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Genotyping for Severe Drug Hypersensitivity

  • ANAPHYLAXIS AND DRUG ALLERGY (DA KHAN AND M CASTELLS, SECTION EDITORS)
  • Published:
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Abstract

Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety.

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References

Papers of particular interest, published recently, have been highlighted as: •Of importance; ••Of major importance

  1. Kongkaew C, Noyce PR, Ashcroft DM. Hospital admissions associated with adverse drug reactions: a systematic review of prospective observational studies. Ann Pharmacother. 2008;42(7):1017–25.

    PubMed  Google Scholar 

  2. Khan LM. Comparative epidemiology of hospital-acquired adverse drug reactions in adults and children and their impact on cost and hospital stay - a systematic review. Eur J Clin Pharmacol. 2013.

  3. Suh DC et al. Clinical and economic impact of adverse drug reactions in hospitalized patients. Ann Pharmacother. 2000;34(12):1373–9.

    CAS  PubMed  Google Scholar 

  4. Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004;329(7456):15–9.

    PubMed  Google Scholar 

  5. Pavlos R, Mallal S, Phillips E. HLA and pharmacogenetics of drug hypersensitivity. Pharmacogenomics. 2012;13(11):1285–306.

    CAS  PubMed  Google Scholar 

  6. Schnyder B et al. Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta T cell clones. J Clin Invest. 1997;100(1):136–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Zanni MP et al. HLA-restricted, processing- and metabolism-independent pathway of drug recognition by human alpha beta T lymphocytes. J Clin Invest. 1998;102(8):1591–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Zanni MP et al. Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta + T cell clones. Int Immunol. 1998;10(4):507–15.

    CAS  PubMed  Google Scholar 

  9. Pichler WJ. Delayed drug hypersensitivity reactions. Ann Intern Med. 2003;139(8):683–93.

    CAS  PubMed  Google Scholar 

  10. Bharadwaj M et al. Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex. Annu Rev Pharmacol Toxicol. 2012;52:401–31.

    CAS  PubMed  Google Scholar 

  11. Norcross MA et al. Abacavir induces loading of novel self-peptides into HLA-B*57: 01: an autoimmune model for HLA-associated drug hypersensitivity. AIDS. 2012;26(11):F21–9. Using abacavir-treated HLA-B*57:01 B-cell lines, the authors demonstrated additional evidence that abacavir alters the quantity and quality of self-peptide loading into HLA-B*57:01.

    CAS  PubMed  Google Scholar 

  12. Wei CY et al. Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome. J Allergy Clin Immunol. 2012;129(6):1562–9 e5. This article demonstrates a direct interaction of HLA molecules with drugs and provides a potential mechanism for HLA-associated drug hypersensitivity reactions. Supportive of altered peptide repertoire model for carbamazepine.

    CAS  PubMed  Google Scholar 

  13. Illing PT et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. 2012;486(7404):554–8. Study supporting the altered peptide repertoire model for abacavir hypersensitivity. Abacavir associates with HLA-B*57:01 non-covalently and alters the shape and chemistry of the antigen-binding cleft. This leads to an altered repertoire of endogenous peptides binding HLA-B*57:01. The crystal structure of abacavir-MHC-peptide was resolved using an endogenous peptide. Preliminary evidence to support the altered peptide repertoire model for was also presented.

    CAS  PubMed  Google Scholar 

  14. Ostrov DA et al. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proc Natl Acad Sci U S A. 2012;109(25):9959–64. Provided structural, biochemical and functional evidence for non-covalent interaction between abacavir and HLA-B*57:01 and the altered repertoire model for abacavir. A synthetic peptide was derived that binds to HLA-B*57:01 only in the presence of abacavir. The crystal structure of abacavir-MHC-peptide was resolved using this peptide.

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Cutrell AG et al. Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir. Ann Pharmacother. 2004;38(12):2171–2.

    PubMed  Google Scholar 

  16. Shapiro M, Ward KM, Stern JJ. A near-fatal hypersensitivity reaction to abacavir: case report and literature review. AIDS Read. 2001;11(4):222–6.

