American Journal of Clinical Dermatology

, Volume 16, Issue 6, pp 475–493 | Cite as

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis: An Update

  • Roni P. Dodiuk-Gad
  • Wen-Hung Chung
  • Laurence Valeyrie-Allanore
  • Neil H. Shear
Review Article

Abstract

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening mucocutaneous reactions, predominantly drug induced. The mortality rates for SJS and TEN are as high as 30 %, and short- and long-term morbidities are very common. SJS/TEN is one of the few dermatological diseases that constitute a true medical emergency. Early recognition and prompt and appropriate management can be lifesaving. In recent years, our understanding of the pathogenesis, clinical presentation, and management of SJS/TEN has improved. Nevertheless, in 2015, there are still no internationally accepted management guidelines. This review summarizes up-to-date insights on SJS/TEN and describes a protocol for assessment and treatment. We hope these suggested guidelines serve as a practical clinical tool in the management of SJS/TEN. The classic manifestation of SJS/TEN consists of initial “flu-like” symptoms (malaise, fever, anorexia) in the prodromal phase, followed by cutaneous and mucous membrane (ocular, oral, and genital) inflammation and pain, and other systemic involvement. Symptoms usually begin 4–28 days after the onset of drug intake. Treatment is multidisciplinary and includes identification and withdrawal of the culprit drug, transfer to a specialist unit, supportive care, medical treatment, communication, and provision of appropriate information and emotional support.

References

  1. 1.
    Stevens A, Johnson F. A new eruptive fever associated with stomatitis and ophthalmia: report of two cases in children. Arch Pediatr Adolesc Med. 1922;24(6):526.Google Scholar
  2. 2.
    Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br J Dermatol. 1956;68(11):355–61.PubMedCrossRefGoogle Scholar
  3. 3.
    Knowles S, Shear NH. Clinical risk management of Stevens–Johnson syndrome/toxic epidermal necrolysis spectrum. Dermatol Ther. 2009;22(5):441–51.PubMedCrossRefGoogle Scholar
  4. 4.
    Roujeau JC, Huynh TN, Bracq C, et al. Genetic susceptibility to toxic epidermal necrolysis. Arch Dermatol. 1987;123(9):1171–3.PubMedCrossRefGoogle Scholar
  5. 5.
    Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens–Johnson syndrome. Nature. 2004;428(6982):486.PubMedCrossRefGoogle Scholar
  6. 6.
    Kaniwa N, Saito Y, Aihara M, 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.PubMedCrossRefGoogle Scholar
  7. 7.
    Kim SH, Lee KW, Song WJ, et al. Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy Res. 2011;97(1–2):190–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Shi YW, Min FL, Qin B, et al. Association between HLA and Stevens–Johnson syndrome induced by carbamazepine in southern Han Chinese: genetic markers besides B*1502? Basic Clin Pharmacol Toxicol. 2012;111(1):58–64.PubMedGoogle Scholar
  9. 9.
    Hsiao YH, Hui RC, Wu T, et al. Genotype–phenotype association between HLA and carbamazepine-induced hypersensitivity reactions: strength and clinical correlations. Journal of dermatological science. 2014;73(2):101–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Kaniwa N, Saito Y, Aihara M, et al. HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics. 2008;9(11):1617–22.PubMedCrossRefGoogle Scholar
  11. 11.
    Kang HR, Jee YK, Kim YS, et al. Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011;21(5):303–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Tassaneeyakul W, Jantararoungtong T, Chen P, et al. Strong association between HLA-B*5801 and allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenet Genomics. 2009;19(9):704–9.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ikeda H, Takahashi Y, Yamazaki E, et al. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia. 2010;51(2):297–300.PubMedCrossRefGoogle Scholar
  15. 15.
    Niihara H, Kakamu T, Fujita Y, 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.PubMedCrossRefGoogle Scholar
  16. 16.
    Ozeki T, Mushiroda T, Yowang A, et al. Genome-wide association study identifies HLA-A*3101 allele as a genetic risk factor for carbamazepine-induced cutaneous adverse drug reactions in Japanese population. Hum Mol Genet. 2011;20(5):1034–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Cheung YK, Cheng SH, Chan EJ, et al. HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013;54(7):1307–14.PubMedCrossRefGoogle Scholar
  18. 18.
    Hung SI, Chung WH, Liu ZS, et al. Common risk allele in aromatic antiepileptic-drug induced Stevens–Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010;11(3):349–56.PubMedCrossRefGoogle Scholar
  19. 19.
