Neuroimaging in Breast Implant Illness: An fMRI Pilot Study.

BACKGROUND: Some women with breast implants report systemic and cognitive symptoms known as breast implant illness (BII), which are very similar to those of fibromyalgia. Functional MRI (fMRI) has shown altered brain activity in fibromyalgia patients. OBJECTIVES: The aim of this pilot study was to investigate whether brain alterations could be observed in BII patients by fMRI. METHODS: Women aged 18 to 76 with silicone breast implants for cosmetic reasons were recruited through a Dutch online BII support organization (MKS) and through the Maastricht University Medical Center. Study participants comprised 12 women with BII and 12 women without symptoms. Participants completed questionnaires regarding demographic characteristics, medical history, psychosocial complaints (Four-Dimensional Symptom Questionnaire), cognitive failure (Mini-Mental State Examination), and pain intensity and pain-related disability (Chronic Pain Grade Scale). Subsequently, brain images of all participants were obtained by resting-state fMRI and diffusion tensor imaging in a 3-T MRI scanner (Siemens Medical System, Erlangen, Germany). RESULTS: Eleven BII patients and 12 healthy controls were included in the analysis. Baseline characteristics were similar in the 2 groups and the mean silicone exposure was 15 years. Patients scored significantly higher than controls on both pain intensity and disability. Patients scored worse on depression, somatization, distress, and anxiety compared with asymptomatic women. Mini-Mental State Examination scores were normal. However, the analyses of both functional connectivity and structural integrity showed no significant differences between the 2 groups. CONCLUSIONS: This pilot study showed no evidence of brain alterations in BII patients. However, patients scored significantly worse on psychosocial symptoms than controls. Psychological factors appear to play an important role in BII and should be further investigated.

Effects of Silicone Breast Implants on Human Cell Types In Vitro: A Closer Look on Host and Implant.

BACKGROUND: Silicone (gel) breast implants (SBI) are used world-wide for breast augmentation, and reconstruction or to correct breast deformities. They consist of two compounds: an elastomer silicone shell (envelope) and a silicone gel filler (core). Breast Implant Illness (BII) is a term used for women with SBI, who suffer from various of symptoms including myalgia, arthralgia, fatigue, fever, dry eyes and/or dry mouth (sicca), as well as cognitive disturbances, which are rated by these woman as response to SBI. The pathogenesis of these adverse effects as well as the histocompatibility and the SBI-cell interaction of silicone and its surrounding tissue (implant-host tissue interface) is a subject of current research. The main purpose of this review is to provide an overview of the current knowledge regarding the effects of silicone (gel and elastomer surfaces) of a SBI on different human cell types from experimental - in vitro - models. METHODS: A comprehensive research was conducted by two independent reviewers in March and July of 2020 in the PubMed, MEDLINE, and Cochrane databases. RESULTS: A number of 1328 articles on this topic were initially identified, of which 62 could be finally included an analysed in this review. CONCLUSION: SBI may lead to a physiologic pro-inflammatory and foreign body host response with fibrous encapsulation accompanied by a disturbed Th17/Treg balance and IL-17 production. No causal relationship is known for systemic symptoms and/or autoimmune outcomes in the context of BII. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Prevalence of Self-Reported Health Complaints and Health-Related Quality of Life in Women With Breast Implants.

BACKGROUND: Some of the millions of women with silicone breast implants (SBIs) report a pattern of systemic complaints, known as ASIA syndrome. However, the association between these complaints and breast implants remains uncertain. OBJECTIVES: This study aimed to evaluate the prevalence of complaints in women with breast implants and healthy controls, and to compare their health-related quality of life. METHODS: Four groups of subjects were requested to fill in a general and a diagnostic questionnaire, and the Short Form 36. Group 1 was recruited from the Dutch foundation for breast implant illness (BII). Two groups were recruited from Dutch hospitals, where they had been augmented or reconstructed with SBIs (group 2) or saline-filled and hydrogel implants (group 3). A control group without breast implants was recruited from friends of subjects from group 2. RESULTS: In total, 238 women completed the questionnaires. ASIA manifestations appeared in the majority of the respondents (72.3%-98.8%), with a latency period of 0 to 35 years. Adjusted for age, smoking, and comorbidities, typical symptoms only occurred significantly more frequently in group 1. The presence of a chronic disease was an independent predictor for ASIA syndrome. The health-related quality of life was lower in women with SBIs than in women without breast implants. CONCLUSIONS: The adjusted prevalence of BII manifestations is not significantly higher in women with SBIs than in women without implants. The findings of this study suggest that results on BII are subject to selection bias. Further studies are needed to prove an association between self-reported complaints and SBIs.

Subjective Cognitive Functioning in Silicone Breast Implant Patients: A Cohort Study.

Cognitive impairment is frequently reported by silicone breast implant (SBI) patients. The aim of our study is to investigate whether subjective cognitive failure indeed is more frequent in a cohort of SBI patients compared with healthy controls (HCs). Furthermore, the severity of this cognitive failure and a possible relation to other symptoms as well as the duration of SBI exposure was examined. In addition, we assessed the effect of ruptures and reinterventions on cognitive failure severity. METHODS: A cohort study was performed, including 376 women and consisting of 3 different groups of patients; 143 SBI patients (group 1), 94 age- and sex-matched HC patients (group 2), and 139 women with SBI and health issues who registered themselves at a Dutch foundation for women with illness due to SBI (group 3). All patients filled in the Cognitive Failure Questionnaire (CFQ). The American College of Rheumatology Fibromyalgia Diagnostic Criteria (2010) were used to score other symptoms. RESULTS: Completed CFQ data from 222 patients were available for analysis: n = 79 for group 1, n = 62 for group 2, and n = 81 for group 3. SBI patients from group 3 had a significantly higher prevalence of subjective cognitive dysfunction (CFQ score ≥ 43) compared with SBI patients from group 1 and HC (60.5% versus 13.9% and 12.9%; P = 0.000). Linear regression showed a statistically significant relation between subjective cognitive functioning scores and other symptoms (P = 0.000). Implant duration as well as rupture rate and reinterventions were not found to significantly influence CFQ scores. CONCLUSION: An increased risk of cognitive failure in consecutive SBI patients when compared with HCs could not be found.

Two hundreds cases of ASIA syndrome following silicone implants: a comparative study of 30 years and a review of current literature.

In this study, we compared one hundred patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) due to silicone implant incompatibility syndrome diagnosed in 2014 in Maastricht, the Netherlands, with one hundred historical patients with adjuvant breast disease diagnosed in the Baylor College of Medicine, Houston, USA, between 1985 and 1992. Similarities and differences between these two cohorts were identified to determine whether the spectrum of silicone-related disease changed during the last 30 years. Patients with complaints possibly due to silicone-filled breast implants were prospectively examined in the Reinaert Clinic, Maastricht, the Netherlands between January 2014 and October 2014. All patients were evaluated for the fulfilment of ASIA criteria. Results were compared to results of the Baylor College cohort and 18 other reviewed historical cohorts. Clinical manifestations between the Maastricht and Baylor College cohorts were comparable. Fatigue was observed in 98 current patients and in 95 historical patients. Arthralgia was observed in 91 versus 81 historical patients. Myalgia was observed in 54 versus 91 patients. Cognitive impairment was observed in 78 versus 81 patients, pyrexia was observed in 64 versus 52 patients, sicca complaints in 73 versus 72 patients and severe neurological manifestations in 20 versus 32 patients. From the 54 patients who underwent removal of their silicone breast implant, 50 % (n = 27) of the patients experienced improvement of complaints after explantation of the implant. Also, in the 18 reviewed historical cohorts, similar clinical manifestations were described. Our findings suggest that no major changes were present in the observed clinical manifestations between the Maastricht and Baylor College cohorts. Also, despite changes in the principal constituents of the silicone implants during the past fifty years, silicone remained an adjuvant that may 'bleed' and subsequently may be a chronic stimulus to the immune system resulting in similar clinical manifestations as observed in the Maastricht cohort, the Baylor College cohort and 18 other large cohorts of patients. We therefore conclude that silicone-related disease has not changed during the last 30 years.

Vitamin D deficiency as a risk factor for the development of autoantibodies in patients with ASIA and silicone breast implants: a cohort study and review of the literature.

The development of autoimmunity and/or autoimmune diseases is multifactorial. Vitamin D is one of the factors that might play a role. We postulated that both the presence of adjuvants and insufficient levels of vitamin D may result in the development of autoimmunity in patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in relation to silicone implant incompatibility. We measured vitamin D levels in 135 patients with ASIA in relation to silicone implant incompatibility and related findings to the presence of autoantibodies that are commonly used to diagnose systemic autoimmune diseases. Furthermore, we systematically reviewed the literature regarding vitamin D deficiency as a risk factor for the development of autoantibodies. Vitamin D measurements were available for analysis in 131 of 135 patients with ASIA in relation to SIIS. Twenty-three patients (18%) tested positive for autoantibodies, from which 18 patients (78%) had either a vitamin D deficiency or insufficiency (median vitamin D level 60.5 mmol/L), whereas five patients (22%) had sufficient vitamin D levels. The risk to develop autoantibodies was significantly increased in vitamin D deficient and/or insufficient patients [RR 3.14; 95% CI, 1.24-7.95; p = 0.009]. Reviewed literature suggested an association between vitamin D levels and the presence and/or titer levels of autoantibodies in different autoimmune diseases. From our current study and from our review of the literature, we conclude that vitamin D deficiency is related to the presence of autoantibodies. Whether vitamin D supplementation results in a decrease of autoimmunity needs to be studied prospectively.