Skip to main navigation menu Skip to main content Skip to site footer
##common.pageHeaderLogo.altText##

Original article

Vol. 154 No. 3 (2024)

Pembrolizumab-associated anti-MDA5 dermatomyositis in a patient with lung cancer: a first case report

DOI
https://doi.org/10.57187/s.3513
Cite this as:
Swiss Med Wkly. 2024;154:3513
Published
04.03.2024

Summary

We report the first case of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis as a systemic immune-related adverse event in a 64-year-old man receiving pembrolizumab to treat advanced lung cancer. The patient experienced hypothyroidism, myalgia, skin involvement, dyspnoea and diarrhoea. Laboratory tests revealed raised inflammatory markers, hypercreatinekinasemia and anti-MDA5 autoantibodies. Electroneuromyography and pathognomonic signs on physical examination confirmed the diagnosis of pauci-myopathic dermatomyositis. Pembrolizumab was discontinued and immunosuppressive therapy led to rapid and progressive improvement, with complete remission of dermatomyositis. This case report widens the spectrum of systemic immune-related adverse events associated with pembrolizumab.

References

  1. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0; c2017-2023 [cited 2023 November 04]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
  2. Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018 Jan;378(2):158–68. 10.1056/NEJMra1703481 DOI: https://doi.org/10.1056/NEJMra1703481
  3. Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, et al.; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov;375(19):1823–33. 10.1056/NEJMoa1606774 DOI: https://doi.org/10.1056/NEJMoa1606774
  4. Takatsuki K, Yanagihara T, Egashira A, Ogo N, Yoshizawa S, Sunami S, et al. A Rare Case of Pembrolizumab-Induced Dermatomyositis in a Patient with Cancer of Unknown Primary Origin. Am J Case Rep. 2021 Apr;22:e930286. 10.12659/AJCR.930286 DOI: https://doi.org/10.12659/AJCR.930286
  5. Kartolo A, Towheed T, Mates M. A case of successful pembrolizumab rechallenge in a patient with non-small-cell lung cancer and grade 3 dermatomyositis. Immunotherapy. 2021 Apr;13(6):477–81. 10.2217/imt-2020-0309 DOI: https://doi.org/10.2217/imt-2020-0309
  6. European Medicines Agency. Keytruda Product Information. Annex I. Summary of product characteristics. [cited 2023 November 04] Available from: https://www.ema.europa.eu/en/documents/product-information/keytruda-epar-product-information_en.pdf
  7. European database of suspected adverse drug reactions reports [cited 2023 November 04] Available from: https://www.adrreports.eu/en/index.html
  8. Nombel A, Fabien N, Coutant F. Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies. Front Immunol. 2021 Oct;12:773352. 10.3389/fimmu.2021.773352 DOI: https://doi.org/10.3389/fimmu.2021.773352
  9. Parronchi P, Radice A, Palterer B, Liotta F, Scaletti C. MDA5-positive dermatomyositis: an uncommon entity in Europe with variable clinical presentations. Clin Mol Allergy. 2015 Nov;13(1):22. 10.1186/s12948-015-0031-y DOI: https://doi.org/10.1186/s12948-015-0031-y
  10. So H, So J, Lam TT, Wong VT, Ho R, Li WL, et al. Seasonal Effect on Disease Onset and Presentation in Anti-MDA5 Positive Dermatomyositis. Front Med (Lausanne). 2022 Feb;9:837024. 10.3389/fmed.2022.837024 DOI: https://doi.org/10.3389/fmed.2022.837024
  11. Zhang SH, Zhao Y, Xie QB, Jiang Y, Wu YK, Yan B. Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis. Br J Dermatol. 2019 May;180(5):1090–8. 10.1111/bjd.16917 DOI: https://doi.org/10.1111/bjd.16917
  12. Holzer MT, Krusche M, Ruffer N, Haberstock H, Stephan M, Huber TB, et al. New-onset dermatomyositis following SARS-CoV-2 infection and vaccination: a case-based review. Rheumatol Int. 2022 Dec;42(12):2267–76. 10.1007/s00296-022-05176-3 DOI: https://doi.org/10.1007/s00296-022-05176-3
  13. Wu M, Karim M, Ashinoff R. COVID-19 vaccine-associated dermatomyositis. JAAD Case Rep. 2022 May;23:58–60. 10.1016/j.jdcr.2022.02.023 DOI: https://doi.org/10.1016/j.jdcr.2022.02.023
  14. Ganatra K, Aggarwal R, Gupta L. Mechanic’s Hand Heralding Relapse in an Indian Adolescent with Anti-MDA5 Positive Juvenile Dermatomyositis. Mediterr J Rheumatol. 2022 Jun;33(2):268–70. 10.31138/mjr.33.2.268 DOI: https://doi.org/10.31138/mjr.33.2.268
  15. Kawakami N, Eda H, Nishiura M, Chaya A, Saito F, Namkoong H. A decade of Gottron’s papules, inverse Gottron’s papules and mechanic’s hand in anti-MDA5-associated interstitial lung disease with clinically amyopathic dermatomyositis. Oxf Med Case Rep. 2020 Jun;2020(6):omaa039. 10.1093/omcr/omaa039 DOI: https://doi.org/10.1093/omcr/omaa039
  16. Tsuji H, Nakashima R, Hosono Y, Imura Y, Yagita M, Yoshifuji H, et al. Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis. Arthritis Rheumatol. 2020 Mar;72(3):488–98. 10.1002/art.41105 DOI: https://doi.org/10.1002/art.41105
  17. Wu W, Guo L, Fu Y, Wang K, Zhang D, Xu W, et al. Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis. Clin Rev Allergy Immunol. 2021 Apr;60(2):293–304. 10.1007/s12016-020-08822-5 DOI: https://doi.org/10.1007/s12016-020-08822-5
  18. Wang LM, Yang QH, Zhang L, Liu SY, Zhang PP, Zhang X, et al. Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Rheumatology (Oxford). 2022 Aug;61(9):3704–10. 10.1093/rheumatology/keab928 DOI: https://doi.org/10.1093/rheumatology/keab928
  19. Chen Z, Wang X, Ye S. Tofacitinib in Amyopathic Dermatomyositis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jul;381(3):291–3. 10.1056/NEJMc1900045 DOI: https://doi.org/10.1056/NEJMc1900045
  20. 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 Sep;16(9):563–80. 10.1038/s41571-019-0218-0 DOI: https://doi.org/10.1038/s41571-019-0218-0