Disease State: Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) (epidermal necrolysis spectrum)
Background
SJS/TEN is a rare, severe, and heterogeneous disease that urgently requires new therapeutic approaches, including combinations of treatments beyond supportive care. Defining core outcome sets is essential for improving biological and prognostic indicators and evaluating both the short- and long-term efficacy of treatments. Proposed short-term outcomes include observed mortality rates, time to cessation of epidermal detachment, time to complete healing, and duration of hospitalization. Long-term outcomes should focus on morbidity, including chronic complications and the impact on patients' quality of life. However, there is no consensus or validation of standardized core outcome sets for therapeutic research in SJS/TEN, which hinders the quality and comparability of clinical trials. Harmonizing these methodologies is crucial to ensure robust evaluation of new therapies and improve the feasibility of future research. To our knowledge, this is a unique project with limited prior work.
Project Goal
COSTEN aims to evaluate existing measures for outcomes in SJS/TEN, develop new measures for outcomes in SJS/TEN (as required) and achieve international stakeholder consensus on outcomes in SJS/TEN for interventional trials.
Project Leads
Saskia Oro
Roni Dodiuk-Gad
Key Project Team Members
Haur-Yueh Lee
Lars E. French
Sarah Walsh
Marie-Charlotte Brüggen
Elizabeth Jane Phillips
C3 Methods Partners
John Ingram
Jan Kottner
Contact
Saskia Oro, saskia.oro@aphp.fr
Roni Dodiuk-Gad, rdodiukgad@gmail.com
Publications
Marks ME, Botta RK, Abe R, Beachkofsky TM, Boothman I, Carleton BC, Chung WH, Cibotti RR, Dodiuk-Gad RP, Grimstein C, Hasegawa A, Hoofnagle JH, Hung SI, Kaffenberger B, Kroshinsky D, Lehloenya RJ, Martin-Pozo M, Micheletti RG, Mockenhaupt M, Nagao K, Pakala S, Palubinsky A, Pasieka HB, Peter J, Pirmohamed M, Reyes M, Saeed HN, Shupp J, Sukasem C, Syu JY, Ueta M, Zhou L, Chang WC, Becker P, Bellon T, Bonnet K, Cavalleri G, Chodosh J, Dewan AK, Dominguez A, Dong X, Ezhkova E, Fuchs E, Goldman J, Himed S, Mallal S, Markova A, McCawley K, Norton AE, Ostrov D, Phan M, Sanford A, Schlundt D, Schneider D, Shear N, Shinkai K, Tkaczyk E, Trubiano JA, Volpi S, Bouchard CS, Divito SJ, Phillips EJ. Updates in SJS/TEN: collaboration, innovation, and community. Front Med (Lausanne). 2023 Oct 11;10:1213889. doi: 10.3389/fmed.2023.1213889. PMID: 37901413; PMCID: PMC10600400. https://pubmed.ncbi.nlm.nih.gov/37901413/
Hama N, Aoki S, Chen CB, Hasegawa A, Ogawa Y, Vocanson M, Asada H, Chu CY, Lan CE, Dodiuk-Gad RP, Fujiyama T, Hsieh TS, Ito K, Jerschow E, Mizukawa Y, Nakajima S, Nakamura K, Nicolas JF, Satoh TK, Shiohara T, Takahashi H, Tohyama M, Ueda T, Ura K, Watanabe H, Yamaguchi Y, Nordmann TM, Chung WH, Naisbitt D, Pincelli C, Pichler WJ, French LE, Phillips E, Abe R. Recent progress in Stevens-Johnson syndrome/toxic epidermal necrolysis: diagnostic criteria, pathogenesis and treatment. Br J Dermatol. 2024 Dec 23;192(1):9-18. doi:10.1093/bjd/ljae321. PMID: 39141587. https://pubmed.ncbi.nlm.nih.gov/39141587/
Ingen-Housz-Oro S, de Prost N, Wolkenstein P. Need for Trial Design Change in Epidermal Necrolysis (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis): Example of Cyclosporine. J Invest Dermatol. 2025 Jan 22:S0022-202X(24)03047-1.doi: 10.1016/j.jid.2024.11.020. Epub ahead of print. PMID: 39846903. https://pubmed.ncbi.nlm.nih.gov/39846903/
Ingen-Housz-Oro, French L, Wolkenstein P. Stevens-Johnson Syndrome and Toxic Eepidermal Necrolysis: How to Improve the Evaluation of Therapeutic Strategies? J Invest Dermatol 2025: in press.
