Skip to main content

Advertisement

SpringerLink
Log in

Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: a Review and Update

  • Hospital-Based Dermatology (L Guggina and A Zhou)
  • Published:
Current Dermatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review highlights current concepts in the management of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).

Recent Findings

A new scoring system, the ABCD-10, was recently developed to better estimate mortality among SJS/TEN patients. Supportive care remains the mainstay of treatment, and includes wound care, fluid and electrolyte management, management of medical co-morbidities, and infection control. The value of adjuvant therapy remains unclear, but new recent retrospective studies suggest that the combination therapies may be efficacious. Recent prospective studies investigating cyclosporine and etanercept have shown promise in the treatment of SJS/TEN.

Summary

SJS and TEN are severe mucocutaneous drug reactions associated with high morbidity and mortality. Supportive care is the most universally accepted therapy, although specific strategies may vary among institutions. Adjuvant therapies include corticosteroids, IVIG, cyclosporine, TNF alpha inhibitors, and plasmapheresis but prospective data is still lacking. Clinical trials that may better elucidate their efficacy are currently under way.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

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

  1. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. Clinical classification of cases of toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme. Arch Dermatol. 1993;129(1):92–6.

    Article  CAS  PubMed  Google Scholar 

  2. Letko E, Papaliodis DN, Papaliodis GN, Daoud YJ, Ahmed AR, Foster CS. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature. Ann Allergy Asthma Immunol. 2005;94(4):419–36; quiz 36–8, 56. https://doi.org/10.1016/S1081-1206(10)61112-X.

    Article  PubMed  Google Scholar 

  3. Goodman H. Nikolsky sign; page from notable contributors to the knowledge of dermatology. AMA Arch Derm Syphilol. 1953;68(3):334–5.

    Article  CAS  PubMed  Google Scholar 

  4. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis. 2010;5:39. https://doi.org/10.1186/1750-1172-5-39.

    Article  PubMed  PubMed Central  Google Scholar 

  5. • Jun I, Rim JH, Kim MK, Yoon KC, Joo CK, Kinoshita S, et al. Association of human antigen class I genes with cold medicine-related Stevens-Johnson syndrome with severe ocular complications in a Korean population. Br J Ophthalmol. 2019;103(4):573–6. https://doi.org/10.1136/bjophthalmol-2018-313263This multicentre case-control study found significant difference in gene frequency for HLA-A*02:06 (37% vs 20%) and HLA-C*03:04 (15% vs 5.4%) in patients with SJS/TEN patients compared with age, sex matched controls, respectively.

    Article  PubMed  Google Scholar 

  6. Nicoletti P, Barrett S, McEvoy L, Daly AK, Aithal G, Lucena MI, et al. Shared genetic risk factors across carbamazepine-induced hypersensitivity reactions. Clin Pharmacol Ther. 2019. https://doi.org/10.1002/cpt.1493.

    Article  CAS  Google Scholar 

  7. Correia O, Delgado L, Ramos JP, Resende C, Torrinha JA. Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement. Arch Dermatol. 1993;129(4):466–8.

    Article  CAS  PubMed  Google Scholar 

  8. Paul C, Wolkenstein P, Adle H, Wechsler J, Garchon HJ, Revuz J, et al. Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis. Br J Dermatol. 1996;134(4):710–4.

    Article  CAS  PubMed  Google Scholar 

  9. Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science (New York, NY). 1998;282(5388):490–3. https://doi.org/10.1126/science.282.5388.490.

    Article  CAS  Google Scholar 

  10. Nassif A, Bensussan A, Boumsell L, Deniaud A, Moslehi H, Wolkenstein P, et al. Toxic epidermal necrolysis: effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol. 2004;114(5):1209–15. https://doi.org/10.1016/j.jaci.2004.07.047.

    Article  CAS  PubMed  Google Scholar 

  11. Wei CY, Chung WH, Huang HW, Chen YT, Hung SI. 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. https://doi.org/10.1016/j.jaci.2011.12.990.

    Article  CAS  PubMed  Google Scholar 

  12. Genin E, Schumacher M, Roujeau JC, Naldi L, Liss Y, Kazma R, et al. Genome-wide association study of Stevens-Johnson syndrome and toxic epidermal Necrolysis in Europe. Orphanet J Rare Dis. 2011;6:52. https://doi.org/10.1186/1750-1172-6-52.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Borchers AT, Lee JL, Naguwa SM, Cheema GS, Gershwin ME. Stevens-Johnson syndrome and toxic epidermal necrolysis. Autoimmun Rev. 2008;7(8):598–605. https://doi.org/10.1016/j.autrev.2008.06.004.

    Article  CAS  PubMed  Google Scholar 

  14. Rzany B, Mockenhaupt M, Baur S, Schroder W, Stocker U, Mueller J, 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. J Clin Epidemiol. 1996;49(7):769–73.

    Article  CAS  PubMed  Google Scholar 

  15. Strom BL, Carson JL, Halpern AC, Schinnar R, Snyder ES, Shaw M, et al. A population-based study of Stevens-Johnson syndrome. Incidence and antecedent drug exposures. Arch Dermatol. 1991;127(6):831–8.

