We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Lichenoid dermatitis following PD-1 inhibitor-induced toxic epidermal necrolysis: a case report and literature review

    Long Zhang

    Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    ,
    Liang Wang

    Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    ,
    Qionghui Cheng

    Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    ,
    Xia Lei

    Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    ,
    Jinjin Wu

    Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    &
    Nian Chen

    *Author for correspondence:

    E-mail Address: cn8068@126.com

    Department of Dermatology, Daping Hospital, Army Medical University, Chongqing, 400042, China

    Published Online:https://doi.org/10.2217/imt-2023-0081

    Immune checkpoint inhibitors such as anti-PD-1 receptor antibodies have been shown to be effective in patients with advanced gastric cancer. However, there is a growing concern about immune-related adverse events. A case of a patient with gastric adenocarcinoma who developed toxic epidermal necrolysis (TEN) induced by sintilimab and subsequently developed lichenoid dermatitis is reported. TEN was diagnosed according to a history of sintilimab use, clinical symptoms and physical examination. During hospitalization, the patient developed recurrent fever caused by bacteremia and recovered from TEN after anti-infection and anti-inflammatory treatments. However, when TEN was controlled, the patient developed the lesional manifestations of lichenoid dermatitis. To date, no cases of lichenoid dermatitis after TEN have been reported following the use of PD-1 inhibitors.

    Plain language summary

    PD-1 inhibitors are drugs that help fight stomach cancer but can sometimes cause skin problems. Most skin problems are minor and do not have a serious impact on the patient's health. However, life-threatening skin problems such as toxic epidermal necrolysis (TEN) can sometimes happen. This case report describes a patient with stomach cancer who had lichenoid dermatitis (another skin problem) after TEN, following the treatment of his cancer with PD-1 inhibitors. To the best of our knowledge, it is very rare to experience both skin problems after treating cancer with PD-1 inhibitors. This rare phenomenon is reported to bring more attention to it. More research is needed to determine how to treat this problem better.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Belum VR, Benhuri B, Postow MA et al. Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur. J. Cancer 60, 12–25 (2016).
    • 2. Hofmann L, Forschner A, Loquai C et al. Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur. J. Cancer 60, 190–209 (2016).
    • 3. Vivar KL, Deschaine M, Messina J et al. Epidermal programmed cell death-ligand 1 expression in TEN associated with nivolumab therapy. J. Cutan. Pathol. 44(4), 381–384 (2017).
    • 4. Bhardwaj M, Chiu MN, Pilkhwal SS. Adverse cutaneous toxicities by PD-1/PD-L1 immune checkpoint inhibitors: pathogenesis, treatment, and surveillance. Cutan. Ocul. Toxicol. 41(1), 73–90 (2022). •• The pathogenesis, treatment and surveillance of adverse cutaneous toxicities caused by anti-PD-1 therapy.
    • 5. Totonchy MB, Ezaldein HH, Ko CJ, Choi JN. Inverse psoriasiform eruption during pembrolizumab therapy for metastatic melanoma. JAMA Dermatol. 152(5), 590–592 (2016).
    • 6. Shi VJ, Rodic N, Gettinger S et al. Clinical and histologic features of lichenoid mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy. JAMA Dermatol. 152(10), 1128–1136 (2016).
    • 7. Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of diagnosis and management. Med. Lith. 57(9), 895 (2021).
    • 8. Wang J, Fei K, Jing H et al. Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit. mAbs 11(8), 1443–1451 (2019).
    • 9. Jiang H, Yu X, Li N et al. Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study. J. Immunother. Cancer. 10(3), e003635 (2022). • Suggests why anti-PD-1 treatment is effective in gastric adenocarcinoma.
    • 10. Baxi S, Yang A, Gennarelli RL et al. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ 360, k793 (2018).
    • 11. Hsu DY, Brieva J, Silverberg NB, Silverberg JI. Morbidity and mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis in United States adults. J. Invest. Dermatol. 136(7), 1387–1397 (2016).
    • 12. Dasanu CA. Late-onset Stevens-Johnson syndrome due to nivolumab use for hepatocellular carcinoma. J. Oncol. Pharm. Pract. 25(8), 2052–2055 (2019).
    • 13. Sotozono C, Ang LP, Koizumi N et al. New grading system for the evaluation of chronic ocular manifestations in patients with Stevens-Johnson syndrome. Ophthalmology 114(7), 1294–1302 (2007).
    • 14. 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. Nat. Med. 14(12), 1343–1350 (2008).
    • 15. Viard-Leveugle I, Gaide O, Jankovic D et al. TNF-alpha and IFN-gamma are potential inducers of Fas-mediated keratinocyte apoptosis through activation of inducible nitric oxide synthase in toxic epidermal necrolysis. J. Invest. Dermatol. 133(2), 489–498 (2013).
    • 16. Ergen EN, Hughey LC. Stevens-Johnson syndrome and toxic epidermal necrolysis. JAMA Dermatol. 153(12), 1344 (2017). •• Description of the mechanism, clinical manifestations, diagnosis and treatments of toxic epidermal necrolysis.
    • 17. Quach HT, Johnson DB, Leboeuf NR, Zwerner JP, Dewan AK. Cutaneous adverse events caused by immune checkpoint inhibitors. J. Am. Acad. Dermatol. 85(4), 956–966 (2021).
    • 18. Hwang A, Iskandar A, Dasanu CA. Stevens-Johnson syndrome manifesting late in the course of pembrolizumab therapy. J. Oncol. Pharm. Pract. 25(6), 1520–1522 (2019).
    • 19. Saw S, Lee HY, Ng QS. Pembrolizumab-induced Stevens-Johnson syndrome in non-melanoma patients. Eur. J. Cancer 81, 237–239 (2017).
    • 20. Huang Y, Zhu L, Ma X et al. A case of sintilimab-induced SJS/TEN: dermatologic adverse reactions associated with programmed cell death protein-1 inhibitors. Dermatol. Ther. 35(9), e15663 (2022). • Description of dermatological adverse events associated with PD-1 inhibitors.
    • 21. Li G, Gong S, Wang N, Yao X. Toxic epidermal necrolysis induced by sintilimab in a patient with advanced non-small cell lung cancer and comorbid pulmonary tuberculosis: a case report. Front. Immunol. 13, 989966 (2022).
    • 22. Li X, Qu L, Ren Y, Hu C. Case report: a case report and literature review on severe bullous skin reaction induced by anti-PD-1 immunotherapy in a cervical cancer patient. Front. Pharmacol. 12, 707967 (2021).
    • 23. Yang H, Ma Q, Sun Y, Zhang K, Xing Y, Li H. Case report: toxic epidermal necrolysis associated with sintilimab in a patient with relapsed thymic carcinoma. Front. Oncol. 12, 1065137 (2022).
    • 24. Yang W, Xu X, Xia D, Wang H, Jiang J, Yang G. Toxic epidermal necrolysis associated with chemoimmunotherapy for lymphoma: case report and literature review. Immunotherapy 14(5), 275–282 (2022).
    • 25. Zhao Y, Cao Y, Wang X, Qian T. Treatment of PD-1 inhibitor-associated toxic epidermal necrolysis: a case report and brief review. OncoTargets Ther. 15, 345–351 (2022).
    • 26. Saw S, Lee HY, Ng QS. Pembrolizumab-induced Stevens-Johnson syndrome in non-melanoma patients. Eur. J. Cancer 81, 237–239 (2017).
    • 27. Kumar R, Bhandari S. Pembrolizumab induced toxic epidermal necrolysis. Curr. Probl. Cancer 44(2), 100478 (2020).
    • 28. Phillips GS, Wu J, Hellmann MD et al. Treatment outcomes of immune-related cutaneous adverse events. J. Clin. Oncol. 37(30), 2746–2758 (2019). • Description of the incidence of lichenoid dermatitis.
    • 29. Geisler AN, Phillips GS, Barrios DM et al. Immune checkpoint inhibitor-related dermatologic adverse events. J. Am. Acad. Dermatol. 83(5), 1255–1268 (2020).
    • 30. Maul JT, Guillet C, Oschmann A et al. Cutaneous lichenoid drug eruptions: a narrative review evaluating demographics, clinical features and culprit medications. J. Eur. Acad. Dermatol. Venereol. 37(5), 965–975 (2023).
    • 31. Reschke R, Mockenhaupt M, Simon JC, Ziemer M. Severe bullous skin eruptions on checkpoint inhibitor therapy–in most cases severe bullous lichenoid drug eruptions. J. Dtsch Dermatol. Ges. 17(9), 942–948 (2019).
    • 32. Armour K, Lowe P. Complicated lichenoid drug eruption. Australas. J. Dermatol. 46(1), 21–24 (2005).
    • 33. Potts J, Lee RR, Hilliard CA. Lichenoid dermatitis preceding Stevens-Johnson syndrome in a patient treated with nivolumab. BMJ Case Rep. 15(8), e251233 (2022).
    • 34. Goldinger SM, Stieger P, Meier B et al. Cytotoxic cutaneous adverse drug reactions during anti-PD-1 therapy. Clin. Cancer Res. 22(16), 4023–4029 (2016).
    • 35. Worsnop F, Wee J, Natkunarajah J, Moosa Y, Marsden R. Reaction to biological drugs: infliximab for the treatment of toxic epidermal necrolysis subsequently triggering erosive lichen planus. Clin. Exp. Dermatol. 37(8), 879–881 (2012).
    • 36. Wagner G, Rose C, Sachse MM. Clinical variants of lichen planus. J. Dtsch Dermatol. Ges. 11(4), 309–319 (2013).
    • 37. Ondhia C, Kaur C, Mee J, Natkunarajah J, Singh M. Lichen planus pemphigoides mimicking toxic epidermal necrolysis. Am. J. Dermatopathol. 41(11), e144–e147 (2019).
    • 38. Kim JH, Kim SC. Paraneoplastic pemphigus: paraneoplastic autoimmune disease of the skin and mucosa. Front. Immunol. 10, 1259 (2019).
    • 39. Lam S, Stone MS, Goeken JA et al. Paraneoplastic pemphigus, cicatricial conjunctivitis, and acanthosis nigricans with pachydermatoglyphy in a patient with bronchogenic squamous cell carcinoma. Ophthalmology 99(1), 108–113 (1992).
    • 40. Joly P, Richard C, Gilbert D et al. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. J. Am. Acad. Dermatol. 43(4), 619–626 (2000).