Ingen-Housz-Oro S, Matei I, Gaillet A, et al. Diagnosing and Managing Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Adults: Review of Evidence 2017-2023. J Invest Dermatol 2025: in press
Kridin K, Brüggen MC, Chua SL, Bygum A, Walsh S, Nägeli MC, Kucinskiene V, French L, Tétart F, Didona B, Milpied B, Ranki A, Salavastru C, Brezinová E, Divani-Patel S, Lorentzen T, Nagel JL, Valiukeviciene S, Karpaviciute V, Tiplica, GS, Oppel E, Oschmann A, de Prost N, Vorobyev A, Ingen-Housz-Oro S. Assessment of Treatment Approaches and Outcomes in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Insights From a Pan-European Multicenter Study. JAMA Dermatol. 2021 Oct 1;157(10):1182-1190. doi: 10.1001/jamadermatol.2021.3154. PMID: 34431984; PMCID: PMC8387938. https://pubmed.ncbi.nlm.nih.gov/34431984/
Brüggen MC, Le ST, Walsh S, Toussi A, de Prost N, Ranki A, Didona B, Colin A, Horváth B, Brezinova E, Milpied B, Moss C, Bodemer C, Meyersburg D, Salavastru C, Tiplica GS, Howard E, Bequignon E, Bouwes Bavinck JN, Newman J, Gueudry J, Nägeli M, Zaghbib K, Pallesen K, Bygum A, Joly P, Wolkenstein P, Chua SL, Le Floch R, Shear NH, Chu CY, Hama N, Abe R, Chung WH, Shiohara T, Ardern-Jones M, Romanelli P, Phillips EJ, Stern RS, Cotliar J, Micheletti RG, Brassard A, Schulz JT, Dodiuk-Gad RP, Dominguez AR, Paller AS, Seminario-Vidal L, Mostaghimi A, Noe MH, Worswick S, Tartar D, Sheridan R, Kaffenberger BH, Shinkai K, Maverakis E, French LE, Ingen-Housz-Oro S. Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus. Br J Dermatol. 2021 Sep;185(3):616-626. doi: 10.1111/bjd.19893. Epub 2021 Apr 27. PMID: 33657677. https://pubmed.ncbi.nlm.nih.gov/33657677/
Ingen-Housz-Oro S, Schmidt V, Ameri MM, Abe R, Brassard A, Mostaghimi A, Paller AS, Romano A, Didona B, Kaffenberger BH, Ben Said B, Thong BYH, Ramsay B, Brezinova E, Milpied B, Mortz CG, Chu CY, Sotozono C, Gueudry J, Fortune DG, Dridi SM, Tartar D, Do-Pham G, Gabison E, Phillips EJ, Lewis F, Salavastru C, Horvath B, Dart J, Setterfield J, Newman J, Schulz JT, Delcampe A, Brockow K, Seminario-Vidal L, Jörg L, Watson MP, Gonçalo M, Lucas M, Torres M, Noe MH, Hama N, Shear NH, O'Reilly P, Wolkenstein P, Romanelli P, Dodiuk-Gad RP, Micheletti RG, Tiplica GS, Sheridan R, Rauz S, Ahmad S, Chua SL, Flynn TH, Pichler W, Le ST, Maverakis E, Walsh S, French LE, Brüggen MC. Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI- based consensus. Orphanet J Rare Dis. 2023 Feb 22;18(1):33. doi: 10.1186/s13023-023-02631-7. PMID: 36814255; PMCID: PMC9945700 https://pubmed.ncbi.nlm.nih.gov/36814255/
Ingen-Housz-Oro S, Matei I, Gaillet A, Gueudry J, Zaghbib K, Assier H, Hua C, Bensaid B, Colin A, Ouedraogo R, Redlich J, Courtois E, Chazelas K, Sbidian E, Nakad L, Bequignon E, Terkmane N, Gaultier F, Schlemmer F, Do-Pham G, Barbaud A, Lebrun-Vignes B, Hoffmann C, Mahé PJ, Le Floch R, Bernier C, Vabres B, Milpied B, Delcampe A, Tétart F, Tauber M, Staumont-Sallé D, Dezoteux F, Descamps V, Misery L, Bursztejn AC, Dereure O, Amazan E, Le Bidre E, Le Pallec S, Lagier C, Laroche A, Ferrat E, Wolkenstein P, de Prost N; French National Reference Center for Toxic Bullous Diseases and Severe Drug Reactions TOXIBUL. French national protocol for diagnosis and management of epidermal necrolysis in adults (Stevens-Johnson syndrome and toxic epidermal necrolysis). Ann Dermatol Venereol. 2024 Jun;151(2):103282. doi: 10.1016/j.annder.2024.103282. Epub 2024 May 28. PMID: 38810539. https://pubmed.ncbi.nlm.nih.gov/38810539/
Hung SI, Mockenhaupt M, Blumenthal KG, Abe R, Ueta M, Ingen-Housz-Oro S, Phillips EJ, Chung WH. Severe cutaneous adverse reactions. Nat Rev Dis Primers. 2024 Apr 25;10(1):30. doi: 10.1038/s41572-024-00514-0. PMID: 38664435. https://pubmed.ncbi.nlm.nih.gov/38664435/
O'Reilly P, Walsh S, Bunker CB, Ryan S, Natella PA, Colin A, Simpson J, Barry LA, Meskell P, Dodiuk-Gad R, Coffey A, Savarimalai R, Fortune DG, Ingen-Housz- Oro S. The quality-of-life impact of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) on patients' lives: an interpretative descriptive qualitative study. Br J Dermatol. 2024 Dec 23;192(1):85-91. doi: 10.1093/bjd/ljae334. PMID: 39162027. https://pubmed.ncbi.nlm.nih.gov/39162027/
Updated on February 3, 2025