ASTHMA IN PATIENTS WITH SILICONE BREAST IMPLANTS: REPORT
OF A CASE SERIES
AND IDENTIFICATION OF HEXACHLOROPLATINATE CONTAMINANT AS A POSSIBLE
Michael R Harbut
Brenda C Churchill*
IJOH; 1999; 3:73-82.
From: Center for Occupational and Environmental Medicine; Wayne State
University, School of Medicine, Detroit, Michigan, and *Department of
Medicine, Providence Hospital, Southfield, Michigan
Address for correspondence:
Michael R. Harbut MD , MPH;
University School of Medicine,
Occupational and Environmental Medicine,
Southfield, Mi. 48075
The following study is of 8 breast implant patients evaluated because of
respiratory systems, pruritus and rhinorrhea. The presence of
hexachoroplatinate in the implants was notes and support for the hypothesis
that this contaminant was related to the symptoms experienced by the patients
is presented. Cases of implant related asthma were defined by episodic
dyspnea, cough, or breathlessness with onset or worsening after implant
placement and objective evidence of reversible airways obstruction, either
during the presence or after the removal of the devices.
All eight patients were found to have asthma, with airway hyper-reactivity
demonstrated by methacholine challenge testing performed in seven patients
and by partially reversible obstruction after nebulized administration of a
beta-agonist in one patient. Eight patients had urticaria and seven had
rhinorrhea. Eight of eight breast implant patients evaluated had findings
consistent with asthma. Hexachloroplatinate, a potent sensitizer and
component of breast implants, is identified as the likely primary etiologic
agent in view of findings consistent with platinosis in these
patients, and the demonstration of the leaching of hexachloroplatinate from
even intact silicone breast implants.
Human illness as a result of toxicity of silicone gel breast implants is
an evolving and controversial area of medical investigation. The nature of
any toxicity has not yet been fully characterized, but at least in part it
appears to be consistent with a hypersensitivity process. The medical
community is moving away from early reports of an autoimmune process, but has
not yet offered a clear explanation for complaints registered by patients who
have had the devices placed. There is also significant uncertainty with
respect to any responsible agents of toxicity.
Silicone breast implants consist of a shell encasing a gel. Both the
shell and gel are complex formulations that include carbon and silicone and
traces of many other elements. Saline implants are comprised of a saline
fluid contained in a silicone shell casing. From an Occupational Medicine
perspective, notable among the agents present in both gel and shell are the
metals chromium, nickel, aluminum and platinum. The presence of platinum in
the implants occurs as a result of its use as a catalyst in its hexasolvent
form (H2PtCl6) in the production of gel and shell. (1). All three metals are
known to be associated with occupational asthma. Hexachloroplatinate,
however, is the most potent of sensitizers reported.
There is an extensive medical literature related to the occupational
disease entity platinosis and airways reactivity, caused by exposure to
complex platinum salts. Respiratory problems in platinum refinery workers
were reported as long ago as 1911 and are extensively reviewed in the World
Health Organization Monograph of the Internal Program of Chemical Safety.
(2). Platinosis or platinum allergy historically
refers to the triad of asthma, dermatitis and rhinitis in workers exposed to
platinum. Pruritis has also been reported. Platinosis is highly prevalent in
workers exposed to platinum with a cumulative prevalent rate 50% or more.
The potency of platinum is such that the *TLV-TWA for platinum salts is 2
mcg/cubic meter of air.
(6). As a comparison, the TLVs for two other toxic metals, lead and
arsenic, are two orders of magnitude greater at 0.15 and 0.2 mg/cubic meter
of air respectively. There have been case reports of platinum sensitivity
from dental work and jewelry. (3,4).
Platinum asthma can be present before, after, or in the absence of
positive skin prick testing. Cold air and methacholine challenge have both
been shown to evoke airways hyper-responsiveness in the
hexachloroplatinate-exposed lung, in the absence of existing exposure and/or
laboratory or abnormal immunologic testing. (5-9).
Eight consecutive patients referred to the clinic with breast implants
and various symptoms were included, l993 with extensive histories, including
a respiratory history that incorporated the questions from the Epidemiology
Standardization Project (10). The patients were questioned about alternative
exposure sources, such as occupational metal exposures and
platinum-containing dental work. This was done to identify any sources of
platinum even in the non-hexasolvent form.
Patients were also asked about their surgical history, type of implant
(silicone or saline), manufacturer, and whether the implants had ruptured.
Symptom onset as related to implant status was also elicited. Pulmonary
function testing was done in the eight patients. All had complaints of cough
or breathlessness. Methacholine challenge testing was done on 7 patients
with fundamentally normal pulmonary function and a beta-agonist (Albuterol)
was administered by nebulizer to the patient whose pulmonary function test
demonstrated airway obstruction.