    CAS  PubMed  Google Scholar 

  17. Symonds W et al. Risk factor analysis of hypersensitivity reactions to abacavir. Clin Ther. 2002;24(4):565–73.

    CAS  PubMed  Google Scholar 

  18. Mallal S 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(9308):727–32.

    CAS  PubMed  Google Scholar 

  19. Hetherington S et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002;359(9312):1121–2.

    CAS  PubMed  Google Scholar 

  20. Hughes AR et al. Association of genetic variations in HLA-B region with hypersensitivity to abacavir in some, but not all, populations. Pharmacogenomics. 2004;5(2):203–11.

    CAS  PubMed  Google Scholar 

  21. Saag M 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.

    CAS  PubMed  Google Scholar 

  22. Mallal S et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–79.

    PubMed  Google Scholar 

  23. Schackman BR et al. The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV. AIDS. 2008;22(15):2025–33.

    PubMed Central  PubMed  Google Scholar 

  24. Rauch A et al. 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.

    CAS  PubMed  Google Scholar 

  25. Guo Y et al. Studies on abacavir-induced hypersensitivity reaction: a successful example of translation of pharmacogenetics to personalized medicine. Sci China Life Sci. 2013;56(2):119–24.

    CAS  PubMed  Google Scholar 

  26. Chessman D et al. Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity. Immunity. 2008;28(6):822–32.

    CAS  PubMed  Google Scholar 

  27. Adam J et al. Avidity determines T-cell reactivity in abacavir hypersensitivity. Eur J Immunol. 2012;42(7):1706–16. Paper providing evidence that abacavir interacts with HLA-B*57:01 in a non-covalent and metabolism-independent fashion. Additionally, this study provided evidence that abacavir-reactive T-cell clones are dependent on the drug concentration, TCR avidity and level of HLA-B*57:01 molecules expressed on APCs.

    CAS  PubMed  Google Scholar 

  28. Knowles SR, Dewhurst N, Shear N. Anticonvulsant hypersensitivity syndrome: an update. Expert Opin Drug Saf. 2012;11(5):767–78.

    CAS  PubMed  Google Scholar 

  29. McCormack M et al. HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011;364(12):1134–43. First GWAS for carbamazepine in Europeans that identified an association with HLA-A*31:01 and individuals of northern European ancestry with various phenotypes of carbamazepine-induced hypersensitivity reactions. Although this study suggested an association between HLA-A*31:01 and carbamazepine SJS/TEN in European populations, not all follow-up studies have supported this.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Chung WH et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004;428(6982):486.

    CAS  PubMed  Google Scholar 

  31. Kulkantrakorn K 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.

    PubMed  Google Scholar 

  32. Mehta TY 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.

    PubMed  Google Scholar 

  33. Then SM et al. 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.

    CAS  PubMed  Google Scholar 

  34. Man CB et al. Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007;48(5):1015–8.

    CAS  PubMed  Google Scholar 

  35. Wang Q 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.

    PubMed  Google Scholar 

  36. Zhang Y et al. Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients. Eur J Clin Pharmacol. 2011;67(9):885–7.

    PubMed  Google Scholar 

  37. Chen P et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364(12):1126–33.

    CAS  PubMed  Google Scholar 

  38. Ko TM 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. Important in vitro study that establishes the essential role of the TCR in the mechanism behind SJS/TEN and explains why some HLA-B*15:02 carriers are tolerant to carbamazepine.

    CAS  PubMed  Google Scholar 

  39. Mizumoto K et al. Case of carbamazepine-induced hypersensitivity syndrome associated with human leukocyte antigen-A*3101. J Dermatol. 2012;39(9):791–2.

    PubMed  Google Scholar 

  40. Niihara H et al. HLA-A31 strongly associates with carbamazepine-induced adverse drug reactions but not with carbamazepine-induced lymphocyte proliferation in a Japanese population. J Dermatol. 2012;39(7):594–601.

    CAS  PubMed  Google Scholar 

  41. Ozeki T 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. GWAS that showed association with HLA-A*31:01 and carbamazepine-induced immunologically mediated adverse drug reactions in those of Japanese ancestry.

