Silicone breast implants: correlation between implant ruptures, magnetic resonance spectroscopically estimated silicone presence in the liver, antibody status and clinical symptoms
M. Gaubitz,
C. Jackisch1,
W. Domschke,
W. Heindel2 and
B. Pfleiderer
Department of Medicine B,
1 Department of Gynecology and
2 Department of Radiology, University of Münster, Münster, Germany
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Abstract
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Objective. To determine the impact of implant integrity on clinical symptoms and antibody status in women with silicone breast implants (SBIs).
Methods. Ninety consecutive women were examined by means of magnetic resonance imaging (MRI) to assess the integrity of their silicone breast implants. The presence of silicone in the liver was estimated by 1H localized stimulated echo acquisition mode (STEAM) magnetic resonance spectroscopy (MRS). Results were correlated with patients' complaints, as evaluated by a standardized questionnaire, physical examination by a rheumatologist and antibody screening.
Results. Breast MRI revealed defects in 24 patients (26.6%); in 13 (54.2%) of these women, silicone was detected in the liver by MRS. Of the 66 patients with MRI-estimated intact implants, 15 (22.7%) had apparent silicone in their liver, arguing for gel bleeding. Clinically, two patients had had rheumatoid arthritis before SBIs, whereas the other patients revealed no typical symptoms of arthritis or connective tissue disease (CTD). The patients with MRS evidence of silicone in the liver had no statistically significant differences in their complaints with the exception of the most frequent symptom, tingling/numbness of the fingers (82.1 vs 51.6%, P=0.006). A positive pattern of antinuclear antibodies (ANA) was obtained in 13 of the 28 MRS-positive patients (46.4%) and in 15 of the 62 MRS-negative patients (24.2%, P=0.033). However, in only one of these 28 ANA-positive patients was a specific weak antibody titre against SS-A detected by ELISA.
Conclusion. Implant integrity has no major impact on rheumatic symptoms of women with SBIs. This finding supports the standpoint that silicone does not cause either a specific CTD or any other distinct disease entity. However, the moderately increased incidences of ANA-positivity and neuropathy-associated symptoms require explanation.
KEY WORDS: Silicone implants, Rheumatic symptoms, MR spectroscopy.
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Introduction
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Silicone breast implants (SBIs) are still a matter of controversy. Initial case studies [1, 2] from the 1980s reported an association of SBIs with some connective tissue diseases (CTD), especially scleroderma. Subsequent analysis by epidemiological studies, however, did not show any difference in the prevalence of CTD between women with and without SBIs [26]. Nevertheless, some authors still speculated about a slightly increased risk of the development of autoimmune disorders [7] or at least autoimmune features, e.g. antibody formation [8, 9]. These studies did not distinguish between women with intact implants and those with defective ones. The most specific non-invasive test to diagnose intra- and extracapsular implant ruptures is magnetic resonance imaging (MRI) [10, 11]. In addition, silicone may migrate from intact implants by gel bleeding; as could be seen in a number of patients with implants that were intact according to MRI assessment, but who had histologically proven nodules containing silicone around their implants [12, 13]. 1H nuclear magnetic resonance (NMR) spectroscopy can detect silicone in the liver. In a previous study, typical spectra with a silicone peak were obtained in 15 patients with SBIs, but none was found in eight healthy controls [14].
We hypothesized that, in women with ruptured SBI and evidence of silicone in the liver, complaints and symptoms, as well as possible autoimmune phenomena, should be more frequent or more severe than in women with intact implants with no evidence of silicone migration. In order to test this hypothesis, we examined women with an average SBI age of more than 9 yr and who had general as well as rheumatic symptoms.
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Patients and methods
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Patients
The study included 90 consecutive female patients with SBIs [age range 2070 yr, mean age (SD) 49.9 (10) yr] from our gynaecological out-patient clinic. They had given informed, written consent to a protocol approved by the Local Ethics Committee of the Münster County and Münster University Hospital. None of the patients we approached refused to participate in the study. Patient characteristics are summarized in Table 1
. The control group for antibody estimations comprise 113 patients without SBIs (62 patients with a previous history of breast cancer and 51 patients who had received hormone substitution therapy).
