Silicone breast implants and Lupus

We read with interest the case reported by Mir et al. on the development of SLE 2 years following the implantation of silicone breast implants. ¹ This is an outstanding case to illustrate the complex link between adjuvant and induction of autoimmunity that underpins the description of the ASIA syndrome.^2–4 The etiopathogenesis of SLE is not fully understood; however, it is believed to be due to a loss of tolerance of the immune system that leads to the production of various autoantibodies. Over recent decades, SLE onset and/or exacerbation has been reported following different types of adjuvants, especially microbial agents, drugs and also vaccines.^5,6 A decade ago, we reported a summary of 10 cases of SLE following hepatitis B virus (HBV) vaccine, and all of them were women patients. ⁷ The mean latency period from the first HBV immunization and onset of autoimmune symptoms was 56.3 days. Two of the patients had a personal history of autoimmunity and two a familial history of autoimmunity. ⁷ Previously, a classical latency period of several weeks was accepted for post-vaccination events, similarly to the time frame suggested for post-infectious autoimmunity (i.e. rheumatic fever). However, substantial evidence for a longer latency period (i.e. several months to years) between infection, vaccination or silicone breast implants and autoimmune phenomena has been also described.^8–10

Recently, we have conducted a large population-based study to assess the risk of autoimmunity in women with SBIs. ¹¹ This study included more than 24,000 women with SBIs and approximately 100,000 age-matched controls. The study has clearly shown that women with SBI have an increased risk of having autoimmune disease, with an adjusted odds-ratio (OR) of 1.22 (95% CI: 1.18–1.26, p < .001). The risk was even higher (OR >1.5, p < .05) in certain conditions such as sarcoidosis, systemic sclerosis and Sjögren’s syndrome. ¹¹

Several mechanisms were proposed for the emergence of post-vaccination and silicone breast implants related immune and inflammatory-related phenomena which include the infectious component as well as other vaccine ingredients including the adjuvant added to stimulate the immune response, or preservatives and residual vaccine excipients.^6,12 Additionally, SLE-like disease can be inflicted in animal models utilizing immunization with several adjuvants including pristane, squalene and the incomplete Freund’s adjuvant. ¹⁰ Adjuvants may act by mimicking specific sets of evolutionarily conserved molecules which include liposomes, LPSs, molecular cages for antigen, components of bacterial cell walls and endocytosed nucleic acids such as double-stranded RNA (ds-RNA), single-stranded DNA (ss-DNA) and unmethylated CpG dinucleotide-containing DNA. As immune systems have evolved to recognize these specific antigenic moieties, the presence of an adjuvant in conjunction with the vaccine can greatly increase the innate immune response to the antigen by augmenting the activities of dendritic cells (DCs), lymphocytes and macrophages by mimicking a natural infection. ¹¹ Further with regard to adjuvant-induced autoimmunity, an increasing number of cases of post-vaccination phenomena have been reported since the ‘conceptualization’ of the unique syndromic entity termed ‘ASIA’ – autoimmune/inflammatory syndrome induced by adjuvants, that we described in 2011. ¹¹ ASIA refers to a spectrum of immune-mediated diseases which are commonly triggered by an immune adjuvant stimulus which induces over-stimulation of the immune system. Substances with an immune adjuvant effect to which humans are routinely exposed include silicone, pristane, aluminum vaccine adjuvants, as well as infectious components. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome.^6,13,14 In conclusion, adjuvants such as silicone implants may trigger emergence of SLE and APS being known to induce autoimmune phenomena as adverse events. Therefore, physicians should be aware of such findings and avoid non-pivotal exposure to silicone especially in those with high risk for autoimmunity in order to prevent the development of autoimmune disease.