ASTHMA IN PATIENTS WITH SILICONE BREAST IMPLANTS: REPORT OF A
CASE SERIES AND IDENTIFICATION OF HEXACHLOROPLATINATE
CONTAMINANT AS A POSSIBLE ETIOLOGIC AGENT
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 Internal
Medicine, Providence Hospital, Southfield, Michigan
Address for correspondence: Michael R. Harbut MD, MPH; Wayne State
University School of Medicine, Detroit, Michigan, and Center for Occupational
and Environmental Medicine, 22255 Greenfield; Southfield, Michigan, 48075
ABSTRACT
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 noted 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.
INTRODUCTION
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
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 athma.
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).
METHODS
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
is 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 SUMMARIES:
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 19821992 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 challenge.
CASE #3: A 54 years 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 increasing
exertional 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 years 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 in FEV1.
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 years 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 years of age, white female, mortgage loan officer underwent
breast augmentation surgery in 1979 using Surgitek silicone implants. She is
currently a nonsmoker who quit smoking 20 years ago after accumulating a 3pack-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 confirmed 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.
DISCUSSION
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 breast implants. 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 data, only 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/kg1 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.
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* Editors note: We included this article because it was the occupational
medicine background of the author which leads him to make the observed
association.
Table 1. Patient history and symptoms
Patient (No) Age* Atopic history Smoking (pack years) Months to symptoms**
Cough Wheezing Puritis Rhinorrhea
1 31 - - 12 - + + +
2 47 + 8 1 +*** - + 3 54 - - 72 + - + +
4 58 - 33 48 + + + +
5 57 - 9-stopped 192 + + + +
6 49 + - 3 + + + +
7 48 + 3 -stopped 12 + + + +
8 53 + - 84 + + + +
*age at presentation
**months after implantation
***cough was productive in all cases
> > >>
> > >>Table 2. Pulmonary function tests
> > >>Patient FVC* FEV1 FEV1/ FVC FEF25-75 TLC DLCO
> > >> Methacholine challenge test**
> > >>1 113 118 82 84 93 88 36
> > >>2 129 118 70 60 105 95 36
> > >>3 113 112 75 63 105 105 34
> > >>4 110 104 70 41 101 75 22
> > >>5 66*** 32 37 7 122 65 improved after 2.5
> > >>mg albuterol (by 29%)
> > >>6 103 106 78 59 126 91 52
> > >>7 103 114 85 85 118 95 20
> > >>8 124 135 82 92 103 97 28
> > >>*percent of predicted
> > >>**percent decrease in FEV1 after the administration of
> methacholine
> (minimal
> > >>dose)