• 1  Hemmi H, Kaisho T, Takeuchi O, et al. Small anti‐viral compounds activate immune cells via the TLR7 MyD88‐dependent signaling pathway. Nat Immunol 2002;3(2):196–200. Cross Ref link Pubmed link
  • 2  Coombs PR, Gell PG. Classification of allergic reactions responsible for clinical hypersensitivity and disease. In: GellRR, ed. Clinical Aspects of Immunology. Oxford: Oxford University Press, 1968:575–96.
  • 3  Bischoff SC. Role of mast cells in allergic and non‐allergic immune responses: comparison of human and murine data. Nat Rev Immunol 2007;7(2):93–104. Cross Ref link Pubmed link
  • 4  Huang CZ, Yang J, Qiao HL, Jia LJ. Polymorphisms and haplotype analysis of IL‐4Ralpha Q576R and I75V in patients with penicillin allergy. Eur J Clin Pharmacol 2009;65(9):895–902. Cross Ref link Pubmed link
  • 5  Qiao HL, Yang J, Zhang YW. Relationships between specific serum IgE, cytokines and polymorphisms in the IL‐4, IL‐4Ralpha in patients with penicillins allergy. Allergy 2005;60(8):1053–9. Cross Ref link Pubmed link
  • 6  Qiao HL, Yang J, Zhang YW. Specific serum IgE levels and FcepsilonRIbeta genetic polymorphism in patients with penicillins allergy. Allergy 2004;59(12):1326–32. Cross Ref link Pubmed link
  • 7  Gueant‐Rodriguez RM, Romano A, Beri‐Dexheimer M, Viola M, Gaeta F, Gueant JL. Gene–gene interactions of IL13 and IL4RA variants in immediate allergic reactions to betalactam antibiotics. Pharmacogenet Genomics 2006;16(10):713–19. Cross Ref link Pubmed link
  • 8  Guglielmi L, Fontaine C, Gougat C, Avinens O, Eliaou JF, Guglielmi P. IL‐10 promoter and IL4‐Ralpha gene SNPs are associated with immediate beta‐lactam allergy in atopic women. Allergy 2006;61(8):921–7. Cross Ref link Pubmed link
  • 9  Ming L, Wen Q, Qiao HL, Dong ZM. Interleukin‐18 and IL18 ‐607A/C and ‐137G/C gene polymorphisms in patients with penicillin allergy. J Int Med Res 2011;39(2):388–98. Cross Ref link Pubmed link
  • 10  Huang CZ, Zou D, Yang J, Qiao HL. Polymorphisms of STAT6 and specific serum IgE levels in patients with penicillin allergy. Int J Clin Pharmacol Ther 2012;50(7):461–7. Cross Ref link Pubmed link
  • 11  Palikhe NS, Kim SH, Cho BY, Ye YM, Hur GY, Park HS. Association of three sets of high‐affinity IgE receptor (FcepsilonR1) polymorphisms with aspirin‐intolerant asthma. Respir Med 2008;102(8):1132–9. Cross Ref link Pubmed link
  • 12  Commins SP, Platts‐Mills TA. Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol 2013;13(4):354–9. Cross Ref link Pubmed link
  • 13  Mauri‐Hellweg D, Bettens F, Mauri D, Brander C, Hunziker T, Pichler WJ. Activation of drug‐specific CD4+ and CD8+ T cells in individuals allergic to sulfonamides, phenytoin, and carbamazepine. J Immunol 1995;155(1):462–72. Pubmed link
  • 14  Pichler WJ. Drug hypersensitivity reactions: classification and relationship to T‐cell activation. In: PichlerWJ, ed. Drug Hypersensitivity. Basel: Karger, 2007:168–89. Cross Ref link
  • 15  Nassif A, Bensussan A, Boumsell L, et al. Toxic epidermal necrolysis: effector cells are drug‐specific cytotoxic T cells. J Allergy Clin Immunol 2004;114(5):1209–15. Cross Ref link Pubmed link
  • 16  Paquet P, Jacob E, Damas P, Pierard GE. Recurrent fatal drug‐induced toxic epidermal necrolysis (Lyell's syndrome) after putative beta‐lactam cross‐reactivity: case report and scrutiny of antibiotic imputability. Crit Care Med 2002;30(11):2580–3. Cross Ref link Pubmed link
  • 17  Yun J, Adam J, Yerly D, Pichler WJ. Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA. Allergy 2013;67(11):1338–46. Cross Ref link
  • 18  Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 1998;282(5388):490–3. Cross Ref link Pubmed link
  • 19  Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H. Toxic epidermal necrolysis and Stevens–Johnson syndrome are induced by soluble Fas ligand. Am J Pathol 2003;162(5):1515–20. Cross Ref link Pubmed link
  • 20  Paquet P, Jacob E, Damas P, Pirson J, Pierard G. Analytical quantification of the inflammatory cell infiltrate and CD95R expression during treatment of drug‐induced toxic epidermal necrolysis. Arch Dermatol Res 2005;297(6):266–73. Cross Ref link Pubmed link