    Locharernkul C, Loplumlert J, Limotai 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.PubMedCrossRefGoogle Scholar
  20. 20.
    Kim SH, Kim M, Lee KW, et al. HLA-B*5901 is strongly associated with methazolamide-induced Stevens–Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics. 2010;11(6):879–84.PubMedCrossRefGoogle Scholar
  21. 21.
    Lonjou C, Borot N, Sekula P, et al. A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenet Genomics. 2008;18(2):99–107.PubMedCrossRefGoogle Scholar
  22. 22.
    Mehta TY, Prajapati LM, Mittal B, 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.PubMedCrossRefGoogle Scholar
  23. 23.
    Tangamornsuksan W, Chaiyakunapruk N, Somkrua R, et al. 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.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    Chen P, Lin JJ, Lu CS, et al. Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. N Engl J Med. 2011;364(12):1126–33.PubMedCrossRefGoogle Scholar
  26. 26.
    Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther. 2013;93(2):153–8.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Genin E, Chen DP, Hung SI, 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.PubMedCrossRefGoogle Scholar
  28. 28.
    Shear NH, Spielberg SP. Anticonvulsant hypersensitivity syndrome: in vitro assessment of risk. J Clin Investig. 1988;82(6):1826–32.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Shear NH, Spielberg SP, Grant DM, et al. Differences in metabolism of sulfonamides predisposing to idiosyncratic toxicity. Ann Intern Med. 1986;105(2):179–84.PubMedCrossRefGoogle Scholar
  30. 30.
    Chung WH, Chang WC, Lee YS, et al. Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA. 2014;312(5):525–34.PubMedCrossRefGoogle Scholar
  31. 31.
    Kesavan R, Narayan SK, Adithan C. Influence of CYP2C9 and CYP2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients. Eur J Clin Pharmacol. 2010;66(7):689–96.PubMedCrossRefGoogle Scholar
  32. 32.
    Depondt C, Godard P, Espel RS, et al. A candidate gene study of antiepileptic drug tolerability and efficacy identifies an association of CYP2C9 variants with phenytoin toxicity. Eur J Neurol Off J Eur Fed Neurol Soc. 2011;18(9):1159–64.Google Scholar
  33. 33.
    Ciccacci C, Di Fusco D, Marazzi MC, et al. Association between CYP2B6 polymorphisms and nevirapine-induced SJS/TEN: a pharmacogenetics study. Eur J Clin Pharmacol. 2013;69(11):1909–16.PubMedCrossRefGoogle Scholar
  34. 34.
    Lerch M, Pichler WJ. The immunological and clinical spectrum of delayed drug-induced exanthems. Curr Opin Allergy Clin Immunol. 2004;4(5):411–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Pichler WJ. Pharmacological interaction of drugs with antigen-specific immune receptors: the p-i concept. Curr Opin Allergy Clin Immunol. 2002;2(4):301–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Yang CW, Hung SI, Juo CG, et al. HLA-B*1502-bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens–Johnson syndrome. J Allergy Clin Immunol. 2007;120(4):870–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Wei CY, Chung WH, Huang HW, 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).PubMedCrossRefGoogle Scholar
  38. 38.
    Torres MJ, Mayorga C, Garcia JJ, et al. New aspects in betalactam recognition. Clin Exp Allergy. 1998;28(Suppl 4):25–8.PubMedGoogle Scholar
  39. 39.
    Ko TM, Chung WH, Wei CY, et al. Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens–Johnson syndrome. J Allergy Clin Immunol. 2011;128(6):1266–76 (e11).PubMedCrossRefGoogle Scholar
  40. 40.
    Posadas SJ, Padial A, Torres MJ, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109(1):155–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Nassif A, Moslehi H, Le Gouvello S, et al. Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Investig Dermatol. 2004;123(5):850–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Caproni M, Torchia D, Schincaglia E, et al. Expression of cytokines and chemokine receptors in the cutaneous lesions of erythema multiforme and Stevens–Johnson syndrome/toxic epidermal necrolysis. Br J Dermatol. 2006;155(4):722–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Liu ZG. Molecular mechanism of TNF signaling and beyond. Cell Res. 2005;15(1):24–7.PubMedCrossRefGoogle Scholar
  44. 44.
    Chavez-Galan L, Arenas-Del Angel MC, Zenteno E, et al. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol. 2009;6(1):15–25.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    Schroder K, Hertzog PJ, Ravasi T, et al. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75(2):163–89.PubMedCrossRefGoogle Scholar
  46. 46.
