Clinical Rheumatology

, Volume 34, Issue 10, pp 1661–1666 | Cite as

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) evolution after silicone implants. Who is at risk?

  • Idan GorenEmail author
  • Gad Segal
  • Yehuda Shoenfeld
Review Article


Silicone implants have been in use since the mid-twentieth century, especially in the field of reconstructive breast surgery, and have long been considered as biologically inert and harmless. However, growing body of evidence from the past two decades links silicone with subsequent autoimmunity-related complications, collectively known as autoimmune/inflammatory syndrome induced by adjuvant—ASIA. Previous data suggest that while some patients tend to develop post-exposure autoimmune phenomena such as ASIA, other do not. However, thus far, no criteria for risk stratification were suggested. This current review summarizes the data linking silicone implants and autoimmunity, suggesting means of defining individuals who are at increased risk to develop silicone-induced ASIA, and therefore, a recommendation was made to avoid silicone implantation, e.g., individuals with previously diagnosed autoimmune disorders or with genetic preponderance for hyperactive immune system should not be considered as candidates for silicone implantation.


Adjuvant ASIA Autoimmune disease Autoimmune/inflammatory syndrome induced by adjuvant Autoimmunity Relative risk Silicone 





  1. 1.
    Derby BM, Codner MA (2015) Textured silicone breast implant use in primary augmentation: core data update and review. Plast Reconstr Surg 135(1):113–124CrossRefPubMedGoogle Scholar
  2. 2.
    Lakshmanan Y, Docimo SG (1997) Testicular implants. J Long-Term Eff Med Implants 7(1):65–74PubMedGoogle Scholar
  3. 3.
    Greenland S, Finkle WD (2000) A retrospective cohort study of implanted medical devices and selected chronic diseases in Medicare claims data. Ann Epidemiol 10(4):205–213CrossRefPubMedGoogle Scholar
  4. 4.
    Aharon-Maor A, Levy Y, Schoenfeld Y (1998) Fibrosarcoma after silicone breast augmentation: is there a connection? Harefuah 134(5):339–341, 424PubMedGoogle Scholar
  5. 5.
    Ehrenfeld M, Shoenfeld Y (1998) Breast silicone implant and autoimmunity—coincidence or cause and effect relationship? Harefuah 134(5):361–364PubMedGoogle Scholar
  6. 6.
    Zandman-Goddard G et al (1999) A comparison of autoantibody production in asymptomatic and symptomatic women with silicone breast implants. J Rheumatol 26(1):73–77PubMedGoogle Scholar
  7. 7.
    Bar-Meir E, Eherenfeld M, Shoenfeld Y (2003) Silicone gel breast implants and connective tissue disease—a comprehensive review. Autoimmunity 36(4):193–197CrossRefPubMedGoogle Scholar
  8. 8.
    Nancy AL, Shoenfeld Y (2008) Chronic fatigue syndrome with autoantibodies—the result of an augmented adjuvant effect of hepatitis-B vaccine and silicone implant. Autoimmun Rev 8(1):52–55CrossRefPubMedGoogle Scholar
  9. 9.
    Levy Y et al (2009) Silicone breast implantation-induced scleroderma: description of four patients and a critical review of the literature. Lupus 18(13):1226–1232CrossRefPubMedGoogle Scholar
  10. 10.
    Shoenfeld Y, Agmon-Levin N (2011) 'ASIA'—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun 36(1):4–8CrossRefPubMedGoogle Scholar
  11. 11.
    Soriano A, Nesher G, Shoenfeld Y (2014) Predicting post-vaccination autoimmunity: who might be at risk? Pharmacol Res 92C:18-22 Google Scholar
  12. 12.
    Perricone C et al (2013) Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun 47:1–16CrossRefPubMedGoogle Scholar
  13. 13.
    Soriano A, Butnaru D, Shoenfeld Y (2014) Long-term inflammatory conditions following silicone exposure: the expanding spectrum of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Clin Exp Rheumatol 32(2):151–154PubMedGoogle Scholar
  14. 14.
    Carvalho JF et al (2011) Asia or Shoenfeld's syndrome: highlighting different perspectives for diffuse chronic pain. Acta Reumatol Port 36(1):10–12PubMedGoogle Scholar
  15. 15.
    Kivity S et al (2012) Autoimmune syndrome induced by adjuvants (ASIA) in the Middle East: morphea following silicone implantation. Lupus 21(2):136–139CrossRefPubMedGoogle Scholar
  16. 16.
    Yoshida SH et al (1995) Silicone breast implants: immunotoxic and epidemiologic issues. Life Sci 56(16):1299–1310CrossRefPubMedGoogle Scholar
  17. 17.
    Thomas WO 3rd et al (1997) Explantation of silicone breast implants. Am Surg 63(5):421–429PubMedGoogle Scholar
  18. 18.
    Barker DE, Retsky MI, Schultz S (1978) "Bleeding" of silicone from bag-gel breast implants, and its clinical relation to fibrous capsule reaction. Plast Reconstr Surg 61(6):836–841CrossRefPubMedGoogle Scholar
  19. 19.
    Flassbeck D et al (2003) Determination of siloxanes, silicon, and platinum in tissues of women with silicone gel-filled implants. Anal Bioanal Chem 375(3):356–362PubMedGoogle Scholar
  20. 20.
    Kossovsky N, Heggers JP, Robson MC (1987) Experimental demonstration of the immunogenicity of silicone-protein complexes. J Biomed Mater Res 21(9):1125–1133CrossRefPubMedGoogle Scholar
  21. 21.
    Naim JO, Lanzafame RJ, van Oss CJ (1995) The effect of silicone-gel on the immune response. J Biomater Sci Polym Ed 7(2):123–132CrossRefPubMedGoogle Scholar
  22. 22.
    Wolfram D et al (2012) T regulatory cells and TH17 cells in peri-silicone implant capsular fibrosis. Plast Reconstr Surg 129(2):327e–337eCrossRefPubMedGoogle Scholar
  23. 23.
    Naim JO, Lanzafame RJ, van Oss CJ (1993) The adjuvant effect of silicone-gel on antibody formation in rats. Immunol Investig 22(2):151–161CrossRefGoogle Scholar
  24. 24.
    Teuber SS et al (1993) Anti-collagen autoantibodies are found in women with silicone breast implants. J Autoimmun 6(3):367–377CrossRefPubMedGoogle Scholar
  25. 25.
    Schaefer CJ, Wooley PH (1999) The influence of silicone implantation on murine lupus in MRL lpr/lpr mice. J Rheumatol 26(10):2215–2221PubMedGoogle Scholar
  26. 26.
    Cuellar ML et al (1995) Serum antinuclear antibodies in women with silicone breast implants. J Rheumatol 22(2):236–240PubMedGoogle Scholar
  27. 27.
    Shoaib BO, Patten BM (1996) Human adjuvant disease: presentation as a multiple sclerosis-like syndrome. South Med J 89(2):179–188CrossRefPubMedGoogle Scholar
  28. 28.
    Cohen Tervaert JW, Kappel RM (2013) Silicone implant incompatibility syndrome (SIIS): a frequent cause of ASIA (Shoenfeld's syndrome). Immunol Res 56(2–3):293–298CrossRefPubMedGoogle Scholar
  29. 29.
    Kappel RM, Cohen Tervaert JW, Pruijn GJ (2014) Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone implant incompatibility syndrome in three sisters. Clin Exp Rheumatol 32(2):256–258PubMedGoogle Scholar
  30. 30.
    Lidar M et al (2012) Silicone and scleroderma revisited. Lupus 21(2):121–127CrossRefPubMedGoogle Scholar
  31. 31.
    Hennekens CH et al (1996) Self-reported breast implants and connective-tissue diseases in female health professionals. A retrospective cohort study. JAMA 275(8):616–621CrossRefPubMedGoogle Scholar
