Response to letter to the editor: Bradford Hill and breast implant illness: evidence for a causal association with breast implants

KEYWORDS:

• Breast implant illness
• causation
• Bradford Hill criteria
• fibromyalgia
• chronic fatigue syndrome/myalgic encephalomyelitis

Dear Madame/Sir,

We thank colleagues from the Dutch Breast Implant Associated Anaplastic Large Cell Lymphoma Research Consortium for their interest in our paper outlining how women who develop systemic complaints after breast implantation should receive a comprehensive medical evaluation and explantation of their breast implants, in certain situations, where the potential harm associated with breast implants may outweigh their benefits.

The authors argue that an association between breast implant illness (BII) and related symptoms is lacking. First, they state that a limitation of our assessment for causality is that BII has only been observed in cohort studies. The authors ignore the reported studies that were described [1]. Importantly, we reported that 23% of unselected patients with silicone breast implants (SBI) had BII commonly reported symptoms such as arthralgias/myalgias, and fatigue/sleep disturbances/cognitive impairment, and sicca/pyrexia, whereas the combination of these three characteristic symptoms was found in only 6% of healthy women without breast implants [1]. In addition, the authors argue that the only study with a formal risk calculation for autoimmune diseases may be hampered by residual confounding such as duration and intensity of smoking since the study by Watad et al. only adjusted for ‘ever versus never’ smoking [2].

While smoking is indeed a risk factor for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis [3–5], it has been demonstrated that smoking is not a risk factor for Sjogren’s syndrome, sarcoidosis, and systemic sclerosis [6–8] and these diseases may even be negatively associated with current smoking [6]. Importantly, Sjogren’s syndrome, sarcoidosis, and systemic sclerosis were the three diseases that demonstrated the highest OR’s (>1.50) for disease development in patients with SBI (n = 24,651) when compared to women without breast implants (n = 98,604) [2]. We agree, however, that residual confounding variables are important factors in all published observational studies that reported the development of autoimmune diseases in SBI [9]. Autoimmune diseases occur in genetically predisposed individuals and are triggered by many different environmental factors such as SBI, chemical agents, infections, vitamin D deficiency, smoking, obesity, microbiome alterations, diet, sex hormones, psychological factors, socioeconomic status, education, and many others [5,10].

Secondly, the authors argue that women with SBI are not comparable to the general population. Importantly, they also postulate that these differences may possibly increase the risk of autoimmune diseases. Interestingly, the studies cited by the authors regarding ‘characteristics of women with implants’ were small studies performed by authors with financial ties to SBI corporations, and were not corrected for residual confounding factors [11]. Moreover, no theoretical explanation was provided by them for why these specific characteristics would result in increased risks for developing an autoimmune disease. Since BII occurs as frequently in patients who had undergone a reconstructive breast procedure as in patients who opted for a cosmetic procedure, it is hard to believe that these ‘characteristics’ are related to the occurrence of BII and/or autoimmune diseases in patients with SBI.

Thirdly, the authors argue that a 45% increased hazard ratio to develop an autoimmune disease represents only a weak association. We strongly disagree with this statement. For instance, it is well established that certain diseases with similar hazard ratios can result in future complications. This is illustrated in patients with peripheral arterial disease, who are known to develop future vascular events [12]. It is also well described with the association of smoking and the development of rheumatoid arthritis [4] which has a notable relative risk similar to autoimmune diseases after SBI [1]. In addition, the authors argue that the ‘condition autoimmune disease’ is rare. This is not correct, since as many as 22% of unexposed women may be diagnosed with an autoimmune disorder [2].

Fourth, the authors argue that there are studies that refute the association between SBI and autoimmune diseases and/or BII. The authors state that in the report by Misere et al. [13] there was no increased risk of BII found in patients with SBI. However, as reported by Misere et al., women with SBI more frequently suffered from chronic fatigue syndrome (10.8% versus 1.8%) and/or fibromyalgia (16.9% versus 3.5%) when compared to women without SBI. In addition, the authors state that Barbosa et al. recently found no increased risk for autoimmune diseases in SBI [14]. In this small study, the authors reported that 70% of women with SBI (n = 513) had a ‘connective tissue disease’ and 85% required the use of NSAIDs whereas 54% of the patients without a SBI (n = 21,550) had a ‘connective tissue disease’ and 68% used NSAIDs. Although the findings from this study are interesting, their study population does not represent the general populations that were studied by others as a much larger frequency in both groups was diagnosed with autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus or connective tissue diseases and most patients required NSAIDs presumably for treating pain.

Fifthly, the authors argue that we ‘uncritically accepted’ the concept of BII/ASIA due to silicone implant incompatibility syndrome. Although it is prudent for scientists to periodically question everything, we firmly disagree with this statement. It is clear that women with SBI may develop symptoms of fatigue, arthralgias, myalgias, sicca, pyrexia, and cognitive impairment after implantation and that a majority of these symptoms disappear in most women after explantation. Further to this observation, explanatory mechanisms have been described [1], and are currently pursued in several research laboratories.

Finally, we agree with the authors that some women may benefit from breast implants. It is important to realize, however, that long-term breast-related and body-related outcomes of autologous breast reconstruction are superior to reconstruction with SBI [15].

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Editor disclosures

One of the senior editors for this journal has served as a medical expert for the United States government, in the US vaccine court, in defense against autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA). He thus recused himself and held no decision-making powers on this or related articles. The decision-making editor for this manuscript has no relevant financial relationships or otherwise to disclose.

Funding

This paper was not funded.