    Steimle V, Siegrist CA, Mottet A, et al. Regulation of MHC class II expression by interferon-gamma mediated by the transactivator gene CIITA. Science. 1994;265(5168):106–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Fruh K, Yang Y. Antigen presentation by MHC class I and its regulation by interferon gamma. Curr Opin Immunol. 1999;11(1):76–81.PubMedCrossRefGoogle Scholar
  48. 48.
    Paquet P, Paquet F, Al Saleh W, et al. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. 2000;22(5):413–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Correia O, Delgado L, Barbosa IL, et al. Increased interleukin 10, tumor necrosis factor alpha, and interleukin 6 levels in blister fluid of toxic epidermal necrolysis. J Am Acad Dermatol. 2002;47(1):58–62.PubMedCrossRefGoogle Scholar
  50. 50.
    Tapia B, Padial A, Sanchez-Sabate E, et al. Involvement of CCL27–CCR10 interactions in drug-induced cutaneous reactions. J Allergy Clin Immunol. 2004;114(2):335–40.PubMedCrossRefGoogle Scholar
  51. 51.
    Chung WH, Hung SI. Genetic markers and danger signals in Stevens–Johnson syndrome and toxic epidermal necrolysis. Allergol Int. 2010;59(4):325–32.PubMedCrossRefGoogle Scholar
  52. 52.
    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.PubMedCrossRefGoogle Scholar
  53. 53.
    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.PubMedCrossRefGoogle Scholar
  54. 54.
    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 Investig Dermatol. 2002;118(4):728–33.PubMedCrossRefGoogle Scholar
  55. 55.
    Wang CW, Chung WH, Cheng YF, et al. A new nucleic acid–based agent inhibits cytotoxic T lymphocyte-mediated immune disorders. J Allergy Clin Immunol. 2013;132(3):713–22 (e11).PubMedCrossRefGoogle Scholar
  56. 56.
    Finn MW, Clayberger C, Krensky AM. Expression and purification of 15 kDa granulysin utilizing an insect cell secretion system. Protein Expr Purif. 2011;75(1):70–4.PubMedCentralPubMedCrossRefGoogle Scholar
  57. 57.
    Tewary P, Yang D, de la Rosa G, et al. Granulysin activates antigen-presenting cells through TLR4 and acts as an immune alarmin. Blood. 2010;116(18):3465–74.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Schlapbach C, Zawodniak A, Irla N, et al. NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions. Allergy. 2011;66(11):1469–76.PubMedCrossRefGoogle Scholar
  59. 59.
    Fournier S, Bastuji-Garin S, Mentec H, et al. Toxic epidermal necrolysis associated with Mycoplasma pneumoniae infection. Eur J Clin Microbiol Infect Dis. 1995;14(6):558–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Mulvey JM, Padowitz A, Lindley-Jones M, et al. Mycoplasma pneumoniae associated with Stevens Johnson syndrome. Anaesth Intensive Care. 2007;35(3):414–7.PubMedGoogle Scholar
  61. 61.
    Harr T, French LE. Toxic epidermal necrolysis and Stevens–Johnson syndrome. Orphanet J Rare Dis. 2010;5:39.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Chung WH, Shih SR, Chang CF, et al. Clinicopathologic analysis of coxsackievirus a6 new variant induced widespread mucocutaneous bullous reactions mimicking severe cutaneous adverse reactions. J Infect Dis. 2013;208(12):1968–78.PubMedCrossRefGoogle Scholar
  63. 63.
    Rzany B, Mockenhaupt M, Baur S, et al. Epidemiology of erythema exsudativum multiforme majus, Stevens–Johnson syndrome, and toxic epidermal necrolysis in Germany (1990–1992): structure and results of a population-based registry. Journal of clinical epidemiology. 1996;49(7):769–73.PubMedCrossRefGoogle Scholar
  64. 64.
    Mockenhaupt M. The current understanding of Stevens–Johnson syndrome and toxic epidermal necrolysis. Expert review of clinical immunology. 2011;7(6):803–13 (quiz 14–5).PubMedCrossRefGoogle Scholar
  65. 65.
    Mockenhaupt M, Viboud C, Dunant A, et al. Stevens–Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Investig Dermatol. 2008;128(1):35–44.PubMedCrossRefGoogle Scholar
  66. 66.
    Huang LY, Liao WC, Chiou CC, et al. Fatal toxic epidermal necrolysis induced by carbamazepine treatment in a patient who previously had carbamazepine-induced Stevens–Johnson syndrome. J Formos Med Assoc Taiwan yi Zhi. 2007;106(12):1032–7.PubMedCrossRefGoogle Scholar
  67. 67.
    Auquier-Dunant A, Mockenhaupt M, Naldi L, et al. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens–Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol. 2002;138(8):1019–24.PubMedCrossRefGoogle Scholar
  68. 68.
    Assier H, Bastuji-Garin S, Revuz J, et al. Erythema multiforme with mucous membrane involvement and Stevens–Johnson syndrome are clinically different disorders with distinct causes. Arch Dermatol. 1995;131(5):539–43.PubMedCrossRefGoogle Scholar
  69. 69.
    Bastuji-Garin S, Rzany B, Stern RS, et al. Clinical classification of cases of toxic epidermal necrolysis, Stevens–Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129(1):92–6.PubMedCrossRefGoogle Scholar
  70. 70.
    Revuz J, Penso D, Roujeau JC, et al. Toxic epidermal necrolysis: clinical findings and prognosis factors in 87 patients. Arch Dermatol. 1987;123(9):1160–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Rajaratnam R, Mann C, Balasubramaniam P, et al. Toxic epidermal necrolysis: retrospective analysis of 21 consecutive cases managed at a tertiary centre. Clin Exp Dermatol. 2010;35(8):853–62.PubMedCrossRefGoogle Scholar
  72. 72.
    Meneux E, Wolkenstein P, Haddad B, et al. Vulvovaginal involvement in toxic epidermal necrolysis: a retrospective study of 40 cases. Obstet Gynecol. 1998;91(2):283–7.PubMedCrossRefGoogle Scholar
  73. 73.
    Gueudry J, Roujeau JC, Binaghi M, et al. Risk factors for the development of ocular complications of Stevens–Johnson syndrome and toxic epidermal necrolysis. Arch Dermatol. 2009;145(2):157–62.PubMedCrossRefGoogle Scholar
  74. 74.
    Sotozono C, Ueta M, Koizumi N, et al. Diagnosis and treatment of Stevens–Johnson syndrome and toxic epidermal necrolysis with ocular complications. Ophthalmology. 2009;116(4):685–90.PubMedCrossRefGoogle Scholar
  75. 75.
    Pereira FA, Mudgil AV, Rosmarin DM. Toxic epidermal necrolysis. J Am Acad Dermatol. 2007;56(2):181–200.PubMedCrossRefGoogle Scholar
  76. 76.
    Lebargy F, Wolkenstein P, Gisselbrecht M, et al. Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study. Intensive care Med. 1997;23(12):1237–44.PubMedCrossRefGoogle Scholar
  77. 77.
    de Prost N, Mekontso-Dessap A, Valeyrie-Allanore L, et al. Acute respiratory failure in patients with toxic epidermal necrolysis: clinical features and factors associated with mechanical ventilation. Crit Care Med. 2014;42(1):118–28.PubMedCrossRefGoogle Scholar
  78. 78.
    Michel P, Joly P, Ducrotte P, et al. Ileal involvement in toxic epidermal necrolysis (Lyell syndrome). Dig Dis Sci. 1993;38(10):1938–41.PubMedCrossRefGoogle Scholar
  79. 79.
    Powell N, Munro JM, Rowbotham D. Colonic involvement in Stevens–Johnson syndrome. Postgrad Med J. 2006;82(968):e10.PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Hung CC, Liu WC, Kuo MC, et al. Acute renal failure and its risk factors in Stevens–Johnson syndrome and toxic epidermal necrolysis. Am J Nephrol. 2009;29(6):633–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Weinand C, Xu W, Perbix W, et al. 27 years of a single burn centre experience with Stevens–Johnson syndrome and toxic epidermal necrolysis: analysis of mortality risk for causative agents. Burns. 2013;39(7):1449–55.PubMedCrossRefGoogle Scholar
  82. 82.
    de Prost N, Ingen-Housz-Oro S, Duong T, et al. Bacteremia in Stevens–Johnson syndrome and toxic epidermal necrolysis: epidemiology, risk factors, and predictive value of skin cultures. Medicine (Baltimore). 2010;89(1):28–36.PubMedCrossRefGoogle Scholar
  83. 83.
    Sekula P, Dunant A, Mockenhaupt M, et al. Comprehensive survival analysis of a cohort of patients with Stevens–Johnson syndrome and toxic epidermal necrolysis. J Investig Dermatol. 2013;133(5):1197–204.PubMedCrossRefGoogle Scholar
  84. 84.
