COSS
kids Nederland
Coalition of Silicone Survivors
Ostermeijer/Patten BP1005
COSSkids is onderdeel van Coalition of Silicone Survivors - Boulder Collorado USA
Oktober 2016
Britta Ostermeyer Shoaib / Bernhard M. Patten
DISQUISITION ON HUMAN ADJUVANT DISEASE
Supported by a grant from the George and Irene Lindler Foundation (Houston). The authors
are grateful to Pam Louis. *Department of Neurology, Baylor College of Medicine, 6550 Fannin
Street, Houston, Texas 77030
Classical rhetoric distinguishes five topics under which any issue may be addressed:
definition, comparison, relationship, circumstance, and testimony. I propose to examine
Human Adjuvant Disease (HAD) in light of these topics.
DEFINITION BY GENUS
Human Adjuvant Disease (HAD) is an autoimmune condition associated with foreign materials in contact with the human
body. Its existence must be inferred because the manufacturer’s package insert says it may occur [1]; numerous medical articles on the subject exist [2-11]; there have been improvements post-explant of foreign materials that have been implanted [12-14]; and in animals, immune stimulation activity of foreign materials has been demonstrated especially epoxyresins, oleoanilides (the cause of Spanish Oil syndrome), vinyl chlorides, chlorinated hydrocarbons and
octamethylpolycyclicsiloxane (D4), and silica [15-20].
HAD means the disease produced by the immune stimulation caused by the effect of foreign material(s). Therefore, this
definition excludes all naturally occurring disorders merely worsened by the immune stimulation of the foreign material.
Such disorders should be classified as “_________ worsened by the adjuvant activity of__________ .” For example,
systemic lupus that is believed to be worsened by adjuvant activity of polyurethane and free silicone in tissue should be
classified as systemic lupus worsened by those adjuvants-and not as HAD.
DEFINITION BY DIVISION
Most cases of HAD would be expected to exhibit the following characteristics, as adapted and modified from Miyoshi’s
original description [21]:
1. Foreign material or materials in the body at some time prior to the development of the autoimmune disease;
2. Local reaction to the implanted material with any one or all of these things: encapsulation, pain, tenderness,
heat, swelling, redness;
3. Some signs and symptoms generally associated with known autoimmune conditions, including but not
necessarily restricted to aches and pains in muscles and joints, stiffness, weakness, and easy fatigue;
4. At least one circulating autodirected antibody at some time after installation of the foreign material. Such
antibodies must be detected in amounts elevated above normal (Only university-based or certified commercial
laboratories can be reasonably and reliably used to fulfill this characteristic’s requirement);
5. No other condition or disease explains the patient’s illness, including infection, malignancy, or naturally occurring
autoimmune disease. If, for instance, the patient meets the accepted criteria of the American Rheumatism
Association for diagnosis of lupus or rheumatoid arthritis, HAD is excluded. The exclusion of typical diseases
makes sense, because HAD usually produces atypical autoimmune disease;
6. Evidence is found for local immunological activation. This commonly consists of foreign body giant cells, but can
be simply a chronic inflammation with plasma cells, some lymphocytes, but mainly lots of macrophages
marginated on or near the foreign material or surrounding the foreign material;
7. Improvement follows explantation when most if not all the foreign material is removed. Time to improvement
depends on the age of the patient, the duration of illness, the severity of the autoimmunity, and many other
influences and conditions not fully understood. In general, significant clinical and laboratory improvement in HAD
occurs within two years of explantation. If improvement fails to occur within this time frame, HAD probably was
ot the cause of the patient’s condition.
These empiric defining criteria, like the criteria for rheumatic diseases in general [22], derive from a dynamic area of
research which at present has an incomplete concept of the disease and an imperfect diagnostic technology. In the years
ahead, improved knowledge and techniques will likely change refine and more accurately describe these characteristics.
Meanwhile, the seven divisions offer a standard against which individual cases or groups of patients can be identified,
measured, and compared.
Comparison
Similarities and differences among cases define HAD and help distinguish it from other conditions. Degree also indicates
the type of illness and cause.
SIMILARITIES
Most HAD patients can be identified by the pattern distribution of abnormalities in their cases and their similarity to
others who have had comparable problems. The usual patient has had foreign material installed within body tissues,
followed sometime later by the development of local difficulties around the site of implantation and, after that, systemic
signs and symptoms of reaction to the material. Local complications include pain, aching, heat, contracture, and
tenderness around the foreign material. Prominent systemic symptoms include morning stiffness, aches and pains in
muscles and joints, gel phenomena, memory loss for recent events, dry eyes, weakness and easy fatigue of skeletal
muscle, regional lymphadenopathy, and skin rash. Signs include local heat, redness, induration, and irregularity around
the implant, and generalized weakness, glove and stocking sensory loss, and evidence of other peripheral or central
nervous system dysfunction or both. This pattern distribution of local complications near the foreign material associated
constitutes a combination unique to HAD. Future studies may show it the sine qua non of this disease, a stereotype of
abnormalities usually not seen in conditions other than HAD. Incidentally, HAD does not occur exclusively in women. It
happens in men in cases associated with ruptured pectoralis and testicular implants.
Laboratory reports show a variety of abnormalities not unique to HAD but occurring in other autoimmune conditions. All
of the abnormalities probably reflect diffuse rather than focal activation of the immune system. The ANA, rheumatoid
factors, positive antibodies against human antigens, the antibodies against the major ganglioside in the central nervous
system, anti-GM1 antibodies, myelin associated glycoprotein antibodies (anti-MAG), antisulfatide, and anti-beta-tubulin
antibodies do not mean the patient has lupus or rheumatoid arthritis or the other relatively specific diseases associated
with those positive blood tests, and certainly do not mean those diseases are present in the absence of clinical disease.
They are immune markers suggesting immune system activation by the foreign material.
Other tests show what organ systems are adversely affected by the immune activation and by how much. So, when
indicated, MRI, SPECT scan, EMG, and so forth can help define the extent of damage already present in an individual
patient and can help organize the approach to treatment.
DIFFERENCES
Patients with HAD differ from other patients in a variety of ways, including the obvious presence of foreign material in
their bodies and also in the multiplicity of signs and symptoms. They usually have at least 20 complaints and commonly
circle over 50% percent of the lists of common symptoms of disease [23,24]. Other patients who do not have HAD have a
much more circumscribed list of complaints. The large number of complaints in HAD makes sense if one considers the
disease is likely due to a diffuse activation of the immune system and not a circumscribed focal activation of one part of
the immune system. If the immune system is diffusely and globally activated, then there should be diffuse and global
complaints referable to virtually every level of the nervous system, to the muscles and nerves, connective tissue, blood
vessels, and skin.
DEGREE
As the severity of local problems increases, the systemic problems do too, especially if the implant has ruptured or if the
immunogenic foreign material directly contacts the immune system by regional or systemic spread. In our series of
implanted patients who had systemic disease, the proven rupture rate was 60 percent at explantation [23,24], a number
higher than the estimate of 1.5 percent by the manufacturer and the 15 to 20 percent mentioned by the FDA. Some foreign materials, such as polyurethane, seem to cause more immune activation and produce more skin rashes and other adverse systemic effects sooner than other materials.
The presence of different time courses and clinical degrees of affliction associated with different foreign materials strongly
suggests that the foreign material plays an etiological role and may actually cause the disease. For instance, the time
course of vinyl chloride disease differs from that of toxic Spanish Oil syndrome. With silicone gel implants, six years
usually elapse from the time of implantation to development of first systemic symptoms; silicone implants surrounded by
polyurethane have a shorter latency.
Taken together, the similarity of disease among patients exposed to the same agent, the differences that the induced
disease bears to other naturally occurring diseases, and the fact that degrees of adversity depend on degrees of exposure, as well as the time-linked nature of the exposure to the subsequent development of the disease, all argue that the agents named actually cause the condition.
Relationship
The topic of relationship divides into three parts: cause and effect, antecedent and consequent, and contraries and
contradictories.
CAUSE AND EFFECT
To assign a cause and make it stick requires four elements. The cause must be sufficient to produce the effect; it must
be the most likely among several possible causes; conditions must not inhibit the cause from exerting its effect; and the
cause must be invariably produce the effect. In the muddy waters of statecraft, real-life situations, the legal arena, and
medicine “invariably” has given way “more likely than not” or with a “reasonable degree of medical certainty.”
In HAD, all four elements apply to foreign materials that are associated with local complications, such as the rupture of
an implant and spill of free silicone into tissue. The rupture of the implant alone is sufficient to produce the spill of silicone
into tissue and to provoke a local inflammatory reaction.
Systemic complications require no small degree of circumspection, and cases must be considered individually. It is not
enough to show that the disease followed implantation. Dry streets get wet after rain and then dry; when rain recurs, they
get wet again. This does not mean dry streets cause rain.
Medicine abounds with post hoc propter hoc errors. There was a time when malaria was considered caused by swampy
land that had bad air. Although we now know that malaria is induced from circumstances more complicated than that, yet
when Roman engineers drained the swamps around the Tiber 2,000 years ago, they abolished malaria in that section of
Italy. These things considered, most people will associate a ruptured implant with the systemic disease that follows,
because most individual cases have strong evidence for unique activation of the immune system.
ANTECEDENT AND CONSEQUENT
This less rigorous form of cause and effect argument generally applies to implants and can be reduced to a rephrased
syllogism: (1) Foreign materials produce local and systemic reactions; (2) an implant is a foreign material; therefore, (3) an implant causes local and systemic reactions. Whether the implant has in fact done so in an individual case depends on the individual evidence adduced.
CONTRARIES AND CONTRADICTIONS
Contraries and contradictions offer an avenue of proof, since two contraries cannot be true simultaneously: either the
implant causes local complications or it doesn’t. To prove that implants cause local complications, it is necessary simply
to demonstrate one case of a local complication. Since numerous cases of local complications are on record-not to
mention the numerous types of local complications-the proof of contraries is more than abundantly fulfilled.
One can make the same argument for the causation of systemic complications. Either implants cause systemic
complications or they don’t. If the implant doesn’t cause autoimmune disease, then why does the manufacturer Dow
Corning state under section 17, paragraph 3, of the package insert that “if an immune response is suspected and the
response persists, removal of the prosthesis is recommended along with the surrounding capsule tissue. Such patients
should not be re-implanted” [1]? Are they suggesting operations for no purpose? Would they endanger the lives of the
implanted patients for no valid reason? If implants and foreign materials cannot cause immune reactions, then why are
there numerous published papers that say they do? Why are there animal studies that show foreign materials are
immunogenic? Clearly the reasoning of contraries proves that implants cause systemic problems. Whether they have done so in an individual case must be determined on the basis of the evidence presented.
Circumstance
The general heading of circumstance comprises two main lines of discourse: the possible and the impossible, and the
past fact and future fact.
THE POSSIBLE AND THE IMPOSSIBLE
The possible and impossible come in five Aristotelian flavors, most of which apply to the matter at hand. Their application
is simple.
First, if one pair of similar items is possible, then the other is possible also. Silicone directly injected into tissue causes
local and systemic reactions; therefore, silicone indirectly injected into tissue after a silicone implant ruptures causes local and systemic complications. Second, if a difficult thing is possible, then the easier thing is possible also. If you can recite the alphabet backwards, chances are likely you can recite it forwards as well. If the bleed of silicone causes a local
inflammatory reaction, then a rupture of an implant will cause a local inflammatory reaction.
Third, if one problem-causing thing can do something, then two problem-causing things together can make things worse.
If silicone causes a local inflammatory reaction, then silicone plus an additional foreign material like polyurethane (probably more irritant) must do so faster, and more severely. Fourth, if a thing is possible without aggravating or complicated conditions, then it is definitely possible with the complications. An intact implant may elicit a surrounding inflammatory reaction; therefore a ruptured implant may do so too.
Finally, if the parts are possible, so is the whole. Hence, if the implant has been associated with Sjogren’s syndrome,
Raynaud’s phenomena, scleroderma, memory loss, muscle weakness, and what have you in individual cases, then a
patient who exhibits all of those afflictions can have a possible complication too.
PAST FACT AND FUTURE FACT
Whether a thing has happened or not is useful in establishing precedent. When companies have settled cases that
purport injuries due to implants for large amounts of money, a precedent is established; the same occurs when a jury
awards a large amount of money for the same reasons. Past fact suggests that reasonable people studying a particular
situation reached a reasonable conclusion, and projects that similar people acting under similar circumstances may reach similar conclusions in the future, establishing a similar or identical future fact. What can be said about past fact hews closely to common sense: two events closely associated (implant and some disease) in the past produce event X
(compensation). It is likely the same associated events will also produce the same consequences in the future, and that
the other cases will be settled or large monetary awards made in compensation. What is right or wrong about this cannot
be determined by this line of argument, since past fact merely predicts future fact-not what is correct, just, or right.
In a larger sense, one can invoke the physical laws of the universe to predict the production of future fact. The second
law of thermodynamics, for example, has never been violated and therefore is considered a sound predictor of what will
happen. It tells us that everything is breaking down, headed towards disintigration and disorder. Since the implant is part of the physical universe, it is governed by the second law and therefore it too must break down. And if it breaks down, it must cause those things known by past fact to be caused by mechanical implant failure-including spilling silicone into tissue, local inflammation, scar formation, pain and tenderness, heat, and of course, deformation of the tissue in which that implant had been placed.
Testimony
Testimony, the last major topic, encompasses six subheads: authority, testimonial, statistics, maxims, law, and
precedent.
AUTHORITY
We tend to imagine some distant past where people unblinkingly accepted the dictates of Church or King, and therefore
say that authority isn’t what it used to be. We try to believe in this modern, scientific, democratic age that people look at
things skeptically and tend not to accept anything unless proven by evidence and reason.
Unfortunately, this belief remains unjustified by the facts: a new age of human intelligence has not dawned. While many
old authorities have been simply shunted aside, they have been replaced by new authorities because humans crave simple answers to complex problems. Appeal to authority-any authority, even the manufacturer of the package insert or the FDA itself-remains illogical, because an authority can be right or can be wrong. What an authority says must be judged by the evidence and not by the position or reputation of the authority.
Nevertheless, provided you cite authority that people accept, arguments citing authority carry considerable weight,
especially if the authority cited is one of the new breed-such as the talk shows, the popular press, or public radio, or even
better a famous movie star, television news personality, or public opinion surveyor. The new authorities are not
disinterested. Instead, they have a financial stake in selling newspapers or getting people to listen to their broadcasts.
Therefore, positions taken by modern authorities tend to be emotionally colored, sensational, and not based on a
dispassionate analysis of evidence.
Plastic surgeons continue to complain about the rather poor press coverage of the breast implant situation and the
overblown emphasis on side effects and the supposed faults of the manufacturers. They railed that there were no scientific studies proving that implants caused problems and even claimed the extreme and untenable position that there were no problems. (Incidentally, this interesting statement itself had little scientific support, since it depended on both the genus definition of the words scientific and study, as well as the division definition of the same words. The statement could be true or false depending on how scientific you wanted to be and how seriously you wanted to examine the studies available.) Thus, plastic surgeons failed to realize the decisions were being made against them emotionally and not rationally, and therefore their arguments in this context meant little. They also failed to understand that as irrational as such media analysis was, it still had the full power of modern authority and as such determined how people viewed the
issue. This remains important, because how the public thinks in a democracy determines how the events will transpire and what future outcomes will happen.
That brings us to the real authorities that have power to enforce the prevailing opinions of our society: the Food and Drug
Administration and the Congress of the United States of America. Let’s examine how these authorities viewed the
situation.
Food and Drug Administration-This organization, empowered by the Congress to regulate food, drugs, and medical
devices, has acted against the implants and put the full weight of law against routine cosmetic augmentation with gel-filled devices. The detailed history of the regulation of the devices shows the FDA had clear-cut fears that the devices had not been tested properly; actual past decisions of the FDA always modified the device classifications into categories requiring tighter and tighter regulation [25].
Furthermore, the FDA document released in February 1993 entitled Silicone Breast Implant Team Leaders’ Report,
Surgical Device Panel, U.S. Food and Drug Administration Critique of Premarketing Applicationdetails the failures of the
manufacturers in their premarketing applications [26]. The FDA failed the applications for defects in sterility, materials
testing, animal studies, human studies, and in a host of other problems. It even accused the manufacturers of fraud,
because information was submitted to FDA that the manufacturer knew or should have known was false. The FDA
concluded that the manufacturers failed to prove their product was safe and effective, despite 30 years of use of the
materials in the United States. (This represents the final authority on the subject.) Consequently, the FDA removed the
silicone gel-filled implants from the American market for cosmetic augmentation. Subsequently, many manufacturers shut down operations, claiming they were afraid of further liability claims. They conveniently failed to mention that the FDA had closed the major market for their product: in fact, most of the market had disappeared overnight. Implants for cosmetic augmentation remain off the American market to this day.
The citation of the FDA’s document and the House of Representatives staff report constitutes a powerful force in the
implant issue because those documents determined whether the implant could continue, and made laws that implants
could not continue. Some brief quotes from the documents follow here to show the style and impact of the statements. The net effect of these stands as a powerful persuasive argument to the reasonable average citizen that the implants were not proved safe and had in the past, and have in the present, substantial adverse effects on health. The documents taken as a whole indicate that the manufacturer failed to prove the devices were safe. They clearly state that the safety and
effectiveness data were inadequate. Any defense of implants must try to get around the force of these papers, which-
because of their authority and impact-appears difficult and may be almost impossible.
In February 1993 the FDA recommended disapproval of the premarketing applications of all implant manufacturers
because of failure to provide adequate clinical, mechanical, and toxicologic testing data [26]. The animal testing employed was considered outdated and nonscientific; the chemical and mechanical descriptions were deemed variable and inadequate; the extractable and leachate propensities were inadequately tested and the metabolic effects of the gel
inadequately tested. In addition, the psychological benefit of the device was improperly tested. Adequate depression,
fatigue, stress, strain, abrasion, and energy to rupture tests were not prepared. Also, cohesivity, valve competence, and
joint integrated tests were inadequate, and the effects of the heat and other risks of sterilization on the materials and the
components were never properly evaluated. The report goes on and raises the question that if this presentation of risk and
benefit, formulated after 30 years of experience in an attempt to obtain governmental approval, fails to support claims of
safety and efficacy, what was the safety data in the past? The FDA concluded that none of the clinical investigation(s)
provided sufficient quantitative data to measure risk.
The Committee on Government Operations of the Human Resources and Intergovernmental Relations Subcommittee of
the House of Representatives issued a report in December 1992 with opinions of the staff and not necessarily the members of the Committee [27]. The 51-page document reviews the local and possible systemic complications of implants and states among other things that “Dow Corning scientists made repeated references to the lack of safety data, expressing concern that company spokesmen were misleading doctors when they said they had evidence that their product was safe.”
It accuses the companies of scientific misconduct because of Dow Corning’s failure to publish or disclose to FDA their
own research results when they showed problems: “For example, the company (Dow Corning) did not report that some of
the animals they studied showed inflammation of the lymph nodes and other symptoms that could indicate immune
disorders. Instead, Dow Corning published reports that indicated no problems, and in their submission to FDA, they
excluded studies which showed problems. As a result, the FDA advisory panel and FDA staff could not judge the true risks of the implants.” Complete discussion of the report exceeds the scope of this disquisition, but the conclusions reached put authority behind the idea that implants must be more tightly regulated and controlled and more complete information about safety and effectiveness obtained. The report warns the women involved by stating that the “FDA [should] require implant manufacturers to provide information about safety and effectiveness to patients as well as physicians… since problems can occur long after the physician is involved in the patient’s medical care.”
TESTIMONIALS
Testimonials come in a jillion forms. All quote the opinion of others who are presumably honest, disinterested, and
unbiased. Testimonials cannot constitute proof because they are not an appeal to reason. When plastic surgeons hire
almost 400 implanted women to fly to Washington to lobby their Senators and Congressmen about the importance of
breast implants to their self-esteem, or when surgeons and their nurses write more than 20,000 letters to the Congress or
FDA [27], these statements appear so biased that they are discredited, all too easily. Similarly, statements that a given
survey by some plastic surgery society or other shows, despite a return rate of only 60 percent, most women are satisfied with their implants cannot mean much. Nor can the statistics associated with such studies mean much, as discussed below.
STATISTICS
As everyone knows, statistics called forth a lot of derision from Mark Twain, who said, “First get your facts together, then
distort them at your leisure.” Some statistics are merely a way of laying out the findings of an opinion survey. They are
therefore testimonials with the characteristic weaknesses of the polling processes: faulty sample, skewed questions,
unwarranted assumptions, and so forth. Even those statistical studies done correctly require intense scrutiny because of
willful distortion by preselection of starting and finishing points.
For example, among women with augmentation mammoplasty for cosmetic reasons, all investigators to date, the author
included, have found that initially the overwhelming majority of recipients are satisfied with the results. The cosmetic effect at first is a dramatic increase in breast size, which was of course what the women wanted. Consequently, these women suddenly feel they look better in a swimsuit and an evening gown. For several years these cosmetic benefits continue, perhaps falling slightly due to gel bleed and partial deflation and sagging of the device. Only later, after variable periods of time-say, after 6 years for the silicone implant and 2.4 for the silicone implant covered with polyurethane-are the local complications in some of these women severe enough to give them second thoughts about what they have done. Further ahead, especially after repeated surgeries for local or systemic problems, the same individuals who once spoke in favor of the device might speak against it. Thus, a statistically significant survey of the same implanted women might show favorable and unfavorable results depending on when the survey was done in relation to the time that the implant had existed in the woman’s body.
Large studies comparing the incidence of various conditions in implanted women with non-implanted controls matched
for age, income, educational level, and other items might or might not reveal significant information [29-33]. Negative
studies mean less than positive studies because of the nature of negative data: failure to show something must always be less impressive than showing something. The reason for this involves the nature of knowledge itself and can be
summarized with the maxims: “Absence of evidence is not evidence of absence” and “If you see it you believe it, if you
don’t see it you don’t know.” If I say that I see no bacteria, my statement is not as powerful if I am looking through a
telescope than looking through a microscope, and both conditions mean nothing if my eyes are shut. So the instrument
used to gather data and the circumstances surrounding that gathering remain as important and sometimes more important than the data itself. And that brings us to the next item: maxims.
Supported by a grant from the George and Irene Lindler Foundation (Houston). The authors
are grateful to Pam Louis. *Department of Neurology, Baylor College of Medicine, 6550 Fannin
Street, Houston, Texas 77030
Classical rhetoric distinguishes five topics under which any issue may be addressed:
definition, comparison, relationship, circumstance, and testimony. I propose to examine
Human Adjuvant Disease (HAD) in light of these topics.
DEFINITION BY GENUS
Human Adjuvant Disease (HAD) is an autoimmune condition associated with foreign materials in contact with the human
body. Its existence must be inferred because the manufacturer’s package insert says it may occur [1]; numerous medical articles on the subject exist [2-11]; there have been improvements post-explant of foreign materials that have been implanted [12-14]; and in animals, immune stimulation activity of foreign materials has been demonstrated especially epoxyresins, oleoanilides (the cause of Spanish Oil syndrome), vinyl chlorides, chlorinated hydrocarbons and
octamethylpolycyclicsiloxane (D4), and silica [15-20].
HAD means the disease produced by the immune stimulation caused by the effect of foreign material(s). Therefore, this
definition excludes all naturally occurring disorders merely worsened by the immune stimulation of the foreign material.
Such disorders should be classified as “_________ worsened by the adjuvant activity of__________ .” For example,
systemic lupus that is believed to be worsened by adjuvant activity of polyurethane and free silicone in tissue should be
classified as systemic lupus worsened by those adjuvants-and not as HAD.
DEFINITION BY DIVISION
Most cases of HAD would be expected to exhibit the following characteristics, as adapted and modified from Miyoshi’s
original description [21]:
1. Foreign material or materials in the body at some time prior to the development of the autoimmune disease;
2. Local reaction to the implanted material with any one or all of these things: encapsulation, pain, tenderness,
heat, swelling, redness;
3. Some signs and symptoms generally associated with known autoimmune conditions, including but not
necessarily restricted to aches and pains in muscles and joints, stiffness, weakness, and easy fatigue;
4. At least one circulating autodirected antibody at some time after installation of the foreign material. Such
antibodies must be detected in amounts elevated above normal (Only university-based or certified commercial
laboratories can be reasonably and reliably used to fulfill this characteristic’s requirement);
5. No other condition or disease explains the patient’s illness, including infection, malignancy, or naturally occurring
autoimmune disease. If, for instance, the patient meets the accepted criteria of the American Rheumatism
Association for diagnosis of lupus or rheumatoid arthritis, HAD is excluded. The exclusion of typical diseases
makes sense, because HAD usually produces atypical autoimmune disease;
6. Evidence is found for local immunological activation. This commonly consists of foreign body giant cells, but can
be simply a chronic inflammation with plasma cells, some lymphocytes, but mainly lots of macrophages
marginated on or near the foreign material or surrounding the foreign material;
7. Improvement follows explantation when most if not all the foreign material is removed. Time to improvement
depends on the age of the patient, the duration of illness, the severity of the autoimmunity, and many other
influences and conditions not fully understood. In general, significant clinical and laboratory improvement in HAD
occurs within two years of explantation. If improvement fails to occur within this time frame, HAD probably was
ot the cause of the patient’s condition.
These empiric defining criteria, like the criteria for rheumatic diseases in general [22], derive from a dynamic area of
research which at present has an incomplete concept of the disease and an imperfect diagnostic technology. In the years
ahead, improved knowledge and techniques will likely change refine and more accurately describe these characteristics.
Meanwhile, the seven divisions offer a standard against which individual cases or groups of patients can be identified,
measured, and compared.
Comparison
Similarities and differences among cases define HAD and help distinguish it from other conditions. Degree also indicates
the type of illness and cause.
SIMILARITIES
Most HAD patients can be identified by the pattern distribution of abnormalities in their cases and their similarity to
others who have had comparable problems. The usual patient has had foreign material installed within body tissues,
followed sometime later by the development of local difficulties around the site of implantation and, after that, systemic
signs and symptoms of reaction to the material. Local complications include pain, aching, heat, contracture, and
tenderness around the foreign material. Prominent systemic symptoms include morning stiffness, aches and pains in
muscles and joints, gel phenomena, memory loss for recent events, dry eyes, weakness and easy fatigue of skeletal
muscle, regional lymphadenopathy, and skin rash. Signs include local heat, redness, induration, and irregularity around
the implant, and generalized weakness, glove and stocking sensory loss, and evidence of other peripheral or central
nervous system dysfunction or both. This pattern distribution of local complications near the foreign material associated
constitutes a combination unique to HAD. Future studies may show it the sine qua non of this disease, a stereotype of
abnormalities usually not seen in conditions other than HAD. Incidentally, HAD does not occur exclusively in women. It
happens in men in cases associated with ruptured pectoralis and testicular implants.
Laboratory reports show a variety of abnormalities not unique to HAD but occurring in other autoimmune conditions. All
of the abnormalities probably reflect diffuse rather than focal activation of the immune system. The ANA, rheumatoid
factors, positive antibodies against human antigens, the antibodies against the major ganglioside in the central nervous
system, anti-GM1 antibodies, myelin associated glycoprotein antibodies (anti-MAG), antisulfatide, and anti-beta-tubulin
antibodies do not mean the patient has lupus or rheumatoid arthritis or the other relatively specific diseases associated
with those positive blood tests, and certainly do not mean those diseases are present in the absence of clinical disease.
They are immune markers suggesting immune system activation by the foreign material.
Other tests show what organ systems are adversely affected by the immune activation and by how much. So, when
indicated, MRI, SPECT scan, EMG, and so forth can help define the extent of damage already present in an individual
patient and can help organize the approach to treatment.
DIFFERENCES
Patients with HAD differ from other patients in a variety of ways, including the obvious presence of foreign material in
their bodies and also in the multiplicity of signs and symptoms. They usually have at least 20 complaints and commonly
circle over 50% percent of the lists of common symptoms of disease [23,24]. Other patients who do not have HAD have a
much more circumscribed list of complaints. The large number of complaints in HAD makes sense if one considers the
disease is likely due to a diffuse activation of the immune system and not a circumscribed focal activation of one part of
the immune system. If the immune system is diffusely and globally activated, then there should be diffuse and global
complaints referable to virtually every level of the nervous system, to the muscles and nerves, connective tissue, blood
vessels, and skin.
DEGREE
As the severity of local problems increases, the systemic problems do too, especially if the implant has ruptured or if the
immunogenic foreign material directly contacts the immune system by regional or systemic spread. In our series of
implanted patients who had systemic disease, the proven rupture rate was 60 percent at explantation [23,24], a number
higher than the estimate of 1.5 percent by the manufacturer and the 15 to 20 percent mentioned by the FDA. Some foreign materials, such as polyurethane, seem to cause more immune activation and produce more skin rashes and other adverse systemic effects sooner than other materials.
The presence of different time courses and clinical degrees of affliction associated with different foreign materials strongly
suggests that the foreign material plays an etiological role and may actually cause the disease. For instance, the time
course of vinyl chloride disease differs from that of toxic Spanish Oil syndrome. With silicone gel implants, six years
usually elapse from the time of implantation to development of first systemic symptoms; silicone implants surrounded by
polyurethane have a shorter latency.
Taken together, the similarity of disease among patients exposed to the same agent, the differences that the induced
disease bears to other naturally occurring diseases, and the fact that degrees of adversity depend on degrees of exposure, as well as the time-linked nature of the exposure to the subsequent development of the disease, all argue that the agents named actually cause the condition.
Relationship
The topic of relationship divides into three parts: cause and effect, antecedent and consequent, and contraries and
contradictories.
CAUSE AND EFFECT
To assign a cause and make it stick requires four elements. The cause must be sufficient to produce the effect; it must
be the most likely among several possible causes; conditions must not inhibit the cause from exerting its effect; and the
cause must be invariably produce the effect. In the muddy waters of statecraft, real-life situations, the legal arena, and
medicine “invariably” has given way “more likely than not” or with a “reasonable degree of medical certainty.”
In HAD, all four elements apply to foreign materials that are associated with local complications, such as the rupture of
an implant and spill of free silicone into tissue. The rupture of the implant alone is sufficient to produce the spill of silicone
into tissue and to provoke a local inflammatory reaction.
Systemic complications require no small degree of circumspection, and cases must be considered individually. It is not
enough to show that the disease followed implantation. Dry streets get wet after rain and then dry; when rain recurs, they
get wet again. This does not mean dry streets cause rain.
Medicine abounds with post hoc propter hoc errors. There was a time when malaria was considered caused by swampy
land that had bad air. Although we now know that malaria is induced from circumstances more complicated than that, yet
when Roman engineers drained the swamps around the Tiber 2,000 years ago, they abolished malaria in that section of
Italy. These things considered, most people will associate a ruptured implant with the systemic disease that follows,
because most individual cases have strong evidence for unique activation of the immune system.
ANTECEDENT AND CONSEQUENT
This less rigorous form of cause and effect argument generally applies to implants and can be reduced to a rephrased
syllogism: (1) Foreign materials produce local and systemic reactions; (2) an implant is a foreign material; therefore, (3) an implant causes local and systemic reactions. Whether the implant has in fact done so in an individual case depends on the individual evidence adduced.
CONTRARIES AND CONTRADICTIONS
Contraries and contradictions offer an avenue of proof, since two contraries cannot be true simultaneously: either the
implant causes local complications or it doesn’t. To prove that implants cause local complications, it is necessary simply
to demonstrate one case of a local complication. Since numerous cases of local complications are on record-not to
mention the numerous types of local complications-the proof of contraries is more than abundantly fulfilled.
One can make the same argument for the causation of systemic complications. Either implants cause systemic
complications or they don’t. If the implant doesn’t cause autoimmune disease, then why does the manufacturer Dow
Corning state under section 17, paragraph 3, of the package insert that “if an immune response is suspected and the
response persists, removal of the prosthesis is recommended along with the surrounding capsule tissue. Such patients
should not be re-implanted” [1]? Are they suggesting operations for no purpose? Would they endanger the lives of the
implanted patients for no valid reason? If implants and foreign materials cannot cause immune reactions, then why are
there numerous published papers that say they do? Why are there animal studies that show foreign materials are
immunogenic? Clearly the reasoning of contraries proves that implants cause systemic problems. Whether they have done so in an individual case must be determined on the basis of the evidence presented.
Circumstance
The general heading of circumstance comprises two main lines of discourse: the possible and the impossible, and the
past fact and future fact.
THE POSSIBLE AND THE IMPOSSIBLE
The possible and impossible come in five Aristotelian flavors, most of which apply to the matter at hand. Their application
is simple.
First, if one pair of similar items is possible, then the other is possible also. Silicone directly injected into tissue causes
local and systemic reactions; therefore, silicone indirectly injected into tissue after a silicone implant ruptures causes local and systemic complications. Second, if a difficult thing is possible, then the easier thing is possible also. If you can recite the alphabet backwards, chances are likely you can recite it forwards as well. If the bleed of silicone causes a local
inflammatory reaction, then a rupture of an implant will cause a local inflammatory reaction.
Third, if one problem-causing thing can do something, then two problem-causing things together can make things worse.
If silicone causes a local inflammatory reaction, then silicone plus an additional foreign material like polyurethane (probably more irritant) must do so faster, and more severely. Fourth, if a thing is possible without aggravating or complicated conditions, then it is definitely possible with the complications. An intact implant may elicit a surrounding inflammatory reaction; therefore a ruptured implant may do so too.
Finally, if the parts are possible, so is the whole. Hence, if the implant has been associated with Sjogren’s syndrome,
Raynaud’s phenomena, scleroderma, memory loss, muscle weakness, and what have you in individual cases, then a
patient who exhibits all of those afflictions can have a possible complication too.
PAST FACT AND FUTURE FACT
Whether a thing has happened or not is useful in establishing precedent. When companies have settled cases that
purport injuries due to implants for large amounts of money, a precedent is established; the same occurs when a jury
awards a large amount of money for the same reasons. Past fact suggests that reasonable people studying a particular
situation reached a reasonable conclusion, and projects that similar people acting under similar circumstances may reach similar conclusions in the future, establishing a similar or identical future fact. What can be said about past fact hews closely to common sense: two events closely associated (implant and some disease) in the past produce event X
(compensation). It is likely the same associated events will also produce the same consequences in the future, and that
the other cases will be settled or large monetary awards made in compensation. What is right or wrong about this cannot
be determined by this line of argument, since past fact merely predicts future fact-not what is correct, just, or right.
In a larger sense, one can invoke the physical laws of the universe to predict the production of future fact. The second
law of thermodynamics, for example, has never been violated and therefore is considered a sound predictor of what will
happen. It tells us that everything is breaking down, headed towards disintigration and disorder. Since the implant is part of the physical universe, it is governed by the second law and therefore it too must break down. And if it breaks down, it must cause those things known by past fact to be caused by mechanical implant failure-including spilling silicone into tissue, local inflammation, scar formation, pain and tenderness, heat, and of course, deformation of the tissue in which that implant had been placed.
Testimony
Testimony, the last major topic, encompasses six subheads: authority, testimonial, statistics, maxims, law, and
precedent.
AUTHORITY
We tend to imagine some distant past where people unblinkingly accepted the dictates of Church or King, and therefore
say that authority isn’t what it used to be. We try to believe in this modern, scientific, democratic age that people look at
things skeptically and tend not to accept anything unless proven by evidence and reason.
Unfortunately, this belief remains unjustified by the facts: a new age of human intelligence has not dawned. While many
old authorities have been simply shunted aside, they have been replaced by new authorities because humans crave simple answers to complex problems. Appeal to authority-any authority, even the manufacturer of the package insert or the FDA itself-remains illogical, because an authority can be right or can be wrong. What an authority says must be judged by the evidence and not by the position or reputation of the authority.
Nevertheless, provided you cite authority that people accept, arguments citing authority carry considerable weight,
especially if the authority cited is one of the new breed-such as the talk shows, the popular press, or public radio, or even
better a famous movie star, television news personality, or public opinion surveyor. The new authorities are not
disinterested. Instead, they have a financial stake in selling newspapers or getting people to listen to their broadcasts.
Therefore, positions taken by modern authorities tend to be emotionally colored, sensational, and not based on a
dispassionate analysis of evidence.
Plastic surgeons continue to complain about the rather poor press coverage of the breast implant situation and the
overblown emphasis on side effects and the supposed faults of the manufacturers. They railed that there were no scientific studies proving that implants caused problems and even claimed the extreme and untenable position that there were no problems. (Incidentally, this interesting statement itself had little scientific support, since it depended on both the genus definition of the words scientific and study, as well as the division definition of the same words. The statement could be true or false depending on how scientific you wanted to be and how seriously you wanted to examine the studies available.) Thus, plastic surgeons failed to realize the decisions were being made against them emotionally and not rationally, and therefore their arguments in this context meant little. They also failed to understand that as irrational as such media analysis was, it still had the full power of modern authority and as such determined how people viewed the
issue. This remains important, because how the public thinks in a democracy determines how the events will transpire and what future outcomes will happen.
That brings us to the real authorities that have power to enforce the prevailing opinions of our society: the Food and Drug
Administration and the Congress of the United States of America. Let’s examine how these authorities viewed the
situation.
Food and Drug Administration-This organization, empowered by the Congress to regulate food, drugs, and medical
devices, has acted against the implants and put the full weight of law against routine cosmetic augmentation with gel-filled devices. The detailed history of the regulation of the devices shows the FDA had clear-cut fears that the devices had not been tested properly; actual past decisions of the FDA always modified the device classifications into categories requiring tighter and tighter regulation [25].
Furthermore, the FDA document released in February 1993 entitled Silicone Breast Implant Team Leaders’ Report,
Surgical Device Panel, U.S. Food and Drug Administration Critique of Premarketing Applicationdetails the failures of the
manufacturers in their premarketing applications [26]. The FDA failed the applications for defects in sterility, materials
testing, animal studies, human studies, and in a host of other problems. It even accused the manufacturers of fraud,
because information was submitted to FDA that the manufacturer knew or should have known was false. The FDA
concluded that the manufacturers failed to prove their product was safe and effective, despite 30 years of use of the
materials in the United States. (This represents the final authority on the subject.) Consequently, the FDA removed the
silicone gel-filled implants from the American market for cosmetic augmentation. Subsequently, many manufacturers shut down operations, claiming they were afraid of further liability claims. They conveniently failed to mention that the FDA had closed the major market for their product: in fact, most of the market had disappeared overnight. Implants for cosmetic augmentation remain off the American market to this day.
The citation of the FDA’s document and the House of Representatives staff report constitutes a powerful force in the
implant issue because those documents determined whether the implant could continue, and made laws that implants
could not continue. Some brief quotes from the documents follow here to show the style and impact of the statements. The net effect of these stands as a powerful persuasive argument to the reasonable average citizen that the implants were not proved safe and had in the past, and have in the present, substantial adverse effects on health. The documents taken as a whole indicate that the manufacturer failed to prove the devices were safe. They clearly state that the safety and
effectiveness data were inadequate. Any defense of implants must try to get around the force of these papers, which-
because of their authority and impact-appears difficult and may be almost impossible.
In February 1993 the FDA recommended disapproval of the premarketing applications of all implant manufacturers
because of failure to provide adequate clinical, mechanical, and toxicologic testing data [26]. The animal testing employed was considered outdated and nonscientific; the chemical and mechanical descriptions were deemed variable and inadequate; the extractable and leachate propensities were inadequately tested and the metabolic effects of the gel
inadequately tested. In addition, the psychological benefit of the device was improperly tested. Adequate depression,
fatigue, stress, strain, abrasion, and energy to rupture tests were not prepared. Also, cohesivity, valve competence, and
joint integrated tests were inadequate, and the effects of the heat and other risks of sterilization on the materials and the
components were never properly evaluated. The report goes on and raises the question that if this presentation of risk and
benefit, formulated after 30 years of experience in an attempt to obtain governmental approval, fails to support claims of
safety and efficacy, what was the safety data in the past? The FDA concluded that none of the clinical investigation(s)
provided sufficient quantitative data to measure risk.
The Committee on Government Operations of the Human Resources and Intergovernmental Relations Subcommittee of
the House of Representatives issued a report in December 1992 with opinions of the staff and not necessarily the members of the Committee [27]. The 51-page document reviews the local and possible systemic complications of implants and states among other things that “Dow Corning scientists made repeated references to the lack of safety data, expressing concern that company spokesmen were misleading doctors when they said they had evidence that their product was safe.”
It accuses the companies of scientific misconduct because of Dow Corning’s failure to publish or disclose to FDA their
own research results when they showed problems: “For example, the company (Dow Corning) did not report that some of
the animals they studied showed inflammation of the lymph nodes and other symptoms that could indicate immune
disorders. Instead, Dow Corning published reports that indicated no problems, and in their submission to FDA, they
excluded studies which showed problems. As a result, the FDA advisory panel and FDA staff could not judge the true risks of the implants.” Complete discussion of the report exceeds the scope of this disquisition, but the conclusions reached put authority behind the idea that implants must be more tightly regulated and controlled and more complete information about safety and effectiveness obtained. The report warns the women involved by stating that the “FDA [should] require implant manufacturers to provide information about safety and effectiveness to patients as well as physicians… since problems can occur long after the physician is involved in the patient’s medical care.”
TESTIMONIALS
Testimonials come in a jillion forms. All quote the opinion of others who are presumably honest, disinterested, and
unbiased. Testimonials cannot constitute proof because they are not an appeal to reason. When plastic surgeons hire
almost 400 implanted women to fly to Washington to lobby their Senators and Congressmen about the importance of
breast implants to their self-esteem, or when surgeons and their nurses write more than 20,000 letters to the Congress or
FDA [27], these statements appear so biased that they are discredited, all too easily. Similarly, statements that a given
survey by some plastic surgery society or other shows, despite a return rate of only 60 percent, most women are satisfied with their implants cannot mean much. Nor can the statistics associated with such studies mean much, as discussed below.
STATISTICS
As everyone knows, statistics called forth a lot of derision from Mark Twain, who said, “First get your facts together, then
distort them at your leisure.” Some statistics are merely a way of laying out the findings of an opinion survey. They are
therefore testimonials with the characteristic weaknesses of the polling processes: faulty sample, skewed questions,
unwarranted assumptions, and so forth. Even those statistical studies done correctly require intense scrutiny because of
willful distortion by preselection of starting and finishing points.
For example, among women with augmentation mammoplasty for cosmetic reasons, all investigators to date, the author
included, have found that initially the overwhelming majority of recipients are satisfied with the results. The cosmetic effect at first is a dramatic increase in breast size, which was of course what the women wanted. Consequently, these women suddenly feel they look better in a swimsuit and an evening gown. For several years these cosmetic benefits continue, perhaps falling slightly due to gel bleed and partial deflation and sagging of the device. Only later, after variable periods of time-say, after 6 years for the silicone implant and 2.4 for the silicone implant covered with polyurethane-are the local complications in some of these women severe enough to give them second thoughts about what they have done. Further ahead, especially after repeated surgeries for local or systemic problems, the same individuals who once spoke in favor of the device might speak against it. Thus, a statistically significant survey of the same implanted women might show favorable and unfavorable results depending on when the survey was done in relation to the time that the implant had existed in the woman’s body.
Large studies comparing the incidence of various conditions in implanted women with non-implanted controls matched
for age, income, educational level, and other items might or might not reveal significant information [29-33]. Negative
studies mean less than positive studies because of the nature of negative data: failure to show something must always be less impressive than showing something. The reason for this involves the nature of knowledge itself and can be
summarized with the maxims: “Absence of evidence is not evidence of absence” and “If you see it you believe it, if you
don’t see it you don’t know.” If I say that I see no bacteria, my statement is not as powerful if I am looking through a
telescope than looking through a microscope, and both conditions mean nothing if my eyes are shut. So the instrument
used to gather data and the circumstances surrounding that gathering remain as important and sometimes more important than the data itself. And that brings us to the next item: maxims.
Dr. Britta Ostermeyer Shoaib M D
by
BERNARD M. PATTEN* and BRITTA OSTERMEYER SHOAIB*
Reprinted from PERSPECTIVES IN BIOLOGY AND MEDICINE
Vol. 38, No.2, Winter 1995
Pages 274-290
BERNARD M. PATTEN* and BRITTA OSTERMEYER SHOAIB*
Reprinted from PERSPECTIVES IN BIOLOGY AND MEDICINE
Vol. 38, No.2, Winter 1995
Pages 274-290