Skip to main content
SpringerLink
Log in

Miscellaneous Rheumatic Syndromes

  • Chapter
  • First Online:
Rheumatic Diseases and Syndromes Induced by Cancer Immunotherapy

  • 347 Accesses

Abstract

Although immune checkpoint inhibitors (ICIs) have shown unprecedented efficacy in advanced malignancies, such as lung cancer, renal cell carcinoma, and melanoma, their use can, in some cases, lead to the development of autoimmune sequelae known as immune-related adverse events (irAEs). Rheumatic irAEs can develop in ~5–10% of patients treated with ICIs. Besides inflammatory arthritis, polymyalgia rheumatica, myositis, sicca syndrome, and sarcoidosis, other less common rheumatic irAEs, such as vasculitis, lupus, scleroderma, and eosinophilic fasciitis, may occur after treatment with ICIs. In this chapter, we summarize the available literature on the clinical manifestations and treatment approaches for these less common rheumatic irAEs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Narváez J, et al. Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors: fasciitis with myositis syndrome as a new complication of immunotherapy. Autoimmun Rev. 2018;17(10):1040–5. https://doi.org/10.1016/j.autrev.2018.05.002.

    Article  CAS  PubMed  Google Scholar 

  2. Richter MD, Crowson C, Kottschade LA, Finnes HD, Markovic SN, Thanarajasingam U. Rheumatic syndromes associated with immune checkpoint inhibitors: a single-center cohort of sixty-one patients. Arthritis Rheumatol. 2019;71(3):468–75. https://doi.org/10.1002/art.40745.

    Article  CAS  PubMed  Google Scholar 

  3. Puzanov I, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):1–28. https://doi.org/10.1186/s40425-017-0300-z.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Brahmer JR, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American society of clinical oncology clinical practice guideline. J Clin Oncol. 2018;36(17):1714–68. https://doi.org/10.1200/JCO.2017.77.6385.

    Article  CAS  PubMed  Google Scholar 

  5. Guidelines CP. Management of toxicities from immunotherapy : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Clinical Practice Guidelines. 2017;28(Supplement 4):119–42. https://doi.org/10.1093/annonc/mdx225.

  6. Thompson JA, et al. Management of immunotherapy-related toxicities, version 1.2019. JNCCN J Natl Compr Cancer Netw. 2019;17(3):255–89. https://doi.org/10.6004/jnccn.2019.0013.

    Article  CAS  Google Scholar 

  7. Daxini A, Cronin K, Sreih AG. Vasculitis associated with immune checkpoint inhibitors—a systematic review. Clin Rheumatol. 2018;37(9):2579–84. https://doi.org/10.1007/s10067-018-4177-0.

    Article  PubMed  Google Scholar 

  8. Watanabe R, Zhang H, Berry G, Goronzy JJ, Weyand CM. Immune checkpoint dysfunction in large and medium vessel vasculitis. Am J Physiol Heart Circ Physiol. 2017;312(5):H1052–9. https://doi.org/10.1152/ajpheart.00024.2017.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wilde B, et al. Aberrant expression of the negative costimulator PD-1 on T cells in granulomatosis with polyangiitis. Rheumatol (United Kingdom). 2012;51(7):1188–97. https://doi.org/10.1093/rheumatology/kes034.

    Article  CAS  Google Scholar 

  10. Slot MC, Sokolowska MG, Savelkouls KG, Janssen RGJH, Damoiseaux JGMC, Cohen Tervaert JW. Immunoregulatory gene polymorphisms are associated with ANCA-related vasculitis. Clin Immunol. 2008;128(1):39–45. https://doi.org/10.1016/j.clim.2008.03.506.

    Article  CAS  PubMed  Google Scholar 

  11. Alberici F, Martorana D, Vaglio A. Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrol Dial Transplant. 2014;30:i37–45. https://doi.org/10.1093/ndt/gfu386.

    Article  CAS  PubMed  Google Scholar 

  12. Salem JE, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19(12):1579–89. https://doi.org/10.1016/S1470-2045(18)30608-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cappelli LC, Shah AA, Bingham CO. Immune-related adverse effects of Cancer immunotherapy— implications for rheumatology. Rheum Dis Clin N Am. 2017;43(1):65–78. https://doi.org/10.1016/j.rdc.2016.09.007.

    Article  Google Scholar 

  14. Roy AK, Tathireddy HR, Roy M. Aftermath of induced inflammation: acute periaortitis due to nivolumab therapy. BMJ Case Rep. 2017;2017:3–5. https://doi.org/10.1136/bcr-2017-221852.

    Article  Google Scholar 

  15. Abdel-Wahab N, Shah M, Suarez-Almazor ME. Adverse events associated with immune checkpoint blockade in patients with Cancer: a systematic review of case reports. PLoS One. 2016;11(7):e0160221. https://doi.org/10.1371/journal.pone.0160221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Goldstein BL, Gedmintas L, Todd DJ. Concise communication. Arthritis Rheumatol. 2014;66(3):768–9. https://doi.org/10.1002/art.38282.

    Article  PubMed  Google Scholar 

  17. Goldstein BL, et al. Immune checkpoint dysfunction in large and medium vessel vasculitis. J Immunother Cancer. 2019;58(1):1. https://doi.org/10.1016/j.ejim.2018.07.023.

    Article  Google Scholar 

  18. Tolaymat OA, et al. Drug-associated vasculitis occurring after treatment with pembrolizumab. Rheumatology (Oxford). 2019;58(8):1501–3. https://doi.org/10.1093/rheumatology/kez051.

    Article  Google Scholar 

  19. Ban B, Crowe J, Graham R. Rheumatology case report: immune-reltaed aortitis associated with ipilimumab. The Rheumatologist, 2017;11(5).

    Google Scholar 

  20. Aya F, Ruiz-Esquide V, Viladot M, Font C, Prieto-Gonzalez S, Prat A. Vasculitic neuropathy induced by pembrolizumab. Ann Oncol. 2017;28(2):433–4.

    Article  CAS  PubMed  Google Scholar 

  21. Kao JC, et al. Neurological complications associated with anti–programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74(10):1216–22. https://doi.org/10.1001/jamaneurol.2017.1912.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Läubli H, et al. Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade. J Immunother Cancer. 2017;5(1):1–6. https://doi.org/10.1186/s40425-017-0249-y.

    Article  Google Scholar 

  23. Bender HJ, Dimitrakopoulou-Strauss A, Enk A. Safety of the PD-1 antibody pembrolizumab in patients with high-grade adverse events under ipilimumab treatment. Ann Oncol. 2016;27(7):1353–4.

    Article  CAS  PubMed  Google Scholar 

  24. Sun R, et al. Anti-PD-1 Vasculitis of the central nervous system or radionecrosis? J Immunother Cancer. 2017;5(1):4–6. https://doi.org/10.1186/s40425-017-0304-8.

    Article  Google Scholar 

  25. van den Brom RRH, et al. Rapid granulomatosis with polyangiitis induced by immune checkpoint inhibition. Rheumatol (United Kingdom). 2016;55(6):1143–5. https://doi.org/10.1093/rheumatology/kew063.

    Article  Google Scholar 

  26. Nabel CS, et al. Anti-PD-1 immunotherapy-induced flare of a known underlying relapsing vasculitis mimicking recurrent cancer. Oncologist. 2019;24(8):1013–21. https://doi.org/10.1634/theoncologist.2018-0633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Roger A, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors. Ann Rheum Dis. 2019;78(8):8–9. https://doi.org/10.1136/annrheumdis-2018-213857.

    Article  Google Scholar 

  28. Padda A, Schiopu E, Sovich J, Ma V, Alva A, Fecher L. Ipilimumab induced digital vasculitis. J Immunother Cancer. 2018;6(1):3–7. https://doi.org/10.1186/s40425-018-0321-2.

    Article  Google Scholar 

  29. Gambichler T, Strutzmann S, Tannapfel A, Susok L. Paraneoplastic acral vascular syndrome in a patient with metastatic melanoma under immune checkpoint blockade. BMC Cancer. 2017;17(1):1–5. https://doi.org/10.1186/s12885-017-3313-6.

    Article  Google Scholar 

  30. Comont T, Sibaud V, Mourey L, Cougoul P, Beyne-Rauzy O. Immune checkpoint inhibitor-related acral vasculitis. J Immunother Cancer. 2018;6(1):120. https://doi.org/10.1186/s40425-018-0443-6.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Khaddour K, Singh V, Shayuk M. Acral vascular necrosis associated with immune-check point inhibitors: case report with literature review. BMC Cancer. 2019;19(1):1–6. https://doi.org/10.1186/s12885-019-5661-x.

    Article  Google Scholar 

  32. Le Burel S, et al. Prevalence of immune-related systemic adverse events in patients treated with anti-programmed cell death 1/anti-programmed cell death-ligand 1 agents: a single-Centre pharmacovigilance database analysis. Eur J Cancer. 2017;82:34–44. https://doi.org/10.1016/j.ejca.2017.05.032.

    Article  CAS  PubMed  Google Scholar 

  33. Arellano K, Mosley JC, Moore DC. Case report of Ipilimumab-induced diffuse, nonnecrotizing granulomatous lymphadenitis and granulomatous Vasculitis. J Pharm Pract. 2018;31(2):227–9. https://doi.org/10.1177/0897190017699762.

    Article  PubMed  Google Scholar 

  34. Weiner R, Hanson B, Rehman J, Sun B. Isolated testicular vasculitis due to immune checkpoint inhibitor. no. 4. 2019. https://doi.org/10.5152/eurjrheum.2019.19061.

  35. Tsui E, Gonzales JA. Retinal vasculitis associated with Ipilimumab. Ocul Immunol Inflamm. 2019;3948:1–3. https://doi.org/10.1080/09273948.2019.1610460.

    Article  CAS  Google Scholar 

  36. Manusow JS, Khoja L, Pesin N, Joshua AM, Mandelcorn ED. Retinal vasculitis and ocular vitreous metastasis following complete response to PD-1 inhibition in a patient with metastatic cutaneous melanoma. J Immunother Cancer. 2015;2(1):2–5. https://doi.org/10.1186/s40425-014-0041-1.

    Article  Google Scholar 

  37. Minor DR, Bunker SR, Doyle J. Lymphocytic vasculitis of the uterus in a patient with melanoma receiving ipilimumab. J Clin Oncol. 2013;31(20):2019. https://doi.org/10.1200/JCO.2012.47.5095.

    Article  Google Scholar 

  38. Tomelleri A, Campochiaro C, De Luca G, Cavalli G, Dagna L. Anti-PD1 therapy-associated cutaneous leucocytoclastic vasculitis: A case series. Eur J Intern Med. 2018;57:e11–2. https://doi.org/10.1016/j.ejim.2018.07.023.

    Article  PubMed  Google Scholar 

  39. Michot JM, et al. Drug-induced lupus erythematosus following immunotherapy with anti-programmed death-(ligand) 1. Ann Rheum Dis. 2019;78(7):1–3. https://doi.org/10.1136/annrheumdis-2018-213677.

    Article  Google Scholar 

  40. Pérez-De-Lis M, et al. Autoimmune diseases induced by biological agents. A review of 12,731 cases (BIOGEAS registry). Expert Opin Drug Saf. 2017; https://doi.org/10.1080/14740338.2017.1372421.

  41. Raschi E, Antonazzo IC, Poluzzi E, De Ponti F. Drug-induced systemic lupus erythematosus: should immune checkpoint inhibitors be added to the evolving list? Ann Rheum Dis. 2019; https://doi.org/10.1136/annrheumdis-2019-215819.

  42. Arnaud L, Lebrun-Vignes B, Salem JE. Checkpoint inhibitor-associated immune arthritis. Ann Rheum Dis. 2019;78(7):1–2. https://doi.org/10.1136/annrheumdis-2018-213470.

    Article  Google Scholar 

  43. Blakeway EA, Elshimy N, Muinonen-Martin A, Marples M, Mathew B, Mitra A. Cutaneous lupus associated with pembrolizumab therapy for advanced melanoma: a report of three cases. Melanoma Res. 2019;29(3):338–41. https://doi.org/10.1097/CMR.0000000000000587.

    Article  PubMed  Google Scholar 

  44. Kosche C, Owen JL, Choi JN. Widespread subacute cutaneous lupus erythematosus in a patient receiving checkpoint inhibitor immunotherapy with ipilimumab and nivolumab. Dermatol Online J. 2019;25(10):0–3.

    Google Scholar 

  45. Liu RC, Sebaratnam DF, Jackett L, Kao S, Lowe PM. Subacute cutaneous lupus erythematosus induced by nivolumab. Australas J Dermatol. 2018;59(2):e152–4. https://doi.org/10.1111/ajd.12681.

    Article  PubMed  Google Scholar 

  46. Fadel KB, El Karoui K. Anti-CTLA4 antibody-induced lupus nephritis. N Engl J Med. 2009;361(2):211–2.

    Article  CAS  PubMed  Google Scholar 

  47. Barbosa NS, Wetter DA, Wieland CN, Shenoy NK, Markovic SN, Thanarajasingam U. Scleroderma induced by Pembrolizumab: a case series. Mayo Clin Proc. 2017;92(7):1158–63. https://doi.org/10.1016/j.mayocp.2017.03.016.

    Article  PubMed  Google Scholar 

  48. Tjarks BJ, Kerkvliet AM, Jassim AD, Bleeker JS. Scleroderma-like skin changes induced by checkpoint inhibitor therapy. J Cutan Pathol. 2018;45(8):615–8. https://doi.org/10.1111/cup.13273.

    Article  PubMed  Google Scholar 

  49. Shenoy N, Esplin B, Barbosa N, Wieland C, Thanarajasingam U, Markovic S. Pembrolizumab induced severe sclerodermoid reaction. Ann Oncol. 2017;28(2):432–3. https://doi.org/10.1093/annonc/mdw543.

    Article  CAS  PubMed  Google Scholar 

  50. Shah AA, Casciola-Rosen L. Cancer and scleroderma: a paraneoplastic disease with implications for malignancy screening. Curr Opin Rheumatol. 2015;27(6):563–70. https://doi.org/10.1097/BOR.0000000000000222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Pinal-Fernandez I, Selva-O’ Callaghan A, Grau JM. Diagnosis and classification of eosinophilic fasciitis. Autoimmun Rev. 2014;13(4–5):379–82. https://doi.org/10.1016/j.autrev.2014.01.019.

    Article  CAS  PubMed  Google Scholar 

  52. Granter SR, Barnhill RL, Hewins ME, Duray PH. Identification of Borrelia burgdorferi in diffuse fasciitis with peripheral eosinophilia: Borrelial fasciitis. Clin Pediatr. 1995; https://doi.org/10.1001/jama.272.16.1283.

  53. Hashimoto Y, et al. Polymerase chain reaction of borrelia burgdorferi flagellin gene in shulman syndrome. Dermatology. 1996; https://doi.org/10.1159/000246339.

  54. Bachmeyer C, Monge M, Dhôte R, Sanguina M, Aractingi S, Mougeot-Martin M. Eosinophilic fasciitis following idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia and Hashimoto’s disease [6]. Dermatology. 1999; https://doi.org/10.1159/000018271.

  55. Imren S, Tüzüner N, Yazici H. Eosinophilic fasciitis with thyroid disease. Clin Exp Rheumatol. 1988;

    Google Scholar 

  56. Boiesen M, Keiding LM, Thomsen K. Eosinophilic fasciitis: report of a case with features of other autoimmune disease. Dermatology. 1983; https://doi.org/10.1159/000249768.

  57. Smiley AM, Husain M, Indenbaum S. Eosinophilic fasciitis in association with thyroid disease: a report of three cases. J Rheumatol. 1980;

    Google Scholar 

  58. Chan KK, et al. Eosinophilic fasciitis following checkpoint inhibitor therapy: four cases and a review of literature. Oncologist. 2019; https://doi.org/10.1634/theoncologist.2019-0508.

  59. Wright NA, Mazori DR, Patel M, Merola JF, Femia AN, Vleugels RA. Epidemiology and treatment of eosinophilic fasciitis: an analysis of 63 patients from 3 tertiary care centers. JAMA Dermatol. 2016; https://doi.org/10.1001/jamadermatol.2015.3648.

  60. Wechsler B, et al. Concise report Eosinophilic fasciitis (Shulman disease ): new insights into the therapeutic management from a series of 34 patients. 2011, p. 557–61. doi: https://doi.org/10.1093/rheumatology/ker366.

  61. Lebeaux D, Sène D. Eosinophilic fasciitis (Shulman disease). Best Pract Res Clin Rheumatol. 2012;26(4):449–58. https://doi.org/10.1016/j.berh.2012.08.001.

    Article  CAS  PubMed  Google Scholar 

  62. Fett N, Arthur M. Eosinophilic fasciitis: current concepts. Clin Dermatol. 2018;36(4):487–97. https://doi.org/10.1016/j.clindermatol.2018.04.006.

    Article  PubMed  Google Scholar 

  63. Kim SR, Charos A, Damsky W, Heald P, Girardi M, King BA. Treatment of generalized deep morphea and eosinophilic fasciitis with the Janus kinase inhibitor tofacitinib. JAAD Case Rep. 2018;4(5):443–5. https://doi.org/10.1016/j.jdcr.2017.12.003.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kostine M, et al. Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer-clinical aspects and relationship with tumour response: a single-Centre prospective cohort study. Ann Rheum Dis. 2018;77(3):393–8. https://doi.org/10.1136/annrheumdis-2017-212257.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, USA

    Tamiko R. Katsumoto

  2. Rhumatologie, Université Paris-Saclay, Assistance Publique – Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, France

    Xavier Mariette

Authors
  1. Tamiko R. Katsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xavier Mariette
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tamiko R. Katsumoto .

Editor information

Editors and Affiliations

  1. Department of Health Services Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Maria E. Suarez-Almazor

  2. Department of Rheumatic and Immunologic Diseases, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    Leonard H. Calabrese

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Katsumoto, T.R., Mariette, X. (2021). Miscellaneous Rheumatic Syndromes. In: Suarez-Almazor, M.E., Calabrese, L.H. (eds) Rheumatic Diseases and Syndromes Induced by Cancer Immunotherapy. Springer, Cham. https://doi.org/10.1007/978-3-030-56824-5_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-56824-5_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-56823-8

  • Online ISBN: 978-3-030-56824-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation