TOXIC EPIDERMAL NECROLYSIS (LYELL SYNDROME): CURRENT INSIGHTS INTO PATHOGENESIS, CLINICAL FEATURES, AND MANAGEMENT STRATEGIES
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.5953Keywords:
Toxic Epidermal Necrolysis, Stevens-Johnson Syndrome, Drug Hypersensitivity, SCORTEN, Keratinocyte Apoptosis, Supportive CareAbstract
Introduction and objectives: Toxic epidermal necrolysis (TEN) is a rare, life-threatening disease of the skin and mucous membranes. It is characterised by extensive desquamation of the epidermis, severe systemic involvement and a high mortality rate. Despite its rarity, it poses a significant clinical challenge due to its rapid progression and the risk of serious complications. The aim of this study was to present the current state of knowledge regarding the etiology, pathogenesis, clinical presentation and treatment strategies for TEN.
Methods: A narrative review was conducted using PubMed and Google Scholar databases. Publications from 2010 to 2026 were included.
Key findings: TEN is most often drug-induced and affects the skin and mucous membranes, with a high risk of mortality. Current evidence points to a key role for cytotoxic immune responses, particularly CD8+ T cells and granzyme B, in the pathogenesis of this disease. The cornerstone of treatment remains rapid discontinuation of the causative agent and intensive supportive care. However, immunomodulatory therapies are increasingly recognized as adjunctive treatment options.
Conclusions: Despite advances in understanding the pathogenesis of TEN, this disease is still associated with high mortality and risk of severe complications. Early diagnosis, prompt discontinuation of the causative agent, and supportive care are crucial to improving prognosis. Further research into targeted therapies and the development of uniform standards for clinical management remain essential.
References
Abtahi-Naeini, B., Pourmahdi-Boroujeni, M., Rastegarnasab, F., & Emamjomeh, A. (2024). A review on toxic epidermal necrolysis-like superficial wound lesions: Issue and challenge on 10 clinical entities. International Wound Journal, 21(12), e70117. https://doi.org/10.1111/iwj.70117
Abulatan, I. T., Ben-David, S. G., Morales-Colon, L. A., Beason, E., & Fakoya, A. O. (2023). A compilation of drug etiologies of Stevens-Johnson syndrome and toxic epidermal necrolysis. Cureus, 15(11), e48728. https://doi.org/10.7759/cureus.48728
Akgun, Z., Can, G. D., & Selver, O. B. (2025). Ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis: A review of current management and changing trends. Indian Journal of Ophthalmology, 73(12), 1711–1722. https://doi.org/10.4103/IJO.IJO_1119_25
Bordeanu-Diaconescu, E. M., Grama, S., Grosu-Bularda, A., Frunză, A., Dumitru, C. Ş., Andrei, M. C., Creangă, C. A., Neagu, T. P., & Lascăr, I. (2024). Toxic epidermal necrolysis—Clinicopathological aspects and therapeutic management. Romanian Journal of Morphology and Embryology, 65(4), 765–773. https://doi.org/10.47162/RJME.65.4.23
Breidung, D., Delavari, S., Megas, I. F., Geierlehner, A., Hitzl, W., Bodenschatz, K. J., Karcz, K., Ehrl, D., & Billner, M. (2025). Epidemiological characteristics and prognostic scoring in toxic epidermal necrolysis and Stevens-Johnson syndrome: Insights from a 17-year burn center experience. Medicina, 61(1), 66. https://doi.org/10.3390/medicina61010066
Canhão, G., Pinheiro, S., & Cabral, L. (2022). Toxic epidermal necrolysis: A clinical and therapeutic review. European Burn Journal, 3(3), 407–424. https://doi.org/10.3390/ebj3030036
Castillo, B., Vera, N., Ortega-Loayza, A. G., & Seminario-Vidal, L. (2018). Wound care for Stevens-Johnson syndrome and toxic epidermal necrolysis. Journal of the American Academy of Dermatology, 79(4), 764–767.e1. https://doi.org/10.1016/j.jaad.2018.03.032
Charlton, O. A., Harris, V., Phan, K., Mewton, E., Jackson, C., & Cooper, A. (2020). Toxic epidermal necrolysis and Stevens-Johnson syndrome: A comprehensive review. Advances in Wound Care, 9(7), 426–439. https://doi.org/10.1089/wound.2019.0977
Chiu, Y. M., & Chiu, H. Y. (2023). Lifetime risk, life expectancy, loss-of-life expectancy, and lifetime healthcare expenditure for Stevens-Johnson syndrome/toxic epidermal necrolysis in Taiwan: Follow-up of a nationwide cohort from 2008 to 2019. British Journal of Dermatology, 189(5), 553–560. https://doi.org/10.1093/bjd/ljad234
Creamer, D., Walsh, S. A., Dziewulski, P., Exton, L. S., Lee, H. Y., Dart, J. K., Setterfield, J., Bunker, C. B., Ardern-Jones, M. R., Watson, K. M., Wong, G. A., Philippidou, M., Vercueil, A., Martin, R. V., Williams, G., Shah, M., Brown, D., Williams, P., Mohd Mustapa, M. F., & Smith, C. H. (2016). U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. British Journal of Dermatology, 174(6), 1194–1227. https://doi.org/10.1111/bjd.14530
de Bustros, P., Baldea, A., Sanford, A., Joyce, C., Adams, W., & Bouchard, C. (2022). Review of culprit drugs associated with patients admitted to the burn unit with the diagnosis of Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome. Burns, 48(7), 1561–1573. https://doi.org/10.1016/j.burns.2021.08.009
DenAdel, M. A., Hendrickson, S. E., & Fuchs, E. (2022). Stevens-Johnson syndrome: Past, present, and future directions—Gynecologic manifestations and management in SJS/TEN. Frontiers in Medicine, 9, 874445. https://doi.org/10.3389/fmed.2022.874445
Dobry, A. S., Himed, S., Waters, M., & Kaffenberger, B. H. (2022). Scoring assessments in Stevens-Johnson syndrome and toxic epidermal necrolysis. Frontiers in Medicine, 9, 883121. https://doi.org/10.3389/fmed.2022.883121
Frantz, R., Huang, S., Are, A., & Motaparthi, K. (2021). Stevens-Johnson syndrome and toxic epidermal necrolysis: A review of diagnosis and management. Medicina, 57(9), 895. https://doi.org/10.3390/medicina57090895
Gallagher, R. M., Kirkham, J. J., Mason, J. R., Bird, K. A., Williamson, P. R., Nunn, A. J., Turner, M. A., Smyth, R. L., & Pirmohamed, M. (2011). Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool. PLOS ONE, 6(12), e28096. https://doi.org/10.1371/journal.pone.0028096
González-Herrada, C., Rodríguez-Martín, S., Cachafeiro, L., Lerma, V., González, O., Lorente, J. A., Rodríguez-Miguel, A., González-Ramos, J., Roustan, G., Ramírez, E., Bellón, T., de Abajo, F. J., & PIELenRed Therapeutic Management Working Group. (2017). Cyclosporine use in epidermal necrolysis is associated with an important mortality reduction: Evidence from three different approaches. Journal of Investigative Dermatology, 137(10), 2092–2100. https://doi.org/10.1016/j.jid.2017.05.022
Hama, N., Aoki, S., Chen, C. B., Hasegawa, A., Ogawa, Y., Vocanson, M., Asada, H., Chu, C. Y., Lan, C. E., Dodiuk-Gad, R. P., Fujiyama, T., Hsieh, T. S., Ito, K., Jerschow, E., Mizukawa, Y., Nakajima, S., Nakamura, K., Nicolas, J. F., Satoh, T. K., . . . Abe, R. (2024). Recent progress in Stevens-Johnson syndrome/toxic epidermal necrolysis: Diagnostic criteria, pathogenesis, and treatment. British Journal of Dermatology, 192(1), 9–18. https://doi.org/10.1093/bjd/ljae321
Hasegawa, A., & Abe, R. (2024). Stevens-Johnson syndrome and toxic epidermal necrolysis: Updates in pathophysiology and management. Chinese Medical Journal, 137(19), 2294–2307. https://doi.org/10.1097/CM9.0000000000003250
Hoffman, M., Chansky, P. B., Bashyam, A. R., Boettler, M. A., Challa, N., Dominguez, A., Estupinan, B., Gupta, R., Hennessy, K., Huckell, S. N., Hylwa-Deufel, S., Karikari, N. A., Keller, J. J., Kroshinsky, D., Kullberg, S. A., Lake, E., Lee, K. J., Martinez, E., Michels, K., . . . Micheletti, R. G. (2021). Long-term physical and psychological outcomes of Stevens-Johnson syndrome/toxic epidermal necrolysis. JAMA Dermatology, 157(6), 712–715. https://doi.org/10.1001/jamadermatol.2021.1136
Hsieh, M. H., Watanabe, T., & Aihara, M. (2021). Recent dermatological treatments for Stevens-Johnson syndrome and toxic epidermal necrolysis in Japan. Frontiers in Medicine, 8, 636924. https://doi.org/10.3389/fmed.2021.636924
Hung, S. I., Mockenhaupt, M., Blumenthal, K. G., Abe, R., Ueta, M., Ingen-Housz-Oro, S., Phillips, E. J., & Chung, W. H. (2024). Severe cutaneous adverse reactions. Nature Reviews Disease Primers, 10(1), 30. https://doi.org/10.1038/s41572-024-00514-0
Ingen-Housz-Oro, S., Schmidt, V., Ameri, M. M., Abe, R., Brassard, A., Mostaghimi, A., Paller, A. S., Romano, A., Didona, B., Kaffenberger, B. H., Ben Said, B., Thong, B. Y. H., Ramsay, B., Brezinova, E., Milpied, B., Mortz, C. G., Chu, C. Y., Sotozono, C., Gueudry, J., . . . Brüggen, M. C. (2023). Post-acute phase and sequelae management of epidermal necrolysis: An international, multidisciplinary Delphi-based consensus. Orphanet Journal of Rare Diseases, 18(1), 33. https://doi.org/10.1186/s13023-023-02631-7
Justice, J., Mukherjee, E., Martin-Pozo, M., & Phillips, E. (2025). Updates in the pathogenesis of SJS/TEN. Allergology International, 74(3), 361–371. https://doi.org/10.1016/j.alit.2025.05.002
Lee, H. Y., Fook-Chong, S., Koh, H. Y., Thirumoorthy, T., & Pang, S. M. (2017). Cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis: Retrospective analysis of a cohort treated in a specialized referral center. Journal of the American Academy of Dermatology, 76(1), 106–113. https://doi.org/10.1016/j.jaad.2016.07.048
Lee, E. Y., Knox, C., & Phillips, E. J. (2023). Worldwide prevalence of antibiotic-associated Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis. JAMA Dermatology, 159(4), 384–392. https://doi.org/10.1001/jamadermatol.2022.6378
Martin-Pozo, M. D., Williams, E. A., Bonnet, K. R., Kaffenberger, B. H., Schlundt, D. G., Phillips, E. J., & SJS Survivor Study. (2026). Recovering from Stevens-Johnson syndrome and toxic epidermal necrolysis. JAMA Dermatology, 162(1), 24–30. https://doi.org/10.1001/jamadermatol.2025.4345
Naik, P. P. (2022). A contemporary snippet on clinical presentation and management of toxic epidermal necrolysis. Scars, Burns & Healing, 8, 20595131221122381. https://doi.org/10.1177/20595131221122381
Noe, M. H., Mostaghimi, A., Rosenbach, M., Shinkai, K., & Micheletti, R. G. (2018). Selective use of cyclosporine for Stevens-Johnson syndrome/toxic epidermal necrolysis may exclude patients with poor prognostic factors. Journal of Investigative Dermatology, 138(9), 2068–2072. https://doi.org/10.1016/j.jid.2018.03.1496
Noe, M. H., Rosenbach, M., Hubbard, R. A., Mostaghimi, A., Cardones, A. R., Chen, J. K., Cotliar, J., Davis, M. D. P., Dominguez, A., Fox, L. P., Hughey, L. C., Kaffenberger, B. H., Kroshinsky, D., Kwong, B. Y., Miller, D. D., Musiek, A., Ortega-Loayza, A. G., Sharon, V. R., Shinkai, K., . . . Micheletti, R. G. (2019). Development and validation of a risk prediction model for in-hospital mortality among patients with Stevens-Johnson syndrome/toxic epidermal necrolysis—ABCD-10. JAMA Dermatology, 155(4), 448–454. https://doi.org/10.1001/jamadermatol.2018.5605
Obed, D., Salim, M., Dastagir, K., Krezdorn, N., Obed, D., & Vogt, P. M. (2025). Stevens-Johnson syndrome and toxic epidermal necrolysis: A 15-year regional burn center experience. JPRAS Open, 44, 83–92. https://doi.org/10.1016/j.jpra.2025.02.003
Sassolas, B., Haddad, C., Mockenhaupt, M., Dunant, A., Liss, Y., Bork, K., Haustein, U. F., Vieluf, D., Roujeau, J. C., & Le Louet, H. (2010). ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: Comparison with case-control analysis. Clinical Pharmacology & Therapeutics, 88(1), 60–68. https://doi.org/10.1038/clpt.2009.252
Schneider, J. A., & Cohen, P. R. (2017). Stevens-Johnson syndrome and toxic epidermal necrolysis: A concise review with a comprehensive summary of therapeutic interventions emphasizing supportive measures. Advances in Therapy, 34(6), 1235–1244. https://doi.org/10.1007/s12325-017-0530-y
Seminario-Vidal, L., Kroshinsky, D., Malachowski, S. J., Sun, J., Markova, A., Beachkofsky, T. M., Kaffenberger, B. H., Ergen, E. N., Mauskar, M., Bridges, A., Calhoun, C., Cardones, A. R., Chen, S. T., Chodosh, J., Cotliar, J., Davis, M. D. P., DeNiro, K. L., Dominguez, A. R., Eljure-Téllez, J., . . . Micheletti, R. G. (2020). Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults. Journal of the American Academy of Dermatology, 82(6), 1553–1567. https://doi.org/10.1016/j.jaad.2020.02.066
Shah, H., Parisi, R., Mukherjee, E., Phillips, E. J., & Dodiuk-Gad, R. P. (2024). Update on Stevens-Johnson syndrome and toxic epidermal necrolysis: Diagnosis and management. American Journal of Clinical Dermatology, 25(6), 891–908. https://doi.org/10.1007/s40257-024-00889-6
Singh, N., & Phillips, M. (2022). Toxic epidermal necrolysis: A review of past and present therapeutic approaches. Skin Therapy Letter, 27(5), 7–13.