    Article  CAS  PubMed  Google Scholar 

  16. Chan HL, Stern RS, Arndt KA, Langlois J, Jick SS, Jick H, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. A population-based study with particular reference to reactions caused by drugs among outpatients. Arch Dermatol. 1990;126(1):43–7.

    Article  CAS  PubMed  Google Scholar 

  17. Roujeau JC, Chosidow O, Saiag P, Guillaume JC. Toxic epidermal necrolysis (Lyell syndrome). J Am Acad Dermatol. 1990;23(6 Pt 1):1039–58.

    Article  CAS  PubMed  Google Scholar 

  18. Schopf E, Stuhmer A, Rzany B, Victor N, Zentgraf R, Kapp JF. Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany. Arch Dermatol. 1991;127(6):839–42.

    Article  CAS  PubMed  Google Scholar 

  19. • Frey N, Jossi J, Bodmer M, Bircher A, Jick SS, Meier CR, et al. The epidemiology of Stevens-Johnson syndrome and toxic epidermal necrolysis in the UK. J Invest Dermatol. 2017;137(6):1240–7. https://doi.org/10.1016/j.jid.2017.01.031This large obersvational study of over 500 patients from the UK calculated an incidence of 5.76 SJS/TEN cases per million person-years between 1995 and 2013. They found black and Aisian patients to be at 2-fold risk. They observed increased odds for patients with epilepsy and gout who were taking a antiepileptics or allopurinol. They also observed assosciations with pre-existing depresion, lupus erythematosus, pneumonia, kidney disease, and cancer.

    Article  CAS  PubMed  Google Scholar 

  20. • 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. 2016;11(11):e0165933. https://doi.org/10.1371/journal.pone.0165933This Korean population-based study obtained records of 938 SJS cases and 229 TEN cases between 2009 and 2013. They observed an incidence of 3.96–5.03 and 0.94 to 1.45 in SJS and TEN, respectively. Incidence was relatively stable for each year of the study. In hosptial mortality was 5.7% for the patients with SJS and 15.1% for the patients with TEN.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Naegele D, Sekula P, Paulmann M, Mockenhaupt M. Incidence of Stevens-Johnson syndrom/toxic epidermal necrolysis: results of 10 years from the German registry. Pharmacoepidemiol Drug Saf. 2017;26:3.

    Google Scholar 

  22. • 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. https://doi.org/10.1016/j.jid.2016.03.023This US cohort consisted of 2591 patients with SJS, 502 with SJS/TEN overlap, and 564 with TEN from a nationwide inpatient sample between 2009 and 2012. The estimated incidences were 9.2, 1.6, and 1.9 per million adults per year, respectively. There was increased odd for Asian (OR 3.27) and black (OR 2.01) patients. Mean adjusted mortality was 4.8% for SJS, 19.4% for overlap, and 14.8% for TEN.

    Article  CAS  PubMed  Google Scholar 

  23. • Micheletti RG, Chiesa-Fuxench Z, Noe MH, Stephen S, Aleshin M, Agarwal A, et al. Stevens-Johnson syndrome/toxic epidermal necrolysis: a multicenter retrospective study of 377 adult patients from the United States. J Invest Dermatol. 2018;138(11):2315–21. https://doi.org/10.1016/j.jid.2018.04.027This multi-center retrospective study of 377 patients with SJS/TEN positviely identified a medications as the cause for 89.7% of patients, most often trimethoprim/sulfamethoxazole (26.3%). Most patients were managed in the intensive care or burn unit and most received pharmacologic therapy compared with supportive care alone. The in-hospital mortality was lower (54 deaths) than predicted by SCORTEN (78 deaths). Standardized mortality ratio (0.52) was lowest for patients receiving combination IVIg and corticosteroids.

    Article  CAS  PubMed  Google Scholar 

  24. 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. https://doi.org/10.1111/j.1365-2133.2012.10965.x.

    Article  CAS  PubMed  Google Scholar 

  25. Sekula P, Dunant A, Mockenhaupt 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. https://doi.org/10.1038/jid.2012.510.

    Article  CAS  PubMed  Google Scholar 

  26. 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 Invest Dermatol. 2006;126(2):272–6. https://doi.org/10.1038/sj.jid.5700068.

    Article  CAS  PubMed  Google Scholar 

  27. • Noe MH, Rosenbach M, Hubbard RA, Mostaghimi A, Cardones AR, Chen JK, et al. Development and validation of a risk prediction model for in-hospital mortality among patients with Stevens-Johnson syndrome/toxic epidermal ncrolysis—ABCD-10Development and validation of a risk prediction model for in-hospital mortality of patients with SJS/TENDevelopment and validation of a risk prediction model for in-hospital mortality of patients with SJS/TEN. JAMA Dermatol. 2019;155(4):448–54. https://doi.org/10.1001/jamadermatol.2018.5605This study utilized a multicenter cohort of 370 patients with SJS/TEN to derive a new risk prediction model called the ABCD-10. The new model give one point for age over 50 years, 10% or greater body surface area of epidermal detachment, and serum bicarbonate less than 20 mmol/L. Two points are given to patients with active cancer status. Three points are given for a history of dialysis within one year of admission. The ABCD-10 model showed good discrimination (AUC 0.816,p= 0.03) but was not significantly different from the SCORTEN (AUC 0.827).

