Severe Cutaneous Adverse Drug Reactions: Presentation, Risk Factors, and Management

  • S. Shahzad Mustafa
  • David Ostrov
  • Daniel Yerly
Allergic Skin Diseases (L Fonacier, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Allergic Skin Diseases


Purpose of Study

Immune-mediated adverse drug reactions occur commonly in clinical practice and include mild, self-limited cutaneous eruptions, IgE-mediated hypersensitivity, and severe cutaneous adverse drug reactions (SCAR). SCARs represent an uncommon but potentially life-threatening form of delayed T cell-mediated reaction. The spectrum of illness ranges from acute generalized exanthematous pustulosis (AGEP) to drug reaction with eosinophilia with systemic symptoms (DRESS), to the most severe form of illness, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).

Recent Findings

There is emerging literature on the efficacy of cyclosporine in decreasing mortality in SJS/TEN.


The purpose of our review is to discuss the typical presentations of these conditions, with a special focus on identifying the culprit medication. We review risk factors for developing SCAR, including HLA alleles strongly associated with drug hypersensitivity. We conclude by discussing current strategies for the management of these conditions.


Severe cutaneous adverse drug reaction (SCAR) Acute generalized exanthematous pustulosis (AGEP) Drug reaction with eosinophilia and systemic symptoms (DRESS) Stevens-Johnson syndrome (SJS) Toxic epidermal necrolysis (TEN) HLA-associated drug hypersensitivity 


Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

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


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

  1. 1.
    Adam J, Wuillemin N, Watkins S, Jamin H, Eriksson KK, Villiger P, et al. Abacavir induced T cell reactivity from drug naive individuals shares features of allo-immune responses. PLoS One. 2014;9(4):e95339.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Dodiuk-GAD RP, Laws PM, Shear NH. Epidemiology of severe cutaneous drug hypersensitivity. Semin Cutan Med Surg. 2014;33(1):2–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Schaerli P, Britschgi M, Keller M, Steiner UC, Steinmann LS, Moser B, et al. Characterization of human T cells that regulate neutrophilic skin inflammation. J Immunol. 2004;173(3):2151–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Fiszenson-Albala F, Auzerie V, Mahe E, Farinotti R, Durand-Stocco C, Crickx B, et al. A 6-month prospective survey of cutaneous drug reactions in a hospital setting. Br J Dermatol. 2003;149(5):1018–22.CrossRefPubMedGoogle Scholar
  5. 5.
    Knowles SR, Shapiro LE, Shear NH. Anticonvulsant hypersensitivity syndrome: incidence, prevention and management. Drug Saf. 1999;21(6):489–501.CrossRefPubMedGoogle Scholar
  6. 6.
    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 syndome really exist? Br J Dermatol. 2007;156(3):609–11.CrossRefPubMedGoogle Scholar
  7. 7.
    Mennicke M, Zawodniak A, Keller M, Wilkens L, Yawalkar N, Stickel F, et al. Fulminant liver failure after vancomycin in a sulfasalazine-induced DRESS syndrome: fatal recurrence after liver transplantation. Am J Transplant. 2009;9(9):2197–202.CrossRefPubMedGoogle Scholar
  8. 8.
    Jorg-Walther L, Schnyder B, Helbling A, Helsing K, Schuller A, Wochner A, et al. Flare-up reactions in severe drug hypersensitivity: infection or ongoing T-cell hyperresponsiveness. Clin Case Rep. 2015;3(10):798–801.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Pichler WJ, Srinoulprasert Y, Yun J, Hausmann O. Multiple drug hypersensitivity. Int Arch Allergy Immunol. 2017;172(3):129–38.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cacoub P, Musette P, Descamps V, Meyer O, Speirs C, Finzi L, et al. The DRESS syndrome: a literature review. Am J Med. 2011;124(7):588–97.CrossRefPubMedGoogle Scholar
  11. 11.
    Rzany B, Hering O, Mockenhaupt M, Schroder W, Goerttler E, Ring J, et al. Histopathological and epidemiological characteristics of patients with erythema exudativum multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 1996;135(1):6–11.CrossRefPubMedGoogle Scholar
  12. 12.
    Yang MS, Lee JY, Kim J, Kim GW, Kim BK, Kim JY, et al. Incidence of Stevens-Johnson syndrome and toxic epidermal necrolysis: a Nationwide population-based study using National Health Insurance Database in Korea. PLoS One. 2015;11(11):e0165933.CrossRefGoogle Scholar
  13. 13.
    Cote B, Wechsler J, Bastuji-Garin S, Assier H, Revuz J, Roujeau JC. Clinicopathologic correlation in erythema multiforme and Stevens-Johnson syndrome. Arch Dermatol. 1995;131(11):1268–72.CrossRefPubMedGoogle Scholar
  14. 14.
    Posadas SJ, Padial A, Torres MJ, Mayorga C, Leyva L, Sanchez E, 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.CrossRefPubMedGoogle Scholar
  15. 15.
    Schlapbach C, Zawodniak A, Irla N, Adam J, Hunger RE, Yerly D, et al. NKp46+ cells express granulysin in multiple cutaneous adverse drug reactions. Allergy. 2011;66(11):1469–76.CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefPubMedGoogle Scholar
  17. 17.
    Morel E, Escamochero S, Cabanas R, Diaz R, Fiandor A, Bellon T. CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Allergy Clin Immunol. 2010;125(3):703–10. 710 e701-710 e708CrossRefPubMedGoogle Scholar
  18. 18.
    Sekula P, Dunant A, Mockenhaupk M, Naldi L, Bouwes-Bavinck JN, Halevy S, et al. Comprehensive survival analysis of a cohort of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. J Invest Dermatol. 2013;133(5):1197–204.CrossRefPubMedGoogle Scholar
  19. 19.
    Hsu DY, Brieva J, Silverberg NB, Silverberg JI. Morbidity and mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis in United States adults. J Invest Dermatol. 2016;136(7):1387–97.CrossRefPubMedGoogle Scholar
  20. 20.
    • Peter JG, Lehloenya R, Diamini S, Risma K, White KD, Konvinse KC. Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice. J Allergy Clin Immunol Pract. 2017;5(3):547–63. A review on SCAR focusing on global epidemiology, clinical phenotypes, diagnostic considerations, and special considerations, including drug re-challenge and SCAR in pregnancy. CrossRefPubMedGoogle Scholar
  21. 21.
    Halevy S, Ghislain PD, Mockenhaupt M, Fagot JP, Bouwes Bavinck JN, Sidoroff A, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008;58(1):25–32.CrossRefPubMedGoogle Scholar
  22. 22.
    Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous disease and drug reactions in HIV infection. NEJM. 1993;328(23):1670–4.CrossRefPubMedGoogle Scholar
  23. 23.
    Okamoto-Uchida Y, Nakamura R, Sai K, Imatoh T, Matsunaga K, Aihara M, et al. Effect of infectious diseases on the pathogenesis of Stevens-Johnson syndrome and toxic epidermal necrolysis. Biol Pharm Bull. 2017;40(9):1576–80.CrossRefPubMedGoogle Scholar
  24. 24.
    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. 2002;359(9312):1121–2.CrossRefPubMedGoogle Scholar
  25. 25.
    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. 2002;359(9308):727–32.CrossRefPubMedGoogle Scholar
  26. 26.
    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.CrossRefPubMedGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    Hung SI, Chung WH, Jee SH, Chen WC, Chang YT, Lee WR, et al. Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenet Genomics. 2006;16(4):297–306.CrossRefPubMedGoogle Scholar
  29. 29.
    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.CrossRefPubMedGoogle Scholar
  30. 30.
    Zhang FR, Liu H, Irwanto A, Fu XA, Li Y, Yu GO, et al. HLA-B*13:01 and the dapsone hypersensitivity syndrome. New Engl J of Med. 2013;369(17):1620–8.CrossRefGoogle Scholar
  31. 31.
    •• White KD, Abe R, Ardern-Jones M, Beachkofsky T, Bouchard C, Carleton B, et al. SJS/TEN 2017: building multidisciplinary networks to drive science and translation. J Allergy Clin Immunol Pract. 2018;6(1):38–69. A review on SJS/TEN discussing global epidemiology and pharmacogenomics networks of SJS/TEN, management, with a focus on special populations, including children, pregnant women, and the elderly, and potential focus of future research. CrossRefPubMedGoogle Scholar
  32. 32.
    Denisov IG, Grinkova YV, Baylon JL, Tajkhorshid E, Sligar SG. Mechanism of drug-drug interactions mediated by human cytochrome P450 CYP3A4 monomer. Biochemistry. 2015;54(13):2227–39.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ota T, Kamada Y, Hayashida M, Iwao-Koizumi K, Murata S, Kinoshita K. Combination analysis in genetic polymorphisms of drug-metabolizing enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A5 in the Japanese population. Int J Med Sci. 2015;12(1):78–82.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Ogese MO, Jenkins RE, Maggs JL, Meng X, Whitaker P, Peckham D, et al. Characterization of peroxidases expressed in human antigen presenting cells and analysis of the covalent binding of nitroso sulfamethoxazole to myeloperoxidase. Chem Res Toxicol. 2015;28(1):144–54.CrossRefPubMedGoogle Scholar
  35. 35.
    Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013;1830(5):3143–53.CrossRefPubMedGoogle Scholar
  36. 36.
    •• 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. Double-blind, prospective, randomized trial that showed HLA-B*57:01 screening decreased the risk of drug hypersensitivity to abacavir. This was a key study leading to the recommendation of genetic screening prior to the administration of certain medications. CrossRefPubMedGoogle Scholar
  37. 37.
    Phillips E, Mallal S. Successful translation of pharmacogenetics into the clinic: the abacavir example. Mol Diagn Therapy. 2009;13(1):1–9.CrossRefGoogle Scholar
  38. 38.
    Palmieri TL, Greenhalgh DG, Saffle JR, Spence RJ, Peck MD, Jeng JC, et al. A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century. J Burn Care Rehab. 2002;23(2):87–96.CrossRefGoogle Scholar
  39. 39.
    Schulz JT, Sheridan RL, Ryan CM, MacKool B, Tompkins RG. A 10-year experience with toxic epidermal necrolysis. J Burn Care Rehab. 2000;21(3):199–204.CrossRefGoogle Scholar
  40. 40.
    Mcgee T, Munster A. Toxic epidermal necrolysis syndrome: mortality rate reduced with early referral to regional burn center. Plast Reconstive Surg. 1998;102(4):1018–22.CrossRefGoogle Scholar
  41. 41.
    Maher PD, Wasiak J, Hii B, Cleland H, Watters DA, Gin D, et al. A systemic review of the management and outcome of toxic epidermal necrolysis treated in burn centres. Burns. 2014;40(7):1245–54.CrossRefGoogle Scholar
  42. 42.
    Garcia-Doval I, LeCleach L, Bocquet H, Otero XL, Roujeau JC. 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.CrossRefPubMedGoogle Scholar
  43. 43.
    Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharma Ther. 1981;30(2):239–45.CrossRefGoogle Scholar
  44. 44.
    Sassolas B, Haddad C, Mockenhaupt M, Dunant A, Liss Y, Bork K, et al. ALDEN an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharma Ther. 2010;88(1):60–8.CrossRefGoogle Scholar
  45. 45.
    Paulmann M, Mockenhaupt M. Severe drug-induced skin reactions: clinical features, diagnosis, etiology, and therapy. English online version of J Dtsch Dermatol Ges. 2015;13(7):625–45.Google Scholar
  46. 46.
    • Guegan S, Bastuji-Garin S, Poszepczynska-Guigne E, Roujeau JC, Revuz J. Performance of the SCORTEN during the first five days of hospitalization to predict the prognosis of epidermal necrolysis. J of Investigative Derm. 2006;126(2):272–6. Study showing the validity of the SCORTEN score, a severity-of-illness tool to predict mortality in SJS/TEN. CrossRefGoogle Scholar
  47. 47.
    Lee HY, Chou D, Pang SM, Thirumoorthy T. Acute generalized exanthematous pustulosis: analysis of cases managed in a tertiary hospital in Singapore. Int J Dermatol. 2010;49(5):507–12.CrossRefPubMedGoogle Scholar
  48. 48.
    Ingen-Housz-Oro S, Hotz C, Valeyrie-Allanore L, Sbidian E, Hernery F, Chosidow O, et al. Acute generalized exanthematous pustulosis: a retrospective audit of practice between 1994 and 2011 at a single centre. Br J Dermatol. 2015;172(5):1455–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Chang SL, Huang YH, Yang CH, Hu S, Hong HS. Clinical manifestations and characteristics of patients with in acute generalized exanthematous pustulosis in Asia. Acta Derm Venereol. 2008;88(4):363–5.PubMedGoogle Scholar
  50. 50.
    Funck-Bretano E, Duong TA, Bouvresse S, Bagot M, Wolkenstein P, Roujeau JC, et al. Therapeutic management of DRESS: a retrospective study of 38 cases. J Amer Acad Dermatol. 2015;72(2):246–52.CrossRefGoogle Scholar
  51. 51.
    Chen YC, Chiu HC, Chu CY. Drug reaction with eosinophilia and systemic symptoms. Arch Dermatol. 2010;146(12):1373–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Singer EM, Wanat KA, Rosenbach MA. A case of recalcitrant DRESS syndrome with multiple autoimmune sequelae treated with intravenous immunoglobulins. JAMA Dermatol. 2013;149(4):494–5.CrossRefPubMedGoogle Scholar
  53. 53.
    Joly P, Janela B, Tetart F, Rogez S, Picard D, D’Incan M, et al. Poor benefit/risk balance of intravenous immunoglobulins in DRESS. Arch Dermatol. 2012;148(4):543–4.CrossRefPubMedGoogle Scholar
  54. 54.
    Dorafshar AH, Dickie SR, Cohn AB, Avcock JK, O’Connor A, Tung A, et al. Antishear therapy for toxic epidermal necrolysis: an alternative treatment approach. Plast Reconstr Surg. 2008;122(1):154–60.CrossRefPubMedGoogle Scholar
  55. 55.
    Abela C, Hartmann CE, De Leo A, de Sica CA, Shah H, Jawad M, et al. Toxic epidermal necrolysis (TEN): the Chelsea and Westminster hospital wound management algorithm. J Plas Reconstr Aestet Surg. 2014;67(8):1026–32.CrossRefGoogle Scholar
  56. 56.
    Gueudry J, Roujeau JC, Binaghi M, Soubrane G, Muraine M. Risk factors for the development of ocular complications of Stevens-Johnson syndrome and toxic epidermal necrolysis. Arch Dermatol. 2009;145(2):157–62.CrossRefPubMedGoogle Scholar
  57. 57.
    Sotozano C, Ueta M, Koizumi N, Inatomi T, Shirakata Y, Ikezawa Z, et al. Diagnosis and treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis with ocular complications. Ophthalmology. 2009;116(4):685–90.CrossRefGoogle Scholar
  58. 58.
    Yip LW, Thong BY, Tan AW, Khin LW, Chng HH, Heng WJ. High-dose intravenous immunoglobulin in the treatment of toxic epidermal necrolysis: a study of ocular benefits. Eye. 2005;19(8):846–53.CrossRefPubMedGoogle Scholar
  59. 59.
    Hsu M, Jayaram A, Verner R, Lin A, Bouchard C. 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.CrossRefPubMedGoogle Scholar
  60. 60.
    • Sharma N, Thenarasun SA, Kaur M, Pushker N, Khanna N, Agarwal T, et al. Adjuvant role of amniotic membrane transplantation in acute ocular Stevens-Johnson syndrome: a randomized control trial. Ophthalmology. 2016;123(3):484–91. Prospective, randomized, controlled trial showing amniotic membrane transplantation improves ocular outcomes in the acute phase of SJS/TEN. CrossRefPubMedGoogle Scholar
  61. 61.
    de Sica-Chapman A, Williams G, Soni N, Bunker CB. Granulocyte-colony stimulating factor in toxic epidermal necrolyisis (TEN) and Chelsea & Westminster TEN protocol. Br J Dermatol. 2010;162(4):860–5.CrossRefPubMedGoogle Scholar
  62. 62.
    Pallesen KA, Robinson S, Toft P, Andersen KE. Successful treatment of toxic epidermal necrolysis/Stevens-Johnson syndrome overlap with human granulocyte colony stimulating factor: a case report. Acta Derm Venereol. 2012;92(2):212–3.CrossRefPubMedGoogle Scholar
  63. 63.
    Ang CC, Tay YK. Hematological abnormalities and the use of granulocyte-colony-stimulating factor in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Int J Dermatol. 2011;50(12):1570–8.CrossRefPubMedGoogle Scholar
  64. 64.
    Han F, Zhang J, Guo Q, Feng Y, Gao Y, Guo L, et al. Successful treatment of toxic epidermal necrolysis using plasmapheresis: a prospective observational study. J Crit Care. 2017;42:65–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Narita YM, Hirahara K, Mizukawa Y, Kano Y, Shiohara T. Efficacy of plasmapheresis for the treatment of severe toxic epidermal necrolysis: is cytokine expression analysis useful in predicting its therapeutic efficacy? J Dermatol. 2011;38(3):236–45.CrossRefPubMedGoogle Scholar
  66. 66.
    Kostal M, Blaha M, Lanska M, Kostalova M, Blaha V, Stepanova E, et al. Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: a series of four cases. J Clin Apher. 2012;27(4):215–20.CrossRefPubMedGoogle Scholar
  67. 67.
    Yavuz H, Emiroglu M. Toxic epidermal necrolysis treated with N-acetylcysteine. Pediatr Int. 2014;56(5):e52–4.CrossRefPubMedGoogle Scholar
  68. 68.
    Velez A, Moreno JC. Toxic epidermal necrolysis treated with N-acetylcysteine. J Am Acad Dermatol. 2002;46(3):469–70.CrossRefPubMedGoogle Scholar
  69. 69.
    Redondo P, de Felipe L, de la Pena A, Aramendia JM, Vanaclocha V. Drug-induced hypersensitivity syndrome and toxic epidermal necrolysis. Treatment with N-acetylcysteine. British J Dermatol. 1997;136(4):645–6.CrossRefGoogle Scholar
  70. 70.
    Frangogiannis NG, Boridy I, Mazhar M, Matthews R, Gangopadhyay S, Cate T. Cyclophosphamide in the treatment of toxic epidermal necrolysis. South Med J. 1996;89(10):1001–3.CrossRefPubMedGoogle Scholar
  71. 71.
    Wolkenstein P, Latarjet J, Roujeau JC, Duguet C, Boudeau S, Vailant L. Randomized comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet. 1998;352(914):1586–9.CrossRefPubMedGoogle Scholar
  72. 72.
    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.PubMedGoogle Scholar
  73. 73.
    • Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014;71(2):278–83. Case series of ten patients with TEN treated with a tumor necrosis factor α antagonist (etanercept). Despite a predicted mortality of 50%, all patients responded promptly to a single treatment. The use of anti- TNF α agents therefore warrants further study in TEN. CrossRefPubMedGoogle Scholar
  74. 74.
    Singh GK, Chatterjee M, Verma R. Cyclosporine in Stevens-Johnson syndrome and toxic epidermal necrolysis and retrospective comparison with systemic corticosteroid. Indian J Dermatol Venereol Leprol. 2013;79(5):686–792.CrossRefPubMedGoogle Scholar
  75. 75.
    • Gonzalez-Herrada C, Rodriguez-Martin S, Cachafeiro L, Lerma V, Gonzalez O, Lorenta JA, et al. Cyclosporine use in epidermal necrolysis is associated with an important mortality reduction: evidence from three different approaches. J Invest Dermatol. 2017;137(10):2092–100. By comparing outcomes in TEN at different centers using predominately different forms of immunomodulatory therapy (typically cyclosporine versus IVIg), cyclosporine was consistently shown to improve mortality in TEN. CrossRefPubMedGoogle Scholar
  76. 76.
    •• Zimmerman S, Sekula P, Venhoff M, Motschall E, Knaus J, Schumacher M, et al. Systemic immunomodulating therapies for Stevens-Johnson syndrome and toxic epidermal necrolysis, a systematic review and meta-analysis. JAMA Dermatol. 2017;153(6):514–22. A review and meta-analysis of systemic immunomodulating therapies in SJS/TEN that shows cyclosporine to have the most promise in decreasing mortality. CrossRefGoogle Scholar
  77. 77.
    • Roujeau JC, Mockenhaupt M, Guillaume JC, Revuz J. New evidence supporting cyclosporine efficacy in epidermal necrolysis. J of Invest Derm. 2017;137(10):2047–9. A review of recently published literature and presentation of expert opinion that cyclosporine is effective in decreasing mortality in TEN and should possibly considered as first line systemic therapy in this life threating condition. CrossRefGoogle Scholar
  78. 78.
    Liu W, Nie X, Zhang L. A retrospective analysis of Stevens-Johnson syndrome/toxic epidermal necrolysis treated with corticosteroids. Int J Dermatol. 2016;55(12):1408–13.CrossRefPubMedGoogle Scholar
  79. 79.
    Huang YC, Li YC, Chen TJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis: a systematic review and meta-analysis. Br J Dermatol. 2012;167(2):424–32.CrossRefPubMedGoogle Scholar
  80. 80.
    Lee HY, Lim YL, Thirumoorthy T, Pang SM. 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.CrossRefPubMedGoogle Scholar
  81. 81.
    Aihara M, Kano Y, Fujita H, Kambara T, Matsukura S, Katayama I, et al. Efficacy of additional IV immunoglobulin to steroid therapy in Stevens-Johnson syndrome and toxic epidermal necrolysis. J Dermatol. 2015;42(8):768–77.CrossRefPubMedGoogle Scholar
  82. 82.
    Zhu QY, Ma L, Luo XQ, Huang HY. 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.CrossRefPubMedGoogle Scholar
  83. 83.
    • Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK. UK guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. Br J of Derm. 2016;174(6):1194–227. Guidelines from the United Kingdom on the diagnosis and management of SJS/TEN. CrossRefGoogle Scholar
  84. 84.
    Lehloenya RJ, Todd G, Badri M, Dheda K. Outcomes of reintroducing anti-tuberculosis drugs following cutaneous adverse drug reactions. Int J Tuberc Lung Dis. 2011;15(12):1649–57.CrossRefPubMedGoogle Scholar
  85. 85.
    Gomes ER, Brockow K, Kuyucu S, Saretta F, Mori F, Blanca-Lopez N, et al. Drug hypersensitivity in children: report from the pediatric task force of the EAACI drug allergy interest group. Allergy. 2016;71(2):149–61.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • S. Shahzad Mustafa
    • 1
    • 2
  • David Ostrov
    • 3
  • Daniel Yerly
    • 4
  1. 1.Allergy and Clinical ImmunologyRochester Regional Health SystemRochesterUSA
  2. 2.University of Rochester School of Medicine and DentistryRochesterUSA
  3. 3.Department of Pathology, Immunology and Laboratory MedicineUniversity of Florida College of MedicineGainesvilleUSA
  4. 4.Department of Rheumatology, Immunology and AllergologyUniversity Hospital and University of BernBernSwitzerland

Personalised recommendations