    Garcia-Doval I, LeCleach L, Bocquet H, et al. Toxic epidermal necrolysis and Stevens–Johnson syndrome: does early withdrawal of causative drugs decrease the risk of death? Arch Dermatol. 2000;136(3):323–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Investig Dermatol. 2000;115(2):149–53.PubMedCrossRefGoogle Scholar
  86. 86.
    Zhu QY, Ma L, Luo XQ, et al. Toxic epidermal necrolysis: performance of SCORTEN and the score-based comparison of the efficacy of corticosteroid therapy and intravenous immunoglobulin combined therapy in China. J Burn Care Res. 2012;33(6):e295–308.PubMedCrossRefGoogle Scholar
  87. 87.
    Cartotto R, Mayich M, Nickerson D, et al. SCORTEN accurately predicts mortality among toxic epidermal necrolysis patients treated in a burn center. J Burn Care Res. 2008;29(1):141–6.PubMedGoogle Scholar
  88. 88.
    Sekula P, Liss Y, Davidovici B, et al. Evaluation of SCORTEN on a cohort of patients with Stevens–Johnson syndrome and toxic epidermal necrolysis included in the RegiSCAR study. J Burn Care Res. 2011;32(2):237–45.PubMedCrossRefGoogle Scholar
  89. 89.
    Guegan S, Bastuji-Garin S, Poszepczynska-Guigne E, et al. Performance of the SCORTEN during the first five days of hospitalization to predict the prognosis of epidermal necrolysis. J Investig Dermatol. 2006;126(2):272–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Fellahi A, Zouhair K, Amraoui A, et al. Stevens–Johnson and Lyell syndromes: mucocutaneous and ocular sequels in 43 cases [in French]. Ann Dermatol Venereol. 2011;138(2):88–92.PubMedCrossRefGoogle Scholar
  91. 91.
    Morales ME, Purdue GF, Verity SM, et al. Ophthalmic manifestations of Stevens–Johnson syndrome and toxic epidermal necrolysis and relation to SCORTEN. Am J Ophthalmol. 2010;150(4):505–10 (e1).PubMedCrossRefGoogle Scholar
  92. 92.
    Gaultier F, Rochefort J, Landru MM, et al. Severe and unrecognized dental abnormalities after drug-induced epidermal necrolysis. Arch Dermatol. 2009;145(11):1332–3.PubMedCrossRefGoogle Scholar
  93. 93.
    Duong TA, de Prost N, Ingen-Housz-Oro S, et al. Stevens–Johnson syndrome and toxic epidermal necrolysis: follow-up of pulmonary function after remission. Br J Dermatol. 2015;172(2):400–5.PubMedCrossRefGoogle Scholar
  94. 94.
    Dodiuk-Gad RP, Olteanu C, Hashimoto R, et al. Long-term emotional and physical complications of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). 23rd World Congress of Dermatology; Vancouver; 2015.Google Scholar
  95. 95.
    Quinn AM, Brown K, Bonish BK, et al. Uncovering histologic criteria with prognostic significance in toxic epidermal necrolysis. Arch Dermatol. 2005;141(6):683–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Fujita Y, Yoshioka N, Abe R, et al. Rapid immunochromatographic test for serum granulysin is useful for the prediction of Stevens–Johnson syndrome and toxic epidermal necrolysis. J Am Acad Dermatol. 2011;65(1):65–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Nigen S, Knowles SR, Shear NH. Drug eruptions: approaching the diagnosis of drug-induced skin diseases. J Drugs Dermatol. 2003;2(3):278–99.PubMedGoogle Scholar
  98. 98.
    Eisen ER, Fish J, Shear NH. Management of drug-induced toxic epidermal necrolysis. J Cutan Med Surg. 2000;4(2):96–102.PubMedGoogle Scholar
  99. 99.
    Mockenhaupt M. Stevens–Johnson syndrome and toxic epidermal necrolysis: clinical patterns, diagnostic considerations, etiology, and therapeutic management. Semin Cutan Med Surg. 2014;33(1):10–6.PubMedCrossRefGoogle Scholar
  100. 100.
    Chavan R, el-Azhary R. Cutaneous graft-versus-host disease: rationales and treatment options. Dermatol Ther. 2011;24(2):219–28.PubMedCrossRefGoogle Scholar
  101. 101.
    Mandelcorn R, Shear NH. Lupus-associated toxic epidermal necrolysis: a novel manifestation of lupus? J Am Acad Dermatol. 2003;48(4):525–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Paradela S, Martinez-Gomez W, Fernandez-Jorge B, et al. Toxic epidermal necrolysis-like acute cutaneous lupus erythematosus. Lupus. 2007;16(9):741–5.PubMedCrossRefGoogle Scholar
  103. 103.
