[开放获取]    Stevens-Johnson综合征/中毒性表皮坏死松解症诊疗专家共识

doi:10.35541/cjd.20201177

中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (5): 376-381.doi: 10.35541/cjd.20201177

[开放获取] Stevens-Johnson综合征/中毒性表皮坏死松解症诊疗专家共识

中华医学会皮肤性病学分会药物不良反应研究中心

中华医学会皮肤性病学分会药物不良反应研究中心

收稿日期:2020-12-09 修回日期:2021-02-10 发布日期:2021-04-29
通讯作者: 张福仁；赖维 E-mail:zhangfuren@hotmail.com; drlaiwei@163.com

Expert consensus on the diagnosis and treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis

Adverse Drug Reaction Research Center of Chinese Society of Dermatology

Adverse Drug Reaction Research Center of Chinese Society of Dermatology

Received:2020-12-09 Revised:2021-02-10 Published:2021-04-29
Contact: Zhang Furen; Lai Wei E-mail:zhangfuren@hotmail.com; drlaiwei@163.com

摘要/Abstract

摘要： 【摘要】 Stevens-Johnson综合征（SJS）/中毒性表皮坏死松解症（TEN）是一种严重的皮肤-黏膜反应，绝大多数由药物引起，以水疱及泛发性表皮松解为特征，可伴发一系列系统症状，包括多器官功能衰竭综合征等，具有较高的死亡风险。中华医学会皮肤性病学分会药物不良反应研究中心组织相关专家，在国内外最新共识、指南及医学证据基础上，结合我国诊疗现状，从SJS/TEN的定义、病因、发病机制、临床特征及诊断、致敏药物的确定、病情进展的评价、治疗和预防等方面制定了SJS/TEN诊疗专家共识，为临床医生的诊疗工作提供参考。

关键词: Stevens-Johnson综合征, 表皮坏死松解症, 中毒性, 药疹, 药物毒性, 专家共识

Abstract: 【Abstract】 Stevens-Johnson syndrome （SJS）/toxic epidermal necrolysis （TEN） is a severe cutaneous-mucosal response that carries a high risk of death, mostly induced by drugs, characterized by blisters and generalized epidermolysis, accompanied by a series of systemic symptoms, including multiple organ dysfunction syndrome. Based on the latest domestic and international consensus, guidelines and medical evidence, and combined with the current status of the diagnosis and treatment of SJS/TEN in China, the Adverse Drug Reaction Research Center of Chinese Society of Dermatology organized relevant experts to develop this consensus on SJS/TEN in terms of the definition, etiology, pathogenesis, clinical characteristics, diagnosis, identification of culprit drugs, evaluation of disease progression, treatment, prevention and so on, aiming to provide a reference for clinicians in clinical practice.

Key words: Stevens-Johnson syndrome, Epidermal necrolysis, toxic, Drug eruptions, Drug toxicity, Expert consensus

中华医学会皮肤性病学分会药物不良反应研究中心. [开放获取] Stevens-Johnson综合征/中毒性表皮坏死松解症诊疗专家共识[J]. 中华皮肤科杂志, 2021,54(5):376-381. doi:10.35541/cjd.20201177

Adverse Drug Reaction Research Center of Chinese Society of Dermatology. Expert consensus on the diagnosis and treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis[J]. Chinese Journal of Dermatology, 2021, 54(5): 376-381.doi:10.35541/cjd.20201177

参考文献 53

［1］	White KD, Abe R, Ardern⁃Jones M, et al. SJS/TEN 2017: building multidisciplinary networks to drive science and translation［J］. J Allergy Clin Immunol Pract, 2018,6（1）:38⁃69. doi: 10.1016/j.jaip.2017.11.023.
［2］	Hsu DY, Brieva J, Silverberg NB, et al. Morbidity and mortality of Stevens⁃Johnson syndrome and toxic epidermal necrolysis in United States adults［J］. J Invest Dermatol, 2016,136（7）:1387⁃1397. doi: 10.1016/j.jid.2016.03.023.
［3］	马慧淼, 陈媚, 刘猛, 等. 纳武单抗导致Stevens⁃Johnson综合征1例［J］. 中国肿瘤临床, 2020,47（2）:105⁃106. doi: 10.3969/j.issn.1000⁃8179.2020.02.449.
［4］	Chung WH, Hung SI, Hong HS, et al. Medical genetics: a marker for Stevens⁃Johnson syndrome［J］. Nature, 2004,428（6982）:486. doi: 10.1038/428486a.
［5］	Mallal S, Nolan D, Witt C, et al. Association between presence of HLA⁃B*5701, HLA⁃DR7, and HLA⁃DQ3 and hypersensitivity to HIV⁃1 reverse⁃transcriptase inhibitor abacavir［J］. Lancet, 2002,359（9308）:727⁃732. doi: 10.1016/s0140⁃6736（02）07873⁃x.
［6］	Hung SI, Chung WH, Liou LB, et al. HLA⁃B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol［J］. Proc Natl Acad Sci U S A, 2005,102（11）:4134⁃4139. doi: 10.1073/pnas.0409500102.
［7］	Yang F, Xuan J, Chen J, et al. HLA⁃B*59:01: a marker for Stevens⁃Johnson syndrome/toxic epidermal necrolysis caused by methazolamide in Han Chinese［J］. Pharmacogenomics J, 2016,16（1）:83⁃87. doi: 10.1038/tpj.2015.25.
［8］	Zhang FR, Liu H, Irwanto A, et al. HLA⁃B*13:01 and the dapsone hypersensitivity syndrome［J］. N Engl J Med, 2013,369（17）:1620⁃1628. doi: 10.1056/NEJMoa1213096.
［9］	Tangamornsuksan W, Lohitnavy M. Association between HLA⁃B*1301 and dapsone⁃induced cutaneous adverse drug reactions: a systematic review and meta⁃analysis［J］. JAMA Dermatol, 2018,154（4）:441⁃446. doi: 10.1001/jamadermatol.2017.6484.
［10］	Yang F, Gu B, Zhang L, et al. HLA⁃B*13:01 is associated with salazosulfapyridine⁃induced drug rash with eosinophilia and systemic symptoms in Chinese Han population［J］. Pharmacogenomics, 2014,15（11）:1461⁃1469. doi: 10.2217/pgs.14.69.
［11］	Chung WH, Hung SI, Yang JY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens⁃Johnson syndrome and toxic epidermal necrolysis［J］. Nat Med, 2008,14（12）:1343⁃1350. doi: 10.1038/nm.1884.
［12］	Viard⁃Leveugle I, Gaide O, Jankovic D, et al. TNF⁃α and IFN⁃γ are potential inducers of Fas⁃mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis［J］. J Invest Dermatol, 2013,133（2）:489⁃498. doi: 10.1038/jid.2012.330.
［13］	夏倩倩, 孙勇虎. Stevens⁃Johnson综合征/中毒性表皮坏死松解综合征的发病机制研究进展［J］. 中国皮肤性病学杂志, 2019,33（6）:713⁃716. doi: 10.13735/j.cjdv.1001⁃7089.201805125.
［14］	Revuz J, Penso D, Roujeau JC, et al. Toxic epidermal necrolysis. Clinical findings and prognosis factors in 87 patients［J］. Arch Dermatol, 1987,123（9）:1160⁃1165. doi: 10.1001/archderm.123. 9.1160.
［15］	Yang L, Shou YH, Li F, et al. Retrospective study of 213 cases of Stevens⁃Johnson syndrome and toxic epidermal necrolysis from China［J］. Burns, 2020,46（4）:959⁃969. doi: 10.1016/j.burns.2019.10.008.
［16］	Gao X, Tang X, Ai L, et al. Acute pancreatic injuries: a complication of Stevens⁃Johnson syndrome/toxic epidermal necrolysis associated with cytotoxic immunocell activation［J］. J Am Acad Dermatol, 2020,84（3）:644⁃653. doi: 10.1016/j.jaad. 2020.06.043.
［17］	Chen CB, Hsu TH, Chung⁃Yee Hui R, et al. Disseminated intravascular coagulation in Stevens⁃Johnson syndrome and toxic epidermal necrolysis［J/OL］. J Am Acad Dermatol, 2020:S0190⁃9622（20）32459⁃2［2021⁃02⁃26］. https://www.sciencedirect.com/science/article/pii/S0190962220324592?via%3Dihub. doi: 10.1016/j.jaad.2020.08.065.
［18］	Friedmann PS, Ardern⁃Jones M. Patch testing in drug allergy［J］. Curr Opin Allergy Clin Immunol, 2010,10（4）:291⁃296. doi: 10.1097/ACI.0b013e32833aa54d.
［19］	Hari Y, Frutig⁃Schnyder K, Hurni M, et al. T cell involvement in cutaneous drug eruptions［J］. Clin Exp Allergy, 2001,31（9）:1398⁃1408. doi: 10.1046/j.1365⁃2222.2001.01164.x.
［20］	Polak ME, Belgi G, McGuire C, et al. In vitro diagnostic assays are effective during the acute phase of delayed⁃type drug hypersensitivity reactions［J］. Br J Dermatol, 2013,168（3）:539⁃549. doi: 10.1111/bjd.12109.
［21］	You J, Sun L, Zhao Q, et al. Dynamic cytokine profiles combined with enzyme⁃linked immunospot assay are useful for immunologically confirming the dapsone hypersensitivity syndrome［J/OL］. J Am Acad Dermatol, 2020:S0190⁃9622（20）31093⁃8［2021⁃02⁃26］. https://www.sciencedirect.com/science/article/pii/S0190962220310938?via%3Dihub. doi: 10.1016/j.jaad. 2020.06.032.
［22］	Khan DA. Pharmacogenomics and adverse drug reactions: primetime and not ready for primetime tests［J］. J Allergy Clin Immunol, 2016,138（4）:943⁃955. doi: 10.1016/j.jaci.2016.08.002.
［23］	Bastuji⁃Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity⁃of⁃illness score for toxic epidermal necrolysis［J］. J Invest Dermatol, 2000,115（2）:149⁃153. doi: 10.1046/j.1523⁃1747.2000.00061.x.
［24］	Trent JT, Kirsner RS, Romanelli P, et al. Use of SCORTEN to accurately predict mortality in patients with toxic epidermal necrolysis in the United States［J］. Arch Dermatol, 2004,140（7）:890⁃892. doi: 10.1001/archderm.140.7.890.
［25］	Micheletti RG, Chiesa⁃Fuxench Z, Noe MH, et al. Stevens⁃Johnson syndrome/toxic epidermal necrolysis: a multicenter retrospective study of 377 adult patients from the United States［J］. J Invest Dermatol, 2018,138（11）:2315⁃2321. doi: 10.1016/j.jid.2018.04.027.
［26］	Cartotto R, Mayich M, Nickerson D, et al. SCORTEN accurately predicts mortality among toxic epidermal necrolysis patients treated in a burn center［J］. J Burn Care Res, 2008,29（1）:141⁃146. doi: 10.1097/BCR.0b013e31815f3865.
［27］	张松, 祁冬冬, 倪静, 等. Stevens⁃Johnson综合征及中毒性表皮坏死松解症48例临床资料分析［J］. 临床皮肤科杂志, 2019,48（11）:665⁃667. doi: 10.16761/j.cnki.1000⁃4963.2019.11. 005.
［28］	Pham TN, Cancio LC, Gibran NS, et al. American Burn Association practice guidelines burn shock resuscitation［J］. J Burn Care Res, 2008,29（1）:257⁃266. doi: 10.1097/BCR.0b013e 31815f3876.
［29］	Wang CW, Yang LY, Chen CB, et al. Randomized, controlled trial of TNF⁃α antagonist in CTL⁃mediated severe cutaneous adverse reactions［J］. J Clin Invest, 2018,128（3）:985⁃996. doi: 10.1172/JCI93349.
［30］	Liu W, Nie X, Zhang L. A retrospective analysis of Stevens⁃Johnson syndrome/toxic epidermal necrolysis treated with corticosteroids［J］. Int J Dermatol, 2016,55（12）:1408⁃1413. doi: 10.1111/ijd.13379.
［31］	Schneck J, Fagot JP, Sekula P, et al. 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］. J Am Acad Dermatol, 2008,58（1）:33⁃40. doi: 10.1016/j.jaad.2007.08.039.
［32］	Kardaun SH, Jonkman MF. Dexamethasone pulse therapy for Stevens⁃Johnson syndrome/toxic epidermal necrolysis［J］. Acta Derm Venereol, 2007,87（2）:144⁃148. doi: 10.2340/00015555⁃0214.
［33］	Hirahara K, Kano Y, Sato Y, et al. Methylprednisolone pulse therapy for Stevens⁃Johnson syndrome/toxic epidermal necrolysis: clinical evaluation and analysis of biomarkers［J］. J Am Acad Dermatol, 2013,69（3）:496⁃498. doi: 10.1016/j.jaad. 2013.04.007.
［34］	Kim KJ, Lee DP, Suh HS, et al. Toxic epidermal necrolysis: analysis of clinical course and SCORTEN⁃based comparison of mortality rate and treatment modalities in Korean patients［J］. Acta Derm Venereol, 2005,85（6）:497⁃502. doi: 10.1080/00015550510038232.
［35］	Viard I, Wehrli P, Bullani R, et al. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin［J］. Science, 1998,282（5388）:490⁃493. doi: 10.1126/science.282.5388.490.
［36］	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［J］. PLoS One, 2016,11（11）:e0167120. doi: 10.1371/journal.pone.0167120.
［37］	Tsai TY, Huang IH, Chao YC, et al. Treating toxic epidermal necrolysis with systemic immunomodulating therapies: a systematic review and network meta⁃analysis［J］. J Am Acad Dermatol, 2021,84（2）:390⁃397. doi: 10.1016/j.jaad.2020.08.122.
［38］	Lee HY, Lim YL, Thirumoorthy T, et al. The role of intravenous immunoglobulin in toxic epidermal necrolysis: a retrospective analysis of 64 patients managed in a specialized centre［J］. Br J Dermatol, 2013,169（6）:1304⁃1309. doi: 10.1111/bjd.12607.
［39］	杨永生, 徐金华, 李锋, 等. 静脉注射丙种球蛋白和糖皮质激素治疗重症大疱性药疹65例［J］. 中华皮肤科杂志, 2009,42（5）:330⁃332. doi: 10.3760/cma.j.issn.0412⁃4030.2009.05.012.
［40］	陈金波, 王宝玺, 王宏伟, 等. Stevens⁃Johnson综合征及中毒性表皮坏死松解症61例回顾性分析［J］. 中华皮肤科杂志, 2008,41（8）:542⁃545.
［41］	Valeyrie⁃Allanore L, Wolkenstein P, Brochard L, et al. Open trial of ciclosporin treatment for Stevens⁃Johnson syndrome and toxic epidermal necrolysis［J］. Br J Dermatol, 2010,163（4）:847⁃853. doi: 10.1111/j.1365⁃2133.2010.09863.x.
［42］	Singh GK, Chatterjee M, Verma R. Cyclosporine in Stevens Johnson syndrome and toxic epidermal necrolysis and retrospective comparison with systemic corticosteroid［J］. Indian J Dermatol Venereol Leprol, 2013,79（5）:686⁃692. doi: 10.4103/0378⁃6323.116738.
［43］	Kirchhof MG, Miliszewski MA, Sikora S, et al. Retrospective review of Stevens⁃Johnson syndrome/toxic epidermal necrolysis treatment comparing intravenous immunoglobulin with cyclosporine［J］. J Am Acad Dermatol, 2014,71（5）:941⁃947. doi: 10.1016/j.jaad.2014.07.016.
［44］	Paradisi A, Abeni D, Bergamo F, et al. Etanercept therapy for toxic epidermal necrolysis［J］. J Am Acad Dermatol, 2014,71（2）:278⁃283. doi: 10.1016/j.jaad.2014.04.044.
［45］	陆晓君, 经晶, 施辛, 等. 重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗中毒性表皮坏死松解症的临床疗效观察［J］. 中华皮肤科杂志, 2020,53（6）:428⁃434. doi: 10.35541/cjd.2020 0068.
［46］	韩锋, 张静静, 侯彦丽, 等. 单纯单次血浆置换疗法治疗17例中毒性表皮坏死松解症临床观察［J］. 中华皮肤科杂志, 2018,51（12）:896⁃898. doi: 10.3760/cma.j.issn.0412⁃4030.2018.12. 010.
［47］	Yamane Y, Matsukura S, Watanabe Y, et al. Retrospective analysis of Stevens⁃Johnson syndrome and toxic epidermal necrolysis in 87 Japanese patients⁃⁃treatment and outcome［J］. Allergol Int, 2016,65（1）:74⁃81. doi: 10.1016/j.alit.2015.09.001.
［48］	陈娜娜, 张立明, 肖汀. Stevens⁃Johnson综合征的治疗及预后:38例回顾性分析［J］. 中国皮肤性病学杂志, 2016,30（8）:796⁃798. doi: 10.13735/j.cjdv.1001⁃7089.201603132.
［49］	张晓, 李冰, 王雷, 等. 注射用重组人Ⅱ型肿瘤坏死因子受体抗体融合蛋白联合甲泼尼龙治疗中毒性表皮坏死松解症5例［J］. 中国皮肤性病学杂志, 2020,34（9）:1018⁃1022. doi: 10.13735/j.cjdv.1001⁃7089.202002017.
［50］	Chen P, Lin JJ, Lu CS, et al. Carbamazepine⁃induced toxic effects and HLA⁃B*1502 screening in Taiwan［J］. N Engl J Med, 2011,364（12）:1126⁃1133. doi: 10.1056/NEJMoa1009717.
［51］	Ke CH, Chung WH, Wen YH, et al. Cost⁃effectiveness analysis for genotyping before allopurinol treatment to prevent severe cutaneous adverse drug reactions［J］. J Rheumatol, 2017,44（6）:835⁃843. doi: 10.3899/jrheum.151476.
［52］	Liu H, Wang Z, Bao F, et al. Evaluation of prospective HLA⁃B*13:01 screening to prevent dapsone hypersensitivity syndrome in patients with leprosy［J］. JAMA Dermatol, 2019,155（6）:666⁃672. doi: 10.1001/jamadermatol.2018.5360.
［53］	Wang CW, Tassaneeyakul W, Chen CB, et al. Whole genome sequencing identifies genetic variants associated with co⁃trimoxazole hypersensitivity in Asians［J/OL］. J Allergy Clin Immunol, 2020:S0091⁃6749（20）31109⁃X［2021⁃02⁃26］. https://www.sciencedirect.com/science/article/pii/S009167492031109X? via%3Dihub. doi: 10.1016/j.jaci.2020.08.003.

[1]	陆佳维鲁严. 肿瘤坏死因子α抑制剂及其他生物制剂相关矛盾性银屑病的临床研究进展[J]. 中华皮肤科杂志, 2024, 57(5): 479-482.
[2]	《乳房外Paget病诊治专家共识（版）》编写委员会专家组. [开放获取] 乳房外Paget病诊治专家共识（2024版）[J]. 中华皮肤科杂志, 2024, 57(5): 400-408.
[3]	中国“一带一路”皮肤病专病联盟分枝杆菌病研究联盟中国麻风防治协会皮肤性病检验与诊断分会. [开放获取] 中国皮肤结核临床诊疗专家共识（2024版）[J]. 中华皮肤科杂志, 2024, 57(5): 426-434.
[4]	中国医师协会皮肤科医师分会中国中西医结合学会皮肤性病学分会. 红皮病型银屑病诊疗中国专家共识（2024版）[J]. 中华皮肤科杂志, 2024, 57(5): 409-417.
[5]	中华医学会皮肤性病学分会中国医师协会皮肤科医师分会中国中西医结合学会皮肤性病专业委员会 . [开放获取] 中国化学剥脱术临床应用专家共识（公众版2024版）[J]. 中华皮肤科杂志, 2024, 0(5): 20230620-e20230620.
[6]	姚曼雪周乃慧. 程序性细胞死亡蛋白1/程序性细胞死亡蛋白配体1抑制剂相关的Stevens-Johnson综合征/中毒性表皮坏死松解症研究进展 [J]. 中华皮肤科杂志, 2024, 0(3): 20220644-e20220644.
[7]	中国医师协会皮肤科医师分会中华医学会皮肤性病学分会中国医疗保健国际交流促进会皮肤医学分会疑难重症及罕见病国家重点实验室国家皮肤与免疫疾病临床医学研究中心. 特应性皮炎治疗药物应用管理专家共识（2024版）[J]. 中华皮肤科杂志, 2024, 57(2): 97-108.
[8]	中国“一带一路”皮肤病专病联盟分枝杆菌病研究联盟中国麻风防治协会皮肤性病检验与诊断分会. 中国皮肤非结核分枝杆菌病诊治专家共识（2024版）[J]. 中华皮肤科杂志, 2024, 57(2): 109-118.
[9]	中国中西医结合学会皮肤性病专业委员会皮肤肿瘤学组中国抗癌协会黑色素瘤专业委员会. [开放获取] 人干扰素α1b治疗黑色素瘤专家共识（2024版）[J]. 中华皮肤科杂志, 2024, 57(1): 1-7.
[10]	中国医师协会皮肤科医师分会. [开放获取] 保湿润肤类产品应用指导专家共识（2023版）[J]. 中华皮肤科杂志, 2023, 56(8): 711-717.
[11]	陈奇权杨显杰顾恒徐金华郝飞姚煦宋志强. [开放获取] 基于德尔菲法构建《中国慢性诱导性荨麻疹诊治专家共识（2023）》[J]. 中华皮肤科杂志, 2023, 56(6): 534-539.
[12]	中华医学会皮肤性病学分会免疫学组. [开放获取] 中国慢性诱导性荨麻疹诊治专家共识（2023）[J]. 中华皮肤科杂志, 2023, 56(6): 479-488.
[13]	中华医学会皮肤性病学分会中国医师协会皮肤科医师分会. [开放获取] 慢性自发性荨麻疹达标治疗专家共识（2023）[J]. 中华皮肤科杂志, 2023, 56(6): 489-495.
[14]	《蕈样肉芽肿治疗中国专家共识》编写专家组. [开放获取] 蕈样肉芽肿治疗中国专家共识（2023）[J]. 中华皮肤科杂志, 2023, 56(5): 402-409.
[15]	中华医学会皮肤性病学分会中国康复医学会皮肤病康复专业委员会中国中西医结合学会皮肤性病学分会中国医药教育协会皮肤病专业委员会. 老年带状疱疹诊疗专家共识[J]. 中华皮肤科杂志, 2023, 56(2): 97-104.

[开放获取] Stevens-Johnson综合征/中毒性表皮坏死松解症诊疗专家共识

Expert consensus on the diagnosis and treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 53

相关文章 15

Metrics

本文评价

推荐阅读 10