  • 21  Marzano AV, Frezzolini A, Caproni M, et al. Immunohistochemical expression of apoptotic markers in drug‐induced erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis. Int J Immunopathol Pharmacol 2007;20(3):557–66. Pubmed link
  • 22  Stur K, Karlhofer FM, Stingl G. Soluble FAS ligand: a discriminating feature between drug‐induced skin eruptions and viral exanthemas. J Invest Dermatol 2007;127(4):802–7. Cross Ref link Pubmed link
  • 23  Chung WH, Hung SI, Yang JY, 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. Cross Ref link Pubmed link
  • 24  Viard‐Leveugle I, Gaide O, Jankovic D, et al. TNF‐alpha and IFN‐gamma are potential inducers of Fas‐mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J Invest Dermatol 2013;133(2):489–98. Cross Ref link Pubmed link
  • 25  Wolkenstein P, Charue D, Laurent P, Revuz J, Roujeau JC, Bagot M. Metabolic predisposition to cutaneous adverse drug reactions. Role in toxic epidermal necrolysis caused by sulfonamides and anticonvulsants. Arch Dermatol 1995;131(5):544–51. Cross Ref link Pubmed link
  • 26  Caproni M, Torchia D, Schincaglia E, et al. The CD40/CD40 ligand system is expressed in the cutaneous lesions of erythema multiforme and Stevens–Johnson syndrome/toxic epidermal necrolysis spectrum. Br J Dermatol 2006;154(2):319–24. Cross Ref link Pubmed link
  • 27  Caproni M, Antiga E, Parodi A, et al. Elevated circulating CD40 ligand in patients with erythema multiforme and Stevens–Johnson syndrome/toxic epidermal necrolysis spectrum. Br J Dermatol 2006;154(5):1006–7. Cross Ref link Pubmed link
  • 28  Nassif A, Bensussan A, Dorothee G, 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. Cross Ref link Pubmed link
  • 29  Paquet P, Pierard GE. Soluble fractions of tumor necrosis factor‐alpha, interleukin‐6 and of their receptors in toxic epidermal necrolysis: a comparison with second‐degree burns. Int J Mol Med 1998;1(2):459–62. Pubmed link
  • 30  Nassif A, Moslehi H, Le Gouvello S, et al. Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Invest Dermatol 2004;123(5):850–5. Cross Ref link Pubmed link
  • 31  Wolkenstein P, Latarjet J, Roujeau JC, et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet 1998;352(9140):1586–9. Cross Ref link Pubmed link
  • 32  Gubinelli E, Canzona F, Tonanzi T, Raskovic D, Didona B. Toxic epidermal necrolysis successfully treated with etanercept. J Dermatol 2009;36(3):150–3. Cross Ref link Pubmed link
  • 33  Wojtkiewicz A, Wysocki M, Fortuna J, Chrupek M, Matczuk M, Koltan A. Beneficial and rapid effect of infliximab on the course of toxic epidermal necrolysis. Acta Derm Venereol 2008;88(4):420–1. Pubmed link
  • 34  Fischer M, Fiedler E, Marsch WC, Wohlrab J. Antitumour necrosis factor‐alpha antibodies (infliximab) in the treatment of a patient with toxic epidermal necrolysis. Br J Dermatol 2002;146(4):707–9. Cross Ref link Pubmed link
  • 35  Hunger RE, Hunziker T, Buettiker U, Braathen LR, Yawalkar N. Rapid resolution of toxic epidermal necrolysis with anti‐TNF‐alpha treatment. J Allergy Clin Immunol 2005;116(4):923–4. Cross Ref link Pubmed link
  • 36  Kardaun SH, Sidoroff A, Valeyrie‐Allanore L, 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. Cross Ref link Pubmed link
  • 37  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. Cross Ref link Pubmed link
  • 38  Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy 2004;59(8):809–20. Cross Ref link Pubmed link
  • 39  Polak ME, Belgi G, McGuire C, et al. In vitro diagnostic assays are effective during the acute phase of delayed‐type drug hypersensitivity reactions. Br J Dermatol 2013;168(3):539–49. Cross Ref link Pubmed link
  • 40  Tohyama M, Yahata Y, Yasukawa M, et al. Severe hypersensitivity syndrome due to sulfasalazine associated with reactivation of human herpesvirus 6. Arch Dermatol 1998;134(9):1113–17. Cross Ref link Pubmed link
  • 41  Suzuki Y, Inagi R, Aono T, Yamanishi K, Shiohara T. Human herpesvirus 6 infection as a risk factor for the development of severe drug‐induced hypersensitivity syndrome. Arch Dermatol 1998;134(9):1108–12. Cross Ref link Pubmed link
  • 42  Descamps V, Valance A, Edlinger C, et al. Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms. Arch Dermatol 2001;137(3):301–4. Pubmed link
  • 43  Ichiche M, Kiesch N, De Bels D. DRESS syndrome associated with HHV‐6 reactivation. Eur J Intern Med 2003;14(8):498–500. Cross Ref link Pubmed link
  • 44  Picard D, Janela B, Descamps V, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): a multiorgan antiviral T cell response. Sci Transl Med 2010;2(46):46–62. Cross Ref link
  • 45  Tohyama M, Hashimoto K, Yasukawa M, et al. Association of human herpesvirus 6 reactivation with the flaring and severity of drug‐induced hypersensitivity syndrome. Br J Dermatol 2007;157(5):934–40. Cross Ref link Pubmed link
  • 46  Hanafusa T, Azukizawa H, Matsumura S, Katayama I. The predominant drug‐specific T‐cell population may switch from cytotoxic T cells to regulatory T cells during the course of anticonvulsant‐induced hypersensitivity. J Dermatol Sci 2012;65(3):213–19. Cross Ref link Pubmed link
  • 47  Nishio D, Izu K, Kabashima K, Tokura Y. T cell populations propagating in the peripheral blood of patients with drug eruptions. J Dermatol Sci 2007;48(1):25–33. Cross Ref link Pubmed link
  • 48  Anliker MD, Wuthrich B. Acute generalized exanthematous pustulosis due to sulfamethoxazol with positive lymphocyte transformation test (LTT). J Invest Allergol Clin Immunol 2003;13(1):66–8.
  • 49  Schaerli P, Britschgi M, Keller M, et al. Characterization of human T cells that regulate neutrophilic skin inflammation. J Immunol 2004;173(3):2151–8. Cross Ref link Pubmed link
  • 50  Girardi M, Duncan KO, Tigelaar RE, Imaeda S, Watsky KL, McNiff JM. Cross‐comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis. Am J Dermatopathol 2005;27(4):343–6. Cross Ref link Pubmed link
  • 51  Britschgi M, Steiner UC, Schmid S, et al. T‐cell involvement in drug‐induced acute generalized exanthematous pustulosis. J Clin Invest 2001;107(11):1433–41. Cross Ref link Pubmed link
  • 52  Kabashima R, Sugita K, Sawada Y, Hino R, Nakamura M, Tokura Y. Increased circulating Th17 frequencies and serum IL‐22 levels in patients with acute generalized exanthematous pustulosis. J Eur Acad Dermatol Venereol 2011;25(4):485–8. Cross Ref link Pubmed link
  • 53  Shiohara T. Fixed drug eruption: pathogenesis and diagnostic tests. Curr Opin Allergy Clin Immunol 2009;9(4):316–21. Cross Ref link Pubmed link
  • 54  Clark RA, Watanabe R, Teague JE, et al. Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab‐treated CTCL patients. Sci Transl Med 2012;4(117):117ra7. Cross Ref link Pubmed link
  • 55  Jiang X, Clark RA, Liu L, Wagers AJ, Fuhlbrigge RC, Kupper TS. Skin infection generates non‐migratory memory CD8+ T(RM) cells providing global skin immunity. Nature 2012;483(7388):227–31. Cross Ref link Pubmed link
  • 56  Baird BJ, De Villez RL. Widespread bullous fixed drug eruption mimicking toxic epidermal necrolysis. Int J Dermatol 1988;27(3):170–4. Cross Ref link Pubmed link
  • 57  Lin TK, Hsu MM, Lee JY. Clinical resemblance of widespread bullous fixed drug eruption to Stevens–Johnson syndrome or toxic epidermal necrolysis: report of two cases. J Formos Med Assoc 2002;101(8):572–6. Pubmed link
  • 58  Lipowicz S, Sekula P, Ingen‐Housz‐Oro S, et al. Prognosis of generalized bullous fixed drug eruption: comparison with Stevens–Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol 2013;168(4):726–32. Cross Ref link Pubmed link
  • 59  Aster RH, Bougie DW. Drug‐induced immune thrombocytopenia. N Engl J Med 2007;357(6):580–7. Cross Ref link Pubmed link
  • 60  Park BK, Pirmohamed M, Kitteringham NR. Idiosyncratic drug reactions: a mechanistic evaluation of risk factors. Br J Clin Pharmacol 1992;34(5):377–95. Cross Ref link Pubmed link
  • 61  Merk HF, Hertl M. Immunologic mechanisms of cutaneous drug reactions. Semin Cutan Med Surg 1996;15(4):228–35. Cross Ref link Pubmed link
