Review

. 2023 Oct 11:10:1213889.

doi: 10.3389/fmed.2023.1213889. eCollection 2023.

Updates in SJS/TEN: collaboration, innovation, and community

Madeline E Marks¹, Ramya Krishna Botta¹, Riichiro Abe², Thomas M Beachkofsky³, Isabelle Boothman⁴, Bruce C Carleton⁵, Wen-Hung Chung⁶, Ricardo R Cibotti⁷, Roni P Dodiuk-Gad^{8

9

10}, Christian Grimstein¹¹, Akito Hasegawa², Jay H Hoofnagle¹², Shuen-Iu Hung¹³, Benjamin Kaffenberger¹⁴, Daniela Kroshinsky¹⁵, Rannakoe J Lehloenya¹⁶, Michelle Martin-Pozo¹, Robert G Micheletti¹⁵, Maja Mockenhaupt¹⁷, Keisuke Nagao⁷, Suman Pakala¹, Amy Palubinsky¹, Helena B Pasieka^{3

18

19}, Jonathan Peter²⁰, Munir Pirmohamed²¹, Melissa Reyes²², Hajirah N Saeed²³, Jeffery Shupp²⁴, Chonlaphat Sukasem²⁵, Jhih Yu Syu²⁶, Mayumi Ueta²⁷, Li Zhou²⁸, Wan-Chun Chang⁵, Patrice Becker²⁹, Teresa Bellon³⁰, Kemberlee Bonnet³¹, Gianpiero Cavalleri⁴, James Chodosh³², Anna K Dewan³³, Arturo Dominguez³⁴, Xinzhong Dong³⁵, Elena Ezhkova³⁶, Esther Fuchs³⁷, Jennifer Goldman³⁸, Sonia Himed³⁹, Simon Mallal⁴⁰, Alina Markova⁴¹, Kerry McCawley⁴², Allison E Norton⁴³, David Ostrov⁴⁴, Michael Phan⁴⁵, Arthur Sanford⁴⁶, David Schlundt³¹, Daniel Schneider⁴⁷, Neil Shear⁸, Kanade Shinkai⁴⁸, Eric Tkaczyk⁴⁹, Jason A Trubiano⁵⁰, Simona Volpi⁵¹, Charles S Bouchard⁵², Sherrie J Divito¹⁵, Elizabeth J Phillips¹

Affiliations

¹ Center for Drug Interactions and Immunology, Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
² Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
³ Departments of Dermatology and Medicine, Uniformed Services University, Bethesda, MD, United States.
⁴ The SFI Centre for Research Training in Genomics Data Science, Dublin, Ireland.
⁵ Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia and the British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.
⁶ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷ National Institute of Arthritis and Musculoskeletal and Skin (NIAMS), National Institutes of Health (NIH), Bethesda, MD, United States.
⁸ Department of Dermatology, Emek Medical Center, Afula, Israel.
⁹ Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Dermatology, Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
¹¹ Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.
¹² Liver Disease Research Branch, Division of Digestive Diseases and Nutrition of NIDDK, National Institutes of Health (NIH), Bethesda, MD, United States.
¹³ Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁴ Department of Dermatology, Ohio State University Wexner Medical Center, Columbus, OH, United States.
¹⁵ Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
¹⁶ Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹⁷ Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Medical Center and Medical Faculty, University of Freiburg, Freiburg, Germany.
¹⁸ The Burn Center, MedStar Washington Hospital Center, Washington, D.C., DC, United States.
¹⁹ Department of Dermatology, MedStar Health/Georgetown University, Washington, D.C., DC, United States.
²⁰ Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
²¹ Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
²² Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
²³ Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States.
²⁴ Department of Surgery, Plastic and Reconstructive Surgery, Biochemistry, and Molecular and Cellular Biology, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, D.C., DC, United States.
²⁵ Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
²⁶ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
²⁷ Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
²⁸ Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
²⁹ Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Disease, Bethesda, MD, United States.
³⁰ Drug Hypersensitivity Laboratory, La Paz Health Research Institute (IdiPAZ), Madrid, Spain.
³¹ Department of Psychology, Vanderbilt University, Nashville, TN, United States.
³² University of New Mexico School of Medicine, Albuquerque, NM, United States.
³³ Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, United States.
³⁴ Department of Dermatology and Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States.
³⁵ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
³⁶ Department of Cell, Developmental, and Regenerative Biology and Dermatology, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, United States.
³⁷ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States.
³⁸ Division of Pediatric Infectious Diseases and Clinical Pharmacology, Children's Mercy, Kansas City, MO, United States.
³⁹ College of Medicine, University of Cincinnati, Cincinnati, OH, United States.
⁴⁰ Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
⁴¹ Department of Dermatology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, United States.
⁴² Stevens-Johnson Syndrome Foundation, Westminster, CO, United States.
⁴³ Division of Pediatric Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
⁴⁴ Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States.
⁴⁵ Division of Pharmacovigilance-I, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.
⁴⁶ Division of Trauma, Surgical Critical Care, and Burns, Loyola University Medical Center, Chicago, IL, United States.
⁴⁷ Department of Psychiatry and Surgery, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, D.C., DC, United States.
⁴⁸ Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
⁴⁹ Department of Veterans Affairs, Vanderbilt Dermatology Translational Research Clinic (VDTRC.org), Nashville, TN, United States.
⁵⁰ Department of Infectious Diseases and Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia.
⁵¹ National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, United States.
⁵² Department of Opthalmology, Loyola University Medical Center, Chicago, IL, United States.

PMID: 37901413
PMCID: PMC10600400
DOI: 10.3389/fmed.2023.1213889

Review

Updates in SJS/TEN: collaboration, innovation, and community

Madeline E Marks et al. Front Med (Lausanne). 2023.

. 2023 Oct 11:10:1213889.

doi: 10.3389/fmed.2023.1213889. eCollection 2023.

Authors

Affiliations

¹ Center for Drug Interactions and Immunology, Division of Infectious Disease, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
² Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
³ Departments of Dermatology and Medicine, Uniformed Services University, Bethesda, MD, United States.
⁴ The SFI Centre for Research Training in Genomics Data Science, Dublin, Ireland.
⁵ Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia and the British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada.
⁶ Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷ National Institute of Arthritis and Musculoskeletal and Skin (NIAMS), National Institutes of Health (NIH), Bethesda, MD, United States.
⁸ Department of Dermatology, Emek Medical Center, Afula, Israel.
⁹ Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁰ Department of Dermatology, Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.
¹¹ Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.
¹² Liver Disease Research Branch, Division of Digestive Diseases and Nutrition of NIDDK, National Institutes of Health (NIH), Bethesda, MD, United States.
¹³ Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁴ Department of Dermatology, Ohio State University Wexner Medical Center, Columbus, OH, United States.
¹⁵ Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
¹⁶ Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹⁷ Dokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Medical Center and Medical Faculty, University of Freiburg, Freiburg, Germany.
¹⁸ The Burn Center, MedStar Washington Hospital Center, Washington, D.C., DC, United States.
¹⁹ Department of Dermatology, MedStar Health/Georgetown University, Washington, D.C., DC, United States.
²⁰ Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
²¹ Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom.
²² Center for Drug Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD, United States.
²³ Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States.
²⁴ Department of Surgery, Plastic and Reconstructive Surgery, Biochemistry, and Molecular and Cellular Biology, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, D.C., DC, United States.
²⁵ Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
²⁶ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
²⁷ Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
²⁸ Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
²⁹ Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Disease, Bethesda, MD, United States.
³⁰ Drug Hypersensitivity Laboratory, La Paz Health Research Institute (IdiPAZ), Madrid, Spain.
³¹ Department of Psychology, Vanderbilt University, Nashville, TN, United States.
³² University of New Mexico School of Medicine, Albuquerque, NM, United States.
³³ Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, United States.
³⁴ Department of Dermatology and Internal Medicine, UT Southwestern Medical Center, Dallas, TX, United States.
³⁵ Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
³⁶ Department of Cell, Developmental, and Regenerative Biology and Dermatology, Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY, United States.
³⁷ Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, United States.
³⁸ Division of Pediatric Infectious Diseases and Clinical Pharmacology, Children's Mercy, Kansas City, MO, United States.
³⁹ College of Medicine, University of Cincinnati, Cincinnati, OH, United States.
⁴⁰ Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States.
⁴¹ Department of Dermatology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, United States.
⁴² Stevens-Johnson Syndrome Foundation, Westminster, CO, United States.
⁴³ Division of Pediatric Allergy, Immunology, and Pulmonary Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States.
⁴⁴ Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States.
⁴⁵ Division of Pharmacovigilance-I, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.
⁴⁶ Division of Trauma, Surgical Critical Care, and Burns, Loyola University Medical Center, Chicago, IL, United States.
⁴⁷ Department of Psychiatry and Surgery, MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, D.C., DC, United States.
⁴⁸ Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
⁴⁹ Department of Veterans Affairs, Vanderbilt Dermatology Translational Research Clinic (VDTRC.org), Nashville, TN, United States.
⁵⁰ Department of Infectious Diseases and Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia.
⁵¹ National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, United States.
⁵² Department of Opthalmology, Loyola University Medical Center, Chicago, IL, United States.