Methods
History and physical examination
All patients answered a questionnaire with 41 items regarding the date of and reason for SBIs, local changes at the implantation site, general complaints (fatigue, dizziness, sweats, fever, trouble with vision, cephalalgias, alopecia, diarrhoea), symptoms correlated with rheumatic diseases (myalgias, arthralgias, erythemas, dry eye, changes in the colour of the fingers, photosensitivity and tingling/numbness of the fingers), comorbidity (diagnosis of a rheumatic disease, diabetes, hypo- or hyperthyroidism, hypertension and allergies), habits with regard to smoking and drugs, family history, and a rating from 1 to 6 concerning general well-being. All patients underwent a physical examination by a rheumatologist focusing on joint, muscle and skin indicators of rheumatoid arthritis or a CTD. In particular assessment was made of whether rheumatic symptoms had developed since implantation of SBIs and were actually present at the time of examination (complaints being reported to be pre-existent were excluded from analysis).
Radiological evaluation
In all patients, conventional MRI of the implant was performed (1.5 T, Magnetom SP, Siemens, Erlangen, Germany). A typical finding of an implant with extracapsular rupture is shown in Fig. 1
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FIG. 1. Coronal MRI showing silicone distribution outside the SBI coat in a woman with 15-yr-old implants (extracapsular rupture). T2-weighted fast spin-echo (repetition time 5500 ms, echo time 104 ms) imaging with water suppression was used. Inside the implant can be seen the typical linguini signs indicative of a ruptured implant shell. Rupture was confirmed at surgical removal.
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Finally all patients underwent a localized stimulated echo acquisition mode (STEAM) 1H NMR spectroscopy (MRS) examination. The technique has been described in detail elsewhere [15]. Briefly, this non-invasive procedure distinguishes proton resonances of human tissue, e.g. water and fat, from silicone-specific resonances Fig. 2
presents a typical spectrum with the water peak around 4.7 p.p.m., a fat peak around 2 p.p.m. and the silicone-specific peak around -1 p.p.m..

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FIG. 2. In vivo MRS spectrum of the liver of a woman with 15-yr-old implants (same patient as in Fig. 1 ) with fat and water suppression, electrocardiographic and respiratory gating, and a voxel size of 27 cm. The resonance of silicone is clearly visible (silicone-OH, silicone and hyrolysed silicone).
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Laboratory assessment
The first stage of antibody screening was double immunofluorescence staining on Hep-2 cells (Biermann, Bad Nauheim, Germany). If a positive pattern was found, this was followed by a semiquantitative antinuclear antibody (ANA) screen test recognizing antibodies against double-stranded DNA (ds DNA), SS-A, SS-B, Jo-1, Sc170 and U1snRNP (Elias, Freiburg, Germany). When this screen showed a positive result, a specific quantitative enzyme-linked immunosorbent assay (ELISA) was performed (Elias).
Statistical analysis
Statistical analysis was performed with SPSS 9.0 (SPSS Inc., Chicago, IL, USA). To assess the statistical significance of differences, we used analysis of variance and the
2 test according to Pearson. Results were considered significant at P<0.05. MANOVA was used for multiple comparisons between groups.
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Results
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Clinical symptoms
All 90 women approached answered the questionnaire and underwent physical examination. The most frequent complaints were arthralgias, myalgias and tingling/numbness of the fingers, as demonstrated in Table 2
. Physical examination by a rheumatologist (M.G.) revealed typical symptoms of longer-lasting rheumatoid arthritis in two patients. The first symptoms appeared and diagnosis was established 4 and 5 yr before implantation respectively. The other patients showed no typical signs of rheumatoid arthritis or CTD; in particular there was no synovialitis, functional restriction due to acute or chronic arthritis, skin abnormalities such as erythema, scleroderma-like thickening or fibrosis, or vasculitic changes. Some patients had subcutaneous nodules or wrinkling close to the SBI. Most patients presented musculoskeletal symptoms, e.g. muscle tenderness, myogelosis and tendomyopathic pain in typical areas (e.g. epicondylitis humeri), but also in the pectoral muscles. However, none of the patients fulfilled the American College of Rheumatology criteria for fibromyalgia [16]. In most cases, tender points were found in the upper part of the body, while there were only a few positive points in the lower body.
Radiological findings
According to the results of the MRI scans, 66 of the 90 women had intact implants, while in 24 patients typical findings of implant rupture were detected. Most ruptures (23) appeared to be intracapsular, while six were extracapsular. In five patients intra- and extracapsular ruptures were detected.
MRS revealed the presence of silicone in the liver in 28 (31.1%) women, while 62 (68.9%) had no hepatic silicone resonance in their spectrum. In 13 of 24 (54.2%) women with MRI-detected implant defects, silicone was found in the liver, compared with 15 out of 51 (22.7%) cases with intact implants according to MRI criteria. In summary, 11 patients with implant ruptures had no detectable silicone in their liver. We also performed MRS in four patients with chronic renal failure and dialysis treatment for at least 10 yr in order to exclude silicone deposition in patients regularly exposed to silicone, e.g. by extracorporeal circulation techniques. None of these patients had evidence of silicone deposits in the liver.
Laboratory assessment
Antinuclear antibodies were found in 28 women (31.1%) by the use of immunofluorescence staining in Hep-2 cells. The intensity was expressed on a scale from (+) to +++. There were 13 samples estimated as (+) and 15 as +. The highest possible intensities of staining (++ and +++) were not encountered. The pattern was fine speckled in 22 cases, coarse speckled in three and homogeneous in three. All sera positive in immunofluorescence were subsequently checked by a semiquantitative screen for extractable nuclear antigens. However, only two of these 28 sera were found to be weakly positive (1.1 and 1.5; n<1.0). One of these sera turned out to be SS-A (Ro)-positive with a low titre. All ANA-positive patients had a normal C-reactive protein concentration; two of the ANA-positive patients were positive for rheumatoid factor in the Latex test, including one of the two patients with previously diagnosed rheumatoid arthritis.
In two control groups, the incidence of positive ANAs was 35.5% (62 patients with a previous history of breast cancer; average age 52.3±13.3 yr) and 49% (51 patients with hormone substitution; average age 47.9±13.5 yr).
Associations
Twenty-four patients (26.6%) had MRI-detected implant rupture. As shown in Table 3
, patients with intact SBIs had a shorter interval since implantation (8.23 vs 11.21 yr) compared with patients with defective SBIs; other patient characteristics (age, indications for SBI) were similarly distributed between the two groups and no statistical differences between the groups could be established. The incidence of clinical complaints was not correlated with MRI-assessed implant integrity (Table 3
).
Of these 24 women with defective SBIs, 13 (54.2%) were found to have silicone in the liver by MRS and 11 (45.8%) did not have silicone in the liver. Of the 66 women with MRI-evaluated intact implants 15 (22.7%) had the typical hepatic silicone spectrum in MRS, while 51 (77.3%) did not. There was a positive association between MRI-detected SBI rupture and the occurrence of silicone in the liver (P=0.006). Silicone in the liver in patients with intact implants according to MRI may be associated with the frequently described gel-bleeding, the migration of silicone through intact membranes.
The association of symptoms with silicone detection in the liver is documented in Table 4
. The only statistically significant difference was the incidence of finger tingling/numbness in the MRS-positive group vs the group without evidence of silicone in the liver (P=0.006). In the ANA-positive group of 28 patients, 13 (46.4%) had evidence of silicone in the liver and 15 did not (53.6%). In 15 (24.2%) of the 62 ANA-negative patients, silicone could be detected in the liver by MRS, and it could not be detected in 47 (75.8%).
Table 5
demonstrates that there was no correlation between ANA-positivity and the prevalence of clinical symptoms. The overall frequency of a positive ANA test was 13 out of 28 (46.4%) in patients with MRI-detected silicone in the liver and 15 out of 47 (24.2%) in the group in whom silicone was not detected. This difference was statistically significant (P<0.033).
Patients with minor complaints/well-being
Twenty-six patients (28.9%) graded their present health status as 1 (very good) or 2 (good) on a scale from 1 to 6. Surprisingly, in this group the incidence of patients with breast cancer in their history was 61.5%, which is higher than the overall incidence of cancer patients (53.3%). These patients also had a considerable incidence of arthralgias and myalgias (46.2 and 34.6% respectively). However, the incidence of self-estimated depression was lower, at 15.4% (vs 28.8% in the entire group). Of these women, 26.9% were members of an association of silicone-damaged women (vs 38.9% in the whole group) and 26.9% had a positive ANA test (vs 31.1% overall). Implant ruptures were found in 19.2% (vs 26.6% overall). MRS detected silicone in the liver in 19.2% of patients (vs 31.1% overall). None of these differences reached statistical significance.
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Discussion
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To our knowledge, this is the first study to evaluate the correlation between implant integrity and clinical symptoms as well as laboratory findings in women with SBIs. The indication for implantation was breast cancer in around 50%; it was around 25% for each of cystic mammopathy and cosmetic reasons. This distribution differs from that in the USA, where cosmetic reasons are most frequent [3, 4]. The range of complaints reported in our series of 90 women is similar to that in comparable investigations. The most frequently mentioned symptoms are arthralgias, paraesthesias, myalgias, night sweats and fatigue. Borenstein [17] and Bridges [18], in their surveys of 100 and 95 patients respectively, found fatigue, arthralgias and myalgias to be the most frequent complaints. Salomon [19] reported a different distribution, with fatigue as a leading complaint (77%), but he also frequently encountered dryness of the eyes and mouth (65%), rashes (4660%) and alopecia (40%). The combination of arthralgias, myalgias, sicca complex, atypical rash and symptoms of peripheral neuropathy was suggested by Bridges [18] as constituting a silicone implant-associated syndrome (SIAS) in 1995.
Our results underline the well-documented finding that specific CTDs do not have a higher prevalence in women with SBI [3, 4, 20]. The detection of definite rheumatic disorders was not the main purpose of our study, in particular since the number of patients was too small to allow any firm conclusion. On the other hand, Brown et al. [21] have published a study on 344 women in whom the possible diagnosis of a rheumatic disorder was checked exclusively by a questionnaire asking if they had been given a diagnosis of selected connective tissue disease. Brown et al. did not find an increased incidence of such reported diagnoses in patients with MRI-detected SBI rupture (which is in accordance with our results). One has to keep in mind, however, that the use of questionnaires in the absence of clinical and laboratory examination by a specialist in rheumatology does not allow differentiation between definite rheumatic disorders that have overlapping symptomatology and complaints and differ widely in aetiology and prognosis.
In the present study, two cases of rheumatoid arthritis, diagnosed several years before SBI, were the only distinct inflammatory rheumatic diseases we found. The majority of patients described musculoskeletal pain but there was no objective pathological finding except for myogeloses and muscle tenderness. This correlates with the recently published results of a postal survey [22] that confirmed a high level of correlation of symptoms in patients with so-called SIAS with those in patients suffering from musculoskeletal diseases, especially fibromyalgia. Accordingly, following SBI explantation the percentage of remissions of myalgic symptoms is relatively low [23].
In our study, 26.6% of patients had implants with MRI-proven ruptures, and 31.1% had silicone in their liver as revealed by MRS. The incidence of SBI ruptures seemed to be higher than in other studies [24], possibly because we used the most sensitive diagnostic method, MRI. Though only six ruptures were considered to be extracapsular, 28 women had the silicone-specific spectrum in their liver. As MRS spectroscopy is generally accepted as a reliable method of detecting silicone in the liver (with negative silicone findings in controls and long-term dialysis patients), this finding confirms the phenomenon of gel bleeding in women with apparently intact SBIs.
The most important question, however, is whether or not migration of silicone from SBIs may cause a specific disease or at least typical symptoms or laboratory findings. As shown in Table 3, patients with defective SBIs according to MRI had complaints similar to patients with intact SBIs. None of the reported symptoms was significantly more frequent in women with defective implants, although more of these women reported tingling/numbness of the fingers and dizziness. This result, however, does not answer the question whether local changes (e.g. scarring) following SBI rupture cause the non-specific symptom of tingling/numbness, or whether the defective implant leaks silicone, which might cause systematically toxic or immunologically transmitted damage [2426]. The MRS test for hepatic silicone was intended to highlight this problem. All in all, the correlation of clinical symptoms with MRS evidence of silicone in the liver was low. Most symptoms were reported at similar frequencies by patients who were positive and negative for silicone in the liver. Dry eyes and photosensitivity were mentioned more often in the group with silicone in the liver, although the difference did not reach statistical significance. More impressively, tingling/numbness of the fingers was reported by 82.1% of women with silicone in the liver but only by 51.6% of women with silicone-negative MRS. This difference proved to be highly significant statistically (P<0.006).
