Immune-checkpoint inhibitor-induced bullous pemphigoid in patients with metastatic renal cell carcinoma: two case reports and systematic review of the literature
DOI:
https://doi.org/10.2340/1651-226X.2026.46088Keywords:
Checkpoint inhibitors, Cancer immunotherapy, Renal cancer, Immune related adverse events, bullous pemphigoidAbstract
Background and purpose: Immune-checkpoint inhibitors (ICIs) improve outcomes in renal cell carcinoma (RCC) but may cause immune-related adverse events (irAEs), including cutaneous toxicity. Bullous pemphigoid (BP) is a rare but clinically significant irAE that can require ICI discontinuation.
Patient/material and methods: We report two cases of BP in patients with metastatic RCC treated with ICIs at Karolinska University Hospital, Stockholm, Sweden. In addition, a systematic review was conducted in Medline, Embase, Cochrane Library, and Web of Science to identify published cases of ICI-associated BP in metastatic RCC. Data on patient characteristics, treatment, clinical presentation, diagnostics, management, and outcomes were extracted and descriptively analysed.
Results: Twenty-eight publications describing 30 cases were identified. Median age at BP onset was 69 years (interquartile range [IQR] 65–73), and 86.7% were male. Nivolumab was the most commonly reported ICI monotherapy. Median time from ICI initiation to BP onset was 35 weeks (IQR 16–76). Typical manifestations included tense bullae and vesiculobullous eruptions on the trunk and extremities. Diagnosis was confirmed by skin biopsy and immunological testing in 80% of cases. Management mainly involved corticosteroids, while ICI interruption or discontinuation was required in over half the cases. Both patients from our center improved after immunosuppressive treatment.
Interpretation: ICI-associated BP is a rare but important irAE in metastatic RCC, often occurring after prolonged ICI exposure and potentially requiring treatment modification. Early recognition may improve multidisciplinary management.
Downloads
References
Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17(8):807–21. DOI: https://doi.org/10.1038/s41423-020-0488-6
Dine J, Gordon R, Shames Y, Kasler MK, Barton-Burke M. Immune checkpoint inhibitors: an innovation in immunotherapy for the treatment and management of patients with cancer. Asia Pac J Oncol Nurs. 2017;4(2):127–35. DOI: https://doi.org/10.4103/apjon.apjon_4_17
Powles T, Albiges L, Bex A, Comperat E, Grünwald V, Kanesvaran R, et al. Renal cell carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(8):692–706. DOI: https://doi.org/10.1016/j.annonc.2024.05.537
Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563–80. DOI: https://doi.org/10.1038/s41571-019-0218-0
Kennedy LB, Salama AKS. A review of cancer immunotherapy toxicity. CA Cancer J Clin. 2020;70(2):86–104. DOI: https://doi.org/10.3322/caac.21596
Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158–68. DOI: https://doi.org/10.1056/NEJMra1703481
Geisler AN, Phillips GS, Barrios DM, Wu J, Leung DYM, Moy AP, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255–68. DOI: https://doi.org/10.1016/j.jaad.2020.03.132
Sibaud V. Dermatologic reactions to immune checkpoint inhibitors: skin toxicities and immunotherapy. Am J Clin Dermatol. 2018;19(3):345–61. DOI: https://doi.org/10.1007/s40257-017-0336-3
Wongvibulsin S, Pahalyants V, Kalinich M, Murphy W, Yu KH, Wang F, et al. Epidemiology and risk factors for the development of cutaneous toxicities in patients treated with immune-checkpoint inhibitors: a United States population-level analysis. J Am Acad Dermatol. 2022;86(3):563–72. DOI: https://doi.org/10.1016/j.jaad.2021.03.094
