Online first
Case report
Published online: 2024-06-05

open access

Page views 64
Article views/downloads 34
Get Citation

Connect on Social Media

Connect on Social Media

Refractory bullous pemphigoid during treatment with pembrolizumab in the first-line treatment of advanced non-small cell lung cancer

Renata Olech1, Monika Rychlik-Grabowska12, Sławomir Mańdziuk12

Abstract

Dermatological toxicity is one of the most common immune-related adverse events (irAEs) of treatment with immune checkpoint inhibitors (ICIs). Bullous pemphigoid (BP) is a rare and serious complication of these drugs that can be difficult to establish, as its initial symptoms may be indistinguishable from mild skin lesions. This paper presents the case of a 68-year-old patient who developed BP after receiving one of the ICI therapies, pembrolizumab, for advanced non-small cell lung cancer (NSCLC). After approximately 7 months of therapy, a grade 3 skin toxicity in the Common Terminology Criteria for Adverse Events (CTCAE) occurred in the form of rash and pruritus. Pembrolizumab was then held and prednisone and antihistamines were introduced. When dermal toxicity improved to grade 1, pembrolizumab was resumed and prednisone was kept at a dose of 10 mg. Immunotherapy was discontinued 3 months later, after the recurrence of grade 3 skin toxicity symptoms. When the patient developed blisters filled with clear fluid, dermatologists suspected pembrolizumab-induced bullous pemphigoid. Bullous pemphigoid was subsequently confirmed using a direct immunofluorescence test and histopathological examination. The patient’s skin condition improved after the use of steroid therapy and methotrexate, and the cancer process stabilized for over one year. Cancer progression and deterioration of the patient’s general condition were observed approximately 4 months after the termination of pembrolizumab therapy. The paper also discusses the key aspects of ICIs-induced BP, especially pembrolizumab induced BP in the first-line treatment of metastatic NSCLC. Early diagnosis of skin lesions and the initiation of appropriate treatment may lead to better outcomes for patients and prevent disruptions in immunotherapy.

Article available in PDF format

View PDF Download PDF file

References

  1. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-Year outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score ≥ 50. J Clin Oncol. 2021; 39(21): 2339–2349.
  2. Wang J, Hu X, Jiang W, et al. Analysis of the clinical characteristics of pembrolizumab-induced bullous pemphigoid. Front Oncol. 2023; 13: 1095694.
  3. Lopez AT, Khanna T, Antonov N, et al. A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors. Int J Dermatol. 2018; 57(6): 664–669.
  4. Shalata W, Weissmann S, Itzhaki Gabay S, et al. A retrospective, single-institution experience of bullous pemphigoid as an adverse effect of immune checkpoint inhibitors. Cancers (Basel). 2022; 14(21): 5451.
  5. Baigrie D, Nookala V. Bullous Pemphigoid. [Updated 2023 Mar 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535374/.
  6. Miyamoto D, Santi CG, Aoki V, et al. Bullous pemphigoid. An Bras Dermatol. 2019; 94(2): 133–146.
  7. Geisler AN, Phillips GS, Barrios DM, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020; 83(5): 1255–1268.
  8. Tsiogka A, Bauer JW, Patsatsi A. Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: a review of the literature. Acta Derm Venereol. 2021; 101(1): adv00377.
  9. Woźniak K, Dmochowski M, Placek W, et al. Pemphigoid – diagnosis and treatment. Polish Dermatological Society Consensus. Dermatol Rev/Przeg Dermatol. 2016; 103(1): 19–34.
  10. Haanen J, Obeid M, Spain L, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022; 33(12): 1217–1238.
  11. Cardona AF, Ruiz-Patiño A, Zatarain-Barron ZL, et al. Refractory bullous pemphigoid in a patient with metastatic lung adenocarcinoma treated with pembrolizumab. Case Rep Oncol. 2021; 14(1): 386–390.
  12. Kaul S, Wang A, Grushchak S, et al. Pembrolizumab-induced reactivation of bullous pemphigoid. Int J Dermatol. 2021; 60(6): 757–758.
  13. Hua C, Boussemart L, Mateus C, et al. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol. 2016; 152(1): 45–51.
  14. Min Lee CK, Li S, Tran DC, et al. Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study. J Am Acad Dermatol. 2018; 79(6): 1047–1052.