    Baldwin BT, Lien MH, Khan H, et al. Case of fatal toxic epidermal necrolysis due to cardiac catheterization dye. J Drugs Dermatol. 2010;9(7):837–40.PubMedGoogle Scholar
  104. 104.
    Ball R, Ball LK, Wise RP, et al. Stevens–Johnson syndrome and toxic epidermal necrolysis after vaccination: reports to the vaccine adverse event reporting system. Pediatr Infect Dis J. 2001;20(2):219–23.PubMedCrossRefGoogle Scholar
  105. 105.
    Sassolas B, Haddad C, Mockenhaupt M, et al. ALDEN, an algorithm for assessment of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis: comparison with case–control analysis. Clin Pharmacol Ther. 2010;88(1):60–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Heelan K, Shear NH. Cutaneous drug reactions in children: an update. Paediatr Drugs. 2013;15(6):493–503.PubMedCrossRefGoogle Scholar
  107. 107.
    Pavlos R, Mallal S, Ostrov D, et al. Fever, rash, and systemic symptoms: understanding the role of virus and HLA in severe cutaneous drug allergy. J Allergy Clin Immunol Pract. 2014;2(1):21–33.PubMedCentralPubMedCrossRefGoogle Scholar
  108. 108.
    Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity. Allergy. 2004;59(8):809–20.PubMedCrossRefGoogle Scholar
  109. 109.
    Porebski G, Pecaric-Petkovic T, Groux-Keller M, et al. In vitro drug causality assessment in Stevens–Johnson syndrome—alternatives for lymphocyte transformation test. Clin Exp Allergy. 2013;43(9):1027–37.PubMedCrossRefGoogle Scholar
  110. 110.
    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).Google Scholar
  111. 111.
    Valeyrie-Allanore L, Bastuji-Garin S, Guegan S, et al. Prognostic value of histologic features of toxic epidermal necrolysis. J Am Acad Dermatol. 2013;68(2):e29–35.PubMedCrossRefGoogle Scholar
  112. 112.
    Endorf FW, Cancio LC, Gibran NS. Toxic epidermal necrolysis clinical guidelines. J Burn Care Res. 2008;29(5):706–12.PubMedCrossRefGoogle Scholar
  113. 113.
    Fromowitz JS, Ramos-Caro FA, Flowers FP, et al. Practical guidelines for the management of toxic epidermal necrolysis and Stevens–Johnson syndrome. Int J Dermatol. 2007;46(10):1092–4.PubMedCrossRefGoogle Scholar
  114. 114.
    Valeyrie-Allanore L, Ingen-Housz-Oro S, Chosidow O, et al. French referral center management of Stevens–Johnson syndrome/toxic epidermal necrolysis. Dermatol Sin. 2013;31(4):191–5.CrossRefGoogle Scholar
  115. 115.
    Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? J Burn Care Res. 2010;31(1):100–4.PubMedCrossRefGoogle Scholar
  116. 116.
    Fernando SL. The management of toxic epidermal necrolysis. Australas J Dermatol. 2012;53(3):165–71.PubMedCrossRefGoogle Scholar
  117. 117.
    Mayes T, Gottschlich M, Khoury J, et al. Energy requirements of pediatric patients with Stevens–Johnson syndrome and toxic epidermal necrolysis. Nutr Clin Pract. 2008;23(5):547–50.PubMedCrossRefGoogle Scholar
  118. 118.
    Bachot N, Revuz J, Roujeau JC. Intravenous immunoglobulin treatment for Stevens–Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression. Arch Dermatol. 2003;139(1):33–6.PubMedCrossRefGoogle Scholar
  119. 119.
    Faye O, Roujeau JC. Treatment of epidermal necrolysis with high-dose intravenous immunoglobulins (IV Ig): clinical experience to date. Drugs. 2005;65(15):2085–90.PubMedCrossRefGoogle Scholar
  120. 120.
    Lee HY, Lim YL, Thirumoorthy T, et al. The role of intravenous immunoglobulin in toxic epidermal necrolysis: a retrospective analysis of 64 patients managed in a specialized centre. Br J Dermatol. 2013;169(6):1304–9.PubMedCrossRefGoogle Scholar
  121. 121.
    Valeyrie-Allanore L, Wolkenstein P, Brochard L, et al. Open trial of ciclosporin treatment for Stevens–Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2010;163(4):847–53.PubMedCrossRefGoogle Scholar
  122. 122.
    Arevalo JM, Lorente JA, Gonzalez-Herrada C, et al. Treatment of toxic epidermal necrolysis with cyclosporin A. J Trauma. 2000;48(3):473–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Kirchhof MG, Miliszewski MA, Sikora S, et al. Retrospective review of Stevens-Johnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. J Am Acad Dermatol. 2014;71(5):941–7.PubMedCrossRefGoogle Scholar
  124. 124.
    Schneck J, Fagot JP, Sekula P, et al. Effects of treatments on the mortality of Stevens–Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in the prospective EuroSCAR study. J Am Acad Dermatol. 2008;58(1):33–40.PubMedCrossRefGoogle Scholar
  125. 125.
    Dodiuk-Gad RP, Chung WH, Yang CH, et al. The 8th International Congress on Cutaneous Adverse Drug Reactions, Taiwan, 2013: focus on severe cutaneous adverse reactions. Drug Saf. 2014;37(6):459–64.PubMedCrossRefGoogle Scholar
  126. 126.
    Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens–Johnson syndrome/toxic epidermal necrolysis. Acta dermato-venereol. 2007;87(2):144–8.CrossRefGoogle Scholar
  127. 127.
    Scott-Lang V, Tidman M, McKay D. Toxic epidermal necrolysis in a child successfully treated with infliximab. Pediatr Dermatol. 2014;31(4):532–4.PubMedCrossRefGoogle Scholar
  128. 128.
    Gubinelli E, Canzona F, Tonanzi T, et al. Toxic epidermal necrolysis successfully treated with etanercept. J Dermatol. 2009;36(3):150–3.PubMedCrossRefGoogle Scholar
  129. 129.
    Paradisi A, Abeni D, Bergamo F, et al. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71(2):278–83.PubMedCrossRefGoogle Scholar
  130. 130.
    Del Pozzo-Magana BR, Lazo-Langner A, Carleton B, et al. A systematic review of treatment of drug-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in children. J Popul Ther Clin Pharmacol. 2011;18:e121–33.PubMedGoogle Scholar
  131. 131.
    Koh MJ, Tay YK. Stevens–Johnson syndrome and toxic epidermal necrolysis in Asian children. J Am Acad Dermatol. 2010;62(1):54–60.PubMedCrossRefGoogle Scholar
  132. 132.
    Hamilton GM, Fish J. Pediatric toxic epidermal necrolysis: an institutional review of patients admitted to an intensive care unit. J Burn Care Res. 2013;34(6):e351–8.PubMedCrossRefGoogle Scholar
  133. 133.
    Paquet P, Pierard GE. Topical treatment options for drug-induced toxic epidermal necrolysis (TEN). Expert Opin Pharmacother. 2010;11(15):2447–58.PubMedCrossRefGoogle Scholar
  134. 134.
    Abela C, Hartmann CE, De Leo A, et al. Toxic epidermal necrolysis (TEN): the Chelsea and Westminster Hospital wound management algorithm. J Plast Reconstr Aesthet Surg. 2014;67(8):1026–32.PubMedCrossRefGoogle Scholar
  135. 135.
    Fu Y, Gregory DG, Sippel KC, et al. The ophthalmologist’s role in the management of acute Stevens–Johnson syndrome and toxic epidermal necrolysis. Ocul Surf. 2010;8(4):193–203.PubMedCrossRefGoogle Scholar
  136. 136.
    Shay E, Kheirkhah A, Liang L, et al. Amniotic membrane transplantation as a new therapy for the acute ocular manifestations of Stevens–Johnson syndrome and toxic epidermal necrolysis. Surv Ophthalmol. 2009;54(6):686–96.PubMedCentralPubMedCrossRefGoogle Scholar
  137. 137.
    Hsu M, Jayaram A, Verner R, et al. Indications and outcomes of amniotic membrane transplantation in the management of acute Stevens–Johnson syndrome and toxic epidermal necrolysis: a case–control study. Cornea. 2012;31(12):1394–402.PubMedCrossRefGoogle Scholar
  138. 138.
    Tomlins PJ, Parulekar MV, Rauz S. “Triple-TEN” in the treatment of acute ocular complications from toxic epidermal necrolysis. Cornea. 2013;32(3):365–9.PubMedCrossRefGoogle Scholar
  139. 139.
    Meneux E, Paniel BJ, Pouget F, et al. Vulvovaginal sequelae in toxic epidermal necrolysis. J Reprod Med. 1997;42(3):153–6.PubMedGoogle Scholar
  140. 140.