  • 62  Davis M, Bjorkman P. T cell antigen receptor genes and T cell recognition. Nature 1988;334(395):395–402. Cross Ref link Pubmed link
  • 63  Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity. Science 1999;286(5441):958–61. Cross Ref link Pubmed link
  • 64  Kenna JG, Satoh H, Christ DD, Pohl LR. Metabolic basis for a drug hypersensitivity: antibodies in sera from patients with halothane hepatitis recognize liver neoantigens that contain the trifluoroacetyl group derived from halothane. J Pharmacol Exp Ther 1988;245(3):1103–9. Pubmed link
  • 65  Martin JL, Kenna JG, Pohl LR. Antibody assays for the detection of patients sensitized to halothane. Anesth Analg 1990;70(2):154–9. Cross Ref link Pubmed link
  • 66  Leeder JS, Gaedigk A, Lu X, Cook VA. Epitope mapping studies with human anti‐cytochrome P450 3A antibodies. Mol Pharmacol 1996;49(2):234–43. Pubmed link
  • 67  Matzinger P. The danger model: a renewed sense of self. Science 2002;296(5566):301–5. Cross Ref link Pubmed link
  • 68  Lavergne SN, Wang H, Callan HE, Park BK, Naisbitt DJ. “Danger” conditions increase sulfamethoxazole‐protein adduct formation in human antigen‐presenting cells. J Pharmacol Exp Ther 2009;331(2):372–81. Cross Ref link Pubmed link
  • 69  Devary Y, Gottlieb RA, Lau LF, Karin M. Rapid and preferential activation of the c‐jun gene during the mammalian UV response. Mol Cell Biol 1991;11(5):2804–11. Cross Ref link Pubmed link
  • 70  Schreck R, Baeuerle PA. A role for oxygen radicals as second messengers. Trends Cell Biol 1991;1(2–3):39–42. Cross Ref link Pubmed link
  • 71  Schreck R, Rieber P, Baeuerle PA. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF‐kappa B transcription factor and HIV‐1. EMBO J 1991;10(8):2247–58. Pubmed link
  • 72  Ishii T, Itoh K, Takahashi S, et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress‐inducible genes in macrophages. J Biol Chem 2000;275(21):16023–9. Cross Ref link Pubmed link
  • 73  Nguyen T, Nioi P, Pickett CB. The Nrf2‐antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009;284(20):13291–5. Cross Ref link Pubmed link
  • 74  Gerber BO, Pichler WJ. Cellular mechanisms of T cell mediated drug hypersensitivity. Curr Opin Immunol 2004;16(6):732–7. Cross Ref link Pubmed link
  • 75  Pichler WJ. Direct T‐cell stimulations by drugs – bypassing the innate immune system. Toxicology 2005;209(2):95–100. Cross Ref link Pubmed link
  • 76  Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte antigen‐b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis 2008;46(7):1111–18. Cross Ref link Pubmed link
  • 77  Hung SI, Chung WH, Liou LB, et al. HLA‐B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 2005;102(11):4134–9. Cross Ref link Pubmed link
  • 78  Hung SI, Chung WH, Jee SH, et al. Genetic susceptibility to carbamazepine‐induced cutaneous adverse drug reactions. Pharmacogenet Genomics 2006;16(4):297–306. Cross Ref link Pubmed link
  • 79  Illing PT, Vivian JP, Dudek NL, et al. Immune self‐reactivity triggered by drug‐modified HLA‐peptide repertoire. Nature 2012;486(7404):554–8. Pubmed link
  • 80  Ostrov DA, Grant BJ, Pompeu YA, et al. Drug hypersensitivity caused by alteration of the MHC‐presented self‐peptide repertoire. Proc Natl Acad Sci USA 2012;109(25):9959–64. Cross Ref link Pubmed link
  • 81  Mallal S, Phillips E, Carosi G, et al. HLA‐B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358(6):568–79. Cross Ref link Pubmed link
  • 82  Clay PG. The abacavir hypersensitivity reaction: a review. Clin Ther 2002;24(10):1502–14. Cross Ref link Pubmed link
  • 83  Hetherington S, McGuirk S, Powell G, et al. Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir. Clin Ther 2001;23(10):1603–14. Cross Ref link Pubmed link
  • 84  Kaniwa N, Saito Y. Pharmacogenomics of severe cutaneous adverse reactions and drug‐induced liver injury. J Hum Genet 2013;58(6):317–26. Cross Ref link Pubmed link
  • 85  Martin AM, Nolan D, Gaudieri S, et al. Predisposition to abacavir hypersensitivity conferred by HLA‐B*5701 and a haplotypic Hsp70‐Hom variant. Proc Natl Acad Sci USA 2004;101(12):4180–5. Cross Ref link Pubmed link