Molina GE, Reynolds KL, Chen ST. Diagnostic and therapeutic differences between immune checkpoint inhibitor-induced and idiopathic bullous pemphigoid: a cross-sectional study. Br J Dermatol. 2020;183(6):1126–8. DOI: https://doi.org/10.1111/bjd.19313
Clark JM, Sanders S, Carter M, Honeyman D, Cleo G, Auld Y, et al. Improving the translation of search strategies using the Polyglot Search Translator: a randomized controlled trial. J Med Libr Assoc. 2020;108(2):195–207. DOI: https://doi.org/10.5195/jmla.2020.834
Bramer WM, Giustini D, de Jonge GB, Holland L, Bekhuis T. De-duplication of database search results for systematic reviews in EndNote. J Med Libr Assoc. 2016;104(3):240–3. DOI: https://doi.org/10.3163/1536-5050.104.3.014
Asdourian MS, Shah N, Jacoby TV, Reynolds KL, Chen ST. Association of bullous pemphigoid with immune checkpoint inhibitor therapy in patients with cancer: a systematic review. JAMA Dermatol. 2022;158(8):933–41. DOI: https://doi.org/10.1001/jamadermatol.2022.1624
Kridin K, Ludwig RJ. The growing incidence of bullous pemphigoid: overview and potential explanations. Front Med (Lausanne). 2018;5:220. DOI: https://doi.org/10.3389/fmed.2018.00220
Joly P, Baricault S, Sparsa A, Bernard P, Bédane C, Duvert-Lehembre S, et al. Incidence and mortality of bullous pemphigoid in France. J Invest Dermatol. 2012;132(8):1998–2004. DOI: https://doi.org/10.1038/jid.2012.35
Scelo G, Li P, Chanudet E, Muller DC. Variability of sex disparities in cancer incidence over 30 years: the striking case of kidney cancer. Eur Urol Focus. 2018;4(4):586–90. DOI: https://doi.org/10.1016/j.euf.2017.01.006
Gotera N, Weilg P, Heleno C, Ferrari-Gabilondo N. A case of bullous pemphigoid associated with nivolumab therapy. Cureus. 2022;14(5):e24804. DOI: https://doi.org/10.7759/cureus.24804
Ellis SR, Vierra AT, Millsop JW, Lacouture ME, Kiuru M. Dermatologic toxicities to immune checkpoint inhibitor therapy: a review of histopathologic features. J Am Acad Dermatol. 2020;83(4):1130–43. DOI: https://doi.org/10.1016/j.jaad.2020.04.105
Tang K, Seo J, Tiu BC, Le TK, Pahalyants V, Raval NS, et al. Association of cutaneous immune-related adverse events with increased survival in patients treated with anti-programmed cell death 1 and anti-programmed cell death ligand 1 therapy. JAMA Dermatol. 2022;158(2):189–93. DOI: https://doi.org/10.1001/jamadermatol.2021.5476
Powers CM, Thakker S, Gulati N, Talia J, Dubin D, Zone J, et al. Bullous pemphigoid: a practical approach to diagnosis and management in the modern era. J Am Acad Dermatol. 2025;92(6):1337–50. DOI: https://doi.org/10.1016/j.jaad.2025.01.086
Elston DM, Stratman EJ, Miller SJ. Skin biopsy: biopsy issues in specific diseases. J Am Acad Dermatol. 2016;74(1):1–16; quiz 7–8. DOI: https://doi.org/10.1016/j.jaad.2015.06.033
Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073–126. DOI: https://doi.org/10.1200/JCO.21.01440
Decruyenaere A, Gennigens C, Rottey S, Laenen A, Seront E, Everaert E, et al. Optimal treatment duration in metastatic renal cell carcinoma patients responding to immune checkpoint inhibitors: should we treat beyond two years? Acta Oncol. 2025;64:979–88. DOI: https://doi.org/10.2340/1651-226X.2025.43876
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2026 Panagiotis Filis, Magnus Lindskog, Philip Curman, Natalia Kuzmina, Åsa Krantz, Katerina Chatzidionysiou, Fernanda Costa Svedman, Ioannis Zerdes
This work is licensed under a Creative Commons Attribution 4.0 International License.