    Article  PubMed  Google Scholar 

  28. Scott-Lang V, Tidman M, McKay D. Toxic epidermal necrolysis in a child successfully treated with infliximab. Pediatr Dermatol. 2014;31(4):532–4. https://doi.org/10.1111/pde.12029.

    Article  PubMed  Google Scholar 

  29. Aires DJ, Fraga G, Korentager R, Richie CP, Aggarwal S, Wick J, et al. Early treatment with nonsucrose intravenous immunoglobulin in a burn unit reduces toxic epidermal necrolysis mortality. J Drugs Dermatol. 2013;12(6):679–84.

    CAS  PubMed  Google Scholar 

  30. • Nizamoglu M, Ward JA, Frew Q, Gerrish H, Martin N, Shaw A, et al. Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal necrolysis: a regional burns centre experience. Burns. 2018;44(3):603–11. https://doi.org/10.1016/j.burns.2017.09.015This retrospective review of 42 patients with TEN or SJS/TEN overlap who were managed in a burn service over a total of 12 years had a total of 4 deaths compared with 16 predicted by SCORTEN. Investigators concluded that the management in a burn service with aggressive wound care involving debridement and synthetic and biologic dressing seems to have a mortality benefit.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang AJ, Nygaard RM, Endorf FW, Hylwa SA. Stevens-Johnson syndrome and toxic epidermal necrolysis: retrospective review of 10-year experience. Int J Dermatol. https://doi.org/10.1111/ijd.14409.

    Article  CAS  PubMed  Google Scholar 

  32. • Creamer D, Walsh SA, Dziewulski P, Exton LS, Lee HY, Dart JK, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol. 2016;174(6):1194–227. https://doi.org/10.1111/bjd.14530These 2016 guidelines were established to help providers in the management of SJS/TEN. These evidence-based recommendations are graded based on strength of the supporting research and include management of initial presentation, supportive care, and adjuvant therapy.

    Article  CAS  PubMed  Google Scholar 

  33. • McPherson T, Exton LS, Biswas S, Creamer D, Dziewulski P, Newell L, et al. Br J Dermatol. 2018. https://doi.org/10.1111/bjd.17841These 2018 guidelines from the British Association of Dermatologists provide up to date, evidence-based recommendations on the diagnosis and management of SJS/TEN in children (0–12 years) and young people (13–17 years). Their recommendations focus primarily on the acute phase of the disease. They appraise all relevant literature, focusing on recent developments and address practical clinical questions as well as areas of uncertainty.

    Article  CAS  PubMed  Google Scholar 

  34. • Gupta LK, Martin AM, Agarwal N, D’Souza P, Das S, Kumar R, et al. Guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis: an Indian perspective. Indian J Dermatol Venereol Leprol. 2016;82(6):603–25. https://doi.org/10.4103/0378-6323.191134The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) prepared these guidelines on management of SJS/TEN. Their recommendations include prompt withdrawal of the culprint drug, meticulous supportive care, and judicious and early initiation of moderate to high doses of oral or parenteral corticosteroids. Cyclosporine use was also recommended either alone or in combination with corticosteroids. A multidisciplinary approach to the management of these patients is recommended as helpful.

    Article  PubMed  Google Scholar 

  35. • Schneider JA, Cohen PR. Stevens-Johnson syndrome and toxic epidermal necrolysis: a concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Adv Ther. 2017;34(6):1235–44. https://doi.org/10.1007/s12325-017-0530-yThis review serves to concisely and comprehensively summarize therapeutic interventions for SJS/TEN. They emphasize supportive care as the mainstay for treatment of these patients. They recommend a case-by-case evaluation of patients for adjuvant therapies, as a standardized management approach for these medications is not yet clear based on current data.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. • 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 This study is on a consecutive sample of 113 patients with SJS/TEN. After adjusting for confounding variables, the study showed that prompt withdrawal of causative drugs was associated with decreased mortality. The authors’ recommendation is thus to promptly withdraw causative drugs, especially when blisters or erosions appear.

    Article  CAS  PubMed  Google Scholar 

  37. • Yamane Y, Matsukura S, Watanabe Y, Yamaguchi Y, Nakamura K, Kambara T, et al. Retrospective analysis of Stevens-Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients--treatment and outcome. Allergol Int. 2016;65(1):74–81. https://doi.org/10.1016/j.alit.2015.09.001This is a retrospective analysis of 52 cases of SJS and 35 cases of TEN, evaluating treatment and outcome. The study showed that treatment with steroid pulse therapy in combination with plasmapheresis and/or immunoglobulin therapy seems to have contributed to prognostic improvement in SJS/TEN.

    Article  CAS  PubMed  Google Scholar 

  38. • Castillo B, Vera N, Ortega-Loayza AG, Seminario-Vidal L. Wound care for Stevens-Johnson syndrome and toxic epidermal necrolysis. J Am Acad Dermatol. 2018;79(4):764–7 e1. https://doi.org/10.1016/j.jaad.2018.03.032This article is a literature review of SJS/TEN wound care, with the aim to assess the effets of dressing used in wound care and present evidence -based recommendations to assist clinicians in the best approach to wound care. The authors concluded that modern dressings should be part of standard therapy because of less frequent changes and improved patient comfort.

    Article  PubMed  Google Scholar 

  39. • Rogers AD, Blackport E, Cartotto R. The use of Biobrane((R)) for wound coverage in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. Burns. 2017;43(7):1464–72. https://doi.org/10.1016/j.burns.2017.03.016This is a retrospective review of 42 patients with SJS/TEN, where Biobrane was applied in 24 cases. The conclusion was that Biobrane was applied to SJS/TEN patients with more extensive epidermal detachment, but had no significant complications and generallly facilitated epidermal healing at a rate not significantly different from dressing-only treated subjects.

    Article  PubMed  Google Scholar 

  40. • Spies M, Sanford AP, Aili Low JF, Wolf SE, Herndon DN. Treatment of extensive toxic epidermal necrolysis in children. Pediatrics. 2001;108(5):1162–8 This is case series studying treatment of SJS/TEN in 15 patients. TEN is a rare disease in patients, and the study found that it was successfully managed in a burn center environment, using early debridement and wound coverage with allograft skin as a biological dressing. The management was unchanged in the past 2 decades, indicating an additional need for information and education about the disease.

    Article  CAS  PubMed  Google Scholar 

  41. • Lee HY. Wound management strategies in Stevens-Johnson syndrome/toxic epidermal necrolysis: an unmet need. J Am Acad Dermatol. 2018;79(4):e87–e8. https://doi.org/10.1016/j.jaad.2018.05.1258This brief letter describes the use of conservative versus surgical approaches for wound care in SJS/TEN. It describes side effects of surgical approaches, including postinflammatory hyperpigmentation.

    Article  PubMed  Google Scholar 

  42. Dorafshar AH, Dickie SR, Cohn AB, Aycock 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. https://doi.org/10.1097/PRS.0b013e3181773d5d.

    Article  CAS  PubMed  Google Scholar 

  43. Mayes T, Gottschlich M, Khoury J, Warner P, Kagan R. Energy requirements of pediatric patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Nutr Clin Pract. 2008;23(5):547–50. https://doi.org/10.1177/0884533608323434.

    Article  PubMed  Google Scholar 

  44. • Koh HK, Chai ZT, Tay HW, Fook-Chong S, Choo KJ, Oh CC, et al. Risk factors and diagnostic markers of bacteraemia in Stevens-Johnson syndrome and toxic epidermal necrolysis: a cohort study of 176 patients. J Am Acad Dermatol. 2019. https://doi.org/10.1016/j.jaad.2019.05.096This single-center retrospective cohort study of 176 patients with SJS/TEN found that 29.5% of patients had bacteremia, which was associated with increased mortality, lonter hosptial stay and higher ICU admission. Isolated included Acinetobacter baumannii (27.7%) and Staphylococcus aureus (21.4%). Other clinical factors that were predictive of bacteraemia include: hemoglobin less than or equal to 10g/dL, existing cardiovascular disease, and body surface area greater than 9%. Hypothermia and elevated pro-calcitonin were predictive of blood culture positivity.

    Article  PubMed  Google Scholar 

  45. 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 Rehabil. 2002;23(2):87–96.

    Article  CAS  PubMed  Google Scholar 

  46. Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol. 2013;69(2):187 e1–16; quiz 203-4. https://doi.org/10.1016/j.jaad.2013.05.002.

    Article  CAS  Google Scholar 

  47. Meneux E, Paniel BJ, Pouget F, Revuz J, Roujeau JC, Wolkenstein P. Vulvovaginal sequelae in toxic epidermal necrolysis. J Reprod Med. 1997;42(3):153–6.

    CAS  PubMed  Google Scholar 

  48. 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.

    PubMed  PubMed Central  Google Scholar 

  49. 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.

    PubMed  PubMed Central  Google Scholar 

  50. Chang YS, Huang FC, Tseng SH, Hsu CK, Ho CL, Sheu HM. Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management. Cornea. 2007;26(2):123–9. https://doi.org/10.1097/ICO.0b013e31802eb264.

    Article  PubMed  Google Scholar 

  51. Yip LW, Thong BY, Lim J, Tan AW, Wong HB, Handa S, et al. Ocular manifestations and complications of Stevens–Johnson syndrome and toxic epidermal necrolysis: an Asian series*. Allergy. 2007;62(5):527–31. https://doi.org/10.1111/j.1398-9995.2006.01295.x.

    Article  CAS  PubMed  Google Scholar 

  52. Morales ME, Purdue GF, Verity SM, Arnoldo BD, Blomquist PH. Ophthalmic manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis and relation to SCORTEN. Am J Ophthalmol. 2010;150(4):505–10.e1. https://doi.org/10.1016/j.ajo.2010.04.026.

    Article  PubMed  Google Scholar 

  53. Gueudry J, Roujeau J-C, Binaghi M, Soubrane G, Muraine M. Risk factors for the development of ocular complications of Stevens-Johnson syndrome and toxic epidermal necrolysis. JAMA Dermatol. 2009;145(2):157–62. https://doi.org/10.1001/archdermatol.2009.540.

    Article  Google Scholar 

  54. Van Zyl L, Carrara H, Lecuona K. Prevalence of chronic ocular complications in Stevens-Johnson syndrome and toxic epidermal necrolysis. Middle East Afr J Ophthalmol. 2014;21(4):332–5. https://doi.org/10.4103/0974-9233.142272.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Sotozono C, Ueta M, Nakatani E, Kitami A, Watanabe H, Sueki H, et al. Predictive factors associated with acute ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis. Am J Ophthalmol. 2015;160(2):228–37.e2. https://doi.org/10.1016/j.ajo.2015.05.002.

    Article  PubMed  Google Scholar 

  56. 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. https://doi.org/10.1016/j.ophtha.2015.10.027.

    Article  PubMed  Google Scholar 

  57. Gregory DG. Treatment of acute Stevens–Johnson syndrome and toxic epidermal necrolysis using amniotic membrane: a review of 10 consecutive cases. Ophthalmology. 2011;118(5):908–14. https://doi.org/10.1016/j.ophtha.2011.01.046.

    Article  PubMed  Google Scholar 

  58. Kohanim S, Palioura S, Saeed HN, Akpek EK, Amescua G, Basu S, et al. Acute and chronic ophthalmic involvement in Stevens-Johnson syndrome/toxic epidermal necrolysis – a comprehensive review and guide to therapy. II Ophthalmic Disease. Ocular Surf. 2016;14(2):168–88. https://doi.org/10.1016/j.jtos.2016.02.001.

    Article  Google Scholar 

  59. Dodiuk-Gad RP, Olteanu C, Feinstein A, Hashimoto R, Alhusayen R, Whyte-Croasdaile S, et al. Major psychological complications and decreased health-related quality of life among survivors of Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2016;175(2):422–4. https://doi.org/10.1111/bjd.14799.

    Article  CAS  PubMed  Google Scholar 

  60. Patmanidis K, Sidiras A, Dolianitis K, Simelidis D, Solomonidis C, Gaitanis G, et al. Combination of infliximab and high-dose intravenous immunoglobulin for toxic epidermal necrolysis: successful treatment of an elderly patient. Case Rep Dermatol Med. 2012;2012:915314. https://doi.org/10.1155/2012/915314.

    Article  PubMed  PubMed Central  Google Scholar 

  61. 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.

    Article  CAS  PubMed  Google Scholar 

  62. Hunger RE, Hunziker T, Buettiker U, Braathen LR, Yawalkar N. Rapid resolution of toxic epidermal necrolysis with anti-TNF-α treatment. J Allergy Clin Immunol. 2005;116(4):923–4. https://doi.org/10.1016/j.jaci.2005.06.029.

    Article  CAS  PubMed  Google Scholar 

  63. Hirahara K, Kano Y, Sato Y, Horie C, Okazaki A, Ishida T, et al. Methylprednisolone pulse therapy for Stevens-Johnson syndrome/toxic epidermal necrolysis: clinical evaluation and analysis of biomarkers. J Am Acad Dermatol. 2013;69(3):496–8. https://doi.org/10.1016/j.jaad.2013.04.007.

    Article  CAS  PubMed  Google Scholar 

  64. • Zimmermann 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. https://doi.org/10.1001/jamadermatol.2016.5668This Ssystemic review of 96 studies and 3248 patients with SJS/TEN provides a comprehensive review of systemic immunomodulating therapies compared to with supportive care. Mortality benefits expressed as OR were found for cyclosporine and glucocoriticoids in unstratified models.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Aoki Y, Kao PN. Cyclosporin A-sensitive calcium signaling represses NFkappaB activation in human bronchial epithelial cells and enhances NFkappaB activation in Jurkat T-cells. Biochem Biophys Res Commun. 1997;234(2):424–31. https://doi.org/10.1006/bbrc.1997.6658.

    Article  CAS  PubMed  Google Scholar 

  66. Roujeau JC, Bastuji-Garin S. Systematic review of treatments for Stevens-Johnson syndrome and toxic epidermal necrolysis using the SCORTEN score as a tool for evaluating mortality. Ther Adv Drug Saf. 2011;2(3):87–94. https://doi.org/10.1177/2042098611404094.

    Article  PubMed  PubMed Central  Google Scholar 

  67. 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. https://doi.org/10.1016/j.jaad.2014.04.044.

    Article  CAS  PubMed  Google Scholar 

  68. • Wang CW, Yang LY, Chen CB, Ho HC, Hung SI, Yang CH, et al. Randomized, controlled trial of TNF-alpha antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Invest. 2018;128(3):985–96. https://doi.org/10.1172/JCI93349This randomized, controlled trial of 96 patients with SJS/TEN found that Eetanercept decreased the SCORTEN-predicted mortality rate compared to with corticosteroids. Investigators also observed a significantly reduced skin-healing time in the moderate-to-severely affected patients (p = 0.010). Enteracept groups had reduced granulysin in blister fluids and plasma and an increased Treg cell population (p = 0.002) - —providing insights on the potential mechanism-of-action.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Shah R, Chen ST, Kroshinsky D. Use of cyclosporine for the treatment of Steven Johnson syndrome/ toxic epidermal necrolysis. J Am Acad Dermatol. 2019. https://doi.org/10.1016/j.jaad.2018.09.063.

  70. • 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. https://doi.org/10.1016/j.jcrc.2017.07.002This prospective observational study evaulated the response of 28 patients to plasmapheresis tehrapy after admission for SJS/TEN. Severity of disease and efficacy of treatments were evaluated by the severity-of-illness score for TEN. Results indicated that plasmapheresis may be superior to conventional therapy, and that plasmapheresis alone may be more beneficial than combination therapies.

    Article  PubMed  Google Scholar 

  71. Morici MV, Galen WK, Shetty AK, Lebouef RP, Gouri TP, Cowan GS, et al. Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome. J Rheumatol. 2000;27(10):2494–7.

    CAS  PubMed  Google Scholar 

  72. Valeyrie-Allanore L, Wolkenstein P, Brochard L, Ortonne N, Maitre B, Revuz J, et al. Open trial of ciclosporin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis. Br J Dermatol. 2010;163(4):847–53. https://doi.org/10.1111/j.1365-2133.2010.09863.x.

    Article  CAS  PubMed  Google Scholar 

  73. Furubacke A, Berlin G, Anderson C, Sjoberg F. Lack of significant treatment effect of plasma exchange in the treatment of drug-induced toxic epidermal necrolysis? Intensive Care Med. 1999;25(11):1307–10.

    Article  CAS  PubMed  Google Scholar 

  74. 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. https://doi.org/10.1111/j.1346-8138.2010.01154.x.

    Article  PubMed  Google Scholar 

  75. 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. https://doi.org/10.1002/jca.21213.

    Article  PubMed  Google Scholar 

  76. Barron SJ, Del Vecchio MT, Aronoff SC. Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with meta-regression of observational studies. Int J Dermatol. 2015;54(1):108–15. https://doi.org/10.1111/ijd.12423.

    Article  PubMed  Google Scholar 

  77. Del Pozzo-Magana BR, Lazo-Langner A, Carleton B, Castro-Pastrana LI, Rieder MJ. 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.

    PubMed  Google Scholar 

  78. Michaels B. The role of systemic corticosteroid therapy in erythema multiforme major and Stevens-Johnson syndrome: a review of past and current opinions. J Clin Aesthet Dermatol. 2009;2(3):51–5.

    PubMed  PubMed Central  Google Scholar 

  79. Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. 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. https://doi.org/10.1016/j.jaad.2007.08.039.

    Article  PubMed  Google Scholar 

  80. • Ng QX, De Deyn M, Venkatanarayanan N, Ho CYX, Yeo WS. A meta-analysis of cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis. J Inflamm Res. 2018;11:135–42. https://doi.org/10.2147/jir.S160964This meta-analysis of 9 studies demonstrated significant mortality reduction with a standardized mortality ratio of 0.320 (p = 0.002). Cyclosporine was well tolerated with few adverse efects. There was observed publication bias (p = 0.0467).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. • Chen Y-T, Hsu C-Y, Chien Y-N, Lee W-R, Huang Y-C. Efficacy of cyclosporine for the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: systemic review and meta-analysis. Dermatol Sin. 2017;35(3):131–7. https://doi.org/10.1016/j.dsi.2017.04.004This systemic review of 7 studies compared mortality rates for patients receiving cyclosporine vs those receiving IVIg (4 studies), corticosteroids (1 study), combination therapy consisting of steroids and cyclophosphamiden 1 study), and supportive therapy (2 studies). Cyclosporine had significantly higher mortality benefit compared to with all other groups.

    Article  Google Scholar 

  82. Kirchhof MG, Miliszewski MA, Sikora S, Papp A, Dutz JP. Retrospective review of Stevens-Johnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine. J Am Acad Dermatol. 2014;71(5):941–7. https://doi.org/10.1016/j.jaad.2014.07.016.

    Article  CAS  PubMed  Google Scholar 

  83. • Gonzalez-Herrada C, Rodriguez-Martin S, Cachafeiro L, Lerma V, Gonzalez O, Lorente 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. https://doi.org/10.1016/j.jid.2017.05.022This retrospective study compared the outcomes at two different burn units in Madrid over the period from 2001 to 2015. On unit utilized cyclosporine while the tother used non-cyclosporine regimens. Investigators also observed outcomes for a case series of 49 patients who were treated in other regions of Madrid and an additional five case series. Investigators found that cyclosporine consistently reduced mortality.

    Article  CAS  PubMed  Google Scholar 

  84. Reese D, Henning JS, Rockers K, Ladd D, Gilson R. Cyclosporine for SJS/TEN: a case series and review of the literature. Cutis. 2011;87(1):24–9.

    PubMed  Google Scholar 

  85. • St John J, Ratushny V, Liu KJ, Bach DQ, Badri O, Gracey LE, et al. Successful use of cyclosporin A for Stevens-Johnson syndrome and toxic epidermal necrolysis in three children. Pediatr Dermatol. 2017;34(5):540–6. https://doi.org/10.1111/pde.13236This case series explored the efficacy of Ccyclosporine A in the treatment of SJS/TEN in three pediatric patients. Treatment with Ccyclosporine A for these patients was successful, with an average of 2.2 days to cessation of disease (range 1.5–-3 days) and 13 days to re-epithelialization (range 10–-15 days). Average hospital stay was 11.7 days (range 4–-19 days).

    Article  PubMed  Google Scholar 

  86. • Poizeau F, Gaudin O, Le Cleach L, Duong TA, Hua C, Hotz C, et al. Cyclosporine for epidermal necrolysis: absence of beneficial effect in a retrospective cohort of 174 patients-exposed/unexposed and propensity score-matched analyses. J Invest Dermatol. 2018;138(6):1293–300. https://doi.org/10.1016/j.jid.2017.12.034This retrospective review of 174 patients with SJS/TEN from 2005–-2016 found no statistically significant beneficial effect on mortality, duration of progression and re-epithelialization status at day 5 or 10 for non-mucosal and mucosal skin, respectively.

    Article  CAS  PubMed  Google Scholar 

  87. 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):686–92. https://doi.org/10.4103/0378-6323.116738.

    Article  CAS  PubMed  Google Scholar 

  88. • Curtis JA, Christensen LC, Paine AR, Collins Brummer G, Summers EM, Cochran AL, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis treatments: an Internet survey. J Am Acad Dermatol. 2016;74(2):379–80. https://doi.org/10.1016/j.jaad.2015.08.033The investigators of this study surveyed 290 providers (of 1927 providers sent the survey link) who had treated a patient with SJS/TEN in the past year. The survey showed that the majority of providers don’t use systemic steroids for any classification of SJS/TEN. Most preferred IVIG in SJS/TEN overlap or TEN, but some did not use IVIG in SJS cases. Cyclosporine was the most frequently used alternative therapy. Most providers did not debride the skin and preferred petrolatum-impregnated gauze and nonadherent dressings with nanocrystalline silver.

    Article  PubMed  Google Scholar 

  89. Trent J, Halem M, French LE, Kerdel F. Toxic epidermal necrolysis and intravenous immunoglobulin: a review. Semin Cutan Med Surg. 2006;25(2):91–3. https://doi.org/10.1016/j.sder.2006.04.004.

    Article  CAS  PubMed  Google Scholar 

  90. Prins C, Vittorio C, Padilla RS, Hunziker T, Itin P, Forster J, et al. Effect of high-dose intravenous immunoglobulin therapy in Stevens-Johnson syndrome: a retrospective, multicenter study. Dermatology. 2003;207(1):96–9. https://doi.org/10.1159/000070957.

    Article  CAS  PubMed  Google Scholar 

  91. Metry DW, Jung P, Levy ML. Use of intravenous immunoglobulin in children with Stevens-Johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature. Pediatrics. 2003;112(6 Pt 1):1430–6. https://doi.org/10.1542/peds.112.6.1430.

    Article  PubMed  Google Scholar 

  92. Jagadeesan S, Sobhanakumari K, Sadanandan SM, Ravindran S, Divakaran MV, Skaria L, et al. Low dose intravenous immunoglobulins and steroids in toxic epidermal necrolysis: a prospective comparative open-labelled study of 36 cases. Indian J Dermatol Venereol Leprol. 2013;79(4):506–11. https://doi.org/10.4103/0378-6323.113080.

    Article  PubMed  Google Scholar 

  93. 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. https://doi.org/10.1097/BCR.0b013e318254d2ec.

    Article  PubMed  Google Scholar 

  94. • Ye LP, Zhang C, Zhu QX. The effect of intravenous immunoglobulin combined with corticosteroid on the progression of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis. PLoS One. 2016;11(11):e0167120. https://doi.org/10.1371/journal.pone.0167120This meta-analysis of 26 studies including 628 patients evaluated the efficacy of IVIG combined with corticosteroids on the progression of SJS/TEN. They found that this combination therapy could reduce recovery time, especially in Asian patients. However, its impact on reducing mortality was not significant.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zarate-Correa LC, Carrillo-Gomez DC, Ramirez-Escobar AF, Serrano-Reyes C. Toxic epidermal necrolysis successfully treated with infliximab. J Investig Allergol Clin Immunol. 2013;23(1):61–3.

    CAS  PubMed  Google Scholar 

  96. Wolkenstein P, Latarjet J, Roujeau JC, Duguet C, Boudeau S, Vaillant L, et al. Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis. Lancet. 1998;352(9140):1586–9. https://doi.org/10.1016/S0140-6736(98)02197-7.

    Article  CAS  PubMed  Google Scholar 

  97. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol. 2000;115(2):149–53. https://doi.org/10.1046/j.1523-1747.2000.00061.x.

    Article  CAS  PubMed  Google Scholar 

  98. • Morita K, Matsui H, Michihata N, Fushimi K, Yasunaga H. Association of early systemic corticosteroid therapy with mortality in patients with Stevens-Johnson syndrome or toxic epidermal necrolysis: a retrospective cohort study using a nationwide claims database. Am J Clin Dermatol. 2019;30:30 This large retrospective cohort study of 1846 patients evaluated the association of early systemic corticosteroid therapy with mortality in patients with SJS/TEN. Their results indicated that eary systemic corticosteroid therapy was not associated with lower in-hospital mortality.

    Google Scholar 

  99. • 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. https://doi.org/10.1111/ijd.13379This study retrospective analysis of 70 patients with SJS/TEN evaluated a response to treatment with corticosteroids. The study supports the use of corticosteroids in SJS/TEN as it was associated with lower mortality rate and serum albumin levels. Investigators conclude that corticosteroids should be administered in accordance with disease severity, age, underlying diseaes, serum albumin level, and concurrent antimicrobial therapy.

    Article  CAS  PubMed  Google Scholar 

  100. Roongpisuthipong W, Prompongsa S, Klangjareonchai T. Retrospective analysis of corticosteroid treatment in Stevens-Johnson syndrome and/or toxic epidermal necrolysis over a period of 10 years in Vajira Hospital, Navamindradhiraj University, Bangkok. Dermatol Res Pract. 2014;2014:237821. https://doi.org/10.1155/2014/237821.

    Article  PubMed  PubMed Central  Google Scholar 

  101. • Lee HY, Fook-Chong S, Koh HY, Thirumoorthy T, Pang SM. Cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis: retrospective analysis of a cohort treated in a specialized referral center. J Am Acad Dermatol. 2017;76(1):106–13. https://doi.org/10.1016/j.jaad.2016.07.048This retrospective analysis of 44 patients sought to evaluate the impact of cyclosporine on hospital mortality in patients with SJS/TEN. 24 patients received cyclosporine and 20 were treated supportively. SCORTEN predicted 7.5 deaths in the cyclosporine group, and 3 were observed. SCORTEN predicted 5.9 deaths in the supportive group, and 6 were observed. Thus, the standardized mortality ratio of SJS/TEN treated with cyclosporine was 0.42. They concluded that the use of cyclosporine may improve mortality in SJS/TEN.

    Article  CAS  PubMed  Google Scholar 

  102. • 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. https://doi.org/10.1111/bjd.12607This retrospective cohort study of 42 patients sought to investigate the association between type of immune modulatory treatment administered and prognosis of patient. They found apparent reduced mortality in patients treated with combination IVIG and corticosteroid therapy.

    Article  CAS  PubMed  Google Scholar 

  103. Chan L, Cook DK. A 10-year retrospective cohort study of the management of toxic epidermal necrolysis and Stevens-Johnson syndrome in a New South Wales state referral hospital from 2006 to 2016. Int J Dermatol. 2019;25:25.

    Google Scholar 

  104. Chen J, Wang B, Zeng Y, Xu H. High-dose intravenous immunoglobulins in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese patients: a retrospective study of 82 cases. Eur J Dermatol. 2010;20(6):743–7. https://doi.org/10.1684/ejd.2010.1077.

    Article  CAS  PubMed  Google Scholar 

  105. Paquet P, Jennes S, Rousseau AF, Libon F, Delvenne P, Piérard GE. Effect of N-acetylcysteine combined with infliximab on toxic epidermal necrolysis. A proof-of-concept study. Burns. 2014;40(8):1707–12. https://doi.org/10.1016/j.burns.2014.01.027.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Texas Southwestern Medical School, Dallas, TX, 75390, USA

    Jennifer L. Coias & Laila F. Abbas

  2. Department of Dermatology, Duke University, Durham, NC, 27710, USA

    Adela R. Cardones

  3. Dermatology Service, Department of Medicine, Durham VA Medical Center, Durham, NC, 27705, USA

    Adela R. Cardones

Authors
  1. Jennifer L. Coias
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laila F. Abbas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adela R. Cardones
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adela R. Cardones.

Ethics declarations

Conflict of Interest

The authors declare no conflict of interest.

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Hospital-Based Dermatology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Coias, J.L., Abbas, L.F. & Cardones, A.R. Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: a Review and Update. Curr Derm Rep 8, 219–233 (2019). https://doi.org/10.1007/s13671-019-00275-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13671-019-00275-0

Keywords

Search

Navigation