Skip to main content


Log in

Silicone implant incompatibility syndrome (SIIS): A frequent cause of ASIA (Shoenfeld’s syndrome)

  • Etio Pathogenesis of Autoimmunity
  • Published:
Immunologic Research Aims and scope Submit manuscript


Silicon has a molecular mass of 28 daltons. In nature, silicon is found as silicon dioxide (silica) or in a variety of silicates (e.g., in talc or asbestos). Furthermore, silicon is present in silicones, polymerized siloxanes, which are often used as medical silicones in breast implants. Silicon exposure is associated with different systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, and vasculitis. Remarkably, silicon in silicone-filled breast implants is considered to be safe, not increasing the risk of developing autoimmune diseases. We analyzed the impact of silicone-filled breast implants on the immune system in 32 consecutive patients attending a specialized autoimmunity clinic. All 32 patients had silicone implant incompatibility syndrome and complaints fulfilling the diagnostic criteria of ASIA (autoimmune/inflammatory syndrome induced by adjuvants). Furthermore, in 17 of the 32 patients, a systemic autoimmune disease was diagnosed, and 15 of the 32 patients had an impaired humoral immune system. Patients developed symptoms and signs after long-term follow-up, suggesting that these symptoms and signs started after implant aging and/or rupture. We postulate that silicon in silicone-filled breast implants may increase the risk of developing (auto) immune diseases and immune deficiencies.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others


  1. Cohen Tervaert JW. Silicon exposure and vasculitis. In: Uversky VN, Kretsinger RH, Permyakov EA (eds). Encyclopedia of metalloproteins. Springer Science + Business Media, LLC: Berlin 2012 doi:10.1007/978-1-4614-1533-6.

  2. Tervaert JW, Stegeman CA, Kallenberg CG. Silicon exposure and vasculitis. Curr Opin Rheumatol. 1998;10:12–7.

    Article  PubMed  CAS  Google Scholar 

  3. Parks CG, et al. Occupational exposure to crystalline silica and autoimmune disease. Environ Health Perspect. 1999;107(S 5):793–802.

    PubMed  Google Scholar 

  4. Cohen Tervaert, et al. Principles and methods for assessing autoimmunity associated with exposure to chemicals. Environmental health criteria; 236. International programme on chemical safety. World Health Organization. 2006; pp.122–130.

  5. Makol A, et al. Prevalence of connective tissue disease in silicosis (1985–2006)—a report from the state of Michigan surveillance system for silicosis. Am J Ind Med. 2011;54:255–62.

    Article  PubMed  Google Scholar 

  6. Yashiro M, et al. Significantly high regional morbidity of MPO-ANCA-related angitis and/or nephritis with respiratory tract involvement after the 1995 great earthquake in Kobe (Japan). Am J Kidney Dis. 2000;35:889–95.

    Article  PubMed  CAS  Google Scholar 

  7. Noonan CW, Pfau JC, Larson TC, Spence MR. Nested case-control study of autoimmune disease in an asbestos-exposed population. Environ Health Perspect. 2006;114:1243–7.

    Article  PubMed  CAS  Google Scholar 

  8. Rocha MC, et al. Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers. Int J Hyg Environm Health. 2012;215:562–9.

    Article  CAS  Google Scholar 

  9. Lee S, et al. Environmental factors producing autoimmune dysregulation—chronic activation of T cells caused by silica exposure. Immunobiology. 2012;217:743–8.

    Article  PubMed  CAS  Google Scholar 

  10. Narins RS, Beer K. Liquid injectable silicone: a review of its history, immunology, technical considerations, complications, and potential. Plast Reconstr Surg. 2006;118(3 Suppl):77S–84S.

    PubMed  CAS  Google Scholar 

  11. Janowsky EC, Kupper LL, Hulka BS. Meta-analyses of the relation between silicone breast implants and the risk of connective-tissue diseases. N Engl J Med. 2000;342:781–90.

    Article  PubMed  CAS  Google Scholar 

  12. SCENIHR (Scientific Committee on Emerging and Newly Identified Health Risks), Breast implant failure, 2012. http://ec.uropa/health/scientific committees/policy/index en.htm.

  13. Shoenfeld Y, Agmon-Levin N. ‘ASIA’—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36:4–8.

    Article  PubMed  CAS  Google Scholar 

  14. Tervaert JW, Limburg PC, Elema JD, Huitema MG, Horst G, The TH, Kallenberg CG. Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. Am J Med. 1991;91:59–66.

    Article  PubMed  CAS  Google Scholar 

  15. Damoiseaux JG, Tervaert JW. From ANA to ENA: how to proceed? Autoimmun Rev. 2006;5:10–7.

    Article  PubMed  CAS  Google Scholar 

  16. Damoiseaux JG, Slot MC, Vaessen M, Stegeman CA, Van Paassen P, Tervaert JW. Evaluation of a new fluorescent-enzyme immuno-assay for diagnosis and follow-up of ANCA-associated vasculitis. J Clin Immunol. 2005;25:202–8.

    Article  PubMed  CAS  Google Scholar 

  17. Tervaert JW, Van Paassen P, Damoiseaux J. Type II cryoglobulinemia is not associated with hepatitis C infection: the Dutch experience. Ann N Y Acad Sci. 2007;1107:251–8.

    Article  PubMed  CAS  Google Scholar 

  18. Drijkoningen J, Damoiseaux J, van Paassen P, Tervaert JW. Clinical manifestations of the anti-phospholipid syndrome as defined by the updated Sapporo classification criteria. Ann Rheum Dis. 2007;66:1407–8.

    Article  PubMed  Google Scholar 

  19. Dennert R, van Paassen P, Wolffs P, Bruggeman C, Velthuis S, Felix S, van Suylen RJ, Crijns HJ, Tervaert JWC, Heymans S. Differences in virus prevalence and load in the hearts of patients with idiopathic dilated cardiomyopathy with and without immune-mediated inflammatory diseases. Clin Vaccine Immunol. 2012;19:1182–7.

    Article  PubMed  CAS  Google Scholar 

  20. Kappel RM, Pruijn GJ. The monobloc hydrogel breast implant, experiences and ideas. Eur J Plast Surg. 2012;35:229–33.

    Article  PubMed  Google Scholar 

  21. Jewell M, Spear SL, Largent J, Oefelein MG, Adams WP Jr. Anaplastic large T-cell lymphoma and breast implants: a review of the literature. Plast Reconstr Surg. 2011;128:651–61.

    Article  PubMed  CAS  Google Scholar 

  22. van Nunen SA, Gatenby PA, Basten A. Post-mammoplasty connective tissue disease. Arthr Rheum. 1982;25:694–7.

    Article  Google Scholar 

  23. Hajdu SD, Agmon-Levin N, Shoenfeld Y. Silicone and autoimmunity. Eur J Clin Invest. 2011;41:203–11.

    Article  PubMed  CAS  Google Scholar 

  24. Brown SL, Pennello G, Berg WA, Soo MS, Middleton MS. Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women. J Rheumatol. 2001;28:996–1003.

    PubMed  CAS  Google Scholar 

  25. Brown SL, Middleton MS, Berg WA, Soo MS, Pennello G. Prevalence of rupture of silicone gel breast implants revealed on MR imaging in a population of women in Birmingham Alabama. AJR Am J Roentgenol. 2000;175:1057–64.

    Article  PubMed  CAS  Google Scholar 

  26. Csako G, Costello R, Shamim EA, O’Hanlon TP, Tran A, Clauw DJ, Williams HJ, Miller FW. Serum proteins and para proteins in women with silicone implants and connective tissue disease: a case-control study. Arthr Res Ther. 2007;9:R95.

    Article  Google Scholar 

  27. Backovic A, Huang HL, Del Frari B, Piza H, Huber LA, Wick G. Identification and dynamics of proteins adhering to the surface of medical silicones in vivo and in vitro. J Proteome Res. 2007;6:376–81.

    Article  PubMed  CAS  Google Scholar 

  28. Warnatz K, Voll RE. Pathogenesis of autoimmunity in common variable immunodeficiency. Front Immunol. 2012;3:210.

    Article  PubMed  Google Scholar 

  29. Vera-Lastra O, Medina G, Cruz-Dominguez P, Mdel P, Ramirez P, Gayosso-Rivera JA, Anduaga Dominguez H, Lievana Torres C, Jara LJ. Human adjuvant disease induced by foreign substances: a new model of ASIA (Shoenfeld’s syndrome). Lupus. 2012;21:128–35.

    Article  PubMed  CAS  Google Scholar 

  30. Davenward S, Bentham P, Wright J, Crome P, Job D, Polwart A, Exley C. Siliconrich mineral water as a non-invasive test of the ‘aluminum hypothesis’ in Alzheimer’s disease. J Alzheimers Dis. 2013;33:423–30.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to J. W. Cohen Tervaert.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cohen Tervaert, J.W., Kappel, R.M. Silicone implant incompatibility syndrome (SIIS): A frequent cause of ASIA (Shoenfeld’s syndrome). Immunol Res 56, 293–298 (2013).

Download citation

  • Published:

  • Issue Date:

  • DOI: