Skip to main content

Advertisement

SpringerLink
Log in

Systemic sclerosis with anti-RNA polymerase III positivity following silicone breast implant rupture: possible role of B-cell depletion and implant removal in the treatment

  • Cases with a Message
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Despite some case reports and small series of women with silicone breast implants (SBI) developing Systemic Sclerosis (SSc), no clear evidence of an association of SBI with SSc is available. However, SSc is characterized by clinical and immunological heterogeneity and autoantibodies are currently the best markers to stratify this heterogeneity of patients. Therefore, we have reviewed the literature for details of autoantibody characterization in reports of SSc associated with SBI. Moreover, the case of an anti-RNA polymerase III-positive SSc with rapid onset and progression, in which SBI rupture was found is described. This case may support a previous observation suggesting a possible role of SBI rupture as a trigger for anti-RNA polymerase III-positive SSc. This possible causal role may be reinforced by the observation that in our patient, despite immunosuppressive treatment, the disease progressed until SBI were removed, and reduction of anti-RNA polymerase III titer was obtained after rituximab treatment. This result may support data suggesting that B-cell depleting therapy may decrease specific autoantibody level in SSc patients, and that these changes are associated with disease improvement.

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

Similar content being viewed by others

References

  1. Miller FW, Alfredsson L, Costenbader KH et al (2012) Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. J Autoimmun 39:259–271

    Article  PubMed  PubMed Central  Google Scholar 

  2. Marie I, Gehanno JF, Bubenheim M et al (2014) Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature. Autoimmun Rev 13:151–156

    Article  CAS  PubMed  Google Scholar 

  3. Lidar M, Agmon-Levin N, Langevitz P, Shoenfeld Y (2012) Silicone and scleroderma revisited. Lupus 21:121–127

    Article  CAS  PubMed  Google Scholar 

  4. Janowsky EC, Kupper LL, Hulka BS (2000) Meta-analyses of the relation between silicone breast implants and the risk of connective-tissue diseases. N Eng J Med 342:781–790

    Article  CAS  Google Scholar 

  5. Steen VD (2008) The many faces of scleroderma. Rheum Dis Clin North Am 34:1–15

    Article  PubMed  Google Scholar 

  6. Saigusa R, Asano Y, Nakamura K et al (2016) Association of anti-RNA polymerase III antibody and silicone breast implants in patients with systemic sclerosis. J Dermatol 43: 808–810

    Article  CAS  PubMed  Google Scholar 

  7. Khanna D, Berrocal VJ, Giannini EH et al (2016) The American College of Rheumatology provisional composite response index for clinical trials in early diffuse cutaneous systemic sclerosis. Arthritis Rheumatol 68:299–311

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kumagai Y, Shiokawa Y, Medsger TA Jr, Rodnan GP (1984) Clinical spectrum of connective tissue disease after cosmetic surgery. Observations on eighteen patients and a review of the Japanese literature. Arthritis Rheum 27:1–12

    Article  CAS  PubMed  Google Scholar 

  9. Okano Y, Nishikai M, Sato A (1984) Scleroderma, primary biliary cirrhosis, and Sjogren’s syndrome after cosmetic breast augmentation with silicone injection: a case report of possible human adjuvant disease. Ann Rheum Dis 43:520–522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Varga J, Schumacher HR, Jimenez SA (1989) Systemic sclerosis after augmentation mammoplasty with silicone implants. Ann Intern Med 111:377–383

    Article  CAS  PubMed  Google Scholar 

  11. Spiera H, Kerr LD (1993) Scleroderma following silicone implantation: a cumulative experience of 11 cases. J Rheumatol 20:958–961

    CAS  PubMed  Google Scholar 

  12. Claman HN, Robertson AD (1994) Antinuclear antibodies and breast implants. West J Med 160:225–228

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Burns CJ, Laing TJ, Gillespie BW et al (1996) The epidemiology of scleroderma among women: assessment of risk from exposure to silicone and silica. J Rheumatol 23:1904–1911

    CAS  PubMed  Google Scholar 

  14. Englert H, Morris D, March L (1996) Scleroderma and silicone gel breast prostheses—the Sydney study revisited. Aust N Z J Med 26:349–355

    Article  CAS  PubMed  Google Scholar 

  15. Hennekens CH, Lee I-M, Cook NR et al (1996) Self-reported breast implants and connective-tissue diseases in female health professionals: a retrospective cohort study. JAMA 275:616–621 (Erratum, JAMA 1998 279:198)

    Article  CAS  PubMed  Google Scholar 

  16. Hochberg MC, Perlmutter DL, Medsger TA Jr et al (1996) Lack of association between augmentation mammoplasty and systemic sclerosis (scleroderma). Arthritis Rheum 39:1125–1131

    Article  CAS  PubMed  Google Scholar 

  17. Friis S, Mellemkjaer L, McLaughlin JK et al (1997) Connective tissue disease and other rheumatic conditions following breast implants in Denmark. Ann Plast Surg 39:1–8

    Article  CAS  PubMed  Google Scholar 

  18. Lacey JV Jr, Laing TJ, Gillespie BW, Schottenfeld D (1997) Epidemiology of scleroderma among women: assessment of risk from exposure to silicone and silica. J Rheumatol 24:1854–1855

    Google Scholar 

  19. Levy Y, Rotman-Pikielny P, Ehrenfeld M, Shoenfeld Y (2009) Silicone breast implantation-induced scleroderma: description of four patients and a critical review of the literature. Lupus 18:1226–1232

    Article  CAS  PubMed  Google Scholar 

  20. Motegi S, Hattori T, Tago O, Shimizu A, Ishikawa O (2013) Systemic sclerosis associated with silicone breast implantation. Eur J Dermatol 23:894–895

    PubMed  Google Scholar 

  21. Al Aranji G, White D, Solanki K (2014) Scleroderma renal crisis following silicone breast implant rupture: a case report and review of the literature. Clin Exp Rheumatol 32:262–266

    CAS  PubMed  Google Scholar 

  22. Psarras A, Gkougkourelas I, Tselios K, Sarantopoulos A, Boura P (2014) Systemic sclerosis and silicone breast implant: a case report and review of the literature. Case Rep Rheumatol. doi:10.1155/2014/809629 (Epub 2014 Sep 30)

    PubMed  PubMed Central  Google Scholar 

  23. Hong C, Sangle SR, Coghlan JG, D’Cruz DP (2015) Scleroderma and breast implants. Q J Med 108:569–570

    Article  CAS  Google Scholar 

  24. Okano Y, Steen VD, Medsger TA Jr (1993) Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med 119:1005–1013

    Article  CAS  PubMed  Google Scholar 

  25. Bunn CC, Denton CP, Shi-wen X, Knight C, Black CM (1998) Anti-RNA polymerases and other autoantibody specificities in systemic sclerosis. Br J Rheumatol 37:15–20

    Article  CAS  PubMed  Google Scholar 

  26. Kuwana M, Kimura K, Kawakami Y (2002) Identification of an immunodominant epitope on RNA polymerase III recognized by systemic sclerosis sera: application to enzyme-linked immunosorbent assay. Arthritis Rheum 46:2742–2747

    Article  CAS  PubMed  Google Scholar 

  27. Cavazzana I, Ceribelli A, Airò P, Zingarelli S, Tincani A, Franceschini F (2009) Anti-RNA polymerase III antibodies: a marker of systemic sclerosis with rapid onset and skin thickening progression. Autoimmun Rev 8:580–584

    Article  CAS  PubMed  Google Scholar 

  28. Ceribelli A, Cavazzana I, Airò P, Franceschini F (2010) Anti-RNA polymerase III antibodies as a risk marker for early gastric antral vascular ectasia (GAVE) in systemic sclerosis. J Rheumatol 37:1544

    Article  PubMed  Google Scholar 

  29. Ghrénassia E, Avouac J, Khanna D et al (2014) Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study. J Rheumatol 41:99–105

    Article  PubMed  Google Scholar 

  30. Shah AA, Rosen A, Hummers L, Wigley F, Casciola-Rosen L (2010) Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum 62:2787–2795

    Article  PubMed  PubMed Central  Google Scholar 

  31. Airò P, Ceribelli A, Cavazzana I, Taraborelli M, Zingarelli S, Franceschini F (2011) Malignancies in Italian patients with systemic sclerosis positive for anti-RNA polymerase III antibodies. J Rheumatol 38:1329–1334

    Article  PubMed  Google Scholar 

  32. Nikpour M, Hissaria P, Byron J et al (2011) Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort. Arthritis Res Ther 13:R211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moinzadeh P, Fonseca C, Hellmich M et al (2014) Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Res Ther 16:R53

    Article  PubMed  PubMed Central  Google Scholar 

  34. Saigusa R, Asano Y, Nakamura K et al (2015) Association of anti-RNA polymerase III antibody and malignancy in Japanese patients with systemic sclerosis. J Dermatol 42:524–527

    Article  CAS  PubMed  Google Scholar 

  35. Shah AA, Hummers LK, Casciola-Rosen L, Visvanathan K, Rosen A, Wigley FM (2015) Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma. Arthritis Rheumatol 67:1053–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lazzaroni MG, Cavazzana I, Dall’Ara F et al (2016) Increased frequency of malignancies, and in particular breast cancer, synchronous to the onset of Systemic Sclerosis in anti-RNA Polymerase III antibodies positive patients: a EUSTAR multicentre study. J Scleroderma Relat Dis 1:33–34 (abstract)

    Google Scholar 

  37. Joseph CG, Darrah E, Shah AA et al (2014) Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 343:152–157

    Article  CAS  PubMed  Google Scholar 

  38. Israeli E, Agmon-Levin N, Blank M, Shoenfeld Y (2009) Adjuvants and autoimmunity. Lupus 18:1217–1225

    Article  CAS  PubMed  Google Scholar 

  39. Dobrota R, Maurer B, Graf N et al (2016) Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Ann Rheum Dis 75:1743–1748

    Article  PubMed  PubMed Central  Google Scholar 

  40. Bosello SL, DeLuca G, Rucco M et al (2015) Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis. Semin Arthritis Rheum 44:428–436

    Article  PubMed  Google Scholar 

  41. Lafyatis R, Kissin E, York M et al (2009) B cell depletion with rituximab in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum 60:578–583

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bonroy C, Smith V, Deschepper E, De Keyser F, Devreese K (2016) Specific antinuclear antibody level changes after B cell depletion therapy in systemic sclerosis are associated with improvement of skin thickening. J Rheumatol 43:247–249

    Article  CAS  PubMed  Google Scholar 

  43. Daoussis D, Liossis SC, Tsamandas AC et al (2012) Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Clin Exp Rheumatol 30:S17–S22

    PubMed  Google Scholar 

  44. Jordan S, Distler JH, Maurer B et al (2015) Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 74:1188–1194

    Article  CAS  PubMed  Google Scholar 

  45. Dimitroulas T, Daoussis D, Garyfallos A, Sfikakis PP, Kitas GD (2015) Molecular and cellular pathways as treatment targets for biologic therapies in systemic sclerosis. Curr Med Chem 22:1943–1955

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Brescia, Italy

    Francesca Dall’Ara & Maria-Grazia Lazzaroni

  2. Rehabilitation Unit, Casa di Cura “Città di Brescia”, Brescia, Italy

    Chiara M. Antonioli

  3. Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Brescia, Italy

    Paolo Airò

Authors
  1. Francesca Dall’Ara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria-Grazia Lazzaroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chiara M. Antonioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Airò
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francesca Dall’Ara.

Ethics declarations

Conflict of interest

Francesca Dall’Ara MD declares that she has no conflict of interest and has not received research grants. Maria Grazia Lazzaroni MD declares that she has no conflict of interest and has not received research grants. Chiara Maria Antonioli MD declares that she has no conflict of interest and has not received research grants. Paolo Airò MD declares that he has no conflict of interest and has not received research grants.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from this patient prior to submission of this article for consideration as a case-based review.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dall’Ara, F., Lazzaroni, MG., Antonioli, C.M. et al. Systemic sclerosis with anti-RNA polymerase III positivity following silicone breast implant rupture: possible role of B-cell depletion and implant removal in the treatment. Rheumatol Int 37, 847–851 (2017). https://doi.org/10.1007/s00296-017-3654-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-017-3654-0

Keywords

Search

Navigation