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Drug-Induced Skin Adverse Reactions: The Role of Pharmacogenomics in Their Prevention

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Abstract

Adverse drug reactions (ADRs) affect many patients and remain a major public health problem, as they are a common cause of morbidity and mortality. It is estimated that ADRs are responsible for about 6% of hospital admissions and about 9% of hospitalization costs. Skin is the organ that is most frequently involved in ADRs. Drug-induced skin injuries vary from mild maculopapular eruptions (MPE) to severe cutaneous adverse reactions (SCARs) that are potentially life threatening. Genetic factors have been suggested to contribute to these SCARs, and most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes. Common drugs associated with SCARs connected with strong genetic risk factors include antiepileptic drugs (AEDs), allopurinol, abacavir, nevirapine, sulfonamides, dapsone, non-steroidal anti-inflammatory drugs (NSAIDs), and analgesic drugs. However, genetic associations vary between different ethnic populations. Differences may in part be explained by the different prevalence of HLA (human leukocyte antigen) alleles among ethnic groups. In this review, we present and discuss the recent advances in genetic associations with ADRs in the skin. Many of these ADRs are now preventable with pharmacogenetic screening.

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References

  1. Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4(2):e4439.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Roychowdhury S, Svensson CK. Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin. AAPS J. 2005;7(4):E834–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–5.

    Article  PubMed  CAS  Google Scholar 

  4. Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ (Clinical research ed). 2004;329(7456):15–9.

    Article  PubMed Central  Google Scholar 

  5. Pirmohamed M. Pharmacogenetics of idiosyncratic adverse drug reactions. Handb Exp Pharmacol. 2010;196:477–91.

    Article  CAS  Google Scholar 

  6. Gomes ER, Demoly P. Epidemiology of hypersensitivity drug reactions. Curr Opin Allergy Clin Immunol. 2005;5(4):309–16.

    Article  PubMed  Google Scholar 

  7. Naisbitt DJ, Pirmohamed M, Park BK. Immunopharmacology of hypersensitivity reactions to drugs. Current Allergy Asthma Rep. 2003;3(1):22–9.

    Article  Google Scholar 

  8. Descotes J, Choquet-Kastylevsky G. Gell and Coombs’s classification: is it still valid? Toxicology. 2001;158(1–2):43–9.

    Article  PubMed  CAS  Google Scholar 

  9. Alfirevic A, Pirmohamed M. Drug induced hypersensitivity and the HLA complex. Pharmaceuticals. 2011;4(1):69–90.

    Article  CAS  Google Scholar 

  10. Zalewska-Janowska A, Spiewak R, Kowalski ML. Cutaneous manifestation of drug allergy and hypersensitivity. Immunol Allergy Clin N Am. 2017;37(1):165–81.

    Article  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Pavlos R, Mallal S, Ostrov D, Buus S, Metushi I, Peters B, et al. T cell-mediated hypersensitivity reactions to drugs. Annu Rev Med. 2015;66:439–54.

    Article  PubMed  CAS  Google Scholar 

  13. Pirmohamed M. Personalized pharmacogenomics: predicting efficacy and adverse drug reactions. Annu Rev Genomics Hum Genet. 2014;15:349–70.

    Article  PubMed  CAS  Google Scholar 

  14. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–79.

    Article  PubMed  Google Scholar 

  15. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe’er I, Floratos A, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009;41(7):816–9.

    Article  PubMed  CAS  Google Scholar 

  16. Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, et al. Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011;141(1):338–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Singer JB, Lewitzky S, Leroy E, Yang F, Zhao X, Klickstein L, et al. A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet. 2010;42(8):711–4.

    Article  PubMed  CAS  Google Scholar 

  18. Lonjou C, Thomas L, Borot N, Ledger N, de Toma C, LeLouet H, et al. A marker for Stevens–Johnson syndrome …: ethnicity matters. Pharmacogenomics J. 2006;6(4):265–8.

    Article  PubMed  CAS  Google Scholar 

  19. 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(6):757–65.

    Article  PubMed  CAS  Google Scholar 

  20. Wilson JT, Hojer B, Tomson G, Rane A, Sjoqvist F. High incidence of a concentration-dependent skin reaction in children treated with phenytoin. BMJ. 1978;1(6127):1583–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Chung WH, Chang WC, Lee YS, Wu YY, Yang CH, Ho HC, et al. Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA. 2014;312(5):525–34.

    Article  PubMed  Google Scholar 

  22. Chaponda M, Pirmohamed M. Hypersensitivity reactions to HIV therapy. Br J Clin Pharmacol. 2011;71(5):659–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Yun J, Adam J, Yerly D, Pichler WJ. Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA. Allergy. 2012;67(11):1338–46.

    Article  PubMed  CAS  Google Scholar 

  24. Ostrov DA, Grant BJ, Pompeu YA, Sidney J, Harndahl M, Southwood S, et al. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proc Natl Acad Sci USA. 2012;109(25):9959–64.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cutaneous drug reaction case reports: from the world literature. Am J Clin Dermatol. 2001;2(4):267–74.

  26. Lee JH, Park KH, Moon HJ, Lee YW, Park JW, Hong CS. Spontaneous reporting of adverse drug reactions through electronic submission from regional society healthcare professionals in Korea. Yonsei Med J. 2012;53(5):1022–7.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Hunziker T, Kunzi UP, Braunschweig S, Zehnder D, Hoigne R. Comprehensive hospital drug monitoring (CHDM): adverse skin reactions, a 20-year survey. Allergy. 1997;52(4):388–93.

    Article  PubMed  CAS  Google Scholar 

  28. Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology. 2005;209(2):123–9.

    Article  PubMed  CAS  Google Scholar 

  29. Roujeau JC, Guillaume JC, Fabre JP, Penso D, Flechet ML, Girre JP. Toxic epidermal necrolysis (Lyell syndrome). Incidence and drug etiology in France, 1981–1985. Arch Dermatol. 1990;126(1):37–42.

    Article  PubMed  CAS  Google Scholar 

  30. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part I. Introduction, history, classification, clinical features, systemic manifestations, etiology, and immunopathogenesis. J Am Acad Dermatol. 2013;69(2):173.e1–13 (quiz 85–6).

  31. Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol. 2007;56(2):181–200.

    Article  PubMed  Google Scholar 

  32. Ko TM, Chung WH, Wei CY, Shih HY, Chen JK, Lin CH, et al. Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens–Johnson syndrome. J Allergy Clin Immunol. 2011;128(6):1266–76.e11.

  33. Chung WH, Hung SI, Yang JY, Su SC, Huang SP, Wei CY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens–Johnson syndrome and toxic epidermal necrolysis. Nat Med. 2008;14(12):1343–50.

    Article  PubMed  CAS  Google Scholar 

  34. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science (New York, NY). 1998;282(5388):490–3.

    Article  CAS  Google Scholar 

  35. Nassif A, Bensussan A, Dorothee G, Mami-Chouaib F, Bachot N, Bagot M, et al. Drug specific cytotoxic T-cells in the skin lesions of a patient with toxic epidermal necrolysis. J Invest Dermatol. 2002;118(4):728–33.

    Article  PubMed  CAS  Google Scholar 

  36. Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331(19):1272–85.

    Article  PubMed  CAS  Google Scholar 

  37. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens–Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94(4):419–36 (quiz 36–8, 56).

  38. Dodiuk-Gad RP, Chung WH, Valeyrie-Allanore L, Shear NH. Stevens–Johnson syndrome and toxic epidermal necrolysis: an update. Am J Clin Dermatol. 2015;16(6):475–93.

    Article  PubMed  Google Scholar 

  39. Mawson AR, Eriator I, Karre S. Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role? Med Sci Monit. 2015;21:133–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Yang MS, Kang MG, Jung JW, Song WJ, Kang HR, Cho SH, et al. Clinical features and prognostic factors in severe cutaneous drug reactions. Int Arch Allergy Immunol. 2013;162(4):346–54.

    Article  PubMed  CAS  Google Scholar 

  41. Kardaun SH, Sekula P, Valeyrie-Allanore L, Liss Y, Chu CY, Creamer D, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. Br J Dermatol. 2013;169(5):1071–80.

    Article  PubMed  CAS  Google Scholar 

  42. Kardaun SH, Sidoroff A, Valeyrie-Allanore L, Halevy S, Davidovici BB, Mockenhaupt M, et al. Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist? Br J Dermatol. 2007;156(3):609–11.

    Article  PubMed  CAS  Google Scholar 

  43. Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. The diagnosis of a DRESS syndrome has been sufficiently established on the basis of typical clinical features and viral reactivations. Br J Dermatol. 2007;156(5):1083–4.

    Article  PubMed  CAS  Google Scholar 

  44. Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg. 1996;15(4):250–7.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  46. Sidoroff A, Dunant A, Viboud C, Halevy S, Bavinck JN, Naldi L, et al. Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157(5):989–96.

    Article  PubMed  CAS  Google Scholar 

  47. Sidoroff A, Halevy S, Bavinck JN, Vaillant L, Roujeau JC. Acute generalized exanthematous pustulosis (AGEP)—a clinical reaction pattern. J Cutan Pathol. 2001;28(3):113–9.

    Article  PubMed  CAS  Google Scholar 

  48. Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis (AGEP): A review and update. J Am Acad Dermatol. 2015;73(5):843–8.

    Article  PubMed  Google Scholar 

  49. Thienvibul C, Vachiramon V, Chanprapaph K. Five-year retrospective review of acute generalized exanthematous pustulosis. Dermatol Res Pract. 2015;2015:260928.

    Article  PubMed  PubMed Central  Google Scholar 

  50. WHO: Neurological disorders: public health challenges. Geneva: WHO; 2006.

  51. Blaszczyk B, Szpringer M, Czuczwar SJ, Lason W. Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions. Pharmacol Rep. 2013;65(2):399–409.

    Article  PubMed  Google Scholar 

  52. Mehta M, Shah J, Khakhkhar T, Shah R, Hemavathi KG. Anticonvulsant hypersensitivity syndrome associated with carbamazepine administration: Case series. J Pharmacol Pharmacother. 2014;5(1):59–62.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Hung SI, Chung WH, Liu ZS, Chen CH, Hsih MS, Hui RC, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11(3):349–56.

    Article  PubMed  CAS  Google Scholar 

  54. Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, et al. Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int. 2006;55(1):17–25.

    Article  PubMed  CAS  Google Scholar 

  55. Shiohara T, Kano Y. A complex interaction between drug allergy and viral infection. Clin Rev Allergy Immunol. 2007;33(1–2):124–33.

    Article  PubMed  CAS  Google Scholar 

  56. Aihara Y, Ito SI, Kobayashi Y, Yamakawa Y, Aihara M, Yokota S. Carbamazepine-induced hypersensitivity syndrome associated with transient hypogammaglobulinaemia and reactivation of human herpesvirus 6 infection demonstrated by real-time quantitative polymerase chain reaction. Br J Dermatol. 2003;149(1):165–9.

    Article  PubMed  CAS  Google Scholar 

  57. Seishima M, Yamanaka S, Fujisawa T, Tohyama M, Hashimoto K. Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome. Br J Dermatol. 2006;155(2):344–9.

    Article  PubMed  CAS  Google Scholar 

  58. Wang Q, Zhou JQ, Zhou LM, Chen ZY, Fang ZY, Chen SD, et al. Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland. Seizure. 2011;20(6):446–8.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  60. Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genom. 2006;16(4):297–306.

    Article  CAS  Google Scholar 

  61. Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007;48(5):1015–8.

    Article  PubMed  CAS  Google Scholar 

  62. Tassaneeyakul W, Tiamkao S, Jantararoungtong T, Chen P, Lin SY, Chen WH, et al. Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia. 2010;51(5):926–30.

    Article  PubMed  Google Scholar 

  63. Locharernkul C, Loplumlert J, Limotai C, Korkij W, Desudchit T, Tongkobpetch S, et al. Carbamazepine and phenytoin induced Stevens–Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008;49(12):2087–91.

    Article  PubMed  Google Scholar 

  64. Kulkantrakorn K, Tassaneeyakul W, Tiamkao S, Jantararoungtong T, Prabmechai N, Vannaprasaht S, et al. HLA-B*1502 strongly predicts carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Thai patients with neuropathic pain. Pain Pract. 2012;12(3):202–8.

    Article  PubMed  Google Scholar 

  65. 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(3):290–3.

    PubMed  CAS  Google Scholar 

  66. Ding WY, Lee CK, Choon SE. Cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia. Int J Dermatol. 2010;49(7):834–41.

    Article  PubMed  Google Scholar 

  67. Mehta TY, Prajapati LM, Mittal B, Joshi CG, Sheth JJ, Patel DB, et al. Association of HLA-B*1502 allele and carbamazepine-induced Stevens–Johnson syndrome among Indians. Indian J Dermatol Venereol Leprol. 2009;75(6):579–82.

    Article  PubMed  Google Scholar 

  68. Alfirevic A, Jorgensen AL, Williamson PR, Chadwick DW, Park BK, Pirmohamed M. HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics. 2006;7(6):813–8.

    Article  PubMed  CAS  Google Scholar 

  69. Ozeki T, Mushiroda T, Yowang A, Takahashi A, Kubo M, Shirakata Y, 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(5):1034–41.

    Article  PubMed  CAS  Google Scholar 

  70. Kashiwagi M, Aihara M, Takahashi Y, Yamazaki E, Yamane Y, Song Y, et al. Human leukocyte antigen genotypes in carbamazepine-induced severe cutaneous adverse drug response in Japanese patients. J Dermatol. 2008;35(10):683–5.

    Article  PubMed  Google Scholar 

  71. Ikeda H, Takahashi Y, Yamazaki E, Fujiwara T, Kaniwa N, Saito Y, et al. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia. 2010;51(2):297–300.

    Article  PubMed  Google Scholar 

  72. Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, Lohitnavy M, Tassaneeyakul W. 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. 2013;149(9):1025–32.

    Article  PubMed  CAS  Google Scholar 

  73. Chung WH, Hung SI. Recent advances in the genetics and immunology of Stevens–Johnson syndrome and toxic epidermal necrosis. J Dermatol Sci. 2012;66(3):190–6.

    Article  PubMed  CAS  Google Scholar 

  74. Wu XT, Hu FY, An DM, Yan B, Jiang X, Kwan P, et al. Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epilepsy Behav. 2010;19(3):405–8.

    Article  PubMed  CAS  Google Scholar 

  75. Genin E, Chen DP, Hung SI, Sekula P, Schumacher M, Chang PY, et al. HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis. Pharmacogenomics J. 2014;14(3):281–8.

    Article  PubMed  CAS  Google Scholar 

  76. McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperaviciute D, Carrington M, et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364(12):1134–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Kim SH, Lee KW, Song WJ, Kim SH, Jee YK, Lee SM, et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res. 2011;97(1–2):190–7.

    Article  PubMed  CAS  Google Scholar 

  78. Cheng CY, Su SC. HLA associations and clinical implications in T-cell mediated drug hypersensitivity reactions: an updated review. J Immunol Res. 2014;2014:565320.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Cheung YK, Cheng SH, Chan EJ, Lo SV, Ng MH, Kwan P. HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013;54(7):1307–14.

    Article  PubMed  CAS  Google Scholar 

  80. Tassaneeyakul W, Prabmeechai N, Sukasem C, Kongpan T, Konyoung P, Chumworathayi P, et al. Associations between HLA class I and cytochrome P450 2C9 genetic polymorphisms and phenytoin-related severe cutaneous adverse reactions in a Thai population. Pharmacogenet Genomics. 2016;26(5):225–34.

    Article  PubMed  CAS  Google Scholar 

  81. Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population. Pharmacogenomics J. 2017;17(2):170–3.

    Article  PubMed  CAS  Google Scholar 

  82. McCormack M, Urban TJ, Shianna KV, Walley N, Pandolfo M, Depondt C, et al. Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. Pharmacogenomics. 2012;13(4):399–405.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Franco V, Perucca E. CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects. Expert Opin Drug Metab Toxicol. 2015;11(8):1269–79.

    Article  PubMed  CAS  Google Scholar 

  84. Zeng T, Long YS, Min FL, Liao WP, Shi YW. 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. 2015;54(4):488–93.

    Article  PubMed  CAS  Google Scholar 

  85. Li LJ, Hu FY, Wu XT, An DM, Yan B, Zhou D. Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese. Epilepsy Res. 2013;106(1–2):296–300.

    Article  PubMed  CAS  Google Scholar 

  86. Koomdee N, Pratoomwun J, Jantararoungtong T, Theeramoke V, Tassaneeyakul W, Klaewsongkram J, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Lonjou C, Borot N, Sekula P, Ledger N, Thomas L, Halevy S, 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(2):99–107.

    Article  PubMed  CAS  Google Scholar 

  88. Kazeem GR, Cox C, Aponte J, Messenheimer J, Brazell C, Nelsen AC, et al. High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenet Genomics. 2009;19(9):661–5.

    Article  PubMed  CAS  Google Scholar 

  89. Park HJ, Kim SR, Leem DW, Moon IJ, Koh BS, Park KH, et al. Clinical features of and genetic predisposition to drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a single Korean tertiary institution patients-investigating the relation between the HLA -B*4403 allele and lamotrigine. Eur J Clin Pharmacol. 2015;71(1):35–41.

    Article  PubMed  CAS  Google Scholar 

  90. Moon J, Park HK, Chu K, Sunwoo JS, Byun JI, Lim JA, et al. The HLA-A*2402/Cw*0102 haplotype is associated with lamotrigine-induced maculopapular eruption in the Korean population. Epilepsia. 2015;56(10):e161–7.

    Article  PubMed  CAS  Google Scholar 

  91. Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: a critical review. Epilepsia. 2004;45(9):1141–9.

    Article  PubMed  CAS  Google Scholar 

  92. Yukawa E, Mamiya K. Effect of CYP2C19 genetic polymorphism on pharmacokinetics of phenytoin and phenobarbital in Japanese epileptic patients using non-linear mixed effects model approach. J Clin Pharm Ther. 2006;31(3):275–82.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  94. Kaniwa N, Sugiyama E, Saito Y, Kurose K, Maekawa K, Hasegawa R, et al. Specific HLA types are associated with antiepileptic drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics. 2013;14(15):1821–31.

    Article  PubMed  CAS  Google Scholar 

  95. Alvestad S, Lydersen S, Brodtkorb E. Cross-reactivity pattern of rash from current aromatic antiepileptic drugs. Epilepsy Res. 2008;80(2–3):194–200.

    Article  PubMed  CAS  Google Scholar 

  96. Hershfield MS, Callaghan JT, Tassaneeyakul W, Mushiroda T, Thorn CF, Klein TE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153–8.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  98. Lee HY, Martanto W, Thirumoorthy T. Epidemiology of Stevens–Johnson syndrome and toxic epidermal necrolysis in Southeast Asia. Dermatol Sin. 2013;31:217–20.

    Article  Google Scholar 

  99. Yun J, Mattsson J, Schnyder K, Fontana S, Largiader CR, Pichler WJ, et al. Allopurinol hypersensitivity is primarily mediated by dose-dependent oxypurinol-specific T cell response. Clin Exp Allergy. 2013;43(11):1246–55.

    Article  PubMed  CAS  Google Scholar 

  100. Yun J, Marcaida MJ, Eriksson KK, Jamin H, Fontana S, Pichler WJ, et al. Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01. J Immunol (Baltimore, Md: 1950). 2014;192(7):2984–93.

  101. Chung WH, Chang WC, Stocker SL, Juo CG, Graham GG, Lee MH, et al. 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. 2015;74(12):2157–64.

    Article  PubMed  CAS  Google Scholar 

  102. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA. 2005;102(11):4134–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Tassaneeyakul W, Jantararoungtong T, Chen P, Lin PY, Tiamkao S, Khunarkornsiri U, 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(9):704–9.

    Article  PubMed  CAS  Google Scholar 

  104. Kang HR, Jee YK, Kim YS, Lee CH, Jung JW, Kim SH, et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011;21(5):303–7.

    Article  PubMed  CAS  Google Scholar 

  105. Kaniwa N, Saito Y, Aihara M, Matsunaga K, Tohkin M, Kurose K, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics. 2008;9(11):1617–22.

    Article  PubMed  CAS  Google Scholar 

  106. Lee MH, Stocker SL, Anderson J, Phillips EJ, Nolan D, Williams KM, et al. Initiating allopurinol therapy: do we need to know the patient’s human leucocyte antigen status? Intern Med J. 2012;42(4):411–6.

    Article  PubMed  CAS  Google Scholar 

  107. Ng CY, Yeh YT, Wang CW, Hung SI, Yang CH, Chang YC, et al. Impact of the HLA-B(*)58:01 allele and renal impairment on allopurinol-induced cutaneous adverse reactions. J Invest Dermatol. 2016;136(7):1373–81.

    Article  PubMed  CAS  Google Scholar 

  108. Somkrua R, Eickman EE, Saokaew S, Lohitnavy M, Chaiyakunapruk N. Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC Med Genet. 2011;12:118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Tohkin M, Kaniwa N, Saito Y, Sugiyama E, Kurose K, Nishikawa J, et al. A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Pharmacogenomics J. 2013;13(1):60–9.

    Article  PubMed  CAS  Google Scholar 

  110. Saksit N, Nakkam N, Konyoung P, Khunarkornsiri U, Tassaneeyakul W, Chumworathayi P, et al. Comparison between the HLA-B(*)58: 01 allele and single-nucleotide polymorphisms in chromosome 6 for prediction of allopurinol-induced severe cutaneous adverse. Reactions. 2017;2017:2738784.

    Google Scholar 

  111. Hetherington S, McGuirk S, Powell G, Cutrell A, Naderer O, Spreen B, et al. Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir. Clin Ther. 2001;23(10):1603–14.

    Article  PubMed  CAS  Google Scholar 

  112. Adam J, Eriksson KK, Schnyder B, Fontana S, Pichler WJ, Yerly D. Avidity determines T-cell reactivity in abacavir hypersensitivity. Eur J Immunol. 2012;42(7):1706–16.

    Article  PubMed  CAS  Google Scholar 

  113. Lucas A, Lucas M, Strhyn A, Keane NM, McKinnon E, Pavlos R, et al. Abacavir-reactive memory T cells are present in drug naive individuals. PLoS One. 2015;10(2):e0117160.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Norcross MA, Luo S, Lu L, Boyne MT, Gomarteli M, Rennels AD, et al. Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity. AIDS (London, England). 2012;26(11):F21–9.

  115. Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z, Bharadwaj M, et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. 2012;486(7404):554–8.

    Article  PubMed  CAS  Google Scholar 

  116. Symonds W, Cutrell A, Edwards M, Steel H, Spreen B, Powell G, et al. Risk factor analysis of hypersensitivity reactions to abacavir. Clin Ther. 2002;24(4):565–73.

    Article  PubMed  CAS  Google Scholar 

  117. Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet (London, England). 2002;359(9312):1121–2.

  118. Park WB, Choe PG, Song KH, Lee S, Jang HC, Jeon JH, et al. Should HLA-B*5701 screening be performed in every ethnic group before starting abacavir? Clin Infect Dis. 2009;48(3):365–7.

    Article  PubMed  Google Scholar 

  119. Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore 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 (London, England). 2002;359(9308):727–32.

  120. Hughes DA, Vilar FJ, Ward CC, Alfirevic A, Park BK, Pirmohamed M. Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics. 2004;14(6):335–42.

    Article  PubMed  Google Scholar 

  121. Rauch A, Nolan D, Martin A, McKinnon E, Almeida C, Mallal S. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clin Infect Dis. 2006;43(1):99–102.

    Article  PubMed  CAS  Google Scholar 

  122. Sousa-Pinto B, Pinto-Ramos J, Correia C, Goncalves-Costa G, Gomes L, Gil-Mata S, et al. Pharmacogenetics of abacavir hypersensitivity: a systematic review and meta-analysis of the association with HLA-B*57:01. J Allergy Clin Immunol. 2015;136(4):1092–4.e3.

  123. Saag M, Balu R, Phillips E, Brachman P, Martorell C, Burman W, 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(7):1111–8.

    Article  PubMed  CAS  Google Scholar 

  124. Phillips EJ, Mallal SA. Pharmacogenetics of drug hypersensitivity. Pharmacogenomics. 2010;11(7):973–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Carr DF, Bourgeois S, Chaponda M, Takeshita LY, Morris AP, Castro EM, et al. Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population. J Antimicrob Chemother. 2017;72(4):1152–62.

    PubMed  PubMed Central  CAS  Google Scholar 

  126. Yuan J, Guo S, Hall D, Cammett AM, Jayadev S, Distel M, et al. Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent. AIDS (London, England). 2011;25(10):1271–80.

  127. Martin AM, Nolan D, James I, Cameron P, Keller J, Moore C, et al. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS (London, England). 2005;19(1):97–9.

  128. Gao S, Gui XE, Liang K, Liu Z, Hu J, Dong B. HLA-dependent hypersensitivity reaction to nevirapine in Chinese Han HIV-infected patients. AIDS Res Hum Retrovir. 2012;28(6):540–3.

    Article  PubMed  CAS  Google Scholar 

  129. Carr DF, Chaponda M, Jorgensen AL, Castro EC, van Oosterhout JJ, Khoo SH, et al. Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population. Clin Infect Dis. 2013;56(9):1330–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Chantarangsu S, Mushiroda T, Mahasirimongkol S, Kiertiburanakul S, Sungkanuparph S, Manosuthi W, 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(2):139–46.

    Article  PubMed  CAS  Google Scholar 

  131. Littera R, Carcassi C, Masala A, Piano P, Serra P, Ortu F, et al. HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients. AIDS (London, England). 2006;20(12):1621–6.

  132. Gatanaga H, Yazaki H, Tanuma J, Honda M, Genka I, Teruya K, et al. HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS (London, England). 2007;21(2):264–5.

  133. Carr DF et al. CYP2B6 c983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations. J Antimicrob Chemother. 2014;(69)12:3329–34. https://doi.org/10.1093/jac/dku315.

    Article  CAS  Google Scholar 

  134. Shirato S, Kagaya F, Suzuki Y, Joukou S. Stevens–Johnson syndrome induced by methazolamide treatment. Arch Ophthalmol (Chicago, Ill: 1960). 1997;115(4):550–3.

  135. Her Y, Kil MS, Park JH, Kim CW, Kim SS. Stevens–Johnson syndrome induced by acetazolamide. J Dermatol. 2011;38(3):272–5.

    Article  PubMed  Google Scholar 

  136. Kim SH, Kim M, Lee KW, Kim SH, Kang HR, Park HW, et al. HLA-B*5901 is strongly associated with methazolamide-induced Stevens–Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics. 2010;11(6):879–84.

    Article  PubMed  CAS  Google Scholar 

  137. Yang F, Xuan J, Chen J, Zhong H, Luo H, Zhou P, 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(1):83–7.

    Article  PubMed  CAS  Google Scholar 

  138. Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GQ, et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med. 2013;369(17):1620–8.

    Article  PubMed  CAS  Google Scholar 

  139. Lorenz M, Wozel G, Schmitt J. Hypersensitivity reactions to dapsone: a systematic review. Acta Dermato-venereol. 2012;92(2):194–9.

    Article  Google Scholar 

  140. Wang H, Yan L, Zhang G, Chen X, Yang J, Li M, et al. Association between HLA-B*1301 and dapsone-induced hypersensitivity reactions among leprosy patients in China. J Invest Dermatol. 2013;133(11):2642–4.

    Article  PubMed  CAS  Google Scholar 

  141. Tempark T, Satapornpong P, Rerknimitr P, Nakkam N, Saksit N, Wattanakrai P, et al. Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13: 01 allele in the Thai population. Pharmacogenet Genomics. 2017;27(12):429–37.

    Article  PubMed  CAS  Google Scholar 

  142. Ueta M, Kaniwa N, Sotozono C, Tokunaga K, Saito Y, Sawai H, et al. Independent strong association of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens–Johnson syndrome with severe mucosal involvement. Sci Rep. 2014;4:4862.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Ueta M, Kannabiran C, Wakamatsu TH, Kim MK, Yoon KC, Seo KY, et al. Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens–Johnson syndrome with severe ocular surface complications. Sci Rep. 2014;4:5981.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Ueta M, Sotozono C, Inatomi T, Kojima K, Tashiro K, Hamuro J, et al. Toll-like receptor 3 gene polymorphisms in Japanese patients with Stevens–Johnson syndrome. Br J Ophthalmol. 2007;91(7):962–5.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Alfirevic A, Pirmohamed M. Genomics of adverse drug reactions. Trends Pharmacol Sci. 2017;38(1):100–9.

    Article  PubMed  CAS  Google Scholar 

  146. 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(10):1543–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Leckband SG, Kelsoe JR, Dunnenberger HM, George AL Jr, Tran E, Berger R, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing. Clin Pharmacol Ther. 2013;94(3):324–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  148. Chen P, Lin JJ, Lu CS, Ong CT, Hsieh PF, Yang CC, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364(12):1126–33.

    Article  PubMed  CAS  Google Scholar 

  149. 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(12):1259–67.

    Article  PubMed  Google Scholar 

  150. Plumpton CO, Yip VL, Alfirevic A, Marson AG, Pirmohamed M, Hughes DA. Cost-effectiveness of screening for HLA-A*31:01 prior to initiation of carbamazepine in epilepsy. Epilepsia. 2015;56(4):556–63.

    Article  PubMed  Google Scholar 

  151. Yip VL, Pirmohamed M. The HLA-A*31:01 allele: influence on carbamazepine treatment. Pharmacogenomics Personal Med. 2017;10:29–38.

    Article  CAS  Google Scholar 

  152. Amstutz U, Shear NH, Rieder MJ, Hwang S, Fung V, Nakamura H, et al. Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions. Epilepsia. 2014;55(4):496–506.

    Article  PubMed  CAS  Google Scholar 

  153. Caudle KE, Rettie AE, Whirl-Carrillo M, Smith LH, Mintzer S, Lee MT, et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and HLA-B genotypes and phenytoin dosing. Clin Pharmacol Ther. 2014;96(5):542–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res. 2012;64(10):1431–46.

    Article  CAS  Google Scholar 

  155. Ko TM, Tsai CY, Chen SY, Chen KS, Yu KH, Chu CS, et al. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study. BMJ (Clinical research ed). 2015;351:h4848.

    PubMed  PubMed Central  Google Scholar 

  156. US Food and Drug Administration. Genomics—table of pharmacogenomic biomarkers in drug labeling. Center for Drug Evaluation and Research. [database on the Internet]. Available from: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm. Accessed: 23 Oct 2017.

  157. European Medicines Agency. Ziagen (abacavir). [database on the Internet]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000252/human_med_001179.jsp&mid=WC0b01ac058001d124. Accessed 24 Oct 2017.

  158. Martin MA, Klein TE, Dong BJ, Pirmohamed M, Haas DW, Kroetz DL. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther. 2012;91(4):734–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Thessaly, Biopolis, 41500, Larissa, Greece

    Kalliopi Gerogianni & Konstantinos Dimas

  2. Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, University of Thessaly, Biopolis, 41500, Larissa, Greece

    Aspasia Tsezou

  3. Department of Biology, Faculty of Medicine, University of Thessaly, Biopolis, 41500, Larissa, Greece

    Aspasia Tsezou

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Gerogianni, K., Tsezou, A. & Dimas, K. Drug-Induced Skin Adverse Reactions: The Role of Pharmacogenomics in Their Prevention. Mol Diagn Ther 22, 297–314 (2018). https://doi.org/10.1007/s40291-018-0330-3

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