Dermatologic Emergencies

dermatology-emergencieskapak-1-0-25

Eythema Multiforme Major (Stevens-Johnson Syndrome)

Gülşah SABIR DEMİR
Hitit University Faculty of Medicine, Çorum Erol Olçok Training and Research Hospital, Department of Emergency Medicine, Çorum, Türkiye

Ahmet Emre AY
Ankara Bilkent City Hospital, Clinic of Emergency Medicine, Ankara, Türkiye

Sabır Demir G, Ay AE. Erythema multiforme major (Stevens-Johnson syndrome). In: Oğuztürk H, Görmeli Kurt N, eds. Dermatologic Emergencies. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.85-90.

ABSTRACT

Stevens-Johnson Syndrome (SJS) is a severe, acute-onset mucocutaneous disorder, typically triggered by drug exposure. It is characterized by the formation of vesicles, bullae, and mucosal erosions. Medications are the most common causative agents, though infectious agents, autoimmune diseases, and malignancies can also contribute to its development. There is no specific therapy for SJS, but immediate discontinuation of the offending drug, along with appropriate supportive care, remains the cornerstone of treatment. The condition is associated with a significant mortality rate, particularly in patients with additional high-risk factors.

Keywords: Erythema; erythema multiforme; Stevens-Johnson syndrome

Referanslar

  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. [Crossref]  [PubMed]
  2. Sassolas B, Haddad C, Mockenhaupt M, Dunant A, liss Y, Bork K, et al. AlDEN, an algorithm for assessment of drug causality in StevensJohnson Syndrome and toxic epidermal necrolysis: comparison with casecontrol analysis. Clin pharmacol Ther. 2010;88(1):60-8. [Crossref]  [PubMed]
  3. 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. [Crossref]  [PubMed]
  4. Ingen-Housz-Oro S, Duong TA, Bensaid B, Bellon N, de prost N, lu D, et al. Epidermal nekroliz Fransız ulusal tanı ve bakım protokolü (pNDS; protocole national de diagnostic et de soins). Orphanet J Nadir Dis. 2018;13:56. [Crossref]  [PubMed]  [PMC]
  5. 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. [Crossref]  [PubMed]
  6. 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. [Crossref]  [PubMed]
  7. Mockenhaupt M, Viboud C, Dunant A, Naldi l, Halevy S, Bouwes Bavinck JN, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128(1):35-44. [Crossref]  [PubMed]
  8. Roujeau JC, Kelly Jp, Naldi l, Rzany B, Stern RS, Anderson T, et al. Medication Use and the Risk of Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. N Engl J Med. 1995;333(24):1600. [Crossref]  [PubMed]
  9. Maloney NJ, Ravi V, Cheng K, Bach DQ, Worswick S. Stevens-Johnson syndrome and toxic epidermal necrolysis-like reactions to checkpoint inhibitors: a systematic review. Int J Dermatol. 2020;59(6):e183-e8. [Crossref]  [PubMed]
  10. Saw S, lee HY, Ng QS. pembrolizumab-induced Stevens-Johnson syndrome in non-melanoma patients. Eur J Cancer. 2017;81:237-9. [Crossref]  [PubMed]
  11. Liew YCC, Choo KJl, Oh CC, pang SM, Yeo YW, lee HY. Mycoplasma-induced Stevens-Johnson syndrome/toxic epidermal necrolysis: Case-control analysis of a cohort managed in a specialized center. J Am Acad Dermatol. 2022;86(4):811-7. [Crossref]  [PubMed]
  12. Kamijima M, Hisanaga N, Wang H, Nakajima T. Occupational trichloroethylene exposure as a cause of idiosyncratic generalized skin disorders and accompanying hepatitis similar to drug hypersensitivities. Int Arch Occup Environ Health. 2007;80(5):357-70. [Crossref]  [PubMed]
  13. Lim JH, Cho SH, lee JD, Kim HS. A Case of Stevens-Johnson Syndrome probably Induced by Herbal Medicine. Ann Dermatol. 2018;30(4):481-3. [Crossref]  [PubMed]  [PMC]
  14. Irani C, Haddad F, Maalouly G, Nemnoum R. Curcumin in stevens-johnsons syndrome: culprit or bystander? World Allergy Organ J. 2009;2(4):59-60. [Crossref]  [PubMed]  [PMC]
  15. Chaby G, Maldini C, Haddad C, lebrus-Vignes B, Hemery F, Ingen-HouszOro S, et al. Incidence of and mortality from epidermal necrolysis (StevensJohnson syndrome/toxic epidermal necrolysis) in France during 2003-16: a four‐source capture-recapture estimate. Br J Dermatol. 2020;182(3):618-24. [Crossref]  [PubMed]
  16. 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. [Crossref]  [PubMed]
  17. Gillis NK, Hicks JK, Bell GC, Daly AJ, Kanetsky pA, Mcleod Hl. Incidence and Triggers of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a large Cancer patient Cohort. J Invest Dermatol. 2017;137(9):2021-3. [Crossref]  [PubMed]  [PMC]
  18. Fagot Jp, Mockenhaupt M, Bouwes-Bavinck JN, Naldi l, Viboud C, Roujeau JC; EuroSCAR Study Group. Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. AIDS. 2001;15(14):1843-8. [Crossref]  [PubMed]
  19. Chimbetete T, Buck C, Choshi p, Selim R, pedretti S, Divito SJ, et al. HIV-Associated Immune Dysregulation in the Skin: A Crucible for Exaggerated Inflammation and Hypersensitivity. J Invest Dermatol. 2023;143(3):362-73. [Crossref]  [PubMed]  [PMC]
  20. Yang C, Mosam A, Mankahla A, Dlova N, Saavedra A. HIV infection predisposes skin to toxic epidermal necrolysis via depletion of skin-directed CD4⁺ T cells. J Am Acad Dermatol. 2014;70(6):1096-102. [Crossref]  [PubMed]
  21. Ziemer M, Kardaun SH, liss Y, Mockenhaupt M. Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with lupus erythematosus: a descriptive study of 17 cases from a national registry and review of the literature. Br J Dermatol. 2012;166(3):575-600. [Crossref]  [PubMed]
  22. Gibson A, Deshpande p, Campbell CN, Krantz MS, Mukherjee E, Mockenhaupt M, et al. Updates on the immunopathology and genomics of severe cutaneous adverse drug reactions. J Allergy Clinical Immunol. 2023;151(2):289-300.e4 [Crossref]  [PubMed]  [PMC]
  23. 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. [Crossref]  [PubMed]
  24. Lonjou C, Borot N, Sekula p, ledger N, Thomas l, Halevy S, et al.; RegiSCAR study group. 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. [Crossref]  [PubMed]
  25. Chung WH, Chang WC, lee YS, Wu YY, Yang CH, Ho HC, et al. ; Taiwan Severe Cutaneous Adverse Reaction Consortium; Japan pharmacogenomics Data Science Consortium. Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA. 2014;312(5):525-34. [Crossref]  [PubMed]
  26. Nicoletti p, Bansal M, lefebvre C, Guarnieri p, Shen Y, pe'er I, et al. ABC transporters and the proteasome complex are implicated in susceptibility to StevensJohnson syndrome and toxic epidermal necrolysis across multiple drugs. ploS One. 2015;10(6):e0131038. [Crossref]  [PubMed]  [PMC]
  27. Lee HY, Chung WH. Toxic epidermal necrolysis: the year in review. Curr Opin Allergy Clin Immunol. 2013;13(4):330-6. [Crossref]  [PubMed]
  28. Torres MJ, Mayorga C, García JJ, Romano A, Juarez C, Blanca M. New aspects in betalactam recognition. Clin Exp Allergy. 1998;28 Suppl 4:25-8. [PubMed]
  29. 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. [Crossref]  [PubMed]
  30. Yang CW, Hung SI, Juo CG, lin Yp, Fang WH, lu IH, 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. [Crossref]  [PubMed]
  31. Ostrov DA, Grant BJ, pompeu YA, Sidney J, Harndahl M, Southwood S, et al. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. proc Natl Acad Sci U S A. 2012;109(25):9959-64. [Crossref]  [PubMed]  [PMC]
  32. Illing pT, Vivian Jp, Dudek Nl, Kostenko l, Chen Z, Bharadwaj M, et al. Immune self-reactivity triggered by drug-modified HlA-peptide repertoire. Nature. 2012;486(7404):554-8. [Crossref]  [PubMed]
  33. Takahashi R, Kano Y, Yamazaki Y, Kimishima M, Mizukawa Y, Shiohara T. Defective regulatory T cells in patients with severe drug eruptions: timing of the dysfunction is associated with the pathological phenotype and outcome. J Immunol. 2009;182(12):8071-9. [Crossref]  [PubMed]
  34. Roujeau JC, Chosidow O, Saiag p, Guillaume JC. Toxic epidermal necrolysis (lyell syndrome). J Am Acad Dermatol. 1990;23(6 pt 1):1039-58. [Crossref]  [PubMed]
  35. Duong TA, Valeyrie-Allanore l, Wolkenstein p, Chosidow O. Severe cutaneous adverse reactions to drugs. lancet. 2017;390(10106):1996-2011. Erratum in: lancet. 2017;390(10106):1948. [Crossref]  [PubMed]
  36. Lee HY, Dunant A, Sekula p, Mockenhaupt M, Wolkenstein p, Valeyrie-Allanore l, et al. The role of prior corticosteroid use on the clinical course of StevensJohnson syndrome and toxic epidermal necrolysis: a case-control analysis of patients selected from the multinational EuroSCAR and RegiSCAR studies. Br J Dermatol. 2012;167(3):555-62. [Crossref]  [PubMed]
  37. Bequignon E, Duong TA, Sbidian E, Valeyrie-Allanore l, Ingen-Housz-Oro S, Chatelin V, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: ear, nose, and throat description at acute stage and after remission. JAMA Dermatol. 2015;151(3):302-7. [Crossref]  [PubMed]