    Niemeijer IC, van Praag MC, van Gemund N. Relevance and consequences of erythema multiforme, Stevens–Johnson syndrome and toxic epidermal necrolysis in gynecology. Arch Gynecol Obstet. 2009;280(5):851–4.PubMedCrossRefGoogle Scholar
  141. 141.
    Kaser DJ, Reichman DE, Laufer MR. Prevention of vulvovaginal sequelae in Stevens–Johnson syndrome and toxic epidermal necrolysis. Rev Obstet Gynecol. 2011;4(2):81–5.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Struck MF, Illert T, Liss Y, et al. Toxic epidermal necrolysis in pregnancy: case report and review of the literature. J Burn Care Res. 2010;31(5):816–21.PubMedCrossRefGoogle Scholar
  143. 143.
    Rodriguez G, Trent JT, Mirzabeigi M, et al. Toxic epidermal necrolysis in a mother and fetus. J Am Acad Dermatol. 2006;55(5 Suppl):S96–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Claessens N, Delbeke L, Lambert J, et al. Toxic epidermal necrolysis associated with treatment for preterm labor. Dermatology. 1998;196(4):461–2.PubMedCrossRefGoogle Scholar
  145. 145.
    Vasicka AI, Lin TJ, Das BK. Erythema multiforme exudativum (Stevens–Johnson syndrome) at term pregnancy: report of one case. Obstet Gynecol. 1958;12(2):225–9.PubMedGoogle Scholar
  146. 146.
    Dube N, Adewusi E, Summers R. Risk of nevirapine-associated Stevens–Johnson syndrome among HIV-infected pregnant women: the Medunsa National Pharmacovigilance Centre, 2007–2012. S Afr Med J. 2013;103(5):322–5.PubMedCrossRefGoogle Scholar
  147. 147.
    Knight L, Muloiwa R, Dlamini S, et al. Factors associated with increased mortality in a predominantly HIV-infected population with Stevens Johnson syndrome and toxic epidermal necrolysis. PloS One. 2014;9(4):e93543.PubMedCentralPubMedCrossRefGoogle Scholar
  148. 148.
    Mittmann N, Knowles SR, Gomez M, et al. Evaluation of the extent of under-reporting of serious adverse drug reactions: the case of toxic epidermal necrolysis. Drug Saf. 2004;27(7):477–87.PubMedCrossRefGoogle Scholar
  149. 149.
    Sanchez-Lopez MP, Dresch V. The 12-Item General Health Questionnaire (GHQ-12): reliability, external validity and factor structure in the Spanish population. Psicothema. 2008;20(4):839–43.Google Scholar
  150. 150.
    Man CB, Kwan P, Baum L, et al. Association between HLA-B*1502 allele and antiepileptic drug–induced cutaneous reactions in Han Chinese. Epilepsia. 2007;48(5):1015–8.PubMedCrossRefGoogle Scholar
  151. 151.
    Carr DF, Chaponda M, Jorgensen AL, 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.PubMedCentralPubMedCrossRefGoogle Scholar
  152. 152.
    Levi N, Bastuji-Garin S, Mockenhaupt M, et al. Medications as risk factors of Stevens–Johnson syndrome and toxic epidermal necrolysis in children: a pooled analysis. Pediatrics. 2009;123(2):e297–304.PubMedCrossRefGoogle Scholar
  153. 153.
    Saka B, Barro-Traore F, Atadokpede FA, et al. Stevens–Johnson syndrome and toxic epidermal necrolysis in sub-Saharan Africa: a multicentric study in four countries. Int J Dermatol. 2013;52(5):575–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Roni P. Dodiuk-Gad
    • 1
    • 2
  • Wen-Hung Chung
    • 3
    • 4
  • Laurence Valeyrie-Allanore
    • 5
    • 6
  • Neil H. Shear
    • 1
    • 7
  1. 1.Division of Dermatology, Department of MedicineSunnybrook Health Sciences CentreTorontoCanada
  2. 2.Department of DermatologyHa’emek Medical CenterAfulaIsrael
  3. 3.Department of Dermatology, Drug Hypersensitivity Clinical and Research CenterChang Gung Memorial HospitalsTaipei, KeelungTaiwan
  4. 4.College of MedicineChang Gung UniversityTaoyuanTaiwan
  5. 5.Department of Dermatology, French Reference Center for Toxic and Autoimmune Blistering DiseasesHenri Mondor HospitalCréteilFrance
  6. 6.Université Paris-Est Créteil Val de MarneCréteilFrance
  7. 7.Division of Clinical Pharmacology and Toxicology, Department of Medicine, Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada

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