These data might be explained by the observation that women with defective or gel-bleeding SBIs do not have a higher risk of CTD nor do they suffer more frequently from a number of general complaints (such as arthralgias, myalgias and sicca syndrome), but experience a higher prevalence of peripheral paraesthesias, pointing to a possible peripheral neuropathy. However, the number of publications dealing with silicone exposure and neurological diseases is small. Two population-based studies provided no support for the proposal that SBIs cause neurological disease [27, 28]. On the other hand, a number of reports of cases with symptoms ranging from memory loss and other cognitive impairment to painful syndromes and fatigue did associate SBIs with neurological symptoms. In the largest study, Vogel [29] looked for pathological changes in 47 consecutive nerve and muscle biopsies taken from patients with SBIs. Eight of 47 nerves showed pathological findings, in seven cases axonal neuropathy. Vogel regarded this frequency as normal in larger series of nerve biopsies; in his opinion, the findings do not support a consistent association between SBI and any neuropathologic entity. However, together with our finding of a statistically significantly higher incidence of symptoms of peripheral neuropathy in the group with MRS-confirmed silicone migration, a neuropathological effect of silicone cannot be excluded. The mode of action by which migrating silicone might eventually cause damage is a matter of speculation. Some authors have suggested an adjuvant function of silicone in provoking a rheumatic disease (e.g. polyarthritis) by increasing the antibody response to foreign antigens [30, 31], while other authors did not find such an effect in mice undergoing silicone implantation [32, 33]. The immunogenic potential of silicone is also a matter of discussion. Relevant to this discussion is the search for a specific antibody in patients with SBI. Two studies examined ANA in women with SBIs: Press et al. [34] stated that, of 24 women referred to a rheumatology unit, 11 had signs and symptoms that met criteria for defined autoimmune disease (seven of these had scleroderma). High ANA titres were found in 10 of these 11 patients; the ANA specificities were similar to those found in the idiopathic forms of the corresponding autoimmune diseases. This report does not militate against our results, since we tested a group of women without clinical evidence of a defined autoimmune disease (with the exception of two women who had already suffered from rheumatoid arthritis before implantation with silicone implants). Consequently, and not surprisingly, we found a lower incidence of ANA-positive patients overall and, particularly, we could not find high ANA titres or ANA specificities apart from one Ro-positive serum. In addition, there were no complaints which were significantly related to ANA positivity (Table 5
). The distribution of complaints was very similar in ANA-positive and negative patients, some complaints (photosensitivity) being more frequent in ANA-negative patients. This result fits well with the publication of Shoenfeld's group [35], which showed a relatively high prevalence of antibodies with widely spread specificities in a group of 86 asymptomatic women with SBI. In contrast to this finding, however, our study revealed the overall incidence of ANA positivity to be higher in women with silicone in their liver (46.4%) than in those without it (24.2%). The pathophysiological background of this difference remains to be clarified.
Our ANA results were compared with those for gynaecological control patients without SBIs; in the breast cancer group and the hormone substitution group, the rate of ANA positivity was comparable to that in women with SBIs and silicone in the liver. Taking all data together, ANA positivity in women with SBIs is not a sufficient indication of an ongoing autoimmune process.
In summary, there is no strong evidence of silicone-related damage in women with SBIs. Women with defective implants or silicone migration have almost the same spectrum of symptoms as those with intact implants. The type of complaint found is not very specific, pointing to a common picture of musculoskeletal complaints with frequently associated functional symptoms rather than to a specific silicone-associated disease. The increased prevalence of tingling/numbness of the fingers has not yet been correlated with an objectively measurable neuropathy. ANA positivity was more frequent in women with silicon migration, but did not differ significantly from that found in women of comparable age with other diseases.
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Acknowledgments
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This work was supported by a grant from the German Research Foundation (DFG; PF 244/4-1, PF 244/4-2).
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Notes
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Correspondence to: M. Gaubitz, Department of Medicine B, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany. 
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Submitted 12 December 2000;
Accepted 14 June 2001