17 April 1996
The Editor
The British Medical Journal
Tavistock House
Tavistock Square
LONDON
Dear Sir,
Silicone Implants Disease and Mineral Oil Adjuvants in Experimental Immune Diseases
The safety of silicone breast implants has been a cause for concern since systemic Illnesses begin to be reported in women with implant complications. The local effects have been accepted as due to inflammation associated with silicone oil droplets, but systemic effects have been controversial and a causal link is often denied. A detailed report has been documented objective laboratory findings in 100 women with systemic complications after implanted silicone prostheses had failed or after direct injection of silicone oil into breast tissue. All of the patients had at least 20 symptoms. The most common complications were fatigue, early morning stiffness, severe myalgia, arthralgia, joint swelling, and polyneuropathy. Some patients developed a multiple sclerosis-like syndrome, others a motor neuron disease. This very mixed bag of diseases has been linked to autoimmunity.
Despite the use of the term silicone adjuvant disease, no comparison appears to have been made with adjuvants used in experimental, so called, auto – immune diseases. These are putative models of many diseases involving organ systems in which disease has been reported as a complication in silicone implant patients. They include multiple sclerosis, polyneuritis, and polyarthritis.
The most widely used is Freund’s Adjuvant Disease, either in its complete form, which includes killed tubercule bacilli is a mixture of mineral oils, or in the incomplete form which is just the mineral oils. Adjuvants were developed in the 1930’s when attempts were being made to find a vaccine against tuberculosis. It was noted that using injections of killed tubercle bacilli injected in an oil emulsion, some animals developed encephalitis. After the Second World War, when autoimmunity became a fashionable concept, organ system disease could be studied by the use of Encephalitis (EAE) using emulsified brain tissue and Freud’s adjuvants. Experimental Allergic Multiple sclerosis. because the brain tissue used is derived from another animal, the description “auto” immune is incorrect.
It had been known for some time that the adjuvant emulsion could be encephalitigenic but, despite forty years of use, controlled experiments have only recently been conducted into the role of adjuvants. They are responsible for increasing vascular permeability, as for example the blood brain barrier, or the blood joint barrier in the synovial membrane. Although there are no reports of adjuvants actually being detected in the circulation, it is difficult to see any other mechanism, which could be responsible for transmission, for example, from an injection site in the peritoneum to the cerebral vessels. Cunmermeyer, has reported that oil injected intra-peritoneally can cause cerebral fat embolism, with blood-brain barrier breakdown evidenced by hemorrhage.
We have investigated the injection of droplets of mineral oil in plasma (5ml) into the carotid artery in the guinea pig. The droplet size was 15+/-5 microns. It is known that fat emboli open the blood brain barrier rapidly, and this is the case with mineral oil. At intervals of one, two and three hours after the injection of emboli, 2 ml of plasma containing 2% Trypan blue dye was injected slowly into either the same carotid artery, or the contralatery artery. Each animal had match control where 5 ml of plasma only was injected and ten animals were used in each group. Trypan blue dye binds to serum albumin and so is a marker of major breakdown of the blood-brain barrier. The results are shown in figure1 (not shown here) ALL test animals had barrier opening at one and two hours and in two, it remained open at three hours. None of the control animals had breakdown of the cortical barrier, although some slight staining was found. In the brain stem of one animal. Figure 2 (not shown here) shows the extravasation from the venules of the right hemisphere after the injection of mineral oil into the right carotid artery, followed one hour later with an injection of Trypan blue into the contra lateral artery.
These experiments indicate that the single passage of a 15-micron droplet of mineral oil opens the cerebral venous blood – brain barrier for up to three hours. We also found staining of the synovial fluid indicating the inflammatory response through the complement of cascade, triggering auto immunity. In animal laboratories, technicians have been accidentally injected with adjuvants and antigen and have developed similar syndromes to those seen in silicone-implanted diseases.
The amount and droplet size of silicone liberated from implants gaining access to the circulation is likely to vary greatly. The routes taken by the droplet emboli can also vary and patients are likely to present with different syndromes. The time of presentation will not be predictable as it is related to the release of the implant material. We believe that adjuvancy is a micro- embolic phenomenon, which allows protein extravasation into the tissue generating complement activation and immune mechanisms. This provides a cogent explanation of the variety of syndromes in silicone implant disease.
Yours faithfully
Dr. Philip James
Wolfson Hyperbaric Medicine Unit
Ninewells Medical School
The University of Dundee
Professor Brian A. Hills
Mater Misericordas Children’s Hospital
South Brisbane
Queensland 4101
Printed with Permission
