Skip to main content

Advertisement

SpringerLink
Log in

Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cause or coincidence?

  • Case Based Review
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Tocilizumab is an anti-interleukin (IL)-6 receptor monoclonal antibody, used since 2010 for the treatment of severe rheumatoid arthritis (RA). It is known to induce infection, similarly to other biotherapies which modulate immune response and cytokines. Few cases of malignancy, however, have as yet been reported. We describe here the case of a patient with severe RA, previously treated with prednisolone, methotrexate, leflunomide, etanercept, and rituximab, who, after 8 months of treatment with tocilizumab, developed rapidly progressive nodular melanoma on a preexisting pigmented lesion on her left cheek. Recently, another case of nodular melanoma under tocilizumab has been published. The possible causative role of tocilizumab and other immunomodulatory agents in the development of this malignancy is discussed. Based on the present case, dermatologic screening is recommended before initiation of tocilizumab.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Uchiyama Y, Yoshida H, Koike N et al (2008) Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production. Int Immunopharmacol 8:1595–1601

    Article  PubMed  CAS  Google Scholar 

  2. Scheller J, Chalaris A, Schmidt-Arras D et al (2011) The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta 1813:878–888

    Article  PubMed  CAS  Google Scholar 

  3. Patel AM, Moreland LW (2010) Interleukin-6 inhibition for treatment of rheumatoid arthritis: a review of tocilizumab therapy. Drug Des Devel Ther 4:263–278

    PubMed  Google Scholar 

  4. Bonny M, Buyse V, Suys E (2012) Rapidly progressive malignant melanoma in a patient treated with tocilizumab. J Am Acad Dermatol 67(2):78–79

    Article  Google Scholar 

  5. Bongartz T, Sutton AJ, Sweeting MJ et al (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285

    Article  PubMed  CAS  Google Scholar 

  6. Chakravarty EF, Michaud K, Wolfe F (2005) Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol 32:2130–2135

    PubMed  CAS  Google Scholar 

  7. Buchbinder R, Barber M, Heuzenroeder L et al (2008) Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 59:794–799

    Article  PubMed  CAS  Google Scholar 

  8. Askling J, Fored CM, Brandt L et al (2005) Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists. Ann Rheum Dis 64:1421–1426

    Article  PubMed  CAS  Google Scholar 

  9. Setoguchi S, Solomon DH, Weinblatt ME et al (2006) Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum 54:2757–2764

    Article  PubMed  CAS  Google Scholar 

  10. Askling J, Fahrbach K, Nordstrom B et al (2011) Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiol Drug Saf 20(2):119–130

    Article  PubMed  CAS  Google Scholar 

  11. Hacard F, Bens G, Maitre F et al (2010) Melanoma at a dysplastic nevus excision site in a patient on etanercept. Ann Dermatol Venereol 137:230–232

    Article  PubMed  CAS  Google Scholar 

  12. Katoulis AC, Kanelleas A, Zambacos G et al (2010) Development of two primary malignant melanomas after treatment with adalimumab: a case report and review of the possible link between biological therapy with TNF-alpha antagonists and melanocytic proliferation. Dermatology 221:9–12

    Article  PubMed  CAS  Google Scholar 

  13. Fulchiero GJ Jr, Salvaggio H, Drabick JJ et al (2007) Eruptive latent metastatic melanomas after initiation of antitumor necrosis factor therapies. J Am Acad Dermatol 56:S65–S67

    Article  PubMed  Google Scholar 

  14. Kowalzick L, Eickenscheidt L, Komar M et al (2009) Long term treatment of psoriasis with TNF-alpha antagonists. Occurrence of malignant melanoma. Hautarzt 60:655–657

    Article  PubMed  CAS  Google Scholar 

  15. Khan I, Rahman L, McKenna DB (2009) Primary cutaneous melanoma: a complication of infliximab treatment? Clin Exp Dermatol 34:524–526

    Article  PubMed  CAS  Google Scholar 

  16. Dewan P, Jawad A, Goldsmith P et al (2009) Melanoma in patients with rheumatoid arthritis treated with antitumour necrosis factor: cause or coincidence? Report of two cases. Br J Dermatol 161:1412–1414

    Article  PubMed  CAS  Google Scholar 

  17. Ogata A, Hirano T, Hishitani Y et al (2012) Safety and efficacy of tocilizumab for the treatment of rheumatoid arthritis. Clin Med Insights Arthritis Musculoskelet Disord 5:27–42

    PubMed  CAS  Google Scholar 

  18. Hong DS, Angelo LS, Kurzrock R (2007) Interleukin-6 and its receptor in cancer: implications for translational therapeutics. Cancer 110:1911–1928

    Article  PubMed  CAS  Google Scholar 

  19. Trikha M, Corringham R, Klein B et al (2003) Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 9:4653–4665

    PubMed  CAS  Google Scholar 

  20. Kudo M, Jono H, Shinriki S et al (2009) Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation. Laboratory investigation. J Neurosurg 111:219–225

    Article  PubMed  CAS  Google Scholar 

  21. Shinriki S, Jono H, Ota K et al (2009) Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res 15:5426–5434

    Article  PubMed  CAS  Google Scholar 

  22. Matsuyama Y, Nagashima T, Honne K et al (2011) Successful treatment of a patient with rheumatoid arthritis and IgA-kappa multiple myeloma with tocilizumab. Intern Med 50(6):639–642

    Article  PubMed  CAS  Google Scholar 

  23. Lu C, Vickers MF, Kerbel RS (1992) Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. Proc Natl Acad Sci U S A 89:9215–9219

    Article  PubMed  CAS  Google Scholar 

  24. Lu C, Kerbel RS (1993) Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression. J Cell Biol 120:1281–1288

    Article  PubMed  CAS  Google Scholar 

  25. Yamanaka H, Tanaka Y, Inoue E et al (2011) Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study). Mod Rheumatol 21:122–133

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosures

None.

Author information

Authors and Affiliations

  1. Dermatology Department, Lyon 1 University, Centre Hospitalier Lyon Sud, chemin du grand revoyet, 69495, Pierre Bénite CEDEX, France

    A. Finet, M. Amini-Adle & L. Thomas

  2. Pathology Department, Lyon 1 University, Centre Hospitalier Lyon Sud, chemin du grand revoyet, 69495, Pierre Bénite CEDEX, France

    B. Balme

  3. Rheumatology Department, Lyon 1 University, Centre Hospitalier Lyon Sud, chemin du grand revoyet, 69495, Pierre Bénite CEDEX, France

    F. Colson

Authors
  1. A. Finet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Amini-Adle
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Balme
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Colson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Finet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Finet, A., Amini-Adle, M., Balme, B. et al. Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cause or coincidence?. Clin Rheumatol 32, 277–280 (2013). https://doi.org/10.1007/s10067-012-2114-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-012-2114-1

Keywords

Search

Navigation