARs globally.

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References

  1. Schnyder B, Pichler WJ (2009) Mechanisms of drug-induced allergy. Mayo Clin Proc 84(3):268–272

    Article  PubMed  PubMed Central  Google Scholar 

  2. Pavlos R, Mallal S, Ostrov D, Pompeu Y, Phillips E (2014) Fever, rash, and systemic symptoms: understanding the role of virus and HLA in severe cutaneous drug allergy. J Allergy Clin Immunol Pract 2(1):21–33

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sukasem C, Puangpetch A, Medhasi S, Tassaneeyakul W (2014) Pharmacogenomics of drug-induced hypersensitivity reactions: challenges, opportunities and clinical implementation. Asian Pac J Allergy Immunol 32(2):111–123

    PubMed  CAS  Google Scholar 

  4. Pichler WJ, Yawalkar N (2000) Allergic reactions to drugs: involvement of T cells. Thorax 55(Suppl 2):S61–S65

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chung WH, Hung SI, Chen YT (2007) Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol 7(4):317–323

    Article  PubMed  CAS  Google Scholar 

  6. Pavlos R, Mallal S, Ostrov D, Buus S, Metushi I, Peters B et al (2015) T cell-mediated hypersensitivity reactions to drugs. Annu Rev Med 66:439–454

    Article  PubMed  CAS  Google Scholar 

  7. Schrijvers R, Gilissen L, Chiriac AM, Demoly P (2015) Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy 5:31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Yun J, Cai F, Lee FJ, Pichler WJ (2016) T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance. Asia Pac Allergy 6(2):77–89

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chung WH, Wang CW, Dao RL (2016) Severe cutaneous adverse drug reactions. J Dermatol 43(7):758–766

    Article  PubMed  CAS  Google Scholar 

  10. Schnyder B, Brockow K (2015) Pathogenesis of drug allergy--current concepts and recent insights. Clin Exp Allergy 45(9):1376–1383

    Article  PubMed  CAS  Google Scholar 

  11. Su SC, Hung SI, Fan WL, Dao RL, Chung WH (2016) Severe cutaneous adverse reactions: the pharmacogenomics from research to clinical implementation. Int J Mol Sci 17(11):1890

    Article  PubMed Central  CAS  Google Scholar 

  12. Ghosh K, Banerjee G, Ghosal AK, Nandi J (2011) Cutaneous drug hypersensitivity: immunological and genetic perspective. Indian J Dermatol 56(2):137–144

    Article  PubMed  PubMed Central  Google Scholar 

  13. Suvichapanich S, Jittikoon J, Wichukchinda N, Kamchaisatian W, Visudtibhan A, Benjapopitak S et al (2015) Association analysis of CYP2C9*3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children. J Hum Genet 60(8):413–417

    Article  PubMed  CAS  Google Scholar 

  14. Yampayon K, Sukasem C, Limwongse C, Chinvarun Y, Tempark T, Rerkpattanapipat T et al (2017) Influence of genetic and non-genetic factors on phenytoin-induced severe cutaneous adverse drug reactions. Eur J Clin Pharmacol 73(7):855–865

    Article  PubMed  CAS  Google Scholar 

  15. Tassaneeyakul W, Prabmeechai N, Sukasem C, Kongpan T, Konyoung P, Chumworathayi P et al (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(5):225–234

    Article  PubMed  CAS  Google Scholar 

  16. Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC et al (2014) Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA 312(5):525–534

    Article  PubMed  Google Scholar 

  17. Chung WH, Chang WC, Stocker SL, Juo CG, Graham GG, Lee MH et al (2015) 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(12):2157–2164

    Article  PubMed  CAS  Google Scholar 

  18. Saksit N, Tassaneeyakul W, Nakkam N, Konyoung P, Khunarkornsiri U, Chumworathayi P (2017) Risk factors of allopurinol-induced severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genomics 27(7):255–263

    Article  PubMed  CAS  Google Scholar 

  19. Chen CB, Hsiao YH, Wu T, Hsih MS, Tassaneeyakul W, Jorns TP et al (2017) Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians. Neurology 88(1):78–86

    Article  PubMed  CAS  Google Scholar 

  20. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC et al (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428(6982):486

    Article  PubMed  CAS  Google Scholar 

  21. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC et al (2010) Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics 11(3):349–356

    Article  PubMed  CAS  Google Scholar 

  22. Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, Yang CC et al (2011) Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med 364(12):1126–1133

    Article  PubMed  CAS  Google Scholar 

  23. Tassaneeyakul W, Tiamkao S, Jantararoungtong T, Chen P, Lin SY, Chen WH et al (2010) Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia 51(5):926–930

    Article  PubMed  Google Scholar 

  24. Martin AM, Nolan D, Gaudieri S, Almeida CA, Nolan R, James I et al (2004) Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci U S A 101(12):4180–4185

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J et al (2008) HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358(6):568–579

    Article  PubMed  Google Scholar 

  26. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP et al (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(11):4134–4139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Ng CY, Yeh YT, Wang CW, Hung SI, Yang CH, Chang YC et al (2016) Impact of the HLA-B(*)58:01 allele and renal impairment on allopurinol-induced cutaneous adverse reactions. J Invest Dermatol 136(7):1373–1381

    Article  PubMed  CAS  Google Scholar 

  28. Sukasem C, Jantararoungtong T, Kuntawong P, Puangpetch A, Koomdee N, Satapornpong P et al (2016) HLA-B (*) 58:01 for allopurinol-induced cutaneous adverse drug reactions: implication for clinical interpretation in Thailand. Front Pharmacol 7:186

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Tassaneeyakul W, Jantararoungtong T, Chen P, Lin PY, Tiamkao S, Khunarkornsiri U et al (2009) Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics 19(9):704–709

    Article  PubMed  CAS  Google Scholar 

  30. 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(2):219–234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY (2008) Granulysin is a key mediator for disseminated keratinocyte death in Stevens-Johnson syndrome and toxic epidermal necrolysis. Nat Med 14(12):1343–1350

    Article  PubMed  CAS  Google Scholar 

  32. Schwartz RA, McDonough PH, Lee BW (2013) Toxic epidermal necrolysis: part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol 69(2):173.e1–173.13

    Article  CAS  Google Scholar 

  33. Ferrandiz-Pulido C, Garcia-Patos V (2013) A review of causes of Stevens-Johnson syndrome and toxic epidermal necrolysis in children. Arch Dis Child 98(12):998–1003

    Article  PubMed  Google Scholar 

  34. Mockenhaupt M (2014) Stevens-Johnson syndrome and toxic epidermal necrolysis: clinical patterns, diagnostic considerations, etiology, and therapeutic management. Semin Cutan Med Surg 33(1):10–16

    Article  PubMed  Google Scholar 

  35. Roujeau JC, Kelly JP, Naldi L, Rzany B, Stern RS, Anderson T et al (1995) Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med 333(24):1600–1607

    Article  PubMed  CAS  Google Scholar 

  36. Levi N, Bastuji-Garin S, Mockenhaupt M, Roujeau JC, Flahault A, Kelly JP et al (2009) Medications as risk factors of Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics 123(2):e297–e304

    Article  PubMed  Google Scholar 

  37. Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A et al (2008) Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 58(1):25–32

    Article  PubMed  Google Scholar 

  38. Kunimi Y, Hirata Y, Aihara M, Yamane Y, Ikezawa Z (2011) Statistical analysis of Stevens-Johnson syndrome caused by mycoplasma pneumonia infection in Japan. Allergol Int 60(4):525–532

    Article  PubMed  Google Scholar 

  39. Forman R, Koren G, Shear NH (2002) Erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of 10 years’ experience. Drug Saf 25(13):965–972

    Article  PubMed  Google Scholar 

  40. Ferrándiz-Pulido C, García-Fernández D, Domínguez-Sampedro P, García-Patos V (2011) Stevens-Johnson syndrome and toxic epidermal necrolysis in children: a review of the experience with paediatric patients in a university hospital. J Eur Acad Dermatol Venereol 25(10):1153–1159

    Article  PubMed  Google Scholar 

  41. Dodiuk-Gad RP, Chung WH, Valeyrie-Allanore L, Shear NH (2015) Stevens-Johnson syndrome and toxic epidermal Necrolysis: an update. Am J Clin Dermatol 16(6):475–493

    Article  PubMed  Google Scholar 

  42. Schwartz RA, McDonough PH, Lee BW (2013) Toxic epidermal necrolysis: Part II Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol 69(2):187.e1–187.16

    Article  CAS  Google Scholar 

  43. Gonçalo M, Coutinho I, Teixeira V, Gameiro AR, Brites MM, Nunes R et al (2013) 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 169(3):660–665

    Article  PubMed  CAS  Google Scholar 

  44. Fernando SL (2014) Drug-reaction eosinophilia and systemic symptoms and drug-induced hypersensitivity syndrome. Australas J Dermatol 55(1):15–23

    Article  PubMed  Google Scholar 

  45. Kano Y, Hirahara K, Mitsuyama Y, Takahashi R, Shiohara T (2007) Utility of the lymphocyte transformation test in the diagnosis of drug sensitivity: dependence on its timing and the type of drug eruption. Allergy 62(12):1439–1444

    Article  PubMed  CAS  Google Scholar 

  46. Wolkenstein P, Chosidow O, Fléchet ML, Robbiola O, Paul M, Dumé L et al (1996) Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Contact Dermatitis 35(4):234–236

    Article  PubMed  CAS  Google Scholar 

  47. Santiago F, Gonçalo M, Vieira R, Coelho S, Figueiredo A (2010) Epicutaneous patch testing in drug hypersensitivity syndrome (DRESS). Contact Dermatitis 62(1):47–53

    Article  PubMed  CAS  Google Scholar 

  48. Yip LW, Thong BY, Lim J, Tan AW, Wong HB, Handa S et al (2007) Ocular manifestations and complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: an Asian series. Allergy 62(5):527–531

    Article  PubMed  CAS  Google Scholar 

  49. Bocquet H, Bagot M, Roujeau JC (1996) Drug-induced pseudolymphoma and drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms: DRESS). Semin Cutan Med Surg 15:250–257

    Article  PubMed  CAS  Google Scholar 

  50. Shiohara T, Inaoka M, Kano Y (2006) Drug-induced hypersensitivity syndrome (DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 55:1–8

    Article  PubMed  Google Scholar 

  51. Chiou CC, Yang LC, Hung SI, Chang YC, Kuo TT, Ho HC et al (2008) Clinicopathological features and prognosis of drug rash with eosinophilia and systemic symptoms: a study of 30 cases in Taiwan. J Eur Acad Dermatol Venereol 22(9):1044

    Article  PubMed  Google Scholar 

  52. Husain Z, Reddy BY, Schwartz RA (2013) DRESS syndrome: part I. Clinical perspectives. J Am Acad Dermatol 68:693.e1–693.14

    Article  CAS  Google Scholar 

  53. Spriet S, Banks TA (2015) Drug reaction with eosinophilia and systemic symptoms syndrome. Allergy Asthma Proc 36(6):501–505

    Article  PubMed  CAS  Google Scholar 

  54. Descamps V, Valance A, Edlinger C, Fillet AM, Grossin M, Lebrun-Vignes B et al (2001) Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms. Arch Dermatol 137:301–304

    PubMed  CAS  Google Scholar 

  55. Shear NH, Spielberg SP (1988) Anticonvulsant hypersensitivity syndrome. In vitro assessment of risk. J Clin Investig 82:1826–1832

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  56. Tas S, Simonart T (1999) Drug-reaction with eosinophilia and systemic symptoms (DRESS syndrome). Acta Clin Belg 54:197–200

    Article  PubMed  CAS  Google Scholar 

  57. Ganeva M, Gancheva T, Lazarova R et al (2008) Carbamazepineinduced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: report of four cases and brief review. Int J Dermatol 47:853–860

    Article  PubMed  Google Scholar 

  58. Ang CC, Wang YS, Yoosuff EL, Tay YK (2010) Retrospective analysis of drug-induced hypersensitivity syndrome: a study of 27 patients. J Am Acad Dermatol 63:219–227

    Article  PubMed  Google Scholar 

  59. Cacoub P, Musette P, Descamps V et al (2011) The DRESS syndrome: a literature review. Am J Med 124:588–597

    Article  PubMed  CAS  Google Scholar 

  60. Gentile I, Talamo M, Borgia G (2010) Is the drug-induced hypersensitivity syndrome (DIH) due to human herpesvirus 6 infection or to allergy-mediated viral reactivation? Report of a case and literature review. BMC Infect Dis 10:49

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Roujeau JC, Stern RS (1994) Severe adverse cutaneous reactions to drugs. N Engl J Med 331:1272–1285

    Article  PubMed  CAS  Google Scholar 

  62. Kano Y, Shiohara T (2009) The variable clinical picture of drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms in relation to the eliciting drug. Immunol Allergy Clin N Am 29:481–501

    Article  PubMed  Google Scholar 

  63. Kano Y, Ishida T, Hirahara K, Shiohara T (2010) Visceral involvements and long-term sequelae in drug-induced hypersensitivity syndrome. Med Clin North Am 94:743–759

    Article  PubMed  Google Scholar 

  64. Bourgeois GP, Cafardi JA, Groysman V, Pamboukian SV, Kirklin JK, Andea AA et al (2011) Fulminant myocarditis as a late sequela of DRESS: two cases. J Am Acad Dermatol 65:889–890

    Article  PubMed  PubMed Central  Google Scholar 

  65. Gupta A, Eggo MC, Uetrecht JP, Cribb AE, Daneman D, Rieder MJ, Shear NH, Cannon M, Spielberg SP (1992) Drug-induced hypothyroidism: the thyroid as a target organ in hypersensitivity reactions to anticonvulsants and sulfonamides. Clin Pharmacol Ther 51(1):56–67

    Article  PubMed  CAS  Google Scholar 

  66. Husain Z, Reddy BY, Schwartz RA (2013) DRESS syndrome: part II. Management and therapeutics. J Am Acad Dermatol 68:709.e1–709.e9

    Article  CAS  Google Scholar 

  67. Elzagallaai AA, Knowles SR, Rieder MJ, Bend JR, Shear NH, Koren G (2009) Patch testing for the diagnosis of anticonvulsant hypersensitivity syndrome: a systematic review. Drug Saf 32:391–408

    Article  PubMed  CAS  Google Scholar 

  68. Pichler WJ, Tilch J (2004) The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 59:809–820

    Article  PubMed  CAS  Google Scholar 

  69. Descamps V, Ben Said B, Sassolas B et al (2010) Management of drug reaction with eosinophilia and systemic symptoms (DRESS). Ann Dermatol Venereol 137:703–708

    Article  PubMed  CAS  Google Scholar 

  70. Peyriere H, Dereure O, Breton H, Demoly P, Cociglio M, Blayac JP et al (2006) Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol 155:422–428

    Article  PubMed  CAS  Google Scholar 

  71. Chen YC, Chiu HC, Chu CY (2010) Drug reaction with eosinophilia and systemic symptoms: a retrospective study of 60 cases. Arch Dermatol 146:1373–1379

    Article  PubMed  Google Scholar 

  72. Roujeau JC (2005) Clinical heterogeneity of drug hypersensitivity. Toxicology 209:123–129

    Article  PubMed  CAS  Google Scholar 

  73. Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC (2001) Acute generalized exanthematous pustulosis (AGEP): a clinical reaction pattern. J Cutan Pathol 28(3):113–119

    Article  PubMed  CAS  Google Scholar 

  74. Sidoroff A, Dunant A, Viboud C et al (2007) Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol 157(5):989–996

    Article  PubMed  CAS  Google Scholar 

  75. Davidovici B, Dodiuk-Gad R, Rozenman D, Halevy S, Israeli RegiSCAR Network (2008) Profile of acute generalized exanthematous pustulosis in Israel during 2002–2005: results of the RegiSCAR study. Isr Med Assoc J 10(6):410–412

    PubMed  Google Scholar 

  76. Halevy S (2009) Acute generalized exanthematous pustulosis. Curr Opin Allergy Clin Immunol 9(4):322–328

    Article  PubMed  Google Scholar 

  77. Szatkowski J, Schwartz RA (2015) Acute generalized exanthematous pustulosis (AGEP): a review and update. J Am Acad Dermatol 73(5):843–848

    Article  PubMed  Google Scholar 

  78. Bär M, John L, Wonschik S, Schmitt J, Kempter W, Bauer A, Meurer M (2008) Acute generalized exanthematous pustulosis induced by high-dose prednisolone in a young woman with optic neuritis owing to disseminated encephalomyelitis. Br J Dermatol 159(1):251–252

    Article  PubMed  Google Scholar 

  79. Belhadjali H, Ghannouchi N, Njim L, Mohamed M, Moussa A, Bayou F et al (2008) Acute generalized exanthematous pustulosis induced by bufexamac in an atopic girl. Contact Dermatitis 58(4):247–248

    Article  PubMed  CAS  Google Scholar 

  80. Matsumoto Y, Okubo Y, Yamamoto T, Ito T, Tsuboi R (2008) Case of acute generalized exanthematous pustulosis caused by ampicillin/cloxacillin sodium in a pregnant woman. J Dermatol 35(6):362–364

    Article  PubMed  Google Scholar 

  81. Schmid S, Kuechler PC, Britschgi M, Steiner UC, Yawalkar N, Limat A et al (2002) Acute generalized exanthematous pustulosis: role of cytotoxic T cells in pustule formation. Am J Pathol 161(6):2079–2086

    Article  PubMed  PubMed Central  Google Scholar 

  82. Britschgi M, Steiner UC, Schmid S, Depta JP, Senti G, Bircher A et al (2001) T-cell involvement in drug-induced acute generalized exanthematous pustulosis. J Clin Invest 107(11):1433–1441

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Kostopoulos TC, Krishna SM, Brinster NK, Ortega-Loayza AG (2015) Acute generalized exanthematous pustulosis: atypical presentations and outcomes. J Eur Acad Dermatol Venereol 29(2):209–214

    Article  PubMed  CAS  Google Scholar 

  84. Buettiker U, Keller M, Pichler WJ, Braathen LR, Yawalkar N (2006) Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group a confirmed by epicutaneous testing and lymphocyte transformation tests. Dermatology 213(1):40–43

    Article  PubMed  CAS  Google Scholar 

  85. Girardi M, Duncan KO, Tigelaar RE, Imaeda S, Watsky KL, McNiff JM (2005) Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis. Am J Dermatopathol 27(4):343–346

    Article  PubMed  Google Scholar 

  86. Fernando SL (2012) Acute generalised exanthematous pustulosis. Australas J Dermatol 53(2):87–92

    Article  PubMed  Google Scholar 

  87. Phillips EJ, Chung W-H, Mockenhaupt M, Roujeau J-C, Mallal SA (2011) Drug hypersensitivity: pharmacogenetics and clinical syndromes. J Allergy Clin Immunol 127:S60–S66

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Pichler WJ (2003) Delayed drug hypersensitivity reactions. Ann Intern Med 139:683–693

    Article  PubMed  CAS  Google Scholar 

  89. 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(6):1562–9.e5

    Article  PubMed  CAS  Google Scholar 

  90. Chaplin DD. (2010) Overview of the immune response. J Allergy Clin Immunol 125(2 Suppl 2):S3–23

    Article  Google Scholar 

  91. Chung W-H, Hung S-I (2012) Recent advances in the genetics and immunology of Stevens-Johnson syndrome and toxic epidermal necrosis. J Dermatol Sci 66:190–196

    Article  PubMed  CAS  Google Scholar 

  92. Ko T-M, Chung W-H, Wei C-Y, Shih H-Y, Chen J-K et al (2011) Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol 128:1266–1276

    Article  PubMed  CAS  Google Scholar 

  93. Pichler WJ, Watkins S (2014) Interaction of small molecules with specific immune receptors: the p-i concept and its consequences. Curr Immunol Rev 10:7–18

    Article  CAS  Google Scholar 

  94. Naisbitt DJ, Gordon SF, Pirmohamed M, Park BK (2000) Immunological principles of adverse drug reactions: the initiation and propagation of immune responses elicited by drug treatment. Drug Saf 23(6):483–507

    Article  PubMed  CAS  Google Scholar 

  95. Pan R-Y, Wu Y-C, Chung W-H, Hung S-I (2014) HLA and TCR recognition of medications in severe cutaneous adverse reactions. Curr Immunol Rev 10:51–61

    Article  CAS  Google Scholar 

  96. Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z, Bharadwaj M et al (2012) Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486(7404):554–558

    Article  PubMed  CAS  Google Scholar 

  97. Parker G (2016) Development of an incipient Stevens-Johnson reaction while on a stable dose of lamotrigine. Australas Psychiatry 24(2):193–194

    Article  PubMed  Google Scholar 

  98. Burkhart KK, Abernethy D, Jackson D (2015) Data mining FAERS to analyze molecular targets of drugs highly associated with Stevens-Johnson syndrome. J Med Toxicol 11(2):265–273

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Ciccacci C et al (2013) Association between CYP2B6 polymorphisms and Nevirapine-induced SJS/TEN: a pharmacogenetics study. Eur J Clin Pharmacol 69(11):1909–1916

    Article  PubMed  CAS  Google Scholar 

  100. Carr DF et al (2014) CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations. J Antimicrob Chemother 69(12):3329–3334

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Tanno LK et al (2015) The absence of CYP3A5*3 is a protective factor to anticonvulsants hypersensitivity reactions: a case-control study in Brazilian subjects. PLoS One 10(8):e0136141

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Khor AH et al (2014) HLA-B*15:02 association with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in an Indian population: a pooled-data analysis and meta-analysis. Epilepsia 55(11):e120–e124

    Article  PubMed  CAS  Google Scholar 

  103. Chang CC et al (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(2):221–224

    Article  PubMed  Google Scholar 

  104. Wu XT et al (2010) Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epilepsy Behav 19(3):405–408

    Article  PubMed  CAS  Google Scholar 

  105. Nguyen DV et al (2015) HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese. Asia Pac Allergy 5(2):68–77

    Article  PubMed  PubMed Central  Google Scholar 

  106. Alfirevic A et al (2006) HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics 7(6):813–818

    Article  PubMed  CAS  Google Scholar 

  107. Song JS et al (2014) Absence of HLA-B*1502 and HLA-A*3101 alleles in 9 Korean patients with antiepileptic drug-induced skin rash: a preliminary study. Ann Lab Med 34(5):372–375

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Tangamornsuksan W et al (2013) Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol 149(9):1025–1032

    Article  PubMed  CAS  Google Scholar 

  109. Jaruthamsophon K et al (2017) HLA-B*15:21 and carbamazepine-induced Stevens-Johnson syndrome: pooled-data and in silico analysis. Sci Rep 7:45553

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Amstutz U et al (2013) HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children. Clin Pharmacol Ther 94(1):142–149

    Article  PubMed  CAS  Google Scholar 

  111. Ozeki T et al (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(5):1034–1041

    Article  PubMed  CAS  Google Scholar 

  112. Kim SH et al (2011) Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res 97(1–2):190–197

    Article  PubMed  CAS  Google Scholar 

  113. McCormack M et al (2011) HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 364(12):1134–1143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Genin E et al (2014) HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis. Pharmacogenomics J 14(3):281–288

    Article  PubMed  CAS  Google Scholar 

  115. Amstutz U et al (2014) Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia 55(4):496–506

    Article  PubMed  CAS  Google Scholar 

  116. Pichler WJ, Hausmann O (2016) Classification of drug hypersensitivity into allergic, p-i, and pseudo-allergic forms. Int Arch Allergy Immunol 171(3–4):166–179

    Article  PubMed  CAS  Google Scholar 

  117. Lv YD et al (2013) The association between oxcarbazepine-induced maculopapular eruption and HLA-B alleles in a northern Han Chinese population. BMC Neurol 13:75

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Moon J et al (2016) HLA-B*40:02 and DRB1*04:03 are risk factors for oxcarbazepine-induced maculopapular eruption. Epilepsia 57(11):1879–1886

    Article  PubMed  CAS  Google Scholar 

  119. Shi YW et al (2011) HLA-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population. Basic Clin Pharmacol Toxicol 109(1):42–46

    Article  PubMed  CAS  Google Scholar 

  120. An DM et al (2010) Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population. Epilepsy Res 92(2–3):226–230

    Article  PubMed  CAS  Google Scholar 

  121. Zeng T et al (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(4):488–493

    Article  PubMed  CAS  Google Scholar 

  122. Koomdee N et al (2017) Association of HLA-A and HLA-B alleles with lamotrigine-induced cutaneous adverse drug reactions in the Thai population. Front Pharmacol 29;8:879. 

    Google Scholar 

  123. Nathan K et al (2015) Lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS). BMJ Case Rep 2015:bcr2014209170

    Article  PubMed  PubMed Central  Google Scholar 

  124. Fricke-Galindo I et al (2014) HLA-A*02:01:01/-B*35:01:01/-C*04:01:01 haplotype associated with lamotrigine-induced maculopapular exanthema in Mexican mestizo patients. Pharmacogenomics 15(15):1881–1891

    Article  PubMed  CAS  Google Scholar 

  125. Moon J et al (2015) The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population. Epilepsia 56(10):e161–e167

    Article  PubMed  CAS  Google Scholar 

  126. Li LJ et al (2013) Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese. Epilepsy Res 106(1–2):296–300

    Article  PubMed  CAS  Google Scholar 

  127. Ramirez E et al (2016) 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 115:168–178

    Article  PubMed  CAS  Google Scholar 

  128. Caudle KE et al (2014) Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther 96(5):542–548

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Chang CC et al (2016) 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

    Article  PubMed  CAS  Google Scholar 

  130. Cheung YK et al (2013) HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia 54(7):1307–1314

    Article  PubMed  CAS  Google Scholar 

  131. Locharernkul C et al (2008) Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia 49(12):2087–2091

    Article  PubMed  Google Scholar 

  132. Ramírez E, et al (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 115:168–178

    Article  PubMed  CAS  Google Scholar 

  133. Ramasamy SN et al (2013) Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012. Drug Saf 36(10):953–980

    Article  PubMed  CAS  Google Scholar 

  134. Wu R et al (2016) Impact of HLA-B*58:01 allele and allopurinol-induced cutaneous adverse drug reactions: evidence from 21 pharmacogenetic studies. Oncotarget 7(49):81870–81879

    PubMed  PubMed Central  Google Scholar 

  135. Cheng L et al (2015) HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese patients: a multicentre retrospective case-control clinical study. Br J Dermatol 173(2):555–558

    Article  PubMed  CAS  Google Scholar 

  136. Tohkin M et al (2013) A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Pharmacogenomics J 13(1):60–69

    Article  PubMed  CAS  Google Scholar 

  137. Osabe M, Tohkin M, Hirayama N (2016) In Silico analysis of interactions between HLA-B*58:01 and allopurinol-related compounds. Chem-Bio Informatics 16:1–4

    Article  CAS  Google Scholar 

  138. Hughes AR et al (2008) Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility. Pharmacogenomics J 8(6):365–374

    Article  PubMed  CAS  Google Scholar 

  139. Sousa-Pinto B et al (2015) Pharmacogenetics of abacavir hypersensitivity: a systematic review and meta-analysis of the association with HLA-B*57:01. J Allergy Clin Immunol 136(4):1092–1094. e3

    Article  PubMed  CAS  Google Scholar 

  140. Martin MA et al (2012) Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther 91(4):734–738

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Mallal S et al (2002) Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 359(9308):727–732

    Article  PubMed  CAS  Google Scholar 

  142. Hughes AR et al (2004) Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations. Pharmacogenomics 5(2):203–211

    Article  PubMed  CAS  Google Scholar 

  143. Hetherington S et al (2002) Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 359(9312):1121–1122

    Article  PubMed  CAS  Google Scholar 

  144. Munderi P et al (2011) Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART. Tropical Med Int Health 16(2):200–204

    Article  Google Scholar 

  145. Saag M et al (2008) High sensitivity of human leukocyte antigen-B*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis 46(7):1111–1118

    Article  PubMed  CAS  Google Scholar 

  146. Guo Y et al (2013) Studies on abacavir-induced hypersensitivity reaction: a successful example of translation of pharmacogenetics to personalized medicine. Sci China Life Sci 56(2):119–124

    Article  PubMed  CAS  Google Scholar 

  147. Kongpan T, et al (2015) Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions. Pharmacogenet Genomics 25(8):402–411

    Article  PubMed  CAS  Google Scholar 

  148. Lonjou C, et al (2008) A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics 18(2):99–107

    Article  PubMed  CAS  Google Scholar 

  149. Zhang FR, et al (2013) HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med 369(17):1620–1628

    Google Scholar 

  150. Tempark T, et al (2017) Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13: 01 allele in the Thai population. Pharmacogenet Genomics 27(12):429–437.

    Article  PubMed  CAS  Google Scholar 

  151. Her Y et al (2011) Stevens-Johnson syndrome induced by acetazolamide. J Dermatol 38(3):272–275

    Article  PubMed  Google Scholar 

  152. Shu C et al (2015) Toxic epidermal necrolysis induced by methazolamide in a Chinese-Korean man carrying HLA-B*59:01. Int J Dermatol 54(11):1242–1245

    Article  PubMed  CAS  Google Scholar 

  153. Flach AJ, Smith RE, Fraunfelder FT (1995) Stevens-Johnson syndrome associated with methazolamide treatment reported in two Japanese-American women. Ophthalmology 102(11):1677–1680

    Article  PubMed  CAS  Google Scholar 

  154. Cotter JB (1998) Methazolamide-induced Stevens-Johnson syndrome: a warning! Arch. Arch Ophthalmol 116(1):117

    Article  PubMed  CAS  Google Scholar 

  155. Kim SH, Kim M, Lee KW, Kim SH, Kang HR, Park HW et al (2010) HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics 11(6):879–884

    Article  PubMed  CAS  Google Scholar 

  156. Xu Y, Wu M, Sheng F, Sun Q (2015) Methazolamide-induced toxic epidermal necrolysis in a Chinese woman with HLA-B5901. Indian J Ophthalmol 63(7):623–624

    PubMed  PubMed Central  Google Scholar 

  157. Yang F, Xuan J, Chen J, Zhong H, Luo H, Zhou P et al (2016) HLA-B*59:01: a marker for Stevens-Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese. Pharmacogenomics J 16(1):83–87

    Article  PubMed  CAS  Google Scholar 

  158. Jee YK, Kim S, Lee JM, Park HS, Kim SH (2017) CD8+ T-cell activation by methazolamide causes methazolamide-induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Clin Exp Allergy 47(7):972–974

    Article  PubMed  Google Scholar 

  159. Nolan SJ, Marson AG, Weston J, Tudur Smith C (2016) Carbamazepine versus phenobarbitone monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev 12:CD001904

    PubMed  Google Scholar 

  160. Visudtibhan A, Chiemchanya S, Visudhiphan P, Soongprasit M (2001) Adverse cutaneous reactions to phenobarbital in epileptic children. J Med Assoc Thail 84(6):831–836

    CAS  Google Scholar 

  161. Mockenhaupt M, Viboud C, Dunant A, Naldi L, Halevy S, Bouwes Bavinck JN et al (2008) Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol 128(1):35–44

    Article  PubMed  CAS  Google Scholar 

  162. Mamishi S et al (2009) Severe cutaneous reactions caused by barbiturates in seven Iranian children. Int J Dermatol 48(11):1254–1261

    Article  PubMed  Google Scholar 

  163. Manuyakorn W, Siripool K, Kamchaisatian W, Pakakasama S, Visudtibhan A, Vilaiyuk S et al (2013) Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children. Pediatr Allergy Immunol 24(3):299–303

    Article  PubMed  Google Scholar 

  164. Manuyakorn W, Mahasirimongkol S, Likkasittipan P, Kamchaisatian W, Wattanapokayakit S, Inunchot W et al (2016) Association of HLA genotypes with phenobarbital hypersensitivity in children. Epilepsia 57(10):1610–1616

    Article  PubMed  CAS  Google Scholar 

  165. Sun D, Yu CH, Liu ZS, He XL, Hu JS, Wu GF et al (2014) Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China. J Huazhong Univ Sci Technolog Med Sci 34(1):146–150

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Chonlaphat Sukasem

  2. Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand

    Chonlaphat Sukasem

  3. Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Therdpong Tempark

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  1. Chonlaphat Sukasem
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Correspondence to Chonlaphat Sukasem .

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  1. University of South Florida Health College of Pharmacy, Tampa, Florida, USA

    Yashwant Pathak

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Sukasem, C., Tempark, T. (2018). Pharmacogenomics: A New Approach for Preventing Severe Cutaneous Adverse Drug Reactions. In: Pathak, Y. (eds) Genomics-Driven Healthcare. Adis, Singapore. https://doi.org/10.1007/978-981-10-7506-3_18

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