Srinoulprasert, Y., Ud-Naen, S., Tansit, T., Tuchinda, P., Wongsa, C., & Klaewsongkram, J. (2026). Pilot study to improve in vitro identification of culprit drugs in SJS/TEN using granzyme B and granulysin secretion assays. Journal of Immunology Research, 2026(1), e8497493. https://doi.org/10.1155/jimr/8497493
Surowiecka, A., Barańska-Rybak, W., & Strużyna, J. (2023). Multidisciplinary treatment in toxic epidermal necrolysis. International Journal of Environmental Research and Public Health, 20(3), 2217. https://doi.org/10.3390/ijerph20032217
Sunaga, Y., Hama, N., Ochiai, H., Kokaze, A., Lee, E. S., Watanabe, H., Kurosawa, M., Azukizawa, H., Asada, H., Watanabe, Y., Yamaguchi, Y., Aihara, M., Mizukawa, Y., Ohyama, M., Abe, R., Hashizume, H., Nakajima, S., Nomura, T., Kabashima, K., . . . Sueki, H. (2022). Risk factors for sepsis and effects of pretreatment with systemic steroid therapy for underlying condition in SJS/TEN patients: Results of a nationwide cross-sectional survey in 489 Japanese patients. Journal of Dermatological Science, 107(2), 75–81. https://doi.org/10.1016/j.jdermsci.2022.07.004
Tian, C. C., Ai, X. C., Ma, J. C., Hu, F. Q., Liu, X. T., Luo, Y. J., Tan, G. Z., Zhang, J. M., Li, X. Q., Guo, Q., Zeng, F. Q., Shi, Z. R., & Wang, L. (2022). Etanercept treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis. Annals of Allergy, Asthma & Immunology, 129(3), 360–365.e1. https://doi.org/10.1016/j.anai.2022.05.009
Torres-Navarro, I., Briz-Redón, Á., & Botella-Estrada, R. (2021). Systemic therapies for Stevens-Johnson syndrome and toxic epidermal necrolysis: A SCORTEN-based systematic review and meta-analysis. Journal of the European Academy of Dermatology and Venereology, 35(1), 159–171. https://doi.org/10.1111/jdv.16685
Watanabe, Y., & Hama, N. (2025). Recent advances in the diagnosis and treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis. Allergology International, 74(3), 345–355. https://doi.org/10.1016/j.alit.2025.05.008
Yuliwulandari, R., Kristin, E., Prayuni, K., Sachrowardi, Q., Suyatna, F. D., Menaldi, S. L., Wichukchinda, N., Mahasirimongkol, S., & Cavallari, L. H. (2017). Association of the HLA-B alleles with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in the Javanese and Sundanese population of Indonesia: The important role of the HLA-B75 serotype. Pharmacogenomics, 18(18), 1643–1648. https://doi.org/10.2217/pgs-2017-0103
Zhang, J., Lu, C. W., Chen, C. B., Wang, C. W., Chen, W. T., Cheng, B., Ji, C., & Chung, W. H. (2022). Evaluation of combination therapy with etanercept and systemic corticosteroids for Stevens-Johnson syndrome and toxic epidermal necrolysis: A multicenter observational study. Journal of Allergy and Clinical Immunology: In Practice, 10(5), 1295–1304.e6. https://doi.org/10.1016/j.jaip.2022.01.038
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