  38. 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. [Crossref]  [PubMed]
  39. Hung CC, liu WC, Kuo MC, lee CH, Hwang SJ, Chen HC. Acute renal failure and its risk factors in Stevens-Johnson syndrome and toxic epidermal necrolysis. Am J Nephrol. 2009;29(6):633-8. [Crossref]  [PubMed]
  40. Papo M, Valeyrie-Allanore l, Razazi K, Carteaux G, Wolkenstein p, Chosidow O, et al. Renal replacement therapy during Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective observational study of 238 patients. Br J Dermatol. 2017;176(5):1370-2. [Crossref]  [PubMed]
  41. de prost N, Mekontso-Dessap A, Valeyrie-Allanore l, Van Nhieu JT, Duong TA, Chosidow O, 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. [Crossref]  [PubMed]
  42. Gendreau S, Amiot A, le Baleur Y, Charpy C, Wolkenstein p, Chosidow O, et al. Gastrointestinal involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis: a retrospective case series. Br J Dermatol. 2019;180(5):1234-5. [Crossref]  [PubMed]
  43. Rzany B, Hering O, Mockenhaupt M, Schröder 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. [Crossref]  [PubMed]
  44. Côté B, Wechsler J, Bastuji-Garin S, Assier H, Revuz J, Roujeau JC. Clinicopathologic correlation in erythema multiforme and StevensJohnson syndrome. Arch Dermatol. 1995;131(11):1268-72. [Crossref]  [PubMed]
  45. de prost N, Ingen-Housz-Oro S, Duong TA, Valeyrie-Allanore l, legrand p, Wolkenstein p, 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. [Crossref]  [PubMed]
  46. Brüggen MC, le ST, Walsh S, Toussi A, de prost N, Ranki A, et al. Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus. Br J Dermatol. 2021;185(3):616-26. [Crossref]  [PubMed]
  47. Boorboor p, Vogt pM, Bechara FG, Alkandari Q, Aust M, Gohritz A, et al. Toxic epidermal necrolysis: use of Biobrane or skin coverage reduces pain, improves mobilisation and decreases infection in elderly patients. Burns. 2008;34(4):487-92. [Crossref]  [PubMed]
  48. 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. [Crossref]  [PubMed]
  49. Shiga S, Cartotto R. What are the fluid requirements in toxic epidermal necrolysis? J Burn Care Res. 2010;31(1):100-4. [Crossref]  [PubMed]
  50. Kelemen JJ 3rd, Cioffi WG Jr, Mason AD Jr, Mozingo DW, McManus WF, pruitt BA Jr. Effect of ambient temperature on metabolic rate after thermal injury. Ann Surg. 1996;223(4):406-12. [Crossref]  [PubMed]  [PMC]
  51. Valeyrie-Allanore l, Ingen-Housz-Oro S, Colin A, Thuillot D, Sigal Ml, Binhas M. prise en charge de la douleur dans le syndrome de Stevens-Johnson/lyell et les autres dermatoses bulleuses étendues [pain management in StevensJohnson syndrome, toxic epidermal necrolysis and other blistering diseases]. Ann Dermatol Venereol. 2011;138(10):694-7; quiz 692-3, 698. French. [Crossref]  [PubMed]
  52. Revuz J, penso D, Roujeau JC, Guillaume JC, payne CR, Wechsler J, et al. Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients. Arch Dermatol. 1987;123(9):1160-5. [Crossref]  [PubMed]
  53. Koh HK, Chai ZT, Tay HW, Fook-Chong S, Choo KJl, Oh CC, et al. Risk factors and diagnostic markers of bacteremia in StevensJohnson syndrome and toxic epidermal necrolysis: A cohort study of 176 patients. J Am Acad Dermatol. 2019;81(3):686-93. [Crossref]  [PubMed]
  54. 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. [Crossref]  [PubMed]
  55. Valeyrie-Allanore l, Wolkenstein p, Brochard l, Ortonne N, Maître 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. [Crossref]  [PubMed]
  56. Wang CW, Yang lY, Chen CB, Ho HC, Hung SI, Yang CH, et al.; the Taiwan Severe Cutaneous Adverse Reaction (TSCAR) Consortium. Randomized, controlled trial of TNF-α antagonist in CTl-mediated severe cutaneous adverse reactions. J Clin Invest. 2018;128(3):985-96. [PubMed]
  57. Halebian pH, Corder VJ, Madden MR, Finklestein Jl, Shires GT. Improved burn center survival of patients with toxic epidermal necrolysis managed without corticosteroids. Ann Surg. 1986;204(5):503-12. [Crossref]  [PubMed]  [PMC]
  58. Roujeau JC, Mockenhaupt M, Guillaume JC, Revuz J. New Evidence Supporting Cyclosporine Efficacy in Epidermal Necrolysis. J Invest Dermatol. 2017;137(10):2047-9. [Crossref]  [PubMed]
  59. Kelemen JJ 3rd, Cioffi WG, McManus WF, Mason AD Jr, pruitt BA Jr. Burn center care for patients with toxic epidermal necrolysis. J Am Coll Surg. 1995;180(3):273-8. [PubMed]