A 72-year-old male patient with right lung squamous cell carcinoma treated with 1 cycle of pembrolizumab combination chemotherapy and pembrolizumab 200  mg monotherapy. After 20 days of treatment, a small amount of erythema appeared around the mouth, head, neck, chest and back, accompanied by itching. Then the lesions aggravated progressively, spreading to the head, limbs, buttocks and perianal area, with blisters and epidermal detachment and necrosis, and the lesions involved >70% of the body surface area, and the pain was obvious. After multidisciplinary consultation, toxic epidermal necrolysis (TEN) was considered. The patient's lesions gradually improved and regressed after treatment with hormones, adjunctive therapy with intravenous immunoglobulin, wound care, infection prevention and nutritional support. TEN adverse reactions were highly likely to be associated with pembrolizumab. This paper reviewed the literature on the cases of TEN induced by pembrolizumab. It analyzed the clinical characteristics and drug treatment strategies of TEN induced by pembrolizumab, to improve clinical staff's ability to recognize and manage immunosuppressant-related skin toxicity and improve the prognosis of tumor patients.

1.Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263. DOI: 10.3322/caac.21834.

2.中国临床肿瘤学会肿瘤支持与康复治疗专家委员会, 中国抗癌协会肿瘤放射治疗专业委员会, 重庆市医药生物技术协会癌症康复与姑息治疗专业委员会. 肺癌姑息治疗中国专家共识[J]. 中华医学杂志, 2022, 102(27): 2084-2095. DOI: 10.3760/cma.j.cn112137-20220401-00680.

3.Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial[J]. Lancet, 2019, 393(10183): 1819-1830. DOI: 10.1016/S0140-6736(18)32409-7.

4.Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events[J]. J Am Acad Dermatol, 2020, 83(5): 1255-1268. DOI: 10.1016/j.jaad.2020.03.132.

5.Machida M, Yamazaki C, Kouda N, et al. A case report involving suppressed nuclear receptor transcription factors 4a1 and Stevens-Johnson syndrome induced by a single dose of pembrolizumab and successfully treated with early steroid administration, resulting in complete remission of stage III lung cancer[J]. J Pharm Health Care Sci, 2022, 8(1): 29. DOI: 10.1186/s40780-022-00261-y.

6.范秀丛, 白荣, 李语玲, 等. 帕博利珠单抗致致死性Stevens-Johnson综合征/中毒性表皮坏死松解症1例 [J]. 中国医院药学杂志, 2021, 41(12): 1281-1282. [Fan XC, Bai R, Li YL, et al. Fatal Stevens-Johnson syndrome/toxic epidermal necrolysis caused by pembrolizumab: one case report[J]. Chinese Journal of Hospital Pharmacy, 2021, 41(12): 1281-1282.] DOI: 10.13286/j.1001-5213.2021.12.21.

7.Vivar KL, Deschaine M, Messina J, et al. Epidermal programmed cell death-ligand 1 expression in TEN associated with nivolumab therapy[J]. J Cutan Pathol, 2017, 44(4): 381-384. DOI: 10.1111/cup.12876.

8.Sassolas B, Haddad C, Mockenhaupt M, et al. ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis[J]. Clin Pharmacol Ther, 2010, 88(1): 60-68. DOI: 10.1038/clpt.2009.252.

9.赵辨, 主编. 临床皮肤病学, 第3版[M]. 南京: 江苏科学技术出版社, 2001: 750-751.

10.Kridin K, Kneiber D, Kowalski EH, et al. Epidermolysis bullosa acquisita: a comprehensive review[J]. Autoimmun Rev, 2019, 18(8): 786-795. DOI: 10.1016/j.autrev.2019.06.007.

11.高国珍, 闫江, 李晓霞, 等. 10例药物性大疱性表皮松解坏死症治疗体会[J]. 河北联合大学学报(医学版), 2013, 15(5): 695-696. DOI: 10.19539/j.cnki.2095-2694. 2013.05.065.

12.Goldinger SM, Stieger P, Meier B, et al. Cytotoxic cutaneous adverse drug reactions during anti-PD-1 therapy[J]. Clin Cancer Res, 2016, 22(16): 4023-4029. DOI: 10.1158/1078-0432.CCR-15-2872.

13.吴迪. 帕博利珠单抗致严重免疫相关皮肤不良反应的文献分析[J]. 中国医院药学杂志, 2022, 42(21): 2282-2287. [Wu D. Literature analysis of severe immuned-related skin adverse reactions induced by pembrolizumab[J]. Chinese Journal of Hospital Pharmacy, 2022, 42(21): 2282-2287.] DOI: 10.13286/j.1001-5213. 2022.21.15.

14.Cai ZR, Lecours J, Adam JP, et al. Toxic epidermal necrolysis associated with pembrolizumab[J]. J Oncol Pharm Pract, 2020, 26(5): 1259-1265. DOI: 10.1177/ 1078155219890659.  

15.中国医师协会呼吸医师分会, 中国医师协会肿瘤多学科诊疗专业委员会. 免疫检查点抑制剂相关毒性防治与管理建议[J]. 中华医学杂志, 2022, 102(24): 1811-1832. DOI: 10.3760/cma.j.cn112137-20211221-02842.

16.Jacobsen A, Olabi B, Langley A, et al. Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome[J]. Cochrane Database Syst Rev, 2022, 3(3): CD013130. DOI: 10.1002/14651858.CD013130.pub2.

17.Houschyar KS, Tapking C, Borrelli MR, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis[J]. J Wound Care, 2021, 30(12): 1012-1019. DOI: 10.12968/jowc.2021.30. 12.1012.

18.中华医学会皮肤性病学分会药物不良反应研究中心. 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. [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.

19.Chang HC, Wang TJ, Lin MH, et al. A review of the systemic treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis[J]. Biomedicines, 2022, 10(9): 2105. DOI: 10.3390/biomedicines10092105.

20.Barron SJ, Del Vecchio MT, Aronoff SC. Intravenous immunoglobulin in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis: a meta-analysis with meta-regression of observational studies[J]. Int J Dermatol, 2015, 54(1): 108-115. DOI: 10.1111/ijd.12423.

21.Chen J, Wang B, Zeng Y, et al. High-dose intravenous immunoglobulins in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese patients: a retrospective study of 82 cases[J]. Eur J Dermatol, 2010, 20(6): 743-747. DOI: 10.1684/ejd.2010. 1077.

22.Kinoshita Y, Saeki H. A review of toxic epidermal necrolysis management in Japan[J]. Allergol Int, 2017, 66(1): 36-41. DOI: 10.1016/j.alit.2016.06.001.

23.Torres-Navarro I, Briz-Redón Á, Botella-Estrada R. Systemic therapies for Stevens-Johnson syndrome and toxic epidermal necrolysis: a SCORTEN-based systematic review and meta-analysis[J]. J Eur Acad Dermatol Venereol, 2021, 35(1): 159-171. DOI: 10.1111/jdv.16685.

24.Roujeau JC, Mockenhaupt M, Guillaume JC, et al. New evidence supporting cyclosporine efficacy in epidermal necrolysis[J]. J Invest Dermatol, 2017, 137(10): 2047-2049. DOI: 10.1016/j.jid.2017.07.828.

25.Chafranska L, Saunte DM, Behrendt N, et al. Pediatric toxic epidermal necrolysis treated successfully with infliximab[J]. Pediatr Dermatol, 2019, 36(3): 342-345. DOI: 10.1111/pde.13778.