  32. 32.
    Karlson EW et al (2001) Serologic evaluations of women exposed to breast implants. J Rheumatol 28(7):1523–1530PubMedGoogle Scholar
  33. 33.
    Speck-Hernandez CA, Montoya-Ortiz G (2012) Silicon, a possible link between environmental exposure and autoimmune diseases: the case of rheumatoid arthritis. Arthritis 2012:604187PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Wallace DJ et al (1996) A comparison of systemic lupus erythematosus and scleroderma patients with and without silicone breast implants. J Clin Rheumatol 2(5):257–261CrossRefPubMedGoogle Scholar
  35. 35.
    Goren I, Dana D, Portnoy O, Shoenfeld Y, Segal G (2014) Silicone breast implants as predisposing factor for non-Hodgkin’s lymphoma: an additional facet of auto-inflammatory syndrome induced by adjuvant. J Med Cases 5:413–416Google Scholar
  36. 36.
    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(2):262–266PubMedGoogle Scholar
  37. 37.
    Jara LJ et al (2012) Still's disease, lupus-like syndrome, and silicone breast implants. A case of 'ASIA' (Shoenfeld's syndrome). Lupus 21(2):140–145CrossRefPubMedGoogle Scholar
  38. 38.
    Stejskal V (2013) Mercury-induced inflammation: yet another example of ASIA syndrome. Isr Med Assoc J 15(11):714–715PubMedGoogle Scholar
  39. 39.
    Harel-Meir M, Sherer Y, Shoenfeld Y (2007) Tobacco smoking and autoimmune rheumatic diseases. Nat Clin Pract Rheumatol 3(12):707–715CrossRefPubMedGoogle Scholar
  40. 40.
    Vera-Lastra O et al (2013) Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome): clinical and immunological spectrum. Expert Rev Clin Immunol 9(4):361–373CrossRefPubMedGoogle Scholar
  41. 41.
    Konstantinou D et al (2001) Two episodes of leukoencephalitis associated with recombinant hepatitis B vaccination in a single patient. Clin Infect Dis 33(10):1772–1773CrossRefPubMedGoogle Scholar
  42. 42.
    Israeli E, Pardo A (2011) The sick building syndrome as a part of the autoimmune (auto-inflammatory) syndrome induced by adjuvants. Mod Rheumatol 21(3):235–239CrossRefPubMedGoogle Scholar
  43. 43.
    Goris A, Liston A (2012) The Immunogenetic Architecture of Autoimmune Disease. Cold Spring Harbor Perspectives in Biology 4(3):a007260. Google Scholar
  44. 44.
    Holmdahl R, Malmstrom V, Burkhardt H (2014) Autoimmune priming, tissue attack and chronic inflammation—the three stages of rheumatoid arthritis. Eur J Immunol 44(6):1593–1599CrossRefPubMedGoogle Scholar
  45. 45.
    Maijers MC et al (2013) Women with silicone breast implants and unexplained systemic symptoms: a descriptive cohort study. Neth J Med 71(10):534–540PubMedGoogle Scholar
  46. 46.
    Somers EC et al (2006) Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiology 17(2):202–217CrossRefPubMedGoogle Scholar
  47. 47.
    Anaya JM et al (2006) Familial clustering of autoimmune diseases in patients with type 1 diabetes mellitus. J Autoimmun 26(3):208–214CrossRefPubMedGoogle Scholar
  48. 48.
    Barcellos LF et al (2006) Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study. Lancet Neurol 5(11):924–931CrossRefPubMedGoogle Scholar
  49. 49.
    Stassen PM et al (2009) HLA-DR4, DR13(6) and the ancestral haplotype A1B8DR3 are associated with ANCA-associated vasculitis and Wegener's granulomatosis. Rheumatology (Oxford) 48(6):622–625CrossRefGoogle Scholar
  50. 50.
    Ringquist S et al (2013) Clustering and alignment of polymorphic sequences for HLA-DRB1 genotyping. PLoS One 8(3):e59835PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Young VL et al (1995) HLA typing in women with breast implants. Plast Reconstr Surg 96(7):1497–1519, discussion 1520CrossRefPubMedGoogle Scholar
  52. 52.
    O'Hanlon T et al (2004) Immunogenetic differences between Caucasian women with and those without silicone implants in whom myositis develops. Arthritis Rheum 50(11):3646–3650CrossRefPubMedGoogle Scholar
  53. 53.
    Smigoc Schweiger D et al (2014) Genetic risk for co-occurrence of type 1 diabetes and celiac disease is modified by HLA-C and killer immunoglobulin-like receptors. Tissue Antigens 84(5):471–478CrossRefPubMedGoogle Scholar
  54. 54.
    Dunstan SJ et al (2014) Variation at HLA-DRB1 is associated with resistance to enteric fever. Nat Genet 46(12):1333–1336CrossRefPubMedGoogle Scholar
  55. 55.
    Arnson Y, Shoenfeld Y, Amital H (2010) Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun 34(3):J258–J265CrossRefPubMedGoogle Scholar
  56. 56.
    Versini M et al (2014) Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev 13(9):981–1000CrossRefPubMedGoogle Scholar
  57. 57.
    Zambacos GJ, Molnar C, Mandrekas AD (2013) Silicone lymphadenopathy after breast augmentation: case reports, review of the literature, and current thoughts. Aesthet Plast Surg 37(2):278–289CrossRefGoogle Scholar
  58. 58.
    Spear SL et al (2007) Inamed silicone breast implant core study results at 6 years. Plast Reconstr Surg 120(7 Suppl 1):8S–16S, discussion 17S-18SCrossRefPubMedGoogle Scholar
  59. 59.
    Andrews AE, Hicklin L (2006) Inflammatory nasal polyps: an unusual late complication of Silastic sheet repair of orbital floor fracture. J Laryngol Otol 120(2):e1CrossRefPubMedGoogle Scholar
  60. 60.
    Kulmala I et al (2004) Local complications after cosmetic breast implant surgery in Finland. Ann Plast Surg 53(5):413–419CrossRefPubMedGoogle Scholar
  61. 61.
    Siggelkow W et al (2004) Analysis of local complications following explantation of silicone breast implants. Breast 13(2):122–128CrossRefPubMedGoogle Scholar
  62. 62.
    Kao CC et al (1997) Internal mammary silicone lymphadenopathy mimicking recurrent breast cancer. Plast Reconstr Surg 99(1):225–229CrossRefPubMedGoogle Scholar
  63. 63.
    Wolfram D et al (2008) Altered systemic serologic parameters in patients with silicone mammary implants. Immunol Lett 118(1):96–100CrossRefPubMedGoogle Scholar
  64. 64.
    Kaiser W et al (1990) Human adjuvant disease: remission of silicone induced autoimmune disease after explanation of breast augmentation. Ann Rheum Dis 49(11):937–938PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Endo LP et al (1987) Silicone and rheumatic diseases. Semin Arthritis Rheum 17(2):112–118CrossRefPubMedGoogle Scholar
  66. 66.
    Meier LG, Barthel HR, Seidl C (1997) Development of polyarthritis after insertion of silicone breast implants followed by remission after implant removal in 2 HLA-identical sisters bearing rheumatoid arthritis susceptibility genes. J Rheumatol 24(9):1838–1841PubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2015

Authors and Affiliations

  1. 1.Department of Internal Medicine “T”, Tel Hashomer, Sackler Faculty of MedicineTel Aviv University, Sheba Medical CenterRamat GanIsrael
  2. 2.The Zabludowicz Center of Autoimmune Diseases, Sackler Faculty of MedicineTel Aviv University, Incumbent of Laura Swarz-Kip Chair for Research of Autoimmune Diseases, Sheba Medical CenterRamat GanIsrael

Personalised recommendations