    CAS  PubMed  Google Scholar 

  42. Yip VL et al. HLA genotype and carbamazepine-induced cutaneous adverse drug reactions: a systematic review. Clin Pharmacol Ther. 2012;92(6):757–65.

    CAS  PubMed  Google Scholar 

  43. Amstutz U et al. HLA-A 31:01 and HLA-B 15:02 as genetic markers for carbamazepine hypersensitivity in children. Clin Pharmacol Ther. 2013;94(1):142–9.

    CAS  PubMed  Google Scholar 

  44. Ramasamy SN et al. Allopurinol Hypersensitivity: A Systematic Review of All Published Cases, 1950-2012. Drug Saf. 2013.

  45. Rundles RW, Metz EN, Silberman HR. Allopurinol in the treatment of gout. Ann Intern Med. 1966;64(2):229–58.

    CAS  PubMed  Google Scholar 

  46. Lang Jr PG. Severe hypersensitivity reactions to allopurinol. South Med J. 1979;72(11):1361–8.

    PubMed  Google Scholar 

  47. Dalbeth N, Stamp L. Allopurinol dosing in renal impairment: walking the tightrope between adequate urate lowering and adverse events. Semin Dial. 2007;20(5):391–5.

    PubMed  Google Scholar 

  48. Chan SH, Tan T. HLA and allopurinol drug eruption. Dermatologica. 1989;179(1):32–3.

    CAS  PubMed  Google Scholar 

  49. Hung SI 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(11):4134–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Dainichi T et al. Stevens-Johnson syndrome, drug-induced hypersensitivity syndrome and toxic epidermal necrolysis caused by allopurinol in patients with a common HLA allele: what causes the diversity? Dermatology. 2007;215(1):86–8.

    PubMed  Google Scholar 

  51. Kaniwa N 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.

    CAS  PubMed  Google Scholar 

  52. Tassaneeyakul W 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.

    CAS  PubMed  Google Scholar 

  53. Jung JW et al. HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency. Nephrol Dial Transplant. 2011;26(11):3567–72.

    CAS  PubMed  Google Scholar 

  54. Kang HR et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011;21(5):303–7.

    CAS  PubMed  Google Scholar 

  55. Lonjou C 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.

    CAS  PubMed  Google Scholar 

  56. Genin E et al. Genome-wide association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe. Orphanet J Rare Dis. 2011;6:52.

    PubMed Central  PubMed  Google Scholar 

  57. Tohkin M 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.

    CAS  PubMed  Google Scholar 

  58. Somkrua R et al. 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Pompeu YA et al. The structural basis of HLA-associated drug hypersensitivity syndromes. Immunol Rev. 2012;250(1):158–66.

    PubMed  Google Scholar 

  60. Pollard RB, Robinson P, Dransfield K. Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. Clin Ther. 1998;20(6):1071–92.

    CAS  PubMed  Google Scholar 

  61. Gangar M et al. Frequency of cutaneous reactions on rechallenge with nevirapine and delavirdine. Ann Pharmacother. 2000;34(7–8):839–42.

    CAS  PubMed  Google Scholar 

  62. Martin AM et al. Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts. AIDS. 2005;19(1):97–9.

    CAS  PubMed  Google Scholar 

  63. Yuan J et al. Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent. AIDS. 2011;25(10):1271–80. Genetic study investigating different clinical presentations of nevirapine hypersensitivity and reporting several new associations with specific HLA alleles.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Vitezica ZG et al. HLA-DRB1*01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS. 2008;22(4):540–1.

    CAS  PubMed  Google Scholar 

  65. Phillips E et al. Associations between HLA-DRB1*0102, HLA-B*5801, and hepatotoxicity during initiation of nevirapine-containing regimens in South Africa. J Acquir Immune Defic Syndr. 2013;62(2):e55–7. A class II allele DRB1*01:02 which is homologous to DRB1*01:01 is related to nevirapine-associated hepatitis in South African Black populations.

    PubMed Central  PubMed  Google Scholar 

  66. Littera R et al. HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients. AIDS. 2006;20(12):1621–6.

    CAS  PubMed  Google Scholar 

  67. Gatanaga H et al. HLA-Cw8 primarily associated with hypersensitivity to nevirapine. AIDS. 2007;21(2):264–5.

    PubMed  Google Scholar 

  68. Gao S et al. HLA-dependent hypersensitivity reaction to nevirapine in Chinese Han HIV-infected patients. AIDS Res Hum Retroviruses. 2012;28(6):540–3.

    CAS  PubMed  Google Scholar 

  69. Chantarangsu 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(2):139–46.

    CAS  PubMed  Google Scholar 

  70. Chantarangsu S et al. Genome-wide association study identifies variations in 6p21.3 associated with nevirapine-induced rash. Clin Infect Dis. 2011;53(4):341–8.

    CAS  PubMed  Google Scholar 

  71. Likanonsakul S et al. HLA-Cw*04 allele associated with nevirapine-induced rash in HIV-infected Thai patients. AIDS Res Ther. 2009;6:22.

    PubMed Central  PubMed  Google Scholar 

  72. Carr DF 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. First study to associate HLA-C*04:01 with nevirapine-associated Stevens-Johnson Syndrome/Toxic epidermal necrolysis in a Black African population.

    CAS  PubMed  Google Scholar 

  73. Daly AK, Day CP. Genetic association studies in drug-induced liver injury. Drug Metab Rev. 2012;44(1):116–26.

    CAS  PubMed  Google Scholar 

  74. Hautekeete ML et al. HLA association of amoxicillin-clavulanate–induced hepatitis. Gastroenterology. 1999;117(5):1181–6.

    CAS  PubMed  Google Scholar 

  75. O’Donohue J et al. Co-amoxiclav jaundice: clinical and histological features and HLA class II association. Gut. 2000;47(5):717–20.

    PubMed  Google Scholar 

  76. Donaldson PT et al. Human leucocyte antigen class II genotype in susceptibility and resistance to co-amoxiclav-induced liver injury. J Hepatol. 2010;53(6):1049–53.

    CAS  PubMed  Google Scholar 

  77. Lucena MI 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Lucena MI et al. Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity: a prospective series from Spain. Hepatology. 2006;44(4):850–6.

    CAS  PubMed  Google Scholar 

  79. Stephens C et al. HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PLoS One. 2013;8(7):e68111.

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Olsson R et al. Liver damage from flucloxacillin, cloxacillin and dicloxacillin. J Hepatol. 1992;15(1–2):154–61.

    CAS  PubMed  Google Scholar 

  81. Russmann S et al. Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: cohort study using data from the UK General Practice Research Database. Br J Clin Pharmacol. 2005;60(1):76–82.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Daly AK 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.

    CAS  PubMed  Google Scholar 

  83. Phillips EJ, Mallal SA. HLA-B*5701 and flucloxacillin associated drug-induced liver disease. AIDS. 2013;27(3):491–2.

    PubMed  Google Scholar 

  84. Ferrell Jr PB, 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Phillips EJ et al. Clinical and immunogenetic correlates of abacavir hypersensitivity. AIDS. 2005;19(9):979–81.

    CAS  PubMed  Google Scholar 

  86. Shear NH et al. A review of drug patch testing and implications for HIV clinicians. AIDS. 2008;22(9):999–1007.

    PubMed  Google Scholar 

  87. Phillips EJ et al. Utility of patch testing in patients with hypersensitivity syndromes associated with abacavir. AIDS. 2002;16(16):2223–5.

    PubMed  Google Scholar 

  88. Lee AY, Choi J, Chey WY. Patch testing with carbamazepine and its main metabolite carbamazepine epoxide in cutaneous adverse drug reactions to carbamazepine. Contact Dermatitis. 2003;48(3):137–9.

    CAS  PubMed  Google Scholar 

  89. Buyuktiryaki AB et al. Patch testing is an effective method for the diagnosis of carbamazepine-induced drug reaction, eosinophilia and systemic symptoms (DRESS) syndrome in an 8-year-old girl. Australas J Dermatol. 2012;53(4):274–7.

    PubMed  Google Scholar 

  90. Lin YT, et al. A patch testing and cross-sensitivity study of carbamazepine-induced severe cutaneous adverse drug reactions. J Eur Acad Dermatol Venereol. 2012.

  91. Phillips EJ, Mallal SA. HLA-B*1502 screening and toxic effects of carbamazepine. N Engl J Med. 2011;365(7):672. author reply 673.

    CAS  PubMed  Google Scholar 

  92. Martin AM et al. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proc Natl Acad Sci U S A. 2004;101(12):4180–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Hammond E et al. External quality assessment of HLA-B*5701 reporting: an international multicentre survey. Antivir Ther. 2007;12(7):1027–32.

    CAS  PubMed  Google Scholar 

  94. Martin AM et al. A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome. Pharmacogenet Genomics. 2006;16(5):353–7.

    CAS  PubMed  Google Scholar 

  95. Melis R et al. Copy number variation and incomplete linkage disequilibrium interfere with the HCP5 genotyping assay for abacavir hypersensitivity. Genet Test Mol Biomarkers. 2012;16(9):1111–4.

    CAS  PubMed  Google Scholar 

  96. Zhang FR et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. N Engl J Med. 2013;369(17):1620–8.

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  98. Kim SH et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res. 2011;97(1–2):190–7.

    CAS  PubMed  Google Scholar 

  99. Kaniwa N et al. HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Epilepsia. 2010;51(12):2461–5.

    CAS  PubMed  Google Scholar 

  100. Ikeda H et al. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia. 2010;51(2):297–300.

    PubMed  Google Scholar 

  101. Hung SI 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.

    CAS  PubMed  Google Scholar 

  102. Lin LC et al. Oxcarbazepine-induced Stevens-Johnson syndrome: a case report. Kaohsiung J Med Sci. 2009;25(2):82–6.

    PubMed  Google Scholar 

  103. Cheung YK et al. HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013;54(7):1307–14.

    CAS  PubMed  Google Scholar 

  104. Locharernkul C 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.

    PubMed  Google Scholar 

  105. Kaniwa N 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.

    CAS  PubMed  Google Scholar 

  106. Kim SH et al. HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics. 2010;11(6):879–84.

    CAS  PubMed  Google Scholar 

  107. Alfirevic A et al. HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics. 2006;7(6):813–8.

    CAS  PubMed  Google Scholar 

  108. Singer JB et al. A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet. 2010;42(8):711–4.

    CAS  PubMed  Google Scholar 

  109. Kindmark A et al. Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. Pharmacogenomics J. 2008;8(3):186–95.

    CAS  PubMed  Google Scholar 

  110. Spraggs CF et al. HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. J Clin Oncol. 2011;29(6):667–73.

    CAS  PubMed  Google Scholar 

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Conflict of Interest

Elizabeth Phillips has served on boards for Merck International Pty, Merck Pty Ltd., Tibotec Pty. Ltd, and ViiV Australia; has received honoraria from ViiV Australia; is a co-director in III Pty Ltd., which holds a patent for HLA-B*57:01; has received royalties from UpToDate; has received payment for development of educational presentations (including service on speakers bureaus) from Merck Pty Ltd. and ViiV Australia; and has had travel/accommodations expenses covered/reimbursed by Gilead Australia.

Eric Karlin declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Vanderbilt University School of Medicine, 1161-21 St Avenue South, A-2200 Medical Center North, Nashville, TN, 37232-2582, USA

    Eric Karlin & Elizabeth Phillips

  2. Institute for Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia

    Elizabeth Phillips

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Correspondence to Elizabeth Phillips.

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This article is part of the Topical Collection on Anaphylaxis and Drug Allergy

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Karlin, E., Phillips, E. Genotyping for Severe Drug Hypersensitivity. Curr Allergy Asthma Rep 14, 418 (2014). https://doi.org/10.1007/s11882-013-0418-0

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