CASE #1: A 31 year old, nonsmoking white female, sales account manager
underwent breast augmentation surgery in 1989 using Surgitek silicone
implants. There was no evidence of rupture or leakage. She had childhood
pneumonia but no respiratory symptoms before implantation. Presenting
complaints include exertional dyspnea with wheezing, severe pruritus several
times each week, scaling and dry skin,
occurring since the implant surgery. The patient had normal resting
pulmonary function tests with a positive methacholine challenge test (36%
decrease in FEV1).
CASE: #2: A 47 year old, white female nurse, who is currently a smoker with
an 8-pack-year history had breast augmentation surgery in 1970 using Dow
Silastic silicone implants. The right breast implant ruptured in 1982,
necessitating removal and replacement. In 1992, both implants were removed
after rupture of the left implant. Spillage of silicone was confirmed
operatively in both 1982 and 1992. The patient presented with complaints of
loss of taste sensation, speech difficulty,
muscular tics and vesiculations, memory loss, episodic confusion,
intermittent rash, pruritus, chronic bronchitis and dyspnea on exertion
occurring since 1970. She has coughing spells and has episodes of dyspnea on
exertion on exposure to some household chemicals. Symptoms worsened after
the 1982-1992 ruptures. She had a history of nonspecific allergies,
bronchitis and pneumonia prior to the implants. The patient had near normal
resting pulmonary function tests and a positive methacholine
CASE #3: A 54 year of age, nonsmoking white female teacher underwent breast
augmentation in 1975 with silicone gel breast implants. There was no definite
evidence of rupture or leakage. The patient presented with severe fatigue,
somnolence, chest and upper extremity burning, paresthesias and urticaria.
Respiratory symptoms developed over the last two years prior to her
evaluation, and included a nonproductive cough, episodic coughing spells, and
dyspnea. Prior to the implant surgery, she had a history of bronchitis but
no documented allergies. She had near normal resting pulmonary function test
and the methacholine challenge test demonstrated a 34% decrease in FEV1.
CASE #4: A 58 year of age, white female homemaker who is a smoker with a
33-pack-year history, underwent breast reconstruction and augmentation in
1981 after bilateral prophylactic mastectomies for multiple nonmalignant
tumors. The implants were removed and replaced three times as a result of
complications, and they were permanently removed in 1993. The patient is
convinced that there was leakage, but this is unconfirmed. Presenting
complaints included severe, progressive fatigue over the eight years prior to
evaluation to the point that she now reports spending up to 75% of her day in
bed. She also complained of paresthesias. Respiratory symptoms which began
or worsened after the implant surgery include cough, wheezing, multiple
episodes of bronchitis, increasingly productive cough and episodic dyspnea.
Despite her smoking history, this patient had near normal resting pulmonary
function tests. Methacholine challenge test was positive with a 22% decrease
CASE #5: A 57 year old white female, employed as a waitress since 1991
underwent breast augmentation with silicone implants in 1974. Suspected
leakage was confirmed at surgery in January of 1993 when the implants were
replaced with a saline type. She is currently a nonsmoker who quit two years
ago. Prior to that, she had accumulated a 9-pack-year history over 38
calendar years. She presented with complaints of constant fatigue, pruritus,
and an intermittently productive chronic cough with
nocturnal wheezing. She also noted burning paresthesias radiating across
the chest and upper extremities. Respiratory symptoms began approximately
three years prior to evaluation. She had a history of bronchitis and
emphysema prior to the implants, but chronic bronchitis only began three
years prior to her evaluation here. The patient had markedly abnormal
resting pulmonary function tests with a 29% improvement after
administration of 2.5 mg of Albuterol by nebulizer. Therefore this patient
probably has asthma superimposed on fixed obstructive lung disease.
CASE #6: A 49 year of age, nonsmoking white female homemaker underwent
bilateral mastectomies for a diagnosis of extensive fibrocystic disease with
small fibroadenomas, locular lobular hyperplasia, and focal intraductal
papillomatosis. The mastectomies were followed by reconstruction using
Surgical Replicon silicone implants in 1983. Within a few months after the
reconstruction, the patient began having leakage around the left implant,
which precipitated a rash and cramping pain at the surgical site.
Approximately three months later, the implants were removed. Bilateral
reconstruction was again performed in 1984 using Heyer Schulte implants. The
patient continued to have difficulty with rashes and breast pain until
finally the implants were removed in 1989. At surgery, the right implant was
found to have ruptured. Presenting complaints included recurrent episodes of
erythema and pruritus across the chest and upper extremities, nonproductive
cough, rhinorrhea, and wheezing. Prior to the implants the patient had
symptoms consistent with hay fever and bronchitis. Methacholine challenge
testing showed a 52% decrease in the
FEV1 with essentially normal resting pulmonary function.
CASE #7: A 48 year of age, white female, mortgage loan officer underwent
breast augmentation surgery in 1979 using Surgitec silicone implants. She is
currently a nonsmoker who quit smoking 20 years ago after accumulating a
3-pack-year history over approximately eight calendar years. She developed
hardening of the left implant within a few months, and in 1980 her surgeon
"broke this by hand" (closed capsulotomy). Subsequently, she began to have
flu-like symptoms, which worsened to include rash and arthralgias. During
1985, she was found to have Hashimoto's thyroiditis and is currently on
thyroid replacement. In 1988, the patient became convinced the implants had
ruptured, and in 1990, she noticed lumps around the left breast. These were
evaluated with various radiographic techniques and found to be nonmalignant.
The patient experienced progressive worsening of her symptoms, including
intolerable pruritus, joint pains, rashes, and intractable allergy symptoms.
As a result, the implants were removed in 1992. The operative report
rupture and leakage. She had respiratory symptoms predating the implants
which included chest tightness. She had allergies for which she had received
desensitization therapy. Episodic dyspnea has been present since 1981 and
became worse after the removal of the implants in 1992. She was seen in the
emergency room with inconclusive findings. The patient was found to have a
normal resting pulmonary function test and a positive methacholine challenge
test with a 20% decrease in FEV1.
CASE #8: A 53 year old, nonsmoking white female, secretary underwent a
double mastectomy in 1977 followed by reconstructive surgery using Dow
Corning silicone implants. In 1993, when the implants were found to have
ruptured by radiographic examination, they were removed and replaced by
McGhan saline implants. The patient presented with complaints of chronic
cough, phlegm, wheezing and dyspnea, the onset of which was approximately
seven years after implants. There was progressive worsening and symptoms
over the last nine years, including frequent urticaria and rhinorrhea. Past
medical history is remarkable for episodic bronchitis and various allergies.
The patient was found to have essentially normal resting pulmonary function
tests and a positive methacholine challenge test with a 20% decrease in FEV1.
The patients presented with cough, wheezing, a productive cough,
rhinorrhea and pruritis. (Table 1). The symptoms began approximately 3 to 192
months after the implantation. Breast implant histories vary widely with
respect to manufacturer of
original and replacement implants. All but three had implants placed at
least once and all but three had implants currently in place at the time of
evaluation. Six had implant rupture, either surgically confirmed or
suspected. Duration of implant exposure ranged from 4 to 22 years. At the
time of evaluation, no reliable methodology existed to analyze urine for the
possible presence of platinum. (11).
Except for the one patient with severe obstructive lung disease, all
had normal chest x-rays and pulmonary function tests (Table 2). All had
positive methacholine change testing or improvement after the administration
of 2.5 mg albuterol.
These eight patients were chosen consecutively from women referred
for an occupational medicine assessment who had pulmonary symptoms and a
history of breast implantations. The Center for Occupational and
Environmental is an Association of Occupational and Environmental Medicine.
The referring rheumatologist was aware of platinum contamination and the fact
that workers from one manufacturer of the devices (Dow-Corning) had been
evaluated at COEM for work-related disease.
All 8 patients met the following two criteria for asthma.
1.Symptoms consistent with asthma such as wheezing, episodic cough or
episodic dyspnea that began or worsened after the presence of silicone gel
2.Reactive airways disease as demonstrated by a positive methacholine
challenge test with at least a 20% drop in the FEV1 using 10 mg or less of
methacholine; or by significant reversibility of airway obstruction after
treatment with the beta-agonist.
We hypothesize that hexachloroplatinate is the causative agent for
"breast implant asthma." It is likely that it is the etiologic agent for the
other symptoms and signs consistent with platinum toxicity reported by this
patient population. Although platinum hypersensitivity is considered to be
largely IgE mediated, (12), more recent studies have shown other more complex
mechanisms of immune system disease. (13,14,15). Consistent with more recent
one of our patients had elevated IgE levels (Table 3).
There is convincing evidence that these patients were exposed to
platinum. El-Jamal and Templeton (16) found 4 mg/kg-1 of platinum in a breast
prosthesis, and Lykissa et al (17) found that in an older, intact, surgically
removed silicone gel breast implant, 20-25 mcg/day/250 grams of platinum
leaks into a lipid medium at 37 degrees..
Asthma was found in these patients during implant presence and after
implant removal. This parallels the experience from occupational platinum
asthma in which symptoms and bronchial hyper-reactivity can exist long after
removal from exposure. (5,18). In this series, however, rupture had occurred
in those patients who had undergone implant removal, and consequently, some
residual sensitizing agents may have escaped into tissue adjacent to the
surgical site. The minimal level of implanted
platinum required to produce and maintain symptoms is unknown but in the
occupational setting allergies in those exposed to any levels of platinum are
considered to be exposure related (19,20) especially considering the high
prevalence of allergic lung disease is such workers.
Asthma in association with platinum-containing breast implants has
not been previously reported. Women with breast implants should be
questioned about respiratory symptoms. If there is a positive symptom
history consistent with asthma, then the patient should be tested for the
presence of reactive airways disease. In women with breast implants perhaps
pulmonary function tests should be done on pre-employment examinations,
especially if their work will involve exposures to allergenic substances.
Prospective studies are warranted to confirm our findings of
the association between breast implants and asthma. Furthermore, animal
studies could be done to prove that the observed disease was due to the
platinum contained in the breast implants.