PMID: 37901413
PMCID: PMC10600400
DOI: 10.3389/fmed.2023.1213889

Abstract

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Keywords: HLA genotyping; SCORTEN; Stevens-Johnson Syndrome; Toxic Epidermal Necrolysis; body surface area; electronic medical record; pharmacogenomics; severe adverse cutaneous drug reactions.

Copyright © 2023 Marks, Botta, Abe, Beachkofsky, Boothman, Carleton, Chung, Cibotti, Dodiuk-Gad, Grimstein, Hasegawa, Hoofnagle, Hung, Kaffenberger, Kroshinsky, Lehloenya, Martin-Pozo, Micheletti, Mockenhaupt, Nagao, Pakala, Palubinsky, Pasieka, Peter, Pirmohamed, Reyes, Saeed, Shupp, Sukasem, Syu, Ueta, Zhou, Chang, Becker, Bellon, Bonnet, Cavalleri, Chodosh, Dewan, Dominguez, Dong, Ezhkova, Fuchs, Goldman, Himed, Mallal, Markova, McCawley, Norton, Ostrov, Phan, Sanford, Schlundt, Schneider, Shear, Shinkai, Tkaczyk, Trubiano, Volpi, Bouchard, Divito and Phillips.

PubMed Disclaimer

Conflict of interest statement

KM was employed by Stevens-Johnson Syndrome Foundation. EJP reports grants from National Institutes of Health (R01HG010863, R01AI152183, U01AI154659) and from the National Health and Medical Research Council of Australia. She receives Royalties and consulting fees from UpToDate and has received consulting fees from Janssen, Verve, Biocryst, Regeneron, AstraZeneca and Novavax. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer OI declared a shared affiliation with the author AS to the handling editor at the time of review.

Figures

**Figure 1**
Pie chart representing the percentage of participants per research/healthcare categories.

**Figure 2**
HLA risk alleles associated with SCAR in different ethnic populations.

**Figure 3**
Pharmacogenomics test clinical workflow to alert physicians for drug prescriptions.

**Figure 4**
Example photograph of Vanderbilt Drug Safety patient (with permission) to guide standardized SJS/TEN scoring by illustrating the categorization of different appearances of skin into different terminology. Photo by Madeline Marks and Austin Cronin, VDTRC.org.

**Figure 5**
Infographic to illustrate the challenges of photographing in burn ICU.

See this image and copyright information in PMC

References

1. Peter JG, Lehloenya R, Dlamini S, Risma K, White KD, Konvinse KC, et al. 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) 5:547–63. doi: 10.1016/j.jaip.2017.01.025, PMID: - DOI - PMC - PubMed
1. Dobry AS, Himed S, Waters M, Kaffenberger BH. Scoring assessments in Stevens-Johnson syndrome and toxic epidermal necrolysis. Front Med (Lausanne). (2022) 9:883121. doi: 10.3389/fmed.2022.883121 - DOI - PMC - PubMed
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1. Chang WC, Abe R, Anderson P, Anderson W, Ardern-Jones MR, Beachkofsky TM, et al. SJS/TEN 2019: from science to translation. J Dermatol Sci. (2020) 98:2–12. doi: 10.1016/j.jdermsci.2020.02.003, PMID: - DOI - PMC - PubMed
1. Gronich N, Maman D, Stein N, Saliba W. Culprit medications and risk factors associated with Stevens-Johnson syndrome and toxic epidermal necrolysis: population-based nested case-control study. Am J Clin Dermatol. (2022) 23:257–66. doi: 10.1007/s40257-021-00661-0, PMID: - DOI - PMC - PubMed

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Updates in SJS/TEN: collaboration, innovation, and community

Affiliations

Updates in SJS/TEN: collaboration, innovation, and community

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials